Cardiovascular health and particulate vehicular emissions: a critical evaluation of the evidence

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM2.5 standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions

Metabolomics as a powerful tool to decipher the biological effects of environmental contaminants in humans

International audienceHumans are exposed daily to a variety of environmental contaminants. For many of these, the associated health effects remain largely unexplored. There is growing evidence that untargeted metabolomics-based techniques could be used to identify simultaneously biomarkers of effect (i.e. disruption of endogenous metabolite profiles) and exposure (i.e. xenobiotic mixtures) in biological samples. This approach is expending quickly and has been used in several studies over the last 5 years to study biological effects of many environmental contaminants in humans. Hence, this review attempts to determine whether metabolomics might constitute a relevant tool to discover new early biomarkers of effects related to chemical exposure in humans. Published results suggest that common metabolic pathways are affected by specific groups of chemicals such as PAHs, metals, organochlorine compounds, pesticides, and endocrine disrupting plasticizers. Remarkably, disruption of cellular signaling pathways associated with oxidative stress may be primary drivers for further effects for all studied chemicals. In the future, the introduction of more sensitive analytical techniques to perform untargeted profiling of biological samples seems to be a good option to improve the coverage of the xeno-metabolome and to provide more relevant information on both chemical exposure and metabolic signatures of environmental contaminants. Some current challenges are finally discussed. © 2018 Elsevier B.V

Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels

International audienceStudy question - Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? Summary answer - Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. What is known already - Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. Study design, size, duration - A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. Participants/materials, setting, methods - Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. Main results and the role of chance - High PCB levels were associated with an increase of SHBG (P-trend < 0.01) and AMH (P-trend < 0.05) and a decrease of fT (P-trend < 0.05) and AI (P-trend < 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P < 0.05) and E2 (P < 0.01) and a decrease of fT (P < 0.05) and AI (P < 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. Limitations, reasons for caution - The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. Wider implications of the findings - Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. Study funding/competing interests - The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare

Bioaccessibility and bioavailability of environmental semi-volatile organic compounds via inhalation. A review of methods and models

International audienceSemi-volatile organic compounds (SVOCs) present in indoor environments are known to cause adverse health effects through multiple routes of exposure. To assess the aggregate exposure, the bioaccessibility and bioavailability of SVOCs need to be determined.In this review, we discussed measurements of the bioaccessibility and bioavailability of SVOCs after inhalation. Published literature related to this issue is available for 2,3,7,8-tetrachlorodibenzo-p-dioxin and a few polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and phenanthrene. Then, we reviewed common modeling approaches for the characterization of the gas- and particle-phase partitioning of SVOCs during inhalation. The models are based on mass transfer mechanisms as well as the structure of the respiratory system, using common computational techniques, such as computational fluid dynamics. However, the existing models are restricted to special conditions and cannot predict SVOC bioaccessibility and bioavailability in the whole respiratory system.The present review notes two main challenges for the estimation of SVOC bioaccessibility and bioavailability via inhalation in humans. First, in vitro and in vivo methods need to be developed and validated for a wide range of SVOCs. The in vitro methods should be validated with in vivo tests to evaluate human exposures to SVOCs in airborne particles. Second, modeling approaches for SVOCs need to consider the whole respiratory system. Alterations of the respiratory cycle period and human biological variability may be considered in future studies