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An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants
Département de santé environnementale et santé au travail, Université de Montréal, CP 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada
Institut national de santé publique du Québec, 190 Boulevard Crémazie Est, Montréal, Québec, H2P 1E2, Canada
* Author to whom correspondence should be addressed.
Received: 9 October 2010; in revised form: 4 November 2010 / Accepted: 12 November 2010 / Published: 17 November 2010
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.
Keywords: drinking water contaminants; inter-individual variability; liter-equivalents; multi-route exposure; physiologically-based pharmacokinetic modeling
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Valcke, M.; Krishnan, K. An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants. Int. J. Environ. Res. Public Health 2010, 7, 4002-4022.
Valcke M, Krishnan K. An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants. International Journal of Environmental Research and Public Health. 2010; 7(11):4002-4022.
Valcke, Mathieu; Krishnan, Kannan. 2010. "An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants." Int. J. Environ. Res. Public Health 7, no. 11: 4002-4022.