Reducing uncertainty of risk estimates for mixtures of chemicals within regulatory constraints

Reducing uncertainty in estimated risks is always desirable. While regulatory assumptions and policies regarding risk assessment of chemicals can be debated, these are the rules under which many risk assessments are currently conducted. Methods for reducing the uncertainty in risk estimates generated under those rules are therefore useful, whether or not one agrees with the models and the underlying assumptions that comprise those rules. The guidance for risk assessment of mixtures of chemicals used by EPA was reexamined to determine methods for reducing the uncertainty in the cumulative risk estimates. It was found that the uncertainty could be significantly reduced if the assumptions concerning the assessment of mixtures of chemicals were combined with the assumptions for evaluating the risks of individual chemicals. Methods are proposed for reducing the uncertainty of mixtures of chemicals whose individual constituents are evaluated by cancer potency factors, hazard quotients, or margins of exposure. The methods developed do not require data beyond that which would be required for generating the current risk estimates for the individual chemicals. These analyses also demonstrated that some of the assumptions currently in use for regulatory risk assessment may lead to inconsistencies that should be reevaluated. As the proposed methods do not require any change in the current assumptions to reduce uncertainty in the risk estimates, the proposed methods should prove useful until such time as the assumptions are reevaluated and possibly changed.