Agency for Toxic Substances and Disease Registry ATSDR

Atlanta, GA, United States

Agency for Toxic Substances and Disease Registry ATSDR

Atlanta, GA, United States
SEARCH FILTERS
Time filter
Source Type

Ingber S.Z.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR | Pohl H.R.,Agency for Toxic Substances and Disease Registry ATSDR | Abadin H.G.,Agency for Toxic Substances and Disease Registry ATSDR | And 2 more authors.
Regulatory Toxicology and Pharmacology | Year: 2013

The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. We searched PubMed and Web of Science for studies published through June 2012 assessing DDT/DDE exposure and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE (1.05; 95% CI: 0.93-1.18) and DDT (1.02; 95% CI: 0.92-1.13). Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls (11.30. ng/g lipid; p= 0.01). No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans. © 2013.


Demchuk E.,Agency for Toxic Substances and Disease Registry Atsdr | Ruiz P.,Agency for Toxic Substances and Disease Registry Atsdr | Chou S.,Agency for Toxic Substances and Disease Registry Atsdr | Fowler B.A.,Agency for Toxic Substances and Disease Registry Atsdr
Toxicology and Applied Pharmacology | Year: 2011

Methods of (Quantitative) Structure-Activity Relationship ((Q)SAR) modeling play an important and active role in ATSDR programs in support of the Agency mission to protect human populations from exposure to environmental contaminants. They are used for cross-chemical extrapolation to complement the traditional toxicological approach when chemical-specific information is unavailable. SAR and QSAR methods are used to investigate adverse health effects and exposure levels, bioavailability, and pharmacokinetic properties of hazardous chemical compounds. They are applied as a part of an integrated systematic approach in the development of Health Guidance Values (HGVs), such as ATSDR Minimal Risk Levels, which are used to protect populations exposed to toxic chemicals at hazardous waste sites. (Q)SAR analyses are incorporated into ATSDR documents (such as the toxicological profiles and chemical-specific health consultations) to support environmental health assessments, prioritization of environmental chemical hazards, and to improve study design, when filling the priority data needs (PDNs) as mandated by Congress, in instances when experimental information is insufficient. These cases are illustrated by several examples, which explain how ATSDR applies (Q)SAR methods in public health practice. © 2010.


Mumtaz M.,Agency for Toxic Substances and Disease Registry ATSDR | Fisher J.,National Center for Toxicological Research (NCTR) | Blount B.,Centers for Disease Control and Prevention | Ruiz P.,Agency for Toxic Substances and Disease Registry ATSDR
Journal of Toxicology | Year: 2012

Post-exposure risk assessment of chemical and environmental stressors is a public health challenge. Linking exposure to health outcomes is a 4-step process: exposure assessment, hazard identification, dose response assessment, and risk characterization. This process is increasingly adopting in silico tools such as physiologically based pharmacokinetic (PBPK) models to fine-tune exposure assessments and determine internal doses in target organs/tissues. Many excellent PBPK models have been developed. But most, because of their scientific sophistication, have found limited field applicationhealth assessors rarely use them. Over the years, government agencies, stakeholders/partners, and the scientific community have attempted to use these models or their underlying principles in combination with other practical procedures. During the past two decades, through cooperative agreements and contracts at several research and higher education institutions, ATSDR funded translational research has encouraged the use of various types of models. Such collaborative efforts have led to the development and use of transparent and user-friendly models. The human PBPK model toolkit is one such project. While not necessarily state of the art, this toolkit is sufficiently accurate for screening purposes. Highlighted in this paper are some selected examples of environmental and occupational exposure assessments of chemicals and their mixtures. Copyright © 2012 Moiz Mumtaz et al.


Scinicariello F.,Agency for Toxic Substances and Disease Registry ATSDR | Buser M.C.,Agency for Toxic Substances and Disease Registry ATSDR | Mevissen M.,University of Bern | Portier C.J.,National Center for Environmental Health
Toxicology and Applied Pharmacology | Year: 2013

Background: Lead exposure is associated with low birth-weight. The objective of this study is to determine whether lead exposure is associated with lower body weight in children, adolescents and adults. Methods: We analyzed data from NHANES 1999-2006 for participants aged ≥. 3 using multiple logistic and multivariate linear regression. Using age- and sex-standardized BMI Z-scores, overweight and obese children (ages 3-19) were classified by BMI ≥. 85th and ≥. 95th percentiles, respectively. The adult population (age ≥. 20) was classified as overweight and obese with BMI measures of 25-29.9 and ≥. 30, respectively. Blood lead level (BLL) was categorized by weighted quartiles. Results: Multivariate linear regressions revealed a lower BMI Z-score in children and adolescents when the highest lead quartile was compared to the lowest lead quartile (β (SE). = -0.33 (0.07), p. <. 0.001), and a decreased BMI in adults (β (SE). =-2.58 (0.25), p. <. 0.001). Multiple logistic analyses in children and adolescents found a negative association between BLL and the percentage of obese and overweight with BLL in the highest quartile compared to the lowest quartile (OR. = 0.42, 95% CI: 0.30-0.59; and OR. = 0.67, 95% CI: 0.52-0.88, respectively). Adults in the highest lead quartile were less likely to be obese (OR. = 0.42, 95% CI: 0.35-0.50) compared to those in the lowest lead quartile. Further analyses with blood lead as restricted cubic splines, confirmed the dose-relationship between blood lead and body weight outcomes. Conclusions: BLLs are associated with lower body mass index and obesity in children, adolescents and adults.© 2013.


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.


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.


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

Loading Agency for Toxic Substances and Disease Registry ATSDR collaborators
Loading Agency for Toxic Substances and Disease Registry ATSDR collaborators