Methods and Software to Analyze Gene-Environment Interactions under a Case-Mother-Control-Mother Design with Partially Missing Child Genotype.

INTRODUCTION: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype. METHODS: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype. RESULTS: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of small-for-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates. CONCLUSION: We recommend the robust version of the modified retrospective likelihood.

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.

The aim of this study was to assess the impact of exposure to tap water lead concentration ([Pb]TW) occurring in schools or daycares on blood lead level (BLL) of attending children. Given the potentially wide variations in space and time of ([Pb]TW) documented in the literature, a simple probabilistic toxicokinetic (STK) model that allows the simulation of the time-varying evolution of BLL in response to these variations was developed. Thus, basic toxicokinetic equations were assembled to simulate BLL in a typical infant, toddler and pupil. The STK model's steady-state BLL predictions showed good correspondence when validated against Integrated Exposure and Uptake BioKinetic model predictions for comparable [Pb]TW values. Exposures to three distributions of [Pb]TW in specific sets of Canadian schools and daycares documented in the scientific literature were simulated probabilistically with Monte Carlo simulations. For the highest distribution of [Pb]TW simulated (median, 90th percentile = 24, 412 µg/L), average annual BLL (median, 97.5th percentile) varies between 1.5 and 6.4 µg/dL in infant and 1.1 and 3 µg/dL in pupils. Toddler's results were midway between those from the infants and pupils. Under this exposure scenario, the infant may present BLL > 5 µg/dL for a significant number of days over the course of the academic year (median; 97.5th: 17; 227 days). However, peak exposure may remain unnoticed if rare and drowned out by the background BLL. In conclusion, even if they may be sparse, peak exposure episodes to [Pb]TW in schools and daycares may suffice to increased BLL in attending individuals. This finding emphasizes the need for further characterization of [Pb]TW in schools and daycares in order to identify potentially problematic institutions and therefore avoid undesirable exposures for the children attending them.

Drinking Water Quality and Human Health: An Editorial.

Drinking water quality is paramount for public health [...].

Chlorination by-product levels in hot tap water: Significance and variability.

People are exposed to chlorinated by-products (CBPs) through the consumption of cold tap water (CTW) (ingestion, inhalation, dermal contact) but also through the use of hot tap water (HTW) in such activities as showering and bathing (inhalation, dermal contact). This study focuses on the impact of residential water heating on CBP levels in tap water. Trihalomethane (THM) and haloacetic acid (HAA) levels were measured in the CTW and HTW of 50 residences located in two distribution systems supplied by chlorinated surface water during summer and winter. Results show important differences between CBP levels measured in cold and hot tap water. However, the magnitude of changes differs according to the specific species of THMs and HAAs, the season, the distribution system and the location within the same distribution system. Residential water heating led to an increase in average THM levels for the two distribution systems studied, which tended to be greater in winter. Residential water heating affected the two main HAA species found in the area studied (dichloroacetic (DCAA) and trichloroacetic (TCAA) acids) differently. In fact, the average DCAA levels increased due to water residential heating while a small change in average levels was observed for TCAA. However, the water heating impact on HAAs (in terms of importance and sometimes of tendency (increase vs. decrease)) may also differed between residences. The influence of seasons on the change in the average DCAA and TCAA levels (in µg/L) from residential water heating was not statistically significant except for TCAA levels in one distribution system. Results show the importance of considering site-specific characteristics of CTW (CBP level, temperature, residual chlorine, etc.) to estimate the levels of CBPs in HTW in CBP exposure assessment studies (and not to generalize for an entire population). The reported data can thus be useful in assessing for exposure to DBPs in epidemiological studies.

Deriving A Drinking Water Guideline for A Non-Carcinogenic Contaminant: The Case of Manganese.

Manganese is a natural contaminant of water sources. It is an essential oligo-element, which may exert toxicity at high doses, particularly via inhalation. Its toxicity by the oral route is less known, but epidemiological and experimental studies tend to support its neurodevelopmental toxicity in infants and children. This paper describes the method used by a middle-size public health institution to derive a Drinking Water Guideline (DWG) for manganese. After reviewing the work done by major public health institutions, authors confirmed the use of experimental data to derive a point-of-departure (POD) of 25 mg of manganese/kg/day, based on neurodevelopmental effects on pup rats. Then, a total uncertainty factor of 450 was applied to calculate a Toxicological Reference Value (TRV) of 55 µg/kg/day. The final DWG proposed for manganese is 60 µg/L and is based on a relative source contribution (RSC) of water of 20% and an infant drinking scenario of 182 mL/kg of body weight (BW) of water (95th percentile of the ingestion rate distribution for 0⁻6 months). Despite its limitations, e.g., starting with the work done by other agencies, such an approach demonstrates in a transparent way the rationale and challenging choices made by regulators when deriving a DWG.

Heterogeneity in the Relationship between Disinfection By-Products in Drinking Water and Cancer: A Systematic Review.

The epidemiological evidence demonstrating the effect of disinfection by-products (DBPs) from drinking water on colon and rectal cancers is well documented. However, no systematic assessment has been conducted to assess the potential effect measure modification (EMM) in the relationship between DBPs and cancer. The objective of this paper is to conduct a systematic literature review to determine the extent to which EMM has been assessed in the relationship between DBPs in drinking water in past epidemiological studies. Selected articles (n = 19) were reviewed, and effect estimates and covariates that could have been used in an EMM assessment were gathered. Approximately half of the studies assess EMM (n = 10), but the majority of studies only estimate it relative to sex subgroups (n = 6 for bladder cancer and n = 2 both for rectal and colon cancers). Although EMM is rarely assessed, several variables that could have a potential modification effect are routinely collected in these studies, such as socioeconomic status or age. The role of environmental exposures through drinking water can play an important role and contribute to cancer disparities. We encourage a systematic use of subgroup analysis to understand which populations or territories are more vulnerable to the health impacts of DBPs.

Availability, Quality, and Relevance of Toxicogenomics Data for Human Health Risk Assessment: A Scoping Review of the Literature on Trihalomethanes.

Human health risk assessment (HHRA) must be adapted to the challenges of the 21st century, and the use of toxicogenomics data in HHRA is among the changes that regulatory agencies worldwide are trying to implement. However, the use of toxicogenomics data in HHRA is still limited. The purpose of this study was to explore the availability, quality, and relevance to HHRA of toxicogenomics publications as potential barriers to their use in HHRA. We conducted a scoping review of available toxicogenomics literature, using trihalomethanes as a case study. Four bibliographic databases (including the Comparative Toxicogenomics Database) were assessed. An evaluation table was developed to characterize quality and relevance of studies included on the basis of criteria proposed in the literature. Studies were selected and analyzed by 2 independent reviewers. Only 9 studies, published between 1997 and 2015, were included in the analysis. Based on the selected criteria, critical methodological details were often missing; in fact, only 3 out of 9 studies were considered to be of adequate quality for HHRA. No studies met >3 (out of 7) criteria of relevance to HHRA (eg, adequate number of doses and sample size). This first scoping review of toxicogenomics publications on trihalomethanes shows that low availability, quality, and relevance to HHRA of toxicogenomics publications presents potential barriers to their use in HHRA. Improved reporting of methodological details and study design is needed in the future so that toxicogenomics studies can be appropriately assessed regarding their quality and value for HHRA.

Public Health Consequences of Lead in Drinking Water.

PURPOSE OF REVIEW: Lead can enter drinking water from lead service lines and lead-containing plumbing, particularly in the presence of corrosive water. We review the current evidence on the role of drinking water as a source of lead exposure and its potential impacts on health, with an emphasis on children. Drinking water guidelines and mitigation strategies are also presented. RECENT FINDINGS: The impact of lead on neurodevelopmental effects in children even at low levels of exposure is well established. Population and toxicokinetic modeling studies have found a clear relationship between water lead levels and blood lead levels in children at low levels of lead in drinking water. Various mitigation strategies can lower lead levels in water. The importance of drinking water as a contributor to total lead exposure depends on water lead levels and the amount consumed, as well as the relative contribution of other sources. Efforts should be made to reduce lead exposure for all sources, including drinking water, considering that no threshold level of exposure exists for the neurodevelopmental effects of lead in children.

Prenatal exposure to drinking-water chlorination by-products, cytochrome P450 gene polymorphisms and small-for-gestational-age neonates.

Genetic susceptibility may modulate chlorination by-products (CBPs) effects on fetal growth, especially genes coding for the cytochrome P450 involved in the metabolism of CBPs and steroidogenesis. In a case-control study of 1432 mother-child pairs, we assessed the association between maternal and child single nucleotide polymorphisms (SNPs) within CYP1A2, CYP2A6, CYP2D6 and CYP17A1 genes and small-for-gestational-age neonates (SGA<10th percentile) as well as interaction between these SNPs and maternal exposure to trihalomethanes or haloacetic acids (HAAs) during the third trimester of pregnancy. Interactions were found between mother and neonate carrying CYP17A1 rs4919687A and rs743572G alleles and maternal exposure to total trihalomethanes or five regulated HAAs species. However, these interactions became non statistically significant after correction for multiple testing. There is some evidence, albeit weak, of a potential effect modification of the association between CBPs and SGA by SNPs in CYP17A1 gene. Further studies are needed to validate these observations.

Associations between cadmium levels in blood and urine, blood pressure and hypertension among Canadian adults.

BACKGROUND: Cadmium has been inconsistently related to blood pressure and hypertension. The present study seeks to clarify the relationship between cadmium levels found in blood and urine, blood pressure and hypertension in a large sample of adults. METHODS: The study sample included participants ages 20 through 79 from multiple cycles of the Canadian Health Measures Survey (2007 through 2013) with measured blood cadmium (n=10,099) and urinary cadmium (n=6988). Linear regression models examined the association between natural logarithm transformed cadmium levels and blood pressure (separate models for systolic and diastolic blood pressure) after controlling for known covariates. Logistic regression models were used to examine the association between cadmium and hypertension. Models were run separately by sex, smoking status, and body mass index category. RESULTS: Men had higher mean systolic (114.8 vs. 110.8mmHg, p<0.01) and diastolic (74.0 vs. 69.6mmHg, p<0.01) blood pressure compared to women. Although, geometric mean blood (0.46 vs. 0.38µg/L, p<0.01) and creatinine-adjusted standardized urinary cadmium levels (0.48 vs. 0.38µg/L, p<0.01) were higher among those with hypertension, these differences were no longer significant after adjustment for age, sex and smoking status. In overall regression models, increases in blood cadmium were associated with increased systolic (0.70mmHg, 95% confidence interval [CI]=0.25-1.16, p<0.01) and diastolic blood pressure (0.74mmHg, 95% CI=0.30-1.19, p<0.01). The associations between urinary cadmium, blood pressure and hypertension were not significant in overall models. Model stratification revealed significant and negative associations between urinary cadmium and hypertension among current smokers (OR=0.61, 95% CI=0.44-0.85, p<0.01), particularly female current smokers (OR=0.52, 95% CI=0.32-0.85, p=0.01). CONCLUSION: This study provides evidence of a significant association between cadmium levels, blood pressure and hypertension. However, the significance and direction of this association differs by sex, smoking status, and body mass index category.

Barriers to the use of toxicogenomics data in human health risk assessment: A survey of Canadian risk assessors.

Regulatory agencies worldwide need to modernize human health risk assessment (HHRA) to meet challenges of the 21st century. Toxicogenomics is at the core of this improvement. Today, however, the use of toxicogenomics data in HHRA is very limited. The purpose of this survey was to identify barriers to the application of toxicogenomics data in HHRA by human health risk assessors. An online survey targeting Canadian risk assessors gathered information on their knowledge and perception of toxicogenomics, their current and future inclusion of toxicogenomics data in HHRA, and barriers to the use of such data. Twenty-nine (29) participants completed a questionnaire after 2 months of solicitation. The results show that the application of toxicogenomics data in Canada is marginal, with 85% of respondents reporting that they never or rarely used such data. Knowledge of toxicogenomics by Canadian risk assessors is also limited: about two-thirds of respondents (68%) were not at all or only slightly familiar with the concept. Lack of guidelines for toxicogenomics data interpretation, data quality assessment and on their use in HHRA, were found to be major barriers. In conclusion, there is a need for interventions aimed at facilitating the use of toxicogenomics data in HHRA, when available.

Disinfection by-products exposure and intra-uterine growth restriction: Do genetic polymorphisms of CYP2E1or deletion of GSTM1 or GSTT1 modify the association?

BACKGROUND: Exposure to disinfection by-products (DBPs) during pregnancy was associated with reduced foetal growth. Genetic susceptibility might play a role, especially for genes encoding for the Cytochrome P450 (CYP2E1) and Glutathione S-Transferase (GST) enzymes, involved in metabolism and activation of DBPs. Few epidemiological studies evaluated these gene-environment interactions and their results were never replicated. OBJECTIVE: This study aims to examine interactions between trihalomethanes (THM) or haloacetic acids (HAA) exposure and genetic polymorphisms on small for gestational age (SGA) neonates by investigating single nucleotide polymorphisms (SNPs) in CYP2E1 gene and GSTM1 and GSTT1 deletions in mothers-children pairs. METHODS: A population-based case-control study of 1549 mothers and 1455 children was conducted on SGA and THM/HAA exposure. DNA was extracted from blood or saliva cells. Targeted SNPs and deletions were genotyped. Statistical interaction between SNPs/deletions and THMs or HAAs in utero exposure with regard to SGA occurrence was evaluated by unconditional logistic regression with control of potential confounders. RESULTS: Previously reported positive modification of the effect of THM uterine exposure by mothers or newborns CYP2E1 rs3813867 C allele or GSTM1 deletion was not replicated. However interactions with CYP2E1 rs117618383 and rs2515641 were observed but were not statistically significant after correction for multiple testing. CONCLUSIONS: Previous positive interactions between THMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported.

Cadmium levels and sources of exposure among Canadian adults.

BACKGROUND: Cadmium is a heavy metal found naturally in the environment that has been associated with negative health outcomes. The present study examines levels of blood cadmium (BCd), urinary cadmium (UCd), and the main sources of cadmium exposure among Canadians aged 20 to 79. DATA AND METHODS: The data are from cycles 1 (2007 to 2009) and 2 (2009 to 2011) of the Canadian Health Measures Survey (CHMS), including measures of BCd and UCd, markers of smoking status (self-reported and second-hand smoke exposure), and self-reported consumption of foods known to be high in cadmium. The relationship between sources of exposure and cadmium levels was examined descriptively. The magnitude of the contribution of different exposure sources was examined in regression models. RESULTS: Age and smoking status were the greatest contributors to BCd and UCd: older people and current smokers had the highest cadmium levels. Dietary exposure, while significant, was a modest contributor overall, but a more important source of cadmium among never-smokers. INTERPRETATION: Smoking was the greatest contributor to cadmium levels among Canadians aged 20 to 79. Dietary differences explained a small percentage of variation in cadmium levels.

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).

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 five 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 significantly 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 first (< 0.2 µg/kg) after adjusting for confounders (19%; 95% CI: 0, 42% and 39%; 95% CI: 15, 67%, respectively). The 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.

Investigating social inequalities in exposure to drinking water contaminants in rural areas.

Few studies have assessed social inequalities in exposure to drinking water contaminants. This study explores this issue in 593 rural municipalities of Québec, Canada. Quartiles of an ecological composite deprivation index were used as a proxy of socioeconomic status. Total trihalomethanes (TTHMs) and lead were chosen as proxies of chemical drinking water quality. The results show that the majority of deprived rural municipalities apply no treatment to their water (26%) or use a basic treatment (51%), whereas a relative majority of the wealthiest municipalities (40%) use advanced treatment. The proportion of municipalities having important lead (>5 µg/L) levels is highest in most deprived municipalities. Moreover, most deprived municipalities have a higher risk of high tap lead levels (RR = 1.33; 95%CI: 1.30, 1.36). Conversely, most deprived municipalities have a lower risk of high TTHMs levels (RR = 0.78; 95%CI: 0.69, 0.86). These findings suggest an environmental inequality in drinking water contaminants distribution in rural municipalities.

Overview of Disinfection By-products and Associated Health Effects.

The presence of chemical compounds formed as disinfection by-products (DBPs) is widespread in developed countries, and virtually whole populations are exposed to these chemicals through ingestion, inhalation, or dermal absorption from drinking water and swimming pools. Epidemiological evidence has shown a consistent association between long-term exposure to trihalomethanes and the risk of bladder cancer, although the causal nature of the association is not conclusive. Evidence concerning other cancer sites is insufficient or mixed. Numerous studies have evaluated reproductive implications, including sperm quality, time to pregnancy, menstrual cycle, and pregnancy outcomes such as fetal loss, fetal growth, preterm delivery, and congenital malformation. The body of evidence suggests only minor effects from high exposure during pregnancy on fetal growth indices such as small for gestational age (SGA) at birth. Populations highly exposed to swimming pools such as pool workers and professional swimmers show a higher prevalence of respiratory symptoms and asthma, respectively, although the direction of the association, and thus causality, is not clear among professional swimmers. The risk of asthma, wheezing, eczema, and other respiratory outcomes among children attending swimming pools has been the object of extensive research. Early studies suggested a positive association, while subsequent larger studies found no correlations or showed a protective association. Future research should develop methods to evaluate the effects of the DBP mixture and the interaction with personal characteristics (e.g., genetics, lifestyle), clarify the association between swimming pools and respiratory health, evaluate the occurrence of DBPs in low- and middle-income countries, and evaluate outcomes suggested by animal studies that have not been considered in epidemiological investigations.

Women exposure during pregnancy to haloacetaldehydes and haloacetonitriles in drinking water and risk of small-for-gestational-age neonate.

BACKGROUND: Past studies have examined the effects of maternal exposure to water chlorination disinfection by-products (DBPs), such as trihalomethanes (THMs) and haloacetic acids (HAAs) during pregnancy. However, no human-based study has yet evaluated the effect of emerging DBPs, such as haloacetaldehydes (HAs) and haloacetonitriles (HANs) on small-for-gestational-age (SGA) status in newborns. OBJECTIVE: This study aims to assess the association between maternal multiroute exposure to HAs and HANs during the third trimester of pregnancy and SGA status at birth, among neonates delivered by women residing in the Quebec City area (Province of Quebec, Canada). We also evaluated the interaction between exposure to these emerging unregulated by-products and regulated DBPs also found in drinking water (THMs and HAAs), for which a positive association with adverse reproductive outcomes has been suggested in previous studies. METHODS: We conducted a population-based case-control study in the Quebec City area. SGA newborns (n=330) were compared to 1100 controls, with matching based on calendar week of birth. HA and HAN concentrations in drinking water at participant's tap were estimated using spatio-temporal strategy based on bimonthly measurements carried out at several locations in the participant's distribution system. A computer-assisted telephone interview was completed to collect information on individual habits of water consumption and water related activities in order to determine individual multiroute exposure. This enabled us to estimate the dose of HAs and HANs absorbed daily by each participant. Associations between total HA, HAN concentrations in drinking water and SGA were analyzed. Associations between the daily-absorbed doses of these emerging DBPs and SGA were also analyzed. Odds ratios (ORs) comparing the 4th quartile of exposure to the reference group (the first three quartiles) were obtained by means of conditional logistic regression, and controlling for potential confounders. RESULTS: Globally, no evidence of increased risk of SGA was found with total HA and HAN concentrations in tap water when participants in the 4th quartile of exposure were compared to the first three quartiles (OR=1.0; 95% CI [0.7-1.5] and OR=0.8; 95% CI [0.6-1.2], respectively). Similarly, no association was found with the daily-absorbed doses of total HAs or HANs (OR=0.9; 95% CI [0.6-1.3] and OR=1.1; 95% CI [0.7-1.6], respectively). However, a small non statistically significant association was found between the dose of brominated HA and SGA (OR=1.4; 95% CI [0.9-2.1]). Also, in spite of the lack of interaction between other DBP classes, an unexpected negative interaction was observed between concentration of chloral hydrate (CH) (which represents the main HA species), and regulated DBPs (P=0.006). CONCLUSION: In this population, exposure to low levels of HAs and HANs during the third trimester of pregnancy through drinking water was not associated to SGA status in newborns. Nonetheless, more research is needed to clarify possible effect of brominated compounds and interaction between different DBPs.

Colder-to-warmer changes in children's blood lead concentrations are related to previous blood lead status: results from a systematic review of prospective studies.

OBJECTIVE: To estimate the extent of changes in mean BLLs from colder to warmer months, in children aged 1-5 years with different status of lead in colder months. METHODOLOGY: We performed a systematic review using an in-house algorithm developed in MEDLINE, EMBASE, Web of Science, and CINHAL. Search was performed between November 2012 and July 2013, and data evaluation and extraction were subsequently conducted. The mean BLLs observed in the warmer months was divided by the one observed in the colder months to obtain the warmer-to-colder ratio (WCR). Study-specific WCRs were pooled using the fixed-effects method of Mantel-Haenszel to estimate the combined WCR. RESULTS: From 4040 papers initially identified, eight cohort studies were considered relevant for inclusion. The combined WCR was inversely related to the BLLs observed during colder months. The values were 1.25 (95% CI: 0.90-1.60), 1.06 (95% CI: 0.92-1.19), and 0.95 (95% CI: 0.51-1.39) for children showing baseline BLLs of <10µgdL(-1), 10-20µgdL(-1)and ≥20µgdL(-1), respectively. The combined WCR was influenced neither by children's age nor place/date of study. CONCLUSION: The extent of the summer increase in BLLs depends on the BLLs in the colder months.

Association between blood lead and blood pressure: Results from the Canadian Health Measures Survey (2007 to 2011).

BACKGROUND: Hypertension is the leading risk factor for cardiovascular disease, but its cause is not always known. Interest is increasing in the potential role of environmental chemicals, including lead. DATA AND METHODS: Data are from the first two cycles of the Canadian Health Measures Survey. Lead in whole blood (PbB), and systolic (SBP) and diastolic (DBP) blood pressure were measured and hypertension status was derived for 4,550 respondents aged 40 to 79. Linear regression estimated associations between PbB and SBP and DBP. Logistic regression estimated associations between PbB and hypertension. Adjusted least squares geometric means of PbB were estimated for hypertensive versus non-hypertensive individuals. RESULTS: Compared with non-hypertensive individuals, those with hypertension had higher average PbB levels, were older, more likely to be male, and more likely to have other hypertension risk factors (diabetes, family history of high blood pressure). In adjusted regression models, a modest association emerged between PbB levels and SBP among 40- to 54-year-olds, and between PbB levels and DBP for the overall population. No association emerged between PbB levels and hypertension prevalence. INTERPRETATION: A modest association was observed between blood lead levels and blood pressure, but not with hypertension, in Canadian adults aged 40 to 79.

Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs.

BACKGROUND: Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. OBJECTIVES: We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. DISCUSSION: Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. CONCLUSIONS: Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants. CITATION: Villanueva CM, Kogevinas M, Cordier S, Templeton MR, Vermeulen R, Nuckols JR, Nieuwenhuijsen MJ, Levallois P. 2014. Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs. Environ Health Perspect 122:213­221; http://dx.doi.org/10.1289/ehp.1206229