General process for the risk assessment of pesticides that interact with or affect the endocrine system

Abstract

The U.S. Environmental Protection Agency's Office of Pesticide Programs evaluates human health risk associated with exposure to pesticide chemicals. Chemical hazard and exposure assessment are components of the risk assessment process. For the risk assessment of single chemical conventional-type pesticides, there may be multiple exposure scenarios depending on the use pattern. Examples include acute and chronic dietary, and short-, intermediate-, and long-term occupational/residential exposures. For hazard assessment, available toxicity data and a weight-of the-evidence approach are used in the process of selecting appropriate toxicity endpoints for relevant exposure scenarios. The pesticide registration process requires that certain types of supporting toxicity data be submitted by the registrant depending in part on the chemical use pattern (e.g., food use). Types of toxicity data that might be submitted and used in hazard assessment include acute, subchronic, chronic, carcinogenicity, mutagenicity, metabolism, reproduction, developmental, neurotoxicity, and mechanistic studies. There may be data from multiple exposure routes (e.g., oral, dermal, inhalation) and from the scientific literature to consider. Dose-response information is also taken into account. In endpoint selection for a chemical, endocrine system-related effect(s) and dose-response relationship(s) are assessed in context of other types of effects, toxicities, and dose-response relationships noted. Endocrine system-related endpoints may include frank effects (e.g., endocrine organ hyperplasia or cancer) or precursor events (blood hormone level elevations). Endocrine system-related endpoints are generally treated like other cancer or non-cancer toxicity endpoints (e.g., hepatic cancer, neurotoxicity) in the risk assessment process. For chemicals with evidence of endocrine system interaction(s), an endocrine system-related effect may or may not be the most sensitive or relevant endpoint for a particular risk assessment exposure scenario. Some chemical examples will be presented. In the final risk assessment, hazard assessment information is integrated with exposure information. The assessment may be adjusted, at some point, for uncertainties in hazard or exposure data. An aggregate risk assessment, in which multiple sources or routes of exposure are considered, is typically performed for occupational and residential exposure scenarios. A cumulative risk assessment may be considered for groups of chemicals with a common mechanism of toxicity.