NOAEL Studies Preservative

Methylparaben NOAEL Studies

INCI: METHYLPARABEN

CAS: 99-76-3

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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CIR_vision_codex 36 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
CIR_vision_codex NOAEL =1000 mg/kg/d rat - - developmental toxicity {"citation":"10; 3; 100","dose":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...","effect":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_001"}
CIR_vision_codex NOAEL =160 mg/kg/d - - - developmental toxicity {"citation":"3; 100; 1,000","dose":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.","effect":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_002"}
CIR_vision_codex NOAEL =10000 ppm rat oral 8 weeks oral toxicity {"citation":"8; 71; 1,000","dose":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...","effect":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1)","page":26,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_003"}
CIR_vision_codex NOAEL =100 mg/ kg rat oral 8 weeks reproductive toxicity {"citation":"36); 5; 20","dose":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...","effect":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...","page":29,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_004"}
CIR_vision_codex NOAEL =67.8 mg/kg/d rat - 5-week NOAEL study {"citation":"72; 53; 10,000","dose":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...","effect":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_005"}
CIR_vision_codex NOAEL =2 mg/ kg bw/d rat - 17 days developmental toxicity {"citation":"1; 18; 4","dose":"The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...","effect":"uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_006"}
CIR_vision_codex NOAEL =1 mg/kg/d rat oral - oral toxicity {"citation":"1,140; 1,100; 3","dose":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.","effect":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ","page":31,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_007"}
CIR_vision_codex NOAEL =4 mg/kg bw/d rat oral 7 days oral toxicity {"citation":"0; 16; 21","dose":"Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...","effect":"epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...","page":40,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_008"}
CIR_vision_codex NOAEL =600 mg/kg bw/d rat oral 28 days oral toxicity {"citation":"(4; 3; 24","dose":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.","effect":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...","page":78,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_009"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat - - developmental toxicity {"citation":"10; 3; 100","dose":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...","effect":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_001"}
CIR_vision_codex NOAEL =160 mg/kg/d - - - developmental toxicity {"citation":"3; 100; 1,000","dose":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.","effect":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_002"}
CIR_vision_codex NOAEL =10000 ppm rat oral 8 weeks oral toxicity {"citation":"8; 71; 1,000","dose":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...","effect":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1)","page":26,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_003"}
CIR_vision_codex NOAEL =100 mg/ kg rat oral 8 weeks reproductive toxicity {"citation":"36); 5; 20","dose":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...","effect":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...","page":29,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_004"}
CIR_vision_codex NOAEL =67.8 mg/kg/d rat - 5-week NOAEL study {"citation":"72; 53; 10,000","dose":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...","effect":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_005"}
CIR_vision_codex NOAEL =2 mg/ kg bw/d rat - 17 days developmental toxicity {"citation":"1; 18; 4","dose":"The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...","effect":"uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_006"}
CIR_vision_codex NOAEL =1 mg/kg/d rat oral - oral toxicity {"citation":"1,140; 1,100; 3","dose":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.","effect":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ","page":31,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_007"}
CIR_vision_codex NOAEL =4 mg/kg bw/d rat oral 7 days oral toxicity {"citation":"0; 16; 21","dose":"Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...","effect":"epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...","page":40,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_008"}
CIR_vision_codex NOAEL =600 mg/kg bw/d rat oral 28 days oral toxicity {"citation":"(4; 3; 24","dose":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.","effect":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...","page":78,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_009"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat - - developmental toxicity {"citation":"10; 3; 100","dose":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...","effect":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_001"}
CIR_vision_codex NOAEL =160 mg/kg/d - - - developmental toxicity {"citation":"3; 100; 1,000","dose":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.","effect":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_002"}
CIR_vision_codex NOAEL =10000 ppm rat oral 8 weeks oral toxicity {"citation":"8; 71; 1,000","dose":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...","effect":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1)","page":26,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_003"}
CIR_vision_codex NOAEL =100 mg/ kg rat oral 8 weeks reproductive toxicity {"citation":"36); 5; 20","dose":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...","effect":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...","page":29,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_004"}
CIR_vision_codex NOAEL =67.8 mg/kg/d rat - 5-week NOAEL study {"citation":"72; 53; 10,000","dose":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...","effect":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_005"}
CIR_vision_codex NOAEL =2 mg/ kg bw/d rat - 17 days developmental toxicity {"citation":"1; 18; 4","dose":"The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...","effect":"uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_006"}
CIR_vision_codex NOAEL =1 mg/kg/d rat oral - oral toxicity {"citation":"1,140; 1,100; 3","dose":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.","effect":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ","page":31,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_007"}
CIR_vision_codex NOAEL =4 mg/kg bw/d rat oral 7 days oral toxicity {"citation":"0; 16; 21","dose":"Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...","effect":"epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...","page":40,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_008"}
CIR_vision_codex NOAEL =600 mg/kg bw/d rat oral 28 days oral toxicity {"citation":"(4; 3; 24","dose":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.","effect":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...","page":78,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_009"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat - - developmental toxicity {"citation":"10; 3; 100","dose":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...","effect":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_001"}
CIR_vision_codex NOAEL =160 mg/kg/d - - - developmental toxicity {"citation":"3; 100; 1,000","dose":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.","effect":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...","page":1,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_002"}
CIR_vision_codex NOAEL =10000 ppm rat oral 8 weeks oral toxicity {"citation":"8; 71; 1,000","dose":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...","effect":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1)","page":26,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_003"}
CIR_vision_codex NOAEL =100 mg/ kg rat oral 8 weeks reproductive toxicity {"citation":"36); 5; 20","dose":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...","effect":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...","page":29,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_004"}
CIR_vision_codex NOAEL =67.8 mg/kg/d rat - 5-week NOAEL study {"citation":"72; 53; 10,000","dose":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...","effect":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_005"}
CIR_vision_codex NOAEL =2 mg/ kg bw/d rat - 17 days developmental toxicity {"citation":"1; 18; 4","dose":"The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...","effect":"uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...","page":30,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_006"}
CIR_vision_codex NOAEL =1 mg/kg/d rat oral - oral toxicity {"citation":"1,140; 1,100; 3","dose":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.","effect":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ","page":31,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_007"}
CIR_vision_codex NOAEL =4 mg/kg bw/d rat oral 7 days oral toxicity {"citation":"0; 16; 21","dose":"Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...","effect":"epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...","page":40,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_008"}
CIR_vision_codex NOAEL =600 mg/kg bw/d rat oral 28 days oral toxicity {"citation":"(4; 3; 24","dose":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.","effect":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...","page":78,"pdf":"PRS746.pdf","row_type":"noael_study","study_id":"PRS746_noael_009"}
COSMOS_DB 11 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB NOAEL 800 mg/kg bw/day rat oral 3 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 5700 mg/kg bw/day rat oral 672 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 550 mg/kg bw/day mouse oral 10 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 300 mg/kg bw/day hamster oral 5 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1180 mg/kg bw/day rat oral 10 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 650 mg/kg bw/day hamster oral 5 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 4000 mg/kg bw/day rat oral 9 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 100 mg/kg bw/day mouse oral 3 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1000 mg/kg bw/day dog oral 365 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 500 mg/kg bw/day cat oral 6 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1030 mg/kg bw/day rat oral 8 week Subchronic SCCS; Food Chemical Toxicology 42: 1845-1849; Oishi S.
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =1030 mg/kg bw/day Rat - 56 days subchronic EFSA AFC - 2004 - OutputID 309 - no adverse effect observed at single/highest dose - Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission related to para hydroxybenzoates (E 214-219) - doi:10.2903/j.efsa.2004.83
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =1030 mg/kg bw/day Rat - 56 days subchronic EFSA AFC - 2004 - OutputID 309 - no adverse effect observed at single/highest dose - Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission related to para hydroxybenzoates (E 214-219) - doi:10.2903/j.efsa.2004.83
NTP_ICE_acute_oral 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 >5000 mg/kg bw Rat oral acute Rat Acute Oral Toxicity record_id=acute_oral_12060; row=7115; data_type=In Vivo; mixture=Chemical; chemical_name=Methylparaben; preferred_name=Methylparaben; dtxsid=DTXSID4022529; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 >5600 mg/kg bw Rat oral acute Rat Acute Oral Toxicity record_id=acute_oral_12061; row=7116; data_type=In Vivo; mixture=Chemical; chemical_name=Methylparaben; preferred_name=Methylparaben; dtxsid=DTXSID4022529; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =2100 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_12059; row=7117; data_type=In Vivo; mixture=Chemical; chemical_name=Methylparaben; preferred_name=Methylparaben; dtxsid=DTXSID4022529; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529; source_file=acute_oral.xlsx
NTP_ICE_adme_parameters 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_adme_parameters Clint 107.5 uL/min/10^6 cells Human - - Measured; httk, Human Hepatic Intrinsic Clearance sheet=Data; excel_row=1636; Record_ID=adme_parameters_405; Data_Type=Measured; DTXSID=DTXSID4022529; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=107.5; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Wetmore 2015; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_adme_parameters Clint 86.2 uL/min/10^6 cells Rat - - Measured; httk, Rat Hepatic Intrinsic Clearance sheet=Data; excel_row=1637; Record_ID=adme_parameters_405; Data_Type=Measured; DTXSID=DTXSID4022529; Assay=httk, Rat Hepatic Intrinsic Clearance; Endpoint=Clint; Response=86.2; Response_Unit=ul/min/10^6 cells; Species=Rat; Reference=httk2.3.1, Honda 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_adme_parameters Fu 0.174 fraction Rat - - Measured; httk, Rat Plasma Fraction Unbound sheet=Data; excel_row=1638; Record_ID=adme_parameters_405; Data_Type=Measured; DTXSID=DTXSID4022529; Assay=httk, Rat Plasma Fraction Unbound; Endpoint=Fu; Response=0.174; Response_Unit=Unitless Fraction; Species=Rat; Reference=httk2.3.1, Honda 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_adme_parameters Fu 0.07056 fraction Human - - Measured; httk, Human Plasma Fraction Unbound sheet=Data; excel_row=1639; Record_ID=adme_parameters_405; Data_Type=Measured; DTXSID=DTXSID4022529; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.07056; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Wetmore 2015; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine 14 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_endocrine AC50 64.1358560333104 uM - - - ERPathway2016; ER Pathway Model, Antagonist sheet=Integrated_approaches; excel_row=11584; RecordID=ERPathway2016_428; DatasetName=ERPathway2016; DTXSID=DTXSID4022529; Assay=ER Pathway Model, Antagonist; Endpoint=AC50; Response=64.1358560333104; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine AC50/EC50/IC50 10200 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=13267; Record_ID=endocrine_invitro_4107; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=AC50/EC50/IC50; Reported_Response=10200; Reported_Response_Unit=nM; Response=10200; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Indiveri et al. 2014; 24972338; 10.1016/j.reprotox.2014.06.004; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine AC50/EC50/IC50 208000 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=13268; Record_ID=endocrine_invitro_4108; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=AC50/EC50/IC50; Reported_Response=208000; Reported_Response_Unit=nM; Response=208000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Ermler et al. 2011; 21945941; 10.1016/j.taap.2011.09.005; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine AC50/EC50/IC50 7800 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=13270; Record_ID=endocrine_invitro_4110; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=AC50/EC50/IC50; Reported_Response=7800; Reported_Response_Unit=nM; Response=7800; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Ma et al. 2014; 24469767; 10.1007/s11356-014-2497-4; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine AC50/EC50/IC50 100000 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=13272; Record_ID=endocrine_invitro_4112; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=AC50/EC50/IC50; Reported_Response=100000; Reported_Response_Unit=nM; Response=100000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine ACC 58.830885379248 uM - - - ERPathway2016; ER Pathway Model, Antagonist sheet=Integrated_approaches; excel_row=11585; RecordID=ERPathway2016_428; DatasetName=ERPathway2016; DTXSID=DTXSID4022529; Assay=ER Pathway Model, Antagonist; Endpoint=ACC; Response=58.830885379248; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine IC01 26900 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=13020; Record_ID=endocrine_invitro_4032; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=IC01; Reported_Response=26900; Reported_Response_Unit=IC01 (nM); Response=26900; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine LEL 1000 nM - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=14966; Record_ID=endocrine_invitro_4403; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=LEL; Reported_Response=1000; Reported_Response_Unit=nM; Response=1000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Chen et al. 2007; 17481686; 10.1016/j.taap.2007.03.015; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine LOEL 55 mg/kg bw/day Rat Subcutaneous Treatment_Duration=3 days; Age_at_First_Dose=PND 21; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 In Vivo; Uterotrophic-Agonist sheet=Data_invivo; excel_row=1053; Record_ID=endocrine_invivo_414; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=55; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Wistar; Strain=Wistar; Sex=Female; Route=Subcutaneous; Maximum_Dose=165; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Lemini et al. 2003; 15697177; 10.1191/0748233703th177oa|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine Model Score 0 unitless - - - ARPathway2016; AR Pathway Model, Antagonist sheet=Integrated_approaches; excel_row=11580; RecordID=ARPathway2016_1823; DatasetName=ARPathway2016; DTXSID=DTXSID4022529; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine Model Score 0.00684 unitless - - - ERPathway2016; ER Pathway Model, Agonist sheet=Integrated_approaches; excel_row=11586; RecordID=ERPathway2016_428; DatasetName=ERPathway2016; DTXSID=DTXSID4022529; Assay=ER Pathway Model, Agonist; Endpoint=Model Score; Response=0.00684; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine Relative potency 8 % - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=15214; Record_ID=endocrine_invitro_4107; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=Relative potency; Reported_Response=8; Reported_Response_Unit=%; Response=8; Response_Unit=%; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Indiveri et al. 2014; 24972338; 10.1016/j.reprotox.2014.06.004; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine Relative potency 53 % - - - In Vitro; AR Transactivation-Antagonist sheet=Data_invitro; excel_row=15215; Record_ID=endocrine_invitro_4407; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=AR Transactivation-Antagonist; Endpoint=Relative potency; Reported_Response=53; Reported_Response_Unit=%; Response=53; Response_Unit=%; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Orton et al. 2014; 24055644; 10.1016/j.taap.2013.09.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_endocrine Uterine weight increase vs control 32 % Rat Subcutaneous Treatment_Duration=3 days; Age_at_First_Dose=PND 21; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 In Vivo; Uterotrophic-Agonist sheet=Data_invivo; excel_row=747; Record_ID=endocrine_invivo_414; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=32; Response_Unit=%; Species=Rat; Reported_Strain=Wistar; Strain=Wistar; Sex=Female; Route=Subcutaneous; Maximum_Dose=165; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Lemini et al. 2003; 15697177; 10.1191/0748233703th177oa|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization 19 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_skin_sensitization CD86, EC150 52 ug/mL - Dermal - In Vitro; Urbisch_SkinSensitization2020; U-SENS sheet=Data_invitro; excel_row=8151; Record_ID=skin_sensitization_invitro_2174; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=U-SENS; Endpoint=CD86, EC150; Reported_Response=341.7679921; Reported_Response_Unit=uM; Conversion_Factor_Value=152.149; Conversion_Factor_Source=EPA Dashboard; Converted_Response=52; Converted_Response_Unit=ug/mL; Response=52; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Concentration, 5% incidence of positive responses 30.625 % Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11562; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, 5% incidence of positive responses; Response=30.625; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Concentration, one positive response 6.25 % Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11560; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, one positive response; Response=6.25; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Depletion Cys 3.6 % - Dermal - In Vitro; Urbisch_SkinSensitization2020; DPRA sheet=Data_invitro; excel_row=69; Record_ID=skin_sensitization_invitro_3; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=3.6; Reported_Response_Unit=%; Response=3.6; Response_Unit=%; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Depletion Lys 0 % - Dermal - In Vitro; Urbisch_SkinSensitization2020; DPRA sheet=Data_invitro; excel_row=161; Record_ID=skin_sensitization_invitro_3; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=0; Reported_Response_Unit=%; Response=0; Response_Unit=%; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization EC1.5 805.4 uM - Dermal - In Vitro; Urbisch_SkinSensitization2020; KeratinoSens sheet=Data_invitro; excel_row=7494; Record_ID=skin_sensitization_invitro_1787; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=805.3529486; Reported_Response_Unit=uM; Response=805.4; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization EC1.5 <381.78 uM - Dermal - In Vitro; Urbisch_SkinSensitization2020; LuSens sheet=Data_invitro; excel_row=7959; Record_ID=skin_sensitization_invitro_1798; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=LuSens; Endpoint=EC1.5; Response_Modifier=<; Reported_Response_Modifier=<; Reported_Response=381.78; Reported_Response_Unit=uM; Response=381.78; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization IC50 >2000 uM - Dermal - In Vitro; Urbisch_SkinSensitization2020; KeratinoSens sheet=Data_invitro; excel_row=7496; Record_ID=skin_sensitization_invitro_1787; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=KeratinoSens; Endpoint=IC50; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=2000; Reported_Response_Unit=uM; Response=2000; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization IC50 >950 uM - Dermal - In Vitro; Urbisch_SkinSensitization2020; LuSens sheet=Data_invitro; excel_row=7630; Record_ID=skin_sensitization_invitro_1798; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=LuSens; Endpoint=IC50; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=950; Reported_Response_Unit=uM; Response=950; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Imax 2.426 ratio - Dermal - In Vitro; Urbisch_SkinSensitization2020; KeratinoSens sheet=Data_invitro; excel_row=7497; Record_ID=skin_sensitization_invitro_1787; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=2.425864785; Reported_Response_Unit=Unitless; Response=2.426; Response_Unit=Ratio; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Imax 6.696 ratio - Dermal - In Vitro; Urbisch_SkinSensitization2020; LuSens sheet=Data_invitro; excel_row=7527; Record_ID=skin_sensitization_invitro_1798; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID4022529; Assay=LuSens; Endpoint=Imax; Reported_Response=6.696184619; Reported_Response_Unit=Unitless; Response=6.696; Response_Unit=Ratio; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Incidence of positive responses 1.02 % Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11558; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=1.02; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Incidence of positive responses 0 % Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11589; Record_ID=skin_sensitization_invivo_2516; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=0.2; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=0; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Induction dose per skin area 4359 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11557; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=4359; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Induction dose per skin area 174.4 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11587; Record_ID=skin_sensitization_invivo_2516; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=0.2; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=174.4; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Induction dose per skin area 871.9 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11603; Record_ID=skin_sensitization_invivo_2519; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=1.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=871.9; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Induction dose per skin area 6975 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11618; Record_ID=skin_sensitization_invivo_2523; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=10.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=6975; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Induction dose per skin area, 5% incidence of positive responses 21360 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11563; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=21360; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
NTP_ICE_skin_sensitization Relative reliability score 3 unitless Human Dermal - In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test sheet=Data_invivo; excel_row=11564; Record_ID=skin_sensitization_invivo_2512; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Formulation_ID=MIX858; Formulation_Name=Methyl and propyl parabens; Concentration=5.0; Concentration_Units=%; Mixture=Mixture; DTXSID=DTXSID4022529; Assay=Human Repeat Insult Patch Test; Endpoint=Relative reliability score; Response=3; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available|Marzulli and Maibach 1976; 801606; 10.1111/j.1600-0536.1976.tb02972.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4022529
SCCS_vision_codex 48 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =1000 mg/kg/day - oral 14 days repeated dose toxicity {"dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","page":38,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_001"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/day - - - NOAEL study {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","page":40,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_003"}
SCCS_vision_codex NOAEL =99 - - oral developmental repeated dose toxicity {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_004"}
SCCS_vision_codex NOAEL =42 - - oral developmental repeated dose toxicity {"dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_005"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/d - - - reproductive toxicity {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat - - NOAEL study {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","page":46,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_019"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day - - developmental reproductive toxicity {"dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","page":50,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_024"}
SCCS_vision_codex NOAEL =0.105 mg/kg bw/day rat - - NOAEL study {"dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","page":64,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_026"}
SCCS_vision_codex NOAEL =24 - - - Chronic NOAEL study {"effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_033"}
SCCS_vision_codex NOAEL =25 - - oral developmental reproductive toxicity {"effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_035"}
SCCS_vision_codex NOAEL =0.1 % rat oral 27-day NOAEL study {"dose":"NOAEL 1000 mg/kg/day | Oishi 2004","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_037"}
SCCS_vision_codex NOAEL =10000 ppm rat oral - reproductive toxicity {"dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_038"}
SCCS_vision_codex NOAEL =1000 mg/kg/day - oral 14 days repeated dose toxicity {"dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","page":38,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_001"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/day - - - NOAEL study {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","page":40,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_003"}
SCCS_vision_codex NOAEL =99 - - oral developmental repeated dose toxicity {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_004"}
SCCS_vision_codex NOAEL =42 - - oral developmental repeated dose toxicity {"dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_005"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/d - - - reproductive toxicity {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat - - NOAEL study {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","page":46,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_019"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day - - developmental reproductive toxicity {"dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","page":50,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_024"}
SCCS_vision_codex NOAEL =0.105 mg/kg bw/day rat - - NOAEL study {"dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","page":64,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_026"}
SCCS_vision_codex NOAEL =24 - - - Chronic NOAEL study {"effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_033"}
SCCS_vision_codex NOAEL =25 - - oral developmental reproductive toxicity {"effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_035"}
SCCS_vision_codex NOAEL =0.1 % rat oral 27-day NOAEL study {"dose":"NOAEL 1000 mg/kg/day | Oishi 2004","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_037"}
SCCS_vision_codex NOAEL =10000 ppm rat oral - reproductive toxicity {"dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_038"}
SCCS_vision_codex NOAEL =1000 mg/kg/day - oral 14 days repeated dose toxicity {"dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","page":38,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_001"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/day - - - NOAEL study {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","page":40,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_003"}
SCCS_vision_codex NOAEL =99 - - oral developmental repeated dose toxicity {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_004"}
SCCS_vision_codex NOAEL =42 - - oral developmental repeated dose toxicity {"dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_005"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/d - - - reproductive toxicity {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat - - NOAEL study {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","page":46,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_019"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day - - developmental reproductive toxicity {"dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","page":50,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_024"}
SCCS_vision_codex NOAEL =0.105 mg/kg bw/day rat - - NOAEL study {"dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","page":64,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_026"}
SCCS_vision_codex NOAEL =24 - - - Chronic NOAEL study {"effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_033"}
SCCS_vision_codex NOAEL =25 - - oral developmental reproductive toxicity {"effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_035"}
SCCS_vision_codex NOAEL =0.1 % rat oral 27-day NOAEL study {"dose":"NOAEL 1000 mg/kg/day | Oishi 2004","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_037"}
SCCS_vision_codex NOAEL =10000 ppm rat oral - reproductive toxicity {"dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_038"}
SCCS_vision_codex NOAEL =1000 mg/kg/day - oral 14 days repeated dose toxicity {"dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","page":38,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_001"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/day - - - NOAEL study {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","page":40,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_003"}
SCCS_vision_codex NOAEL =99 - - oral developmental repeated dose toxicity {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_004"}
SCCS_vision_codex NOAEL =42 - - oral developmental repeated dose toxicity {"dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_005"}
SCCS_vision_codex NOAEL =1000 mg/kg bw/d - - - reproductive toxicity {"dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat - - NOAEL study {"dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","page":46,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_019"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day - - developmental reproductive toxicity {"dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","page":50,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_024"}
SCCS_vision_codex NOAEL =0.105 mg/kg bw/day rat - - NOAEL study {"dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","page":64,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_026"}
SCCS_vision_codex NOAEL =24 - - - Chronic NOAEL study {"effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_033"}
SCCS_vision_codex NOAEL =25 - - oral developmental reproductive toxicity {"effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_035"}
SCCS_vision_codex NOAEL =0.1 % rat oral 27-day NOAEL study {"dose":"NOAEL 1000 mg/kg/day | Oishi 2004","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_037"}
SCCS_vision_codex NOAEL =10000 ppm rat oral - reproductive toxicity {"dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","page":45,"pdf":"sccs_o_276.pdf","row_type":"noael_study","study_id":"sccs_o_276_noael_038"}
ToxValDB_ECHA_IUCLID 5 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID NOAEL =550 mg/kg bw/day Rat oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d24ce4b0a7c65d2328c6; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/30649/7/9/3?documentUUID=3a6960ce-3ffa-42a8-82cd-3311aacc0e80; YEAR=2001; ORIGINAL_YEAR=2001; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821380_15823776_15825361:M/F:-fetal; 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_f8c0234231053782009746837ceaa420
ToxValDB_ECHA_IUCLID NOAEL >300 mg/kg bw/day Rabbit oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabc6e4b0a7c65d1bbb5a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13843/7/9/3?documentUUID=5d187420-ccbf-4439-a44f-786ba7ccf43b; YEAR=1978; ORIGINAL_YEAR=1978; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15823716_15825360:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2759073566d725a75548c5269f1a5d94
ToxValDB_ECHA_IUCLID NOAEL =1000 mg/kg bw/day Rat oral - developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac9ce4b0a7c65d1c003f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/30649/7/9/3?documentUUID=3a6960ce-3ffa-42a8-82cd-3311aacc0e80; YEAR=2001; ORIGINAL_YEAR=2001; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821380_15823776_15825361:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_62a48ac33d219053115b66480e1b413f
ToxValDB_ECHA_IUCLID NOEL >1030 mg/kg bw/day Rat oral - repeat dose other QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaf9ee4b0a7c65d1cea84; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22106/7/6/2?documentUUID=a050fc07-152c-4b11-8ba0-92b9df3fb49f; YEAR=2009; ORIGINAL_YEAR=2009; TOXICOLOGICAL_EFFECT=clinical biochemistry|clinical signs|food consumption and compound intake|mortality|organ weights and organ / body weight ratios|serum/plasma biochemistry|serum/plasma hormone analyses|sperm measures; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|clinical signs|food and/or water consumption|mortality/survival|organ weight|reproduction; STUDY_GROUP=ECHA IUCLID:15850084:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_596d623aa1f1e6d87d3c07d88b66323f
ToxValDB_ECHA_IUCLID NOEL =1000 mg/kg bw/day Rat oral subchronic; 90 days subchronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1d9c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13843/7/6/2?documentUUID=5d187420-ccbf-4439-a44f-786ba7ccf43b; YEAR=1978; ORIGINAL_YEAR=1978; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15850490_15850491:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_3e5261cabf65ffdfe038d88df96cc832
ToxValDB_EFSA 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EFSA NOAEL =1030 mg/kg bw/day Rat oral subchronic; 8 weeks subchronic LONG_REF=EFSA AFC (2004). Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission related to para hydroxybenzoates (E 214-219). doi:10.2903/j.efsa.2004.83.; TITLE=Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission related to para hydroxybenzoates (E 214-219); AUTHOR=EFSA AFC; DOI=doi:10.2903/j.efsa.2004.83; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2004; ORIGINAL_YEAR=2004; TOXICOLOGICAL_EFFECT=no effects; STUDY_GROUP=EFSA:15614256:M:--; 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_040184ccd577119a1d0edead44322d0c
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =176.3 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:15633411:-:--; 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_5d9f1b1f7290fb9d07c37b802109a2a8
ToxValDB_Uterotrophic_Hershberger_DB 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_Uterotrophic_Hershberger_DB LEL =16.5 mg/kg bw/day Mouse injection short-term; 3 days uterotrophic LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713525_15713577_15713628:-:--; 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_a67a9267b8378fb659a276a99a1da164
ToxValDB_Uterotrophic_Hershberger_DB LEL =55 mg/kg bw/day Rat injection short-term; 3 days uterotrophic LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713576:-:--; 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_2c1650c71d4bafc2c44c744209a833ae
ToxValDB_Uterotrophic_Hershberger_DB LEL =165 mg/kg bw/day Mouse injection short-term; 3 days uterotrophic LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713525_15713577_15713628:-:--; 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_baef90db66c25256c4db7a9512a9626a
UnifiedCodex:CIR:beta.noael_studies 9 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:CIR:beta.noael_studies - 67.8 mg/kg/d rat - 5-week - SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=67.8; DOSE=y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P  0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...; EFFECT=y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P  0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...; CITATION=72; 53; 10,000; CITATION_NUMBERS=[72,53,10]; REFERENCE=72; 53; 10,000; DETAILS_JSON={"cas_number":"99-76-3","citation":"72; 53; 10,000","dose":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters eval...","duration":"5-week","effect":"y 72% and 53%, respectively) in the 10,000 ppm Butylparaben-treated group compared with the control group LH concentrations were statistically significantly lower (P \u0006 0.01) in the 1,000 ppm (by 35%) and 10,000 ppm (by 30%) exposure groups, compared with controls, but only at the 5-week exposure point The authors concluded that none of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects, and the NOAEC was the highest concentration tested (10,000 ppm), corresponding to a NOAEL of 1,141.1 + 58.9 and 1,087.6 + 67.8 mg/kg/d for Methylparaben and Butylparaben, respectively Subcutaneous Butylparaben Rat (Wistar) Male, 2 days of age, N ¼ 8, n ¼ 3 or 5/group, 2 groups 2 mg/kg bw /d in corn oil (vehicle), by subcutaneous injection Male rats were dosed subcutaneously for 17 days starting on PND2; control group contained 5 rats, and Butylparaben-treated group contained 3 rats; parameters evaluated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the wate...","endpoint":"","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg/d","noael_value":"67.8","page":30,"route":"","species":"rat","study_id":"PRS746_noael_005"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 1000 mg/kg/d rat - - developmental toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=1,000; DOSE=ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...; EFFECT=ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...; CITATION=10; 3; 100; CITATION_NUMBERS=[10,3,100]; REFERENCE=10; 3; 100; DETAILS_JSON={"cas_number":"99-76-3","citation":"10; 3; 100","dose":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this s...","duration":"","effect":"ity (DART) study indicated reduced sperm counts and reduced expression of a specific enzyme and a reduction in a specific cell marker in the testes of offspring of female rats orally dosed with 10 mg/kg/d Butylparaben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredie...","endpoint":"developmental toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg/d","noael_value":"1,000","page":1,"route":"","species":"rat","study_id":"PRS746_noael_001"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 160 mg/kg/d - - - developmental toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=160; DOSE=aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.; EFFECT=aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...; CITATION=3; 100; 1,000; CITATION_NUMBERS=[3,100,1]; REFERENCE=3; 100; 1,000; DETAILS_JSON={"cas_number":"99-76-3","citation":"3; 100; 1,000","dose":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study.","duration":"","effect":"aben during gestation and lactation periods.3 Reductions in anogenital dis- tance (AGD) and other effects were reported at 100 mg/kg/d in this study. In comparison, the previous Panel safety assessment of parabens included the calculation of margin of safety (MOS) values for adults and infants, assuming a no observed adverse effect level (NOAEL) of 1,000 mg/kg/d from an older DART study.2 After careful consideration of all the new data regarding endocrine activity and DART studies, the Panel determined an adequate NOAEL value of 160 mg/kg/d for Butylparaben. An MOS was recalculated accordingly, considering the different 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Washington, DC, USA 2 Cosmetic Ingredient Review Toxicologist, Washington, DC, USA 3 Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 4 Former Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA 5 Cosmetic Ingredient Review Executive Director, Washington, DC, USA Corresponding Author: Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Su...","endpoint":"developmental toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg/d","noael_value":"160","page":1,"route":"","species":"","study_id":"PRS746_noael_002"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 2 mg/ kg bw/d rat - 17 days developmental toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=2; DOSE=The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...; EFFECT=uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...; CITATION=1; 18; 4; CITATION_NUMBERS=[1,18,4]; REFERENCE=1; 18; 4; DETAILS_JSON={"cas_number":"99-76-3","citation":"1; 18; 4","dose":"The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL...","duration":"17 days","effect":"uated included testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water AQP-1. The epithelial cells of the efferent ducts decrease in height coincident with reduced expression of the water channel protein AQP-1; animals that were sampled on day 18 were killed 4 hours after injection No detectable effect on any of the measured reproductive parameters after subcu- taneous administration of Butylparaben for 17 days (PND 2-18); the NOEL was 2 mg/ kg bw/d 158 Isobutylparaben Rat (Sprague Dawley) Female (# of animals not stated) NR NR Decrease of plasma corticosterone concentration and increased uterus weight in dams as well as uterine sensitivity to estrogen in adult female offspring was noted 18 Ethylparaben and Butylparaben Rat (Wistar) 15/group 400 mg/kg d Ethylparaben; 200 or 400 mg/kg/d Butylparaben on GD 7- 21 Animals treated on gestation days 7-21. No treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERb mRNA expres...","endpoint":"developmental toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/ kg bw/d","noael_value":"2","page":30,"route":"","species":"rat","study_id":"PRS746_noael_006"}
UnifiedCodex:CIR:beta.noael_studies oral toxicity 10000 ppm rat oral 8 weeks oral toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=10,000; DOSE=lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...; EFFECT=lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1); CITATION=8; 71; 1,000; CITATION_NUMBERS=[8,71,1]; REFERENCE=8; 71; 1,000; DETAILS_JSON={"cas_number":"99-76-3","citation":"8; 71; 1,000","dose":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altere...","duration":"8 weeks","effect":"lparaben for 8 weeks.71 Methylparaben was associated with a statistically signifi- cant higher incidence of abnormal sperm in rats exposed to 1,000 ppm or 10,000 ppm in the diet for 8 weeks, mostly sperm with no head in 4% to 5% of sperm, compared with 2.3% in 100 ppm and control groups.50 Measurements of hormone concen- trations were generally not altered, except that T and FSH concentrations were higher in the 10,000 ppm Butylparaben- treated group, compared with the control group. The authors concluded that the no observed adverse effect concentration was the highest concentration tested (10,000 ppm), 30S International Journal of Toxicology 39(Supplement 1)","endpoint":"oral toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":26,"route":"oral","species":"rat","study_id":"PRS746_noael_003"}
UnifiedCodex:CIR:beta.noael_studies oral toxicity 1 mg/kg/d rat oral - oral toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=1; 100; DOSE=corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.; EFFECT=corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ; CITATION=1,140; 1,100; 3; CITATION_NUMBERS=[1,140,100,3]; REFERENCE=1,140; 1,100; 3; DETAILS_JSON={"cas_number":"99-76-3","citation":"1,140; 1,100; 3","dose":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively.","duration":"","effect":"corresponding to a NOAEL of about 1,140 and 1,100 mg/kg/d for Methylparaben and Butylparaben, respectively. Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 Terminal deoxynucleotidyl transferase– mediated fluorescein-dUTP nick end labeling (TUNEL) assays revealed a substantial increase in the number of apoptotic sper- matogenic cells in the treated rats; the effect was maximal at 6 hours. Subcutaneous. Subcutaneous DART studies are also summ","endpoint":"oral toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg/d","noael_value":"1; 100","page":31,"route":"oral","species":"rat","study_id":"PRS746_noael_007"}
UnifiedCodex:CIR:beta.noael_studies oral toxicity 4 mg/kg bw/d rat oral 7 days oral toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=4 and 0.8; DOSE=Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with 0.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...; EFFECT=epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with 0.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...; CITATION=0; 16; 21; CITATION_NUMBERS=[16,21]; REFERENCE=0; 16; 21; DETAILS_JSON={"cas_number":"99-76-3","citation":"0; 16; 21","dose":"Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectivel...","duration":"7 days","effect":"epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR binding activity. Relative uterine weights were elevated in immature Sprague Dawley rats after treatment with \u00050.16 mg/kg bw/d Benzyl- paraben via gavage on PNDs 21 to 23.94 Lowest observed effect levels for increased relative uterine weight after treat- ment of immature female rats with Methylparaben or Ethylpar- aben on PNDs 21 to 23 were 20 and 4 mg/kg bw/d, respectively.95 No observed effect levels (NOELs) for Methyl- paraben and Ethylparaben were 4 and 0.8 mg/kg bw/d, respec- tively. Ethylparaben and Propylparaben were negative for estrogen agonism and antagonism in ovariectomized female mice exposed to 1,000 mg/kg bw/d by gavage for 7 days.96 Histopathologic examination revealed progressive detach- ment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules and reduction and/or disappearance of tubular lumen 3 hours after a single 1,000 mg/kg oral dosage of Butylparaben in rats.72 The TUNEL assays revealed a substan- tial increase in the number of apoptotic spermatogen...","endpoint":"oral toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4 and 0.8","page":40,"route":"oral","species":"rat","study_id":"PRS746_noael_008"}
UnifiedCodex:CIR:beta.noael_studies oral toxicity 600 mg/kg bw/d rat oral 28 days oral toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=600; 50; DOSE=ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.; EFFECT=ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...; CITATION=(4; 3; 24; CITATION_NUMBERS=[4,3,24]; REFERENCE=(4; 3; 24; DETAILS_JSON={"cas_number":"99-76-3","citation":"(4; 3; 24","dose":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben.","duration":"28 days","effect":"ed parabens and their major, nonspecific metabolites (4-Hydroxybenzoic Acid and p hydroxyhippuric acid) were detected in the urine samples of 3 subjects 24 hours after an oral dose of deuterated Methyl- paraben, Butylparaben, and Isobutylparaben. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/d Isopropylparaben or Isobutylparaben for 28 days. Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No observed adverse effect levels for Isobutylparaben and Isopropylparaben were 600 and 50 mg/kg bw/d, respectively. At 100 and 300 mg/kg bw/d Propylparaben administered orally, rats exhibited statistically significant increases in relative liver weights, serum ALT, AST, ALP, and LDH activ- ities. Significant decreases in total serum protein and albumin, GSH, CAT and SOD activities, serum T concentrations, and T/ E2 ratios were also reported. Livers of affected rats exhibited dilated congested central and portal veins, highly proliferated bile ducts with fibrotic reactio...","endpoint":"oral toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"600; 50","page":78,"route":"oral","species":"rat","study_id":"PRS746_noael_009"}
UnifiedCodex:CIR:beta.noael_studies reproductive toxicity 100 mg/ kg rat oral 8 weeks reproductive toxicity SOURCE_SUBDIR=PRS746; REPORT_TITLE=Amended Safety Assessment of Parabens as Used in Cosmetics Priya Cherian1, Jinqiu Zhu2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill4, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks, Jr.3, Ronald C. Shank3, Thomas J. Slag; OPINION_NUMBER=PRS746; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=1 In 2017; VALUE_TEXT=100 and 1,000; DOSE=n]) Lactating females (n ¼ 36), each with a litter 5 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...; EFFECT=n]) Lactating females (n ¼ 36), each with a litter 5 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...; CITATION=36); 5; 20; CITATION_NUMBERS=[36,5,20]; REFERENCE=36); 5; 20; DETAILS_JSON={"cas_number":"99-76-3","citation":"36); 5; 20","dose":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the wei...","duration":"8 weeks","effect":"n]) Lactating females (n ¼ 36), each with a litter \u00055 male pups supplied on PND14, n ¼ 20 pups/group (10/ subgroup) 0, 10, 100, 1,000 mg/kg bw/d, 2% suspended in a 1% aqueous hydroxycellulose, by gavage Juvenile male rats were dosed for 8 weeks starting on PND21; all animals were sacrificed after the treatment There was no evidence of an effect on the weight of the male reproductive organs, epididymal sperm parameters, hormone concentrations, or histopathology The highest dosage rate tested (1,000 mg/kg/d) was the NOAEL 71 Butylparaben Rat (Sprague Dawley) Males, 7-week-old, n ¼ 5/ group, 4 groups 0, 10, 100 and 1,000 mg/ kg in corn oil (vehicle), by gavage Performed in accordance with OECD TG 407 for repeated 28-day oral toxicity studies; 24 hours after the last dose, testes, tails, and epididymal spermatozoa samples were collected, DNA was extracted, and the DNA samples from each group were pooled, digested (methylation- specific restricted restriction digestion), and analyzed by differential display random amplification of polymorphic DNA (RAPD) Among 57 RAPD amplicons, 6 were...","endpoint":"reproductive toxicity","ingredient":"Parabens","loael_value":"","noael_unit":"mg/ kg","noael_value":"100 and 1,000","page":29,"route":"oral","species":"rat","study_id":"PRS746_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 76 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.; EFFECT=controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","duration":"","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":40,"route":"","species":"","study_id":"sccs_o_276_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/d rat oral Chronic - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls.; EFFECT=significantly lower mean thyroxine hormone (T4) levels in male rats (64.51 ± 11.87 in HD vs 78.16 ± 12.08 nmol/L in C (n=10 animals) were measured without corresponding histopathological findings in the thyroid/parathyroid. No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls. Based on the results of this study, the SCCS concurs with the study authors and considers 1000 mg/kg bw/d as NOAEL. 3.4.4.3 Chronic (> 12 months) toxicity According to the Applicant Table 24: Chronic toxicity studies Study Species Duration Dose (mg/kg/day) Observations Chronic 1-2 years Matthews (1956) Rat n=24 96 weeks 2 or 8% Methylparaben in the diet Rats dosed at 8% MP had decreased body weight in the early part of the study, which resolved and there were no other toxic effects.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls.","duration":"Chronic","effect":"significantly lower mean thyroxine hormone (T4) levels in male rats (64.51 ± 11.87 in HD vs 78.16 ± 12.08 nmol/L in C (n=10 animals) were measured without corresponding histopathological findings in the thyroid/parathyroid. No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls. Based on the results of this study, the SCCS concurs with the study authors and considers 1000 mg/kg bw/d as NOAEL. 3.4.4.3 Chronic (> 12 months) toxicity According to the Applicant Table 24: Chronic toxicity studies Study Species Duration Dose (mg/kg/day) Observations Chronic 1-2 years Matthews (1956) Rat n=24 96 weeks 2 or 8% Methylparaben in the diet Rats dosed at 8% MP had decreased body weight in the early part of the study, which resolved and there were no other toxic effects.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":43,"route":"oral","species":"rat","study_id":"sccs_o_276_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg/day rat oral 27-day - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group.; EFFECT=Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 45 Male Crj:Wistar 25- 27-day old rats (n=5 per group) 8 weeks study Oral 0.1% and 1% in rat diet No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group.","duration":"27-day","effect":"Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 45 Male Crj:Wistar 25- 27-day old rats (n=5 per group) 8 weeks study Oral 0.1% and 1% in rat diet No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected or; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected or","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"1000","page":46,"route":"","species":"rat","study_id":"sccs_o_276_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=250; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"250","page":46,"route":"","species":"rat","study_id":"sccs_o_276_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=250; DOSE=__________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: __________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"__________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS-rejected applicant NOAEL: __________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"250","page":46,"route":"","species":"rat","study_id":"sccs_o_276_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000 mg/kg bw/day). The study by Vo et al. (2010) was well designed and the measured effects on vaginal opening, oestrous cycle and organ weights are relevant. Nevertheless, the RIVM recommends that further study for these or comparable effects is needed at the same dose level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al.","duration":"","effect":"SCCS-rejected applicant NOAEL: vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000 mg/kg bw/day). The study by Vo et al. (2010) was well designed and the measured effects on vaginal opening, oestrous cycle and organ weights are relevant. Nevertheless, the RIVM recommends that further study for these or comparable effects is needed at the same dose level","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"1000","page":46,"route":"","species":"rat","study_id":"sccs_o_276_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.105 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=0.1050; DOSE=The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):; EFFECT=ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","duration":"","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.1050","page":64,"route":"","species":"rat","study_id":"sccs_o_276_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben.; EFFECT=ed. Methylparaben caused morphological changes in gerbil prostates in all experimental groups. These animals displayed similar alterations, such as prostate epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR-positive cells. The RIVM noted that no adverse effects were measured, but it is unclear how the morphological effects were quantified. Only one dosage was measured. RIVM conclusion: Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben. The available in vivo studies all have weaknesses in study design (e.g. with regard to statistics, small number of animals, no dose–response relationship measured) and in some, no adverse ED effects were found. The (intermediate) endpoints measured in the studies described above suggest an endocrine MOA for all the parabens evaluated, but more data with regard to in vivo effects are needed. Ref: Brand et al., 2017 3.4.10.1.3. In vivo assays providing data on adverse effect; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben.","duration":"","effect":"ed. Methylparaben caused morphological changes in gerbil prostates in all experimental groups. These animals displayed similar alterations, such as prostate epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR-positive cells. The RIVM noted that no adverse effects were measured, but it is unclear how the morphological effects were quantified. Only one dosage was measured. RIVM conclusion: Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben. The available in vivo studies all have weaknesses in study design (e.g. with regard to statistics, small number of animals, no dose–response relationship measured) and in some, no adverse ED effects were found. The (intermediate) endpoints measured in the studies described above suggest an endocrine MOA for all the parabens evaluated, but more data with regard to in vivo effects are needed. Ref: Brand et al., 2017 3.4.10.1.3. In vivo assays providing data on adverse effect","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":65,"route":"","species":"","study_id":"sccs_o_276_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 24 - - - Chronic - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.; EFFECT=Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"","duration":"Chronic","effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"route":"","species":"","study_id":"sccs_o_276_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw - - Chronic - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=1000 mg/kg bw/ | d as NOAEL.; EFFECT=Table 24: Chronic toxicity studies: 1000 mg/kg bw/ | d as NOAEL.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"1000 mg/kg bw/ | d as NOAEL.","duration":"Chronic","effect":"Table 24: Chronic toxicity studies: 1000 mg/kg bw/ | d as NOAEL.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1000","page":43,"route":"","species":"","study_id":"sccs_o_276_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.1 % rat oral 27-day - SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=0.1; DOSE=NOAEL 1000 mg/kg/day | Oishi 2004; EFFECT=Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL 1000 mg/kg/day | Oishi 2004","duration":"27-day","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"0.1","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.; EFFECT=controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The study authors derived a NOAEL of 1000 mg/kg bw/day from that study.","duration":"","effect":"controls; a moderate increase in absolute and relative mean uterus with cervix weight was observed in females of the HD recovery group, when compared to the controls. Slight but statistically significantly lower mean calculated weight of testicular parenchyma in HD groups was observed, when compared to concurrent controls at the end of treatment of main groups. No treatment related effects on the mean testis weight and mean testicular sperm counts in the recovery periods were observed. The study authors derived a NOAEL of 1000 mg/kg bw/day from that study. SCCS comment","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":40,"route":"","species":"","study_id":"sccs_o_276_final_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/d rat oral Chronic - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls.; EFFECT=significantly lower mean thyroxine hormone (T4) levels in male rats (64.51 ± 11.87 in HD vs 78.16 ± 12.08 nmol/L in C (n=10 animals) were measured without corresponding histopathological findings in the thyroid/parathyroid. No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls. Based on the results of this study, the SCCS concurs with the study authors and considers 1000 mg/kg bw/d as NOAEL. 3.4.4.3 Chronic (> 12 months) toxicity According to the Applicant Table 24: Chronic toxicity studies Study Species Duration Dose (mg/kg/day) Observations Chronic 1-2 years Matthews (1956) Rat n=24 96 weeks 2 or 8% Methylparaben in the diet Rats dosed at 8% MP had decreased body weight in the early part of the study, which resolved and there were no other toxic effects.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls.","duration":"Chronic","effect":"significantly lower mean thyroxine hormone (T4) levels in male rats (64.51 ± 11.87 in HD vs 78.16 ± 12.08 nmol/L in C (n=10 animals) were measured without corresponding histopathological findings in the thyroid/parathyroid. No statistically significant effects were observed on pup thyroid weight and T4 level in PND 13 pups (male and female) of the Methylparaben-treated groups when compared to the controls. Based on the results of this study, the SCCS concurs with the study authors and considers 1000 mg/kg bw/d as NOAEL. 3.4.4.3 Chronic (> 12 months) toxicity According to the Applicant Table 24: Chronic toxicity studies Study Species Duration Dose (mg/kg/day) Observations Chronic 1-2 years Matthews (1956) Rat n=24 96 weeks 2 or 8% Methylparaben in the diet Rats dosed at 8% MP had decreased body weight in the early part of the study, which resolved and there were no other toxic effects.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":43,"route":"oral","species":"rat","study_id":"sccs_o_276_final_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg/day rat oral 27-day - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group.; EFFECT=Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 45 Male Crj:Wistar 25- 27-day old rats (n=5 per group) 8 weeks study Oral 0.1% and 1% in rat diet No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group.","duration":"27-day","effect":"Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 45 Male Crj:Wistar 25- 27-day old rats (n=5 per group) 8 weeks study Oral 0.1% and 1% in rat diet No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day Oishi 2004 Crj:Wistar rat (n=16 per group) Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_final_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected or; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected or","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"1000","page":46,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=250; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS-rejected applicant NOAEL: igendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"250","page":46,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=250; DOSE=__________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: __________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"__________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day.","duration":"","effect":"SCCS-rejected applicant NOAEL: __________________ ___________________________________________________________________________________________ 46 of 1000 mg/kg bw/day. This NOAEL does not take possible spermatogenic effects identified by Hoberman et al. (2008) into account, nor the delay in the date of vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"250","page":46,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al.; LOAEL_VALUE=1000 mg/kg bw/day; EFFECT=SCCS-rejected applicant NOAEL: vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000 mg/kg bw/day). The study by Vo et al. (2010) was well designed and the measured effects on vaginal opening, oestrous cycle and organ weights are relevant. Nevertheless, the RIVM recommends that further study for these or comparable effects is needed at the same dose level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al.","duration":"","effect":"SCCS-rejected applicant NOAEL: vaginal opening in pre- pubertal rats and decrease in length of the oestrous cycle with a NOAEL of 250 mg/kg bw/day identified by Vo et al. (2010). The Vo et al. (2010) study was also taken into account by the SCCS. Vo et al. (2010) identified a NOAEL of 250 mg/kg bw/day and a LOAEL of 1000 mg/kg bw/day (effects on the date of vaginal opening, the length of the oestrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)). The SCCS concluded that this study could not be used to determine the NOAEL since it was not an OECD TG study and the effects were not dose-response related. The RIVM does not completely agree with the SCCS opinion, since effects on the oestrous cycle and organ weights occurred only at the highest dose level tested (1000 mg/kg bw/day). The study by Vo et al. (2010) was well designed and the measured effects on vaginal opening, oestrous cycle and organ weights are relevant. Nevertheless, the RIVM recommends that further study for these or comparable effects is needed at the same dose level","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"1000 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"1000","page":46,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.105 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=0.1050; DOSE=The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):; EFFECT=ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day):","duration":"","effect":"ey rats. The expression of the following genes was affected in the Methylparaben-exposed group (0.8, 4 and 20 mg/kg bw/day): Icabp, Itmap1, CaBP-9k, Pgr. Relative uterine weight was increased in the Methylparaben-exposed group (20 mg/kg bw/day). RIVM concluded that the study was performed properly; however, it focused on a limited set of effects. The measured effects (gene expression, uterine weight) suggesting an ED MOA should be confirmed by other studies. By themselves the results are not sufficient to derive a NOAEL. Manservisi et al. (2015) This study determined whether low doses of Methylparaben affect the development and proliferative activity of the mammary glands. Female animals treated with Methylparaben (0.1050 mg/kg bw/day) showed evident histological differences from controls: the alveoli of the mammary gland were not always milk-filled and an increase in adipose tissue was noted. The collapsed alveolar and duct structures showed residual secretory content. Gene expression was affected. The RIVM noted that part of t","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.1050","page":64,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben.; EFFECT=ed. Methylparaben caused morphological changes in gerbil prostates in all experimental groups. These animals displayed similar alterations, such as prostate epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR-positive cells. The RIVM noted that no adverse effects were measured, but it is unclear how the morphological effects were quantified. Only one dosage was measured. RIVM conclusion: Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben. The available in vivo studies all have weaknesses in study design (e.g. with regard to statistics, small number of animals, no dose–response relationship measured) and in some, no adverse ED effects were found. The (intermediate) endpoints measured in the studies described above suggest an endocrine MOA for all the parabens evaluated, but more data with regard to in vivo effects are needed. Ref: Brand et al., 2017 3.4.10.1.3. In vivo assays providing data on adverse effect; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben.","duration":"","effect":"ed. Methylparaben caused morphological changes in gerbil prostates in all experimental groups. These animals displayed similar alterations, such as prostate epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR-positive cells. The RIVM noted that no adverse effects were measured, but it is unclear how the morphological effects were quantified. Only one dosage was measured. RIVM conclusion: Findings in the in vivo studies performed after the SCCS Opinions did not contradict the current NOAEL of 1000 mg/kg bw/day for Methylparaben. The available in vivo studies all have weaknesses in study design (e.g. with regard to statistics, small number of animals, no dose–response relationship measured) and in some, no adverse ED effects were found. The (intermediate) endpoints measured in the studies described above suggest an endocrine MOA for all the parabens evaluated, but more data with regard to in vivo effects are needed. Ref: Brand et al., 2017 3.4.10.1.3. In vivo assays providing data on adverse effect","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":65,"route":"","species":"","study_id":"sccs_o_276_final_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 24 - - - Chronic - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.; EFFECT=Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"","duration":"Chronic","effect":"Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 24: Chronic toxicity studies: The study author | s derived a NOAEL | of 1000 m | g/kg bw/d | from that | study.","page":43,"route":"","species":"","study_id":"sccs_o_276_final_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg bw - - Chronic - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=1000 mg/kg bw/ | d as NOAEL.; EFFECT=Table 24: Chronic toxicity studies: 1000 mg/kg bw/ | d as NOAEL.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"1000 mg/kg bw/ | d as NOAEL.","duration":"Chronic","effect":"Table 24: Chronic toxicity studies: 1000 mg/kg bw/ | d as NOAEL.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1000","page":43,"route":"","species":"","study_id":"sccs_o_276_final_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.1 % rat oral 27-day - SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=0.1; DOSE=NOAEL 1000 mg/kg/day | Oishi 2004; EFFECT=Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL 1000 mg/kg/day | Oishi 2004","duration":"27-day","effect":"Unlabeled table on page 45: Male Crj:Wistar 25- 27-day old rats (n=5 per group) | 8 weeks study | Oral | 0.1% and 1% in rat diet | No effects on organ weights. MP did not exhibit antispermatogenic effects. There was no effect on male reproduction. There were no changes in testosterone, LH and FSH hormones. NOAEL 1000 mg/kg/day | Oishi 2004","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"0.1","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_final_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral 14 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.; EFFECT=animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","duration":"14 days","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":38,"route":"oral","species":"","study_id":"sccs_o_276_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Some effects in spleen to body weight ratio observed in males in high dose group only.; EFFECT=o have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Some effects in spleen to body weight ratio observed in males in high dose group only.","duration":"subchronic","effect":"o have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":38,"route":"oral","species":"","study_id":"sccs_o_276_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 99 - - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...; EFFECT=n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","duration":"developmental","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"route":"oral","species":"","study_id":"sccs_o_276_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 42 - - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD; DOSE=________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.; EFFECT=________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","duration":"developmental","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"route":"oral","species":"","study_id":"sccs_o_276_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.; EFFECT=SCCS-rejected applicant NOAEL: hroughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during t; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: hroughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during t","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health.; EFFECT=SCCS-rejected applicant NOAEL: al toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: al toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity.; EFFECT=ation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity.","duration":"90-day","effect":"ation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.; EFFECT=ose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.","duration":"90-day","effect":"ose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 300 mg/kg bw/day - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested.; EFFECT=ycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested. The decrease of AGD was considered as the parameter to determine the PoD. It can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, according to the new BMD guidance from EFSA (2022). This resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro According to the Applicant The in vitro mutagenicity and genotoxicity studies that have been performed are summarised in Tables 23; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested.","duration":"90-day","effect":"ycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested. The decrease of AGD was considered as the parameter to determine the PoD. It can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, according to the new BMD guidance from EFSA (2022). This resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro According to the Applicant The in vitro mutagenicity and genotoxicity studies that have been performed are summarised in Tables 23","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":51,"route":"oral","species":"","study_id":"sccs_o_276_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day human oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.; EFFECT=ith paraben mixtures and show that paraben sensitisation is rare, and is related to medical applications and not to cosmetics. Human skin sensitisation data specifically for Methylparaben are not available. Taking all the data into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.","duration":"subchronic","effect":"ith paraben mixtures and show that paraben sensitisation is rare, and is related to medical applications and not to cosmetics. Human skin sensitisation data specifically for Methylparaben are not available. Taking all the data into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":70,"route":"oral","species":"human","study_id":"sccs_o_276_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.; EFFECT=ta into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological fi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.","duration":"subchronic","effect":"ta into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological fi","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"oral","species":"","study_id":"sccs_o_276_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL of 1000 mg/kg/day was derived.; EFFECT=NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Finding; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL of 1000 mg/kg/day was derived.","duration":"90-day","effect":"NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Finding","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"oral","species":"","study_id":"sccs_o_276_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 300 mg/kg bw/day - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA.; EFFECT=dy (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, which resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. Mutagenicity / genotoxicity Methylparaben was tested for gene mutations in three Ames tests, out of which one was considered as valid by the SCCS. All studies were negative. Methylparaben was also tested in one valid mammalian cell gene mutation study on CHO cel; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA.","duration":"90-day","effect":"dy (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, which resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. Mutagenicity / genotoxicity Methylparaben was tested for gene mutations in three Ames tests, out of which one was considered as valid by the SCCS. All studies were negative. Methylparaben was also tested in one valid mammalian cell gene mutation study on CHO cel","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":70,"route":"oral","species":"","study_id":"sccs_o_276_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral 14 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.; EFFECT=animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health.","duration":"14 days","effect":"animals also had 14 days recovery. 0, 50, 250, 1000 mg/kg/day of MP in propylene glycol by oral gavage Two animals appeared to have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":38,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Some effects in spleen to body weight ratio observed in males in high dose group only.; EFFECT=o have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Some effects in spleen to body weight ratio observed in males in high dose group only.","duration":"subchronic","effect":"o have suffered misdosing and were sacrificed due to ill health. Some effects in spleen to body weight ratio observed in males in high dose group only. Some females displayed rales and gasping, with piloerection. All observations resolved. No histopathological findings; No other adverse observations in any toxicological parameters. No effects on oestrous cycle or spermatological parameters. NOAEL 1000 mg/kg/day SCCS comment From oral subchronic (28 days) repeated dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived for Methylparaben.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":38,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 99 - - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic; DOSE=202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...; EFFECT=n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the...","duration":"developmental","effect":"n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:n on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemic","page":42,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 42 - - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD; DOSE=________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.; EFFECT=________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery.","duration":"developmental","effect":"________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:________________________________________________________________________________ 42 In conclusion, the effects on 49 functional observation parameters were slightly or inconsistently changed throughout the dose groups before and at the end of treatment/recovery. These can therefore not be related to adverse effects and are not useful for the derivation of the NOAEL or LOAEL. In the absence of histopathological changes and due to reversibility of some of the effects observed, the SCCS considers the highest dose as NOEL. The sperm findings may be indicative for an anti-androgenic MoA (see also section3.4.10). Oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test In addition to the oral 90-day repeated dose toxicity study described above, based on Article 41 of Regulation (EC) No 1907/2006 (REACH-Regulation), the European Chemicals Agency (ECHA) has requested an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD","page":42,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day - oral developmental repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.; EFFECT=SCCS-rejected applicant NOAEL: hroughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during t; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: hroughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during t","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health.; EFFECT=SCCS-rejected applicant NOAEL: al toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: al toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause serious effects to health. No data were available on toxicity relating to repeated dermal exposure and inhalation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity.; EFFECT=ation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction; CITATION=Ref: Brand et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Brand et al; DETAILS_JSON={"cas_number":"99-76-3","citation":"Ref: Brand et al","dose":"Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity.","duration":"90-day","effect":"ation. Ref: Brand et al., 2017 SCCS comment All repeated dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to a NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.; EFFECT=ose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.","duration":"90-day","effect":"ose toxicity. Two further oral in vivo repeated dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day RDT study was indicative of changes pointing to an endocrine mediated MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. 3.4.5 Reproductive toxicity From the Applicant Table 25: Reproductive toxicity and developmental toxicity studies Species Method Route of exposure Dosage Results Reference Male Reproduction","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 300 mg/kg bw/day - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested.; EFFECT=ycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested. The decrease of AGD was considered as the parameter to determine the PoD. It can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, according to the new BMD guidance from EFSA (2022). This resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro According to the Applicant The in vitro mutagenicity and genotoxicity studies that have been performed are summarised in Tables 23; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested.","duration":"90-day","effect":"ycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested. The decrease of AGD was considered as the parameter to determine the PoD. It can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, according to the new BMD guidance from EFSA (2022). This resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro According to the Applicant The in vitro mutagenicity and genotoxicity studies that have been performed are summarised in Tables 23","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":51,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg/day human oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.; EFFECT=ith paraben mixtures and show that paraben sensitisation is rare, and is related to medical applications and not to cosmetics. Human skin sensitisation data specifically for Methylparaben are not available. Taking all the data into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.","duration":"subchronic","effect":"ith paraben mixtures and show that paraben sensitisation is rare, and is related to medical applications and not to cosmetics. Human skin sensitisation data specifically for Methylparaben are not available. Taking all the data into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":70,"route":"oral","species":"human","study_id":"sccs_o_276_final_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.; EFFECT=ta into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological fi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived.","duration":"subchronic","effect":"ta into consideration, together with the data from animal tests, the SCCS considers that Methylparaben is not a skin sensitiser. Acute toxicity Methylparaben is not acutely toxic. Repeated dose toxicity From oral subchronic (28 days) repeated-dose toxicity studies provided by the Applicant, a NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological fi","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1000 mg/kg bw/d - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL of 1000 mg/kg/day was derived.; EFFECT=NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Finding; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL of 1000 mg/kg/day was derived.","duration":"90-day","effect":"NOAEL of 1000 mg/kg/day was derived. All repeated-dose toxicity studies provided and discussed in the Applicants dossier and the information provided by RIVM in their 2017 report during the call for information point to an NOAEL of 1000 mg/kg bw/d for repeated dose toxicity. Two further oral in vivo 90-day repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Finding","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 300 mg/kg bw/day - oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA.; EFFECT=dy (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, which resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. Mutagenicity / genotoxicity Methylparaben was tested for gene mutations in three Ames tests, out of which one was considered as valid by the SCCS. All studies were negative. Methylparaben was also tested in one valid mammalian cell gene mutation study on CHO cel; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA.","duration":"90-day","effect":"dy (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from cohort 1B at the highest dose tested, which can be considered as an indication for an anti-androgenic MoA. The latter is also supported by effects on sperm which were observed in an oral 90-day repeated dose toxicity study. From this study, a NOAEL of 300 mg/kg bw/day could be derived. The SCCS in parallel did BMD modelling, which resulted in a BMDL5% of 374 mg/kg bw/day. As the BMDL5% value is the preferred PoD value according to the SCCS Notes of Guidance, this will be used in the MoS calculation. Mutagenicity / genotoxicity Methylparaben was tested for gene mutations in three Ames tests, out of which one was considered as valid by the SCCS. All studies were negative. Methylparaben was also tested in one valid mammalian cell gene mutation study on CHO cel","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":70,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/d - - - reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.; EFFECT=in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","duration":"","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":43,"route":"","species":"","study_id":"sccs_o_276_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg/day dog oral 422 days reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.; EFFECT=SCCS-rejected applicant NOAEL: ____________________________________________ ___________________________________________________________________________________________ 44 Matthews (1956) Dog 378-422 days 1g/kg/day dosed to n = 6 dogs; 0.5g/kg/day dosed to n = 3 dogs No toxicity was observed. All animals were in excellent condition throughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.","duration":"422 days","effect":"SCCS-rejected applicant NOAEL: ____________________________________________ ___________________________________________________________________________________________ 44 Matthews (1956) Dog 378-422 days 1g/kg/day dosed to n = 6 dogs; 0.5g/kg/day dosed to n = 3 dogs No toxicity was observed. All animals were in excellent condition throughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":44,"route":"oral","species":"dog","study_id":"sccs_o_276_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.; EFFECT=SCCS-rejected applicant NOAEL: ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"oral","species":"","study_id":"sccs_o_276_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg/day - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered.; EFFECT=SCCS-rejected applicant NOAEL: e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":45,"route":"","species":"","study_id":"sccs_o_276_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day rat - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.; EFFECT=no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.","duration":"developmental","effect":"no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"","species":"rat","study_id":"sccs_o_276_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.; EFFECT=NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.","duration":"","effect":"NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"","species":"rat","study_id":"sccs_o_276_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":"SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"","species":"","study_id":"sccs_o_276_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=______________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attribute; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":"______________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attribute","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"","species":"","study_id":"sccs_o_276_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 300 mg/kg bw/day - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":50,"route":"","species":"","study_id":"sccs_o_276_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/d - - 90-day reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.; EFFECT=y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Findings from the Vo et al. (2010) study (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.","duration":"90-day","effect":"y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Findings from the Vo et al. (2010) study (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"","species":"","study_id":"sccs_o_276_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 - - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal; EFFECT=Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"","duration":"developmental","effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 - - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose; DOSE=T | wo further | oral in vivo re | peated dose; EFFECT=Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"T | wo further | oral in vivo re | peated dose","duration":"developmental","effect":"Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose","page":44,"route":"oral","species":"","study_id":"sccs_o_276_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 10000 ppm rat oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_276; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=10,000; DOSE=In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.; EFFECT=Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","duration":"","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_noael_038"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/d - - - reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.; EFFECT=in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The study authors derived a NOAEL of 1000 mg/kg bw/d from that study.","duration":"","effect":"in females of the MD group. There was no histological evidence of toxicity in the reproductive organs and tissues including testes, epididymides, prostate gland, seminal vesicles, coagulating glands, ovaries, uterus, cervix, and vagina. No treatment-related effects on the testicular histomorphology and interstitial cell structure were noticed. Substance treatment did not induce histomorphological effects in the reproductive organs of the non-pregnant females and their pairing partners. The study authors derived a NOAEL of 1000 mg/kg bw/d from that study. SCCS comment Most of the changes observed in this study were not statistically significant and for several observations, dose-dependency was not observed. In addition, the effects reported were not accompanied by histopathological changes. Regarding AGD, no difference was observed in male and female pups on PND 0 and in nipple retention of male pups on PND 12. In female pups, the relative AGD in the LD group was statistically significantly lower when compared to controls, which","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":43,"route":"","species":"","study_id":"sccs_o_276_final_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg/day dog oral 422 days reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.; EFFECT=SCCS-rejected applicant NOAEL: ____________________________________________ ___________________________________________________________________________________________ 44 Matthews (1956) Dog 378-422 days 1g/kg/day dosed to n = 6 dogs; 0.5g/kg/day dosed to n = 3 dogs No toxicity was observed. All animals were in excellent condition throughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day.","duration":"422 days","effect":"SCCS-rejected applicant NOAEL: ____________________________________________ ___________________________________________________________________________________________ 44 Matthews (1956) Dog 378-422 days 1g/kg/day dosed to n = 6 dogs; 0.5g/kg/day dosed to n = 3 dogs No toxicity was observed. All animals were in excellent condition throughout the study, Conclusion of the Applicant: Although the study by Matthews was performed in 1956, prior to the development of OECD Test Guidelines, the study has been used for many decades to define an oral NOAEL for general toxicity for Methylparaben as 1000 mg/kg/day. Subsequent studies investigating reproductive and developmental effects (i.e. Oishi (2004) and the Charles River 2005 study published as Hoberman et al. 2008, and a 28-day study by Beerens- Heijnen (2009) have further corroborated this oral NOAEL. There are no effects seen in dermal toxicity studies. RIVM report, 2017 Based on the available repeated-dose toxicity studies, repeated oral exposure to methyl-, ethyl- or propylparaben is not considered to cause","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":44,"route":"oral","species":"dog","study_id":"sccs_o_276_final_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.; EFFECT=SCCS-rejected applicant NOAEL: ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: ne) and testosterone Oral 0, 100, 1000 and 10,000 ppm in food There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg/day - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered.; EFFECT=SCCS-rejected applicant NOAEL: e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: e small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day Hoberman et al. 2008; Charles River 2005. Applicant conclusions from reproduction and developmental toxicology studies: Methylparaben showed no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":45,"route":"","species":"","study_id":"sccs_o_276_final_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day rat - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.; EFFECT=no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.","duration":"developmental","effect":"no relevant adverse effects in reproductive and developmental studies. The NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.; EFFECT=NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation.","duration":"","effect":"NOAEL of 1000 mg/kg/day can be used as the point of departure in safety evaluation. RIVM report, 2017 For Methylparaben no OECD TG studies on reproductive toxicity were performed, but relevant peer-reviewed studies were performed and summarized in this paragraph. All these studies investigated the effects of methyl-, ethyl- and propylparaben exposure on the reproduction of male and female animals. As previously stated, for Methylparaben, a NOAEL of 1000 mg/kg bw/day was derived from the study by Oishi (2004). The NOAEL of 1000 mg/kg bw/day from this study also supported the establishment of the ADI for Methylparaben by EFSA. Oishi (2004) did not find any reproductive effects in rats after Methylparaben exposure up to a level","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":45,"route":"","species":"rat","study_id":"sccs_o_276_final_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":"SCCS/1652/23 Final Opinion Corrigendum February 2024 Opinion on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7) _________________________________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"","species":"","study_id":"sccs_o_276_final_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=______________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attribute; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":"______________________________________________________________________ ___________________________________________________________________________________________ 50 histopathological evaluation of lymph nodes, Peyer’s patches, spleen and thymus of parental and Cohort 1A animals, where no test item related effects were observed. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attribute","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"","species":"","study_id":"sccs_o_276_final_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 300 mg/kg bw/day - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=300; DOSE=In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.; EFFECT=. In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study.","duration":"developmental","effect":". In the absence of indication of toxicity, the NOAEL for developmental and reproductive toxicity, developmental neurotoxicity and developmental immunotoxicity the study authors derived a NOAEL of 1000 mg/kg body weight/day from this study. SCCS comment Cohort 1 The most remarkable findings in Cohort 1 was the statistically significantly (p<0.001) reduced relative AGD in male F2 pups at the highest dose tested, which can be considered indicative for an anti-androgenic mode of action. Based on this observation, a NOAEL of 300 mg/kg bw/day is derived from this study. The statistically significantly reduced percentage of static sperm count in all Methylparaben treated groups of cohort 1A might be attributed to the high variability observed in the control group. In addition, the finding might be compensated by increasing percentages of motile and rapid counts observed at the same time. For this reason, the SCCS did not use this observation for the PoD derivation. Cohort 2 The SCCS has carefully evaluated the effects on development","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":50,"route":"","species":"","study_id":"sccs_o_276_final_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1000 mg/kg bw/d - - 90-day reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=1000; DOSE=y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.; EFFECT=y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Findings from the Vo et al. (2010) study (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS.","duration":"90-day","effect":"y repeated-dose toxicity studies that had been requested in the context of another legislation have been made available to the SCCS. While the combined repeat-dose toxicity/reproductive toxicity study confirmed a NOAEL of 1000 mg/kg bw/d, the 90-day repeated-dose toxicity study was indicative of changes pointing to an endocrine mediated (anti-androgenic) MoA and effects on male reproductive parameters, however without histopathological findings. Therefore, the highest dose of 1000 mg/kg bw/d can be regarded as the NOAEL. Reproductive toxicity Apart from studies provided by the Applicant and described in the RIVM report, two further studies were made available to the SCCS (one OECD TG422 study and dan OECD TG 443 study). Findings from the Vo et al. (2010) study (effects on the date of vaginal opening, the length of the estrous cycle and affected organ weight (thyroid, liver, adrenal gland and ovary)) were not confirmed by the new guideline studies (OECD TG 422/421; OECD 443). However, reduction of AGD was observed in F2 pups from","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":70,"route":"","species":"","study_id":"sccs_o_276_final_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 - - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal; EFFECT=Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"","duration":"developmental","effect":"Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 25: Reproductive toxicity and developmental toxicity studies: Heijnen (2009) ha | ve further cor | roborated t | his oral NOAEL | . There ar | e no effects se | en in dermal","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 - - oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=unclear:Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose; DOSE=T | wo further | oral in vivo re | peated dose; EFFECT=Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"T | wo further | oral in vivo re | peated dose","duration":"developmental","effect":"Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 25: Reproductive toxicity and developmental toxicity studies: NOAEL of 1000 m | g/kg bw/d for | repeated d | ose toxicity. T | wo further | oral in vivo re | peated dose","page":44,"route":"oral","species":"","study_id":"sccs_o_276_final_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 10000 ppm rat oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_276_final; REPORT_TITLE=Final Opinion Corrigendum February 2024 Scientific Committee on Consumer Safety SCCS OPINION on Methylparaben (CAS No. 99-76-3, EC No. 202-785-7); OPINION_NUMBER=SCCS/1652/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 December 2023; VALUE_TEXT=10,000; DOSE=In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.; EFFECT=Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-76-3","citation":"","dose":"In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups.","duration":"","effect":"Unlabeled table on page 45: Crj:Wistar rat (n=16 per group) | Repetition of the Oishi study (2004) under GLP with MP using the same strain of rats at a higher number of animals per group. In addition to the parameters of the Oishi study, blood samples were taken weekly for the analysis of LH (luteinizing hormone), FSH (follicle stimulating hormone) and testosterone | Oral | 0, 100, 1000 and 10,000 ppm in food | There were no relevant treatment related effects on testes, ventral prostates and preputial glands in any of the groups. There were no relevant effects on male reproductive parameters. The small but statistically significant increase in abnormal sperm in the 10,000 ppm group was not considered relevant due to the low magnitude and the fact that no other reproductive parameters were altered. The highest dose level in food corresponds approximately to a NOAEL of 1000 mg/kg bw/day | Hoberman et al. 2008; Charles River 2005.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":45,"route":"oral","species":"rat","study_id":"sccs_o_276_final_noael_038"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier A2I8C7HI9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"A2I8C7HI9T"}
openFDA substances FDA UNII substance identifier A2I8C7HI9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"A2I8C7HI9T"}
openFDA substances FDA UNII substance identifier A2I8C7HI9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"A2I8C7HI9T"}
openFDA substances FDA UNII substance identifier A2I8C7HI9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"A2I8C7HI9T"}