An Empirical Approach to Sufficient Similarity: A Whole Mixture Strategy for Setting Exposure Limits for Chemical Mixtures

• Activity Number: 72
• Type: Topic Contributed
• Date/Time: Sunday, August 4, 2013 : 4:00 PM to 5:50 PM
• Sponsor: Section on Statistics and the Environment
• Author(s): Chris Gennings*+ and Scott Marshall and LeAnna Stork
• Companies: Viginia Commonwealth Univ and BioStat Solutions, Inc and Monsanto Company
• Keywords: risk assessment ; whole mixtures ; exposure ; benchmark dose

Abstract

When assessing risks posed by environmental chemical mixtures, whole mixture approaches are preferred to component approaches. When toxicological data on whole mixtures as they occur in the environment are not available, EPA guidance states that, toxicity data from a mixture considered "sufficiently similar" to the environmental mixture can serve as a surrogate. We define sufficient similarity using equivalence testing methodology comparing the distance between benchmark dose estimates for mixtures in both data rich and data poor cases. We construct a "similar mixtures risk indicator" (SMRI; analogous to the hazard index) on sufficiently similar mixtures linking exposure data with mixtures toxicology data. The methods are illustrated using pyrethroid mixtures occurrence data collected in child care centers (CCC) and dose-response data examining acute neurobehavioral effects of pyrethroid mixtures in rats. Mixtures from 90% of the CCCs were sufficiently similar to the dose-response study mixture. Using exposure estimates for a hypothetical child, the 95th percentile of the (weighted) SMRI for these sufficiently similar mixtures was 0.20 (i.e., SMRI< 1, less; >1, more concern).