In Vivo and In Vitro Metabolism of Di-(2-ethylhexyl) Adipate a Peroxisome Proliferator, in the Rat

Abstract

Di-(2-ethylhexyl) adipate (DEHA) is a plasticizer commonly used in PVC films for its qualities of stretch and cling, and can constitute up to 40% of the film. This lipophilic chemical could migrate into the food due to its high solubility in lipids and also because it is not covalently bound to the matrix polymer. On the other hand, previous results obtained with di-(2-ethylhexyl) phthalate (DEHP) (Mitchell et al. 1984) have shown that monoester and 2-ethylhexanol (EH) are involved in peroxisome proliferation induced by DEHP. Induction of peroxisome proliferation in rat has also been demonstrated with DEHA (Moody and Reddy 1978; Reddy and Lalwani 1983). According to Reddy et al. (1980), peroxisome proliferators appear to be a novel class of chemical carcinogens, and carcinogenic properties of DEHA have been established in B6C3F1 female mice (NTP 1982). Primary rat hepatocyte cultures have been used previously (Gray et al. 1982; Mitchell et al. 1985) in order to determine to the ultimate proximate peroxisome proliferator issued from DEHP. This study, performed in vivo and in vitro, was designed in order to obtain a better knowledge of the different metabolic steps involved in the hepatic concentration of the major peroxisomal proliferator (2-ethylhexanoic acid: EHA) (Cornu 1987) following DEHA administration. This study is also part of broader research devoted to a better understanding of the relationship between metabolism differences and species differences in hepatic peroxisome proliferation.