An empirical approach to sufficient similarity: Combining exposure data and mixtures toxicology data

Scott Marshall, Chris Gennings, Linda K. Teuschler, Leanna G. Stork, Rogelio Tornero-Velez, Kevin M. Crofton, Glenn E. Rice

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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, Environmental Protection Agency guidance states that toxicity data from a mixture considered "sufficiently similar" to the environmental mixture can serve as a surrogate. We propose a novel method to examine whether mixtures are sufficiently similar, when exposure data and mixture toxicity study data from at least one representative mixture are available. 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. Our method shows that the 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., where SMRI <1, less concern; >1, more concern).

Original languageEnglish
Pages (from-to)1582-1595
Number of pages14
JournalRisk Analysis
Issue number9
StatePublished - Sep 2013
Externally publishedYes


  • Cumulative risk assessment
  • Hazard index
  • Pyrethroids
  • Sufficient similarity
  • Whole mixtures


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