In FY2014, 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. Clinical work for this project was conducted in 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. Work continued on this project in FY2014. 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 several brominated flame retardant components in rats or mice were conducted in the PI's research laboratory in FY2014. These studies were as follows: 1) Evidence indicates that the uterus is a target tissue in female rats chronically exposed by the oral route to the major flame retardant tetrabromobisphenol A (TBBPA). Data were collected in the laboratory to correlate the presence of TBBPA-derived material in gavaged rats with uterine toxicity, as well as determine the overall disposition of the chemical in the rodent model. It has been speculated that interference of TBBPA with estrogen metabolism may contribute to the toxicity;therefore, an investigation of the effects of TBBPA on gene expression was conducted to support the hypothesis. The data are currently being analyzed and a manuscript is in preparation. The disposition work for TBBPA female rats was completed and published in the literature in FY2014. The extent of dermal penetration of TBBPA was also investigated in female rats and by an in vitro method in rat and human skin (manuscript in preparation). 2) 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. The data were used to support a PBPK model of BDE-47 excretion in the mouse (published in FY2014). 3) A relatively new flame retardant product contains two brominated components of toxicological concern, 1-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), and di(2-ethylhexyl)tetrabromophthalate (TBPH). Kinetic studies of both chemicals are being conducted in the laboratory and preliminary findings were reported at scientific meetings in FY2014. 4) Preparations were begun in FY2014 to study the novel BFR, decabromodiphenyl ethane (DBDPE). Lastly, the PI contributed time and effort in FY2014 resulting in authorship in works associated with the research goals of this project, but not conducted in the present laboratory. These are shown in the """"""""publications section"""""""".

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011476-02
Application #
8938144
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Emond, Claude; DeVito, Michael J; Diliberto, Janet J et al. (2018) The Influence of Obesity on the Pharmacokinetics of Dioxin in Mice: An Assessment Using Classical and PBPK Modeling. Toxicol Sci 164:218-228
Schecter, Arnold; Kincaid, Jenevieve; Quynh, Hoang Trong et al. (2018) Biomonitoring of Metals, Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and Persistent Pesticides in Vietnamese Female Electronic Waste Recyclers. J Occup Environ Med 60:191-197
Knudsen, Gabriel A; Hall, Samantha M; Richards, Alicia C et al. (2018) TBBPA disposition and kinetics in pregnant and nursing Wistar Han IGS rats. Chemosphere 192:5-13
Petriello, Michael C; Charnigo, Richard; Sunkara, Manjula et al. (2018) Relationship between serum trimethylamine N-oxide and exposure to dioxin-like pollutants. Environ Res 162:211-218
Hall, Samantha M; Coulter, Sherry J; Knudsen, Gabriel A et al. (2017) Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett 272:68-74
Callahan, Catherine L; Pavuk, Marian; Birnbaum, Linda S et al. (2017) Serum polychlorinated biphenyls and leukocyte telomere length in a highly-exposed population: The Anniston Community Health Survey. Environ Int 108:212-220
Knudsen, Gabriel A; Sanders, J Michael; Birnbaum, Linda S (2017) Disposition of the emerging brominated flame retardant, bis(2-ethylhexyl) tetrabromophthalate, in female Sprague Dawley rats: effects of dose, route and repeated administration. Xenobiotica 47:245-254
Knudsen, Gabriel A; Sanders, J Michael; Hughes, Michael F et al. (2017) The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration. Xenobiotica 47:894-902
Thigpen Tart, Kimberly; Dilworth, Caroline H; Birnbaum, Linda S et al. (2017) The Epidemiologic Silver Lining of Climate Change. Epidemiology 28:313-315
Kwok, Richard K; Engel, Lawrence S; Miller, Aubrey K et al. (2017) The GuLF STUDY: A Prospective Study of Persons Involved in the Deepwater Horizon Oil Spill Response and Clean-Up. Environ Health Perspect 125:570-578

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