Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc

Background

Humans are exposed to low-dose bisphenol A (BPA) through plastic consumer products and dental sealants containing BPA. Although a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies.

Objective

The objective of this study was to investigate the effect and the mechanism of low-dose BPA in mammary gland cells.

Methods

We evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA’s effects.

Results

Low-dose BPA significantly promoted DNA damage, up-regulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells.

Conclusions

Low-dose BPA exerted c-Myc–dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.

Citation

Pfeifer D, Chung YM, Hu MC. 2015. Effects of low-dose bisphenol A on DNA damage and proliferation of breast cells: the role of c-Myc. Environ Health Perspect 123:1271–1279; http://dx.doi.org/10.1289/ehp.1409199     

Children’s Health in Latin America: The Influence of Environmental Exposures

Background

Chronic diseases are increasing among children in Latin America.

Objective and Methods

To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data.

Results

Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children’s health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces.

Conclusions

To control environmental threats to children’s health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards—indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children’s environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders.

Citation

Laborde A, Tomasina F, Bianchi F, Bruné MN, Buka I, Comba P, Corra L, Cori L, Duffert CM, Harari R, Iavarone I, McDiarmid MA, Gray KA, Sly PD, Soares A, Suk WA, Landrigan PJ. 2015. Children’s health in Latin America: the influence of environmental exposures. Environ Health Perspect 123:201–209; http://dx.doi.org/10.1289/ehp.1408292     

Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in Pregnant Women: A Repeated Measures Analysis

Background

Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action.

Objectives

In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy.

Methods

Women were participants in a nested case–control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability.

Results

Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites.

Conclusions

Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates.

Citation

Ferguson KK, McElrath TF, Chen YH, Mukherjee B, Meeker JD. 2015. Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: a repeated measures analysis. Environ Health Perspect 123:210–216; http://dx.doi.org/10.1289/ehp.1307996     

Src-Mediated EGF Receptor Activation Regulates Ozone-Induced Interleukin 8 Expression in Human Bronchial Epithelial Cells

Background:

Human exposure to ozone (O₃) results in pulmonary function decrements and airway inflammation. The mechanisms underlying these adverse effects remain unclear. Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of lung inflammation.

Objective

We examined the role of EGFR activation in O₃-induced expression of the chemokine interleukin 8 (IL-8) in human bronchial epithelial cells (HBEC).

Methods

We detected phosphorylated EGFR using immunoblotting. EGFR dimerization was examined through cross-linking reaction and immunoblotting, and levels of IL-8 protein were measured using ELISA.

Results

Exposure to O₃ (0.25–1.0 ppm) induced rapid and marked increase in EGFR phosphorylation at the autophosphorylation site Y1068 and the transphosphorylation site Y845, implicating the involvement of Src kinase. Further investigation showed that O₃ stimulation induced phosphorylation of Src at Y416, indicative of Src activation. Pharmacological inhibition of Src kinase activity abrogated O₃-induced EGFR phosphorylation at tyrosines 1068 and 845. Moreover, pretreatment of BEAS-2B cells with inhibitor of either EGFR or Src kinase activities significantly blocked O₃-induced IL-8 expression.

Conclusion

Conclusion: O₃ exposure increased IL-8 expression through Src-mediated EGFR transactivation in HBEC.

Citation>

Wu W, Wages PA, Devlin RB, Diaz-Sanchez D, Peden DB, Samet JM. 2015. Src-mediated EGF receptor activation regulates ozone-induced interleukin 8 expression in human bronchial epithelial cells. Environ Health Perspect 123:231–236; http://dx.doi.org/10.1289/ehp.1307379     

Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

Background

Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown.

Objectives

In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles.

Methods

We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm.

Results

We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue.

Conclusions

Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers.

Citation

Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human placental perfusion model. Environ Health Perspect 123:1280–1286; http://dx.doi.org/10.1289/ehp.1409271     

Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice

Background

Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities.

Objectives

The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet–induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies.

Methods

Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water.

Results

HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects.

Conclusions

Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease.

Citation

Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA. 2015. Effects of combined exposure to lead and high-fat diet on bone quality in juvenile male mice. Environ Health Perspect 123:935–943; http://dx.doi.org/10.1289/ehp.1408581     

Antibiotics,Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter

Background:

Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized.

Objectives:

The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards.

Methods:

PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing.

Results:

Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 μg/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind.

Conclusions:

Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs.

Citation:

McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic resistance genes: aerial transport from cattle feed yards via particulate matter. Environ Health Perspect 123:337–343; http://dx.doi.org/10.1289/ehp.1408555     

Reducing Periconceptional Methylmercury Exposure: Cost–Utility Analysis for a Proposed Screening Program for Women Planning a Pregnancy in Ontario,Canada

Background

The assessment of neurodevelopmental effects in children associated with prenatal methylmercury exposure, from contaminated fish and seafood in the maternal diet, has recently been strengthened by adjustment for the negative confounding resulting from co-exposure to beneficial polyunsaturated fatty acids (PUFAs).

Objectives

We aimed to determine the cost-effectiveness of a periconceptional screening program of blood mercury concentration for women planning to become pregnant in Ontario, Canada. Fish intake recommendations would be provided for those found to have blood mercury levels above the intervention threshold.

Methods

Analysis was conducted using a combined decision tree/Markov model to compare the proposed screening intervention with standard care from a societal perspective over a lifetime horizon. We used the national blood mercury distributions of women 20–49 years of age reported in the Canadian Health Measures Survey from 2009 through 2011 to determine the cognitive deficits associated with prenatal methylmercury exposure for successful planned pregnancies. Outcomes modeled included the loss in quality of life and the remedial education costs. Value of information analysis was conducted to assess the underlying uncertainty around the model results and to identify which parameters contribute most to this uncertainty.

Results

The incremental cost per quality-adjusted life year (QALY) gained for the proposed screening intervention was estimated to be Can$18,051, and the expected value for a willingness to pay of Can$50,000/QALY to be Can$0.61.

Conclusions

Our findings suggest that the proposed periconceptional blood mercury screening program for women planning a pregnancy would be highly cost-effective from a societal perspective. The results of a value of information analysis confirm the robustness of the study’s conclusions.

Citation

Gaskin J, Rennie C, Coyle D. 2015. Reducing periconceptional methylmercury exposure: cost–utility analysis for a proposed screening program for women planning a pregnancy in Ontario, Canada. Environ Health Perspect 123:1337–1344; http://dx.doi.org/10.1289/ehp.1409034     

Predicting Hospitalization for Heat-Related Illness at the Census-Tract Level: Accuracy of a Generic Heat Vulnerability Index in Phoenix,Arizona (USA)

Background

Vulnerability mapping based on vulnerability indices is a pragmatic approach for highlighting the areas in a city where people are at the greatest risk of harm from heat, but the manner in which vulnerability is conceptualized influences the results.

Objectives

We tested a generic national heat-vulnerability index, based on a 10-variable indicator framework, using data on heat-related hospitalizations in Phoenix, Arizona. We also identified potential local risk factors not included in the generic indicators.

Methods

To evaluate the accuracy of the generic index in a city-specific context, we used factor scores, derived from a factor analysis using census tract–level characteristics, as independent variables, and heat hospitalizations (with census tracts categorized as zero-, moderate-, or high-incidence) as dependent variables in a multinomial logistic regression model. We also compared the geographical differences between a vulnerability map derived from the generic index and one derived from actual heat-related hospitalizations at the census-tract scale.

Results

We found that the national-indicator framework correctly classified just over half (54%) of census tracts in Phoenix. Compared with all census tracts, high-vulnerability tracts that were misclassified by the index as zero-vulnerability tracts had higher average income and higher proportions of residents with a duration of residency < 5 years.

Conclusion

The generic indicators of vulnerability are useful, but they are sensitive to scale, measurement, and context. Decision makers need to consider the characteristics of their cities to determine how closely vulnerability maps based on generic indicators reflect actual risk of harm.

Citation

Chuang WC, Gober P. 2015. Predicting hospitalization for heat-related illness at the census-tract level: accuracy of a generic heat vulnerability index in Phoenix, Arizona (USA). Environ Health Perspect 123:606–612; http://dx.doi.org/10.1289/ehp.1307868     

A Case-Only Study of Vulnerability to Heat Wave–Related Mortality in New York City (2000–2011)

Background

As a result of climate change, the frequency of extreme temperature events is expected to increase, and such events are associated with increased morbidity and mortality. Vulnerability patterns, and corresponding adaptation strategies, are most usefully conceptualized at a local level.

Methods

We used a case-only analysis to examine subject and neighborhood characteristics that modified the association between heat waves and mortality. All deaths of New York City residents from 2000 through 2011 were included in this analysis. Meteorological data were obtained from the National Climatic Data Center. Modifying characteristics were obtained from the death record and geographic data sets.

Results

A total of 234,042 adult deaths occurred during the warm season of our study period. Compared with other warm-season days, deaths during heat waves were more likely to occur in black (non-Hispanic) individuals than other race/ethnicities [odds ratio (OR) = 1.08; 95% CI: 1.03, 1.12], more likely to occur at home than in institutions and hospital settings (OR = 1.11; 95% CI: 1.06, 1.16), and more likely among those living in census tracts that received greater public assistance (OR = 1.05; 95% CI: 1.01, 1.09). Finally, deaths during heat waves were more likely among residents in areas of the city with higher relative daytime summer surface temperature and less likely among residents living in areas with more green space.

Conclusion

Mortality during heat waves varies widely within a city. Understanding which individuals and neighborhoods are most vulnerable can help guide local preparedness efforts.

Citation

Madrigano J, Ito K, Johnson S, Kinney PL, Matte T. 2015. A case-only study of vulnerability to heat wave–related mortality in New York City (2000–2011). Environ Health Perspect 123:672–678; http://dx.doi.org/10.1289/ehp.1408178     

A Case–Control Study of Prenatal Thallium Exposure and Low Birth Weight in China

Background

Thallium (Tl) is a highly toxic heavy metal widely present in the environment. Case reports have suggested that maternal exposure to high levels of Tl during pregnancy is associated with low birth weight (LBW), but epidemiological data are limited.

Objectives

This study was designed to evaluate whether prenatal Tl exposure is associated with an increased risk of LBW.

Methods

This case–control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted in Hubei Province, China, in 2012–2014. Tl concentrations were measured in maternal urine collected at delivery, and associations with LBW were evaluated using conditional logistic regression.

Results

Higher maternal urinary Tl levels were significantly associated with increased risk of LBW [crude odds ratio (OR) = 1.52; 95% CI: 1.00, 2.30 for the highest vs. lowest tertile], and the association was similarly elevated after adjustment for potential confounders (adjusted OR = 1.90; 95% CI: 1.01, 3.58 for the highest vs. lowest tertile). Stratified analyses showed slightly higher risk estimates for LBW associated with higher Tl levels for mothers < 28 years old and for mothers with lower household income; however, there was no statistical evidence of heterogeneity in risk according to maternal age (p for heterogeneity = 0.18) or household income (p for heterogeneity = 0.28).

Conclusion

To our knowledge, ours is the first case–control study to investigate the association between prenatal Tl exposure and LBW. The results suggest that prenatal exposure to high levels of Tl may be associated with an increased risk of LBW.

Citation

Xia W, Du X, Zheng T, Zhang B, Li Y, Bassig BA, Zhou A, Wang Y, Xiong C, Li Z, Yao Y, Hu J, Zhou Y, Liu J, Xue W, Ma Y, Pan X, Peng Y, Xu S. 2016. A case–control study of prenatal thallium exposure and low birth weight in China. Environ Health Perspect 124:164–169; http://dx.doi.org/10.1289/ehp.1409202     

Associations of Plasma Concentrations of Dichlorodiphenyldichloroethylene and Polychlorinated Biphenyls with Prostate Cancer: A Case–Control Study in Guadeloupe (French West Indies)

Background:

Long-term exposure to persistent pollutants with hormonal properties (endocrine-disrupting chemicals; EDCs) may contribute to the risk of prostate cancer (PCa). However, epidemiological evidence remains limited.

Objectives:

We investigated the relationship between PCa and plasma concentrations of universally widespread pollutants, in particular p,p´-dichlorodiphenyl dichloroethene (DDE) and the non-dioxin-like polychlorinated biphenyl congener 153 (PCB-153).

Methods:

We evaluated 576 men with newly diagnosed PCa (before treatment) and 655 controls in Guadeloupe (French West Indies). Exposure was analyzed according to case–control status. Associations were assessed by unconditional logistic regression analysis, controlling for confounding factors. Missing data were handled by multiple imputation.

Results:

We estimated a significant positive association between DDE and PCa [adjusted odds ratio (OR) = 1.53; 95% CI: 1.02, 2.30 for the highest vs. lowest quintile of exposure; p_trend = 0.01]. PCB-153 was inversely associated with PCa (OR = 0.30; 95% CI: 0.19, 0.47 for the highest vs. lowest quintile of exposure values; p_trend < 0.001). Also, PCB-153 was more strongly associated with low-grade than with high-grade PCa.

Conclusions:

Associations of PCa with DDE and PCB-153 were in opposite directions. This may reflect differences in the mechanisms of action of these EDCs; and although our findings need to be replicated in other populations, they are consistent with complex effects of EDCs on human health.

Citation:

Emeville E, Giusti A, Coumoul X, Thomé JP, Blanchet P, Multigner L. 2015. Associations of plasma concentrations of dichlorodiphenyldichloroethylene and polychlorinated biphenyls with prostate cancer: a case–control study in Guadeloupe (French West Indies). Environ Health Perspect 123:317–323; http://dx.doi.org/10.1289/ehp.1408407     

Association of Supply Type with Fecal Contamination of Source Water and Household Stored Drinking Water in Developing Countries: A Bivariate Meta-analysis

Background

Access to safe drinking water is essential for health. Monitoring access to drinking water focuses on water supply type at the source, but there is limited evidence on whether quality differences at the source persist in water stored in the household.

Objectives

We assessed the extent of fecal contamination at the source and in household stored water (HSW) and explored the relationship between contamination at each sampling point and water supply type.

Methods

We performed a bivariate random-effects meta-analysis of 45 studies, identified through a systematic review, that reported either the proportion of samples free of fecal indicator bacteria and/or individual sample bacteria counts for source and HSW, disaggregated by supply type.

Results

Water quality deteriorated substantially between source and stored water. The mean percentage of contaminated samples (noncompliance) at the source was 46% (95% CI: 33, 60%), whereas mean noncompliance in HSW was 75% (95% CI: 64, 84%). Water supply type was significantly associated with noncompliance at the source (p < 0.001) and in HSW (p = 0.03). Source water (OR = 0.2; 95% CI: 0.1, 0.5) and HSW (OR = 0.3; 95% CI: 0.2, 0.8) from piped supplies had significantly lower odds of contamination compared with non-piped water, potentially due to residual chlorine.

Conclusions

Piped water is less likely to be contaminated compared with other water supply types at both the source and in HSW. A focus on upgrading water services to piped supplies may help improve safety, including for those drinking stored water.

Citation

Shields KF, Bain RE, Cronk R, Wright JA, Bartram J. 2015. Association of supply type with fecal contamination of source water and household stored drinking water in developing countries: a bivariate meta-analysis. Environ Health Perspect 123:1222–1231; http://dx.doi.org/10.1289/ehp.1409002     

A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas

Background

Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities.

Objective

Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas.

Methods

We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal).

Results

Among 35 publications identified (published 1995–2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified.

Conclusions

Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies.

Citation

Deziel NC, Friesen MC, Hoppin JA, Hines CJ, Thomas K, Beane Freeman LE. 2015. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect 123:515–524; http://dx.doi.org/10.1289/ehp.1408273     

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background

Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy.

Objectives

We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population.

Methods

The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy.

Results

Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy.

Conclusions

In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk.

Citation

Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472     

First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women

Background

There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may affect disease propensity through epigenetic mechanisms.

Objective

The objective of this study was to determine whether prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and whether miRNA alterations are associated with birth outcomes.

Methods

Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR.

Results

For three miRNAs—miR-142-3p, miR15a-5p, and miR-185—we detected associations between Σphthalates or Σphenols on expression levels (p < 0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden.

Conclusions

Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans.

Citation

LaRocca J, Binder AM, McElrath TF, Michels KB. 2016. First-trimester urine concentrations of phthalate metabolites and phenols and placenta miRNA expression in a cohort of U.S. women. Environ Health Perspect 124:380–387; http://dx.doi.org/10.1289/ehp.1408409     

Occupational Exposure to Benzene and Non-Hodgkin Lymphoma in a Population-Based Cohort: The Shanghai Women’s Health Study

Background

The association between benzene exposure and non-Hodgkin lymphoma (NHL) has been the subject of debate as a result of inconsistent epidemiologic evidence. An International Agency for Research on Cancer (IARC) working group evaluated benzene in 2009 and noted evidence for a positive association between benzene exposure and NHL risk.

Objective

We evaluated the association between occupational benzene exposure and NHL among 73,087 women enrolled in the prospective population-based Shanghai Women’s Health Study.

Methods

Benzene exposure estimates were derived using a previously developed exposure assessment framework that combined ordinal job-exposure matrix intensity ratings with quantitative benzene exposure measurements from an inspection database of Shanghai factories collected between 1954 and 2000. Associations between benzene exposure metrics and NHL (n = 102 cases) were assessed using Cox proportional hazard models, with study follow-up occurring from December 1996 through December 2009.

Results

Women ever exposed to benzene had a significantly higher risk of NHL [hazard ratio (HR) = 1.87, 95% CI: 1.19, 2.96]. Compared with unexposed women, significant trends in NHL risk were observed for increasing years of benzene exposure (p_trend = 0.006) and increasing cumulative exposure levels (p_trend = 0.005), with the highest duration and cumulative exposure tertiles having a significantly higher association with NHL (HR = 2.07, 95% CI: 1.07, 4.01 and HR = 2.16, 95% CI: 1.17, 3.98, respectively).

Conclusions

Our findings, using a population-based prospective cohort of women with diverse occupational histories, provide additional evidence that occupational exposure to benzene is associated with NHL risk.

Citation

Bassig BA, Friesen MC, Vermeulen R, Shu XO, Purdue MP, Stewart PA, Xiang YB, Chow WH, Zheng T, Ji BT, Yang G, Linet MS, Hu W, Zhang H, Zheng W, Gao YT, Rothman N, Lan Q. 2015. Occupational exposure to benzene and non-Hodgkin lymphoma in a population-based cohort: the Shanghai Women’s Health Study. Environ Health Perspect 123:971–977; http://dx.doi.org/10.1289/ehp.1408307     

Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden: A Longitudinal Study

Background

Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia.

Objectives

We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden.

Methods

Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed using a land-use regression model with a spatial resolution of 50 m × 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) were used as markers for long-term exposure to air pollution.

Results

Out of 1,806 participants at baseline, 191 were diagnosed with Alzheimer’s disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the group with the highest exposure were more likely than those in the group with the lowest exposure to be diagnosed with dementia (Alzheimer’s disease or vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the highest vs. the lowest quartile). The estimates were similar for Alzheimer’s disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A subanalysis that excluded a younger sample that had been retested after only 5 years of follow-up suggested stronger associations with exposure than were present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the lowest quartile).

Conclusions

If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer’s disease.

Citation

Oudin A, Forsberg B, Nordin Adolfsson A, Lind N, Modig L, Nordin M, Nordin S, Adolfsson R, Nilsson LG. 2016. Traffic-related air pollution and dementia incidence in northern Sweden: a longitudinal study. Environ Health Perspect 124:306–312; http://dx.doi.org/10.1289/ehp.1408322     

Exposure to Endocrine-Disrupting Chemicals during Pregnancy and Weight at 7 Years of Age: A Multi-pollutant Approach

Background

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce weight gain and obesity in children, but the obesogenic effects of mixtures have not been studied.

Objective

We evaluated the associations between pre- and perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years of age.

Methods

In pregnant women enrolled in a Spanish birth cohort study between 2004 and 2006, we measured the concentrations of 10 phthalate metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470 children at 7 years, body mass index (BMI) z-scores were calculated, and overweight was defined as BMI > 85th percentile. We estimated associations with EDCs in single-pollutant models and applied principal-component analysis (PCA) on the 27 pollutant concentrations.

Results

In single-pollutant models, HCB (hexachlorobenzene), βHCH (β-hexachlorocyclohexane), and polychlorinated biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z-scores; and HCB, βHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene) with overweight risk. PCA generated four factors that accounted for 43.4% of the total variance. The organochlorine factor was positively associated with BMI z-scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19, 5.63), and these associations were robust to adjustment for other EDCs. Exposure in the second tertile of the phthalate factor was inversely associated with overweight.

Conclusions

Prenatal exposure to organochlorines was positively associated with overweight at age 7 years in our study population. Other EDCs exposures did not confound this association.

Citation

Agay-Shay K, Martinez D, Valvi D, Garcia-Esteban R, Basagaña X, Robinson O, Casas M, Sunyer J, Vrijheid M. 2015. Exposure to endocrine-disrupting chemicals during pregnancy and weight at 7 years of age: a multi-pollutant approach. Environ Health Perspect 123:1030–1037; http://dx.doi.org/10.1289/ehp.1409049     

A Case-Cohort Study of Cadmium Body Burden and Gestational Diabetes Mellitus in American Women

Background

Environmental cadmium (Cd) exposure is associated with type 2 diabetes. However, the association of Cd and gestational diabetes mellitus (GDM) is unknown.

Objectives

We examined the association between body burden of Cd and GDM risk.

Methods

We used 140 GDM cases and 481 randomly selected noncase subcohort members from the Omega Study to conduct a case-cohort study. Creatinine (Cr)–corrected Cd in early pregnancy urine (U-Cd) was measured by inductively coupled plasma mass spectrometry. Tertiles (< 0.29; 0.29–0.42; ≥ 0.43 μg/g Cr) were defined using the subcohort’s U-Cd distribution. GDM was diagnosed using the 2004 American Diabetes Association guidelines. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.

Results

GDM cases had higher geometric mean U-Cd (0.39 μg/g Cr; 95% CI: 0.37, 0.41) than noncases (0.31 μg/g Cr; 95% CI: 0.29, 0.33). Odds ratios for GDM increased with increasing U-Cd tertile (OR = 1.64; 95% CI: 0.88, 3.05 for middle vs. low tertile; OR = 2.07; 95% CI: 1.15, 3.73 for high vs. low tertile; p-trend = 0.015). Overweight/obesity (body mass index ≥ 25 kg/m²) did not modify the association between U-Cd and GDM (p = 0.26).

Conclusions

Our findings suggest that body burden of Cd increases risk of GDM in a dose-dependent manner. Improved understanding of environmental factors influencing GDM may facilitate early identification of women at high risk of GDM.

Citation

Romano ME, Enquobahrie DA, Simpson CD, Checkoway H, Williams MA. 2015. A case-cohort study of cadmium body burden and gestational diabetes mellitus in American women. Environ Health Perspect 123:993–998; http://dx.doi.org/10.1289/ehp.1408282