Bisphenol A diglycidyl ether
MAK Value Documentation, supplement – Translation of the German version from 2020
Andrea Hartwig1 (Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft)MAK Commission2
1 Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany
2 Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany
Abstract
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated bisphenol A diglycidyl ether [1675-54-3] considering all toxicological end points. The critical effects of bisphenol A diglycidyl ether in humans and in animals are skin sensitization and spleen toxicity in rats after oral exposure. In several studies in mice, bisphenol A diglycidyl ether was not carcinogenic to the skin. In a guideline study in rats with gavage application of up to 100 mg/kg body weight and day, the substance was not carcinogenic and no effects were observed in the stomach, the site of first contact. After dermal application of bisphenol A diglycidyl ether, the promutagenic DNA adduct hydroxymethylethenodeoxyadenosine-3′-monophosphate was found in the skin of mice. However, as local carcinogenicity was not induced even after the substance was administered as an oral bolus (see above), DNA adduct formation is assumed to be insufficient for tumour induction. This might be due to adequate detoxification of the substance in vivo. There is strong evidence that epoxide hydrolase has a greater detoxification capacity in human skin than in mouse skin. Thus, the assignment to Carcinogen Category 3 A is withdrawn. As aerosol exposure to bisphenol A diglycidyl ether at the workplace is to be assumed and inhalation studies are not available, a maximum concentration at the workplace (MAK value) cannot be derived. In prenatal toxicity studies in rats and rabbits, developmental toxicity was not observed up to the highest doses tested of 540 (rat, oral), 180 (rabbit, oral) and 300 (rabbit, dermal) mg/kg body weight and day. Bisphenol A diglycidyl ether induces mutations in bacteria and is clastogenic to mammalian cells. The substance was neither clastogenic nor mutagenic in several tests in vivo, including 2 dominant lethal tests, and is thus not a systemic genotoxin in vivo. Clinical data from humans and animal experiments show clear evidence of a contact sensitizing potential and the designation with “Sh” is retained. Respiratory sensitizing effects are suspected, but the data are not sufficient to label the substance with “Sa”. The dose taken up via the skin as calculated from in vitro experiments is considerably lower than the tolerable systemic dose extrapolated from chronic oral administration in rats. Hence, the designation with “H” is not retained.
