Risk assessment of arsenic-induced internal cancer at long-term low dose exposure

J Hazard Mater. 2009 Jun 15;165(1-3):652-63. doi: 10.1016/j.jhazmat.2008.10.095. Epub 2008 Nov 5.

Abstract

Previous epidemiological studies have indicated that ingested inorganic arsenic is strongly associated with a wide spectrum of internal cancers. Little is conducted, however, to assess health effects at long-term low dose exposures by linking biologically based mechanistic models and arsenic epidemiological data. We present an integrated approach by linking the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate reference arsenic guideline. The proposed epidemiological data are based on an 8 years follow-up study of 10,138 residents in arseniasis-endemic areas in southwestern and northeastern Taiwan. The 0.01% and 1% excess lifetime cancer risk based point-of-departure analysis were adopted to quantify the internal cancer risks from arsenic in drinking water. Positive relationships between arsenic exposures and cumulative incidence ratios of bladder, lung, and urinary-related cancers were found using Weibull dose-response model r(2)=0.58-0.89). The result shows that the reference arsenic guideline is recommended to be 3.4 microg L(-1) based on male bladder cancer with an excess risk of 10(-4) for a 75-year lifetime exposure. The likelihood of reference arsenic guideline and excess lifetime cancer risk estimates range from 1.9-10.2 microg L(-1) and 2.84 x 10(-5) to 1.96 x 10(-4), respectively, based on the drinking water uptake rates of 1.08-6.52 L d(-1). This study implicates that the Weibull model-based arsenic epidemiological and the PBPK framework can provide a scientific basis to quantify internal cancer risks from arsenic in drinking water and to further recommend the reference drinking water arsenic guideline.

MeSH terms

  • Arsenic / pharmacokinetics
  • Arsenic / toxicity*
  • Dose-Response Relationship, Drug
  • Environmental Exposure / adverse effects
  • Environmental Exposure / statistics & numerical data
  • Female
  • Humans
  • Male
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology
  • Pharmacokinetics
  • Risk Assessment
  • Taiwan
  • Water Pollutants, Chemical / adverse effects*
  • Water Pollutants, Chemical / pharmacokinetics

Substances

  • Water Pollutants, Chemical
  • Arsenic