US EPA

Notice

EPA’s National Center for Environmental Assessment has recently published several papers that provide background information on cumulative risk assessment and approaches to characterize and quantify combined exposures and risks due to multiple agents or stressors, with an emphasis on chemical mixtures exposures, toxicity and risk.

Abstract

This collection of eight publications on cumulative risk assessment was developed collaboratively among scientists within EPA’s Office of Research and Development and three other organizations. These include scientific collaborations through an Interagency Agreement with Argonne National Laboratory, an ILSI Health and Environmental Science Institute (HESI) Expert Panel on Chemical Mixtures Assessment, and an Expert Workshop on Mixture Toxicity cosponsored by the Society of Environmental Toxicology and Chemistry (SETAC) and the Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe (NoMiracle).

Cumulative risk has been defined by the U.S. Environmental Protection Agency (EPA) as the combined risks from aggregate exposures (i.e., multiple route exposures) to multiple agents or stressors, where agents or stressors may include chemical and nonchemical stressors (U.S. EPA, 2003). Cumulative risk assessment (CRA) is an analysis, characterization and possible quantification of the combined risks to health or the environment from exposures to multiple agents or stressors. CRA differs from traditional chemical risk assessments as it has a population focus, and there is an emphasis on stakeholder involvement and population vulnerabilities. Further, CRA focuses on both human health and ecology, although an individual CRA may involve only a subset of these features.

This project summary and its related publications provide information and methods for evaluating combined exposures and cumulative risks in human health risk assessment, with an emphasis on chemical mixtures exposures, toxicity and risk. Lambert et al. (2011) present an overview of current thinking on CRA for chemical and nonchemical stressors (physical, biological, socio-economic) that includes a discussion of CRA initiating factors and population vulnerabilities. Rice et al. (2010) and Rice and MacDonell (2008) discuss an iterative approach for assessing multiple route exposures to environmental chemical mixtures and describe the utility of grouping the chemicals to be analyzed based on both physical-chemical properties and an understanding of environmental fate. Lipscomb et al. (2010) detail the state of the practice for estimating chemical mixtures toxicity and risk and discuss criteria for grouping chemicals by common toxic modes of action. Boobis et al. (2011) explore whether synergistic interactions can occur among chemicals at low, environmentally relevant exposure levels, finding only six studies out of 90 identified in the literature that could be used to quantify the magnitude of low dose synergy; for this small set of data, the magnitude of synergy at low doses did not exceed the levels predicted by additivity models by more than a factor of 4. Ragas et al. (2011) provide a comparison of chemical mixture risk assessment methods from human health and ecological risk assessment and propose approaches for integrating information from the two fields of study. Finally, Hertzberg et al. (2008) and Simmons and Teuschler (2010) discuss the risk assessment of complex mixtures of chemicals in drinking water, with an emphasis on multiple route exposures to drinking water disinfection byproducts.

This set of publications advances the science of analyzing the effects from chemical mixtures and the field of CRA and disseminates information to the scientific community and the general public to promote increased understanding of this area of research.

History/Chronology

Date	Description
01-Apr 2006	SETAC/NoMiracle Mixture Toxicity Workshop. Krakow, Poland.
02-Aug 2007	EPA released the report, Concepts, Methods and Data Sources for Health Risk Assessment of Multiple Chemicals (U.S. EPA, 2007)
03-Dec 2007	HESI expert panel on Chemical Mixtures Assessment meeting to discuss synergy review. Washington, DC.
04-Dec 2008	EPA gave presentations at the Society for Risk Analysis Annual Meeting on Cumulative Risk Assessment Methods, Resources and Applications. Boston, MA.
05-2008 - 2011	Project results are published in peer-reviewed journals and book chapters.
06-Sep 2012	EPA releases this project summary (Web summary).

• Boobis, A., et al. 2011. Critical analysis of literature on low dose synergy for use in screening chemical mixtures for risk assessment. Critical Reviews in Toxicology. 2011 May;41(5):369-83. 2011.
• Hertzberg, et al. 2008. Health Risk Assessment of Chemical Mixtures in Drinking Water. In Risk Assessment for Chemicals in Drinking Water. John Wiley and Sons Inc. Hoboken, NJ. pp. 123-170.33 
• Rice, G., et al. 2008. An approach for assessing human exposures to chemical mixtures in the environment. Toxicol Appl Pharmacol. 233:126−136.
• Lambert, J.C., et al. 2011. Cumulative environmental risk. In: Nriagu JO (ed.) Encyclopedia of Environmental Health, Volume 1, pp. 852–859 Burlington: Elsevier. 
• Lipscomb, J.C., JC Lambert, LK Teuschler. 2010. Chemical Mixtures and Cumulative Risk Assessment. In: Principles and Practices of Mixtures Toxicology. Wiley. pp. 253-282 
• Ragas, AMJ, et al. 2011. Human and Ecological Risk Assessment of Chemical Mixtures. In: Mixture Toxicity: Linking Approaches from Ecological and Human Toxicology. Ed. SETAC. Pensacola, FL. pp. 157. 
• Rice, G. and M. MacDonell. 2010. Chemical Mixtures in the Environment: Exposure Assessment. In: Principles and Practices of Mixtures Toxicology. M. Mumtaz, Ed. Wiley. pp. 27-65. 
• Simmons, JE, LK Teuschler. 2010. Chemistry, Toxicity, and Health Risk Assessment of Drinking Water Disinfection By-Products. In: Principles and Practices of Mixtures Toxicology. Ed. Wiley. pp. 401.