Report on Carcinogenesis Bioassay of Technical Grade Chlordecone (Kepone) (CAS No. 143-50-0)

Chlordecone is the common name for the chlorinated insecticide, decachlorooctahydro-1,3,4-methene-2H-cyclobuta(cd)pentalen-2-one, which is commercially available under the trade name of Kepone. The compound, first introduced in 1958, has been used as an insecticide against leaf-eating insects, ants and cockroaches, and as a larvicide against flies. A carcinogenesis bioassay of technical grade chlordecone (Kepone) was conducted using Osborne-Mendel rats and B6C3F1 mice. Chlordecone was administered in the diet for 80 weeks at two dose levels, with the rats sacrificed at 112 weeks and the mice at 90 weeks. The starting dose levels were 15 and 30 ppm for male rats, 30 and 60 ppm for female rats, 70 ppm for male mice and 40 and 80 ppm for female mice. As these dose levels were not well tolerated, the dose levels were reduced during the course of the experiment such that the average dose levels were as follows: 8 and 24 ppm for male rats, 18 and 26 ppm for female rats, 20 and 23 ppm for male mice and 20 and 40 ppm for female mice. Clinical signs of toxicity were observed in both species including generalized tremors and dermatologic changes. A significant increase (P<.05) was found in the incidence of hepatocellular carcinomas of high dose level rats and of mice at both dose levels of chlordecone. The incidences in the high dose groups were 7% and 22% for male and female rats (compared with 0 in controls for both sexes) and 88% and 47% for male and female mice (compared with 16% for male room controls and 0 in females); for the low dose groups of mice the incidences were 81% for males and 52% for females. In addition, the time to detection of the first hepatocellular carcinoma observed at death was shorter for treated than control mice and, in both sexes and both species, it appeared inversely related to the dose. In chlordecone-treated mice and rats extensive hyperplasia of the liver was also found. The incidence of tumors other than in the liver for chlordecone- treated groups did not appear significantly different from that in controls

decachlorooctahydro-1,3,4-methene-2H-cyclobuta(cd)pentalen-2-one, Kepone LEVELS OF EVIDENCE OF CARCINOGENICITY: Male Rats: Positive; Female Rats: Positive; Male Mice: Positive; Female Mice: Positive.