Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence

After 30 years of experience with human exposure to dichlorvos (DDVP) in the home, workplace, and sickroom, the U.S. EPA has published its intent to revoke the food additive registration of this cholinesterase-inhibiting insecticide. The basis for the Agency action is the result of the National Toxicology Program (NTP) toxicology and carcinogenesis study of DDVP in rats and mice (NTP Technical Report No. 342, September 1989). In those experiments the NTP considered the result in the female mouse portion of the study to afford unequivocal evidence of carcinogenicity. The NTP considered the interpretations of the male and female rat and the male mouse studies to be less than clear. Despite the NTP interpretation, the EPA considers the male rat data (increased incidence of mononuclear cell leukemia) to be sufficient to warrant the regulatory change. The purpose of this report is to summarize a review of the interpretation of the NTP data and to assess the predictive validity of the results relative to potential human health impact. Critical review of experimental data indicates that the evidence for a carcinogenic effect of DDVP in animals is equivocal. Further, DDVP possess no in vivo mutagenic activity in mammalian assay systems and it bears no significant structural similarity to known carcinogens. Therefore, a weight-of-the-evidence analysis leads to the conclusion that DDVP poses neither mutagenic nor carcinogenic risks to humans exposed under normal conditions of use of foreseeable conditions of misuse.