Blood Pressure,Left Ventricular Geometry,and Systolic Function in Children Exposed to Inorganic Arsenic

Background:

Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure–related cardiovascular disease in children.

Objective:

In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children.

Methods:

A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation–cryotrapping–atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography.

Results:

U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: –7.14, –0.20) and 3.41% (95% CI: –6.44, –0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL.

Conclusion:

Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Citation:

Osorio-Yáñez C, Ayllon-Vergara JC, Arreola-Mendoza L, Aguilar-Madrid G, Hernández-Castellanos E, Sánchez-Peña LC, Del Razo LM. 2015. Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic. Environ Health Perspect 123:629–635; http://dx.doi.org/10.1289/ehp.1307327     

Effects of Arsenite Exposure during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Disease in Male Mice

Background

Chronic exposure to arsenicals at various life stages and across a range of exposures has been implicated in cardiometabolic and liver disease, but disease predisposition from developmental exposures remains unclear.

Objectives

In utero and post-weaning exposure to trivalent arsenic (As^III) was examined on the background of a Western-style diet to determine whether As^III exposure affects metabolic disease.

Methods

Male Swiss Webster mice were exposed to 100 ppb As^III in utero, after weaning, or both. Ad libitum access to a Western-style diet was provided after weaning, and the plasma metabolome, liver histopathology, liver enzyme activity, and gene expression were analyzed.

Results

Hepatic lipid composition and histopathology revealed that developmental As^III exposure exacerbated Western-style diet–induced fatty liver disease. Continuous As^III exposure increased cardiometabolic risk factors including increased body weight, insulin resistance, hyperglycemia, and plasma triglycerides. As^III exposure produced a decrease in the intermediates of glycolysis and the TCA cycle while increasing ketones. Hepatic isocitrate dehydrogenase activity was also decreased, which confirmed disruption of the TCA cycle. Developmental As^III exposure increased the expression of genes involved in fatty acid synthesis, lipogenesis, inflammation, and packaging of triglycerides, suggesting an increased acetyl coenzyme A (acetyl-CoA) load.

Conclusions

In utero and continuous early-life exposure to As^III disrupted normal metabolism and elevated the risk for fatty liver disease in mice maintained on a high-fat diet. Our findings suggest that individuals exposed to As^III during key developmental periods and who remain exposed to As^III on the background of a Western-style diet may be at increased risk for metabolic disease later in life.

Citation

Ditzel EJ, Nguyen T, Parker P, Camenisch TD. 2016. Effects of arsenite exposure during fetal development on energy metabolism and susceptibility to diet-induced fatty liver disease in male mice. Environ Health Perspect 124:201–209; http://dx.doi.org/10.1289/ehp.1409501     

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     

Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity

Background

Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers.

Objective

We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that influence benzene-induced genotoxicity.

Methods

We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). The study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis.

Results

We observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. This estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identified a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity.

Conclusions

The genetically diverse DO mice provided a reproducible response to benzene exposure. The DO mice display interindividual variation in toxicity response and, as such, may more accurately reflect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. The identification of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity.

Citation

French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. 2015. Diversity Outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environ Health Perspect 123:237–245; http://dx.doi.org/10.1289/ehp.1408202     

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     

Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

Background

Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear.

Objectives

We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood.

Methods

Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood.

Results

Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance.

Conclusion

Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice.

Citation

Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic parameters in female CD-1 mice. Environ Health Perspect 124:336–343; http://dx.doi.org/10.1289/ehp.1509703     

Confusion about Cadmium Risks: The Unrecognized Limitations of an Extrapolated Paradigm

Background

Cadmium (Cd) risk assessment presently relies on tubular proteinuria as a critical effect and urinary Cd (U-Cd) as an index of the Cd body burden. Based on this paradigm, regulatory bodies have reached contradictory conclusions regarding the safety of Cd in food. Adding to the confusion, epidemiological studies implicate environmental Cd as a risk factor for bone, cardiovascular, and other degenerative diseases at exposure levels that are much lower than points of departure used for setting food standards.

Objective

The objective was to examine whether the present confusion over Cd risks is not related to conceptual or methodological problems.

Discussion

The cornerstone of Cd risk assessment is the assumption that U-Cd reflects the lifetime accumulation of the metal in the body. The validity of this assumption as applied to the general population has been questioned by recent studies revealing that low-level U-Cd varies widely within and between individuals depending on urinary flow, urine collection protocol, and recent exposure. There is also evidence that low-level U-Cd increases with proteinuria and essential element deficiencies, two potential confounders that might explain the multiple associations of U-Cd with common degenerative diseases. In essence, the present Cd confusion might arise from the fact that this heavy metal follows the same transport pathways as plasma proteins for its urinary excretion and the same transport pathways as essential elements for its intestinal absorption.

Conclusions

The Cd risk assessment paradigm needs to be rethought taking into consideration that low-level U-Cd is strongly influenced by renal physiology, recent exposure, and factors linked to studied outcomes.

Citation

Bernard A. 2016. Confusion about cadmium risks: the unrecognized limitations of an extrapolated paradigm. Environ Health Perspect 124:1–5; http://dx.doi.org/10.1289/ehp.1509691     

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     

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     

Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality

Background

With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified.

Objectives

We aimed to assess dose–response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality.

Methods

In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose–response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression.

Results

Clear dose–response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination.

Conclusion

The novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies.

Citation

Zhang Y, Schöttker B, Florath I, Stock C, Butterbach K, Holleczek B, Mons U, Brenner H. 2016. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ Health Perspect 124:67–74; http://dx.doi.org/10.1289/ehp.1409020     

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     

Prediagnostic Serum Organochlorine Concentrations and Metastatic Prostate Cancer: A Nested Case–Control Study in the Norwegian Janus Serum Bank Cohort

Background

Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.

Objectives

We conducted a nested case–control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.

Methods

Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.

Results

Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log–transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).

Conclusions

Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.

Citation

Koutros S, Langseth H, Grimsrud TK, Barr DB, Vermeulen R, Portengen L, Wacholder S, Beane Freeman LE, Blair A, Hayes RB, Rothman N, Engel LS. 2015. Prediagnostic serum organochlorine concentrations and metastatic prostate cancer: a nested case–control study in the Norwegian Janus Serum Bank cohort. Environ Health Perspect 123:867–872; http://dx.doi.org/10.1289/ehp.1408245     

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     

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     

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     

Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures

Background

Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals.

Objectives

We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used.

Methods

We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps.

Discussion

In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures.

Conclusions

We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

Citation

Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC. 2016. Endocrine-disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures. Environ Health Perspect 124:256–264; http://dx.doi.org/10.1289/ehp.1409535     

A Standard of Knowledge for the Professional Practice of Toxicology

Background

Employers, courts, and the general public judge the credibility of professionals based on credentials such as academic degrees, publications, memberships in professional organizations, board certifications, and professional registrations. However, the relevance and merit of these credentials can be difficult to determine objectively. Board certification can be a reliable indicator of proficiency if the certifying organization demonstrates, through regularly scheduled independent review, that its processes meet established standards and when a certificate holder is required to periodically demonstrate command of a body of knowledge that is essential to current professional practice.

Objective

We report herein a current Standard of Knowledge in general toxicology compiled from the experience and opinions of 889 certified practicing professional toxicologists.

Discussion

An examination is the most commonly used instrument for testing a certification candidate’s command of the body of knowledge. However, an examination-based certification is only creditable when the body of knowledge, to which a certification examination tests, is representative of the current knowledge, skills, and capabilities needed to effectively practice at the professional level. Thus, that body of knowledge must be the current “Standard of Knowledge” for the profession, compiled in a transparent fashion from current practitioners of the profession.

Conclusion

This work was conducted toward ensuring the scientific integrity of the products produced by professional toxicologists.

Citation

Hulla JE, Kinter LB, Kelman B. 2015. A Standard of Knowledge for the professional practice of toxicology. Environ Health Perspect 123:743–748; http://dx.doi.org/10.1289/ehp.1408643     

Environmental Lead Exposure and Attention Deficit/Hyperactivity Disorder Symptom Domains in a Community Sample of South Korean School-Age Children

Background

Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms.

Objectives

We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains.

Methods

Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A).

Results

Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models.

Conclusions

Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.

Citation

Hong SB, Im MH, Kim JW, Park EJ, Shin MS, Kim BN, Yoo HJ, Cho IH, Bhang SY, Hong YC, Cho SC. 2015. Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children. Environ Health Perspect 123:271–276; http://dx.doi.org/10.1289/ehp.1307420