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J T Corbett

Publications and source records attributed to J T Corbett.

38 records · Page 3Linked to original sources

Identification of the metabolites of di-(2-ethylhexyl) phthalate in urine from the African green monkey.

The metabolites of di-(2-ethylhexyl) phthalate (DEHP) found in urine from African Green monkeys after intravenous administration of the 14C-labeled parent compound were isolated and identified. Criteria of identification included cochromatography with rat-derived standards on direct-phase HPLC and a variety of gas-chromatographic columns, as well as correspondence of mass spectra (70-eV electron impact and methane positive chemical ionization) with those of known standards. Approximately 80% of the urinary metabolites were excreted in the form of glucuronide conjugates. This is analogous to what has been reported for the urinary metabolites of DEHP from humans, but in clear contrast to the metabolites found in rat urine. Rat urinary metabolites of DEHP are excreted unconjugated, and consist primarily of derivatives more highly oxidized than the major metabolites produced by monkey or human. It is suggested that the African Green monkey may be a better model for human metabolism of DEHP than is the rat.

Animals↗

In vitro metabolism of mono-2-ethylhexyl phthalate by microsomal enzymes. Similarity to omega- and (omega-1) oxidation of fatty acids.

Mono-2-ethylhexyl pthalate (MEHP) is oxidized to omega-, omega-1-, and omega-2-hydroxylation products as well as (very slightly) to a dicarboxylic acid by washed microsomes from rat liver and kidney, and rabbit but not rat lung. The reactions involve molecular oxygen, are strongly inhibited by carbon monoxide and oxidized cytochrome c, and NADPH is preferred over NADH. Piperonyl butoxide inhibits hydroxylation of MEHP, but clofibrate does not. The differential effects of inducers (phenobarbital and clofibrate) and inhibitors (sodium laurate, n-decane, metyrapone) on terminal and subterminal hydroxylation as well as differences in apparent Km for the two suggest that rat liver contains at least two different MEHP hydroxylases. Comparisons of tissue distribution, susceptibility to inhibitors, and induction properties suggest that the hydroxylation of MEHP is more likely to be mediated by the P-450 isozymes associated with omega- and (omega-1)-hydroxylation of fatty acids than with those that utilize hydrocarbons as substrates.

Animals↗