Polychlorinated biphenyls (PCBs) contaminate seafood and freshwater fish worldwide. Current risk assessment is based on immunotoxicity in rodents, although they differ from humans in regard to immune system development; epidemiological confirmation is lacking. We have carried out a pilot study in the Faroe Islands and found that prenatal exposure to dioxin-related PCB congeners appears to affect the antibody response to childhood vaccinations, possibly mediated via a toxic effect on prenatal T-cell programming. This North Atlantic fishing community is unique and highly suitable for prospective population-based studies. Average PCB exposures vary more than 100-fold within the population, and confounding variables other than marine food contaminants are of limited concern. We now propose to examine a birth cohort of 547 children born over a 2-year period from 1 April 1998 at the Faroes. The children will first be examined just before the final vaccination booster against tetanus and diphtheria at age 5 years. An additional blood sample will be obtained 4-8 weeks later. The children will again be examined at approximately age 7 years. Outcome variables will include antibody responses to vaccines, acute-phase reactants, and questionnaire information on childhood infections. Stored maternal serum from late pregnancy, and serum from the children will be analyzed for PCBs and other PHAH contaminants, and we will use a novel method to assess the in vitro activation of the arylhydrocarbon receptor (AhR or 'dioxin' receptor) by the contaminants present in serum. Mercury will be measured in cord blood, postnatal blood and hair. Statistical analyses will include multiple regression analysis, supplemented by mixed model analyses, structural equation models, and determination of benchmark doses of individual contaminants, their mixtures, and integrated exposure measures. These results are expected to extend substantially the current documentation for PCB risk assessment. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES012199-03
Application #
6993653
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Gray, Kimberly A
Project Start
2004-01-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
3
Fiscal Year
2006
Total Cost
$300,313
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Budtz-Jørgensen, Esben; Grandjean, Philippe (2018) Application of benchmark analysis for mixed contaminant exposures: Mutual adjustment of perfluoroalkylate substances associated with immunotoxicity. PLoS One 13:e0205388
Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming et al. (2018) Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources? Environ Health 17:11
Oulhote, Y; Shamim, Z; Kielsen, K et al. (2017) Children's white blood cell counts in relation to developmental exposures to methylmercury and persistent organic pollutants. Reprod Toxicol 68:207-214
Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold et al. (2017) Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination. J Immunotoxicol 14:39-49
Karlsen, Martina; Grandjean, Philippe; Weihe, Pal et al. (2017) Early-life exposures to persistent organic pollutants in relation to overweight in preschool children. Reprod Toxicol 68:145-153
Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal et al. (2017) Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years. J Immunotoxicol 14:188-195
Valvi, Damaskini; Oulhote, Youssef; Weihe, Pal et al. (2017) Gestational diabetes and offspring birth size at elevated environmental pollutant exposures. Environ Int 107:205-215
Timmermann, Clara Amalie Gade; Choi, Anna L; Petersen, Maria Skaalum et al. (2017) Secondary sex ratio in relation to exposures to polychlorinated biphenyls, dichlorodiphenyl dichloroethylene and methylmercury. Int J Circumpolar Health 76:1406234
Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal et al. (2017) Serum Vaccine Antibody Concentrations in Adolescents Exposed to Perfluorinated Compounds. Environ Health Perspect 125:077018
Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Petersen, Maria Skaalum et al. (2017) Shorter duration of breastfeeding at elevated exposures to perfluoroalkyl substances. Reprod Toxicol 68:164-170

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