The investigators propose a targeted investigation of endocrine-related outcomes in individuals in the Michigan PBB Registry and their offspring to follow up intriguing findings of a study recently completed by this team. In 1973, inadvertent substitution of a livestock feed supplement with fire retardant led to widespread contamination of meat and dairy products in Michigan with polybrominated biphenyls (PBBs), a class of chemicals toxicologically similar to PCBs, PBDE, DDE and other halogenated organics suspected to disrupt endocrine function. Over 4000 individuals with high likelihood of exposure were subsequently enrolled into the Michigan PBB Registry, and serum samples were analyzed for PBB. The proposers recently completed a twenty-year follow up survey of women in the registry regarding occurrence of endocrine-related outcomes, and the current application will pursue key findings of this survey as follows. The observation of an association of perinatal PBB exposure with reduced age at menarche in the daughters of registry participants will be followed up in two ways: 1) an expanded assessment of ovarian function in a subgroup of the daughters, using menstrual diaries and hormonal assays of daily urine samples (50 high exposure, 50 low exposure), and 2) an investigation of pubertal development in the sons of women in the registry to assess whether analogous impacts on pubertal development are observed in the boys, using a questionnaire assessment of Tanner stages and other pubertal landmarks in sons less than 18 years of age (n=204). The suggestion of an excessive spontaneous abortion rate among the exposed daughters of reproductive age will be followed up by: 1) updating the reproductive histories of the daughters over age 18 (n=214), and 2) by determining reproductive success in the sons over 18 years of age (n=218). Finally, the finding of altered menstrual cycle characteristics among the women in the registry will, be pursued by performing a menstrual diary and urinary hormone study in the adult women (50 high exposure, 50 low exposure) similar to that proposed for the daughters. Each of the proposed investigations allows targeted, efficient follow up of the important findings observed in the previous study, and will provide further insight into possible impacts of this class of chemicals on pubertal development, reproductive health and ovarian function.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Gray, Kimberly A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Public Health & Prev Medicine
Schools of Public Health
United States
Zip Code
Jacobson, Melanie H; Howards, Penelope P; Darrow, Lyndsey A et al. (2018) Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women. Paediatr Perinat Epidemiol 32:225-234
Jacobson, Melanie H; Darrow, Lyndsey A; Barr, Dana Boyd et al. (2017) Serum Polybrominated Biphenyls (PBBs) and Polychlorinated Biphenyls (PCBs) and Thyroid Function among Michigan Adults Several Decades after the 1973-1974 PBB Contamination of Livestock Feed. Environ Health Perspect 125:097020
Marder, M Elizabeth; Panuwet, Parinya; Hunter, Ronald E et al. (2016) Quantification of Polybrominated and Polychlorinated Biphenyls in Human Matrices by Isotope-Dilution Gas Chromatography-Tandem Mass Spectrometry. J Anal Toxicol 40:511-8
Sun, Xiaoyan; Peng, Limin; Manatunga, Amita et al. (2016) Quantile regression analysis of censored longitudinal data with irregular outcome-dependent follow-up. Biometrics 72:64-73
Wainstock, Tamar; Pearce, Brad; Barr, Dana B et al. (2016) Exposure to PBB-153 and Digit Ratio. Early Hum Dev 103:33-35
Terrell, Metrecia L; Rosenblatt, Karin A; Wirth, Julie et al. (2016) Breast cancer among women in Michigan following exposure to brominated flame retardants. Occup Environ Med 73:564-7
Terrell, Metrecia L; Hartnett, Kathleen P; Lim, Hyeyeun et al. (2015) Maternal exposure to brominated flame retardants and infant Apgar scores. Chemosphere 118:178-86
Small, Chanley M; Murray, Deanna; Terrell, Metrecia L et al. (2011) Reproductive outcomes among women exposed to a brominated flame retardant in utero. Arch Environ Occup Health 66:201-8
Yard, Ellen E; Terrell, Metrecia L; Hunt, Danielle Rentz et al. (2011) Incidence of thyroid disease following exposure to polybrominated biphenyls and polychlorinated biphenyls, Michigan, 1974-2006. Chemosphere 84:863-8
Jamieson, Denise J; Terrell, Metrecia L; Aguocha, Nnenna N et al. (2011) Dietary exposure to brominated flame retardants and abnormal Pap test results. J Womens Health (Larchmt) 20:1269-78

Showing the most recent 10 out of 20 publications