A tiered approach to prioritizing registered pesticides for potential cancer hazard evaluations: Implications for decision making

Abstract

Background: The U.S. Environmental Protection Agency (EPA) conducts cancer hazard evaluations of pesticides during the registration process when often only limited pre-market animal data is available. Due to the prolonged nature of the re-registration process, new population-based observational studies on the carcinogenicity of pesticides may not be readily incorporated into updated assessments. We aim to identify new cancer epidemiology studies that could inform future hazard evaluations for pesticides currently used in high volumes and considered potentially carcinogenic by EPA. Methods: We used a two-step systematic, tiered review approach to scope the literature for epidemiologic studies of pesticide exposure and carcinogenicity. First, we identified pesticides in EPA databases that are currently registered for use, considered potentially carcinogenic (classified by EPA as “possible”, “suggestive”, or “likely” carcinogenic), and used in high volumes. We excluded carcinogens listed by National Toxicology Program’s Report on Carcinogens or the International Agency for Research on Cancer. Second, using PubMed we identified studies published after EPA’s last publicly-available cancer hazard evaluation, then used Health Assessment Workplace Collaborative and Tableau to map evidence by cancer type, pesticide type, and number of studies. Results: We identified 17 potentially carcinogenic high-volume pesticides of which over half were evaluated initially 20-35 years ago; epidemiology data were available for 15 pesticides. Most pesticides were primarily applied as herbicides and insecticides, or in household or agricultural settings. The most frequent reported cancer types include lymphohematopoietic cancers (i.e., adult leukemia, non-Hodgkin lymphoma, multiple myeloma), childhood leukemia, childhood cancers, and prostate cancer. There were ≥5 studies for one or more cancer sites for seven pesticides: carbaryl, chlorothalonil, dimethoate, mancozeb, metolachlor, permethrin and trifluralin. Conclusions: These results highlight the potential need for updated hazard evaluations. Our multi-step approach and utilization of evidence mapping can be used to inform future decision-making to update cancer hazard evaluations.