388 VOLUME 124 | NUMBER 3 | March 2016 • Environmental Health Perspectives Research | Children’s Health A Section 508–conformant HTML version of this article is available at http://dx.doi.org/10.1289/ehp.1409144. Introduction Adverse effects of lead in children have been widely studied for years. Exposure to lead has been linked to anemia (Flanagan et al. 1982; Jain et al. 2005; Schwartz et al. 1990; Waldron 1966), renal dysfunction (de Burbure et al. 2006), impaired hearing and postnatal growth [U.S. National Toxicology Program (NTP) 2012], and neurotoxic effects (Lidsky and Schneider 2003; Ronchetti et al. 2006). Pooled results of cohort studies indicated that, in young children, blood lead levels (BPb) < 7.5 μg/dL were associated with intellec- tual deficit, without any obvious threshold (Lanphear et al. 2005). Drinking water has been identified as a source of oral exposure to lead (Brown et al. 2011; Triantafyllidou and Edwards 2012). Children can absorb 40–50% of an oral dose of water-soluble lead, compared with 3–10% for adults [Agency for Toxic Substances and Disease (ATSDR) 2007]. Despite great interest for the influence of environmental lead on children’s health, few studies have investigated the impact of water lead levels (WLL) on BPb in those < 6 years of age. However, young children represent the most sensitive population and are at higher risk of deleterious effects of lead from drinking water (ATSDR 2007; Gulson et al. 1997; Triantafyllidou and Edwards 2012). A few epidemiologic studies including children < 6 years of age have reported a strong asso- ciation between WLL and BPb (Lacey et al. 1985; Lanphear et al. 1998, 2002; Levallois et al. 2014), but others have not (Gasana et al. 2006; Rabinowitz et al. 1985). The distribution of absorbed lead to organ systems appears to be quite similar in children and adults (ATSDR 2007; Barry 1975; Gross et al. 1975), with bone lead accounting for about 73% of the body burden in children (ATSDR 2007; Barry 1975). It has been reported that the half- life of blood lead is approximately 30 days for adults [ATSDR 2007; World Health Organization (WHO) 1995]. For young children, to our knowledge, no specifc value has been reported. Duggan (1983) considered that the clearance rate of blood lead may be higher in children than in adults. However, the true value of this half-life, though shorter, might be very speculative. Te time required to reach the steady-state is about fve to six times the elimination half-life time (i.e., 5–6 months) after a repeated exposure (Greenblatt 1985). Terefore, BPb at a given time is related to the cumulative exposure over the previous 5 months. Tat is, 50% of blood lead is eliminated after approximately 1 month, 75% after 2 months, 87.5% after 3 months, etc. Several authors reported that lead concen- tration in tap water increases with water temperature (Cartier et al. 2011; Schock 1990), suggesting that WLL is likely to show seasonal fluctuations. More recently, we reported marked winter-to-summer changes in WLL in the Montreal area and a potential impact on children’s BPb using the integrated exposure uptake biokinetic model (IEUBK) (Ngueta et al. 2014). Te geometric means of WLL (± SE) were 2.7 ± 2.2 μg/L during winter and 8.1 ± 1.5 μg/L during summer. However, previous cross-sectional studies did not take into account the fact that the tap water lead concentration may vary season- ally and did not consider the cumulative exposure to lead from water in the months preceding the blood sampling (Gasana et al. 2006; Lanphear et al. 1998; Levallois et al. 2014; Morse et al. 1979; Oulhote et al. Address correspondence to P. Levallois, Institut National de Santé Publique de Québec, 945, Rue Wolfe, Québec, Qc. Canada, G1V 5B3. Telephone: 1 (418) 650-5115, ext. 5216. E-mail address: Patrick.Levallois@msp.ulaval.ca Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1409144). We thank M. Prévost, A. Trudelle, D. Gauvin, C. Campagna, S. Nour, F. Lemieux, and M. D’Amour for their contribution to the study and for their useful comments on previous versions of the paper. Te initial study was funded by the Canadian Water Network (CWN), Health Canada, and the Ministère de la santé et des services sociaux du Québec (Quebec, Canada). The water follow-up study was funded by the Ministère du Développement durable, de l’Environnement et de la Lutte contre les changements climatiques (Quebec, Canada). Te authors declare they have no actual or potential competing fnancial interests. Received: 28 August 2014; Accepted: 12 June 2015; Advance Publication: 16 June 2015; Final Publication: 1 March 2016. Use of a Cumulative Exposure Index to Estimate the Impact of Tap Water Lead Concentration on Blood Lead Levels in 1- to 5-Year-Old Children (Montréal, Canada) Gerard Ngueta, 1,2 Belkacem Abdous, 1,2 Robert Tardif, 3 Julie St-Laurent, 1 and Patrick Levallois 1,2,4 1 Axe Santé des populations et pratiques optimales en Santé, Centre de recherche du CHU (Centre hospitalier universitaire) de Québec, Québec, Québec, Canada; 2 Département de médecine sociale et préventive, Faculté de médecine, Université Laval, Québec, Québec, Canada; 3 Département de santé environnementale et de santé au travail, École de Santé Publique de l’Université de Montréal (ESPUM), Montréal, Québec, Canada; 4 Direction de la santé environnementale et de la toxicologie, Institut national de santé publique du Québec, Québec, Québec, Canada BACKGROUND: Drinking water is recognized as a source of lead (Pb) exposure. However, questions remain about the impact of chronic exposure to lead-contaminated water on internal dose. OBJECTIVE: Our goal was to estimate the relation between a cumulative water Pb exposure index (CWLEI) and blood Pb levels (BPb) in children 1–5 years of ages. METHODS: Between 10 September 2009 and 27 March 2010, individual characteristics and water consumption data were obtained from 298 children. Venous blood samples were collected (one per child) and a total of fve 1-L samples of water per home were drawn from the kitchen tap. A second round of water collection was performed between 22 June 2011 and 6 September 2011 on a subsample of houses. Pb analyses used inductively coupled plasma mass spectroscopy. Multiple linear regressions were used to estimate the association between CWLEI and BPb. RESULTS: Each 1-unit increase in CWLEI multiplies the expected value of BPb by 1.10 (95% CI: 1.06, 1.15) after adjustment for confounders. Mean BPb was signifcantly higher in children in the upper third and fourth quartiles of CWLEI (0.7–1.9 and ≥ 1.9 μg/kg of body weight) compared with the frst (< 0.2 μg/kg) after adjusting for confounders (19%; 95% CI: 0, 42% and 39%; 95% CI: 15, 67%, respectively). Te trends analysis yielded a p-value < 0.0001 after adjusting for confounders suggesting a dose–response relationship between percentiles of CWLEI and BPb. CONCLUSIONS: In children 1–5 years of age, BPb was significantly associated with water lead concentration with an increase starting at a cumulative lead exposure of ≥ 0.7 μg Pb/kg of body weight. In this age group, an increase of 1 μg/L in water lead would result in an increase of 35% of BPb after 150 days of exposure. CITATION: Ngueta G, Abdous B, Tardif R, St-Laurent J, Levallois P. 2016. Use of a cumulative exposure index to estimate the impact of tap water lead concentration on blood lead levels in 1- to 5-year-old children (Montreal, Canada). Environ Health Perspect 124:388–395; http://dx.doi. org/10.1289/ehp.1409144