Maximum Cumulative Ratio (MCR) as a Tool for Assessing the Value of Performing a Cumulative Risk Assessment

Paul S Price,Xianglu Han

doi:10.3390/ijerph8062212

Abstract

Due to the vast number of possible combinations of chemicals to which individuals are exposed and the resource-intensive nature of cumulative risk assessments, there is a need to determine when cumulative assessments are most required. This paper proposes the use of the maximum cumulative ratio (MCR) as a tool for this evaluation. MCR is the ratio of the cumulative toxicity received by an individual from exposure to multiple chemical stressors to the largest toxicity from a single chemical stressor. The MCR is a quantitative measure of the difference in an individual’s toxicity estimated using a chemical-by-chemical approach and using an additive model of toxicity. As such, it provides a conservative estimate of the degree to which individuals’ toxicities could be underestimated by not performing a cumulative risk assessment. In an example application, MCR is shown to be applicable to the evaluation of cumulative exposures involving up to 81 compounds and to provide key insights into the cumulative effects posed by exposures to multiple chemicals. In this example, MCR values suggest that individuals exposed to combinations of chemicals with the largest Hazard Indices were dominated by the contributions of one or two compounds.

Highlights

IntroductionHumans are constantly exposed to multiple chemicals from multiple sources [1,2,3,4]
In this paper we describe a simple tool, the Maximum Cumulative Ratio (MCR) that provides a quantitative measure of the magnitude of the toxicity that is underestimated by not performing a cumulative risk assessment
Results from the Wilcoxon Test showed that the maximum cumulative ratio (MCR) values of samples with Hazard Index (HI) greater than 1 are significantly lower than samples with HI values less than 1

Summary

Introduction

Humans are constantly exposed to multiple chemicals from multiple sources [1,2,3,4]. Regulatory programs such as TSCA in the United States and REACH in the European Union evaluate risks on a chemical-by-chemical basis and do not require the consideration of cumulative exposures when determining human health effects. The chemical-by-chemical approach is believed to underestimate toxicity when the combined exposures to chemicals result in a cumulative toxicity that exceeds the toxicity of the most toxic of the individual chemicals In these instances, a chemical-by-chemical approach could find that each chemical posed no unacceptable risk, but the mixture of chemicals could result in unacceptable effects

Results

Discussion

Conclusion