Risk Assessment for Chemical Mixtures

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The Issue | Science Objectives | Research Highlights | Impact and Outcome

The Issue

We live in a world where chemicals found in the air, water, backyards, and homes can and do interact with each other. As a result, EPA is examining risks associated with exposure to mixtures of chemicals. As fundamental questions are answered by science, EPA can move away from regulation based on a single chemical exposure to one based on exposure to chemicals with similar effects.

Core (i.e., basic) research is needed first by the Agency to understand the risk of chemical mixtures and to answer questions such as, "How do chemicals of concern interact to cause effects?" "What are their common biological pathways?" and "What happens to interactions after repeated exposures?" With this information, EPA can move forward to develop risk assessments for chemical mixtures.

As part of this effort, EPA's Office of Research and Development is evaluating two classes of chemicals, (1) carbamate insecticides and (2) pyrethroid insecticides, and halogenated disinfection by-products to determine whether the assumptions used in the risk assessments are valid.

Science Objectives

The goal of this research effort is to reduce the uncertainties surrounding the default assumptions in risk assessments by testing the validity of these assumptions. The elucidation of the limitations of the default assumptions should help assess and predict risk of exposure to mixtures of toxicants. The research also will establish general principles to improve cumulative risk assessment decisions for a variety of chemicals, including environmental toxicants (e.g., pesticides) and the residual risk of hazardous air pollutants.

Research Goals:

Provide data from chemical classes that will directly support ongoing risk assessment decisions by EPA, including carbamate and pyrethroid pesticides
Develop and implement dose-time-response models for calculating the relative potencies of N-methyl carbamate pesticides and develop models to assess cumulative risk of N-methyl carbamate exposure
Address issues of extrapolating mixture data across dosing scenarios, dose levels, methodologies, and populations
Enable an understanding of the influence of dose and mixture composition on the joint toxic action of mixtures
Develop predictive models that will link in vitro, pharmacokinetic and in vivo pharmacodynamic components

Research Goals

Ongoing studies are examining the relationship between behavioral and in vitro endpoints, and their linkages to pharmacokinetic, and genomic changes after exposure to pyrethroid pesticides.
Ongoing studies are looking at thyroid-disrupting agents with multiple modes of action, and how they may interact as a chemical mixture.
Repeated exposure to pesticides is compared to single exposures to assess alterations in responses that occur following repeated exposures. Behavioral, physiological, and biochemical measures are used. Future work will assess mechanisms by which differences in responses occur.
Developmental, behavioral, and carcinogenetic endpoints will be measured for animals exposed to multiple chemicals in drinking water. This research is a collaborative effort that crosses several areas of scientific expertise.

Impact and Outcomes

Human Health Research Contributions:

Research results have assisted EPA to formulate a cumulative risk assessment for organophosphorous pesticides. Methods and models were used to develop models of exposure to mixtures of these pesticides, as well as innovative statistical approaches for evaluating cumulative risk assessment.
Research with the organophosphate pesticides led to a generic approach that can be used by EPA risk assessors for the cumulative risk assessment of other pesticides that have a similar mode of action, such as the carbamates.
Through its research on organophosphate cumulative risk, scientists have been able to develop interventions that have been adopted by local governments and grower-shipper associations.
Data has been used by EPA to develop empirical approaches to develop relative potency factors to be used in the cumulative risk assessment of N-methyl carbamate pesticides.
Research has played a critical role in helping EPA develop a cumulative risk assessment for the pesticide atrazine and its metabolites.
Research contributed to drafting a framework for conducting cumulative risk assessment (PDF) (120 pp, 1.1 MB, About PDF).