Benzylbutylphthalat [MAK Value Documentation in German language, 2018

Abstract

Abstract The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated benzyl butyl phthalate [ 85‐68‐7 ] to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. Critical effect is the toxicity to kidneys and liver. In higher doses benzyl butyl phthalate acts adversely to male reproductive organs, fertility and fetal development. The NOAEC of 218 mg/m 3 derived from a 13‐week inhalation study in rats is used to set a MAK value of 20 mg/m 3 for the respirable fraction (R), the MAK value is supported by the long‐term feeding studies in rats and mice. Since a systemic effect is critical, Peak Limitation Category II is assigned. The default excursion factor of 2 is set as no half‐life in blood is known. In prenatal toxicity studies in rats at 450 mg/kg body weight and day and above an increased number of resorptions and at 750 mg/kg body weight and day increased mortality and teratogenicity occurred, with a NOAEL of 350 mg/kg body weight and day. From a 2‐generation study in rats a NOAEL for fetotoxicity of 100 mg/kg body weight and day was derived. In a prenatal study in mice the LOAEL for increased resorptions and malformations was 910 mg/kg body weight and day with a NOAEL of 182 mg/kg body weight and day. The NOAELs can be scaled to concentrations of 613 mg/m 3 (rat, prenatal), 182 mg/m 3 (mice, prenatal) and 245 mg/m 3 (rat, pre‐ and postnatal), respectively, at the workplace. Thus, damage to the embryo or foetus is unlikely when the MAK value is observed, and benzyl butyl phthalate is classified in Pregnancy Risk Group C. Available in vitro and in vivo data predominantly show no genotoxic effects. A contribution of cytotoxic effects for some positive test results cannot be excluded. A dominant lethal test with subcutaneous administration to rats was negative. Therefore, the substance is not regarded as a germ cell mutagen. No increased tumour incidence was observed in chronic feeding studies in mice. In F344 rats at high doses an increased incidence of mononuclear cell leukemia is observed, which was within the range of the historical control. Furthermore in F344 rats incidences of adenomas (pancreas tumours, adrenal phaeochromocytomas, urinary bladder tumours), but not of carcinomas are increased. The adenoma incidences were mainly within the range of historical controls. A carcinogenic effect in humans, therefore, is unlikely. Skin contact is not expected to contribute significantly to systemic toxicity. Data in humans and limited data in animals do not show a skin sensitizing potential.