Altered oxidative stress and antioxidant biomarkers concentrations in pregnant individuals exposed to oil and gas sites in northeastern British Columbia.

Northeastern British Columbia is a region of prolific unconventional oil and gas activity (UOG). UOG activity can release volatile organic compounds (VOCs) which can elevate oxidative stress and disrupt antioxidant activity in exposed pregnant individuals, potentially increasing the risk of adverse pregnancy outcomes. This study measured biomarkers of oxidative stress and antioxidant activity in pooled urine samples of 85 pregnant individuals living in Northeastern British Columbia, to analyze associations between indoor air VOCs, oil and gas well density and proximity metrics, and biomarker concentrations. Concentrations of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), total antioxidant capacity (TAC), 6-hydroxymelatonin sulfate (aMT6s), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane (8-IP) were measured using assay kits. Associations between exposure metrics and biomarker concentrations were determined using multiple linear regression models adjusted for biomarker-specific covariables. UOG proximity was associated with decreased SOD and 8-OHdG. Decreased 8-OHdG was associated with increased proximity to all wells. Decreased aMT6s was observed with increased indoor air hexanal concentrations. MDA was negatively associated with indoor air 1,4-dioxane concentrations. No statistically significant associations were found between other biomarkers and exposure metrics. While some associations linked oil and gas activity to altered oxidative stress and antioxidant activity, the possibility of chance findings due to the large number of tests can not be discounted. This study shows that living near UOG wells may alter oxidative stress and antioxidant activity in pregnant individuals. More research is needed to elucidate underlying mechanisms and to what degree UOG activity affects oxidative stress and antioxidant activity.

Trace elements alone or in mixtures associated with unconventional natural gas exploitation affect rat fetal steroidogenesis and testicular development in vitro.

Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 µg/l), barium (500 µg/l) and strontium (500 µg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3ß-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.

Using in vitro data to derive acceptable exposure levels: A case study on PBDE developmental neurotoxicity.

BACKGROUND: Current acceptable chemical exposure levels (e.g., tolerable daily intake) are mainly based on animal experiments, which are costly, time-consuming, considered non-ethical by many, and may poorly predict adverse outcomes in humans. OBJECTIVE: To evaluate a method using human in vitro data and biological modeling to calculate an acceptable exposure level through a case study on 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) developmental neurotoxicity (DNT). METHODS: We reviewed the literature on in vitro assays studying BDE-47-induced DNT. Using the most sensitive endpoint, we derived a point of departure using a mass-balance in vitro disposition model and benchmark dose modeling for a 5% response (BMC05) in cells. We subsequently used a pharmacokinetic model of gestation and lactation to estimate administered equivalent doses leading to four different metrics of child brain concentration (i.e., average prenatal, average postnatal, average overall, and maximum concentration) equal to the point of departure. The administered equivalent doses were translated into tolerable daily intakes using uncertainty factors. Finally, we calculated biomonitoring equivalents for maternal serum and compared them to published epidemiological studies of DNT. RESULTS: We calculated a BMC05 of 164 µg/kg of cells for BDE-47 induced alteration of differentiation in neural progenitor cells. We estimated administered equivalent doses of 0.925-3.767 µg/kg/day in mothers, and tolerable daily intakes of 0.009-0.038 µg/kg/day (composite uncertainty factor: 100). The lowest derived biomonitoring equivalent was 19.75 ng/g lipids, which was consistent with reported median (0.9-23 ng/g lipids) and geometric mean (7.02-26.9 ng/g lipids) maternal serum concentrations from epidemiological studies. CONCLUSION: This case study supports using in vitro data and biological modeling as a viable alternative to animal testing to derive acceptable exposure levels.

Density and proximity of oil and gas wells and concentrations of trace elements in urine, hair, nails and tap water samples from pregnant individuals living in Northeastern British Columbia.

BACKGROUND: Oil and gas exploitation can release several contaminants in the environment, including trace elements, with potentially deleterious effects on exposed pregnant individuals and their developing fetus. Currently, there is limited data on pregnant individuals' exposure to contaminants associated with oil and gas activity. OBJECTIVES: We aimed to 1)measure concentrations of trace elements in biological and tap water samples collected from pregnant individuals participating in the EXPERIVA study; 2)compare with reference populations and health-based guidance values; 3)assess correlations across matrices; and 4)evaluate associations with the density/proximity of oil and gas wells. METHODS: We collected tap water, hair, nails, and repeated urine samples from 85pregnant individuals, and measured concentrations of 21trace elements. We calculated oil and gas well density/proximity (Inverse Distance Weighting [IDW]) for 4buffer sizes (2.5 km, 5 km, 10 km, no buffer). We performed Spearman's rank correlation analyses to assess the correlations across elements and matrices. We used multiple linear regression models to evaluate the associations between IDWs and concentrations. RESULTS: Some study participants had urinary trace element concentrations exceeding the 95th percentile of reference values; 75% of participants for V, 29% for Co, 22% for Ba, and 20% for Mn. For a given trace element, correlation coefficients ranged from -0.23 to 0.65 across matrices; correlations with tap water concentrations were strongest for hair, followed by nails, and urine. Positive (e.g., Cu, Cr, Sr, U, Ga, Ba, Al, Cd) and negative (e.g., Fe) associations were observed between IDW metrics and the concentrations of certain trace elements in water, hair, and nails. SIGNIFICANCE: Our results suggest that pregnant individuals living in an area of oil and gas activity may be more exposed to certain trace elements (e.g., Mn, Sr, Co, Ba) than the general population. Association with density/proximity of wells remains unclear.

Biomonitoring equivalents for perfluorooctanoic acid (PFOA) for the interpretation of biomonitoring data.

BACKGROUND: Perfluorooctanoic acid (PFOA) is detected in the blood of virtually all biomonitoring study participants. Assessing health risks associated with blood PFOA levels is challenging because exposure guidance values (EGVs) are typically expressed in terms of external dose. Biomonitoring equivalents (BEs) consistent with EGVs could facilitate health-based interpretations. OBJECTIVE: To i) derive BEs for serum/plasma PFOA corresponding to non-cancer EGVs of the U.S. Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR) and Health Canada, and ii) compare with PFOA concentrations from national biomonitoring surveys. METHODS: Starting from EGV points of departure, we employed pharmacokinetic data/models and uncertainty factors. Points of departure in pregnant rodents (U.S. EPA 2016, ATSDR) were converted into fetus and pup serum concentrations using an animal gestation/lactation pharmacokinetic model, and equivalent human fetus and child concentrations were converted into BEs in maternal serum using a human gestation/lactation model. The point of departure in adult rodents (Health Canada) was converted into a BE using experimental data. For epidemiology-based EGVs (U.S. EPA 2023, draft), BEs were directly based on epidemiological data or derived using a human gestation/lactation pharmacokinetic model. BEs were compared with Canadian/U.S. biomonitoring data. RESULTS: Non-cancer BEs (ng/mL) were 684 (Health Canada, 2018) or ranged from 15 to 29 (U.S. EPA, 2016), 6-10 (ATSDR, 2021) and 0.2-0.8 (U.S. EPA, 2023, draft). Ninety-fifth percentiles of serum levels from the 2018-2019 Canadian Health Measures Survey (CHMS) and the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were slightly below the BE for ATSDR, and geometric means were above the non-cancer BEs for the U.S. EPA (2023, draft). CONCLUSION: Non-cancer BEs spanned three orders of magnitude. The lowest BEs were for EGVs based on developmental endpoints in epidemiological studies. Concentrations in Canadian/U.S. national surveys were higher than or close to BEs for the most recent non-cancer EGVs.

Assessing gestational exposure to trace elements in an area of unconventional oil and gas activity: comparison with reference populations and evaluation of variability.

BACKGROUND: Located in Northeastern British Columbia, the Montney formation is an important area of unconventional oil and gas exploitation, which can release contaminants like trace elements. Gestational exposure to these contaminants may lead to deleterious developmental effects. OBJECTIVES: Our study aimed to (1) assess gestational exposure to trace elements in women living in this region through repeated urinary measurements; (2) compare urinary concentrations to those from North American reference populations; (3) compare urinary concentrations between Indigenous and non-Indigenous participants; and (4) evaluate inter- and intra-individual variability in urinary levels. METHODS: Eighty-five pregnant women participating in the Exposures in the Peace River Valley (EXPERIVA) study provided daily spot urine samples over 7 consecutive days. Samples were analyzed for 20 trace elements using inductively-coupled mass spectrometry (ICP-MS). Descriptive statistics were calculated, and inter- and intra-individual variability in urinary levels was evaluated through intraclass correlation coefficient (ICC) calculation for each trace element. RESULTS: When compared with those from North American reference populations, median urinary levels were higher in our population for barium (~2 times), cobalt (~3 times) and strontium (~2 times). The 95th percentile of reference populations was exceeded at least 1 time by a substantial percentage of participants during the sampling week for barium (58%), cobalt (73%), copper (29%), manganese (28%), selenium (38%), strontium (60%) and vanadium (100%). We observed higher urinary manganese concentrations in self-identified Indigenous participants (median: 0.19 µg/g creatinine) compared to non-Indigenous participants (median: 0.15 µg/g of creatinine). ICCs varied from 0.288 to 0.722, indicating poor to moderate reliability depending on the trace element. SIGNIFICANCE: Our results suggest that pregnant women living in this region may be more exposed to certain trace elements (barium, cobalt, copper, manganese, selenium, strontium, and vanadium), and that one urine spot sample could be insufficient to adequately characterize participants' exposure to certain trace elements. IMPACT STATEMENT: Unconventional oil and gas (UOG) is an important industry in the Peace River Valley region (Northeastern British Columbia, Canada). Information on the impacts of this industry is limited, but recent literature emphasizes the risk of environmental contamination. The results presented in this paper highlight that pregnant women living near UOG wells in Northeastern British Columbia may be more exposed to some trace elements known to be related to this industry compared to reference populations. Furthermore, our results based on repeated urinary measurements show that one urine sample may be insufficient to adequately reflect long-term exposure to certain trace elements.

Per- and polyfluoroalkyl substances (PFAS) in breast milk and infant formula: A global issue.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are transferred from mother to infants through breastfeeding, a time when children may be particularly vulnerable to PFAS-mediated adverse health effects. Infants can also be exposed to PFAS from infant formula consumption. Our recent literature-based scoping of breast milk levels reported that four PFAS often exceeded the United States Agency for Toxic Substances and Disease Registry (ATSDR) children's drinking water screening levels in both the general population and highly impacted communities in the U.S. and Canada. This work presents a comparison of global breast milk and infant formula PFAS measurements with the only reported health-based drinking water screening values specific to children. METHODS: We focused on four PFAS for which ATSDR has developed children's drinking water screening values: PFOA (perfluorooctanoic acid), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexanesulfonic acid), and PFNA (perfluorononanoic acid). Published literature on PFAS levels in breast milk and infant formula were identified via PubMed searches. Data were compared to children's drinking water screening values. DISCUSSION: Breast milk concentrations of PFOA and PFOS often exceed children's drinking water screening values, regardless of geographic location. The limited information on infant formula suggests its use does not necessarily result in lower PFAS exposures, especially for formulas reconstituted with drinking water containing PFAS. Unfortunately, individuals generally cannot know whether their infant's exposures exceed children's drinking water screening values. Thus, it is essential that pregnant and lactating women and others, especially those having lived in PFAS-contaminated communities, have data required to make informed decisions on infant nutrition. An international monitoring effort and access to affordable testing are needed for breast milk, drinking water and infant formula to fully understand infant PFAS exposures. Currently, our understanding of demonstrable methods for reducing exposures to emerging PFAS is limited, making this research and the communications surrounding it even more important.

Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

Dynamic Mass Balance Modeling for Chemical Distribution Over Time in In Vitro Systems With Repeated Dosing.

As toxicologists and risk assessors move away from animal testing and more toward using in vitro models and biological modeling, it is necessary to produce tools to quantify the chemical distribution within the in vitro environment prior to extrapolating in vitro concentrations to human equivalent doses. Although models predicting chemical distribution in vitro have been developed, very little has been done for repeated dosing scenarios, which are common in prolonged experiments where the medium needs to be refreshed. Failure to account for repeated dosing may lead to inaccurate estimations of exposure and introduce bias into subsequent in vitro to in vivo extrapolations. Our objectives were to develop a dynamic mass balance model for repeated dosing in in vitro systems; to evaluate model accuracy against experimental data; and to perform illustrative simulations to assess the impact of repeated doses on predicted cellular concentrations. A novel dynamic in vitro partitioning mass balance model (IV-MBM DP v1.0) was created based on the well-established fugacity approach. We parameterized and applied the dynamic mass balance model to single dose and repeat dosing scenarios, and evaluated the predicted medium and cellular concentrations against available empirical data. We also simulated repeated dosing scenarios for organic chemicals with a range of partitioning properties and compared the in vitro distributions over time. In single dose scenarios, for which only medium concentrations were available, simulated concentrations predicted measured concentrations with coefficients of determination (R 2) of 0.85-0.89, mean absolute error within a factor of two and model bias of nearly one. Repeat dose scenario simulations displayed model bias <2 within the cell lysate, and ∼1.5-3 in the medium. The concordance between simulated and available experimental data supports the predictive capacity of the IV-MBM DP v1.0 tool, but further evaluation as empirical data becomes available is warranted, especially for cellular concentrations.

A Generic Pharmacokinetic Model for Quantifying Mother-to-Offspring Transfer of Lipophilic Persistent Environmental Chemicals.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Proximity and density of unconventional natural gas wells and mental illness and substance use among pregnant individuals: An exploratory study in Canada.

BACKGROUND: Hydraulic fracturing (fracking) is a method used to extract unconventional natural gas (UNG). Living near UNG operations has been associated with various health outcomes, but few have explored the association between UNG and mental health and substance use. Our objective was to evaluate the association between metrics of residential UNG well density/proximity and mental illness and substance use among pregnant individuals in Northeastern British Columbia, Canada. METHODS: Individuals who gave birth at the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6278) were included in the study. Exposure was determined using inverse distance weighting (IDW) to calculate the density and proximity of UNG wells to the postal code centroid ofindividual's residential address at delivery. Four exposure metrics, categorized by quartiles, were calculated based on 50, 10, 5 and 2.5 km buffer zones around each postal code centroid. Logistic regression was used to separately evaluate associations between IDW quartiles of each metric and diagnosis of depression and anxiety prior to or during pregnancy, and self-reported substance use during pregnancy, controlling for relevant and available confounders. RESULTS: The second and third quartile (Q) of the 10 km IDW were associated with greater odds of depression (Q2: adjusted (aOR) 1.30, 95% (confidence interval) CI 1.03-1.64; Q3: aOR 1.35, 95% CI 1.07-1.70) compared to the first quartile, but not the fourth. Using the 5 km IDW, we observed a suggestive positive association with depression in the second and third quartile (aOR Q2: 1.21, 95% CI 0.96-1.53; aOR Q3: 1.24, 95% CI 0.98-1.57) compared to the first quartile. No statistically significant association was observed using the 2.5 km IDW exposure metric. CONCLUSION: We observed some evidence of greater odds of mental illness prior to or during pregnancy, and substance use during pregnancy in pregnant individuals living in postal codes with increased UNG well density/proximity, although associations were not observed in smaller buffer zones. This study adds to the growing literature on the adverse health outcomes surrounding living in proximity to UNG operations.

Current Breast Milk PFAS Levels in the United States and Canada: After All This Time, Why Don't We Know More?

BACKGROUND: 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. OBJECTIVES: The objectives of this work are to: a) document published PFAS breast milk concentrations in the United States and Canada; b) estimate breast milk PFAS levels from maternal serum concentrations in national surveys and communities impacted by PFAS; and c) compare measured/estimated milk PFAS concentrations to screening values. METHODS: 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. DISCUSSION: 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.

Volatile organic compounds (VOCs) in indoor air and tap water samples in residences of pregnant women living in an area of unconventional natural gas operations: Findings from the EXPERIVA study.

BACKGROUND: Northeastern British Columbia (Canada) is an area of unconventional natural gas (UNG) exploitation by hydraulic fracturing, which can release several contaminants, including volatile organic compounds (VOCs). To evaluate gestational exposure to contaminants in this region, we undertook the Exposures in the Peace River Valley (EXPERIVA) study. OBJECTIVES: We aimed to: 1) measure VOCs in residential indoor air and tap water from EXPERIVA participants; 2) compare concentrations with those in the general population and explore differences related to sociodemographic and housing characteristics; and 3) determine associations between VOC concentrations and density/proximity to UNG wells. METHODS: Eighty-five pregnant women participated. Passive air samplers were analyzed for 47 VOCs, and tap water samples were analyzed for 44 VOCs. VOC concentrations were compared with those from the Canadian Health Measure Survey (CHMS). We assessed the association between different metrics of well density/proximity and indoor air and tap water VOC concentrations using multiple linear regression. RESULTS: 40 VOCs were detected in >50% of air samples, whereas only 4 VOCs were detected in >50% of water samples. We observed indoor air concentrations >95th percentile of CHMS in 10-60% of samples for several compounds (acetone, 2-methyl-2-propanol, chloroform, 1,4-dioxane, hexanal, m/p-xylene, o-xylene, styrene, decamethylcyclopentasiloxane, dodecane and decanal). Indoor air levels of chloroform and tap water levels of total trihalomethanes were higher in Indigenous participants compared to non-Indigenous participants. Indoor air levels of chloroform and acetone, and tap water levels of total trihalomethanes were positively associated with UNG wells density/proximity metrics. Indoor air BTEX (benzene, toluene, ethylbenzene, xylenes) levels were positively correlated with some well density/proximity metrics. CONCLUSION: Our results suggest higher exposure to certain VOCs in pregnant women living in an area of intense unconventional natural gas exploitation compared with the general Canadian population, and that well density/proximity is associated with increased exposure to certain VOCs.

Genotoxic effect of meat consumption: A mini review.

In 2015, the International Agency for Research on Cancer classified the consumption of processed meat as carcinogenic to humans (Group 1) and red meat as probably carcinogenic to humans (Group 2A) based on sufficient data from animal models and epidemiological studies. However, research characterising the mechanisms underlying this carcinogenic process in humans are limited, particularly with respect to measures of direct DNA damage. The current review sought to evaluate and summarize the recent literature, published since 2000, regarding the associations of meat consumption and three biomarkers of genotoxicity in humans: DNA strand breaks (measured using the comet assay), DNA adducts, and micronucleus formation. After screening 230 potential articles, 35 were included, and then were classified as experimental or observational in design, the latter of which were further categorized according to their dietary assessment approach. Among the 30 observational studies, 4 of which used two different assays, 3 of 5 comet assay studies, 13 of 20 DNA adduct studies, and 7 of 9 micronucleus studies reported a positive association between meat consumption and DNA damage. Among the 5 experimental studies, 1 of 1 using the comet assay, 3 of 3 measuring DNA adducts and 0 of 1 measuring micronuclei reported significant positive associations with meat consumption. Nevertheless, common limitations among the selected publications included small sample size, and poor methodological reporting of both exposure and outcome measures. Moreover, the vast majority of studies only measured DNA damage in one biological sample using a single assay and we cannot exclude the possibility of publication bias. Ultimately, our review of the literature, published since 2000, revealed a preponderance of studies that support mechanisms of genotoxicity in playing an important role in the meat-cancer association.

Density and proximity to hydraulic fracturing wells and birth outcomes in Northeastern British Columbia, Canada.

BACKGROUND: Hydraulic 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. OBJECTIVE: To evaluate the association between the hydraulic fracturing well density/proximity and birth outcomes (birthweight, head circumference, preterm birth and small for gestational age (SGA)). METHODS: We 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. RESULTS: No 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 (ß [95% confidence interval (CI)]: -47.28 g [-84.30; -10.25]), and in the 2nd (ß [95% CI]: -40.87 g [-78.01; -3.73]) and 3rd (ß [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]). CONCLUSIONS: This 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.

How Many Urine Samples Are Needed to Accurately Assess Exposure to Non-Persistent Chemicals? The Biomarker Reliability Assessment Tool (BRAT) for Scientists, Research Sponsors, and Risk Managers.

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.

Can Silicone Passive Samplers be Used for Measuring Exposure of e-Waste Workers to Flame Retardants?

Silicone passive samplers were assessed for measuring personal exposure to 37 flame retardants at three Québec e-waste recycling facilities. Silicone brooches (n = 45), wristbands (n = 28), and armbands (n = 9) worn during a ∼8 h work shift accumulated detectable amounts of 95-100% of the target compounds. Brooch concentrations were significantly correlated with those from active air samplers from which we conclude that the brooches could be used to approximate inhalation exposure and other exposures related to air concentrations such as dermal exposure. The generic sampling rate of the brooch (19 ± 11 m3 day-1 dm-2) was 13 and 22 times greater than estimated for home and office environments, respectively, likely because of the dusty work environment and greater movement of e-waste workers. BDE-209 concentrations in brooches and wristbands were moderately and significantly (p < 0.05) correlated with levels in blood plasma; organophosphorus esters in brooches and wristbands were weakly and insignificantly correlated with their metabolite biomarkers in post-shift spot urine samples. Silicone brooches and wristbands deployed over a single shift in a dusty occupational setting can be useful for indicating the internal exposure to compounds with relatively long biological half-lives, but their use for compounds with relatively short half-lives is not clear and may require either a longer deployment time or an integrated biomarker measure.

Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

BACKGROUND: Children are exposed to p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children's exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. METHODS: We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development. p,p'-DDT and p,p'-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0-6 months, 6-12 months, 12-24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. RESULTS: We found no significant association between levels of p,p'-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p'-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p'-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0-6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6-12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12-24 months exposure period. CONCLUSION: In this study of Japanese children, estimated postnatal p,p'-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure to p,p'-DDE may be associated with higher BMI during childhood.

Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.

INTRODUCTION: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444.