Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man
Certain phthalate esters and hypolipidemic agents are known to induce morphological and biochemical changes in the liver of rodents, which have been associated with an increased incidence of hepatocellular tumors in these species. There is evidence that hypolipidemic agents do not induce these effects in either subhuman primates or man. The oral and intraperitoneal administration of di(2-ethylhexyl) phthalate (DEHP) to the marmoset monkey at doses up to 5 mmole DEHP/kg body weight/day for 14 days did not induce morphological or biochemical changes in the liver or testis comparable with those obtained in rats given the same amount of DEHP. In the marmoset, the excretion profile of (/sup 14/C)-DEHP following oral, IP, and IV administration and the lower tissue levels of radioactivity demonstrated a considerably reduced absorption in this species compared to the rat. The urinary metabolite pattern in the marmoset was in many respects qualitatively similar to but quantitatively different from that in the rat. The pharmacokinetic differences between these two species indicate that the tissues of the marmoset are exposed to a level of DEHP metabolites equivalent to the complete absorption of a dose of Ca. 0.1 to 0.25 mmole DEHP/kg body weight/day without significant toxicological effects. The evidence suggests that in some nonrodent species the hepatocellular and testicular response to DEHP is considerably less than that in rodents and is dose-dependent.
- Research Organization:
- Imperial Chemical Industries PLC, Macclesfield, England
- OSTI ID:
- 5430246
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 65
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CARBON 14 COMPOUNDS
EXCRETION
PHTHALIC ACID ESTERS
PHARMACOLOGY
TOXICITY
DOSE-RESPONSE RELATIONSHIPS
LIVER
MAN
MONKEYS
RATS
RODENTS
TESTES
ANIMALS
BODY
CLEARANCE
DIGESTIVE SYSTEM
ESTERS
GLANDS
GONADS
LABELLED COMPOUNDS
MALE GENITALS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
551001 - Physiological Systems- Tracer Techniques