Explore the vast range of titles available.

BackgroundHydraulic fracturing, a method used in Northeastern British Columbia (Canada) to extract natural gas, can release contaminants with potential deleterious health effects on fetal development. To date, the association between hydraulic fracturing activity and birth outcomes has not been evaluated in this region.ObjectiveTo evaluate the association between the hydraulic fracturing well density/proximity and birth outcomes (birthweight, head circumference, preterm birth and small for gestational age (SGA)).MethodsWe used birth records from the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6333 births). To estimate gestational exposure, we used inverse distance weighting (IDW) to calculate the density/proximity of hydraulic fracturing wells to pregnant women’s postal code centroid. For each birth, we calculated three IDWs using 2.5, 5, and 10 km buffer zones around women’s postal code centroid. We used linear and logistic regressions to evaluate associations between quartiles of postal code well density/proximity and birth outcomes, controlling for relevant covariates.ResultsNo associations were found between postal code well density/proximity and head circumference or SGA. A negative association was found between postal code well density/proximity and birthweight for infants born to women in the 2nd quartile of the 10 km buffer (β [95% confidence interval (CI)]: −47.28 g [−84.30; −10.25]), and in the 2nd (β [95% CI]: −40.87 g [−78.01; −3.73]) and 3rd (β [95% CI]: −42.01 g [−79.15; −4.87]) quartiles of the 5 km buffer. Increased odds of preterm birth were observed among women in the 2nd quartile of the 2.5 km buffer (odds ratio (OR) [95% CI]: 1.60 [1.30; 2.43]).ConclusionsThis is the first epidemiological study in Northeastern British Columbia evaluating associations between hydraulic fracturing and health outcomes. Our results show inconsistent patterns of association between hydraulic fracturing, preterm birth and reduced birthweight, and effect estimates did not match expected dose-response relationships.

BackgroundNortheastern British Columbia (Canada) is an area of intense natural gas exploitation by hydraulic fracturing. Hydraulic fracturing can release contaminants, including trace metals, many of which are known developmental toxicants. To date, there is limited data on human exposure to contaminants in this region.ObjectiveWe aimed to examine trace metals in urine and hair samples from 29 Indigenous and non-Indigenous pregnant women from two communities (Chetwynd and Dawson Creek) in Northeastern British Columbia.MethodsWe recruited 29 pregnant women who provided spot urine samples over five consecutive days and one hair sample. We measured 19 trace metals in pooled urine samples from each participant and in the first 2 cm of hair closest to the scalp. We compared urinary and hair concentrations to those measured in women from the general population using data from the Canadian Health Measure Survey (CHMS), or reference values found in the literature for trace metals not measured in the CHMS.ResultsMedian urinary (0.49 μg/L) and hair (0.16 μg/g) concentrations of manganese were higher in our participants than in the CHMS (<0.05 µg/L in urine) or reference population (0.067 μg/g in hair). In hair, median values for barium (4.48 μg/g), aluminum (4.37 μg/g) and strontium (4.47 μg/g) were respectively 16, 3, and 6 times higher compared with median values in a reference population. Concentrations of barium and strontium in hair were higher in self-identified Indigenous participants (5.9 and 5.46 μg/g, respectively) compared to non-Indigenous participants (3.88 and 2.60 μg/g) (p-values = 0.02 and 0.03).ConclusionOur results suggest higher gestational exposure to certain trace metals in our study population compared to reference populations.

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects.Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity).Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure.Results: We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01).Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels.

Purpose of Review We offer here a review of intraindividual variability in urinary biomarkers for assessing exposure to nonpersistent chemicals. We provide thoughts on how to better evaluate exposure to nonpersistent chemicals. Recent Findings We summarized reported values of intraclass correlation coefficients and found that most values fall into categories that indicate only poor to good reproducibility. Even within the “good” classification, a large percentage of study participants is likely to be misclassified as to their exposure. Summary There is sufficient information to support the statement that studies using only one spot measurement of a nonpersistent chemical will be unreliable. It is unequivocal that multiple samples have to be collected over a period of toxicological relevance and with consideration of exposure patterns. Sponsors of research and researchers themselves should be vocal about ensuring that sufficient resources are made available to properly characterize exposures when studying nonpersistent chemicals. Otherwise, we will continue to see an ever-growing body of literature yielding inconsistent and/or uninterpretable results.

Background: It has been suggested that pre- and postnatal exposure to persistent organic pollutants (POPs) can promote several adverse effects in children, such as altered neurodevelopment. Epidemiologic studies to date have relied on the analysis of biological samples drawn pre- or postnatally for exposure assessment, an approach that might not capture some key events in the toxicokinetics of POPs. Objectives: We aimed to build a generic physiologically based pharmacokinetic (PBPK) modeling framework for neutral POPs to assess infant toxicokinetic profiles and to validate the model using data on POP levels measured in mothers and infants from a Northern Québec Inuit population. Methods: The PBPK model developed herein was based upon a previously published model to which an infant submodel was added. Using the model and maternal blood levels at the time of delivery, exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB-180) in mothers was estimated to subsequently simulate infant blood, breast milk, and cord blood POP concentration. Simulations were then compared with corresponding measured levels through Spearman correlation analyses. Results: Predictions were highly correlated with measured concentrations for PCB-153, PCB-180, PCB-138, HCB, and p,p'-DDE (r = 0.83-0.96). Weaker correlations were observed for p,p'-DDT and β-HCH for which levels were near the limits of detection. Conclusion: This is the first study to validate a PBPK model of POPs in infants on an individual basis. This approach will reduce sampling efforts and enable the use of individualized POP toxicokinetic profiles in the epidemiologic studies of POP adverse effects on child development.

In epidemiologic and exposure research, biomonitoring is often used as the basis for assessing human exposure to environmental chemicals. Studies frequently rely on a single urinary measurement per participant to assess exposure to non-persistent chemicals. However, there is a growing consensus that single urine samples may be insufficient for adequately estimating exposure. The question then arises: how many samples would be needed for optimal characterization of exposure? To help researchers answer this question, we developed a tool called the Biomarker Reliability Assessment Tool (BRAT). The BRAT is based on pharmacokinetic modeling simulations, is freely available, and is designed to help researchers determine the approximate number of urine samples needed to optimize exposure assessment. The BRAT performs Monte Carlo simulations of exposure to estimate internal levels and resulting urinary concentrations in individuals from a population based on user-specified inputs (e.g., biological half-life, within- and between-person variability in exposure). The BRAT evaluates—through linear regression and quantile classification—the precision/accuracy of the estimation of internal levels depending on the number of urine samples. This tool should guide researchers towards more robust biomonitoring and improved exposure classification in epidemiologic and exposure research, which should in turn improve the translation of that research into decision-making.

Despite experimental evidence, most epidemiologic studies to date have not supported an association between exposure to persistent organic pollutants (POP) and breast cancer incidence in humans. This may be attributable to difficulties in estimating blood/tissue POP concentration at critical time periods of carcinogenesis. In this work we aimed to develop a tool to estimate lifetime POP blood/tissue exposure and levels during any hypothesized time window of susceptibility in breast cancer development. We developed a physiologically based pharmacokinetic (PBPK) model that can account for any given physiologic lifetime history. Using data on pregnancies, height, weight, and age, the model estimates the values of physiologic parameters (e.g., organ volume, composition, and blood flow) throughout a woman's entire life. We assessed the lifetime toxicokinetic profile (LTP) for various exposure scenarios and physiologic factors (i.e., breast-feeding, growth, pregnancy, lactation, and weight changes). Simulations for three POPs [hexachlorobenzene, polychlorinated biphenyl (PCB)-153, PCB-180] using different lifetime physiologic profiles showed that the same blood concentration at 55 years of age can be reached despite totally different LTP. Aside from exposure levels, lactation periods and weight profile history were shown to be the factors that had the greatest impact on the LTP. This new lifetime PBPK model, which showed the limitations of using a single sample value obtained around the time of diagnosis for lifetime exposure assessment, will enable researchers conducting environmental epidemiology studies to reduce uncertainty linked to past POP exposure estimation and to consider exposure during time windows that are hypothesized to be mechanistically critical in carcinogenesis.

IntroductionSex hormones have been implicated in the etiology of colorectal cancer. Endocrine disruptors (EDCs) are compounds that can interfere with sex hormone signalling and cause adverse health effects, including cancer. Exposure to EDCs is ubiquitous, but exposure in some workplaces occurs at much higher levels than in the general population.ObjectiveTo determine whether occupational exposure to EDCs is associated with colorectal cancer risk.Material and MethodsA case-cohort study was nested in the Alberta’s Tomorrow Project (ATP) and in the Ontario Health Study (OHS). Incident cases of colorectal cancer were identified (NATP=202, NOHS=605); a sub-cohort of 3,464 participants was selected at baseline (NATP=565, NOHS=2,899). Occupational exposure to 17 EDCs was estimated via linkage to CANJEM, a job-exposure matrix, for participants’ longest-held job. Specifically, CANJEM provides a frequency-weighted intensity metric of exposure and it was used to categorize participants into never exposed, exposed and substantially exposed to each individual EDC. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer associated with occupational exposure to EDCs while controlling for confounders identified using a directed acyclic graph.ResultsIn ATP, exposure to arsenic (OR=2.86, 95%CI: 1.06–7.63), copper (OR=0.53, 95%CI: 0.29–0.92), lead (OR=0.58, 95%CI: 0.34–0.97) and substantial exposure to arsenic (OR=2.87, 95%CI: 1.01–1.80), phenol (OR=0.25, 95%CI: 0.08–0.61), and trichloroethylene (OR=0.45, 95%CI: 0.21–0.90) were associated with colorectal cancer. In OHS, exposure to polychlorinated biphenyls (OR=3.95, 95%CI: 1.82–8.55), styrene (OR=0.47, 95%CI: 0.26–0.79), and substantial exposure to aluminum (OR=1.32, 95%CI: 1.03–1.68), cadmium (OR=0.59, 95%CI: 0.38–0.87), lead (OR=1.29, 95%CI: 1.03–1.60), phthalates (OR=0.52, 95%CI: 0.25–0.96), and trichloroethylene (OR=1.43, 95%CI: 1.08–1.88) were associated with colorectal cancer.ConclusionOf the 17 EDCs, five were associated with an increased risk, and seven with a decreased colorectal cancer risk; however, none of the associations were consistent between the two cohorts.

In our recent paper (Verner et al. 2013), we suggested that gestational weight gain (GWG) confounded the association between prenatal PCB-153 (polychlorinated biphenyl-153) exposure and birth weight observed in the meta-analysis by Govarts et al.

Despite 20 y of biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) in both serum and urine, we have an extremely limited understanding of PFAS concentrations in breast milk of women from the United States and Canada. The lack of robust information on PFAS concentrations in breast milk and implications for breastfed infants and their families were brought to the forefront by communities impacted by PFAS contamination. The objectives of this work are to: ) document published PFAS breast milk concentrations in the United States and Canada; ) estimate breast milk PFAS levels from maternal serum concentrations in national surveys and communities impacted by PFAS; and ) compare measured/estimated milk PFAS concentrations to screening values. We used three studies reporting breast milk concentrations in the United States and Canada We also estimated breast milk PFAS concentrations by multiplying publicly available serum concentrations by milk:serum partitioning ratios for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Measured and estimated breast milk concentrations were compared to children's drinking water screening values. Geometric means of estimated breast milk concentrations ranged over approximately two orders of magnitude for the different surveys/communities. All geometric mean and mean estimated and measured breast milk PFOA and PFOS concentrations exceeded drinking water screening values for children, sometimes by more than two orders of magnitude. For PFHxS and PFNA, all measured breast milk levels were below the drinking water screening values for children; the geometric mean estimated breast milk concentrations were close to-or exceeded-the children's drinking water screening values for certain communities. Exceeding a children's drinking water screening value does not indicate that adverse health effects will occur and should not be interpreted as a reason to not breastfeed; it indicates that the situation should be further evaluated. It is past time to have a better understanding of environmental chemical transfer to-and concentrations in-an exceptional source of infant nutrition. https://doi.org/10.1289/EHP10359.