Development of Physiologically Based Toxicokinetic Models for Improving the Human Indoor Exposure Assessment to Water Contaminants: Trichloroethylene and Trihalomethanes

*The present study was made possible due to funding from the Environmental Health Research Network (Réseau de recherche en santé environnementale) of the Fonds de la recherche en santé du Québec (FRSQ).

Abstract

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.

Notes

*The present study was made possible due to funding from the Environmental Health Research Network (Réseau de recherche en santé environnementale) of the Fonds de la recherche en santé du Québec (FRSQ).

^aValues from Williams et al. (1980).

^aTaken from McKone (1987) and McKone and Knevzovich (1991).

^aValues taken from Tardif et al. (1997).

^b Values taken from MacDougal et al. (1986), Chen and Blancato (1989), and Lévesque et al. (2000).

^aMeasured experimentally by McKone and Knevzovich (1991).

^bEstimated in this study.

^cTaken from Clewell et al. (2000).

^dTaken from Nakai et al. (1999).

^eTaken from Shatkin and Brown (1991).

^fTaken from Gargas et al. (1985).

^gTaken from Luciene da Silva et al. (1999).

^hTaken from Smith et al. (1995).

ⁱTaken from Xu et al. (2002).

^jTaken from Batterman et al. (2002).

^kTaken from Lévesque et al. (2000).

^lTaken from OMS (2000).

^mTaken from Corley et al. (1990).

* Same equations used as per Price et al. (2003b).

† Same equations used as per Price et al. (2003b) for regression to data but derived numerical values are different.

‡ Different equations used than Price et al. (2003b) for regression to data.

^aEstimated assuming a lognormal distribution with mean values from Table 4 and assuming coefficients of variation similar to those estimated for toluene by Tardif et al. (2002).

^aValues estimated from 5000 values generated from P3M model (Price et al. 2003b) for each gender.

^aFrom Ershow and Cantor (1989).

^arepresents a Cmax of 0.011 mg/L.

^brepresents a Cmax of 0.015 mg/L.

^crepresents a Cmax of 0.017 mg/L.

^drepresents a Cmax of 0.024 mg/L.

^erepresents a Cmax of 0.018 mg/L.

Santé Canada. 2000. Sous-produit chlorés de désinfection (SPCD). Santé Canada

Schlouch, E. 1998. “Modélisation toxicocinétiquede l'exposition au chloroforme consécutive à la prise de douche ou bains.” Thesis, Université de Montréal