The human health effects of unconventional oil and gas development (UOGD): A scoping review of epidemiologic studies.

OBJECTIVE: Unconventional oil and gas development (UOGD, sometimes termed "fracking" or "hydraulic fracturing") is an industrial process to extract methane gas and/or oil deposits. Many chemicals used in UOGD have known adverse human health effects. Canada is a major producer of UOGD-derived gas with wells frequently located in and around rural and Indigenous communities. Our objective was to conduct a scoping review to identify the extent of research evidence assessing UOGD exposure-related health impacts, with an additional focus on Canadian studies. METHODS: We included English- or French-language peer-reviewed epidemiologic studies (January 2000-December 2022) which measured exposure to UOGD chemicals directly or by proxy, and where health outcomes were plausibly caused by UOGD-related chemical exposure. Results synthesis was descriptive with results ordered by outcome and hierarchy of methodological approach. SYNTHESIS: We identified 52 studies from nine jurisdictions. Only two were set in Canada. A majority (n = 27) used retrospective cohort and case-control designs. Almost half (n = 24) focused on birth outcomes, with a majority (n = 22) reporting one or more significant adverse associations of UOGD exposure with: low birthweight; small for gestational age; preterm birth; and one or more birth defects. Other studies identified adverse impacts including asthma (n = 7), respiratory (n = 13), cardiovascular (n = 6), childhood acute lymphocytic leukemia (n = 2), and all-cause mortality (n = 4). CONCLUSION: There is a growing body of research, across different jurisdictions, reporting associations of UOGD with adverse health outcomes. Despite the rapid growth of UOGD, which is often located in remote, rural, and Indigenous communities, Canadian research on its effects on human health is remarkably sparse. There is a pressing need for additional evidence.

RéSUMé: OBJECTIF: L'exploitation pétrolière et gazière non conventionnelle (EPGNC, parfois appelée « fracturation ¼ ou « fracturation hydraulique ¼) est un processus industriel d'extraction du méthane et/ou de gisements de pétrole. De nombreux produits chimiques utilisés dans l'EPGNC ont des effets indésirables connus sur la santé humaine. Le Canada est un grand producteur de gaz dérivé de l'EPGNC, dont les puits sont souvent situés à l'intérieur et autour de communautés rurales et autochtones. Nous avons mené une étude de champ pour déterminer l'étendue des données de recherche évaluant les effets sur la santé de l'exposition à l'EPGNC, en nous concentrant plus particulièrement sur les études canadiennes. MéTHODE: Nous avons inclus des études épidémiologiques en anglais ou en français évaluées par les pairs (janvier 2000 à décembre 2022) qui mesuraient l'exposition directe ou indirecte aux produits chimiques de l'EPGNC et dans lesquelles les résultats cliniques étaient plausiblement causés par l'exposition aux produits chimiques liés à l'EPGNC. La synthèse des résultats est descriptive, et les résultats sont ordonnés selon les résultats cliniques et l'approche méthodologique. SYNTHèSE: Nous avons identifié 52 études menées dans neuf juridictions. Deux seulement étaient canadiennes. La majorité (n = 27) faisaient appel à des cohortes rétrospectives ou étaient des études cas-témoins. Près de la moitié (n = 24) portaient sur les issues de la grossesse, et la majorité (n = 22) déclaraient une ou plusieurs associations indésirables significatives entre l'exposition à l'EPGNC et : l'insuffisance de poids à la naissance; la petite taille du bébé pour son âge gestationnel; la naissance avant terme; et une ou plusieurs anomalies congénitales. D'autres études faisaient état d'effets indésirables, dont l'asthme (n = 7), les troubles respiratoires (n = 13), les troubles cardiovasculaires (n = 6), la leucémie aiguë lymphoblastique infantile (n = 2) et la mortalité toutes causes confondues (n = 4). CONCLUSION: Il existe dans différents pays un corpus croissant d'études qui font état d'associations entre l'EPGNC et des résultats sanitaires indésirables. Malgré la croissance rapide de l'EPGNC, souvent présente dans des communautés éloignées, rurales et autochtones, la recherche canadienne sur ses effets sur la santé humaine est remarquablement clairsemée. Il y a un besoin urgent de recueillir d'autres données probantes à ce sujet.

Modelling spatial & temporal variability of air pollution in an area of unconventional natural gas operations.

Despite the growing unconventional natural gas production industry in northeastern British Columbia, Canada, few studies have explored the air quality implications on human health in nearby communities. Researchers who have worked with pregnant women in this area have found higher levels of volatile organic compounds (VOCs) in the indoor air of their homes associated with higher density and closer proximity to gas wells. To inform ongoing exposure assessments, this study develops land use regression (LUR) models to predict ambient air pollution at the homes of pregnant women by using natural gas production activities as predictor variables. Using the existing monitoring network, the models were developed for three temporal scales for 12 air pollutants. The models predicting monthly, bi-annual, and annual mean concentrations explained 23%-94%, 54%-94%, and 73%-91% of the variability in air pollutant concentrations, respectively. These models can be used to investigate associations between prenatal exposure to air pollutants associated with natural gas production and adverse health outcomes in northeastern British Columbia.

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.

Cardiometabolic health and per and polyfluoroalkyl substances in an Inuit population.

INTRODUCTION: The cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing to this since PFAAs have been linked with hypercholesterolemia, diabetes, and high blood pressure. The aim of this study was to examine the association between a PFAAs mixture and lipid profiles, Type II diabetes, prediabetes, and high blood pressure in this Inuit population. METHODS: We included 1212 participants of the Qanuilirpitaa? 2017 survey aged 16-80 years. Two mixture models (quantile g-computation and Bayesian Kernel Machine Regression (BKMR)) were used to investigate the associations between six PFAAs (PFHxS, PFOS, PFOA and three long-chain PFAAs (PFNA, PFDA and PFUnDA)) with five lipid profiles and three cardiometabolic outcomes. Non-linearity and interaction between PFAAs were further assessed. RESULTS: An IQR increase in all PFAAs congeners resulted in an increase in total cholesterol (ß 0.15, 95% confidence interval (CI) 0.06, 0.24), low-density lipoprotein cholesterol (LDL) (ß 0.08, 95% CI 0.01, 0.16), high-density lipoprotein cholesterol (HDL) (ß 0.04, 95% CI 0.002, 0.08), apolipoprotein B-100 (ß 0.03, 95% CI 0.004, 0.05), and prediabetes (OR 1.80, 95% CI 1.11, 2.91). There was no association between PFAAs and triglycerides, diabetes, or high blood pressure. Long-chain PFAAs congeners were the main contributors driving the associations. Associations were largely linear, and there was no evidence of interaction between the PFAAs congeners. CONCLUSIONS: Our study provides further evidence of increasing circulating lipids with increased exposure to PFAAs. The increased risk of prediabetes points to the influence of PFAAs on potential clinical outcomes. International regulation of PFAAs is essential to curb PFAAs exposure and related health effects in Arctic communities.

Estimation of exposure to particulate matter in pregnant individuals living in an area of unconventional oil and gas operations: Findings from the EXPERIVA study.

Northeastern British Columbia (Canada) is an area of oil and gas exploitation, which may result in release of fine (PM2.5) and inhalable (PM10) particulate matter. The aims of this study were to: 1) apply extrapolation methods to estimate exposure to PM2.5 and PM10 concentrations among EXPERIVA (Exposures in the Peace River Valley study) participants using air quality data archives; and 2) conduct exploratory analyses to investigate correlation between PM exposure and metrics of oil and gas wells density, proximity, and activity. Gestational exposure to PM2.5 and PM10 of the EXPERIVA participants (n = 85) was estimated by averaging the concentrations measured at the closest or three closest air monitoring stations during the pregnancy period. Drilling metrics were calculated based upon the density and proximity of conventional and unconventional oil and gas wells to each participant's residence. Phase-specific metrics were determined for unconventional wells. The correlations (ρ) between exposure to PM2.5 and PM10 and metrics of well density/proximity were determined using Spearman's rank correlation test. Estimated PM ambient air concentrations ranged between 4.73 to 12.13 µg/m3 for PM2.5 and 7.14 to 26.61 µg/m3 for PM10. Conventional wells metrics were more strongly correlated with PM10 estimations (ρ between 0.28 and 0.79). Unconventional wells metrics for all phases were positively correlated with PM2.5 estimations (ρ between 0.23 and 0.55). These results provide evidence of a correlation between density and proximity of oil and gas wells and estimated PM exposure in the EXPERIVA participants.

Perfluoroalkyl acid and bisphenol-A exposure via food sources in four First Nation communities in Quebec, Canada.

OBJECTIVE: To document perfluoroalkyl acids (PFAA) and bisphenol-A (BPA) exposure in four First Nation communities in northern Quebec compared with the Canadian Health Measures Survey (CHMS Cycle 5 2016-2017) and examine the associations between dietary consumption and chemical exposure. DESIGN: We used cross-sectional data from the JES-YEH! project conducted in collaboration with four First Nation communities in 2015. A FFQ collected information on diet, and PFAA and BPA were measured in biological samples. We used generalised linear models to test the associations between food intake and chemical biomarkers. SETTING: Northern Quebec. PARTICIPANTS: Youth aged 3-19 years (n 198). RESULTS: Mean perfluorononanoic acid (PFNA) levels were significantly higher in JES-YEH! than CHMS, and BPA levels were higher among those aged 12-19 years compared with CHMS. Dairy products were associated with PFNA among Anishinabe and Innu participants (geometric mean ratio 95 % CI: 1·53 (95 % CI 1·03, 2·29) and 1·52 (95 % CI 1·05, 2·20), respectively). PFNA was also associated with ultra-processed foods (1·57 (95 % CI 1·07, 2·31)) among Anishinabe, and with wild fish and berries (1·44 (95 % CI 1·07, 1·94); 1·75 (95 % CI 1·30, 2·36)) among Innu. BPA was associated with cheese (1·72 (95 % CI 1·19, 2·50)) and milk (1·53 (95 % CI 1·02, 2·29)) among Anishinabe, and with desserts (1·71 (95 % CI 1·07, 2·74)), processed meats (1·55 (95 % CI 1·00, 2·38)), wild fish (1·64 (95 % CI 1·07, 2·49)) and wild berries (2·06 (95 % CI 1·37, 3·10)) among Innu. CONCLUSIONS: These results highlight the importance of better documenting food-processing and packaging methods, particularly for dairy products, and their contribution to endocrine disruptors exposures as well as to promote minimally processed and unpackaged foods to provide healthier food environments for youth in Indigenous communities and beyond.

Associations between dietary profiles and perfluoroalkyl acids in Inuit youth and adults.

BACKGROUND: Perfluoroalkyl acids (PFAAs), a subset of perfluoroalkyl substances (PFAS), are synthetic chemicals used in industrial and consumer applications. They are exceptionally stable and highly mobile in the environment, and were detected in high concentrations in Arctic wildlife and Nunavik Inuit. The study's objective was to study the association between dietary profiles in Nunavik and plasma PFAAs concentrations. METHODS: The study used data from the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) (N = 1172) on Inuit adults aged 16-80 years. Nine PFAAs congeners were measured in plasma samples (six were detected). Dietary profiles were identified using latent profile analysis. Two sets of dietary profiles were included; the first included market (store-bought) and country foods (harvested/hunted from the land), and the second included only country foods. Multiple linear regression models regressed log-transformed PFAAs concentrations against the dietary profiles, adjusting for sociodemographic variables. RESULTS: We identified statistically significant 24.54-57.55 % increases in all PFAAs congeners (PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS) in the dietary profile defined by frequent country food consumption compared to the dietary profile defined by frequent market food consumption. Individuals defined by low consumption of foods (related to food insecurity) had higher concentrations of six PFAAs compared to individuals with frequent market food consumption. The associations were stronger with profiles defined by more frequent country food consumption, and particularly those with increased marine mammal consumption. PFDA, PFUnDA, and PFOS were particularly associated with high country food consumption frequency, such that their concentrations increased by approximately 67-83 % compared to those reporting no or very little consumption of any country foods. CONCLUSIONS: Increased country food consumption was strongly associated with higher PFAAs concentrations, particularly PFOS, PFDA, and PFUnDA. The results provide further evidence that the quality of country foods is being threatened by PFAAs contamination. Additional national and international regulations are required to protect the Arctic and its inhabitants from these pollutants.

Plasma concentrations of perfluoroalkyl acids and their determinants in youth and adults from Nunavik, Canada.

Perfluoroalkyl acids (PFAAs), a subset of per- and poly-fluoroalkyl substances (PFAS), are environmentally stable, mobile and bioaccumulative compounds. This leads to high concentrations in wildlife species essential to the cultural identity and subsistence of Arctic populations. Our objective was to characterize the distribution and exposure determinants of PFAAs among Nunavik Inuit adults. The study included up to 1322 Nunavik residents aged 16-80 years who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017). Plasma concentrations were compared to those the general Canadian population using data from the Canadian Health Measures Survey Cycle 5 (2016-2017). Associations between plasma concentrations of nine PFAAs, determined by liquid chromatography-tandem mass spectrometry, and sociodemographic factors and traditional activity participation were examined using multiple linear regression models. Overall exposure to PFAAs was twice as high compared to the general Canadian population and less regulated perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) concentrations were 7-fold higher, and perfluorodecanoic acid (PFDA) concentrations were 4-fold higher. Males had higher concentrations of perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS), whereas females had higher concentrations of PFDA and PFUnDA. PFAAs concentrations increased with age and were highest among those aged 60+ years. PFNA and PFOA concentrations followed a J-shaped pattern: those aged 16-29 years had higher concentrations than those aged 20-29 and 30-39 years. Ungava Bay generally had lower concentrations of all PFAAs congeners compared to Hudson Bay and Hudson Strait, with the exception of PFNA, which tended to have the lowest concentration in Hudson Strait. PFAAs concentrations were highly associated with hunting activity, omega-3 polyunsaturated fatty acids, and drinking water from environmental sources. The results highlight the importance of characterizing PFAAs exposure sources in Arctic communities and provide further evidence for the long-range transport of long-chain PFAAs and their precursors that necessitate international action.

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.

Non-persistent exposures from plasticizers or plastic constituents in remote Arctic communities: a case for further research.

BACKGROUND: Persistent organic pollutant exposures are well-documented in the Arctic, but fewer studies examined non-persistent chemicals, despite increased market food and consumer product consumption. OBJECTIVE: To measure phenol, paraben, phthalate, and alternative plasticizer concentrations in Inuit adults. METHODS: The study included 30 pooled urine samples from Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) participants. Creatinine-adjusted geometric mean concentrations (GM) and 95% confidence intervals (CI) were compared across sex, age, and regions, and compared to those in the Canadian Health Measures Survey (CHMS) and the First Nations Biomonitoring Initiative (FNBI). RESULTS: Q2017 bisphenol-A concentrations were double the CHMS 2018-2019 concentrations [GM (95% CI): 1.98 (1.69-2.31) versus 0.71 (0.60-0.84) µg/g creatinine], but in line with FNBI [1.74 (1.41-2.13) µg/g creatinine]. Several phthalate concentrations were higher in Q2017 versus CHMS, particularly monobenzyl phthalate, which was was 19-fold higher in Q2017 versus CHMS 2018-2019 [45.26 (39.35-52.06) versus 2.4 (2.0-2.9) µg/g creatinine] and four-fold higher than FNBI. There were also four-fold higher concentrations of the two alternate plasticizer 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TIXB) metabolites in Q2017 compared to CHMS 2018-2019. Women and people living in Ungava Bay had generally higher concentrations of non-persistent chemicals. SIGNIFICANCE: The results suggest higher concentrations of certain non-persistent chemicals in Inuit versus the general Canadian population. IMPACT: Few studies have explored non-persistent chemical distributions in Northern communities, despite the increasing consumer product and market food consumption. We analyzed 30 pooled samples from the Qanuilirpitaa? Nunavik Inuit Health Survey 2017 to assess exposures to common plasticizes and plastic constituents and compare their levels with the general Canadian population and First Nation groups. We observed particularly higher levels of bisphenol-A, of monobenzyl phthalate, and of two 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) metabolites among Nunavimmiut compared to the general Canadian population, notably among women and Ungava Bay residents. Larger studies are required to confirm our findings and identify potential adverse health effects from these exposures.

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.

Exposure to benzene, toluene and polycyclic aromatic hydrocarbons in Nunavimmiut aged 16 years and over (Nunavik, Canada) - Qanuilirpitaa 2017 survey.

There are numerous volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) that Inuit may be exposed to from combustion, cooking, heating, vehicle exhaust, active and passive smoking and other local sources of contaminants such as oil spills or open-air burning in landfills. To better assess the levels of exposure to these non-persistent chemicals, we measured a suite of benzene, toluene (two VOCs) and PAHs metabolites in pooled urine samples from youth and adults aged 16 years old and over who participated in the Qanuilirpitaa? 2017 Inuit Health Survey (Q2017), a population health survey conducted in Nunavik. A cost-effective pooling strategy was established and 30 different pools from individual urine samples (n = 1266) were created by grouping individual urine samples by sex, age groups and regions. To assess smoking and exposure to second-hand smoke, cotinine levels were measured in individual urine samples. We found that benzene, toluene, all detected PAHs metabolites and cotinine levels were significantly higher in Q2017 compared to adults in the Canadian Health Measure Survey Cycle 4 (2014-2015) or the general U.S population (2015-2016). Moreover, mean levels of one benzene metabolite, S-phenylmercapturic acid, and several PAHs metabolites, 1-naphthol, 2-and 3-hydroxyfluorene, and 4- and 9-hydroxyphenanthrene, known to be associated with smoking habits, were higher in Q2017 compared to reference values (RV95) established for non-smokers in the general Canadian population. Furthermore, benzene and PAHs metabolites were all correlated with cotinine levels. Our results suggest that the high smoking prevalence in Nunavik is an important contributor to the elevated benzene and PAHs exposure. Other local sources may add to that exposure, although we were not able to account for their contribution. These data highlight the importance of regional and community efforts for reducing smoking and to encourage smoke-free homes in Nunavik, while continuing to investigate and reduce other possible local sources of exposure to benzene, toluene and PAHs.

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.

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.

Perfluoroalkyl acids in pregnant women from Nunavik (Quebec, Canada): Trends in exposure and associations with country foods consumption.

BACKGROUND: Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)). OBJECTIVES: From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016-2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016-2017. METHODS: Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and -6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016-2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016-2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data. RESULTS: Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016-2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016-2017, mean concentrations for PFNA (GM: 2.4 µg/L), PFDA (0.53 µg/L) and PFUdA (0.61 µg/L) were higher than those measured in women aged 18-40 years old in the Cycle 5 (2016-2017) of the CHMS. PFOA (0.53 µg/L) and PFHxS (0.26 µg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016-2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016-2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016-2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs. CONCLUSIONS: The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik.

Urinary and hair concentrations of trace metals in pregnant women from Northeastern British Columbia, Canada: a pilot study.

BACKGROUND: Northeastern 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. OBJECTIVE: We 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. METHODS: We 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. RESULTS: Median 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). CONCLUSION: Our results suggest higher gestational exposure to certain trace metals in our study population compared to reference populations.

Exposure to perfluoroalkyl substances (PFAS) and associations with thyroid parameters in First Nation children and youth from Quebec.

BACKGROUND: Perfluoroalkyl substances (PFASs) are found in several consumer goods. Exposure to PFASs in children has been associated with alteration in thyroid hormones, which have critical roles in brain function. OBJECTIVE: In 2015, 198 children and youth (3-19 y) were recruited as part of the pilot project Jeunes, Environnement et Santé/Youth, Environment and Health (JES!-YEH!), realized in collaboration with four First Nation communities in Quebec. We aimed to evaluate serum concentrations of PFASs in relation to concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4) and thyroglobulin while adjusting for relevant confounders. METHODS: PFASs (PFOS, PFOA, PFHxS, PFNA), 2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47) thyroid parameters (TSH, free T4, and thyroglobulin) were measured in serum samples of 186 participants. Iodine, creatinine, and cotinine were measured in urine samples. Serum levels of PFASs were compared to those measured in the general Canadian population and elsewhere. Multivariate regression analyses were performed to determine associations between PFASs and TSH, free T4 and thyroglobulin. RESULTS: PFOS, PFOA and PFHxS serum concentrations were low. However, PFNA concentrations among participants aged 12 to 19 years old from Anishinabe communities were three times higher than those measured in the Canadian Health Measures Survey (2009-2011) for the same age group (Geometric Means: 3.01 µg/L and 0.71 µg/L, respectively) and were particularly higher in the Anishinabe participants aged 6 to 11 years old (GM: 9.44 µg/L). Few participants had levels of TSH, free T4, and thyroglobulin outside age-specific paediatric ranges. When adjusted for relevant covariates and other contaminants, PFNA serum concentrations were positively associated with free T4 levels (Adjusted ß = 0.36; p = 0.0014), but not with TSH and thyroglobulin levels. No association was observed between the other PFAS and thyroid hormones parameters. CONCLUSION: This pilot project reveals among the highest exposure to PFNA in children reported until today, and suggests effects of PFNA as an endocrine disruptor, highlighting the importance of investigating the sources and effects of disproportionate exposure to emerging contaminants in some indigenous communities and ban all PFAS at the international scale.

Effects of Neonicotinoid Pesticides on Promoter-Specific Aromatase (CYP19) Expression in Hs578t Breast Cancer Cells and the Role of the VEGF Pathway.

BACKGROUND: Aromatase (CYP19) is a key enzyme in estrogens biosynthesis. In the mammary gland, CYP19 gene is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, fibroblast cells surrounding the tumor express increased levels of CYP19 mRNA due to a decrease of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter activity. Little is known about the effects of environmental chemicals on the promoter-specific CYP19 expression. OBJECTIVE: We aimed to determine the effects of two neonicotinoids (thiacloprid and imidacloprid) on promoter-specific CYP19 expression in Hs578t breast cancer cells and understand the signaling pathways involved. METHODS: Hs578t cells were exposed to various signaling pathway stimulants or neonicotinoids for 24 h. Promoter-specific expression of CYP19 was determined by real-time quantitative polymerase chain reaction and catalytic activity of aromatase by tritiated water release assay. RESULTS: To our knowledge, we are the first to demonstrate that the normal I.4 promoter and the breast cancer-relevant PII, I.3, and I.7 promoters of CYP19 are active in these cells. We found that the expression of CYP19 via promoters PII, I.3, and I.7 in Hs578t cells was, in part, dependent on the activation of two VEGF signaling pathways: mitogen-activated protein kinase (MAPK) 1/3 and phospholipase C (PLC). Exposure of Hs578t cells to environmental concentrations of imidacloprid and thiacloprid resulted in a switch in CYP19 promoter usage, involving inhibition of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter-mediated CYP19 expression and aromatase catalytic activity. Greater effects were seen at lower concentrations. Our results suggest that thiacloprid and imidacloprid exert their effects at least partially by inducing the MAPK 1/3 and/or PLC pathways. CONCLUSIONS: We demonstrated in vitro that neonicotinoids may stimulate a change in CYP19 promoter usage similar to that observed in patients with hormone-dependent breast cancer. https://doi.org/10.1289/EHP2698.

Gestational exposure to volatile organic compounds (VOCs) in Northeastern British Columbia, Canada: A pilot study.

BACKGROUND: Northeastern British Columbia (Canada) is an area of intense hydraulic fracturing for unconventional natural gas exploitation. There have been multiple reports of air and water contamination by volatile organic compounds in the vicinity of gas wells. Although these chemicals are known developmental toxicants, no biomonitoring effort has been carried out in the region. OBJECTIVE: To evaluate gestational exposure to benzene and toluene in the Peace River Valley, Northeastern British Columbia (Canada). METHODS: Urine samples were collected over five consecutive days from 29 pregnant women. Metabolites of benzene (s-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t,t-MA)) and toluene (s-benzylmercapturic acid (S-BMA)) were measured in pooled urine samples from each participant. Levels of benzene metabolites were compared to those from the general Canadian population and from a biomonitoring study of residents from an area of active gas exploitation in Pavillion, Wyoming (USA). Levels measured in participants from the two recruitment sites, and self-identifying as Indigenous or non-Indigenous, were also compared. RESULTS: Whereas the median S-PMA level (0.18µg/g creatinine) in our study was similar to that in the general Canadian population, the median t,t-MA level (180µg/g creatinine) was approximately 3.5 times higher. Five women had t,t-MA levels above the biological exposure index® proposed by the American Conference of Governmental Industrial Hygienists. The median urinary S-BMA level in our pilot study was 7.00µg/g creatinine. Urinary metabolite levels were slightly higher in self-identifying Indigenous women, but this difference was only statistically significant for S-PMA. DISCUSSION: Urinary t,t-MA levels, but not S-PMA levels, measured in our study are suggestive of a higher benzene exposure in participating pregnant women from the Peace River Valley than in the general Canadian population. Given the small sample size and limitations of t,t-MA measurements (e.g., non-specificity), more extensive monitoring is warranted.

The use of a unique co-culture model of fetoplacental steroidogenesis as a screening tool for endocrine disruptors: The effects of neonicotinoids on aromatase activity and hormone production.

Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid. Aromatase catalytic activity was determined in both cell lines using the tritiated water-release assay. Hormone production was measured by ELISA. The three neonicotinoids induced aromatase activity in our fetoplacental co-culture and concordingly, estradiol and estrone production were increased. In contrast, estriol production was strongly inhibited by the neonicotinoids. All three pesticides induced the expression of CYP3A7 in H295R cells, and this induction was reversed by co-treatment of H295R cells with exogenous estriol. CYP3A7 is normally expressed in fetal liver and is a key enzyme involved in estriol synthesis. We suggest that neonicotinoids are metabolized by CYP3A7, thus impeding the 16α-hydroxylation of fetal DHEA(-sulfate), which is normally converted to estriol by placental aromatase. We successfully used the fetoplacental co-culture as a physiologically relevant tool to highlight the potential effects of neonicotinoids on estrogen production, aromatase activity and CYP3A7 expression during pregnancy.