4-hydroxybenzoic acid

Carcinogenicity

Description of key information

A 96 weeks feeding study with Wistar rats was performed with dosages of 0%, 2%, 8% Methyl-4-hydroxy benzoate (methylparaben) in the diet. Please refer to the detailed justification of the read across approach in the separate read across rationale annexed to the Chemical Safety Report (in section 13 of IUCLID). In treatments with 8% drug diet reduced body weight gain was observed. Gross pathology and histopathology revealed no abnormal findings. Mongrel dogs were dosed with Methy-4-hydroxy benzoate in gelatine capsules. The highest dose group received 1000 mg/kg bw per day for 6 days a week for at least 378 days. Clinical observations, body weights, haematology, urine analysis, gross pathology and histopathology revealed no abnormalities. As the studies with repeated administration revealed toxicity at lower dose levels, these levels are also taken for evaluation of carcinogenicity.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Justification for classification or non-classification

Two longterm studies one with rats another one with dogs revealed no hints for a carcinogenic patential of 4 -HBA.

Additional information

Data of methylparaben and ethylparaben can be taken for the evaluation of 4-HBA as there is a close structural similarity and the fact that 4-HBA is the main breakdown product of the precursor methylparaben and ethylparaben after oral administration. Justification for read-across: similar chemical structure (common functional group) and common precursors and/or the likelihood of common breakdown products via physical and biological processes, which result in structurally similar chemicals (for justification see annex with read across rationale to the Chemical Safety Report (in section 13 of IUCLID)).

A 96 weeks feeding study with the read across substance Methy-4-hydroxy benzoate (methylparaben) with Wistar rats was performed with dosages of 0%, 2%, 8% drug diet. In treatments with 8% drug diet reduced body weight gain was observed. Gross pathology and histopathology revealed no abnormal findings. Mongrel dogs were dosed with Methy-4-hydroxy benzoate in gelatine capsules. The highest dose group received 1000 mg/kg bw per day for 6 days a week for at least 378 days. Clinical observations, body weights, haematology, urine analysis, gross pathology and histopathology revealed no abnormalities.

Phamacokinetic investigations showed that Metyl-4 -hydroxy benzoate is transformed to 4-HBA in the body. Therefore, these studies can be used to assess carcinogenic effects of 4-HBA. Please refer to the detailed justification of the read across approach in the separate read across rationale annexed to the Chemical Safety Report (in section 13 of IUCLID). As the studies with repeated administration revealed toxicity at lower dose levels, these levels are also taken for evaluation of carcinogenicity.