[Toxicological assessment of 2,5,2',5'-tetrachlorobiphenyl and its major metabolite, 3-hydroxy-2,5,2',5'-tetrachlorobiphenyl in rats].
We observed previously that polychlorinated biphenyl (PCB) could be classified to two groups, 3-methylcholanthrene (MC)-type and phenobarbital (PB)-type, in term of inducibility of the hepatic enzymes. MC-type PCBs such as 3,4,3',4'-tetrachlorobiphenyl (TCB), 3,4,5,3',4'-pentachlorobiphenyl (PenCB) and 3,4,5,3',4',5'-hexachlorobiphenyl (HexCB) exhibited high acute toxicity in parallel with their induction ability of microsomal benzo[a]pyrene 3-hydroxylase and cytosolic DT-diaphorase. On the contrary, PB-type PCBs such as 2,5,2',5'-TCB and 2,4,5,2',4',5'-HexCB which induce microsomal benzphetamine N-demethylase and NADPH-cytochrome P-450 reductase activities showed virtually no or very low toxicity. In the present study, we examined effects of 2,5,2',5'-TCB and its major metabolite 3-hydroxy-2,5,2',5'-TCB on body weight gain, organ weights and activities of hepatic enzymes in rats and assessed acute toxicity of these compounds. As the results, in both 2,5,2',5'-TCB and 3-hydroxy-2,5,2',5'-TCB groups, the body weights were increased during the experiment, but the rate of growth was significantly suppressed after 3 days. Significant hypertrophy of the liver and decrease of total liver lipid content were observed in 2,5,2',5'-TCB group, but the atrophy of spleen and thymus was not affected in both groups. On the other hand, in 2,5,2',5'-TCB group, benzo[a]pyrene 3-hydroxylase and benzphetamine N-demethylase activities were increased to 2. 4-fold and 1.5-fold, respectively, but were not increased in 3-hydroxy-2,5,2',5'-TCB group. After injection of 2,5,2',5'-TCB, 45% of the dose was excreted as 3-hydroxy-2,5,2',5'-TCB in feces for 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Hygienic and Forensic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka.
N
N
Hanioka
H K
HK
Saeki
C
C
Ishida
N
N
Koga
H
H
Yoshimura
D000818:Animals; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
C009407:2,5,2',5'-tetrachlorobiphenyl; C071173:3-hydroxy-2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls