IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Evidence for reproductive health effects following exposure to hydraulic fracturing chemical mixtures.

In Brief: Unconventional oil and natural gas (UOG) operations, particularly hydraulic fracturing, have revolutionized oil and gas production, using and containing complex mixtures of chemicals that may impact reproductive health. While there is growing evidence for effects on births in hydraulic fracturing/UOG regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about these practices and reproductive health. Abstract: Unconventional oil and natural gas (UOG) operations have emerged over the last four decades to transform oil and gas production in the United States and globally by unlocking previously inaccessible hydrocarbon deposits. UOG development utilizes many compounds associated with conventional oil and gas, as well as some specific to UOG extraction, particularly during hydraulic fracturing (HF). While research is increasing on UOG chemicals and their mixtures, this review discusses the current evidence for reproductive toxicity following exposures to UOG/HF mixtures. These complex chemical mixtures have been demonstrated to interact with numerous mechanisms known to influence reproductive health. A growing number of environmental and controlled laboratory testing studies have reported adverse reproductive health effects in animals exposed to various UOG chemical mixtures. An expanding body of epidemiological literature has assessed adverse birth outcomes, although none has directly examined reproductive measures such as time to pregnancy, semen quality, and other direct measures of fertility. The existing literature provides moderate evidence for decreased birth weights, increased risk of small for gestational age and/or preterm birth, increased congenital abnormalities, and increased infant mortality, though importantly, studies are widely variable in methods used. Most studies utilized distance from UOG operations as an exposure proxy and did not measure actual chemical exposures experienced by those living near these operations. As such, while there is growing evidence for effects on births in these regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about UOG development and reproductive health.

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.

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.

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.

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.

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 (UOG) activity. 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, superoxide dismutase (SOD), glutathione S-transferase, total antioxidant capacity, 6-hydroxymelatonin sulfate (aMT6s), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane 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 were 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. Although 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 cannot 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.

Exposure to organophosphate esters among Inuit adults of Nunavik, Canada.

Halogenated organophosphate esters (OPEs) are increasingly used as flame retardants to replace polybrominated diphenyl ethers (PBDEs), which have been phased out due to their confirmed persistence, toxicity, and ability to undergo long range atmospheric transport. Non-halogenated OPEs are primarily used as plasticizers. While human exposure to PBDEs in the Canadian Arctic is well documented, it is not the case for OPEs. To assess the exposure to OPEs in Inuit living in Nunavik (northern Québec, Canada), we measured 16 metabolites of halogenated and non-halogenated OPEs in pooled urine samples from the last population health survey conducted in Nunavik, the Qanuilirpitaa? 2017 Inuit Health Survey (Q2017). Urine samples (n = 1266) were pooled into 30 pools by sex (female; male), age groups (16-19; 20-29; 30-39; 40-59; 60+ years old) and regions (Hudson Bay; Hudson Strait; Ungava Bay). Q2017 geometric means and 95 % confidence intervals were compared with data from the Canadian Health Measures Survey Cycle 6 (2018-2019) (CHMS). Halogenated OPEs were systematically detected and generally found at higher concentrations than non-halogenated OPEs in both Q2017 and CHMS. Furthermore, urinary levels of BCIPP and BDCIPP (halogenated) were lower in Q2017 compared to CHMS while concentrations of DPhP, DpCP and DoCP (non-halogenated) were similar between Q2017 and CHMS. Across the 16 metabolites measured in Q2017, BCIPHIPP (halogenated) had the highest levels (geometric mean: 1.40 µg/g creatinine). This metabolite was not measured in CHMS and should be included in future surveys. Overall, our results show that Inuit in Nunavik are exposed to lower or similar OPEs levels than the rest of the general Canadian population suggesting that the main current exposure to OPEs may be from consumer goods containing flame retardants and imported from the south rather than long-range atmospheric transport to the Arctic.

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.

The human health effects of unconventional oil and gas (UOG) chemical exposures: a scoping review of the toxicological literature.

Many chemicals associated with unconventional oil and natural gas (UOG) are known toxicants, leading to health concerns about the effects of UOG. Our objective was to conduct a scoping review of the toxicological literature to assess the effects of UOG chemical exposures in models relevant to human health. We searched databases for primary research studies published in English or French between January 2000 and June 2023 on UOG-related toxicology studies. Two reviewers independently screened abstracts and full texts to determine inclusion. Seventeen studies met our study inclusion criteria. Nine studies used solely in vitro models, while six conducted their investigation solely in animal models. Two studies incorporated both types of models. Most studies used real water samples impacted by UOG or lab-made mixtures of UOG chemicals to expose their models. Most in vitro models used human cells in monocultures, while all animal studies were conducted in rodents. All studies detected significant deleterious effects associated with exposure to UOG chemicals or samples, including endocrine disruption, carcinogenicity, behavioral changes and metabolic alterations. Given the plausibility of causal relationships between UOG chemicals and adverse health outcomes highlighted in this review, future risk assessment studies should focus on measuring exposure to UOG chemicals in human populations.

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.

Residential proximity to conventional and unconventional wells and exposure to indoor air volatile organic compounds in the Exposures in the Peace River Valley (EXPERIVA) study.

BACKGROUND: In a previous study located in Northeastern British Columbia (Canada), we observed associations between density and proximity of oil and gas wells and indoor air concentrations of certain volatile organic compounds (VOCs). Whether conventional or unconventional well types and phases of unconventional development contribute to these associations remains unknown. OBJECTIVE: To investigate the associations between proximity-based metrics for conventional and unconventional wells and measured indoor air VOC concentrations in the Exposures in the Peace River Valley (EXPERIVA) study samples. METHODS: Eighty-four pregnant individuals participated in EXPERIVA. Passive indoor air samplers were analyzed for 47 VOCs. Oil and gas well legacy data were sourced from the British Columbia Energy Regulator. For each participant's home, 5 km, 10 km and no buffer distances were delineated, then density and Inverse Distance Square Weighted (ID2W) metrics were calculated to estimate exposure to conventional and unconventional wells during pregnancy and the VOC measurement period. Multiple linear regression models were used to test for associations between the well exposure metrics and indoor air VOCs. For exposure metrics with >30% participants having a value of 0, we dichotomized exposure (0 vs. >0) and performed ANOVAs to assess differences in mean VOCs concentrations. RESULTS: Analyses indicated that: 1) conventional well density and ID2W metrics were positively associated with indoor air acetone and decanal; 2) unconventional well density and ID2W metrics were positively associated with indoor air chloroform and decamethylcyclopentasiloxane, and negatively associated with decanal; 3) drilling specific ID2W metrics for unconventional wells were positively associated with indoor air chloroform. CONCLUSION: Our analysis revealed that the association between the exposure metrics and indoor air acetone could be attributed to conventional wells and the association between exposure metrics and indoor air chloroform and decamethylcyclopentasiloxane could be attributed to unconventional wells.

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.

Levels and trends of metals in human populations living in the Arctic.

The 2021 Arctic Monitoring Assessment Program (AMAP)'s Human Health Assessment report presents a summary of the presence of contaminants in human populations across the circumpolar Arctic and provides an update to the previous assessment released in 2015. The primary objective of this paper is to summarise some of these findings by describing the current levels of metals across the Arctic, including key regional and temporal trends based on available national data and literature, and highlight knowledge gaps. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of mercury (Hg) were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada). Still, concentrations of several metals are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The 2021 AMAP human health assessment report and this paper provide an extensive summary of levels of metals and trace elements in adults, pregnant women, and children across the Arctic.

Levels and trends of persistent organic pollutants in human populations living in the Arctic.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only. Concentrations of most POPs are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The exceptions are per- and polyfluoroalkyl substances, with concentrations of some long-chain PFAS such as perfluorononanoic acid increasing in populations in Nunavik, Greenland and Sweden. This paper provides a more extensive summary of levels of contaminants in adults, pregnant women, and children across the Arctic than previous AMAP human health assessments, particularly for levels of long-chain PFAS, which are currently under consideration for inclusion in the Stockholm Convention.

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.

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.