Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos.

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Predictors of Toxic Metal/Metalloid Exposures Among Mexican Americans in Starr County, Texas.

BACKGROUND: Arsenic, cadmium, and lead are toxic elements that widely contaminate our environment. These toxicants are associated with acute and chronic health problems, and evidence suggests that minority communities, including Hispanic/Latino Americans, are disproportionately exposed. Few studies have assessed culturally specific predictors of exposure to understand the potential drivers of racial/ethnic exposure disparities. OBJECTIVE: We sought to evaluate acculturation measures as predictors of metal/metalloid (hereafter "metal") concentrations among Mexican American adults to illuminate potential exposure sources that may be targeted for interventions. METHODS: As part of a longitudinal cohort, 510 adults, aged 35 to 69 years, underwent baseline interview, physical examination, and urine sample collection. Self-reported acculturation was assessed across various domains using the Short Acculturation Scale for Hispanics (SASH). Multivariable linear regression was used to assess associations between acculturation and urinary concentrations of arsenic, cadmium, and lead. Ordinal logistic regression was utilized to assess associations between acculturation and a metal mixture score. Lastly, best subset selection was used to build a prediction model for each toxic metal with a combination of the acculturation predictors. RESULTS: After adjustment, immigration factors were positively associated with arsenic and lead concentrations. For lead alone, English language and American media and food preferences were associated with lower levels. Immigration and parental heritage from Mexico were positively associated with the metal mixture, while preferences for English language, media, and food were negatively associated. CONCLUSION: Acculturation-related predictors of exposure provide information about potential sources of toxic metals, including international travel, foods, and consumer products. The findings in this research study provide information to empower future efforts to identify and address specific acculturation-associated toxicant exposures in order to promote health equity through clinical guidance, patient education, and public policy.

Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study.

Background: Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years. Methods: We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development. Results: In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI: .72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development. Conclusion: Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study.

Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Thyroid Hormones and Diabetes in Euthyroid Hispanic/Latino Adults of Diverse Backgrounds: HCHS/SOL.

Context: Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. Objective: This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. Methods: The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Results: Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P = .001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P = .047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P = .011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Conclusion: Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes.

Association of Acculturation and Hispanic/Latino Background with Endogenous Sex and Thyroid-Related Hormones Among Middle-Aged and Older Hispanic/Latino Adults: the HCHS/SOL Study.

BACKGROUND: Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations. METHODS: We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis. RESULTS: In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (ß = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (ß = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively. CONCLUSION: Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation.

Sex Hormones and Diabetes in 45- to 74-year-old Men and Postmenopausal Women: The Hispanic Community Health Study.

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.

Association of Blood Total Mercury with Dyslipidemia in a sample of U.S. Adolescents: Results from the National Health and Nutrition Examination Survey Database, 2011-2018.

Background: Abnormal lipid profiles in adolescents predict metabolic and cardiovascular diseases in adulthood. While seafood consumption is the primary source of mercury exposure, it also provides beneficial nutrients such as omega-3 fatty acids (O3FA). Prior studies indicate that blood total mercury (TBHg) has endocrine disrupting effects and may be associated with abnormal lipid profiles in adolescents. However, the impact of beneficial nutrients on this relationship has not been examined. Our study investigated the relationship of TBHg with dyslipidemia and lipid profiles and potential confounding and modification of these relationships by sex, body mass index (BMI), selenium and O3FA from seafood consumption. Methods: We examined 1,390 National Health and Nutrition Examination Survey participants 12-19 years of age from the 2011-2018 cycles. Using logistic and linear regression adjusted for survey design variables and stratified by sex a priori, we estimated the associations of TBHg and methylmercury with dyslipidemia, and with total cholesterol (TC), high (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and triglycerides. Results: The geometric mean of TBHg in this adolescent population was 0.44 µg/L. After controlling for socio-demographic covariates, BMI, serum selenium, age at menarche (females only) and average daily intake of O3FA; TBHg was significantly associated with higher TC levels (ß=3.34, 95% CI: 0.19, 6.50; p<0.05) in females but not males. Methyl Hg was also associated with increased TC, as well as decreased HDL-C in females but not males. We did not find significant associations of Hg exposure with dyslipidemia, LDL-C or triglycerides levels in either male or female adolescents. However, we observed evidence of effect modification by BMI and serum selenium for associations of TBHg with TC levels in male and female adolescents, respectively. Conclusion: Our findings of elevated TC levels in females but not males necessitates further research to better understand the underlying mechanisms driving these sex-specific associations.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007-2012.

BACKGROUND: Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. METHODS: Data included 2399 men and 1988 women from the 2007-2012 National Health and Nutrition Examination Survey (2007-2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. RESULTS: There were associations of the total metal mixture with thyroid hormones for T3 (beta: -0.023, 95% CI: -0.04, -0.01, in women), T4 (beta: -0.03, 95% CI: -0.05, -0.01, in men; beta: -0.026, 95% CI: -0.04, -0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. CONCLUSION: Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

Statistical Methods for Assessing the Explained Variation of a Health Outcome by a Mixture of Exposures.

Exposures to environmental pollutants are often composed of mixtures of chemicals that can be highly correlated because of similar sources and/or chemical structures. The effect of an individual chemical on a health outcome can be weak and difficult to detect because of the relatively low level of exposures to many environmental pollutants. To tackle the challenging problem of assessing the health risk of exposure to a mixture of environmental pollutants, we propose a statistical approach to assessing the proportion of the variation of an outcome explained by a mixture of pollutants. The proposed approach avoids the difficult task of identifying specific pollutants that are responsible for the effects and may also be used to assess interactions among exposures. Extensive simulation results demonstrate that the proposed approach has very good performance. Application of the proposed approach is illustrated by investigating the main and interaction effects of the chemical pollutants on systolic and diastolic blood pressure in participants from the National Health and Nutrition Examination Survey.

Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods.

Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.

A pilot study characterizing tetrachloroethylene exposure with exhaled breath in an impacted community.

Martinsville, Indiana overlays four groundwater contamination plumes, including a U.S. Environmental Protection Agency (EPA)-designated Superfund site. The primary contaminants are tetrachloroethylene (PCE), trichloroethylene (TCE), and other volatile organic compounds (VOCs). Martinsville represents many similar communities facing the challenge of groundwater and soil contamination and vapor intrusion, where residents are often frustrated by the lack of help in understanding and addressing the problem. The objective of this study was to evaluate PCE in exhaled breath to identify and quantify exposure to PCE and to explore the extent and level of PCE exposure among community residents. We measured chlorinated VOCs in exhaled breath samples from 38 healthy individuals who lived either in a contamination area or outside any plume area. We also measured VOCs in indoor air and tap water samples collected from 10 homes. PCE was detected in all exhaled breath samples (mean: 6.6 µg/m3; range: 1.9-44 µg/m3) and tap water samples (mean: 0.74 µg/L; range: 0.39-0.92 µg/L). PCE was detected in six of nine (66%) homes with air concentrations ranging from 1.6 to 70 µg/m3, exceeding the EPA action level of 42 µg/m3. We did not detect TCE or any other chlorinated VOCs in these samples. PCE exposure occurred among individuals living on the EPA Superfund site, as well as among those living on other plume sites and those living outside any known plumes. Preventive measures should focus on identifying highly exposed groups and reducing their exposures, followed by addressing moderately elevated exposures in the community. Our results demonstrated that PCE in exhaled breath can be used as an effective tool in community engaged environmental health research to evaluate the extent and level of community exposure, increase awareness, and promote residents' participation in research and site cleanup decision-making.

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China.

Per- and polyfluoroalkyl substances (PFASs) are widely detected in the environment and may cause adverse human health effects after exposure. Studies on the effect of PFASs on some health end points, including cancer, are still limited and show inconsistent results. In this research, 319 participants were recruited from Shandong Province, East China, consisting of patients with thyroid cancer and healthy controls. Seven novel and legacy PFASs were frequently detected (detection rate > 75%) in the serum samples of the participants. The concentrations of perfluorooctanoic acid (PFOA) were the highest in the case and control groups. Males showed significantly higher concentrations of PFASs than females. Exposure to PFASs was inversely associated with the risk of thyroid cancer. In the control group, we identified significant positive associations between PFASs and free thyroxine (FT4) as well as between PFOA and thyroid stimulating hormone (TSH) in females. A significant negative association between perfluorononanoic acid (PFNA) and triiodothyronine (T3) was observed in males. Our results suggest that exposure to certain PFASs could interfere with thyroid function. To our knowledge, this is the first case-control study demonstrating associations between novel and legacy PFASs in human and thyroid cancer.

Persistent and toxic chemical pollutants in fish consumed by Asians in Chicago, United States.

Consumption of seafood brings health benefits but may increase the ingestion of contaminants. Compared with other ethnic groups in the U.S., Asians consume seafood more frequently. However, there is little information about how culturally specific fish consumption contributes to exposure to toxicants. In this work, we surveyed fish consumption among Chinese, Korean and Vietnamese communities and purchased 103 seafood samples from local markets in Chicago. Each sample was analyzed for mercury (Hg) and 92 organic chemicals including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and Dechlorane Plus and related compounds (DPs). The rank order of pollutant concentration in all samples was Hg â‰« Σ66PCBs > Σ17OCPs > Σ8PBDEs > Σ8DPs. Positive correlations were noted among most contaminant groups. Bluefish, pike and tuna steak had the highest mean Hg (>1 mg/kg). The mean Σ66PCBs was highest in pike and bluefish (>100 ng/g) followed by pollock and mackerel (>40 ng/g). Overall, octopus, shrimp and tilapia were the least contaminated; while pike, bluefish, and pollock were the most contaminated. Omega-3 fatty acids were more strongly affiliated with the organic contaminants than mercury. A risk assessment identified seven types of fish that should have consumption limitations and six that should not be consumed. For these seafoods, consumption advice based on Hg levels would adequately protect health. In the survey participants, 17% of seafood mass consumed is from types of fish that should be limited to 1 or 2 meals/week, while 7% of the seafood mass consumed comes from types that should not be consumed at all. This work adds additional contaminants to the profile of health risks resulting from fish consumption among Asian Americans, which can be used in interventions aimed at conserving consumption of healthy fish while avoiding contaminants.

Prevalence and Predictors of Per- and Polyfluoroalkyl Substances (PFAS) Serum Levels among Members of a Suburban US Volunteer Fire Department.

BACKGROUND: Per-and polyfluoroalkyl substances (PFAS), are ubiquitous pollutants associated with adverse health outcomes. High PFAS levels have been demonstrated among career firefighters; less is known about PFAS levels among volunteer firefighters who comprise two-thirds of US firefighters. METHODS: Volunteer fire department members completed a survey and provided blood samples. We calculated geometric means and 95% CIs for PFAS reported by the National Health and Nutrition Examination Survey (NHANES). We compared PFAS distribution and levels among non-Hispanic white adult male study participants to those in the 2015-2016 and 2017-2018 NHANES cycles. We assessed associations between PFAS serum levels and years of firefighting controlling demographics and occupation using linear regression. RESULTS: Participant's average age was 46.6 years (sd. 17.1). Perfluorododecanoic acid (PFDoA) was detected in almost half study but <3% of NHANES participants; serum levels of PFDoA, perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were elevated among participants compared with NHANES. Serum levels of both PFDA and PFDoA were positively associated with years of firefighting. CONCLUSIONS: Volunteer firefighters may have a different serum profile and levels of PFAS than the general population. Future work in this area should include volunteer firefighters from other geographic locations and assess sources of PFAS exposure.

Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children's Study cohort.

BACKGROUND: Prenatal exposure to metals may play an important role in fetal growth. However, the epidemiologic evidence for certain metals is sparse, and most of the existing research has focused on evaluating single metals in highly exposed target populations. OBJECTIVES: We evaluated associations of cadmium, lead, manganese, selenium, and total mercury exposures during pregnancy with fetal growth using data from mother-infant pairs participating in the National Children's Study. METHODS: Prenatal metal exposures were measured using maternal blood collected from 6 to 32 weeks of gestation. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth or abstraction from medical records. Regression coefficients and their 95% confidence intervals were estimated from multivariable linear regression models in the overall study population as well as among male and female infants. We further evaluated pairwise metal-metal interactions. RESULTS: Sex-specific associations were observed for lead, with inverse associations for birthweight, birth length, head circumference, and gestational age observed only among female infants. Sex-specific associations were also observed for selenium, with a positive association for birthweight observed among male infants; selenium was also positively associated with ponderal index and inversely associated with birth length among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index, and the association with birthweight was stronger among female infants. No significant associations were observed with cadmium and manganese. In the metal-metal interaction analyses, we found evidence of a synergistic interaction between lead and total mercury and antagonistic interaction between selenium and total mercury with selected birth outcomes. CONCLUSIONS: Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.

Multiple organochlorine pesticide exposures and measures of sex steroid hormones in adult males: Cross-sectional findings from the 1999-2004 National Health and Nutrition Examination Survey.

BACKGROUND: Organochlorine pesticides are detectable in serum from most adults. Animal studies provide evidence of pesticide effects on sex hormones, suggesting that exposures may impact human reproductive function. Mounting evidence of sex differences in chronic diseases suggest that perturbations in endogenous sex hormones may influence disease risk. However, the association between organochlorine pesticide exposure and sex hormone levels in males across the lifespan is not well understood. METHODS: We evaluated cross-sectional associations of lipid-adjusted serum concentrations of ß-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethylene (DDE), p,p'-dichlorodiphenyltrichloroethane (DDT), trans-nonachlor, and mirex in relation to sex steroid hormone levels [testosterone (ng/dL), sex hormone binding globulin (SHBG; nmol/L), estradiol (pg/mL), and androstanediol glucuronide (ng/dL)] in a sample of 748 males aged 20 years and older from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression models were performed to estimate geometric means (GM) and their 95% confidence intervals (CIs) for quartiles of lipid-adjusted pesticide concentrations, adjusting for age, race, body mass index, serum lipids, smoking, education, and survey cycle. RESULTS: Hexachlorobenzene concentration was positively associated with total estradiol (GM Q4 = 43.2 pg/mL (95% CI 36.5-51.1) vs. Q1 GM = 25.6 pg/mL (24.1-27.3), p-trend <0.0001) and free estradiol (GM Q4 = 0.77 pg/mL (95% CI 0.64-0.93) vs. Q1 GM = 0.47 pg/mL (0.44-0.51), p-trend = 0.002). Serum DDT concentration was positively associated with total estradiol (GM Q4 = 31.6 pg/mL (95% CI 25.9-38.5) vs. Q1 GM = 27.3 pg/mL (25.9-28.7), p-trend = 0.05) and free estradiol (GM Q4 = 0.60 pg/mL (95% CI 0.48-0.76) vs. Q1 GM = 0.50 pg/mL (0.47-0.53), p-trend 0.02). There was a suggestive inverse association of DDT and SHBG (GM Q4 = 29.2 nmol/L (95% CI 23.8-35.9) vs. Q1 GM = 33.9 nmol/L (32.3-35.5), p-trend 0.07). A positive association of ß-hexachlorocyclohexane with total estradiol (GM Q4 = 30.3 pg/mL (95% CI 26.5-34.6) vs. Q1 GM = 26.7 pg/mL (24.5-29.0), p-trend = 0.09) was also suggestive but did not reach statistical significance. No distinct associations were observed for other hormone levels or other organochlorine pesticides. CONCLUSIONS: Our findings suggest that select organochlorine pesticides may alter male estradiol levels. The positive associations with estradiol may implicate sex hormones as a possible mechanism for disease risk among those with organochlorine pesticide exposure.

Associations of PCBS, dioxins and furans with follicle-stimulating hormone and luteinizing hormone in postmenopausal women: National Health and Nutrition Examination Survey 1999-2002.

BACKGROUND: The general population is exposed to the group of endocrine disrupting chemicals persistent organic pollutants (POPs), that includes polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). OBJECTIVES: The aim of this research was to evaluate the associations of serum levels of PCB, PCDD, and PCDF congeners with follicle stimulating hormone (FSH) and luteinizing hormone (LH) in postmenopausal women not taking exogenous hormones. We hypothesized that associations of POPs with these gonadotropins could be modified by factors affecting endogenous hormones. METHODS: Cross-sectional analyses were conducted on data from 89 postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES). POPs were summarized based on classification schemes thought to reflect toxicological properties. Associations of POPs and gonadotropin hormones were modeled with multivariable regression models. When evidence of interaction was found, conditional effects were estimated. RESULTS: We found inverse associations of LH, but not FSH, with exposure to anti-estrogenic and/or dioxin-like POPs, but not with non dioxin-like PCBs. A doubling of dioxin-like toxic equivalents (TEQs) was associated with a decrease in LH of 11.9% (95% CI = -21.3%, -1.4%, p = 0.03). Inverse associations were enhanced by potential effect modifiers related to both direct and indirect estrogenicity, including obesity and the obesity-related condition inflammation. CONCLUSIONS: These investigations support a pattern of endocrine-disrupting effects by dioxin-like POPs among postmenopausal women, especially those with conditions related to peripheral estrogenicity.