BETA-OXIDATION OF 2-ETHYL-5-CARBOXYPENTYL PHTHALATE IN RODENT LIVER

[7-14C]-2-Ethyl-5-carboxypentylphthalate was isolated and purified from urine of rats given [7-14C]-di-(2-ethylhexyl)phthalate. This metabolite was shown to serve as a precursor for 2-ethyl-3-carboxypropylphthalate in vivo. 2-Ethyl-5-carboxypentylphthalate was oxidized to 2-ethyl-3-carboxypropylphthalate in liver slices from control or, much more rapidly, from clofibrate-pretreated rats. Inhibition by KCN in liver slices from untreated rats, and strong inhibition by acrylate, suggested that formation of 2-ethyl-3-carboxypropylphthalate involved mitochondrial .beta.-oxidation. The strong enhancement of the production of this compound by clofibrate (a very weak inducer for mitochondrial dehydrogenases), and strong inhbition by chlorpromazine suggested that peroxisomes may also be able to oxidize 2-ethyl-5-carboxypentylphthalate. We were able to detect .beta.-oxidation of 2-ethyl-5-carboxypentylphthalate to 2-ethyl-3-carboxypropylphthalate using purified mitochondria, but strong phthalate monoester hydrolase activity observed during incubation of the former compound with purified peroxisomes made it impossible to determine whether 2-ethyl-3-carboxypropylphthalate could be produced in the latter organelle or not. 2-Ethyl-5-carboxypentylphthalate was such an inefficient substrate for .beta.-oxidation compared to palmitic acid that it is unlikely that it contributes significantly to the production of H2O2 in rats chronically exposed to di-(2-ethylhexyl) phthalate. Normal fatty acids are most likely to serve as the dominant substrates for peroxisomal .beta.-oxidase.