An Abstract of Results of Laboratory Examinations of Patients with Yusho and of Animal Experiments

An extensive clinical study of Yusho and many animal experiments were carried out by the Yusho study group in Kyushu University in order to clarify the mechanism of toxic actions of Kanechlor. Most of the findings have been published in Japanese with brief English abstracts. I hope this abstract will help in the understanding of the important observations obtained by these studies. Table 1. Laboratory findings of patients with Yusho.

clarify the mechanism of toxic actions of Kanechlor. Most of the findings have been published in Japanese with brief English abstracts. I hope this abstract will help in the understanding of the important observations obtained by these studies.        other tissues. Tetrachlorobiphenyls were almost completely eliminated from tissues in three to four weeks, but penta-and hexa-chlcrobiphenyls were retained 9 to 10 weeks after administration. 6. Distribution and excretion of Radioactivity in skin, adipose tissue, liver, adrenal gland and 3H-Kanechlor orally adminis-gastrointestinal tract was higher than in plasma 3 days after tered in a single dose of 500 administration. Radioactivity was noted in some tissues after ,pc or 25 mg/body to Wistar 8 weeks. Urinary excretion of Kanechlor was limited, while King male rats weighing 70% of the dose given was in feces. A small portion of radioabout 150 g. activity excreted during the first day was in the phenolic fraction. More phenolic metabolites and less unchanged components were excreted in the feces on the second and third day. 7. Effect of oral administration Kanechlor 400, 500, 600: Hepatomegaly. Microsomal protein of Kanechlor 400, 500, 600 per gram of liver increased in proportion to chlorine content and their components, 0.2 ml of Kanechlor. Amount of cytochrome P-450 and specific acof a solution of 6.8 mg/0.2 tivities of O-dealkylase (p-nitrophenetol), N-demethylase ml/100 g of body weight, (p-chloro-N-methylaniline), and aniline hydroxylase, indaily for 3 days, on liver mi-creased, particularly with Kanechlor 500.
crosomes of male rats.
3,4,2',4'-tetrachlorobiphenyl'l: Increases noted, but less than 3, 4, 3', 4'-tetrachlorobiphenylJ with Kanechlor 400. 3,4,3', 4'-tetrachlorobiphenyl was a more potent inducer than the others. 2,4,5,3', 4'-pentachlorobiphenyl: Most marked increases were noted in cyt. P450 and specific activities of 3 enzymes. 3, 4, 5, 3', 4', 5'-hexachlorobiphenyl: The increase was larger than that induced with the tetra chlorobiphenyls but less than that with the pentachlorobiphenyl. Phenobarbital: Resembling Kanechlor 400 in enzyme induction capability. The above microsomal enzyme activities and the microsomal components started to increase 12 hours after administration of 3,4, 3', 4'-tetrachlobiphenyl, reaching the maximum after about 1 week. Thereafter, activity levels tended to decrease but did not return to normal even after 6 weeks. Microsomes, particularly their membranes, contained the largest amount of H3-Kanechlor-400 administered orally, as compared with mitochondria or lysosomes.  Oral administration of daily dose of 8 ml of olive oil containing 1% Kanechlor for 3 and 11 days to 2 female rabbits. tive dose was daily 5 mg and 2 mg/Kg for 3 days for Kanechlor 400 and 500, respectively. When 40 mg/Kg of Kanechlor 400 or 500 was given daily for 3 days, the effect lasted for 3 weeks by the former and for 6 weeks by the latter.
Ethionine inhibited the shortening of hexobarbital sleeping time by Kanechlor.
Anabolic steroids, chloroquine, glutathione, a-mercaptopropionylglyeine, essential phospholipids, diphenyl, and sulfadiazine did not modify the sleeping time reduction by Kanechlor. Growth was inhibited by the treatments. No weight increase at daily dose of 5 mg, and a weight decrease at 50 mg. Plasma triglycerides did not increase at daily dose up to 5 mg, and slightly exceeded the control at dose of 50 mg, while plasma cholesterol and phospholipid increased definitely by increas-