THE INSECTICIDE ENDOSULFAN AND ITS 2 STEREOISOMERS PROMOTE THE GROWTH OF ALTERED HEPATIC FOCI IN RATS

The non-genotoxic, chlorinated cyclodiene insecticide endosulfan was studied for its ability to act as a tumour promoter in a two-stage, altered hepatic foci bioassay in male Sprague-Dawley rats. Two stereoisomers of endosulfan, alpha-endosulfan (ENDOalpha) and beta-endosulfan (ENDObeta) were used, as well as a commercially-occurring mixture of the alpha- and beta-isomers (ENDOalphabeta). The animals were initiated by intraperitoneal injection of nitrosodiethylamine 24 h after a two-thirds-partial hepatectomy. Five weeks later the animals were transferred to diets containing 30, 100 and 300 p.p.m. of either ENDOalphabeta, ENDOalpha or ENDObeta. The study was terminated 25 weeks after initiation and the development of foci of gamma-glutamyltranspeptidase-positive hepatocytes was evaluated by stereological methods. The results show that endosulfan and its two stereoisomers promote the development of altered hepatic foci, suggesting that endosulfan is a tumour-promoting agent acting by clonal expansion of initiated cells.