Haddad Sami, Tardif Ginette-Charest, Tardif Robert
Département des sciences biologiques, TOXEN, Université du Québec à Montréal, Montréal, Qc, Canada.
J Toxicol Environ Health A. 2006 Dec;69(23):2095-136. doi: 10.1080/15287390600631789.
Generally, ingestion is the only route of exposure that is considered in the risk assessment of drinking water contaminants. However, it is well known that a number of these contaminants are volatile and lipophilic and therefore highly susceptible to being absorbed through other routes, mainly inhalation and dermal. The objective of this study was to develop physiologically based human toxicokinetic (PBTK) models for trihalomethanes (THM) and trichloroethylene (TCE) that will facilitate (1) the estimation of internal exposure to these chemicals for various multimedia indoor exposure scenarios, and (2) consideration of the impact of biological variability in the estimation of internal doses. Five PBTK models describing absorption through ingestion, inhalation and skin were developed for these contaminants. Their concentrations in ambient air were estimated from their respective tap water concentrations and their physicochemical characteristics. Algebraic descriptions of the physiological parameters, varying as a function of age, gender and diverse anthropometric parameters, allow the prediction of the influence of interindividual variations on absorbed dose and internal dosimetry. Simulations for various scenarios were done for a typical human (i.e., 70 kg, 1.7 m) as well as for humans of both genders varying in age from 1 to 90 years. Simulations show that ingestion contributes to less than 50% of the total absorbed dose or metabolized dose for all chemicals. This contribution to internal dosimetry, such as maximal venous blood concentrations (Cmax) and the area under the venous blood concentration time curve (AUC), decreases markedly (e.g., as low as 0.9% of Cmax for bromodichloromethane). The importance of this contribution varies mainly as a function of shower duration. Moreover, model simulations indicate that multimedia exposure is more elevated in children than adults (i.e., up to 200% of the adult internal dose). The models developed in this study allow characterization of the influence of the different routes of exposure and an improved estimation of the realistic multimedia exposure to volatile organic chemicals present in drinking water. Hence, such models will greatly improve health risk assessment for these chemicals.
一般来说，摄入是饮用水污染物风险评估中唯一考虑的暴露途径。然而，众所周知，这些污染物中有许多是挥发性和亲脂性的，因此极易通过其他途径吸收，主要是吸入和皮肤接触。本研究的目的是建立基于生理学的人体毒物动力学（PBTK）模型，用于三卤甲烷（THM）和三氯乙烯（TCE），这将有助于：（1）估计各种多媒体室内暴露场景下这些化学物质的体内暴露量；（2）在估计体内剂量时考虑生物变异性的影响。针对这些污染物开发了五个描述通过摄入、吸入和皮肤吸收的PBTK模型。根据它们各自的自来水浓度及其物理化学特性估计它们在环境空气中的浓度。生理参数的代数描述随年龄、性别和各种人体测量参数而变化，从而可以预测个体间差异对吸收剂量和体内剂量测定的影响。针对典型人体（即70千克、身高1.7米）以及年龄从1岁到90岁的不同性别的人体进行了各种场景的模拟。模拟结果表明，对于所有化学物质，摄入对总吸收剂量或代谢剂量的贡献小于50%。这种对体内剂量测定的贡献，如最大静脉血浓度（Cmax）和静脉血浓度时间曲线下面积（AUC），显著降低（例如，对于溴二氯甲烷，低至Cmax的0.9%）。这种贡献的重要性主要随淋浴时间而变化。此外，模型模拟表明，儿童的多媒体暴露比成人更高（即高达成人体内剂量的200%）。本研究中开发的模型能够表征不同暴露途径的影响，并改进对饮用水中挥发性有机化学物质实际多媒体暴露的估计。因此，此类模型将大大改善对这些化学物质的健康风险评估。
