Probabilistic analysis of human health risks associated with background concentrations of inorganic arsenic: Use of a margin of exposure approach

Catherine Petito Boyce, Ari S. Lewis, Sonja N. Sax, Michal Eldan, Samuel M. Cohen, Barbara D. Beck

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1159-1201
Number of pages43
JournalHuman and Ecological Risk Assessment
Issue number6
StatePublished - Nov 2008


  • Arsenic
  • Background exposures
  • Carcinogenicity
  • Dose-response relationship
  • Margin of exposure

ASJC Scopus subject areas

  • Ecological Modeling
  • Pollution
  • Health, Toxicology and Mutagenesis


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