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[Evaluation of toxic effects on yusho causal substances by chick embryo hepatic microsomal enzymes activities]
Abstract:
PCBs, non-ortho chlorine substituted PCBs (Co-PCBs), PCQs and (PCDFs + PCDDs), all of which contained similar compositions of those corresponding in yusho oil, were prepared from a PCB preparation used as a heat exchanger fluid. After dissolved in 1, 4-dioxane, they were applied into the air sac of white leghorn eggs incubated for 16.5 days at 37.5 degrees C. Forty eight hours after injection, the hepatic benzo(a)pyrene hydroxylase (AHH) and 7-ethoxyresorufin deethylase (EROD) activities were assayed. The average relative potencies of induction for the two microsomal drug metabolizing enzymes by (PCDFs + PCDDs), Co-PCBs, PCBs and PCQs were 100, 13.4, 0.0006 and 0.0004, respectively. The toxic effects for yusho disease by these substances were calculated from the relative enzyme induction potencies and the average concentrations in yusho oils with the production dates of February 9 and 10, 1968. Consequently, the relative toxicities of (PCDFs+PCDDs), Co-PCBs, PCBs and PCQs were 100, 13.2, 0.06 and 0.12, respectively. This result, as well as our previous investigations using rats and monkeys, insists that (PCDFs+PCDDs) are the primary causal agents for yusho disease. However, the Co-PCBs, which were recently detected in the yusho oils by us, were revealed to be fairly effective in yusho manifestation. In addition, it was cleared that the hepatic enzyme induction by the Co-PCBs fraction, which contained other several PCB isomers, was almost completely contributed by only Co-PCBs such as 3,4,3',4'-tetra- 3,4,5,3',4'-penta- and 3,4,5,3',4',5'-hexachlorinated biphenyls present in the fraction. A chemical uptake rate from the air sac by the chick embryo decreased significantly in the cases of extremely high doses of PCBs (10,000 micrograms/egg) and PCQs (3,333 and 10,000 micrograms/egg), and result the elevations of hepatic enzymes activities were depressed, indicating that the suitable chemical dose amount to be less than about 1,000 micrograms/egg.