This study investigated the occurrence of a comprehensive suite of polybrominated diphenyl ethers (PBDEs) and current-use flame retardants (FRs) in ring-billed gulls breeding in a highly industrialized section of the St. Lawrence River, downstream from Montreal (QC, Canada). Despite major point-sources and diffuse contamination by FRs, nearly no FR data have been reported in birds from this area. Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEHTBP) was detected in 89% of ring-billed gull livers (mean: 2.16 ng/g ww; max: 17.6 ng/g ww). To our knowledge, this is the highest detection frequency and highest concentrations reported thus far in any avian species or populations. Dechlorane Plus (DP) isomers were also particularly abundant (anti-DP detected in 100% and syn-DP in 93% of livers). Other detected FR compounds (3-14% detection) included 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB), hexachlorocyclopentenyl-dibromocyclooctane (HCDBCO) and β-1,2-dibromo-4-(1.2-dibromoethyl)-cyclohexane (β-TBECH). Mean BDE-209 (57.2 ± 12.2 ng/g ww) in ring-billed gull livers was unexpectedly high for this midtrophic gull species, exceeding levels reported in several apex raptors such as peregrine falcons. BDE-209's relative contribution to ∑PBDEs was on average 25% (exceeding BDE-47 and BDE-99) and contrasted with profiles typically reported for fish-eating gull species. The present study highlighted preoccupying gaps in upcoming FR regulations and stressed the need for further investigation of the sources of FR exposure in highly urbanized areas.

The enzyme aromatase (CYP19; cytochrome P450 19) in humans undergoes highly tissue- and promoter-specific regulation. In hormone-dependent breast cancer, aromatase is over-expressed via several normally inactive promoters (PII, I.3, I.7). Aromatase biosynthesizes estrogens, which stimulate breast cancer cell proliferation. The placenta produces estrogens required for healthy pregnancy and the major placental CYP19 promoter is I.1. Exposure to certain pesticides, such as atrazine, is associated with increased CYP19 expression, but little is known about the effects of neonicotinoid insecticides on CYP19. We developed sensitive and robust RT-qPCR methods to detect the promoter-specific expression of CYP19 in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells, and determined the potential promoter-specific disruption of CYP19 expression by atrazine and the commonly used neonicotinoids imidacloprid, thiacloprid, and thiamethoxam. In H295R cells, atrazine concentration-dependently increased PII- and I.3-mediated CYP19 expression and aromatase catalytic activity. Thiacloprid and thiamethoxam induced PII- and I.3-mediated CYP19 expression and aromatase activity at relatively low concentrations (0.1-1.0 µM), exhibiting non-monotonic concentration-response curves with a decline in gene induction and catalytic activity at higher concentrations. In HUVEC cells, atrazine slightly induced overall (promoter-indistinct) CYP19 expression (30 µM) and aromatase activity (≥ 3 µM), without increasing I.1 promoter activity. None of the neonicotinoids increased CYP19 expression or aromatase activity in HUVEC cells. Considering the importance of promoter-specific (over)expression of CYP19 in disease (breast cancer) or during sensitive developmental periods (pregnancy), our newly developed RT-qPCR methods will be helpful tools in assessing the risk that neonicotinoids and other chemicals may pose to exposed women.

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

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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.

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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 (β [95% confidence interval (CI)]: −47.28 g [−84.30; −10.25]), and in the 2nd (β [95% CI]: −40.87 g [−78.01; −3.73]) and 3rd (β [95% CI]: −42.01 g [−79.15; −4.87]) quartiles of the 5 km buffer. Increased odds of preterm birth were observed among women in the 2nd quartile of the 2.5 km buffer (odds ratio (OR) [95% CI]: 1.60 [1.30; 2.43]). 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.