NOAEL Studies Cosmetic Ingredient

Diethylene Glycol NOAEL Studies

INCI: DIETHYLENE GLYCOL

CAS: 111-46-6

Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.

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COSMOS_DB 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB LOAEL 100 mg/kg bw/day rat oral 225 day Chronic SCCS; Gaunt, IF, et al. (1976) In BIBRA Inf Bull 15: 217-218
COSMOS_DB NOAEL 50 mg/kg bw/day rat oral 225 day Chronic SCCS; Gaunt, IF, et al. (1976) In BIBRA Inf Bull 15: 217-218
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI (group) =0.5 mg/kg bw/day Consumers - - ADI (group) EFSA ANS - 2017 - OutputID 2967 - Consumers - Safety of the proposed amendment of the specifications for the food additive polyvinyl alcohol-polyethylene glycol-graft-co-polymer (E 1209) - doi:10.2903/j.efsa.2017.4865
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI (group) =0.5 mg/kg bw/day Consumers - - ADI (group) EFSA ANS - 2017 - OutputID 2967 - Consumers - Safety of the proposed amendment of the specifications for the food additive polyvinyl alcohol-polyethylene glycol-graft-co-polymer (E 1209) - doi:10.2903/j.efsa.2017.4865
NTP_ICE_acute_oral 9 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 =15600 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_1039; row=13190; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =15650 mg/kg bw Rat oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1040; row=13191; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =16600 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_1042; row=13192; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =20760 mg/kg bw Rat (Male) oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1043; row=13193; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =28733 mg/kg bw Rat oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1044; row=13194; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =30186 mg/kg bw Rat (Male) oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1045; row=13195; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =16547 mg/kg bw Rat (Male/Female) oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1041; row=13196; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =12565 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_1037; row=13197; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =12570 mg/kg bw Rat (Female) oral acute Rat Acute Oral Toxicity JRC AcutoxBase (undated); record_id=acute_oral_1038; row=13198; data_type=In Vivo; mixture=Chemical; chemical_name=Diethylene glycol; preferred_name=Diethylene glycol; dtxsid=DTXSID8020462; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID8020462; source_file=acute_oral.xlsx
NTP_ICE_adme_parameters 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_adme_parameters Fu 0.97 fraction Human - - Measured; httk, Human Plasma Fraction Unbound sheet=Data; excel_row=3090; Record_ID=adme_parameters_2032; Data_Type=Measured; DTXSID=DTXSID8020462; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.97; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, ECVAM; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_dart 5 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_dart LOEL 4472 mg/kg bw/day Rat Oral - In Vivo; DART, In life observation sheet=Data; excel_row=116577; Record_ID=dart_24214; Data_Type=In Vivo; DTXSID=DTXSID8020462; Assay=DART, In life observation; Endpoint=LOEL; Response=4472; Response_Unit=mg/kg/day; Species=Rat; Strain=Other; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0013123;CUI;Water consumption|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0013123;CUI;Water consumption; Reference=ToxRefDB v2 , ID = 5350; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_dart LOEL 4472 mg/kg bw/day Rat Oral - In Vivo; DART, Developmental malformation sheet=Data; excel_row=116578; Record_ID=dart_24303; Data_Type=In Vivo; DTXSID=DTXSID8020462; Assay=DART, Developmental malformation; Endpoint=LOEL; Response=4472; Response_Unit=mg/kg/day; Species=Rat; Strain=Other; 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;C0443239;CUI;Interrupted; Reference=ToxRefDB v2 , ID = 5350; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_dart LOEL 4472 mg/kg bw/day Rat Oral - In Vivo; DART, Developmental malformation sheet=Data; excel_row=116579; Record_ID=dart_24304; Data_Type=In Vivo; DTXSID=DTXSID8020462; Assay=DART, Developmental malformation; Endpoint=LOEL; Response=4472; Response_Unit=mg/kg/day; Species=Rat; Strain=Other; 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;C0205394;CUI;Other; Reference=ToxRefDB v2 , ID = 5350; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_dart LOEL 2795 mg/kg bw/day Mouse Oral - In Vivo; DART, In life observation sheet=Data; excel_row=116580; Record_ID=dart_24417; Data_Type=In Vivo; DTXSID=DTXSID8020462; Assay=DART, In life observation; Endpoint=LOEL; Response=2795; Response_Unit=mg/kg/day; Species=Mouse; Strain=Crl:CD-1(ICR)BR; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0013123;CUI;Water consumption|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0013123;CUI;Water consumption; Reference=ToxRefDB v2 , ID = 5351; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_dart LOEL 11180 mg/kg bw/day Mouse Oral - In Vivo; DART, In life observation sheet=Data; excel_row=116581; Record_ID=dart_24438; Data_Type=In Vivo; DTXSID=DTXSID8020462; Assay=DART, In life observation; Endpoint=LOEL; Response=11180; Response_Unit=mg/kg/day; Species=Mouse; Strain=Crl:CD-1(ICR)BR; Sex=Male/Female; Life_Stage=Fetal; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0005910;CUI;Body Weight|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0751992;CUI;Fetal Weight; Reference=ToxRefDB v2 , ID = 5351; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
NTP_ICE_endocrine 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_endocrine Model Score 0 unitless - - - ARPathway2016; AR Pathway Model, Antagonist sheet=Integrated_approaches; excel_row=7952; RecordID=ARPathway2016_569; DatasetName=ARPathway2016; DTXSID=DTXSID8020462; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID8020462; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID8020462
SCCS_vision_codex 32 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral 225 days NOAEL study {"citation":"Ref.: 4 3","dose":"Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).","effect":"male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats","page":9,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_001"}
SCCS_vision_codex NOAEL =200 mg/kg/day rat - - NOAEL study {"citation":"(ref. 6)","dose":"As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.","effect":"y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - - genotoxicity {"citation":"(Ref. 7)","dose":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","effect":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_004"}
SCCS_vision_codex NOAEL =559 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-","dose":"For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.","effect":"ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]","page":13,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_006"}
SCCS_vision_codex NOAEL =1118 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat","dose":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.","effect":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant","page":14,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_007"}
SCCS_vision_codex NOAEL =612 mg/kg bw/day rat oral - reproductive toxicity {"dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","effect":"ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with","page":22,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_010"}
SCCS_vision_codex NOAEL =1.6 mg/kg bw/day - dermal chronic NOAEL study {"dose":"The lethal dose has only been estimated in a few studies.","effect":"rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,","page":23,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_011"}
SCCS_vision_codex NOAEL =10 - rat - - NOAEL study {"effect":"Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_012"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral 225 days NOAEL study {"citation":"Ref.: 4 3","dose":"Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).","effect":"male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats","page":9,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_001"}
SCCS_vision_codex NOAEL =200 mg/kg/day rat - - NOAEL study {"citation":"(ref. 6)","dose":"As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.","effect":"y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - - genotoxicity {"citation":"(Ref. 7)","dose":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","effect":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_004"}
SCCS_vision_codex NOAEL =559 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-","dose":"For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.","effect":"ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]","page":13,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_006"}
SCCS_vision_codex NOAEL =1118 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat","dose":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.","effect":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant","page":14,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_007"}
SCCS_vision_codex NOAEL =612 mg/kg bw/day rat oral - reproductive toxicity {"dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","effect":"ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with","page":22,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_010"}
SCCS_vision_codex NOAEL =1.6 mg/kg bw/day - dermal chronic NOAEL study {"dose":"The lethal dose has only been estimated in a few studies.","effect":"rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,","page":23,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_011"}
SCCS_vision_codex NOAEL =10 - rat - - NOAEL study {"effect":"Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_012"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral 225 days NOAEL study {"citation":"Ref.: 4 3","dose":"Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).","effect":"male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats","page":9,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_001"}
SCCS_vision_codex NOAEL =200 mg/kg/day rat - - NOAEL study {"citation":"(ref. 6)","dose":"As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.","effect":"y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - - genotoxicity {"citation":"(Ref. 7)","dose":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","effect":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_004"}
SCCS_vision_codex NOAEL =559 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-","dose":"For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.","effect":"ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]","page":13,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_006"}
SCCS_vision_codex NOAEL =1118 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat","dose":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.","effect":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant","page":14,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_007"}
SCCS_vision_codex NOAEL =612 mg/kg bw/day rat oral - reproductive toxicity {"dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","effect":"ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with","page":22,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_010"}
SCCS_vision_codex NOAEL =1.6 mg/kg bw/day - dermal chronic NOAEL study {"dose":"The lethal dose has only been estimated in a few studies.","effect":"rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,","page":23,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_011"}
SCCS_vision_codex NOAEL =10 - rat - - NOAEL study {"effect":"Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_012"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral 225 days NOAEL study {"citation":"Ref.: 4 3","dose":"Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).","effect":"male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats","page":9,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_001"}
SCCS_vision_codex NOAEL =200 mg/kg/day rat - - NOAEL study {"citation":"(ref. 6)","dose":"As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.","effect":"y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - - genotoxicity {"citation":"(Ref. 7)","dose":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","effect":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_004"}
SCCS_vision_codex NOAEL =559 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-","dose":"For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.","effect":"ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]","page":13,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_006"}
SCCS_vision_codex NOAEL =1118 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat","dose":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.","effect":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant","page":14,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_007"}
SCCS_vision_codex NOAEL =612 mg/kg bw/day rat oral - reproductive toxicity {"dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","effect":"ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with","page":22,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_010"}
SCCS_vision_codex NOAEL =1.6 mg/kg bw/day - dermal chronic NOAEL study {"dose":"The lethal dose has only been estimated in a few studies.","effect":"rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,","page":23,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_011"}
SCCS_vision_codex NOAEL =10 - rat - - NOAEL study {"effect":"Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","page":10,"pdf":"sccp_o_139.pdf","row_type":"noael_study","study_id":"sccp_o_139_noael_012"}
ToxValDB_DOE_Protective_Action_Criteria 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_DOE_Protective_Action_Criteria LEL =69445.6 mg/m3 Human inhalation - acute LONG_REF=U.S. Department of Energy (DOE) Protective Action Criteria (PAC). 2023. PAC Chemical Database. Updated 11 October 2023. Available: https://edms3.energy.gov/pac/ (Accessed November 16, 2023); TITLE=U.S. Department of Energy (DOE) Protective Action Criteria (PAC) Chemical Database; AUTHOR=U.S. Department of Energy; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65428efee4b045b9ff7cc432; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://edms3.energy.gov/pac/TeelDocs; YEAR=2012; ORIGINAL_YEAR=2012; STUDY_GROUP=DOE Protective Action Criteria:15514524:-:--; 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_854a26cf64f3886f0918c1cfb5ac00c1
ToxValDB_GESTIS_DNEL 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL local =60 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15630214_15630215:-:--; 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_c2cb090e84c5231c26e2e018bff09be6
ToxValDB_GESTIS_DNEL DNEL systemic =44 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15630214_15630215:-:--; 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_0d32b5488ac4a69981bd0e7758385a63
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 12 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 50 mg/kg bw/day rat oral 225 days - SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=50; DOSE=Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).; EFFECT=male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats; CITATION=Ref.: 4 3; CITATION_NUMBERS=[4,3]; REFERENCE=Ref.: 4 3; DETAILS_JSON={"cas_number":"111-46-6","citation":"Ref.: 4 3","dose":"Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day).","duration":"225 days","effect":"male and 10 female Wistar rats received 0.085, 0.17, and 2.0% DEG in the feed for 225 days. Oxalate crystals were found in the kidneys at 0.17% DEG (100 mg/kg bw/day). Kidney damage was observed at higher doses. It was assumed that the kidney damage was due to a result of the formation of oxalate crystals and that the kidney was the primary target organ. Effects in the liver were assumed to be due to secondary unspecific effects. Stones in the urinary bladder were observed at high doses. It was concluded that the NOAEL was 50 mg/kg bw/day. Ref.: 4 3.3.5.3. Chronic (> 12 months) toxicity A long term rat feeding study showed that 1% DEG in the diet over a two year period resulted in slight growth depression, a few calcium oxalate bladder stones, minimal kidney damage, and occasional liver damage. At 4% dietary level, there was increased mortality, a marked depression of growth rate, bladder stones, severe kidney damage, and moderate liver damage. Bladder tumours, mostly benign, occurred at 1,500 and 3,000 mg/kg/day in male rats","endpoint":"","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":9,"route":"oral","species":"rat","study_id":"sccp_o_139_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 200 mg/kg/day rat - - - SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=200; DOSE=As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.; EFFECT=y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg; CITATION=(ref. 6); CITATION_NUMBERS=[6]; REFERENCE=(ref. 6); DETAILS_JSON={"cas_number":"111-46-6","citation":"(ref. 6)","dose":"As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG.","duration":"","effect":"y 0.031% ethylene glycol. The French authority (ref. 6) points out that data on toxicity with DEG are rare in the scientific literature and that DEG and ethylene glycol have similar toxicity. However, quantitatively, DEG is less toxic than ethylene glycol. As a result, in the first instance, they used the dose-effect correlations relating to ethylene glycol to propose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg","endpoint":"","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":10,"route":"","species":"rat","study_id":"sccp_o_139_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1.6 mg/kg bw/day - dermal chronic - SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=1.6; DOSE=The lethal dose has only been estimated in a few studies.; EFFECT=rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"111-46-6","citation":"","dose":"The lethal dose has only been estimated in a few studies.","duration":"chronic","effect":"rd- degree burns following dermal exposure of DEG. The lethal dose has only been estimated in a few studies. The best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning. This dose is in agreement with the calculated dose (1200 mg/kg bw/day) from the Elixir Sulfanilamide disaster in USA in 1937. By using a safety factor of 1000 (10 for intraspecies variation, 10 for converting acute dose to chronic dose and 10 for converting LOAEL to NOAEL and considering the seriousness (death) of the effect). Thus, if the results from the mass poisonings are used, a dose of 1.6 mg/kg bw/day should be safe. Based on animal data, the TDI in the EU has been determined to be 0.5 mg/kg bw/day. This is in agreement with the value considered safe in the risk assessment by the German authorities. Thus, a maximum concentration of up to 0.1% DEG from impurities in ingredients like glycerine and polyethylene glycols in the finished cosmetic products is considered to be safe,","endpoint":"","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1.6","page":23,"route":"dermal","species":"","study_id":"sccp_o_139_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 10 - rat - - - SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=unclear:Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200; EFFECT=Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"111-46-6","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","endpoint":"","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 10: renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200","page":10,"route":"","species":"rat","study_id":"sccp_o_139_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 559 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=559; DOSE=For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.; EFFECT=ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]; CITATION=Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-; CITATION_NUMBERS=[11,25]; REFERENCE=Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-; DETAILS_JSON={"cas_number":"111-46-6","citation":"Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-","dose":"For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance.","duration":"developmental","effect":"ratios was unaffected. For all foetuses and female foetuses body weights were significantly reduced at 11,180 mg/kg bw/day, male foetal weights at the high dose were reduced but not with statistical significance. There were no statistically significant increases in the incidences of malformations or variations by category (external, visceral or skeletal) or in the incidences of individual malformations or variations. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over gestation days 6–15 was 559 mg/kg bw/day for maternal toxicity, and 2795 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in mice at any dosage. Ref.: 11 Rats Guideline: / Species/strain: Virgin male and virgin female Crl: CD (ICR) BR albino rats Group size: 25 timed pregnant per dose Test substance: Diethylene glycol Batch: TFJ-44408 PL26032 Purity: 99.87%, [ethylene glycol 0.02%, triethylene glycol 0.11%]","endpoint":"developmental toxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"559","page":13,"route":"oral","species":"rat","study_id":"sccp_o_139_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 1118 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=1118; DOSE=s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.; EFFECT=s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant; CITATION=Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat; CITATION_NUMBERS=[11,8,100,250,450]; REFERENCE=Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat; DETAILS_JSON={"cas_number":"111-46-6","citation":"Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestat","dose":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10.","duration":"developmental","effect":"s were increased in the 8944 mg/kg bw/day group; poorly ossified interparietal, poorly ossified thoracic centre #10 and #13, and bilobed thoracic centre #10. Also, split anterior arch of the atlas was increased in this high dosage group, but not with statistical significance. At 4472 mg/kg bw/day split anterior arch of the atlas and bilobed thoracic ossification centre #10 were increased with statistical significance. The authors concluded that under the conditions of these studies, the no-observed-effect- level (NOEL) for DEG given by gavage over GD 6–15 was 1118 mg/kg bw/day for maternal toxicity, and 1118 mg/kg bw/day for developmental toxicity (foetotoxicity). There were no indications of embryotoxicity or teratogenic effects in rats at any dosage. Ref.: 11 Rabbits Teratogenicity was evaluated in pregnant Dutch rabbits (8/group) exposed by inhalation to diethylene glycol at nominal concentrations of 0, 100, 250 or 450 ppm on gestation days (GD) 6-18. All surviving rabbits were sacrificed on GD 21. There were significant","endpoint":"developmental toxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1118","page":14,"route":"oral","species":"rat","study_id":"sccp_o_139_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies genotoxicity 50 mg/kg bw/day rat - - genotoxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=50; DOSE=Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.; EFFECT=opose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicol; CITATION=(Ref. 7); CITATION_NUMBERS=[7]; REFERENCE=(Ref. 7); DETAILS_JSON={"cas_number":"111-46-6","citation":"(Ref. 7)","dose":"Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","duration":"","effect":"opose a Toxicity Reference Value (TRV) for DEG. Given that the critical effect of ethylene glycol at repeated doses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicol","endpoint":"genotoxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":10,"route":"","species":"rat","study_id":"sccp_o_139_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies genotoxicity 200 mg/kg bw/day rat - - genotoxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=200; DOSE=ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.; EFFECT=ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur; CITATION=(Ref. 7); CITATION_NUMBERS=[7]; REFERENCE=(Ref. 7); DETAILS_JSON={"cas_number":"111-46-6","citation":"(Ref. 7)","dose":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref.","duration":"","effect":"ses is renal tubular damage, and that the NOAEL in the most sensitive species (rat) is 200 mg/kg/day (Ref. 7), applying factors of uncertainty of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimur","endpoint":"genotoxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":10,"route":"","species":"rat","study_id":"sccp_o_139_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies genotoxicity 200 mg/kg bw/day rat - - genotoxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=200; DOSE=100 in total) led to the proposal of a TRV of 2 mg/kg bw/day.; EFFECT=of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. DEG was negative in these; CITATION=(ref. 4); CITATION_NUMBERS=[4]; REFERENCE=(ref. 4); DETAILS_JSON={"cas_number":"111-46-6","citation":"(ref. 4)","dose":"100 in total) led to the proposal of a TRV of 2 mg/kg bw/day.","duration":"","effect":"of 10 for the rat-to-man extrapolation and a factor of 10 to take account of interpersonal variability in humans (i.e. 100 in total) led to the proposal of a TRV of 2 mg/kg bw/day. SCCP is of the opinion that for a safety assessment based on animal experiments, a NOAEL of 50 mg/kg bw/day (formation of calcium oxalate crystals in the rat bladder) (ref. 4) may be used. Since NOAEL in rat for ethylene glycol was 200 mg/kg bw/day, it seems unlikely that the presence of ethylene glycol as impurity in DEG should give a NOAEL lower than for ethylene glycol itself. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro DEG was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. DEG was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 µg/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. DEG was negative in these","endpoint":"genotoxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":10,"route":"","species":"rat","study_id":"sccp_o_139_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 50 mg/kg bw/day rat - - repeated dose toxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=50; DOSE=A daily dose of more than 0.5 mg/kg bw/day was considered unsafe.; EFFECT=the amount of oxalic acid in urine is increased. It is noted that in humans, oxalic acid is not increased, but that the hygroscopic swelling of the parenchymatous cells of the kidney tubule lumen is of concern and that the rat study in connection with a safety factor may be used. A daily dose of more than 0.5 mg/kg bw/day was considered unsafe. This value is also in agreement with accepted TDI in the EU. As stated in section 3.3.5, the SCCP considers that for safety assessment based on experimental animal data a NOAEL of 50 mg/kg bw/day (calcium oxalate crystals in rat bladder) may be used. This figure is in agreement with the German authority view, which was also based on animal data. However, since the repeated dose animal studies are old and of unknown quality, human data should have precedence over the animal data. As pointed out above, the best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning (ref. 24). By using a safety factor of 10, the; CITATION=(ref. 24); CITATION_NUMBERS=[24]; REFERENCE=(ref. 24); DETAILS_JSON={"cas_number":"111-46-6","citation":"(ref. 24)","dose":"A daily dose of more than 0.5 mg/kg bw/day was considered unsafe.","duration":"","effect":"the amount of oxalic acid in urine is increased. It is noted that in humans, oxalic acid is not increased, but that the hygroscopic swelling of the parenchymatous cells of the kidney tubule lumen is of concern and that the rat study in connection with a safety factor may be used. A daily dose of more than 0.5 mg/kg bw/day was considered unsafe. This value is also in agreement with accepted TDI in the EU. As stated in section 3.3.5, the SCCP considers that for safety assessment based on experimental animal data a NOAEL of 50 mg/kg bw/day (calcium oxalate crystals in rat bladder) may be used. This figure is in agreement with the German authority view, which was also based on animal data. However, since the repeated dose animal studies are old and of unknown quality, human data should have precedence over the animal data. As pointed out above, the best estimate for toxic effects resulting in death is probably the median estimated DEG dose of 1600 mg/kg bw/day from the Haiti poisoning (ref. 24). By using a safety factor of 10, the","endpoint":"repeated dose toxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":19,"route":"","species":"rat","study_id":"sccp_o_139_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 50 mg/kg bw/day rat oral - reproductive toxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=50; DOSE=SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.; EFFECT=ts is considered to be safe, when compared to safe limits derived from both human and animal data. 3.3.14. Discussion Physico-chemical specifications DEG is a colourless syrupy liquid, practically odourless with a sharply sweetish taste. It is highly hygroscopic. No information is available concerning stability. General toxicity The data on repeated toxicity of DEG are old and it can not be excluded that the presence of ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"111-46-6","citation":"","dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","duration":"","effect":"ts is considered to be safe, when compared to safe limits derived from both human and animal data. 3.3.14. Discussion Physico-chemical specifications DEG is a colourless syrupy liquid, practically odourless with a sharply sweetish taste. It is highly hygroscopic. No information is available concerning stability. General toxicity The data on repeated toxicity of DEG are old and it can not be excluded that the presence of ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/","endpoint":"reproductive toxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":22,"route":"oral","species":"rat","study_id":"sccp_o_139_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 612 mg/kg bw/day rat oral - reproductive toxicity SOURCE_SUBDIR=sccp_o_139; REPORT_TITLE=OPINION ON Diethylene glycol; OPINION_NUMBER=SCCP/1181/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=24 June 2008; VALUE_TEXT=612; DOSE=SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.; EFFECT=ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"111-46-6","citation":"","dose":"SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used.","duration":"","effect":"ethylene glycol as impurity in the DEG may have influenced the results. SCCP consider that a NOAEL of 50 mg/kg bw/day based on formation of calcium oxalate crystals in the rat bladder could be used. DEG at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect. No effects were observed at 0.35 % (612 mg/kg bw/day). The NOEL for DEG given by gavage over gestation days 6–15 was 559 mg/kg/day with the mouse and 1118 mg/kg bw/day for rats for maternal toxicity, and 2795 mg/kg/day with","endpoint":"reproductive toxicity","ingredient":"s with respect to their impact on consumer","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"612","page":22,"route":"oral","species":"rat","study_id":"sccp_o_139_noael_010"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 61BR964293 UNII - - - chemical {"approval_status":null,"molecular_formula":"C4H10O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"61BR964293"}
openFDA substances FDA UNII substance identifier 61BR964293 UNII - - - chemical {"approval_status":null,"molecular_formula":"C4H10O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"61BR964293"}
openFDA substances FDA UNII substance identifier 61BR964293 UNII - - - chemical {"approval_status":null,"molecular_formula":"C4H10O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"61BR964293"}
openFDA substances FDA UNII substance identifier 61BR964293 UNII - - - chemical {"approval_status":null,"molecular_formula":"C4H10O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"61BR964293"}