Impaired metabolism of di(2‐ethylhexyl) phthalate (DEHP) in old rats‐an in vitro study

Abstract

Liver, kidney, and lung homogenates from 45‐ and 630‐d‐old rats were incubated with 0.5 μCi of ¹⁴ C‐labeled di(2‐ethylhexyl) phthalate (DEHP) for 40 min at 37°C. Radiochromatogram scans of the ether extracts of the incubated mixtures showed the presence of a peak corresponding to the hydrolytic product monoethylhexyl phthalate (MEHP), in addition to the parent DEHP. Preparations from old animals revealed another radioactive zone along with MEHP. A dramatic reduction in the formation of MEHP was observed only with homogenates of livers from the old animals. It is shown that this difference is probably attributable to differences in K_m values of the enzymes from adult and old rats respectively. Protein content in the three tissues did not differ between young and old animals. Formation of MEHP is a major step in the metabolic pathway of the plasticizer DEHP. Impairment of this conversion could possibly alter the rate of its excretion and hence its toxicologic significance.