NOAEL Studies
Preservative
Polyaminopropyl Biguanide NOAEL Studies
INCI: POLYAMINOPROPYL BIGUANIDE
CAS: 32289-58-0
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_dart 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, Developmental malformation | sheet=Data; excel_row=44907; Record_ID=dart_38160; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, Developmental malformation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Male/Female; Life_Stage=Fetal; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0000768;CUI;Congenital Abnormality|UMLS;C0265509;CUI;Congenital anomaly of skeletal bone|UMLS;C0699952;CUI;Fused; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, Developmental malformation | sheet=Data; excel_row=44908; Record_ID=dart_38185; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, Developmental malformation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Male/Female; Life_Stage=Fetal; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0000768;CUI;Congenital Abnormality|UMLS;C0265509;CUI;Congenital anomaly of skeletal bone|UMLS;C4086922;CUI;Unossified; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45013; Record_ID=dart_38147; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0009264;CUI;Cold Temperature; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45014; Record_ID=dart_38148; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0011135;CUI;Defecation; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45015; Record_ID=dart_38151; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0023380;CUI;Lethargy; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45016; Record_ID=dart_38152; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0009264;CUI;Cold Temperature; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45017; Record_ID=dart_38153; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C2983605;CUI;Food Consumption|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C2983605;CUI;Food Consumption; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
| NTP_ICE_dart | LOEL | 40 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=45018; Record_ID=dart_38154; Data_Type=In Vivo; DTXSID=DTXSID2035726; Assay=DART, In life observation; Endpoint=LOEL; Response=40; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0009264;CUI;Cold Temperature; Reference=ToxRefDB v2 , ID = 6106; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2035726 |
SCCS_vision_codex 180 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat","page":17,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | % | mouse | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr","page":32,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_005"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":35,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | mouse | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | - | - | - | NOAEL study | {"dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.","effect":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":38,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.","effect":"e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_012"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_013"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | genotoxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_014"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul","page":48,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_015"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_016"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_017"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 94 3","dose":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_018"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.","effect":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_019"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nced by the test substance at any dose level.","effect":"nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_020"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"ions were not influenced by the test substance at any dose level.","effect":"ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_021"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","effect":"at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_022"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_027"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...","effect":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_028"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand","page":20,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_001"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | 2-year | NOAEL study | {"citation":"Ref.: 46","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","page":42,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,","page":43,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_005"} |
| SCCS_vision_codex | NOAEL | =0.257 | - | - | - | - | irritation | {"effect":"significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","page":45,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_006"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":46,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | - | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.","page":47,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in","page":48,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":50,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_011"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_012"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | reproductive toxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_013"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_014"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_015"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 90 3","dose":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d","page":53,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_016"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.","effect":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_017"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ced by the test substance at any dose level.","effect":"ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_018"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","effect":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_020"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu","page":65,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_021"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","effect":"r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_023"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...","effect":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_024"} |
| SCCS_vision_codex | NOAEL | =1581 | - | - | - | - | repeated dose toxicity | {"dose":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","page":78,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_030"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat","page":17,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | % | mouse | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr","page":32,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_005"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":35,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | mouse | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | - | - | - | NOAEL study | {"dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.","effect":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":38,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.","effect":"e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_012"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_013"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | genotoxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_014"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul","page":48,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_015"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_016"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_017"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 94 3","dose":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_018"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.","effect":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_019"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nced by the test substance at any dose level.","effect":"nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_020"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"ions were not influenced by the test substance at any dose level.","effect":"ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_021"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","effect":"at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_022"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_027"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...","effect":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_028"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand","page":20,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_001"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | 2-year | NOAEL study | {"citation":"Ref.: 46","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","page":42,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,","page":43,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_005"} |
| SCCS_vision_codex | NOAEL | =0.257 | - | - | - | - | irritation | {"effect":"significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","page":45,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_006"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":46,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | - | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.","page":47,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in","page":48,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":50,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_011"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_012"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | reproductive toxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_013"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_014"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_015"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 90 3","dose":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d","page":53,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_016"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.","effect":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_017"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ced by the test substance at any dose level.","effect":"ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_018"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat","page":17,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | % | mouse | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr","page":32,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_005"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":35,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | mouse | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | - | - | - | NOAEL study | {"dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.","effect":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":38,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.","effect":"e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_012"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_013"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | genotoxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_014"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul","page":48,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_015"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_016"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_017"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 94 3","dose":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_018"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.","effect":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_019"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nced by the test substance at any dose level.","effect":"nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_020"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"ions were not influenced by the test substance at any dose level.","effect":"ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_021"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","effect":"at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_022"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_027"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...","effect":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_028"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand","page":20,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_001"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | 2-year | NOAEL study | {"citation":"Ref.: 46","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","page":42,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,","page":43,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_005"} |
| SCCS_vision_codex | NOAEL | =0.257 | - | - | - | - | irritation | {"effect":"significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","page":45,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_006"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":46,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | - | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.","page":47,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in","page":48,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":50,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_011"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_012"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | reproductive toxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_013"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_014"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_015"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 90 3","dose":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d","page":53,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_016"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.","effect":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_017"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ced by the test substance at any dose level.","effect":"ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_018"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","effect":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_020"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu","page":65,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_021"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","effect":"r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_023"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...","effect":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_024"} |
| SCCS_vision_codex | NOAEL | =1581 | - | - | - | - | repeated dose toxicity | {"dose":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","page":78,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_030"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","effect":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_020"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu","page":65,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_021"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","effect":"r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_023"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...","effect":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_024"} |
| SCCS_vision_codex | NOAEL | =1581 | - | - | - | - | repeated dose toxicity | {"dose":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","page":78,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_030"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat","page":17,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | % | mouse | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr","page":32,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":33,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_005"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":35,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | mouse | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | - | - | - | NOAEL study | {"dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.","page":36,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.","effect":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":38,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.","effect":"e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_012"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_013"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | genotoxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125","page":39,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_014"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul","page":48,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_015"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_016"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 73 3","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP","page":49,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_017"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 94 3","dose":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_018"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.","effect":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_019"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nced by the test substance at any dose level.","effect":"nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","page":50,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_020"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"ions were not influenced by the test substance at any dose level.","effect":"ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_021"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","effect":"at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf","page":51,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_022"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_027"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...","effect":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati","page":61,"pdf":"sccs_o_157.pdf","row_type":"noael_study","study_id":"sccs_o_157_noael_028"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | {"citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","effect":"e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand","page":20,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_001"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | 2-year | NOAEL study | {"citation":"Ref.: 46","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","page":42,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_002"} |
| SCCS_vision_codex | NOAEL | =20.2 | % | rat | oral | 2-year | NOAEL study | {"citation":"Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,","page":43,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rabbit | dermal | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rabbit | oral | - | irritation | {"citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","page":44,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_005"} |
| SCCS_vision_codex | NOAEL | =0.257 | - | - | - | - | irritation | {"effect":"significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","page":45,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_006"} |
| SCCS_vision_codex | NOAEL | =26 | - | rat | - | - | irritation | {"citation":"Ref.: 15","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":46,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_007"} |
| SCCS_vision_codex | NOAEL | =92.3 | mg/kg bw/d | - | oral | - | NOAEL study | {"dose":"r 6000 ppm at interim and/or terminal kill.","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.","page":47,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_008"} |
| SCCS_vision_codex | NOAEL | =224 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in","page":48,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_009"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw/d | rat | - | - | NOAEL study | {"citation":"Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","page":50,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | {"citation":"Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_011"} |
| SCCS_vision_codex | NOAEL | =54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_012"} |
| SCCS_vision_codex | NOAEL | =36 | mg/kg bw/d | rat | oral | 2-year | reproductive toxicity | {"dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes","page":51,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_013"} |
| SCCS_vision_codex | NOAEL | =600 | ppm | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_014"} |
| SCCS_vision_codex | NOAEL | =79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | {"citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197","page":52,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_015"} |
| SCCS_vision_codex | NOAEL | =130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | {"citation":"Ref.: 90 3","dose":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","effect":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d","page":53,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_016"} |
| SCCS_vision_codex | NOAEL | =200 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.","effect":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_017"} |
| SCCS_vision_codex | NOAEL | =1000 | ppm | mouse | - | developmental | developmental toxicity | {"citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ced by the test substance at any dose level.","effect":"ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_018"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","effect":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in","page":54,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_020"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | {"citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu","page":65,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_021"} |
| SCCS_vision_codex | NOAEL | =8.5 | % | rat | oral | 104 week | NOAEL study | {"citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","effect":"r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_023"} |
| SCCS_vision_codex | NOAEL | =3.1 | mg/kg bw/d | rat | oral | 104 week | NOAEL study | {"dose":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...","effect":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","page":73,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_024"} |
| SCCS_vision_codex | NOAEL | =1581 | - | - | - | - | repeated dose toxicity | {"dose":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","page":78,"pdf":"sccs_o_1581_16.pdf","row_type":"noael_study","study_id":"sccs_o_1581_16_noael_030"} |
ToxRefDB_ToxRefDB_v3_pod.csv 23 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =258.2 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F0_F_systemic; toxval_effect_list=in life observation-food consumption-food efficiency|in life observation-body weight-body weight; dose_level=3; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =69.6 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F0_M_systemic; toxval_effect_list=organ weight-kidney-nos|organ weight-epididymis-nos|in life observation-body weight-body weight|in life observation-food consumption-food efficiency; dose_level=2; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =270.5 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F1_F_systemic; toxval_effect_list=pathology microscopic-kidney-foreign body|pathology microscopic-kidney-hydronephrosis|in life observation-food consumption-food efficiency; dose_level=3; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =60 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | dermal | 0 day to 21 day | SAC | study_id=6103; toxval_study_source_id=studyid6103_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-scabbing|in life observation-clinical signs-erythema|pathology microscopic-skin-edema|pathology microscopic-skin-infiltration cellular; dose_level=2; study_year=1993; study_citation=Lees, D and AM Leah. 1993. PHMB: 21-day dermal toxicity study in the rat. Zeneca Central Tox Lab, Study no. LR0559. MRID 43047701.; dsstox_substance_id=DTXSID2035726; admin_method=Topical; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =40 | mg/kg bw/day | rabbit (new zealand white; New Zealand White) | oral | 8 GD to 20 GD | DEV | study_id=6106; toxval_study_source_id=studyid6106_Adult Pregnancy_F0_F_reproductive; toxval_effect_list=reproductive performance-implantations-implantations|reproductive performance-estrous cycle-corpora lutea|reproductive performance-aborted-aborted|offspring survival early-birth index-birth index|reproductive performance-preimplantation loss-preimplantation loss; dose_level=3; study_year=1993; study_citation=Brammer, A. 1993. Polyhexamethylene biguanide: Developmental toxicity study in the rabbit. Zeneca Central Tox Lab., Study no. RBO 614. MRID 42865901.; dsstox_substance_id=DTXSID2035726; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =7.5 | mg/kg bw/day | dog (beagle; beagle) | oral | 0 week to 52 week | CHR | study_id=6107; toxval_study_source_id=studyid6107_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-fur (altered appearance)|pathology gross-uterus-discolored|in life observation-clinical signs-tremors|in life observation-clinical signs-scabbing|pathology microscopic-liver-hypertrophy|in life observation-clinical signs-emaciation|pathology microscopic-liver-pigmentation|clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|pathology microscopic-skin-inflammation|pathology gross-skin-mass|in life observation-mortality-mortality|pathology gross-oral mucosa-mass|in life observation-clinical signs-reduced activity|pathology microscopic-kidney-concretion|in life observation-clinical signs-skin ulceration|pathology microscopic-nerve-mineralization|in life observation-clinical signs-abnormal gait|pathology gross-skin-discolored|pathology gross-stomach-discolored|pathology microscopic-liver-inclusion body intracytoplasmic; dose_level=1; study_year=1995; study_citation=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =217 | mg/kg bw/day | mouse (cd1) | oral | 0 week to 104 week | CHR | study_id=6109; toxval_study_source_id=studyid6109_Adult_F0_F_systemic; toxval_effect_list=pathology microscopic-liver-hypertrophy|organ weight-liver-absolute|pathology microscopic-liver-hemosiderosis|in life observation-body weight-body weight gain|pathology microscopic-liver-inflammation|hematology-hemoglobin (hgb)-hemoglobin (hgb)|pathology microscopic-liver-lipofuscin deposits|pathology microscopic-gallbladder-dilatation|pathology microscopic-intestine large-metaplasia|pathology gross-liver-mass|pathology microscopic-liver-nuclear alteration|pathology gross-ear-lesion(s) (nos)|hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|pathology microscopic-skin-depletion|hematology-hematocrit (hct)-hematocrit (hct)|pathology gross-skin-reduced size|pathology microscopic-intestine large-inflammation|pathology microscopic-intestine large-hyperplasia|organ weight-adrenal gland-absolute|in life observation-clinical signs-swelling|pathology gross-intestine large-enlarged|pathology microscopic-intestine large-squamous cell carcinoma|pathology microscopic-spleen-hemangiosarcoma|pathology microscopic-liver-hemangiosarcoma|in life observation-food consumption-food consumption|pathology microscopic-gallbladder-hyperplasia|pathology microscopic-spleen-hematopoietic cell proliferation|organ weight-adrenal gland-relative to body weight|in life observation-body weight-body weight|in life observation-food consumption-food efficiency|pathology gross-intestine large-distended|in life observation-mortality-mortality|pathology gross-gallbladder-distended|pathology gross-intestine large-[other]|pathology microscopic-ovary-hemangiosarcoma; dose_level=2; study_year=1996; study_citation=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =55 | mg/kg bw/day | mouse (cd1) | oral | 0 week to 104 week | CHR | study_id=6109; toxval_study_source_id=studyid6109_Adult_F0_M_systemic; toxval_effect_list=pathology microscopic-intestine large-inflammation|pathology gross-ear-lesion(s) (nos)|in life observation-body weight-body weight gain|organ weight-liver-absolute|pathology microscopic-intestine large-metaplasia|pathology gross-liver-mass|pathology microscopic-liver-hemosiderosis|in life observation-clinical signs-swelling|pathology microscopic-intestine large-hyperplasia|pathology microscopic-liver-hypertrophy|pathology microscopic-liver-lipofuscin deposits|pathology microscopic-liver-nuclear alteration|pathology microscopic-gallbladder-hyperplasia|pathology gross-gallbladder-distended|in life observation-mortality-mortality|pathology gross-skin-reduced size|organ weight-testes-absolute|hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|pathology microscopic-intestine large-squamous cell carcinoma|in life observation-food consumption-food efficiency|pathology gross-intestine large-[other]|pathology gross-intestine large-mass|pathology microscopic-gallbladder-papilloma|hematology-hematocrit (hct)-hematocrit (hct)|pathology microscopic-liver-inflammation|pathology microscopic-gallbladder-dilatation|pathology gross-intestine large-discolored|pathology microscopic-liver-hemangiosarcoma|in life observation-food consumption-food consumption|pathology microscopic-skin-depletion|organ weight-testes-relative to body weight|pathology gross-testes-reduced size|hematology-hemoglobin (hgb)-hemoglobin (hgb)|pathology gross-intestine large-distended|in life observation-body weight-body weight|pathology microscopic-spleen-hematopoietic cell proliferation|pathology gross-intestine large-enlarged|pathology gross-intestine large-prolapse; dose_level=1; study_year=1996; study_citation=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =45.3 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 0 week to 105 week | CHR | study_id=6110; toxval_study_source_id=studyid6110_Adult_F0_F_systemic; toxval_effect_list=in life observation-mortality-mortality|in life observation-body weight-body weight|organ weight-liver-absolute|pathology microscopic-liver-hemangiosarcoma|in life observation-food consumption-food efficiency|clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk); dose_level=2; study_year=1996; study_citation=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LEL | =275 | mg/kg bw/day | dog (beagle) | oral | 0 day to 90 day | SUB | study_id=6126; toxval_study_source_id=studyid6126_Adult_F0_F_systemic; toxval_effect_list=in life observation-body weight-body weight gain; dose_level=2; study_year=1966; study_citation=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs (Imperial Chemical Industries Limited, Industrial Hygiene Research Laboratories Report No. IHR, September 1966.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LOAEL | =75 | mg/kg bw/day | dog (beagle; beagle) | oral | 0 week to 52 week | CHR | study_id=6107; toxval_study_source_id=studyid6107_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-tremors|clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|in life observation-clinical signs-reduced activity|in life observation-clinical signs-abnormal gait; dose_level=3; study_year=1995; study_citation=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LOAEL | =167 | mg/kg bw/day | mouse (cd1) | oral | 0 week to 104 week | CHR | study_id=6109; toxval_study_source_id=studyid6109_Adult_F0_M_systemic; toxval_effect_list=in life observation-body weight-body weight gain|pathology microscopic-liver-hemosiderosis|pathology microscopic-liver-hypertrophy|pathology microscopic-intestine large-inflammation|pathology microscopic-liver-lipofuscin deposits|pathology microscopic-liver-nuclear alteration; dose_level=2; study_year=1996; study_citation=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | LOAEL | >126.1 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 0 week to 105 week | CHR | study_id=6110; toxval_study_source_id=studyid6110_Adult_F0_F_NA; dose_level=3; study_year=1996; study_citation=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =77 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F0_F_systemic; toxval_effect_list=in life observation-body weight-body weight|in life observation-food consumption-food efficiency; dose_level=2; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =23 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F0_M_systemic; toxval_effect_list=organ weight-epididymis-nos|organ weight-kidney-nos|in life observation-food consumption-food efficiency|in life observation-body weight-body weight; dose_level=1; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =79.2 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 10 weeks (premating) to 2 generation | MGR | study_id=2360; toxval_study_source_id=studyid2360_Adult_F1_F_systemic; toxval_effect_list=pathology microscopic-kidney-hydronephrosis|pathology microscopic-kidney-foreign body|in life observation-food consumption-food efficiency; dose_level=2; study_year=1995; study_citation=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =20 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | dermal | 0 day to 21 day | SAC | study_id=6103; toxval_study_source_id=studyid6103_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-scabbing|in life observation-clinical signs-erythema|pathology microscopic-skin-infiltration cellular|pathology microscopic-skin-edema; dose_level=1; study_year=1993; study_citation=Lees, D and AM Leah. 1993. PHMB: 21-day dermal toxicity study in the rat. Zeneca Central Tox Lab, Study no. LR0559. MRID 43047701.; dsstox_substance_id=DTXSID2035726; admin_method=Topical; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | >0 | mg/kg bw/day | dog (beagle; beagle) | oral | 0 week to 52 week | CHR | study_id=6107; toxval_study_source_id=studyid6107_Adult_F0_F_systemic; toxval_effect_list=pathology gross-skin-mass|in life observation-mortality-mortality|in life observation-clinical signs-skin ulceration|pathology gross-oral mucosa-mass|in life observation-clinical signs-reduced activity|pathology microscopic-kidney-concretion|pathology microscopic-nerve-mineralization|in life observation-clinical signs-fur (altered appearance)|in life observation-clinical signs-abnormal gait|pathology microscopic-liver-inclusion body intracytoplasmic|pathology gross-stomach-discolored|pathology gross-skin-discolored|in life observation-clinical signs-tremors|pathology gross-uterus-discolored|in life observation-clinical signs-scabbing|pathology microscopic-liver-hypertrophy|pathology microscopic-liver-pigmentation|in life observation-clinical signs-emaciation|clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|pathology microscopic-skin-inflammation; dose_level=0; study_year=1995; study_citation=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =69 | mg/kg bw/day | mouse (cd1) | oral | 0 week to 104 week | CHR | study_id=6109; toxval_study_source_id=studyid6109_Adult_F0_F_systemic; toxval_effect_list=pathology gross-skin-reduced size|in life observation-mortality-mortality|pathology microscopic-intestine large-inflammation|pathology microscopic-intestine large-hyperplasia|pathology gross-intestine large-distended|in life observation-food consumption-food efficiency|in life observation-body weight-body weight|hematology-hematocrit (hct)-hematocrit (hct)|pathology microscopic-skin-depletion|pathology microscopic-ovary-hemangiosarcoma|pathology gross-intestine large-[other]|pathology gross-ear-lesion(s) (nos)|pathology microscopic-intestine large-metaplasia|pathology microscopic-liver-nuclear alteration|pathology gross-liver-mass|hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|pathology gross-gallbladder-distended|pathology microscopic-spleen-hemangiosarcoma|pathology microscopic-intestine large-squamous cell carcinoma|pathology gross-intestine large-enlarged|pathology microscopic-gallbladder-dilatation|in life observation-clinical signs-swelling|pathology microscopic-liver-lipofuscin deposits|pathology microscopic-liver-inflammation|organ weight-adrenal gland-absolute|hematology-hemoglobin (hgb)-hemoglobin (hgb)|organ weight-adrenal gland-relative to body weight|pathology microscopic-spleen-hematopoietic cell proliferation|in life observation-body weight-body weight gain|pathology microscopic-liver-hemosiderosis|pathology microscopic-gallbladder-hyperplasia|pathology microscopic-liver-hypertrophy|in life observation-food consumption-food consumption|organ weight-liver-absolute|pathology microscopic-liver-hemangiosarcoma; dose_level=1; study_year=1996; study_citation=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =14.9 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 0 week to 105 week | CHR | study_id=6110; toxval_study_source_id=studyid6110_Adult_F0_F_systemic; toxval_effect_list=organ weight-liver-absolute|pathology microscopic-liver-hemangiosarcoma|in life observation-food consumption-food efficiency|clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk)|in life observation-mortality-mortality|in life observation-body weight-body weight|organ weight-liver-relative to body weight; dose_level=1; study_year=1996; study_citation=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =36.3 | mg/kg bw/day | rat (sprague dawley; Alpk: APSD) | oral | 0 week to 105 week | CHR | study_id=6110; toxval_study_source_id=studyid6110_Adult_F0_M_systemic; toxval_effect_list=organ weight-liver-relative to body weight|pathology microscopic-liver-fatty change|clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk)|pathology microscopic-liver-spongiosis hepatis|in life observation-body weight-body weight|in life observation-food consumption-food efficiency|organ weight-liver-absolute; dose_level=2; study_year=1996; study_citation=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NEL | =137.5 | mg/kg bw/day | dog (beagle) | oral | 0 day to 90 day | SUB | study_id=6126; toxval_study_source_id=studyid6126_Adult_F0_F_systemic; toxval_effect_list=in life observation-body weight-body weight gain; dose_level=1; study_year=1966; study_citation=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs (Imperial Chemical Industries Limited, Industrial Hygiene Research Laboratories Report No. IHR, September 1966.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| ToxRefDB_ToxRefDB_v3_pod.csv | NOAEL | =37.5 | mg/kg bw/day | dog (beagle; beagle) | oral | 0 week to 52 week | CHR | study_id=6107; toxval_study_source_id=studyid6107_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-abnormal gait|pathology microscopic-liver-inclusion body intracytoplasmic|pathology gross-stomach-discolored|pathology gross-skin-discolored|pathology microscopic-nerve-mineralization|in life observation-clinical signs-fur (altered appearance)|in life observation-mortality-mortality|in life observation-clinical signs-skin ulceration|pathology microscopic-kidney-concretion|pathology gross-oral mucosa-mass|in life observation-clinical signs-reduced activity|pathology gross-skin-mass|pathology microscopic-skin-inflammation|pathology microscopic-liver-pigmentation|in life observation-clinical signs-emaciation|clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|pathology microscopic-liver-hypertrophy|in life observation-clinical signs-tremors|pathology gross-uterus-discolored|in life observation-clinical signs-scabbing; dose_level=2; study_year=1995; study_citation=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; dsstox_substance_id=DTXSID2035726; admin_method=Feed; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
ToxValDB_AU_DWG 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_AU_DWG | NOEL | =20 | mg/kg bw/day | Rabbit | oral | (developmental) | reproduction developmental | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c82db5e4b02565fc7d237c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.nhmrc.gov.au; SUBSOURCE_URL=https://www.nhmrc.gov.au/sites/default/files/documents/attachments/publications/Australian_Drinking_Water_Guidelines_ADWG_V3-8_Sep2022.pdf; TOXICOLOGICAL_EFFECT=maternotoxicity in pregnant rabbits; STUDY_GROUP=AU DWG:15951727:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_c3a8397d05993e9f88f63709a33b13c9 |
ToxValDB_EPA_OPP 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_EPA_OPP | PAD (RfD) | =0.2 | mg/kg bw/day | Human | oral | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/63d99625e4b02a0c3a37c5d8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/sdwa/2021-human-health-benchmarks-pesticides; YEAR=2021; ORIGINAL_YEAR=2021; STUDY_GROUP=EPA OPP_dup_HHBP_15789894_15789896:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_2fa3c50dac7acf3bef7fd3608145064b |
ToxValDB_ToxRefDB 22 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_ToxRefDB | LEL | =258.2 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-food consumption-food efficiency|systemic: in life observation-body weight-body weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption; STUDY_GROUP=ToxRefDB_dup_-_15693918_15693919_15693920_15693921:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_54b56001791f0da0eeee6fb37ffc1a34 |
| ToxValDB_ToxRefDB | LEL | =69.6 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: organ weight-epididymis-nos|systemic: organ weight-kidney-nos|systemic: in life observation-body weight-body weight|systemic: in life observation-food consumption-food efficiency; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15693922_15693923_15693924_15693925:M:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0149a29c47036433bd27ae36ddf04eb9 |
| ToxValDB_ToxRefDB | LEL | =270.5 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: pathology microscopic-kidney-foreign body|systemic: pathology microscopic-kidney-hydronephrosis|systemic: in life observation-food consumption-food efficiency; TOXICOLOGICAL_EFFECT_CATEGORY=food and/or water consumption|nonneoplastic histopathology; STUDY_GROUP=ToxRefDB_dup_-_15693926_15693927_15693928_15693929:F:F1adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d4fa2c6587721b00f05bebc306914f51 |
| ToxValDB_ToxRefDB | LEL | =60 | mg/kg bw/day | Rat | dermal | short-term; 21 days | short-term | LONG_REF=Lees, D & AM Leah. 1993. PHMB: 21-day dermal toxicity study in the rat. Zeneca Central Tox Lab, Study no. LR0559. MRID 43047701.; TITLE=PHMB: 21-day dermal toxicity study in the rat; AUTHOR=Lees, D & AM Leah; EXTERNAL_SOURCE_ID=6103; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=systemic: in life observation-clinical signs-scabbing|systemic: in life observation-clinical signs-erythema|systemic: pathology microscopic-skin-edema|systemic: pathology microscopic-skin-infiltration cellular; STUDY_GROUP=ToxRefDB_dup_-_15710929_15710930_15710931_15710932:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_bc8b49ef9f05a4a53068c8e838498796 |
| ToxValDB_ToxRefDB | LEL | =40 | mg/kg bw/day | Rabbit | oral | short-term (developmental); 13 days | reproduction developmental | LONG_REF=Brammer, A. 1993. Polyhexamethylene biguanide: Developmental toxicity study in the rabbit. Zeneca Central Tox Lab., Study no. RBO 614. MRID 42865901.; TITLE=Polyhexamethylene biguanide: Developmental toxicity study in the rabbit; AUTHOR=Brammer, A; EXTERNAL_SOURCE_ID=6106; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=reproductive: offspring survival early-birth index-birth index|reproductive: reproductive performance-implantations-implantations|reproductive: reproductive performance-estrous cycle-corpora lutea|reproductive: reproductive performance-aborted-aborted|reproductive: reproductive performance-preimplantation loss-preimplantation loss; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ToxRefDB_dup_-_15710937_15710938:F:F0adult-pregnancy; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_575ce294626617f276d389dcba38741c |
| ToxValDB_ToxRefDB | LEL | =7.5 | mg/kg bw/day | Dog | oral | chronic; 52 weeks | chronic | LONG_REF=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; TITLE=Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6107; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-clinical signs-fur (altered appearance)|systemic: pathology gross-skin-mass|systemic: pathology gross-uterus-discolored|systemic: in life observation-clinical signs-emaciation|systemic: pathology microscopic-liver-pigmentation|systemic: in life observation-clinical signs-tremors|systemic: pathology microscopic-nerve-mineralization|systemic: in life observation-clinical signs-scabbing|systemic: clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|systemic: in life observation-clinical signs-abnormal gait|systemic: in life observation-mortality-mortality|systemic: pathology microscopic-skin-inflammation|systemic: pathology gross-skin-discolored|systemic: pathology gross-oral mucosa-mass|systemic: in life observation-clinical signs-reduced activity|systemic: pathology microscopic-kidney-concretion|systemic: pathology gross-stomach-discolored|systemic: pathology microscopic-liver-inclusion body intracytoplasmic|systemic: pathology microscopic-liver-hypertrophy|systemic: in life observation-clinical signs-skin ulceration; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|clinical signs|gross pathology|mortality/survival|nonneoplastic histopathology; STUDY_GROUP=ToxRefDB_dup_-_15710949_15710950_15710951:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8e1e97b40678f7ed3ccf8f879ccb97b3 |
| ToxValDB_ToxRefDB | LEL | =217 | mg/kg bw/day | Mouse | oral | chronic; 104 weeks | chronic | LONG_REF=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; TITLE=Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice; AUTHOR=Milburn G.M; EXTERNAL_SOURCE_ID=6109; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: pathology microscopic-intestine large-metaplasia|systemic: pathology gross-liver-mass|systemic: pathology microscopic-liver-hypertrophy|systemic: pathology microscopic-liver-nuclear alteration|systemic: pathology microscopic-liver-inflammation|systemic: pathology gross-ear-lesion(s) (nos)|systemic: hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|systemic: organ weight-liver-absolute|systemic: hematology-hemoglobin (hgb)-hemoglobin (hgb)|systemic: pathology microscopic-skin-depletion|systemic: hematology-hematocrit (hct)-hematocrit (hct)|systemic: pathology gross-skin-reduced size|systemic: pathology microscopic-liver-lipofuscin deposits|systemic: pathology microscopic-liver-hemosiderosis|systemic: in life observation-body weight-body weight gain|systemic: pathology microscopic-intestine large-inflammation|systemic: pathology microscopic-gallbladder-dilatation|systemic: pathology microscopic-intestine large-hyperplasia|systemic: in life observation-body weight-body weight|systemic: pathology gross-gallbladder-distended|systemic: pathology microscopic-liver-hemangiosarcoma|systemic: in life observation-food consumption-food consumption|systemic: organ weight-adrenal gland-absolute|systemic: pathology microscopic-gallbladder-hyperplasia|systemic: in life observation-food consumption-food efficiency|systemic: pathology gross-intestine large-[other]|systemic: pathology microscopic-ovary-hemangiosarcoma|systemic: pathology microscopic-spleen-hematopoietic cell proliferation|systemic: in life observation-clinical signs-swelling|systemic: pathology gross-intestine large-distended|systemic: pathology gross-intestine large-enlarged|systemic: pathology microscopic-intestine large-squamous cell carcinoma|systemic: pathology microscopic-spleen-hemangiosarcoma|systemic: in life observation-mortality-mortality|systemic: organ weight-adrenal gland-relative to body weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical signs|food and/or water consumption|gross pathology|hematology|mortality/survival|nonneoplastic histopathology|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710956_15710957_15710958_15710959:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_3f89de2672bf99f0902ade6308e585f4 |
| ToxValDB_ToxRefDB | LEL | =55 | mg/kg bw/day | Mouse | oral | chronic; 104 weeks | chronic | LONG_REF=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; TITLE=Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice; AUTHOR=Milburn G.M; EXTERNAL_SOURCE_ID=6109; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: pathology microscopic-intestine large-inflammation|systemic: organ weight-liver-absolute|systemic: in life observation-clinical signs-swelling|systemic: pathology gross-ear-lesion(s) (nos)|systemic: in life observation-body weight-body weight gain|systemic: pathology microscopic-intestine large-hyperplasia|systemic: pathology microscopic-liver-hypertrophy|systemic: pathology microscopic-intestine large-metaplasia|systemic: pathology gross-liver-mass|systemic: pathology microscopic-liver-nuclear alteration|systemic: pathology microscopic-liver-hemosiderosis|systemic: pathology microscopic-liver-lipofuscin deposits|systemic: pathology microscopic-gallbladder-hyperplasia|systemic: pathology gross-intestine large-[other]|systemic: pathology gross-intestine large-mass|systemic: hematology-hematocrit (hct)-hematocrit (hct)|systemic: pathology microscopic-gallbladder-papilloma|systemic: pathology microscopic-liver-inflammation|systemic: pathology microscopic-gallbladder-dilatation|systemic: pathology gross-gallbladder-distended|systemic: pathology gross-intestine large-distended|systemic: in life observation-mortality-mortality|systemic: pathology gross-intestine large-discolored|systemic: pathology gross-skin-reduced size|systemic: organ weight-testes-absolute|systemic: pathology microscopic-liver-hemangiosarcoma|systemic: in life observation-body weight-body weight|systemic: hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|systemic: in life observation-food consumption-food consumption|systemic: pathology microscopic-spleen-hematopoietic cell proliferation|systemic: pathology microscopic-skin-depletion|systemic: organ weight-testes-relative to body weight|systemic: pathology microscopic-intestine large-squamous cell carcinoma|systemic: pathology gross-intestine large-enlarged|systemic: pathology gross-intestine large-prolapse|systemic: pathology gross-testes-reduced size|systemic: in life observation-food consumption-food efficiency|systemic: hematology-hemoglobin (hgb)-hemoglobin (hgb); TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical signs|food and/or water consumption|gross pathology|hematology|mortality/survival|nonneoplastic histopathology|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710960_15710961_15710962:M:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_4befb5bb06554af366e4d741a13d0027 |
| ToxValDB_ToxRefDB | LEL | =45.3 | mg/kg bw/day | Rat | oral | chronic; 105 weeks | chronic | LONG_REF=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; TITLE=Polyhexamethylene biguanide: 2-year feeding study in rats; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6110; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: in life observation-mortality-mortality|systemic: in life observation-body weight-body weight|systemic: pathology microscopic-liver-hemangiosarcoma|systemic: clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk)|systemic: in life observation-food consumption-food efficiency|systemic: organ weight-liver-absolute; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical chemistry|food and/or water consumption|mortality/survival|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710963_15710964_15710965_15710966:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0df19c733d350a9f1c3abe2877d106ef |
| ToxValDB_ToxRefDB | LEL | =275 | mg/kg bw/day | Dog | oral | subchronic; 90 days | subchronic | LONG_REF=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs (Imperial Chemical Industries Limited, Industrial Hygiene Research Laboratories Report No. IHR, September 1966.; TITLE=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs; AUTHOR=Imperial Chemical Industries Limited; EXTERNAL_SOURCE_ID=6126; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1966; ORIGINAL_YEAR=1966; TOXICOLOGICAL_EFFECT=systemic: in life observation-body weight-body weight gain; TOXICOLOGICAL_EFFECT_CATEGORY=body weight; STUDY_GROUP=ToxRefDB_dup_-_15710991_15710992_15710993_15710994:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_29cc5938aa713ae379f772410ec2b1d4 |
| ToxValDB_ToxRefDB | LOAEL | =75 | mg/kg bw/day | Dog | oral | chronic; 52 weeks | chronic | LONG_REF=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; TITLE=Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6107; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-clinical signs-tremors|systemic: clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|systemic: in life observation-clinical signs-abnormal gait|systemic: in life observation-clinical signs-reduced activity; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|clinical signs; STUDY_GROUP=ToxRefDB_dup_-_15710949_15710950_15710951:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_03ce4592deca9e2a6915cb79c52f4576 |
| ToxValDB_ToxRefDB | LOAEL | =167 | mg/kg bw/day | Mouse | oral | chronic; 104 weeks | chronic | LONG_REF=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; TITLE=Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice; AUTHOR=Milburn G.M; EXTERNAL_SOURCE_ID=6109; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: in life observation-body weight-body weight gain|systemic: pathology microscopic-liver-hypertrophy|systemic: pathology microscopic-intestine large-inflammation|systemic: pathology microscopic-liver-nuclear alteration|systemic: pathology microscopic-liver-hemosiderosis|systemic: pathology microscopic-liver-lipofuscin deposits; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|nonneoplastic histopathology; STUDY_GROUP=ToxRefDB_dup_-_15710960_15710961_15710962:M:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a9ecb385529e1ce77054d6011883a9ad |
| ToxValDB_ToxRefDB | LOAEL | >126.1 | mg/kg bw/day | Rat | oral | chronic; 105 weeks | chronic | LONG_REF=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; TITLE=Polyhexamethylene biguanide: 2-year feeding study in rats; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6110; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; STUDY_GROUP=ToxRefDB_dup_-_15710963_15710964_15710965_15710966:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b9ff89ceb4a1a46c362d9308cb5415c1 |
| ToxValDB_ToxRefDB | NEL | =77 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-body weight-body weight|systemic: in life observation-food consumption-food efficiency; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption; STUDY_GROUP=ToxRefDB_dup_-_15693918_15693919_15693920_15693921:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_3bc793f04b662abad4d12715b55addce |
| ToxValDB_ToxRefDB | NEL | =23 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-body weight-body weight|systemic: organ weight-kidney-nos|systemic: in life observation-food consumption-food efficiency|systemic: organ weight-epididymis-nos; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15693922_15693923_15693924_15693925:M:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ba77734bb65e333269e035d5b99c1fee |
| ToxValDB_ToxRefDB | NEL | =79.2 | mg/kg bw/day | Rat | oral | chronic (developmental) | reproduction developmental | LONG_REF=PMRA; Milburn, G.M. (1995)Polyhexamethylene Biguanide: Multigeneration Study in the Rat. Sudy performed by Zeneca Central Toxicology Laboratory Study Nos: RR0621/F0; RR0621/F1. Study Completed March 8, 1995. Unpublished. MRID # 43617401.; TITLE=Polyhexamethylene Biguanide: Multigeneration Study in the Rat; AUTHOR=Milburn, G.M; EXTERNAL_SOURCE_ID=2360; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: in life observation-food consumption-food efficiency|systemic: pathology microscopic-kidney-foreign body|systemic: pathology microscopic-kidney-hydronephrosis; TOXICOLOGICAL_EFFECT_CATEGORY=food and/or water consumption|nonneoplastic histopathology; STUDY_GROUP=ToxRefDB_dup_-_15693926_15693927_15693928_15693929:F:F1adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0c8ca0f9fccc9fa8204e84d08b84e2df |
| ToxValDB_ToxRefDB | NEL | =20 | mg/kg bw/day | Rat | dermal | short-term; 21 days | short-term | LONG_REF=Lees, D & AM Leah. 1993. PHMB: 21-day dermal toxicity study in the rat. Zeneca Central Tox Lab, Study no. LR0559. MRID 43047701.; TITLE=PHMB: 21-day dermal toxicity study in the rat; AUTHOR=Lees, D & AM Leah; EXTERNAL_SOURCE_ID=6103; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=systemic: in life observation-clinical signs-scabbing|systemic: in life observation-clinical signs-erythema|systemic: pathology microscopic-skin-infiltration cellular|systemic: pathology microscopic-skin-edema; STUDY_GROUP=ToxRefDB_dup_-_15710929_15710930_15710931_15710932:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_307605357839d4b0c72c88fbcf976652 |
| ToxValDB_ToxRefDB | NEL | =69 | mg/kg bw/day | Mouse | oral | chronic; 104 weeks | chronic | LONG_REF=Milburn G.M. (1996) Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ. Laboratory Study No. PM0937. June 21, 1996. MRID 44074201. Unpublished; TITLE=Polyhexamethylene Biguanide: Two Year Oncogenicity Study in Mice; AUTHOR=Milburn G.M; EXTERNAL_SOURCE_ID=6109; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: hematology-hematocrit (hct)-hematocrit (hct)|systemic: organ weight-adrenal gland-relative to body weight|systemic: pathology gross-skin-reduced size|systemic: in life observation-mortality-mortality|systemic: pathology microscopic-spleen-hemangiosarcoma|systemic: pathology microscopic-skin-depletion|systemic: pathology microscopic-intestine large-squamous cell carcinoma|systemic: pathology gross-intestine large-enlarged|systemic: pathology microscopic-gallbladder-dilatation|systemic: pathology microscopic-intestine large-inflammation|systemic: in life observation-clinical signs-swelling|systemic: pathology microscopic-intestine large-hyperplasia|systemic: pathology gross-intestine large-distended|systemic: pathology microscopic-spleen-hematopoietic cell proliferation|systemic: in life observation-body weight-body weight gain|systemic: pathology microscopic-liver-hemosiderosis|systemic: pathology microscopic-ovary-hemangiosarcoma|systemic: pathology microscopic-liver-lipofuscin deposits|systemic: pathology gross-intestine large-[other]|systemic: pathology gross-ear-lesion(s) (nos)|systemic: in life observation-food consumption-food efficiency|systemic: pathology microscopic-liver-inflammation|systemic: pathology microscopic-intestine large-metaplasia|systemic: pathology microscopic-gallbladder-hyperplasia|systemic: pathology microscopic-liver-hypertrophy|systemic: pathology microscopic-liver-nuclear alteration|systemic: pathology gross-liver-mass|systemic: organ weight-adrenal gland-absolute|systemic: hematology-hemoglobin (hgb)-hemoglobin (hgb)|systemic: in life observation-food consumption-food consumption|systemic: hematology-erythrocyte (rbc) count differential-erythrocyte (rbc)|systemic: organ weight-liver-absolute|systemic: pathology gross-gallbladder-distended|systemic: pathology microscopic-liver-hemangiosarcoma|systemic: in life observation-body weight-body weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical signs|food and/or water consumption|gross pathology|hematology|mortality/survival|nonneoplastic histopathology|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710956_15710957_15710958_15710959:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_e37d370629439bf35e67f9bf97f4e83e |
| ToxValDB_ToxRefDB | NEL | =14.9 | mg/kg bw/day | Rat | oral | chronic; 105 weeks | chronic | LONG_REF=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; TITLE=Polyhexamethylene biguanide: 2-year feeding study in rats; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6110; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: pathology microscopic-liver-hemangiosarcoma|systemic: in life observation-body weight-body weight|systemic: in life observation-food consumption-food efficiency|systemic: in life observation-mortality-mortality|systemic: clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk)|systemic: organ weight-liver-relative to body weight|systemic: organ weight-liver-absolute; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical chemistry|food and/or water consumption|mortality/survival|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710963_15710964_15710965_15710966:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a10affe3bd4890e7d8a59c1a17d4dfd9 |
| ToxValDB_ToxRefDB | NEL | =36.3 | mg/kg bw/day | Rat | oral | chronic; 105 weeks | chronic | LONG_REF=Horner, SA. (1996) Polyhexamethylene biguanide: 2-year feeding study in rats. Zeneca Central Tox Lab, Alderley Park, Macclesfield, Cheshire, UK. Lab Project ID CTL/P/4663, Study no. PR0936, June 5, 1996. MRID 44059301.; TITLE=Polyhexamethylene biguanide: 2-year feeding study in rats; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6110; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1996; ORIGINAL_YEAR=1996; TOXICOLOGICAL_EFFECT=systemic: in life observation-food consumption-food efficiency|systemic: in life observation-body weight-body weight|systemic: pathology microscopic-liver-fatty change|systemic: clinical chemistry-alkaline phosphatase (alp/alk)-alkaline phosphatase (alp/alk)|systemic: organ weight-liver-absolute|systemic: pathology microscopic-liver-spongiosis hepatis|systemic: organ weight-liver-relative to body weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|clinical chemistry|food and/or water consumption|nonneoplastic histopathology|organ weight; STUDY_GROUP=ToxRefDB_dup_-_15710967_15710968_15710969_15710970:M:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1c9f02b17acf159a6903d3e72bed1e86 |
| ToxValDB_ToxRefDB | NEL | =137.5 | mg/kg bw/day | Dog | oral | subchronic; 90 days | subchronic | LONG_REF=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs (Imperial Chemical Industries Limited, Industrial Hygiene Research Laboratories Report No. IHR, September 1966.; TITLE=Ninety-Day Oral Toxicity of Antibacterial 9073-Beagle Dogs; AUTHOR=Imperial Chemical Industries Limited; EXTERNAL_SOURCE_ID=6126; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1966; ORIGINAL_YEAR=1966; TOXICOLOGICAL_EFFECT=systemic: in life observation-body weight-body weight gain; TOXICOLOGICAL_EFFECT_CATEGORY=body weight; STUDY_GROUP=ToxRefDB_dup_-_15710991_15710992_15710993_15710994:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_507ff09edf708a3d3a0567920bd4adfa |
| ToxValDB_ToxRefDB | NOAEL | =37.5 | mg/kg bw/day | Dog | oral | chronic; 52 weeks | chronic | LONG_REF=Horner, SA. (1995) Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs. Zeneca Central Tox Lab, Cheshire, UK. Lab report no. CTL/P/4488; Study no. PD0947. MRID 43620501.; TITLE=Polyhexamethylene biguanide: 1 year dietary toxicity study in dogs; AUTHOR=Horner, SA; EXTERNAL_SOURCE_ID=6107; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=systemic: pathology microscopic-skin-inflammation|systemic: in life observation-mortality-mortality|systemic: in life observation-clinical signs-abnormal gait|systemic: pathology microscopic-liver-pigmentation|systemic: in life observation-clinical signs-skin ulceration|systemic: pathology microscopic-liver-hypertrophy|systemic: pathology microscopic-liver-inclusion body intracytoplasmic|systemic: pathology gross-stomach-discolored|systemic: pathology microscopic-kidney-concretion|systemic: pathology gross-oral mucosa-mass|systemic: in life observation-clinical signs-reduced activity|systemic: pathology gross-skin-discolored|systemic: pathology microscopic-nerve-mineralization|systemic: in life observation-clinical signs-tremors|systemic: in life observation-clinical signs-emaciation|systemic: pathology gross-uterus-discolored|systemic: pathology gross-skin-mass|systemic: clinical chemistry-alanine aminotransferase (alt/sgpt)-alanine aminotransferase (alt/sgpt)|systemic: in life observation-clinical signs-scabbing|systemic: in life observation-clinical signs-fur (altered appearance); TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|clinical signs|gross pathology|mortality/survival|nonneoplastic histopathology; STUDY_GROUP=ToxRefDB_dup_-_15710949_15710950_15710951:F:F0adult; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ab45e3197680f8a693b72cc2e0e5bfc0 |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 59 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | % | mouse | oral | 2-year | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20; DOSE=Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.; EFFECT=clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr; CITATION=Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B; CITATION_NUMBERS=[47,2,57,10,20]; REFERENCE=Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution B","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","duration":"2-year","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Guideline: / (range-finding study for 2 year drinking water study) Species/strain: Mouse, C57Bl/10JfAP/Alpk Group size: 10/sex/dose Test substance: PHMB, 20 % aqueous solution Batch: D4097 Purity: no details given Vehicle: sterilised water Dose levels: 0, 0.1, 0.3, 0.6, 1.2 mg/ml Route: oral Administration: dr","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"20","page":32,"route":"oral","species":"mouse","study_id":"sccs_o_157_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20.2 | % | rat | oral | 2-year | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20.2; DOSE=Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.; EFFECT=ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /; CITATION=Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20; CITATION_NUMBERS=[48,410,5,20]; REFERENCE=Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","duration":"2-year","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 48 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive, 6 hr /","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"20.2","page":33,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 92.3 | mg/kg bw/d | mouse | oral | - | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=92.3; DOSE=r 6000 ppm at interim and/or terminal kill.; EFFECT=r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"r 6000 ppm at interim and/or terminal kill.","duration":"","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL. Results in mice: There were treatment-related effects on initial food consumption in males. Reduced body weights were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding stu","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"92.3","page":36,"route":"oral","species":"mouse","study_id":"sccs_o_157_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 224 | mg/kg bw/d | - | - | - | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=224; DOSE=ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.; EFFECT=ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","duration":"","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study.","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"224","page":36,"route":"","species":"","study_id":"sccs_o_157_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 54 | mg/kg bw/d | rat | - | - | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=54; DOSE=) as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.; EFFECT=) as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females); CITATION=Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; CITATION_NUMBERS=[52,81,82]; REFERENCE=Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm.","duration":"","effect":") as well as in the liver, kidney (males only) and testes of animals that received 4500/3000 ppm. There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"54","page":38,"route":"","species":"rat","study_id":"sccs_o_157_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 54 | mg/kg bw/d | rat | oral | 104 weeks | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=54; DOSE=There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment.; EFFECT=There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females) Route: oral Administration: diet Exposure period: 104 weeks GLP: yes Study period: 1992 – 1994, re; CITATION=Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; CITATION_NUMBERS=[52,81,82]; REFERENCE=Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment.","duration":"104 weeks","effect":"There were no histopathological changes in animals receiving 300 or 1500 ppm that were considered attributable to treatment. The elevated plasma alanine transaminase and aspartate transaminase activities in isolated animals receiving 300 or 1500 ppm, in the absence of any associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 52, 81, 82 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females) Route: oral Administration: diet Exposure period: 104 weeks GLP: yes Study period: 1992 – 1994, re","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"54","page":38,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =36 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT== 36; DOSE=SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...; EFFECT=SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was n; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","duration":"104 week","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was n","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 36","page":61,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 8.5 | % | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=8.5; DOSE=SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...; EFFECT=SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)...","duration":"104 week","effect":"SCCS/1535/14 2nd Revision of the opinion on the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Dir","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"8.5","page":61,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =3.1 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT== 3.1; DOSE=the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...; EFFECT=the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d...","duration":"104 week","effect":"the safety of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products _________________________________________________________________________________________ 61 Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.066555 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED = 46 3.3.14 Discussion Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Directive 98/8/EC for uses as a disinfectant and it is used as a preservati","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3.1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | - | - | oral | 2-year | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=unclear:clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46; DOSE=Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.; EFFECT=clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46; CITATION=Ref.: 46; CITATION_NUMBERS=[46]; REFERENCE=Ref.: 46; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 46","dose":"Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect.","duration":"2-year","effect":"clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"","noael_value":"unclear:clinical condition. Dose-related loss in bodyweight/body weight gain and reduced water and/or food consumption predominantly occurring during the first days of treatment (and recovery thereafter) were considered as a palatability effect. Further treatment-related findings consisted of increases in plasma cholesterol levels and ALP and AST activities at the highest dose tested, increased liver weight at 1 mg/ml and decreased liver weight at 2 mg/ml and a dose-related increase in kidney weight at all dose levels. No NOAEL could be derived from the study. A highest dose level of 1.0 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 46","page":42,"route":"oral","species":"","study_id":"sccs_o_1581_16_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20.2 | % | rat | oral | 2-year | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=20.2; DOSE=Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.; EFFECT=ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,; CITATION=Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20; CITATION_NUMBERS=[47,410,5,20]; REFERENCE=Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20","dose":"Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance.","duration":"2-year","effect":"ead on day 13. Dose-related initial loss of body weight, reduction in food and water consumption and continued reduction in body weight and water consumption were considered to be due to palatability of the substance. Changes considered to be treatment-related included a decrease in plasma ALT activity and a decrease in liver weight for males given 0.6 and 1.2 mg/ml and were most probably associated with the poor nutritional status. As effects on bodyweights and water consumption were present at all dose levels, a NOAEL could not be derived. A highest dose level of 0.3 mg/ml was recommended for the 2-year drinking water study. 0.1 mg/ml should be considered as LOAEL based on the results from this study. Ref.: 47 Dermal Guideline: / (similar to OECD TG 410) Species/strain: Rat, Alpk:APfSD (Wistar-derived) Group size: 5/sex/dose Test substance: Vantocil P (20.2 % aqueous solution of PHMB) Batch: ASG9112994 Purity: impurities < 0.76 % Vehicle: / Dose levels: 0, 20, 60, 200 mg PHMB/kg Route: dermal Administration: occlusive,","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"%","noael_value":"20.2","page":43,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 92.3 | mg/kg bw/d | - | oral | - | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=92.3; DOSE=r 6000 ppm at interim and/or terminal kill.; EFFECT=r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"r 6000 ppm at interim and/or terminal kill.","duration":"","effect":"r 6000 ppm at interim and/or terminal kill. As only limited histopathological examination was performed, the toxicological significance of macroscopic changes in the gastrointestinal tract, liver and hepatic lymph node in some terminal kill animals at 6000 ppm could not be assessed. It was concluded that a dose level of 2000 ppm would be suitable for use as the high dose level in a long-term dietary study. The authors considered 1000 ppm (corresponding to 83.9 mg/kg bw/d in males and 92.3 mg/kg bw/d in females) as NOAEL.","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"92.3","page":47,"route":"oral","species":"","study_id":"sccs_o_1581_16_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 224 | mg/kg bw/d | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=224; DOSE=ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.; EFFECT=ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in; CITATION=Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; CITATION_NUMBERS=[49,50,90,9073,25]; REFERENCE=Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB","dose":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm.","duration":"90-day","effect":"ghts were noted in males at 2000 ppm and marked effects on body weight gain were observed in males and females at 4000 ppm. The highest dose caused marked toxicity leading to termination of this group by day 11. There were no treatment-related effects on liver and kidney weights and no gross or histopathological findings. 4000 ppm was considered as the highest dose to be applied in a long-term feeding study. The authors considered 1000 ppm (corresponding to 162 mg/kg bw/d in males and 224 mg/kg bw/d in females) as NOAEL of this study. Ref.: 49, 50 An older, non-guideline compliant 90-day dietary study was performed with antibacterial 9073 (25 % aqueous solution of PHMB; Batch WEM/G/680) in Alderley Park Wistar Rats at dose levels of 0, 625 and 1250 ppm a.i. There was no mortality at any dose level. The dietary administration of 1250 ppm led to a retardation of body weight gain most likely due to reduced food consumption due to decreased palatability. At this dose level, deposits of an iron- pigment in","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"224","page":48,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 54 | mg/kg bw/d | rat | - | - | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=54; DOSE=The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females); CITATION=Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; CITATION_NUMBERS=[51,77,78]; REFERENCE=Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL","dose":"The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study.","duration":"","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 50 associated histopathological changes, were considered to be of no toxicological importance. The study authors considered 1500 ppm (54 mg/kg bw/d) as NOAEL of the study. Ref.: 51, 77, 78 SCCS comment SCCS is aware that RAC and ANSES agreed to this NOAEL. Guideline: Considered comparable to OECD TG 453 Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 64/sex/dose (12 animals/sex/dose used for interim kill) Test substance: Vantocil P ASG9112994, 20.2 % aqueous solution Batch: D4097 Purity: impurities < 0.76 % Dose levels: 0, 200, 600, 2000 ppm (corresponding to about 0, 12.1, 36.3, 126.1 mg/kg bw/day in males, 0, 14.9, 45.3, 162.3 mg/kg bw/day in females)","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"54","page":50,"route":"","species":"rat","study_id":"sccs_o_1581_16_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =36 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT== 36; DOSE=Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...; EFFECT=on to consumer exposure is considered to be insignificant for this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw; CITATION=Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4; CITATION_NUMBERS=[4,5,1]; REFERENCE=Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","duration":"104 week","effect":"on to consumer exposure is considered to be insignificant for this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 36","page":73,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 8.5 | % | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=8.5; DOSE=Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...; EFFECT=r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d; CITATION=Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4; CITATION_NUMBERS=[4,5,1]; REFERENCE=Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4","dose":"Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x...","duration":"104 week","effect":"r this product. Ref.: Add 4, 5 CALCULATION OF THE MARGIN OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"%","noael_value":"8.5","page":73,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =3.1 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT== 3.1; DOSE=OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...; EFFECT=OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d...","duration":"104 week","effect":"OF SAFETY (Dap= dermis+ receptor fluid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3.1","page":73,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =3.1 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT== 3.1; DOSE=uid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NO...; EFFECT=uid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"uid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NO...","duration":"104 week","effect":"uid+ 1SD) Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 258 + exposure from non-cosmetic use Absorption through the skin DAp (%) = 4.09 % Amount of cosmetic product applied daily A (g/d) = 17.4 g/d Concentration of ingredient in finished product C (%)= 0.1% Typical body weight of human = 60 kg Systemic exposure dose (SED) = A (g/d) x 1000 mg/g x C (%)/100 x Dap (%)/100 /60 = 0.012 mg/kg bw/d","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3.1","page":73,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =36 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT== 36; DOSE=0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:","duration":"104 week","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 36","page":74,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 8.5 | % | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=8.5; DOSE=0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:","duration":"104 week","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"%","noael_value":"8.5","page":74,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =3.1 | mg/kg bw/d | rat | oral | 104 week | - | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT== 3.1; DOSE=0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Biocides Regulation (EU) No 528/ 2012 and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion:","duration":"104 week","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 74 + exposure form non-cosmetic use : 0.00161 mg/kg/d = 0.01361 mg/kg bw/d No adverse observed effect level NOAEL = 36 mg/kg bw/d (104 week oral rat study) Corrected NOAEL based on 8.5 % oral absorption = 3.1 mg/kg bw/d MOS = Corrected NOAEL/SED Margin of Safety adjusted NOAEL/SED = 227 3.6 Discussion: Physico-chemical properties PHMB is a polymer which in is neat form represents a solid/powder of > 94.2 % purity. It has a good water solubility of around 40 % and is usually marketed as an appr. 20 % aqueous solution. Average molecular weights in the range between 2670 and 4216 Da have been reported. Molecular weight distribution of the polymer was not provided. Function and uses PHMB is supported under Biocides Regulation (EU) No 528/ 2012 and","endpoint":"","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3.1","page":74,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20; DOSE=After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.; EFFECT=the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat; CITATION=Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref; CITATION_NUMBERS=[30]; REFERENCE=Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","duration":"30 d","effect":"the application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 65) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand Group size: 1 male animal Test substance: PHMB DS6274 Batch: PC 100-02 Purity: reference is given to a non-attached appendix; submission states: 96 % Vehicle: / Dose levels: 0.1 ml neat substance Administration: instillation in the conjunctival sac of the right eye GLP: yes Study period: 2002, test report 2003 Neat","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":17,"route":"dermal","species":"rat","study_id":"sccs_o_157_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=15; DOSE=An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.; EFFECT=cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul; CITATION=Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed; CITATION_NUMBERS=[17]; REFERENCE=Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","duration":"chronic","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascul","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"15","page":48,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 20 | mg/kg bw/d | rat | dermal | 30 d | carcinogenicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=20; DOSE=After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.; EFFECT=e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand; CITATION=Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref; CITATION_NUMBERS=[30]; REFERENCE=Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref","dose":"After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals.","duration":"30 d","effect":"e application of solid PHMB (96 %) to the skin of rabbits according to OECD 404 induced no signs of skin irritation. After dermal application of a 20 % aqueous PHMB solution moderate erythema was recorded 24 hr after application on the treated area of all three animals. The reaction was completely reversible between days 6 and 8. No oedema was observed with the 20 % aqueous solution. Ref.: 30 SCCS comment on skin irritation Skin irritation was also observed in a 30 d repeat-dose study in rats (Ref.: 64) with a NOAEL of 20 mg/kg bw/d and in dermal carcinogenicity study in mice (Ref. 17). 3.3.2.2 Mucous membrane irritation / Eye irritation Guideline: OECD TG 405 (EU B.5) Species/strain: Rabbit, White New Zealand","endpoint":"carcinogenicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":20,"route":"dermal","species":"rat","study_id":"sccs_o_1581_16_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 15 | mg/kg bw/d | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=15; DOSE=An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.; EFFECT=cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu; CITATION=Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed; CITATION_NUMBERS=[17]; REFERENCE=Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed","dose":"An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study.","duration":"chronic","effect":"cterised by a severe hepatitis in some animals. There was a slight increase in the incidence of liver tumors observed at 30 mg/mouse/day (four in the control and ten at 30 mg/mouse/day). This was statistically significant only in the case of liver tumors of endothelial origin (both benign and malignant; two in the control and six at 30 mg/mouse/day), when the data were pooled over the whole study period and both sexes. There was no evidence of such an effect in animals receiving 0.6 or 6.0 mg/mouse/day. An overall NOAEL of 0.6 mg/mouse/day corresponding to 15 mg/kg bw/d was derived from this study. Ref.: 17 SCCS conclusion on carcinogenicity In a rat oral chronic toxicity/carcinogenicity assay, an increased incidence of haemangiosarcomas (statistically not significant) was observed at the highest dose of 2000 ppm PHMB. Recently it has been concluded (Ref. 30) that evidence from the chronic rat study is not sufficient to demonstrate a clear treatment-related effect. In an oral study in mice, PHMB increased the incidence of vascu","endpoint":"carcinogenicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"15","page":65,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 200 | ppm | mouse | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=200; DOSE=ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.; EFFECT=ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80; CITATION=Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; CITATION_NUMBERS=[46,414,47,49]; REFERENCE=Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level.","duration":"developmental","effect":"ber of implantation sites, pre- and post-implantation losses were not influenced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"200","page":50,"route":"","species":"mouse","study_id":"sccs_o_157_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | ppm | mouse | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=1000; DOSE=nced by the test substance at any dose level.; EFFECT=nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80; CITATION=Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; CITATION_NUMBERS=[46,414,47,49]; REFERENCE=Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nced by the test substance at any dose level.","duration":"developmental","effect":"nced by the test substance at any dose level. No dose-related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 46 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"1000","page":50,"route":"","species":"mouse","study_id":"sccs_o_157_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=40; DOSE=ions were not influenced by the test substance at any dose level.; EFFECT=ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev; CITATION=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; CITATION_NUMBERS=[45,33,34,414,20]; REFERENCE=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"ions were not influenced by the test substance at any dose level.","duration":"developmental","effect":"ions were not influenced by the test substance at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose lev","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"40","page":51,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=10; DOSE=There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.; EFFECT=at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf; CITATION=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; CITATION_NUMBERS=[45,33,34,414,20]; REFERENCE=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","duration":"developmental","effect":"at any dose level. Fetal weight and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously perf","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg/d","noael_value":"10","page":51,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=10; DOSE=There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.; EFFECT=and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously performed range-finding studies. Test; CITATION=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; CITATION_NUMBERS=[45,33,34,414,20]; REFERENCE=Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20","dose":"There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d.","duration":"developmental","effect":"and sex distribution was not affected by treatment. There were indications of slight retardation of ossification from examination of forelimb and hindlimb digits and numbers of caudal vertebrae at 20 and 40 mg/kg bw/d. The incidence of wide fontanels and poorly ossified frontal bones in the skull at these dose levels indicated also retarded ossification. The study authors concluded that based on the conditions of this study the maternal NOAEL was 40 mg/kg bw/d and the developmental NOAEL was 10 mg/kg/d. the latter NOAEL was confirmed in a reevaluation of the study. Ref.: 45, 33, 34 Rabbits Guideline: Comparable to OECD 414 Species/strain: Rabbit, White New Zealand Group size: 20 females/dose Test substance: PHBM (20.2 % aqueous solution) Batch: D 4097 Purity: impurities < 0.76 % Dose levels: 0, 10, 20, 40 mg/kg bw/d Vehicle: deionised water Route: oral (gavage) Exposure period: gestation days 8 – 20 GLP: yes Study period: 1993 Dose levels were selected based on two previously performed range-finding studies. Test","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg/d","noael_value":"10","page":51,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20; DOSE=The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.; EFFECT=sing period began after implantation. The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance-related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormali; CITATION=Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab; CITATION_NUMBERS=[9,7,8,780,5642,14,15]; REFERENCE=Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab","dose":"The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","duration":"developmental","effect":"sing period began after implantation. The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance-related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormali","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":52,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=40; DOSE=ostimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.; EFFECT=ostimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance-related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in the; CITATION=Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab; CITATION_NUMBERS=[9,7,8,780,5642,14,15]; REFERENCE=Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rab","dose":"ostimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","duration":"developmental","effect":"ostimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance-related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 9, 7, 8 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in the","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"40","page":52,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 200 | ppm | mouse | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=200; DOSE=nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.; EFFECT=nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD; CITATION=Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; CITATION_NUMBERS=[45,414,47,49]; REFERENCE=Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level.","duration":"developmental","effect":"nide (PHMB) - Submission III 54 implantation losses were not influenced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD","endpoint":"developmental toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"ppm","noael_value":"200","page":54,"route":"","species":"mouse","study_id":"sccs_o_1581_16_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | ppm | mouse | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=1000; DOSE=ced by the test substance at any dose level.; EFFECT=ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin; CITATION=Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; CITATION_NUMBERS=[45,414,47,49]; REFERENCE=Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups","dose":"ced by the test substance at any dose level.","duration":"developmental","effect":"ced by the test substance at any dose level. No dose- related effects were observed on fetal or litter weights. There was an increase in extra ribs at the high dose which was considered to be a consequence of maternal toxicity at this dose level. There was no further substance-related effect on fetal morphology including ossification of the skeleton in any of the treated groups. Based on reduced food consumption and body weight, a maternal NOAEL of 200 ppm (corresponding to about 13 mg/kg bw/d) and a developmental NOAEL of 1000 ppm (corresponding to about 54 mg/kg bw/d) were derived. Ref.: 45 Mice Guideline: Comparable to OECD 414 Species/strain: Mouse/Alderly Park strain Group size: 47 – 49 mice in dosed groups; 25 control animals Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 10, 20, 40 mg/kg bw/d (expressed as a.i.) Vehicle: 0.5 % aqueous Tween 80 Exposure period: gestation days 6 – 15 (mating day taken as GD 0) GLP: / Study period: 1976 Results In dams at the top dose, the followin","endpoint":"developmental toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"ppm","noael_value":"1000","page":54,"route":"","species":"mouse","study_id":"sccs_o_1581_16_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=20; DOSE=The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.; EFFECT=ing period began after implantation. The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnorm; CITATION=Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand; CITATION_NUMBERS=[33,34,44,780,5642,14,15]; REFERENCE=Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","duration":"developmental","effect":"ing period began after implantation. The postimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnorm","endpoint":"developmental toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":54,"route":"oral","species":"rabbit","study_id":"sccs_o_1581_16_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 40 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=40; DOSE=stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.; EFFECT=stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in; CITATION=Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand; CITATION_NUMBERS=[33,34,44,780,5642,14,15]; REFERENCE=Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand","dose":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment.","duration":"developmental","effect":"stimplantation loss at 20 mg/kg was not seen at the highest dose and in the absence of dose-response relationship, this effect was not attributed to treatment. There was no evidence for teratogenicity. The percentage of fetuses with unossified 5th sternebrae or with fused 4th and 5th sternebrae was increased at the top dose, but in the absence of changes in fetal development associated with PHMB, this finding was considered as unlikely to be substance- related. A maternal NOAEL of 20 mg/kg bw/d and a developmental NOAEL of 40 mg/kg bw/d were derived from this study. Ref.: 33, 34, 44 In an older, non GLP- and non-Guideline compliant teratology study, test material IL 780, SDGM 5642 was investigated in groups of 14 – 15 mated female White New Zealand rabbits at dose levels of 0, 10, 40 and 160 mg/kg bw/d after oral (gavage) administration. The administration of 10 and 40 mg/kg bw/day had no effect on pregnancy or on maternal and fetal survival. The number of soft tissue or skeletal abnormalities did not differ from the number in","endpoint":"developmental toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"40","page":54,"route":"oral","species":"rabbit","study_id":"sccs_o_1581_16_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 36 | mg/kg bw/d | rat | oral | 2-year | genotoxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=36; DOSE=In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.; EFFECT=pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","duration":"2-year","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD TG 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Replicates: Triplicate plates Test substance: Vantocil IB, 19.6 % aqueous solution Batch: Bx2125","endpoint":"genotoxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"36","page":39,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 200 | mg/kg bw/day | rabbit | dermal | - | irritation | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=200; DOSE=Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.; EFFECT=istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu; CITATION=Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; CITATION_NUMBERS=[65,23]; REFERENCE=Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","duration":"","effect":"istry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":33,"route":"dermal","species":"rabbit","study_id":"sccs_o_157_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 20 | mg/kg bw/day | rabbit | oral | - | irritation | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20; DOSE=of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.; EFFECT=of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex; CITATION=Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; CITATION_NUMBERS=[65,23]; REFERENCE=Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","duration":"","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound- related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 65 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":33,"route":"oral","species":"rabbit","study_id":"sccs_o_157_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 20 | % | rat | inhalation | 5 days | irritation | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=20; DOSE=4/sex/dose Test substance:; EFFECT=al significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non-resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study. Ref.: 76, 77, 78 Guideline: / (precedes guideline program) Species/strain: Rat, Alderley Park SPF albino strain Group size: 4/sex/dose Test substance: Vantocil IB (20 % aqueous solution of PHMB) Batch: Std Sample BX 16, 17, 18, 19 ADOH. 4848/73 Purity: not stated Vehicle: Dose levels: 0.025; 0.25; 2.75, 12.5 and 26 mg/m3 Route: inhalation Administration: snout-only: 6 hr/day; 5 days/week Duration: 3 weeks GLP: / Study period: 1976 Animals were exposed as indicated to; CITATION=Ref.: 76, 77, 78 Guideline: / (precedes guideline program) Species/strain: Rat, Alderley Park SPF albino strain Group size: 4/sex/dose Test substance: Vantocil IB (20 % aqueous solution; CITATION_NUMBERS=[76,77,78,4,20]; REFERENCE=Ref.: 76, 77, 78 Guideline: / (precedes guideline program) Species/strain: Rat, Alderley Park SPF albino strain Group size: 4/sex/dose Test substance: Vantocil IB (20 % aqueous solution; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 76, 77, 78 Guideline: / (precedes guideline program) Species/strain: Rat, Alderley Park SPF albino strain Group size: 4/sex/dose Test substance: Vantocil IB (20 % aqueous solution","dose":"4/sex/dose Test substance:","duration":"5 days","effect":"al significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non-resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study. Ref.: 76, 77, 78 Guideline: / (precedes guideline program) Species/strain: Rat, Alderley Park SPF albino strain Group size: 4/sex/dose Test substance: Vantocil IB (20 % aqueous solution of PHMB) Batch: Std Sample BX 16, 17, 18, 19 ADOH. 4848/73 Purity: not stated Vehicle: Dose levels: 0.025; 0.25; 2.75, 12.5 and 26 mg/m3 Route: inhalation Administration: snout-only: 6 hr/day; 5 days/week Duration: 3 weeks GLP: / Study period: 1976 Animals were exposed as indicated to","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"20","page":35,"route":"inhalation","species":"rat","study_id":"sccs_o_157_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 26 | - | rat | - | - | irritation | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=unclear:three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15; EFFECT=three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15; CITATION=Ref.: 15; CITATION_NUMBERS=[15]; REFERENCE=Ref.: 15; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 15","dose":"","duration":"","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":35,"route":"","species":"rat","study_id":"sccs_o_157_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 200 | mg/kg bw/day | rabbit | dermal | - | irritation | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=200; DOSE=Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.; EFFECT=mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu; CITATION=Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; CITATION_NUMBERS=[64,23]; REFERENCE=Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","duration":"","effect":"mistry. Gross pathology and histopathology revealed no evidence of systemic toxicity. Signs of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occlu","endpoint":"irritation","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":44,"route":"dermal","species":"rabbit","study_id":"sccs_o_1581_16_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 20 | mg/kg bw/day | rabbit | oral | - | irritation | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=20; DOSE=of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.; EFFECT=of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex; CITATION=Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; CITATION_NUMBERS=[64,23]; REFERENCE=Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the fo","dose":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day.","duration":"","effect":"of skin irritation were dose-dependently noted at 60 or 200 mg/kg bw/day. At 60 mg/kg bw/day there was slight irritation, which in most animals had regressed by the end of the study. At 200 mg/kg bw/day all the animals showed moderate irritation, which in most animals persisted until the end of the study. The irritation noted during the study was confirmed microscopically and was indicative of a compound-related effect. The NOAEL for systemic toxicity was 200 mg/kg bw/day, the highest dose level investigated. The NOAEL for local dermal irritation was 20 mg/kg bw/day. Ref.: 64 In an earlier study, comparable results have been obtained: PHMB (Vantocil IB) was applied to a group of six female albino rabbits daily to their shorn backs for 23 hr in the form of 1.0 ml of a 12,000 ppm solution. The skin was then washed with soap and water and the solution was re-applied one hour later for a total of 21 daily applications. The skin was not occluded and oral contamination was prevented by means of a plastic collar. At the end of the ex","endpoint":"irritation","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":44,"route":"oral","species":"rabbit","study_id":"sccs_o_1581_16_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 0.257 | - | - | - | - | irritation | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=unclear:significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.; EFFECT=significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"","duration":"","effect":"significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","endpoint":"irritation","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"","noael_value":"unclear:significance. PHMB exposure to concentrations of 0.257 or 2.47 mg/m³ resulted in some transient histopathological changes in the larynx and trachea that were characteristic of exposure to a respiratory tract irritant. These changes were clearly reversible following cessation of exposure. Some bodyweight changes were also present at these exposure concentrations. Some non - resolving histopathology changes in the lungs (pneumonitis and bronchitis) were limited to the highest exposure concentration of 2.47 mg/m³. A NOAEL of 0.0239 mg/m³ was derived from the study.","page":45,"route":"","species":"","study_id":"sccs_o_1581_16_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 26 | - | rat | - | - | irritation | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=unclear:three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15; EFFECT=three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15; CITATION=Ref.: 15; CITATION_NUMBERS=[15]; REFERENCE=Ref.: 15; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 15","dose":"","duration":"","effect":"three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","endpoint":"irritation","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"","noael_value":"unclear:three days of exposure, all animals lost weight and their intake of food and water was very low. One female rat died towards the end of the fourth exposure and the remainder died overnight. Exposure of rats to 26.0 mg/m3 resulted in severe nasal irritation and dyspnoea. During the first three days of exposure all animals lost weight and their intake of food and water was very low. As in the test with 12.5 mg/m3 exposure, one female rat died towards the end of the fourth exposure and the remainder died overnight. A NOAEL of 0.025 mg/m3 was derived from this study. Ref.: 15","page":46,"route":"","species":"rat","study_id":"sccs_o_1581_16_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=2000; DOSE=Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.; EFFECT=e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc; CITATION=Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; CITATION_NUMBERS=[53,13,21,30,3,2]; REFERENCE=Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB.","duration":"3 weeks","effect":"e in the interpretation of this equivocal result. Following the PWG review and confirmed by a further independent expert, it was concluded that the overall weight of evidence indicated that the slightly higher number of high dose animals having vascular neoplasms of the liver is not associated with the dietary administration of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 53, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subc","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"2000","page":39,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=54; DOSE=In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.; EFFECT=t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","duration":"subchronic","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"54","page":39,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=54; DOSE=In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.; EFFECT=eagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters. However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","duration":"subchronic","effect":"eagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters. However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"54","page":63,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 2000 | ppm | rat | oral | 3 weeks | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=2000; DOSE=Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch; CITATION=Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; CITATION_NUMBERS=[52,13,21,30,3,2]; REFERENCE=Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water","dose":"Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively.","duration":"3 weeks","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 51 of PHMB. RAC concluded that evidence from this rat study is not sufficient to conclude a clear treatment-related effect with respect to vascular tumours. Based on the findings of this study, a NOAEL of 2000 ppm PHMB in diet corresponding to 36 and 45 mg/kg bw/d was derived for male and female animals, respectively. Ref.: 52, 13, 21, 30 Summary repeat-dose toxicity Repeat-dose toxicity studies using different durations (3 weeks up to 2 years) and different application routes (oral – drinking water; oral – diet; dermal; inhalation) have been performed in different animal species (rat, mouse, Beagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subch","endpoint":"repeated dose toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"ppm","noael_value":"2000","page":51,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=54; DOSE=In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.; EFFECT=t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","duration":"subchronic","effect":"t-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters (ALP, ALT, ASP). However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","endpoint":"repeated dose toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw","noael_value":"54","page":51,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 54 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=54; DOSE=In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.; EFFECT=eagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters. However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived.","duration":"subchronic","effect":"eagle dog). Short-term and subchronic oral studies mainly served as range finder for studies of longer duration. Subchronic dietary studies performed in rats and mice caused reductions in body weight and effects on weight gain. In rats, the kidney was identified as target organ; there were changes in renal function as well as changes in some plasma parameters. However, interpretation of the dietary subchronic studies was hampered by limited histopathologic examination. In a dietary 12-month study in beagle dogs, a NOAEL of 54 mg/kg bw was derived. At the highest dose tested there were adverse effects on scrotal skin, indications of liver impairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further,","endpoint":"repeated dose toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw","noael_value":"54","page":76,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1581 | - | - | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=unclear:SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.; DOSE=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.; EFFECT=SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","duration":"","effect":"SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","endpoint":"repeated dose toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1581/16 Final Opinion on Polyaminopropyl Biguanide (PHMB) - Submission III 78 Special investigation / Safety evaluation SCCS used repeated dose toxicity for NOAEL setting and did not make a calculation based on carcinogenic effects as PHMB is not a genotoxic carcinogen.","page":78,"route":"","species":"","study_id":"sccs_o_1581_16_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 600 | ppm | rat | oral | 9 week | reproductive toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=600; DOSE=weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.; EFFECT=weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio; CITATION=Ref.: 73 3; CITATION_NUMBERS=[73,3]; REFERENCE=Ref.: 73 3; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 73 3","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","duration":"9 week","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating perio","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"600","page":49,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=79; DOSE=eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.; EFFECT=eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP; CITATION=Ref.: 73 3; CITATION_NUMBERS=[73,3]; REFERENCE=Ref.: 73 3; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 73 3","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","duration":"9 week","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 73 3.3.8.2 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"79","page":49,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_157; REPORT_TITLE=OPINION ON the safety of poly(hexamethylene) biguanide hydrochloride (PHMB); OPINION_NUMBER=SCCS/1535/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=13 July 2015; VALUE_TEXT=130; DOSE=_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.; EFFECT=_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin; CITATION=Ref.: 94 3; CITATION_NUMBERS=[94,3]; REFERENCE=Ref.: 94 3; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 94 3","dose":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","duration":"Developmental","effect":"_________________________________________________________________________________________ 50 Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 94 3.3.8.3 Developmental Toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (matin","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"130","page":50,"route":"oral","species":"rat","study_id":"sccs_o_157_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 36 | mg/kg bw/d | rat | oral | 2-year | reproductive toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=36; DOSE=In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.; EFFECT=pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"32289-58-0","citation":"","dose":"In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively.","duration":"2-year","effect":"pairment and histopathological findings in skin, liver and – for males only – in kidneys and testes. In a dietary 2-year rat study NOAELs of 36 and 45 mg/kg bw/d were derived for male and female animals, respectively. At the highest dose tested, most prominent findings were reductions in body weight, changes in plasma parameters, the incidence of hepatocyte fat and spongiosis hepatis. Further, the incidence of haemangiosarcomas was increased at the highest dose tested. From the latter study, the SCCS will take the NOAEL of 36 mg/kg bw/d for MoS calculation /safety evaluation. 3.3.6 Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity Two generation reproduction toxicity Guideline: / Species/strain: Rat/Alpk:APfSD (Wistar derived) Group size: 26/sex/dose Test substance: Vantocil P, 20.2% aqueous PHMB solution Batch: D4097 Purity: 0.76 % impurities Dose levels: 0, 200, 600, 2000 ppm Route: Oral (diet) Exposure period: Two successive generations including 10 week premating period GLP: Yes","endpoint":"reproductive toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"36","page":51,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 600 | ppm | rat | oral | 9 week | reproductive toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=600; DOSE=weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.; EFFECT=weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen; CITATION=Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs; CITATION_NUMBERS=[70,83,4,10,20]; REFERENCE=Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","duration":"9 week","effect":"weights of livers and kidneys in adults receiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd gen","endpoint":"reproductive toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"ppm","noael_value":"600","page":52,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 79 | mg/kg bw/d | rat | oral | 9 week | reproductive toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=79; DOSE=eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.; EFFECT=eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197; CITATION=Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs; CITATION_NUMBERS=[70,83,4,10,20]; REFERENCE=Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test subs","dose":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels.","duration":"9 week","effect":"eiving 2000 ppm Vantocil P and in F2 offspring at all dose levels. In the absence of related pathological changes these were considered not to be biologically significant. There was no evidence of an effect of Vantocil P on any of the reproductive parameters assessed. There was no evidence of an effect of PHMB on any of the pup parameters measured including growth and development. Based on decreased body weights in parental animals the authors derived a systemic, parental NOAEL of 600 ppm (70 – 79 mg/kg bw/d). The NOAEL for reproductive and offspring effects was 2000 ppm (239 – 270 mg/kg bw/d). Ref.: 70 Other data on fertility and reproduction toxicity Guideline: US EPA 83-4 with some deviations Species/strain: Rat, Sprague-Dawley Group size: 10 males, 20 females/dose Test substance: PHBM, 20 % aqueous solution Batch: ADGM 5642 Purity: / Dose levels: 0, 200, 650, 1300 ppm (dietary levels adjusted for 20 % a.i.) Route: oral, diet Exposure period: 9 week premating period until 3rd generation GLP: preceded GLP Study period: 197","endpoint":"reproductive toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"79","page":52,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 130 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_1581_16; REPORT_TITLE=OPINION ON Polyaminopropyl Biguanide (PHMB); OPINION_NUMBER=SCCS/1581/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=07 April 2017; VALUE_TEXT=130; DOSE=of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.; EFFECT=of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d; CITATION=Ref.: 90 3; CITATION_NUMBERS=[90,3]; REFERENCE=Ref.: 90 3; DETAILS_JSON={"cas_number":"32289-58-0","citation":"Ref.: 90 3","dose":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups.","duration":"Developmental","effect":"of the various reproductive indices, sex ratios, and body weight data of the foetuses taken by Caesarean section and the offspring maintained through weaning revealed no meaningful differences between the control and treated groups. Necropsy of weanlings did not reveal any compound-related gross pathology. No findings indicative of embryotoxicity or teratogenicity were noted in the fetuses taken by Caesarean section. The dose level of 1300 ppm (corresponding to approximately 130 mg/kg bw/d) was concluded to be the NOAEL for general toxicity, reproductive function and fertility as well as for pre- and postnatal development. Ref.: 90 3.3.6.2 Developmental toxicity Rats Guideline: Comparable to OECD 414 Species/strain: Rat/Alderly Park strain Group size: 20 rats per group evaluated Test substance: Baquacil SB (20 % aqueous PHMB solution) Batch: no data Dose levels: 0, 200, 1000, 2000 ppm (expressed as a.i.) (corresponding to about 0, 13, 54, 112 mg/kg bw/day) Route: Oral (diet) Exposure period: gestation days 1 – 20 (mating d","endpoint":"reproductive toxicity","ingredient":"Polyaminopropyl Biguanide, is currently listed in Annex V","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"130","page":53,"route":"oral","species":"rat","study_id":"sccs_o_1581_16_noael_016"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 4XI6112496 | UNII | - | - | - | polymer | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"polymer","unii_code":"4XI6112496"} |
| openFDA substances | FDA UNII substance identifier | 4XI6112496 | UNII | - | - | - | polymer | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"polymer","unii_code":"4XI6112496"} |
| openFDA substances | FDA UNII substance identifier | 4XI6112496 | UNII | - | - | - | polymer | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"polymer","unii_code":"4XI6112496"} |
| openFDA substances | FDA UNII substance identifier | 4XI6112496 | UNII | - | - | - | polymer | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"polymer","unii_code":"4XI6112496"} |