A probabilistic toxicokinetic modeling approach to the assessment of the impact of daily variations of lead concentrations in tap water from schools and daycares on blood lead levels in children
Graphical abstract
Introduction
Lead (Pb) is a systemic human toxicant that notably affects neurological function in exposed children. This translates into adverse effects such as altered behavior and mood, deficit in neuromotor and neurosensory function, and decrement in cognitive function and learning capacities (ATSDR, 2020). Intellectual disability caused by Pb exposure in children is a concern worldwide (Carrington et al., 2019). In this regard, it is now recognized that loss in intellectual quotient (IQ) may result from exposures leading to blood Pb levels (BLL) below 10 μg/dL (Jusko et al., 2008; Lanphear et al., 2005; Surkan et al., 2007; Téllez-Rojo et al., 2006) or even 5 μg/dL (Desrochers-Couture et al., 2018; Santa Maria et al., 2019). In the seminal pooling study from Lanphear et al. (2005), blood samples were taken at least four times in more than 1300 children between birth and the end of the follow-up period, when the IQ test was administered (between 5 and 10 years old). The authors observed that greater IQ loss was observed, relatively per blood Pb concentration unit, below 10 μg/dL as compared to above this level, the reference value at the time. This relation, further validated by Crump et al. (2013), has become the basis for Pb's risk assessment by the public health authorities, and the scientific community now considers that there is no safe threshold identified for Pb exposure (AAP, 2017; EFSA, 2010; Joint FAO/WHO Expert Committee on Food Additives, 2011; WHO, 2010a). However, given the above-mentioned studies, the CDC sets the threshold for intervention at 5 μg/dL (CDC, 2012).
In view of these evidences, the International Society for Environmental Epidemiology has called for the reduction as much as possible of human Pb exposure, particularly in children (ISEE, 2015). Tap water, distributed either in residential settings as well as in schools and daycares (SDC), is a source of exposure to target in this regard. Indeed, among the various sources of lead exposure, it appears as the one on which actions can more readily be taken (Lanphear et al., 1998; Levallois et al., 2014; Oulhote et al., 2013; Stanek et al., 2020; Triantafyllidou and Edwards, 2012). As a matter of facts, regulation of lead in drinking water has been constantly improved and various protocols and standards have been proposed to guide drinking water providers on this issue (Levallois et al., 2018). Currently Health Canada's maximum acceptable concentration (MAC) is 5 μg/L (Health Canada, 2019).
The quantitative evaluation of Pb exposure through tap water is a complex issue. In particular, some Pb concentrations measured in tap water of SDC may, depending of the sampling protocol and existence of corrosion control, exhibit spatio-temporal variations that exceed three orders of magnitude within a given SDC, sometimes superating the mg/L value (Barn et al., 2014; Deshommes et al., 2016; Doré et al., 2018; Triantafyllidou et al., 2014b; Triantafyllidou and Edwards, 2009). A single fountain within a given SDC can present close to 100-fold variations in Pb concentrations (Deshommes et al., 2016; Doré et al., 2018). Yet, some authors suggested that even as sparse as they might be, peak concentrations within this variation pattern could contribute to a worrying increase BLL of attending children (Lakind, 1998; Lambrinidou et al., 2010; Triantafyllidou et al., 2014a). Besides, Pb in drinking water from schools have recently been associated with significant, though mild, deprivation of educational outcomes in Ontario, Canada (Buajitti et al., 2021).
The unpredictable nature of such peak exposures is quite specific to the case of Pb levels in tap water distributed in large buildings such as SDC (Deshommes et al., 2016), and it precludes the design of experimental settings using blood measurements to verify their impact on exposure. Else, toxicokinetic models can be used, but available ones present important limitations. Indeed, US EPA's Integrated Exposure and Uptake Biokinetic (IEUBK) model, the most commonly used toxicokinetic model to calculate BLL in children as a result of environmental exposures to Pb (Laidlaw et al., 2017; Li et al., 2016; Zartarian et al., 2017; Zhong et al., 2017), relies on a premise of continuous exposure to constant concentrations of Pb in the various environmental media (Hogan et al., 1998). At best, it can reflect exposure conditions that are averaged over a 30-days period (Deshommes et al., 2013; Ngueta et al., 2014; Zartarian et al., 2017). Thus, its design and settings are not built to reflect the impact of short term (daily) variations in exposure concentrations such as those describe above for tap water concentrations in SDC. Other pharmacokinetic models exist for Pb, such as the International Commission on Radioprotection (ICRP) model (Leggett, 1993) and the O'Flaherty, 1993, O'Flaherty, 1995 model, but their parametrization and use is more complex. Noteworthingly, the probability of occurrence of high BLL levels in given exposure conditions through tap water can also not be determined with these models, as they are fundamentally deterministic. This lack of probabilistic dimension to the available models limits the possibilities in terms of interpretation of BLL modeling results by risk managers, and the present work also aims to address this caveat.
Therefore, the objective of the present work was to probabilistically assess the relative impact of daily variations of exposure to tap water Pb concentration in SDC on BLL of attending children. Conceptually, this requires the development of a simple stochastic toxicokinetic modeling tool that allows the estimation of time-varying BLL in response to the specific rapid, and potentially wide, time-varying nature of Pb levels mentioned above.
Section snippets
Materials and methods
The methodological approach followed in the present study relies on the probabilistic simulation of the BLL resulting from Pb tap water exposure in SDC. It has required the building of a toxicokinetic model following four steps: 1) the mathematical conception of the model, inspired from the one used by Ngueta et al. (2016); 2) the determination, or selection from the scientific literature, of the model parameters' values; 3) the validation of the model built; and 4) its adjustment by the
Results
An example of a BLL's simulation profile in infants, toddlers and pupils exposed as per scenario 3 of Pb concentration in tap water is depicted in Fig. 2. Specifically, exposure concentration varies from day to day around a median daily value of 24 μg/L over the course of the entire exposure period. For comparison purpose, the BLL reached assuming a constant daily concentration in tap water of 24 μg/L are also shown. For equivalent median exposure, the variable daily pattern leads to greater
STK model features
The STK model proved to be an efficient and relatively simple tool to examine the impact of daily variations in tap water Pb concentration of SDC on the BLL of attending individuals. Beyond its application to the specific case of Pb occurrence in tap water from SDC, the capacity of the STK model to probabilistically estimate daily-varying BLL in response to daily-varying Pb exposure conditions is a novelty which deserves to be emphasized. It could thus be used for the assessment of other types
Conclusion
A simple Pb toxicokinetic model, significantly improved from a previously published one and suitable for probabilistic assessment related to episodic peak exposures, which constitutes a primer, was developed. It could be useful to risk managers to orientate decisions associated with the tap water surveillance results for Pb in SDC. Despite some limitations, this study demonstrates that episodic peak tap water concentrations in such institutions can translate into a significant increase of BLL
CRediT authorship contribution statement
Mathieu Valcke: Conceptualization, Data curation, Formal analysis, Methodology, Software, Writing - original draft, Writing - review & editing. Marie-Hélène Bourgault: Conceptualization, Formal analysis; Methodology, Data curation, Validation, Writing - review & editing. Michelle Gagné: Conceptualization, Formal analysis, Methodology, Validation, Writing - review & editing. Patrick Levallois: Project administration, Methodology, Supervision, Writing - review & editing.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work takes over certain features of a broader study on the risk assessment and management of the presence of Pb in tap water distributed in schools and daycares from the Province of Quebec, Canada (https://www.inspq.qc.ca/publications/2550). The authors thank Denis Gauvin and Stéphane Buteau at INSPQ, as well as Michèle Prévost, Élise Deshommes and Évelyne Doré from the NSERC industrial Chair on Drinking Water at Polytechnique Montreal for their comments and collaboration over the course
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