Subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl in rats.
The subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl (PCB 128) was investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for 13 wk. The growth rate was not affected by treatment and no apparent clinical signs of toxicity were observed. There was a significant increase in liver weight in the 50 ppm females. The liver ethoxyresorufin deethylase (EROD) activity was increased by five- and fourfold in the highest dose males and females, respectively, while aminopyrine demethylase (ADPM) activity was significantly increased only in the highest dose females. Liver vitamin A was significantly reduced in the highest dose females. No other biochemical or hematological effects were observed. Treatment-related histopathological changes were seen in the thyroid and liver, and to a lesser extent in the bone marrow and thymus. Residue data showed a dose-dependent accumulation of PCB 128 in the following tissues: fat, liver, kidney, brain, spleen, and serum, with the highest concentration being found in fat followed by liver and kidney. Based on these data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm in diet or 42 micrograms/kg body weight.
Lecavalier
P
P
Health Protection Branch, Health Canada, Ottawa, Ontario, Canada.
Chu
I
I
Yagminas
A
A
Villeneuve
D C
DC
Poon
R
R
Feeley
M
M
Håkansson
H
H
Ahlborg
U G
UG
Valli
V E
VE
Bergman
A
A
Seegal
R F
RF
Kennedy
S W
SW
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014801:Vitamin A / Q000378:metabolism
D014801:Vitamin A; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; C014218:2,3,4,2',3',4'-hexachlorobiphenyl