Final Report: Endocrine Disrupting Chemicals and Thyroid Outcomes

EPA Grant Number: R830254
Title: Endocrine Disrupting Chemicals and Thyroid Outcomes
Investigators: Anderson, Henry A.
Institution: Wisconsin Department of Health and Family Services
EPA Project Officer: Chung, Serena
Project Period: March 1, 2003 through February 28, 2007 (Extended to February 28, 2009)
Project Amount: $2,288,208
RFA: Endocrine Disruptors: Epidemiologic Approaches (2001) RFA Text |  Recipients Lists
Research Category: Economics and Decision Sciences , Endocrine Disruptors , Health , Safer Chemicals

Objective:

The goals of this project were to determine associations between fish consumption, PBDE, and other halogenated compounds and endocrine function, and to assess whether there are interactions among organohalogen exposures, fish consumption, and endocrine function.

Summary/Accomplishments (Outputs/Outcomes):

Analysis of the temporal changes in PCB and DDE levels between 1994-1995 and 2001-2003 or 2004-2005 showed that although there was a trend for increasing overall fish consumption among most participant groups (captains, anglers, and referents), sport fish and Great Lakes sport fish consumption decreased significantly among captains. Serum DDE concentrations, which were highest in men in the captain and angler groups, declined in 90 percent of study participants.  Mean DDE levels fell from 5.6 to 3.2 µg/L.  Total PCB levels declined in 80 percent of participants with the mean concentration falling from 4.2 to 2.8 µg/L.  Annual declines in serum DDE and PCB concentrations averaged 4.6 and 3.5 percent, respectively (Knobeloch et al., 2008). 
 
In contrast, PBDEs increased significantly from 1994-1995 to 2001-2003 (manuscript in preparation). ∑PBDE was associated with years of sport fish consumption.  ∑PBDE was weakly associated with ∑PCB and DDE, and was generally not associated with recent sport fish consumption.  Only ∑PBDE (not ∑PCB or DDE) was independently associated with shellfish and catfish consumption.  In our cohort, Great Lakes sport fish consumption does not contribute strongly to PBDE exposure (Anderson et al., 2008)
 
Mixed effects analysis of human exposures to PBDEs from household furnishings and appliances, vehicles, vacuum samples, and indoor settled dust revealed that bromine content in the participant’s sleeping pillow and primary vehicle car seat were significantly correlated with log-transformed, lipid-adjusted blood serum PBDE concentrations (Imm, submitted 2009).
 
Exposure to PBDE and other halogenated compounds and endocrine function and associated diseases were examined among cohort members.  Exposure to PBDEs at levels comparable to the general U.S. population was associated with hormone levels in adult men without thyroid disease or diabetes (Turyk et al., 2008).  PBDEs were positively related to measures of T4 and inversely related to total T3 and TSH. Participants with PBDEs over the 95th percentile were more likely to have thyroglobulin antibodies. Our results suggest that fish consumption may modify the effect of PBDEs on thyroid function and are consistent with an interaction between PBDEs and other contaminants in fish on thyroid hormones.  A major strength of our study is the measurement of specific hormones and BDE congeners, which offered insights into potential biological pathways, and a rationale for future mechanistic studies of how PBDE exposures may be linked to changes in thyroid hormone metabolism.  This is the first large study to link PBDE exposure with changes in thyroid hormones and antibodies and supports the need for further epidemiological investigations of the effect of PBDE exposure on thyroid disease.
 
In men, we found negative associations of free T4 and total T4 with PCBs, but the PCB-total T4 association was of borderline significance.  Comparisons with our earlier findings suggest a weaker association of PCBs and total T4, possibly corresponding to decreased PCB body burdens in the current study.  YRSCF was also negatively associated with total T4 similar to our findings in 1995-1996. Total T3 and TSH were not associated with PCBs, DDE, or YRSCF.
 
In 1995-1996, we found decreased total T4 and free thyroxine index with increasing PCB levels and YRSCF in women.  In 2004-2005, we did not find the negative association of PCBs with total T4 that was noted in the 1995-1996 study, although we did note a negative relationship of PCBs with free T4 in reproductive age women.   DDE was negatively associated with total T3 in all women and premenopausal and reproductive age women, and negatively associated with free T4 in all women and reproductive age women.  YRSCF was positively associated with free T3 in premenopausal and reproductive age women and positively associated with total T4 in reproductive age women.  PBDEs were not significantly associated with thyroid hormones in women. 
 
In 1995-1996, we found significant negative associations of SHBG-bound testosterone with PCBs and YRSCF, and of testosterone with PCBs in men.  These findings were not replicated in the current study, where testosterone was significantly positively associated with BDE 47, ΣPCBs, ΣPCBs-dioxin-like, ΣPCB inducers, and DDE.  SHBG and SHBG-bound testosterone were not associated with any exposures. 
 
FSH was negatively associated with PBDEs and PCBs in all women, and with PCBs in postmenopausal women; a response consistent with estrogenization. SHBG was negatively associated with PCBs and DDE in postmenopausal women, and SHBG-bound estradiol was negatively associated with DDE.  Reproductive hormones in women were not studied in 1995-1996.  We noted effect modification was found among sport fish and organohalogen exposures.  In addition, we found a substantial number of other factors modified the effect of POPs and sport fish on hormones, including age, smoking, alcohol, serum lipids, antilipid medication use, iodide, and hemoglobin A1c levels.  It is possible that differences in our current findings compared with the prior study are related to changes in some of these factors in the population.  
 
This investigation found significant associations of prevalent diabetes with DDE and dioxin-like mono-ortho PCBs exposure, but not non-dioxin like PCBs, PBDEs or years of sport fish consumption (Turyk et al., 2009).  DDE exposure was also associated with incident diabetes, but not mono-ortho PCB 118, sum PCBs, or years of sport fish consumption (Turyk et al., 2009, in press).   This is the first analysis to use a longitudinal study design to investigate disease risk in the cohort based on POP body burdens in 1994-1995, and this methodology will be important in future studies using a variety of disease outcomes.   Results of the cross-sectional disease analyses from the current study will provide rationale for these investigations, and suggest that a focus on reproductive and cardiovascular health outcomes may be productive, in addition to diabetes and thyroid diseases.  With further followup of the cohort for health outcomes, the POP body burdens measured in 2004-2005 will also be incorporated into longitudinal study designs.

Conclusions:

PBDEs increased significantly during the 1990s, but body burdens remained stable from 2001-2002 to 2004-2005.  PBDE exposure, at levels comparable to the general U.S. population, was associated with increased thyroglobulin antibodies and increased thryoxine in adult males.  Thyroxine was negatively associated with PCBs and years of sport fish consumption in men.  Free thyroxine was negatively associated with PCBs and DDE in reproductive age women.  PCBs, DDE, and BDE 47 were positively associated with testosterone in men.  In women, FSH was negatively associated with PCBs and PBDEs, and SHBG was negatively associated with PCBs and DDE.  The current study also confirmed cross-sectional associations of DDE and dioxin-like PCB exposure with diabetes, which had been noted in other investigations.  There was a non-significant association of PBDEs with diabetes in persons with thyroid disease.  We also observed an increased incidence of diabetes among those exposed to higher levels of DDE at baseline, along with the observation that diabetes status did not affect half-lives of DDE and PCB congeners.  These observations suggest the possibility of a causal relationship.  Future studies should explore the biologic pathways by which individual POPs affect glucose homeostatsis.
 
Lastly, data from this cohort found that fish consumption was only weakly correlated with PBDE serum levels.  However, comparison of lipid-adjusted serum PBDE levels to XRF bromine readings from bedding items, furnishings, floor coverings, car interiors, TVs, and computers, as well as PBDE levels in passive air samplers and vacuum cleaner contents, suggests that frequently used household items can be important sources of exposures to these chemicals.
 


Journal Articles on this Report : 25 Displayed | Download in RIS Format

Other project views: All 54 publications 26 publications in selected types All 25 journal articles
Type Citation Project Document Sources
Journal Article Anderson HA, Hanrahan LP, Smith A, Draheim L, Kanarek M, Olsen J. The role of sport-fish consumption advisories in mercury risk communication:a 1998-1999 12-state survey of women age 18-45. Environmental Research 2004;95(3):315-324. R830254 (Final)
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  • Journal Article Anderson HA, Wolff MS. Special fish contaminants issue. Environmental Research 2005;97(2):125-126 (introductory commentary). R830254 (Final)
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  • Journal Article Anderson HA. Eighth International Conference on Mercury as a Global Pollutant (ICMGP): human health and exposure to methylmercury. Environmental Research 2008;107(1):1-3. R830254 (Final)
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  • Journal Article Anderson HA, Imm P, Knobeloch L, Turyk M, Mathew J, Buelow C, Persky V. Polybrominated diphenyl ethers (PBDE) in serum: findings from a US cohort of consumers of sport-caught fish. Chemosphere 2008;73(2):187-194. R830254 (Final)
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  • Journal Article Freels S, Chary LK, Turyk M, Piorkowski J, Mallin K, Dimos J, Anderson H, McCann K, Burse V, Persky V. Congener profiles of occupational PCB exposure versus PCB exposure from fish consumption. Chemosphere 2007;69(3):435-443. R830254 (2007)
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  • Journal Article Gliori G, Imm P, Anderson HA, Knobeloch L. Fish consumption and advisory awareness among expectant women. Wisconsin Medical Journal 2006;105(2):41-44. R830254 (Final)
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  • Journal Article Imm P, Knobeloch L, Anderson HA. Fish consumption and advisory awareness in the Great Lakes basin. Environmental Health Perspectives 2005;113(10):1325-1329. R830254 (Final)
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  • Journal Article Imm P, Knobeloch L, Anderson HA. Maternal recall of children's consumption of commercial and sport-caught fish:findings from a multi-state study. Environmental Research 2007;103(2):198-204. R830254 (Final)
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  • Journal Article Imm P, Knobeloch L, Buelow C, Anderson HA. Household exposures to polybrominated diphenyl ethers (PBDEs) in a Wisconsin cohort. Environmental Health Perspectives 2009;117(12):1890-1895. R830254 (Final)
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  • Journal Article Knobeloch L, Anderson HA. Human biomonitoring to optimize fish consumption advice. American Journal of Public Health 2005;95(8):1304. R830254 (Final)
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  • Journal Article Knobeloch L, Anderson HA, Imm P, Peters D, Smith A. Fish consumption, advisory awareness, and hair mercury levels among women of childbearing age. Environmental Research 2005;97(2):220-227. R830254 (Final)
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  • Journal Article Knobeloch L, Steenport D, Schrank C, Anderson H. Methylmercury exposure in Wisconsin:a case study series. Environmental Research 2006;101(1):113-122. R830254 (Final)
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  • Journal Article Knobeloch L, Gliori G, Anderson H. Assessment of methylmercury exposure in Wisconsin. Environmental Research 2007;103(2):205-210. R830254 (Final)
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  • Journal Article Knobeloch L, Turyk M, Imm P, Schrank C, Anderson H. Temporal changes in PCB and DDE levels among a cohort of frequent and infrequent consumers of Great Lakes sportfish. Environmental Research 2009;109(1):66-72. R830254 (Final)
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  • Journal Article McElroy JA, Kanarek MS, Trentham-Dietz A, Robert SA, Hampton JM, Newcomb PA, Anderson HA, Remington PL. Potential exposure to PCBs, DDT, and PBDEs from sport-caught fish consumption in relation to breast cancer risk in Wisconsin. Environmental Health Perspectives 2004;112(2):156-162. R830254 (Final)
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  • Journal Article Mergler D, Anderson HA, Chan LHM, Mahaffey KR, Murray M, Sakamoto M, Stern AH. Methylmercury exposure and health effects in humans: a worldwide concern. Ambio 2007;36(1):3-11. R830254 (Final)
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  • Journal Article Turyk ME, Anderson HA, Freels S, Chatterton Jr. R, Needham LL, Patterson Jr. DG, Steenport DN, Knobeloch L, Imm P, Persky VW, Great Lakes Consortium. Associations of organochlorines with endogenous hormones in male Great Lakes fish consumers and nonconsumers. Environmental Research 2006;102(3):299-307. R830254 (2005)
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  • Journal Article Turyk ME, Anderson HA, Persky VW. Relationships of thyroid hormones with polychlorinated biphenyls, dioxins, furans, and DDE in adults. Environmental Health Perspectives 2007;115(8):1197-1203. R830254 (2007)
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  • Journal Article Turyk ME, Persky VW, Imm P, Knobeloch L, Chatterton Jr. R, Anderson HA. Hormone disruption by PBDEs in adult male sport fish consumers. Environmental Health Perspectives 2008;116(12):1635-1641. R830254 (Final)
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  • Journal Article Turyk M, Anderson HA, Hanrahan LP, Falk C, Steenport DN, Needham LL, Patterson Jr. DG, Freels S, Persky V, Great Lakes Consortium. Relationship of serum levels of individual PCB, dioxin, and furan congeners and DDE with Great Lakes sport-caught fish consumption. Environmental Research 2006;100(2):173-183. R830254 (2004)
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  • Journal Article Turyk M, Anderson H, Knobeloch L, Imm P, Persky V. Organochlorine exposure and incidence of diabetes in a cohort of Great Lakes sport fish consumers. Environmental Health Perspectives 2009;117(7):1076-1082. R830254 (Final)
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  • Journal Article Turyk M, Anderson HA, Knobeloch L, Imm P, Persky VW. Prevalence of diabetes and body burdens of polychlorinated biphenyls, polybrominated diphenyl ethers, and p,p'-diphenyldichloroethene in Great Lakes sport fish consumers. Chemosphere 2009;75(5):674-679. R830254 (Final)
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  • Journal Article Weisskopf MG, Anderson HA, Hanrahan LP, The Great Lakes Consortium. Decreased sex ratio following maternal exposure to polychlorinated biphenyls from contaminated Great Lakes sport-caught fish:a retrospective cohort study. Environmental Health:A Global Access Science Source 2003;2(1):2. R830254 (Final)
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  • Journal Article Weisskopf MG, Anderson HA, Hanrahan LP, Kanarek MS, Falk CM, Steenport DM, Draheim LA, Great Lakes Consortium. Maternal exposure to Great Lakes sport-caught fish and dichlorodiphenyl dichloroethylene, but not polychlorinated biphenyls, is associated with reduced birth weight. Environmental Research 2005;97(2):149-162. R830254 (2005)
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  • Journal Article Wolff MS, Anderson HA, Britton JA, Rothman N. Pharmacokinetic variability and modern epidemiology-the example of dichlorodiphenyltrichloroethane, body mass index, and birth cohort. Cancer Epidemiology Biomarkers & Prevention 2007;16(10):1925-1930. R830254 (Final)
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  • Supplemental Keywords:

    PBDE, PCB, DDE, Great Lakes, sport fish consumption, endocrine, thyroid, hormone
     
    , RFA, Health, Scientific Discipline, POLLUTANTS/TOXICS, HUMAN HEALTH, Health Risk Assessment, Exposure, Chemicals, Epidemiology, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Biochemistry, Molecular Biology/Genetics, Endocrine Disruptors - Human Health, pesticide exposure, chemical exposure, fish, bioavailability, endocrine disrupting chemicals, exposure studies, PCBs, altered sexual development, fish consumption, hormone degradation, DDT, human exposure, human growth and development, PCB, reproductive processes, thyroid function, groundwater contamination, thyroid, dietary exposure, agrochemicals, epidemiologic studies, Great Lakes, human health risk

    Relevant Websites:

     

    Progress and Final Reports:

    Original Abstract
  • 2003 Progress Report
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • 2007 Progress Report