Linking a life-stage PBPK model and epidemiological data to enhance cancer risk assessment of human exposed to arsenicals
Date Issued
2006
Date
2006
Author(s)
Shen, Huan-Hsiang
DOI
zh-TW
Abstract
The purpose of this thesis is to evaluate a reasonable range of drinking water standard based on the arsenic epidemiological data in the southwestern Blackfoot disease-endemic area and northeastern Lanyang Plain in Taiwan. We present an integrated approach by linking the Weibull model-based dose-response profile and a physiologically based pharmacokinetic (PBPK) model to construct the interplay among arsenic exposure dose, age and response, and to model arsenic concentration varied with methylating activity and drinking water consumption rates. Furthermore, we use bioaccumulation model to establish a risk assessment for ingesting farmed tilapia in southwestern coast to estimate the pond water quality criteria. A life-stage PBPK model is used to describe the absorption, distribution, metabolism, and excretion of the four major metabolites: arsenate (As5+), arsenite (As3+), methylarsonic acid (MMA) and dimethylarsinic acid (DMA) in target tissue groups, considering the potential impact by physiologically life-stage differences. The results show that arsenic exposure dose, age and the cumulative incidence ratio of the bladder, kidney, urinary and lung cancers are correlated significantly. The safe arsenic drinking water standard is estimated to be 3.4 μg L-1 based on the index cancer (bladder cancer) with cumulative incidence ratio equals 10-4 for a life time 75-yr male. The standard concentration and cumulative incidence ratio range from 1.9 – 10.2 μg L-1 and 2.84×10-5 – 1.96×10-4, respectively, which are varied with the drinking water consumption rates ranging from 1.08 – 6.52 L d-1. The risk of ingesting farmed tiliapia are lower than 10-4 in Putai, Yichu, Paiman and Hsuehchia, and the average risk of 90% belows 2.0×10-5 in southwestern coast. The pond water standard of inorganic arsenic for farmed tilapia is estimated to be 45 μg L-1. In conclusion, this study offers a environmental-risk-management framework to establish regulations and administrating process by linking epidemiological data and environmental bioassays.
Subjects
砷
Weibull模式
PBPK
飲用水標準
吳郭魚
風險評估
流行病學。
Arsenic
Weibull model
Drinking water standard
Tilapia
Risk assessment
Epidemiology
Type
thesis
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