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Background: Endocrine disrupting compounds (EDCs) such as phthalates and phenols can affect placental functioning and fetal health, potentially via epigenetic modifications. We investigated the associations between pregnancy exposure to synthetic phenols and phthalates estimated from repeated urine sampling and genome wide placental DNA methylation., Methods: The study is based on 387 women with placental DNA methylation assessed with Infinium MethylationEPIC arrays and with 7 phenols, 13 phthalates, and two non-phthalate plasticizer metabolites measured in pools of urine samples collected twice during pregnancy. We conducted an exploratory analysis on individual CpGs (EWAS) and differentially methylated regions (DMRs) as well as a candidate analysis focusing on 20 previously identified CpGs. Sex-stratified analyses were also performed., Results: In the exploratory analysis, when both sexes were studied together no association was observed in the EWAS. In the sex-stratified analysis, 114 individual CpGs (68 in males, 46 in females) were differentially methylated, encompassing 74 genes (36 for males and 38 for females). We additionally identified 28 DMRs in the entire cohort, 40 for females and 42 for males. Associations were mostly positive (for DMRs: 93% positive associations in the entire cohort, 60% in the sex-stratified analysis), with the exception of several associations for bisphenols and DINCH metabolites that were negative. Biomarkers associated with most DMRs were parabens, DEHP, and DiNP metabolite concentrations. Some DMRs encompassed imprinted genes including APC (associated with parabens and DiNP metabolites), GNAS (bisphenols), ZIM2;PEG3;MIMT1 (parabens, monoethyl phthalate), and SGCE;PEG10 (parabens, DINCH metabolites). Terms related to adiposity, lipid and glucose metabolism, and cardiovascular function were among the enriched phenotypes associated with differentially methylated CpGs. The candidate analysis identified one CpG mapping to imprinted LGALS8 gene, negatively associated with ethylparaben., Conclusions: By combining improved exposure assessment and extensive placental epigenome coverage, we identified several novel genes associated with the exposure, possibly in a sex-specific manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: Policies aiming at decreasing air pollutants (e.g., fine particulate matter, PM 2.5 ) are often designed without targeting an explicit health benefit nor carrying out cost-benefit analyses., Methods: We developed a transdisciplinary backward and forward approach at the conurbation level: from health objectives set by local decision-makers, we estimated which reductions in PM 2.5 exposures and emissions would allow to reach them, and identified urban policies leading to these reductions (backward approach). We finally conducted health impact and cost-benefit analyses of these policies (forward approach). The policies were related to the most emitting sectors in the considered area (Grenoble, France), wood heating and transport sectors. The forward approach also considered the health impact and co-benefits of these policies related to changes in physical activity and CO 2 emissions., Findings: Decision-makers set three health targets, corresponding to decreases by 33% to 67% in PM 2.5 -attributable mortality in 2030, compared to 2016. A decrease by 42% in PM 2.5 exposure (from 13.9 µg/m 3 ) was required to reach the decrease by 67% in PM 2.5 -attributable mortality. For each Euro invested, the total benefit was about 30€ for policies focusing on wood heating, and 1 to 68€ for traffic policies. Acting on a single sector was not enough to attain a 67% decrease in PM 2.5 -attributable mortality. This target could be achieved by replacing all inefficient wood heating equipment by low-emission pellet stoves and reducing by 36% the traffic of private motorized vehicles. This would require to increase the share of active modes (walking, biking…), inducing increases in physical activity and additional health benefits beyond the initial target. Annual net benefits were between €484 and €629 per capita for policies with report on active modes, compared to between €162 and €270 without., Conclusions: Urban policies strongly reducing air pollution-attributable mortality can be identified by our approach. Such policies can be cost-efficient., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is only scant evidence that air pollution increases the risk of breast cancer., Objectives: We investigated this relationship for three air pollutants: nitrogen dioxide (NO 2 ) and particulate matter with an aerodynamical diameter below 10 µm (PM 10 ) and 2.5 µm (PM 2.5 )., Methods: We conducted a population-based case-control study on breast cancer in two French départements, including 1,229 women diagnosed with breast cancer in 2005-2007 and 1,316 control women frequency-matched on age. Concentrations of NO 2 , PM 10 and PM 2.5 at participants' addresses occupied during the last 10 years were assessed using a chemistry transport model. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models where each woman was assigned a weight depending on her probability of selection into the study., Results: The OR for breast cancer per 10-µg/m 3 increase in NO 2 was 1.11 (95% CI, 0.98, 1.26), and 1.41 (95% CI 1.07, 1.86) in the highest exposure quintile (Q5), compared to the first. The ORs per 10-µg/m 3 NO 2 did not markedly differ between pre- (OR 1.09, 95% CI 0.89, 1.35)) and post-menopausal women (OR 1.14, 95% CI 0.97, 1.33)), but the OR was substantially higher for hormone-receptor positive (ER+/PR+) breast tumor subtypes (OR 1.15, 95% CI 1.00, 1.31) than for ER-/PR- tumors (OR 0.95, 95% CI 0.72, 1.26). Breast cancer risk was not associated with either PM 10 (OR per 1 µg/m 3 1.01, 95% CI, 0.96, 1.06) or PM 2.5 (OR per 1 µg/m 3 1.02, 95% CI 0.95, 1.08), regardless of the menopausal status or of the breast tumor subtype., Discussion: Our study provides evidence that NO 2 exposure, a marker of traffic-related air pollutants, may be associated with an increased risk of breast cancer, particularly ER+/PR+ tumors., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Fine particulate matter (PM 2.5 ) exposure entails large health effects in many urban areas. Public measures aiming at decreasing air pollution are often designed without targeting an explicit health benefit. Our objective was to investigate the health and economic benefits and the social inequalities in exposure resulting from several scenarios of reduction of PM 2.5 exposure, in order to support decisions about urban policies., Material and Methods: In the French conurbations of Grenoble and Lyon (0.4 and 1.4 million inhabitants, respectively), PM 2.5 yearly average exposure was estimated on a 10-m grid by coupling a PM 2.5 dispersion model to population density. Changes in death cases, life expectancy, lung cancer and term low birth weight incident cases as well as associated health economic costs were estimated for ten PM 2.5 reduction scenarios differing in terms of amplitude of reduction and spatial extent. Changes in social differences in PM 2.5 exposure were also assessed., Results: During the 2015-2017 period, PM 2.5 average exposure was 13.9 μg/m 3 in Grenoble and 15.3 μg/m 3 in Lyon conurbations. Exposure to PM 2.5 led to an estimated 145 (95% Confidence Interval, CI, 90-199) and 531 (95% CI, 330-729) premature deaths, 16 (95% CI, 8-24) and 65 (95% CI, 30-96) incident lung cancers, and 49 (95% CI, 19-76) and 193 (95% CI, 76-295) term low birth weight cases each year in Grenoble and Lyon conurbations, respectively, compared to a situation without PM 2.5 anthropogenic sources, i.e. a PM 2.5 concentration of 4.9 μg/m 3 . The associated costs amounted to 495 (Grenoble) and 1767 (Lyon) M€/year for the intangible costs related to all-cause non-accidental mortality and 27 and 105 M€ for the tangible and intangible costs induced by lung cancer. A PM 2.5 exposure reduction down to the WHO air quality guideline (10 μg/m 3 ) would reduce anthropogenic PM 2.5 -attributable mortality by half while decreases by 2.9 μg/m 3 (Grenoble) and 3.3 μg/m 3 (Lyon) were required to reduce it by a third. Scenarios focusing only on the most exposed areas had little overall impact. Scenarios seeking to reach a homogeneous exposure in the whole study area were the most efficient in alleviating social inequalities in exposure., Conclusions: Reduction scenarios targeting only air pollution hotspots had little expected impact on population health. We provided estimates of the PM 2.5 change required to reduce PM 2.5 -attributable mortality by one third or more. Our approach can help targeting air pollution reduction scenarios expected to entail significant benefits, and it could easily be transposed to other urban areas., (Copyright © 2019. Published by Elsevier Ltd.)