Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume
Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2',4'-TCB or 3,4,3',4'-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pair-fed to the 3,4,3',4'-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3',4'-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3',4'-TCB- but not in the 2,4,2',4'-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2',4'-TCB and in mink after 3,4,3',4'-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2',4'-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2',4'-TCB than for 3,4,3',4'-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction.
- Research Organization:
- Univ. of California, Davis
- OSTI ID:
- 6785659
- Journal Information:
- Fundam. Appl. Toxicol.; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORINATED AROMATIC HYDROCARBONS
TOXICITY
ENDOPLASMIC RETICULUM
ULTRASTRUCTURAL CHANGES
LIVER
ENZYME ACTIVITY
MAMMALS
SENSITIVITY
ADIPOSE TISSUE
BODY BURDEN
COMPARATIVE EVALUATIONS
CYTOCHROMES
RATS
STRUCTURE-ACTIVITY RELATIONSHIPS
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CELL CONSTITUENTS
CONNECTIVE TISSUE
DIGESTIVE SYSTEM
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
MORPHOLOGICAL CHANGES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
PROTEINS
RODENTS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology