title: A Weibull-PBPK model for assessing risk of arsenic-induced skin lesions in children.
abstract: Chronic arsenic exposure and skin lesions (keratosis and hyperpigmentation) are inextricably linked. This paper was to quantify the children skin lesions risks and to further recommend safe drinking water arsenic standard based on reported arsenic epidemiological data. We linked the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate safe drinking water arsenic concentrations and to perform the risk characterization. We calculated odds ratios (ORs) to assess the relative magnitude of the effect of the arsenic exposure on the likelihood of the prevalence of children skin lesions by calculating proposed Weibull-based prevalence ratios of exposed to control groups associated with the age group-specific PBPK model predicted dimethylarsinite (MMA(III)) levels in urine. Positive relationships between arsenic exposures and cumulative prevalence ratios of skin lesions were found using Weibull dose-response model (r2=0.91-0.96). We reported that the safe drinking water arsenic standards were recommended to be 2.2 and 1 microg/L for male and 6 and 2.8 microg/L for female in 0-6 and 7-18 years age groups, respectively, based on hyperpigmentation with an excess risk of 10(-3) for a 75 years lifetime exposure. Risk predictions indicate that estimated ORs have 95% confidence intervals of 1.33-5.12, 1.74-19.15, and 2.81-19.27 based on mean drinking water arsenic contents of 283.19, 282.65, and 468.81 microg/L, respectively, in West Bengal, India, Bangladesh, and southwestern Taiwan. Our findings also suggest that increasing urinary monomethylarsonic acid (MMA) levels are associated with an increase in risks of arsenic-induced children skin lesions.
authors.affiliation: Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan ROC. cmliao@ntu.edu.tw
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Liao
authors.forename: Tzu-Ling
authors.initials: TL
authors.lastname: Lin
authors.forename: Szu-Chieh
authors.initials: SC
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D001459:Bangladesh / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000139:chemically induced* / Q000453:epidemiology; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D007642:Keratosis / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008954:Models, Biological; D018570:Risk Assessment; D013624:Taiwan / Q000453:epidemiology; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*; D014881:Water Supply
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic