Chemical industry voluntary test program for phthalate esters: health effects studies
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.
- Research Organization:
- Eastman Kodak Co., Rochester, NY
- OSTI ID:
- 5267600
- Journal Information:
- Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PHTHALIC ACID ESTERS
TOXICITY
CARCINOGENESIS
CATALASE
CHEMICAL INDUSTRY
CHOLESTEROL
LIVER
METABOLITES
MICE
MONKEYS
RATS
TRIGLYCERIDES
ANIMALS
BODY
DIGESTIVE SYSTEM
ENZYMES
ESTERS
GLANDS
HYDROXY COMPOUNDS
INDUSTRY
LIPIDS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATHOGENESIS
PEROXIDASES
PRIMATES
RODENTS
STEROIDS
STEROLS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)