[Induction of rat liver foci by inhaled diisocyanate exposure]

Abstract

Diisocyanates are increasingly used for manufacturing polyurethane foam, elastomers, adhesives, coatings, insecticides and many other products. The large number of workers being exposed to these chemicals has a concentration-dependent risk of developing chronic airway disorders. The clinical role of genotoxic effects of diisocyanates demonstrable in vivo and in vitro is still unclear just as their possible cancerogenic potential. The possible initiating effect of diisocyanates in liver carcinogenesis was studied using a rat liver foci bioassay (RFLA). The RLFA is based on the histochemical demonstration of foci of hepatocytes with altered enzyme equipment, which are induced by carcinogens. These foci are generally regarded as early preneoplastic lesions. Rats were exposed either to 20 ppb TDI (Toluene diisocyanate) or 20 ppb HDI (Hexamethylene diisocyanate) for two hours a day over a period of four weeks. After a break of one week the rats received 10 mg Clophen A50/kg body weight as promotor for possible isocyanate induced tumorigenic lesions twice a week for eight weeks. For positive control the hepatocarcinogen diethylnitrosamin (DEN) was given as a single dose of 10 mg and 20 mg. All animals were sacrificed aged 16 weeks. Serial cryostat sections were prepared for ATPase and gamma GT staining. The foci number was determined and calculated as foci/animal as a mean value taken from both staining protocols. Preneoplastic liver foci were observed in positive control rats treated with a single dose of 10 mg as well as with 20 mg DEN (4.3 +/- 3.2 and 1.8 +/- 1.4 respectively). In none of the animals exposed to TDI or HDI preneoplastic foci were detectable.(ABSTRACT TRUNCATED AT 250 WORDS)