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1.  Systematic Review and Evidence Integration for Literature-Based Environmental Health Science Assessments 
Environmental Health Perspectives  2014;122(7):711-718.
Background: Systematic-review methodologies provide objectivity and transparency to the process of collecting and synthesizing scientific evidence in reaching conclusions on specific research questions. There is increasing interest in applying these procedures to address environmental health questions.
Objectives: The goal was to develop a systematic-review framework to address environmental health questions by extending approaches developed for clinical medicine to handle the breadth of data relevant to environmental health sciences (e.g., human, animal, and mechanistic studies).
Methods: The Office of Health Assessment and Translation (OHAT) adapted guidance from authorities on systematic-review and sought advice during development of the OHAT Approach through consultation with technical experts in systematic review and human health assessments, as well as scientific advisory groups and the public. The method was refined by considering expert and public comments and through application to case studies.
Results and Discussion: Here we present a seven-step framework for systematic review and evidence integration for reaching hazard identification conclusions: 1) problem formulation and protocol development, 2) search for and select studies for inclusion, 3) extract data from studies, 4) assess the quality or risk of bias of individual studies, 5) rate the confidence in the body of evidence, 6) translate the confidence ratings into levels of evidence, and 7) integrate the information from different evidence streams (human, animal, and “other relevant data” including mechanistic or in vitro studies) to develop hazard identification conclusions.
Conclusion: The principles of systematic review can be successfully applied to environmental health questions to provide greater objectivity and transparency to the process of developing conclusions.
Citation: Rooney AA, Boyles AL, Wolfe MS, Bucher JR, Thayer KA. 2014. Systematic review and evidence integration for literature-based environmental health science assessments. Environ Health Perspect 122:711–718; http://dx.doi.org/10.1289/ehp.1307972
doi:10.1289/ehp.1307972
PMCID: PMC4080517  PMID: 24755067
2.  Mercury Exposure and Health Impacts among Individuals in the Artisanal and Small-Scale Gold Mining Community: A Comprehensive Review 
Environmental Health Perspectives  2014;122(7):667-672.
Background: Mercury (Hg) is used in gold mining to extract gold from ore by forming “amalgam”—a mixture composed of approximately equal parts mercury and gold. Approximately 15 million people, including approximately 3 million women and children, participate in artisanal small-scale gold mining (ASGM) in developing countries. Thirty-seven percent of global air emissions of Hg are produced by ASGM. The recently adopted Minamata Convention calls for nations to gather health data, train health-care workers, and raise awareness in regard to ASGM activity.
Objective: The purpose of our review was to evaluate the current literature regarding the health effects of Hg among those working and/or living in or near ASGM communities.
Methods: We searched PubMed, ScienceDirect, and Google Scholar for studies relating to health effects and biomarkers of Hg exposure in ASGM communities. Articles published from 1990 through December 2012 were evaluated for relevance.
Discussion: Studies reporting health assessments, kidney dysfunction, neurological disorders and symptoms, and immunotoxicity/autoimmune dysfunction in individuals living in or near an ASGM community were identified. More than 60 studies that measured biomarkers of Hg exposure in individuals living in or near ASGM communities were also identified. These studies, conducted in 19 different countries in South America, Asia, and Africa, demonstrated that hair and urine concentrations are well above World Health Organization health guidance values in ASGM communities.
Conclusions: ASGM workers and their families are exposed to Hg vapor, and workers, workers’ families, and residents of nearby and downstream communities are consuming fish heavily contaminated with methylmercury.
Citation: Gibb H, O’Leary KG. 2014. Mercury exposure and health impacts among individuals in the artisanal and small-scale gold mining community: a comprehensive review. Environ Health Perspect 122:667–672; http://dx.doi.org/10.1289/ehp.1307864
doi:10.1289/ehp.1307864
PMCID: PMC4080518  PMID: 24682486
3.  CpG Sites Associated with Cigarette Smoking: Analysis of Epigenome-Wide Data from the Sister Study 
Environmental Health Perspectives  2014;122(7):673-678.
Background: Smoking increases the risk of many diseases, and it is also linked to blood DNA methylation changes that may be important in disease etiology.
Objectives: We sought to identify novel CpG sites associated with cigarette smoking.
Methods: We used two epigenome-wide data sets from the Sister Study to identify and confirm CpG sites associated with smoking. One included 908 women with methylation measurements at 27,578 CpG sites using the HumanMethylation27 BeadChip; the other included 200 women with methylation measurements for 473,844 CpG sites using the HumanMethylation450 BeadChip. Significant CpGs from the second data set that were not included in the 27K assay were validated by pyrosequencing in a subset of 476 samples from the first data set.
Results: Our study successfully confirmed smoking associations for 9 previously established CpGs and identified 2 potentially novel CpGs: cg26764244 in GNG12 (p = 9.0 × 10–10) and cg22335340 in PTPN6 (p = 2.9 × 10–05). We also found strong evidence of an association between smoking status and cg02657160 in CPOX (p = 7.3 × 10–7), which has not been previously reported. All 12 CpGs were undermethylated in current smokers and showed an increasing percentage of methylation in former and never-smokers.
Conclusions: We identified 2 potentially novel smoking related CpG sites, and provided independent replication of 10 previously reported CpGs sites related to smoking, one of which is situated in the gene CPOX. The corresponding enzyme is involved in heme biosynthesis, and smoking is known to increase heme production. Our study extends the evidence base for smoking-related changes in DNA methylation.
Citation: Harlid S, Xu Z, Panduri V, Sandler DP, Taylor JA. 2014. CpG sites associated with cigarette smoking: analysis of epigenome-wide data from the Sister Study. Environ Health Perspect 122:673–678; http://dx.doi.org/10.1289/ehp.1307480
doi:10.1289/ehp.1307480
PMCID: PMC4080519  PMID: 24704585
5.  Associations of Short-Term Particle and Noise Exposures with Markers of Cardiovascular and Respiratory Health among Highway Maintenance Workers 
Environmental Health Perspectives  2014;122(7):726-732.
Background: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, both of which have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies.
Objectives: We aimed to investigate short-term health effects related to particle and noise exposure.
Methods: We monitored 18 maintenance workers, during as many as five 24-hr periods from a total of 50 observation days. We measured their exposure to fine particulate matter (diameter ≤ 2.5 μm; PM2.5), ultrafine particles, and noise, and the cardiopulmonary health end points: blood pressure, proinflammatory and prothrombotic markers in the blood, lung function, and fractional exhaled nitric oxide (FeNO) measured approximately 15 hr after work. Heart rate variability was assessed during a sleep period approximately 10 hr after work.
Results: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and was negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased high-frequency and low-frequency power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and nonsignificantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO.
Conclusions: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.
Citation: Meier R, Cascio WE, Ghio AJ, Wild P, Danuser B, Riediker M. 2014. Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers. Environ Health Perspect 122:726–732; http://dx.doi.org/10.1289/ehp.1307100
doi:10.1289/ehp.1307100
PMCID: PMC4080522  PMID: 24647077
6.  The Influence of Declining Air Lead Levels on Blood Lead–Air Lead Slope Factors in Children 
Environmental Health Perspectives  2014;122(7):754-760.
Background: It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB–PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards.
Objectives: The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature.
Methods: We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 9908 (1999–2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA.
Results: Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0–11 years of age.
Conclusion: These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.
Citation: Richmond-Bryant J, Meng Q, Davis A, Cohen J, Lu SE, Svendsgaard D, Brown JS, Tuttle L, Hubbard H, Rice J, Kirrane E, Vinikoor-Imler LC, Kotchmar D, Hines EP, Ross M. 2014. The Influence of declining air lead levels on blood lead–air lead slope factors in children. Environ Health Perspect 122:754–760; http://dx.doi.org/10.1289/ehp.1307072
doi:10.1289/ehp.1307072
PMCID: PMC4080523  PMID: 24667492
7.  Water Distribution System Deficiencies and Gastrointestinal Illness: A Systematic Review and Meta-Analysis 
Environmental Health Perspectives  2014;122(7):651-660.
Background: Water distribution systems are vulnerable to performance deficiencies that can cause (re)contamination of treated water and plausibly lead to increased risk of gastrointestinal illness (GII) in consumers.
Objectives: It is well established that large system disruptions in piped water networks can cause GII outbreaks. We hypothesized that routine network problems can also contribute to background levels of waterborne illness and conducted a systematic review and meta-analysis to assess the impact of distribution system deficiencies on endemic GII.
Methods: We reviewed published studies that compared direct tap water consumption to consumption of tap water re-treated at the point of use (POU) and studies of specific system deficiencies such as breach of physical or hydraulic pipe integrity and lack of disinfectant residual.
Results: In settings with network malfunction, consumers of tap water versus POU-treated water had increased GII [incidence density ratio (IDR) = 1.34; 95% CI: 1.00, 1.79]. The subset of nonblinded studies showed a significant association between GII and tap water versus POU-treated water consumption (IDR = 1.52; 95% CI: 1.05, 2.20), but there was no association based on studies that blinded participants to their POU water treatment status (IDR = 0.98; 95% CI: 0.90, 1.08). Among studies focusing on specific network deficiencies, GII was associated with temporary water outages (relative risk = 3.26; 95% CI: 1.48, 7.19) as well as chronic outages in intermittently operated distribution systems (odds ratio = 1.61; 95% CI: 1.26, 2.07).
Conclusions: Tap water consumption is associated with GII in malfunctioning distribution networks. System deficiencies such as water outages also are associated with increased GII, suggesting a potential health risk for consumers served by piped water networks.
Citation: Ercumen A, Gruber JS, Colford JM Jr. 2014. Water distribution system deficiencies and gastrointestinal illness: a systematic review and meta-analysis. Environ Health Perspect 122:651–660; http://dx.doi.org/10.1289/ehp.1306912
doi:10.1289/ehp.1306912
PMCID: PMC4080524  PMID: 24659576
8.  Building a Solid Case: Cigarette Smoking and Epigenomic Alterations 
doi:10.1289/ehp.122-A194
PMCID: PMC4080525  PMID: 24984253
9.  Long-Term Aircraft Noise Exposure and Body Mass Index, Waist Circumference, and Type 2 Diabetes: A Prospective Study 
Environmental Health Perspectives  2014;122(7):687-694.
Background: Long-term aircraft noise exposure may increase the risk of cardiovascular disease, but no study has investigated chronic effects on the metabolic system.
Objectives: The aim of this study was to investigate effects of long-term aircraft noise exposure on body mass index (BMI), waist circumference, and type 2 diabetes. Furthermore, we explored the modifying effects of sleep disturbance.
Methods: This prospective cohort study of residents of Stockholm County, Sweden, followed 5,156 participants with normal baseline oral glucose tolerance tests (OGTT) for up to 10 years. Exposure to aircraft noise was estimated based on residential history. Information on outcomes and confounders was obtained from baseline and follow-up surveys and examinations, and participants who developed prediabetes or type 2 diabetes were identified by self-reported physician diagnosis or OGTT at follow-up. Adjusted associations were assessed by linear, logistic, and random-effects models.
Results: The mean (± SD) increases in BMI and waist circumference during follow-up were 1.09 ± 1.97 kg/m2 and 4.39 ± 6.39 cm, respectively. The cumulative incidence of prediabetes and type 2 diabetes was 8% and 3%, respectively. Based on an ordinal noise variable, a 5-dB(A) increase in aircraft noise was associated with a greater increase in waist circumference of 1.51 cm (95% CI: 1.13, 1.89), fully adjusted. This association appeared particularly strong among those who did not change their home address during the study period, which may be a result of lower exposure misclassification. However, no clear associations were found for BMI or type 2 diabetes. Furthermore, sleep disturbances did not appear to modify the associations with aircraft noise.
Conclusions: Long-term aircraft noise exposure may be linked to metabolic outcomes, in particular increased waist circumference.
Citation: Eriksson C, Hilding A, Pyko A, Bluhm G, Pershagen G, Östenson CG. 2014. Long-term aircraft noise exposure and body mass index, waist circumference, and type 2 diabetes: a prospective study. Environ Health Perspect 122:687–694; http://dx.doi.org/10.1289/ehp.1307115
doi:10.1289/ehp.1307115
PMCID: PMC4080526  PMID: 24800763
14.  Science, Policy, and the Transparency of Values 
Environmental Health Perspectives  2014;122(7):647-650.
Background: Opposing groups of scientists have recently engaged in a heated dispute over a preliminary European Commission (EC) report on its regulatory policy for endocrine-disrupting chemicals. In addition to the scientific issues at stake, a central question has been how scientists can maintain their objectivity when informing policy makers.
Objectives: Drawing from current ethical, conceptual, and empirical studies of objectivity and conflicts of interest in scientific research, we propose guiding principles for communicating scientific findings in a manner that promotes objectivity, public trust, and policy relevance.
Discussion: Both conceptual and empirical studies of scientific reasoning have shown that it is unrealistic to prevent policy-relevant scientific research from being influenced by value judgments. Conceptually, the current dispute over the EC report illustrates how scientists are forced to make value judgments about appropriate standards of evidence when informing public policy. Empirical studies provide further evidence that scientists are unavoidably influenced by a variety of potentially subconscious financial, social, political, and personal interests and values.
Conclusions: When scientific evidence is inconclusive and major regulatory decisions are at stake, it is unrealistic to think that values can be excluded from scientific reasoning. Thus, efforts to suppress or hide interests or values may actually damage scientific objectivity and public trust, whereas a willingness to bring implicit interests and values into the open may be the best path to promoting good science and policy.
Citation: Elliott KC, Resnik DB. 2014. Science, policy, and the transparency of values. Environ Health Perspect 122:647–650; http://dx.doi.org/10.1289/ehp.1408107
doi:10.1289/ehp.1408107
PMCID: PMC4080531  PMID: 24667564
15.  Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia 
Environmental Health Perspectives  2014;122(7):747-753.
Background: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups.
Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease.
Methods: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population.
Results: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease.
Conclusions: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions.
Citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundbäck M, Cassee FR, Donaldson K, Sandström T, Blomberg A, Newby DE, Mills NL. 2014. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect 122:747–753; http://dx.doi.org/10.1289/ehp.1307337
doi:10.1289/ehp.1307337
PMCID: PMC4080532  PMID: 24667535
16.  Drinking-Water Disinfection By-products and Semen Quality: A Cross-Sectional Study in China 
Environmental Health Perspectives  2014;122(7):741-746.
Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent.
Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population.
Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples.
Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) μg/L (interquartile range, 6.01–10.96 μg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility.
Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.
Citation: Zeng Q, Wang YX, Xie SH, Xu L, Chen YZ, Li M, Yue J, Li YF, Liu AL, Lu WQ. 2014. Drinking-water disinfection by-products and semen quality: a cross-sectional study in China. Environ Health Perspect 122:741–746; http://dx.doi.org/10.1289/ehp.1307067
doi:10.1289/ehp.1307067
PMCID: PMC4080533  PMID: 24695319
17.  Rethinking Sterile: The Hospital Microbiome 
Environmental Health Perspectives  2014;122(7):A182-A187.
doi:10.1289/ehp.122-A182
PMCID: PMC4080534  PMID: 24983914
18.  Predictors of Blood Trihalomethane Concentrations in NHANES 1999–2006 
Environmental Health Perspectives  2014;122(7):695-702.
Background: Trihalomethanes (THMs) are water disinfection by-products that have been associated with bladder cancer and adverse birth outcomes. Four THMs (bromoform, chloroform, bromodichloromethane, dibromochloromethane) were measured in blood and tap water of U.S. adults in the National Health and Nutrition Examination Survey (NHANES) 1999–2006. THMs are metabolized to potentially toxic/mutagenic intermediates by cytochrome p450 (CYP) 2D6 and CYP2E1 enzymes.
Objectives: We conducted exploratory analyses of blood THMs, including factors affecting CYP2D6 and CYP2E1 activity.
Methods: We used weighted multivariable regressions to evaluate associations between blood THMs and water concentrations, survey year, and other factors potentially affecting THM exposure or metabolism (e.g., prescription medications, cruciferous vegetables, diabetes, fasting, pregnancy, swimming).
Results: From 1999 to 2006, geometric mean blood and water THM levels dropped in parallel, with decreases of 32%–76% in blood and 38%–52% in water, likely resulting, in part, from the lowering of the total THM drinking water standard in 2002–2004. The strongest predictors of blood THM levels were survey year and water concentration (n = 4,232 total THM; n = 4,080 bromoform; n = 4,582 chloroform; n = 4,374 bromodichloromethane; n = 4,464 dibromochloromethane). We detected statistically significant inverse associations with diabetes and eating cruciferous vegetables in all but the bromoform model. Medications did not consistently predict blood levels. Afternoon/evening blood samples had lower THM concentrations than morning samples. In a subsample (n = 230), air chloroform better predicted blood chloroform than water chloroform, suggesting showering/bathing was a more important source than drinking.
Conclusions: We identified several factors associated with blood THMs that may affect their metabolism. The potential health implications require further study.
Citation: Riederer AM, Dhingra R, Blount BC, Steenland K. 2014. Predictors of blood trihalomethane concentrations in NHANES 1999–2006. Environ Health Perspect 122:695–702; http://dx.doi.org/10.1289/ehp.1306499
doi:10.1289/ehp.1306499
PMCID: PMC4080535  PMID: 24647036
19.  Tetrachloroethylene Exposure and Bladder Cancer Risk: A Meta-Analysis of Dry-Cleaning-Worker Studies 
Environmental Health Perspectives  2014;122(7):661-666.
Background: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as “probably carcinogenic to humans” based on limited evidence of an increased risk of bladder cancer in dry cleaners.
Objectives: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry.
Methods: Random-effects meta-analyses were carried out separately for occupational exposure to tetrachloroethylene and employment as a dry cleaner. We qualitatively summarized exposure–response data because of the limited number of studies available.
Results: The meta-relative risk (mRR) among tetrachloroethylene-exposed workers was 1.08 (95% CI: 0.82, 1.42; three studies; 463 exposed cases). For employment as a dry cleaner, the overall mRR was 1.47 (95% CI: 1.16, 1.85; seven studies; 139 exposed cases), and for smoking-adjusted studies, the mRR was 1.50 (95% CI: 0.80, 2.84; 4 case–control studies).
Conclusions: Our meta-analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case–control studies, and some evidence for an exposure–response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because it is the primary solvent used and it is the only chemical commonly used by dry cleaners that is currently identified as a potential bladder carcinogen. Relatively crude approaches in exposure assessment in the studies of “tetrachloroethylene-exposed workers” may have attenuated the relative risks.
Citation: Vlaanderen J, Straif K, Ruder A, Blair A, Hansen J, Lynge E, Charbotel B, Loomis D, Kauppinen T, Kyyronen P, Pukkala E, Weiderpass E, Guha N. 2014. Tetrachloroethylene exposure and bladder cancer risk: a meta-analysis of dry-cleaning-worker studies. Environ Health Perspect 122:661–666; http://dx.doi.org/10.1289/ehp.1307055
doi:10.1289/ehp.1307055
PMCID: PMC4080536  PMID: 24659585
20.  Plasma microRNA Expression and Micronuclei Frequency in Workers Exposed to Polycyclic Aromatic Hydrocarbons 
Environmental Health Perspectives  2014;122(7):719-725.
Background: Ubiquitous polycyclic aromatic hydrocarbons (PAHs) have been shown to alter gene expression patterns and elevate micronuclei (MN) frequency, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are key gene regulators that may be influenced by PAH exposures and mediate their effects on MN frequency.
Objectives: We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency.
Methods: We performed a two-stage study in healthy male coke oven workers to identify miRNAs associated with PAH exposures quantified using urinary monohydroxy-PAHs and plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE–Alb) adducts. In the discovery stage, we used Solexa sequencing to test differences in miRNA expression profiles between pooled plasma samples from 20 exposed workers and 20 controls. We then validated associations with eight selected miRNAs in 365 workers. We further evaluated associations between the PAH-associated miRNAs and MN frequency.
Results: In the discovery stage, miRNA expression profiles differed between the exposed and control groups, with 68 miRNAs significantly down-regulated [fold change (FC) ≤ –5] and 3 miRNAs mildly up-regulated (+2 ≤ FC < +5) in the exposed group. In the validation analysis, urinary 4-hydroxyphenanthrene and/or plasma BPDE–Alb adducts were associated with lower miR-24-3p, miR-27a-3p, miR-142-5p, and miR-28-5p expression (p < 0.030). Urinary 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyphenanthrene, and the sum of monohydroxy-PAHs were associated with higher miR-150-5p expression (p < 0.030). These miRNAs were associated with higher MN frequency (p < 0.005), with stronger associations in drinkers (pinteraction < 0.015).
Conclusions: Associations of PAH exposures with miRNA expression, and of miRNA expression with MN frequency, suggest potential mechanisms of adverse effects of PAHs that are worthy of further investigation.
Citation: Deng Q, Huang S, Zhang X, Zhang W, Feng J, Wang T, Hu D, Guan L, Li J, Dai X, Deng H, Zhang X, Wu T. 2014. Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons. Environ Health Perspect 122:719–725; http://dx.doi.org/10.1289/ehp.1307080
doi:10.1289/ehp.1307080
PMCID: PMC4080537  PMID: 24633190
21.  Predictors and Variability of Repeat Measurements of Urinary Phenols and Parabens in a Cohort of Shanghai Women and Men 
Environmental Health Perspectives  2014;122(7):733-740.
Background: Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations.
Objectives: We sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults.
Methods: We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997–2006 from 50 participants of the Shanghai Women’s Health Study cohort and during 2002–2006 from 50 participants of the Shanghai Men’s Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs).
Results: Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54–0.60, SCC = 0.43–0.56), but lower for other analytes (ICC = 0.20–0.29). Reproducibility among women was low (ICC = 0.13–0.39), but increased when restricted to morning-only urine samples.
Conclusions: Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women.
Citation: Engel LS, Buckley JP, Yang G, Liao LM, Satagopan J, Calafat AM, Matthews CE, Cai Q, Ji BT, Cai H, Engel SM, Wolff MS, Rothman N, Zheng W, Xiang YB, Shu XO, Gao YT, Chow WH. 2014. Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men. Environ Health Perspect 122:733–740; http://dx.doi.org/10.1289/ehp.1306830
doi:10.1289/ehp.1306830
PMCID: PMC4080538  PMID: 24659570
22.  Research Wranglers: Initiatives to Improve Reproducibility of Study Findings 
Environmental Health Perspectives  2014;122(7):A188-A191.
doi:10.1289/ehp.122-A188
PMCID: PMC4080539  PMID: 24984077
23.  Association between Source-Specific Particulate Matter Air Pollution and hs-CRP: Local Traffic and Industrial Emissions 
Environmental Health Perspectives  2014;122(7):703-710.
Background: Long-term exposures to particulate matter air pollution (PM2.5 and PM10) and high traffic load have been associated with markers of systemic inflammation. Epidemiological investigations have focused primarily on total PM, which represents a mixture of pollutants originating from different sources.
Objective: We investigated associations between source-specific PM and high-sensitive C-reactive protein (hs-CRP), an independent predictor of cardiovascular disease.
Methods: We used data from the first (2000–2003) and second examination (2006–2008) of the Heinz Nixdorf Recall study, a prospective population-based German cohort of initially 4,814 participants (45–75 years of age). We estimated residential long-term exposure to local traffic- and industry-specific fine particulate matter (PM2.5) at participants’ residences using a chemistry transport model. We used a linear mixed model with a random participant intercept to estimate associations of source-specific PM and natural log-transformed hs-CRP, controlling for age, sex, education, body mass index, low- and high-density lipoprotein cholesterol, smoking variables, physical activity, season, humidity, and city (8,204 total observations).
Results: A 1-μg/m3 increase in total PM2.5 was associated with a 4.53% increase in hs-CRP concentration (95% CI: 2.76, 6.33%). hs-CRP was 17.89% (95% CI: 7.66, 29.09%) and 7.96% (95% CI: 3.45, 12.67%) higher in association with 1-μg/m3 increases in traffic- and industry-specific PM2.5, respectively. Results for PM10 were similar.
Conclusions: Long-term exposure to local traffic-specific PM (PM2.5, PM10) was more strongly associated with systemic inflammation than total PM. Associations of local industry-specific PM were slightly stronger but not significantly different from associations with total PM.
Citation: Hennig F, Fuks K, Moebus S, Weinmayr G, Memmesheimer M, Jakobs H, Bröcker-Preuss M, Führer-Sakel D, Möhlenkamp S, Erbel R, Jöckel KH, Hoffmann B, Heinz Nixdorf Recall Study Investigative Group. 2014. Association between source-specific particulate matter air pollution and hs-CRP: local traffic and industrial emissions. Environ Health Perspect 122:703–710; http://dx.doi.org/10.1289/ehp.1307081
doi:10.1289/ehp.1307081
PMCID: PMC4080540  PMID: 24755038
24.  Differences in BMI z-Scores between Offspring of Smoking and Nonsmoking Mothers: A Longitudinal Study of German Children from Birth through 14 Years of Age 
Environmental Health Perspectives  2014;122(7):761-767.
Background: Children of mothers who smoked during pregnancy have a lower birth weight but have a higher chance to become overweight during childhood.
Objectives: We followed children longitudinally to assess the age when higher body mass index (BMI) z-scores became evident in the children of mothers who smoked during pregnancy, and to evaluate the trajectory of changes until adolescence.
Methods: We pooled data from two German cohort studies that included repeated anthropometric measurements until 14 years of age and information on smoking during pregnancy and other risk factors for overweight. We used longitudinal quantile regression to estimate age- and sex-specific associations between maternal smoking and the 10th, 25th, 50th, 75th, and 90th quantiles of the BMI z-score distribution in study participants from birth through 14 years of age, adjusted for potential confounders. We used additive mixed models to estimate associations with mean BMI z-scores.
Results: Mean and median (50th quantile) BMI z-scores at birth were smaller in the children of mothers who smoked during pregnancy compared with children of nonsmoking mothers, but BMI z-scores were significantly associated with maternal smoking beginning at the age of 4–5 years, and differences increased over time. For example, the difference in the median BMI z-score between the daughters of smokers versus nonsmokers was 0.12 (95% CI: 0.01, 0.21) at 5 years, and 0.30 (95% CI: 0.08, 0.39) at 14 years of age. For lower BMI z-score quantiles, the association with smoking was more pronounced in girls, whereas in boys the association was more pronounced for higher BMI z-score quantiles.
Conclusions: A clear difference in BMI z-score (mean and median) between children of smoking and nonsmoking mothers emerged at 4–5 years of age. The shape and size of age-specific effect estimates for maternal smoking during pregnancy varied by age and sex across the BMI z-score distribution.
Citation: Riedel C, Fenske N, Müller MJ, Plachta-Danielzik S, Keil T, Grabenhenrich L, von Kries R. 2014. Differences in BMI z-scores between offspring of smoking and nonsmoking mothers: a longitudinal study of German children from birth through 14 years of age. Environ Health Perspect 122:761–767; http://dx.doi.org/10.1289/ehp.1307139
doi:10.1289/ehp.1307139
PMCID: PMC4080541  PMID: 24695368
25.  Science and Policy: Understanding the Role of Value Judgments 
doi:10.1289/ehp.122-A192
PMCID: PMC4080542  PMID: 24984147

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