title: Risk assessment of arsenic-induced internal cancer at long-term low dose exposure.
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.
authors.affiliation: Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan ROC. cmliao@ccms.ntu.edu.tw
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Liao
authors.forename: Huan-Hsiang
authors.initials: HH
authors.lastname: Shen
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Tzu-Ling
authors.initials: TL
authors.lastname: Lin
authors.forename: Szu-Chieh
authors.initials: SC
authors.lastname: Chen
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D010599:Pharmacokinetics; D018570:Risk Assessment; D013624:Taiwan; D014874:Water Pollutants, Chemical / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic