摘要：The Chemical Manufacturers' Association voluntary test program on phthalate esters is described, and the results of certain key aspects of the program are presented. Representative phthalate esters were chosen for genotoxicity testing and peroxisome proliferation screening, and di-2-ethylhexyl phthalate (DEHP) and its initial metabolic products were tested in the genotoxicity battery. A comparative metabolism study was performed with DEHP in the mouse, rat, and cynomologus monkey, together with a study of the metabolism of DEHP in the rodent at several dose levels, and after prolonged feeding. A standard test for peroxisome proliferation in the rat, employing 21 days of feeding and several end points is described, based on DEHP as a reference compound. DEHP is shown to be nongenotoxic in the test battery, and its initial major metabolites are also nongenotoxic. A nonlinear dose response with respect to the beta-oxidation of DEHP in the rodent is demonstrated. Quantitative differences exist between the mouse and rat, and the cynomologus monkey with respect to the beta-oxidation of DEHP, beta-oxidation being a much less used pathway in the monkey. The significance of these results in interpreting the hepatocellular carcinogenesis of DEHP in the Fischer 344 rat is discussed. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 329 330 331 332 333 334 335 336
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