Liao Chung-Min, Shen Huan-Hsiang, Chen Chi-Ling, Hsu Ling-I, Lin Tzu-Ling, Chen Szu-Chieh, Chen Chien-Jen
Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan ROC.
J Hazard Mater. 2009 Jun 15;165(1-3):652-63. doi: 10.1016/j.jhazmat.2008.10.095. Epub 2008 Nov 5.
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.
以往的流行病学研究表明，摄入的无机砷与多种体内癌症密切相关。然而，通过将基于生物学的机制模型与砷的流行病学数据相联系来评估长期低剂量暴露的健康影响的研究却很少。我们提出了一种综合方法，将威布尔剂量反应函数与基于生理的药代动力学（PBPK）模型相联系，以估计参考砷准则。所提出的流行病学数据基于对台湾西南部和东北部砷中毒流行地区10138名居民进行的为期8年的随访研究。采用基于0.01%和1%终生超额癌症风险的出发分析来量化饮用水中砷导致的体内癌症风险。使用威布尔剂量反应模型（r(2)=0.58 - 0.89）发现砷暴露与膀胱癌、肺癌和泌尿系统相关癌症的累积发病率之间存在正相关关系。结果表明，基于男性膀胱癌，对于75年的终生暴露，参考砷准则建议为3.4微克/升，超额风险为10^(-4)。基于1.08 - 6.52升/天的饮用水摄入量，参考砷准则的可能性和终生超额癌症风险估计值分别为1.9 - 10.2微克/升和2.84×10^(-5)至1.96×10^(-4)。本研究表明，基于威布尔模型的砷流行病学和PBPK框架可为量化饮用水中砷导致的体内癌症风险以及进一步推荐参考饮用水砷准则提供科学依据。
