Substantial evidence exists from epidemiological and mechanistic studies supporting a sublinear or threshold dose-response relationship for the carcinogenicity of ingested arsenic; nonetheless, current regulatory agency evaluations have quantified arsenic risks using default, generic risk assessment procedures that assume a linear, no-threshold dose-response relationship. The resulting slope factors predict risks from U.S. background arsenic exposures that exceed certain regulatory levels of concern, an outcome that presents challenges for risk communication and risk management decisions. To better reflect the available scientific evidence, this article presents the results of a Margin of Exposure (MOE) analysis to characterize risks associated with typical and high-end background exposures of the U.S. population to arsenic from food, water, and soil. MOE values were calculated by comparing a no-observable-adverse-effect-level (NOAEL) derived from the epidemiological literature with exposure estimates generated using a probabilistic (Monte Carlo) model. The plausibility and conservative nature of the exposure and risk estimates evaluated in this analysis are supported by sensitivity and uncertainty analyses and by comparing predicted urinary arsenic concentrations with empirical data. Using the more scientifically supported MOE approach, the analysis presented in this article indicates that typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity.
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margin of exposure
Document Type: Research Article
Gradient Corporation, Seattle, WA, USA
Gradient Corporation, Cambridge, MA, USA
MAA Research Task Force (MAATF), Washington, DC, USA
Department of Pathology and Microbiology and Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, USA
Publication date: 01 November 2008