Bis(2-ethylhexyl)phthalate (DEHP)

Executive Summary

Abstract

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of bis(2-ethylhexyl)phthalate (DEHP) (CAS No.117-81-7) as a substance related to revision of the standards and criteria for apparatuses, containers and packages. The primary adverse effects of DEHP were observed on reproductive and developmental toxicity and carcinogenicity in the tested animals. Maternal exposure to DEHP during gestational and lactational periods resulted in adverse effects on the reproductive tract in male offspring. For carcinogenicity, DEHP has been reported to induce hepatic tumors in mice and rats, but the carcinogenicity in humans is unclear after oral exposure. With regard to the genotoxicity of DEHP, most of data in vitro and in vivo were negative. DEHP and its metabolites were thus likely to interact indirectly with DNA. Thus, FSCJ regarded it as possible to establish the tolerable daily intake (TDI) of DEHP. The lowest no-observed-adverse-effect level (NOAEL) of all the tests is 3 mg/kg body weight/day, which was obtained in gavage administration study in rats during the period from gestation day 7 to postnatal day 16. FSCJ established a TDI of DEHP of 0.03 mg/kg body weight/day, applying uncertainty factor of 100, which consists of 10 for species difference and 10 for individual difference, to the lowest NOAEL of 3mg/kg body weight/day.