title: An assessment of the interindividual variability of internal dosimetry during multi-route exposure to drinking water contaminants.
abstract: The objective of this study was to evaluate inter-individual variability in absorbed and internal doses after multi-route exposure to drinking water contaminants (DWC) in addition to the corresponding variability in equivalent volumes of ingested water, expressed as liter-equivalents (LEQ). A multi-route PBPK model described previously was used for computing the internal dose metrics in adults, neonates, children, the elderly and pregnant women following a multi-route exposure scenario to chloroform and to tri- and tetra-chloroethylene (TCE and PERC). This scenario included water ingestion as well as inhalation and dermal contact during a 30-min bathroom exposure. Monte Carlo simulations were performed and distributions of internal dose metrics were obtained. The ratio of each of the dose metrics for inhalation, dermal and multi-route exposures to the corresponding dose metrics for the ingestion of drinking water alone allowed computation of LEQ values. Mean BW-adjusted LEQ values based on absorbed doses were greater in neonates regardless of the contaminant considered (0.129-0.134 L/kg BW), but higher absolute LEQ values were obtained in average adults (3.6-4.1 L), elderly (3.7-4.2 L) and PW (4.1-5.6 L). LEQ values based on the parent compound's AUC were much greater than based on the absorbed dose, while the opposite was true based on metabolite-based dose metrics for chloroform and TCE, but not PERC. The consideration of the 95th percentile values of BW-adjusted LEQ did not significantly change the results suggesting a generally low intra-subpopulation variability during multi-route exposure. Overall, this study pointed out the dependency of the LEQ on the dose metrics, with consideration of both the subpopulation and DWC.
authors.affiliation: Département de santé environnementale et santé au travail, Université de Montréal, CP 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada. mathieu.valcke@inspq.qc.ca
authors.forename: Mathieu
authors.initials: M
authors.lastname: Valcke
authors.forename: Kannan
authors.initials: K
authors.lastname: Krishnan
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009010:Monte Carlo Method; D011247:Pregnancy; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D014881:Water Supply
chemical_list: D014874:Water Pollutants, Chemical