Lack of carcinogenicity of pesticide mixtures administered in the diet at acceptable daily intake (ADI) dose levels in rats

Carcinogenic effects of pesticide mixtures were examined with our medium-term carcinogenesis protocols using male F344 rats. In the 8-week liver model, combined dietary administration of 20 pesticides (19 organophosphorus compounds and 1 organochlorine), each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of 100 times ADI significantly increased the number and area of liver lesions. In the second experiment using a multi-organ carcinogenicity protocol of 28 weeks, mixtures of 40 pesticides (high volume compounds) and 20 pesticides (suspected carcinogens) added to the diet at their respective ADI levels did not enhance carcinogenesis in any organ initiated by 5 different known carcinogens in combination. These results provide support for the safety factor (usually 100) approach presently used for the quantitative hazard evaluation of pesticides.