In FY2013, project ZIA BC 011476 funded several investigations of human exposure to environmental contaminants as follows: 1) Study Title: "Anniston community health survey: Follow-up study and dioxin analyses". This is a major cross-sectional epidemiology investigation in residents of Anniston, Alabama. The subjects have been exposed over time to PCBs and other contaminants produced in a nearby chemical manufacturing facility. A previous study conducted by the Agency for Toxic Substances and Disease Registry (ATSDR) of the Centers for Disease Control found elevated blood levels of PCBs associated with a high incidence of both hypertension and diabetes in the population. The new study partners with ATSDR to assess current blood concentrations of non-dioxin-like and dioxin-like PCBs, other dioxin-like chemicals, and heavy metals in the participants of the earlier study. The results will be used for health and risk management for the exposed individuals. To date, the study has been designed, approved, and funded by the current project. Clinical work is scheduled to begin in early FY2014. 2) Study Title: "Toxic organic chemicals and heavy metals in blood and urine of electronic waste recycling workers and the general population in rural Vietnam". This study examines concentrations of heavy metals, PCBs, dioxins, and other persistent organic pollutants (POPs) in e-waste recyclers in Vietnam and is being conducted by researchers in Vietnam and the University of Texas School of Public Health, Dallas TX. Elevated levels of some contaminants of concern have been observed in the workers. The preliminary results have been presented at scientific meetings in FY2013. 3) Study Title: "The determination of persistent organic pollutants (POPs) and their metabolites in brain tissue and ventricular fluid". This study seeks to establish a correlation with POPs exposure to neurological disorders in humans by determining concentrations of POPs in post-mortem brain and ventricular fluid of subjects with/without neuropsychiatric illness. The study (in progress) is being conducted by researchers from Duke University and the National Toxicology Program (NTP). 4) Study title: "Bisphenol A (BPA) pharmacokinetics: Controlled exposure study". This study (in progress) is being conducted in the clinical center of the National Institute of Environmental Health Sciences (NIEHS) by NIEHS and NTP researchers to assess the pharmacokinetics of bisphenol A (BPA) in healthy human volunteers. These data will be used for further understanding of the fate of this potential endocrine disruptor in humans. Studies of the fate of five brominated flame retardant components in rats or mice were conducted in the PI's research laboratory in FY2013. These studies are as follows: 1) Beta-HBCD is one of three major isomers (alpha, beta, and gamma) contained in the high production volume HBCD flame retardant mixture. An investigation of the disposition of beta-HBCD in mice was completed in the laboratory and the results were published in the scientific literature. This work completes a series of kinetic studies of the three isomers and provides critical information for risk assessment of the mixture. 2) Evidence indicates that the ovary is a target tissue in female rats chronically exposed to the major flame retardant tetrabromobisphenol A (TBBPA) by the oral route. Data were collected in the laboratory to correlate the presence of TBBPA-derived material in gavaged rats with toxicity in the ovary, as well as determine the overall disposition of the chemical in the rodent model. No correlation was found;however, it was noted that interference of TBBPA with estrogen metabolism may contribute to the toxicity. An investigation of the effects of TBBPA on gene expression is underway to support the hypothesis. The extent of absorption by the dermal route is also being investigated in female rats. Portions of the TBBPA work were presented at scientific meetings and are submitted for publication. 3) Lower molecular weight polybrominated diphenyl ethers (PBDEs), extensively produced for use as flame retardants, accumulate in the environment, wildlife, and humans. Prior research established that excretion, and therefore internal dose of a major PBDE congener, BDE-47, differs between rats and mice. The finding is relevant to assessment of human risk;therefore, data were collected in the laboratory in genetically-altered mice to characterize protein transporters involved in differential excretion. This work supports a PBPK model of BDE-47 excretion in the mouse (manuscript in press). 4 and 5) A relatively new flame retardant product contains two brominated components,), 1-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), and di(2-ethylhexyl)tetrabromophthalate (TBPH), of toxicological concern. Kinetic studies of both chemicals are currently underway in the laboratory. The data will be used to support future toxicity studies in rodents. In FY2013, The PI contributed time and effort to various research articles associated with the goals and objectives of the present research project, as listed in the publication section.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011476-01
Application #
8763552
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$726,675
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Hoffman, Kate; Fang, Mingliang; Horman, Brian et al. (2014) Urinary tetrabromobenzoic acid (TBBA) as a biomarker of exposure to the flame retardant mixture Firemaster® 550. Environ Health Perspect 122:963-9
Parks, Christine G; Miller, Frederick W; Satoh, Minoru et al. (2014) Reproductive and hormonal risk factors for antinuclear antibodies (ANA) in a representative sample of U.S. women. Cancer Epidemiol Biomarkers Prev 23:2492-502
Lam, Thuy; Williams, Paige L; Lee, Mary M et al. (2014) Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys. Environ Int 73:135-42
Sueyoshi, Tatsuya; Li, Linhao; Wang, Hongbing et al. (2014) Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes. Toxicol Sci 137:292-302
Frawley, Rachel; DeVito, Michael; Walker, Nigel J et al. (2014) Relative potency for altered humoral immunity induced by polybrominated and polychlorinated dioxins/furans in female B6C3F1/N mice. Toxicol Sci 139:488-500
La Merrill, Michele; Emond, Claude; Kim, Min Ji et al. (2013) Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect 121:162-9
Birnbaum, Linda S (2013) When environmental chemicals act like uncontrolled medicine. Trends Endocrinol Metab 24:321-3
Sanders, J Michael; Knudsen, Gabriel A; Birnbaum, Linda S (2013) The fate of *-hexabromocyclododecane in female C57BL/6 mice. Toxicol Sci 134:251-7
Birnbaum, Linda S (2013) Designing safer chemicals. Environ Health Perspect 121:A9
van den Berg, Martin; Denison, Michael S; Birnbaum, Linda S et al. (2013) Polybrominated dibenzo-p-dioxins, dibenzofurans, and biphenyls: inclusion in the toxicity equivalency factor concept for dioxin-like compounds. Toxicol Sci 133:197-208

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