title: Development of physiologically based toxicokinetic models for improving the human indoor exposure assessment to water contaminants: trichloroethylene and trihalomethanes.
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.
authors.affiliation: Département des sciences biologiques, TOXEN, Université du Québec à Montréal, Montréal, Qc, Canada. haddad.sami@uqam.ca
authors.forename: Sami
authors.initials: S
authors.lastname: Haddad
authors.forename: Ginette-Charest
authors.initials: GC
authors.lastname: Tardif
authors.forename: Robert
authors.initials: R
authors.lastname: Tardif
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000367:Age Factors; D000886:Anthropometry; D019540:Area Under Curve; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008954:Models, Biological; D018570:Risk Assessment; D012737:Sex Factors; D014241:Trichloroethylene / Q000493:pharmacokinetics*; D022882:Trihalomethanes / Q000493:pharmacokinetics*; D014835:Volatilization; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics*; D014881:Water Supply
chemical_list: D022882:Trihalomethanes; D014874:Water Pollutants, Chemical; D014241:Trichloroethylene