Risk metrics and cumulative risk assessment methodology for the FQPA

The Food Quality Protection Act (FQPA) of 1996 mandates that the U.S. Environmental Protection Agency consider both aggregate and cumulative risks. Aggregate assessments account for multiple sources and routes of exposure for a single chemical. Cumulative assessments combine exposures to two or more chemicals that share a common mechanism of toxicity. Probabilistic risk assessment methods are described for determining a population's distribution of the dose from exposure and the combination of that exposure characterization with appropriate toxicological information to form a risk assessment. An individual's dose from exposure is characterized as a set of chemical- and route-specific dose profiles over time. For each individual and each chemical and route, a margin of exposure (MOE) is calculated by dividing a toxicologically relevant benchmark dose (e.g., an ED(10)) by the individual's dose from exposure. The set of these MOEs for an individual is combined into the individual's Total MOE. The distribution of the Total MOEs in a population is compared to an Acceptable MOE. Advantages of the Total MOE approach over approaches based on reference doses are discussed. Some general comments on risk metrics are made, and some general guidance for cumulative risk assessments is provided.