Peroxisome Induction Studies On Di(2-Ethylhexyl)Terephthalate

Author:

Topping Douglas C.1,Ford Graham P.2,Evans John G.2,Lake Brian G.2,O'Donoghue John L.1,Lockhart Haines B.1

Affiliation:

1. Health and Environment Laboratories Eastman Kodak Company Rochester, New York

2. British Industrial Biological Research Association Carshalton, Surrey England

Abstract

Groups of five male and five female rats were fed diets containing from 0% to 2.5% di(2-ethylhexyl)terephthalate (DEHT) or 1.2% di(2-ethylhexyl)phthalate (DEHP) for 21 days. Feed consumption and body weight gains were collected and, at study termination, animals were examined for alterations in body weight, differences in serum lipids, changes in the activities of certain enzymes associated with fat metabolism, and proliferatiort of hepatic peroxisomes. Feed consumption and weight gain were greatly decreased in DEHT-fed animals only at 2.5%. No biologically significant alterations in absolute liver weight occurred with DEHT. Relative liver weights were increased at 2.5% in both sexes and at 1.0% and 1.2% in females. The alterations were due wholly to decreased terminal body weights. Serum triglyceride and cholesterol levels were not found useful in interpreting the effects of DEHT Cyanide-insensitive palmitoyl CoA oxidation and lauric acid 11- and 12-hydroxylation were increased in animals cortsuming 2.5%, but no lower levels of DEHT. Induction of hepatic peroxisomes did not occur at 1.2% DEHT. Interpretation of minimal peroxisomal effects with 2.5% DEHT ivas confounded by reduced feed consumption. Slight decreases in weight gain occurred in males consuming the 1.2% DEHP diet, but differences were minor relative to effects observed at 2.5% DEHT. Results with DEHP contrasted with those obtained with DEHT. Absolute and relative liver weights, activities of enzymes of lipid metabolism, and peroxisorne content were all significantly increased at 1.2% DEHP. Reduction of feed intake was implicated in the effects observed at 2.5% DEHT, since the amount of DEHT consumed by 2.5% animals ivas only 1.4 times as much as by 1.2% animals. A possible explanation for the observed differences between DEHP and DEHT was related to the results of a metabolic fate study on DEHT. Metabolism of DEHT by the rat appears to occur via rapid hydrolysis of both ester linkages to give two moles of 2-ethylhexanol and one mole of terephthalic acid. Although 2-ethylhexanol has been shown to induce peroxisome proliferation, it appears to be less active in this respect than the monoester of DEHP. The relatively smaller amounts of monoester produced during the metabolism of DEHT may explain the differences seen in these experiments.

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Toxicology

Reference17 articles.

1. Metabolism of diethylhexyl phthalate by rats

2. Barber, E.D., Astill, B.D., Moran, E.J., Schneider, B.F., Gray, T.J.B., Lake, B.G. and Evans, J.G. (1987). The results of peroxisome induction studies on seven phthalate esters. Toxicol. Indus. Hlth. 3.

3. Peroxisomal effects of phthalate esters in primary cultures of rat hepatocytes

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