Agency for Toxic Substances and Disease Registry ATSDR

Atlanta, GA, United States

Agency for Toxic Substances and Disease Registry ATSDR

Atlanta, GA, United States
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Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR | Feroe A.G.,Bowdoin College | Attanasio R.,Georgia State University
Environmental Research | Year: 2017

Background Antimony is used as a flame-retardant in textiles and plastics, in semiconductors, pewter, and as pigments in paints, lacquers, glass and pottery. Subacute or chronic antimony poisoning has been reported to cause sleeplessness. The prevalence of short sleep duration (<7 h/night) has been reported to be 37.1% in the general US population, and obstructive sleep apnea (OSA) affects 12–28 million US adults. Insufficient sleep and OSA have been linked to the development of several chronic conditions including diabetes, cardiovascular disease, obesity and depression, conditions that pose serious public health threats. Objective To investigate whether there is an association between antimony exposure and sleep-related disorders in the US adult population using the National Health and Nutrition Examination Survey (NHANES) 2005–2008. Methods We performed multivariate logistic regression to analyze the association of urinary antimony with several sleep disorders, including insufficient sleep and OSA, in adult (ages 20 years and older) participants of NHANES 2005–2008 (n=2654). Result We found that participants with higher urinary antimony levels had higher odds to experience insufficient sleep (≤6 h/night) (OR 1.73; 95%CI; 1.04, 2.91) as well as higher odds to have increased sleep onset latency (>30 min/night). Furthermore, we found that higher urinary antimony levels in participants were associated with OSA (OR 1.57; 95%CI; 1.05, 2.34), sleep problems, and day-time sleepiness. Conclusion In this study, we found that urinary antimony was associated with higher odds to have insufficient sleep and OSA. Because of the public health implications of sleep disorders, further studies, especially a prospective cohort study, are warranted to evaluate the association between antimony exposure and sleep-related disorders. © 2017


Bove F.J.,Agency for Toxic Substances and Disease Registry ATSDR | Ruckart P.Z.,Agency for Toxic Substances and Disease Registry ATSDR | Larson T.C.,Agency for Toxic Substances and Disease Registry ATSDR
Environmental Health: A Global Access Science Source | Year: 2014

Background: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. Methods. We conducted a retrospective cohort mortality study of Marine and Naval personnel who began service during 1975-1985 and were stationed at Camp Lejeune or Camp Pendleton, California during this period. Camp Pendleton's drinking water was uncontaminated. Mortality follow-up was 1979-2008. Standardized Mortality Ratios were calculated using U.S. mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune (N = 154,932) and Camp Pendleton (N = 154,969) cohorts and assess effects of cumulative exposures to contaminants within the Camp Lejeune cohort. Models estimated monthly contaminant levels at residences. Confidence intervals (CIs) indicated precision of effect estimates. Results: There were 8,964 and 9,365 deaths respectively, in the Camp Lejeune and Camp Pendleton cohorts. Compared to Camp Pendleton, Camp Lejeune had elevated mortality hazard ratios (HRs) for all cancers (HR = 1.10, 95% CI: 1.00, 1.20), kidney cancer (HR = 1.35, 95% CI: 0.84, 2.16), liver cancer (HR = 1.42, 95% CI: 0.92, 2.20), esophageal cancer (HR = 1.43 95% CI: 0.85, 2.38), cervical cancer (HR = 1.33, 95% CI: 0.24, 7.32), Hodgkin lymphoma (HR = 1.47, 95% CI: 0.71, 3.06), and multiple myeloma (HR = 1.68, 95% CI: 0.76, 3.72). Within the Camp Lejeune cohort, monotonic categorical cumulative exposure trends were observed for kidney cancer and total contaminants (HR, high cumulative exposure = 1.54, 95% CI: 0.63, 3.75; log 10 β = 0.06, 95% CI: -0.05, 0.17), Hodgkin lymphoma and trichloroethylene (HR, high cumulative exposure = 1.97, 95% CI: 0.55, 7.03; β = 0.00005, 95% CI: -0.00003, 0.00013) and benzene (HR, high cumulative exposure = 1.94, 95% CI: 0.54, 6.95; β = 0.00203, 95% CI: -0.00339, 0.00745). Amyotrophic Lateral Sclerosis (ALS) had HR = 2.21 (95% CI: 0.71, 6.86) at high cumulative vinyl chloride exposure but a non-monotonic exposure-response relationship (β = 0.0011, 95% CI: 0.0002, 0.0020). Conclusion: The study found elevated HRs at Camp Lejeune for several causes of death including cancers of the kidney, liver, esophagus, cervix, multiple myeloma, Hodgkin lymphoma and ALS. CIs were wide for most HRs. Because <6% of the cohort had died, long-term follow-up would be necessary to comprehensively assess effects of drinking water exposures at the base. © 2014 Bove et al.; licensee BioMed Central Ltd.


Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Scinicariello F.,Centers for Disease Control and Prevention | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR
Psychological Medicine | Year: 2015

Background. Genetic and environmental factors contribute to the risk of depression and several studies have noted an association between tobacco smoke and depression. Cadmium is a neurotoxicant and the main source of non-occupational exposure is tobacco smoke. Method. We conducted a cross-sectional analysis of data from 2892 young adult (aged 20-39 years) participants of the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariate logistic regressions, adjusted for age, sex, race/ethnicity, education, poverty income ratio (PIR), obesity, alcohol intake, blood lead (BPb) and smoking status, were used to analyze the association between blood cadmium (BCd) and depressive symptoms, as determined by the score on the nine-item Patient Health Questionnaire (PHQ-9). Results. Individuals in the highest BCd quartile had higher odds of having depressive symptoms [odds ratio (OR) 2.79, 95% confidence interval (CI) 1.84-4.25] than those in the lowest BCd quartile. Smoking status, but not BPb, was statistically significantly associated with depressive symptoms. Stratification by smoking status found that BCd was significantly associated with depressive symptoms in both non-smokers (OR 2.91, 95% CI 1.12-7.58) and current smokers (OR 2.69, 95% CI 1.13-6.42). Conclusions. This is the first study to report an association between BCd levels and depressive symptoms using a nationally representative sample. The association of cadmium with depressive symptoms was independent of smoking status. If this association is further confirmed, the continued efforts at reducing cadmium exposures, mainly through tobacco smoking cessation programs, may decrease the incidence of depression. Copyright © 2014 Cambridge University Press.


Feroe A.G.,Bowdoin College | Attanasio R.,Georgia State University | Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR
Environmental Research | Year: 2016

Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-. l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-. l-cysteine (CEMA) and their molar sum (∑acrolein) with diabetes using data from investigated 2027 adults who participated in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA-IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-β, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and ∑Acrolein with evidence of a dose-response relationship (p<0.05). The highest 3rd and 4th quartiles of CEMA compared to the lowest quartile were significantly associated with higher HOMA-IR, HOMA-β and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and ∑Acrolein were positively and significantly associated with HOMA-IR, HOMA-β and fasting insulin. These results suggest a need of further studies to fully understand the implications of acrolein with type 2 diabetes and insulin. © 2016 Published by Elsevier Inc.


Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR
Environmental Health Perspectives | Year: 2014

Background: Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens and suspected endocrine disruptors. Prenatal exposure to PAHs has been associated with obesity in early childhood. Objective: We examined the association of urinary PAH metabolites with adiposity outcomes [body mass index (BMI) z-score, waist circumference (WC), and rate of obesity] in children and adolescents. Methods: We performed whole-sample analyses of 3,189 individuals 6-19 years of age who participated in the 2001-2006 National Health and Nutrition Examination Survey. We performed multivariate linear and logistic regression to analyze the association of BMI z-score, WC, and obesity with concentrations of single urinary PAH compounds and the sum of PAHs. Furthermore, the analyses were stratified by developmental stage [i.e., children (6-11 years) and adolescents (12-19 years)]. Results: BMI z-score, WC, and obesity were positively associated with the molecular mass sum of the PAHs and the total sum of naphthalene metabolites. Most associations increased monotonically with increasing quartiles of exposure among children 6-11 years of age, whereas dose-response trends were less consistent for adolescents (12-19 years of age). Neither total PAHs nor total naphthalene metabolites were associated with overweight in either age group, and there was little evidence of associations between the outcomes and individual PAHs. Conclusions: Total urinary PAH metabolites and naphthalene metabolites were associated with higher BMI, WC, and obesity in children 6-11 years of age, with positive but less consistent associations among adolescents.


Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR | Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR
Environment International | Year: 2016

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are a class of organic compounds that are persistent in the environment due to their stable carbon-fluorine backbone, which is not susceptible to degradation. Research suggests these chemicals may exert an immunotoxic effect. The aim of this study is to investigate the associations between four PFASs - perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) - with food sensitization and food allergies in adolescent participants (ages 12-19. years) in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2010, respectively. We performed multivariate logistic regression to analyze the association between individual PFASs with food sensitization (defined as having at least 1 food-specific IgE level. ≥. 0.35. kU/L) in NHANES 2005-2006 and food allergies (self-reported) in NHANES 2007-2010. Serum PFOA, PFOS, and PFHxS were statistically significantly associated with higher odds to have self-reported food allergies in NHANES 2007-2010. When using IgE levels as a marker of food sensitization, we found that serum PFNA was inversely associated with food sensitization (NHANES 2005-2006). In conclusion, we found that serum levels of PFASs were associated with higher odds to have self-reported food allergies. Conversely, adolescents with higher serum PFNA were less likely to be sensitized to food allergens. These results, along with previous studies, warrant further investigation, such as well-designed longitudinal studies. © 2015.


Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR
EBioMedicine | Year: 2015

Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999-2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08-13.88) and 11.63% (95% CI: 6.18-17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose-response relationship (p-trend < 0.01). The association of the sum PCBs with longer LTL was found in both sexes.Additionally, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin were associated with longer LTL. The age independent association between longer LTL and environmental exposures to PCBs, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin may support a role as tumor promoter of these compounds. Further studies to evaluate the effect of these compounds on LTL are needed to more fully understand the implications of our finding. © 2015.


Fowler B.A.,Agency for Toxic Substances and Disease Registry ATSDR
EXS | Year: 2012

Over the last 30 years, the field of biomarkers has greatly expanded as early and specific endpoints for monitoring cellular responses to various disease states and exposures to drugs and chemical agents. They have enjoyed some success as predictors of health outcomes for a number of clinical diseases, but the application to chemical exposure risk assessments has been more limited. Biomarkers may be classified into categories of markers of exposure, effect, and susceptibility. Currently, "omics" biomarkers (i.e., genomic, proteomic, and metabolomic/metabonomic) are the major classes of biomarkers under development. These markers represent a continuum of cellular responses to drug or chemical exposures and provide linkages to mechanisms of cell injury/cell death or carcinogenic transformation. On the other hand, translation and application of these biomarkers for risk assessment has been limited due to validation and interpretation issues that need to be addressed in order for these potentially extremely valuable endpoints to reach their full potential as predictive tools for public health. This short chapter will briefly review these three "omics" biomarker classes and examine some validation/translation aspects needed in order for them to reach their full potential and acceptance as valuable tools for application to risk assessment.


Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR | Murray H.E.,Agency for Toxic Substances and Disease Registry ATSDR | Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR
International Journal of Hygiene and Environmental Health | Year: 2014

Background: Exposure to environmental chemicals may play a role in the development of obesity. Evidence suggests phthalate exposure may be associated with obesity in children and adults. Objective: To examine the association of ten urinary phthalate metabolites mono-n-butyl phthalate (MnBP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethylhexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(carboxylnonyl) phthalate (MCNP), and mono-(carboxyoctyl) phthalate (MCOP) grouped by molecular weight of their parent compounds with body weight outcomes in children, adolescent and adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Methods: We performed multinomial logistic regression to analyze the association between obesity and urinary phthalate metabolite concentrations in children and adolescents and adults. Results: Low molecular weight (LMW) phthalate metabolites (MnBP, MEP and MiBP) are significantly (p<. 0.05) associated with higher odds for obesity in male children and adolescents. High molecular weight (HMW) phthalate metabolites (MECPP, MEHHP, MEOHP, MEHP, MBzP, MCNP, and MCOP) and di-2-ethylhexyl phthalate (DEHP) metabolites (MEHHP, MEOHP, MEHP and MECPP) are significantly (p<. 0.05) associated with higher OR for obesity in all adults. Additionally, DEHP metabolites are significantly associated with obesity in all female adults; whereas DEHP and HMW metabolites are significantly associated with OR for obesity in males 60 years and older. Conclusions: We found age and sex differences in the association between urinary phthalate metabolite concentrations and body weight outcomes. Reverse causation cannot be excluded since overweight and obese people will have more fat mass, they may store more phthalates, thus leading to higher excretion concentrations. © 2014.


Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR
Environmental Research | Year: 2016

Telomeres are repetitive DNA sequences (TTAGGG) at the end of chromosomes. Cells with critically short telomeres enter replicative senescence and apoptosis. Several in vitro studies report that antimony causes cell apoptosis in human leukocyte cell lines. The goal of this analysis was to investigate whether there is an association between antimony exposure and leukocyte telomere length (LTL) among US adults aged 20 and older based on the National Health and Nutrition Examination Survey (NHANES) 1999–2002. We used multivariate linear regression to analyze the association of urinary antimony with LTL. LTL was log-natural transformed and the results were re-transformed and presented as percent differences. After adjustment for potential confounders, individuals in the 3rd and 4th quartiles of urinary antimony had statistically significantly shorter LTL (−4.78%, 95% CI: −8.42,−0.90; and −6.11%, 95% CI: −11.04,−1.00, respectively) compared to the lowest referent quartile, with evidence of a dose-response relationship (p-value for trend =0.03). Shorter LTL with antimony was driven by middle aged (40–59 years) and older (60–85 years) adult groups. The association may be biologically plausible because of reported oxidative stress and apoptosis effects of antimony on blood cells, effects known to shorten telomere length. © 2016

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