Subchronic toxicity of PCB 105 (2,3,3',4,4'-pentachlorobiphenyl) in rats.
The toxicity of 2,3,3',4,4'-pentachlorobiphenyl (PCB 105) was investigated in Sprague-Dawley rats following dietary exposure to this substance at levels of 0, 0.05, 0.5, 5 or 50 ppm for 13 weeks. Growth rate and food consumption were not affected and no clinical signs of toxicity were observed. Increased incidences of enlarged, fatty liver and decreased thymic weight were observed in the highest-dose groups of both genders; these groups also had elevated hepatic microsomal ethoxyresorufin deethylase activity and uroporphyrin. Significant increases in serum cholesterol and hepatic pentoxyresorufin dealkylase activity were observed in the highest-dose males and two highest-dose females. By contrast, liver UDP-glucuronosyl transferase activity was elevated in the two highest-dose males and the highest-dose females. Urinary ascorbic acid excretion was increased in the highest-dose males. While the amount of vitamin A was decreased dose-dependently, starting at 0.5 ppm in the liver of both sexes and in the lung of the females, the level in the kidney of the highest-dose group was increased. Administration of PCB 105 resulted in decreased dopamine in the caudate nucleus region of the brain in males and homovanillic acid in caudate nucleus and nucleus accumbens of females. Increased 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed in the substantia nigra region of both sexes, with most of the increases being seen in highest-dose females. Anemia, characterized by decreased hemoglobin, hematocrit and red cell indices, occurred in the highest-dose group, as did eosinophilia. Treatment with PCB 105 caused dose-dependent histopathological changes in the liver and thyroid. Thymic changes were observed in the highest-dose males and two highest-dose females. Tissue residue data showed a dose-dependent accumulation of this congener in fat, liver and spleen, kidney and brain. Based on these data the no-observable-effect level of PCB 105 was judged to be 0.05 ppm or 3.9 microg kg(-1) body wt. day(-1) in males and 4.2 microg kg(-1) body wt. day(-1) in females.
Chu
I
I
Health Protection Branch, Tunney's Pasture, Ottawa, Ontario, Canada.
Poon
R
R
Yagminas
A
A
Lecavalier
P
P
Håkansson
H
H
Valli
V E
VE
Kennedy
S W
SW
Bergman
A
A
Seegal
R F
RF
Feeley
M
M
D000284:Administration, Oral; D000588:Amines / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006403:Hematologic Tests; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D018675:Toxicity Tests; D014801:Vitamin A / Q000032:analysis
D000588:Amines; C067940:2,3,3',4,4'-pentachlorobiphenyl; D014801:Vitamin A; D011078:Polychlorinated Biphenyls