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Peroxisome Induction Studies On Seven Phthalate Esters

Eastman Kodak Company Rochester, New York

Bernard D. Astill

Eastman Kodak Company Rochester, New York

Elizabeth J. Moran

Chemical Manufacturers Association Washington, D.C.

Bernard F. Schneider

Case Western Reserve University Cleveland, Ohio

Tim J.B. Gray

British Industrial Biological Research Association Carshalton, Surrey, England

Brian G. Lake

British Industrial Biological Research Association Carshalton, Surrey, England

John G. Evans

British Industrial Biological Research Association Carshalton, Surrey, England

Seven phthalate esters, representing a variety of chain lengths and degrees of branching in the alcohol moiety, were tested for their ability to produce peroxisome proliferation in the Fischer 344 rat. Di(2-ethylhexyl)adipate (DEHA) was tested using the same protocol and di(2-ethylhexyl)phthalate (DEHP) was run with each study as an internal control. Each ester was administered in the feed for a period of 21 days at levels of 2.5%, 1.2% and either 0.6% or 0.3%. DEHP and DEHA were also fed at levels of 0.1% and 0.01%. The animals were sacrificed and samples of liver were prepared for both light and electron microscopy. Serum samples were assayed for both triglyceride and cholesterol. The remaining portion of the liver was homogenized and assayed for cyanide-insensitive palmitoyl-CoA oxidation, lauric acid 11-hydroxylase and lauric acid 12-hydroxylase. The results show that there is approximately a ten-fold difference between the weakest and strongest esters in terms of their potency to induce changes in relative liver weight and in several of the biochemical parameters. In general, the longer chain esters were more potent than the shorter chain ones, and branched chain esters seemed more potent than straight. Several statistical analyses of the dataset have been performed and all render similar conehcsions. The results of one of these evaluations are presented elsewhere in this volume (Lin, 1987).

Key Words: Fischer 344 rat • peroxisome proliferation • phthalate esters • structure • activity relationships.

Toxicology and Industrial Health, Vol. 3, No. 2, 7-24 (1987)
DOI: 10.1177/074823378700300203


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