Faroe Islands

Epidemiology of Immunotoxicant Exposure in Children
(Grant: # R01ES012199 )  Publications
Grandjean, Philippe A (pgrand@hohp.harvard.edu ) - Harvard University (Sch of Public Hlth)
Abstract: 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.

Health Effects of Lifetime Exposure to Food Contaminants
(Grant: # R01ES013692 )  Publications
Grandjean, Philippe (pgrand@hohp.harvard.edu ) - Harvard University (Sch of Public Hlth)
Abstract: Toxic effects to the nervous system may become detectable only after latent a period when the deficits become unmasked as a result of age-related degenerative processes. This hypothesis would take a long time to test in prospective studies, and retrospective assessment of prenatal exposure is bound to be seriously imprecise. This epidemiologic conundrum will now be resolved in the Faroe Islands, where prenatal exposure to methylmercury (MeHg) may be estimated, because the MeHg exposure primarily originated from ingestion of whale meat. Local catches of whale pods varied substantially between islands and from year to year, and dissemination of whale meat was difficult until about 1950, when more advanced transportation between the islands and refrigeration became available. A subject's potential exposure to MeHg prenatally can therefore be classified from the detailed whaling data for the pregnancy period at the place of birth. The Faroese have a very high intake of seafood, but their cardiovascular mortality is nonetheless higher than elsewhere in Scandinavia, and Parkinson's disease is about twice as common as expected. We will therefore examine two groups each consisting of about 250 men and women, who were all born around 1935, when variation in whale catches was the greatest. Matched by sex and age, one group's place of birth will be communities with great availability of whale, and the second group's place of birth will be communities without. Each subject will be approximately 70 years at the time of the study and will undergo a series of neurobehavioral and cardiovascular function tests. Postnatal exposure to MeHg and to polychlorinated biphenyls and related contaminants will be assessed by detailed questionnaire and by analysis of appropriate exposure biomarkers. In addition, essential nutrients from seafood, such as n-3 fatty acids and selenium will also be measured in blood samples. The effects of prenatal and/or postnatal neurotoxicant exposures will be determined after confounder control in statistical analyses that will include structural equation models. These results will provide evidence on long-term health implications of developmental and postnatal exposures to these neurotoxicants, which are widely present in freshwater fish and seafood, and the possible compensatory effects of concomitant intakes of essential nutrients. This study will provide unique evidence on adverse health effects of prenatal contaminant exposure as they appear at an advanced age. The results may therefore provide new information that could very likely have an impact on the preventive efforts and standard-setting of the EPA and other regulatory agencies in the U.S and elsewhere.

Mercury Associated Neurobehavioral Deficit in Children
(Grant: # R01ES009797 )  Publications
Grandjean, Philippe (pgrand@hohp.harvard.edu ) - Harvard University (Sch of Public Hlth)
Abstract: Methylmercury occurs as a contaminant of seafood and freshwater fish worldwide. Tragic pollution episodes have demonstrated that the fetal brain is particularly susceptible to methylmercury toxicity; the adverse effects on the nervous system appear to be irreversible and are much more widespread and serious in children than in adults, especially when exposures have occurred prenatally. This application builds upon the extensive data already collected on a cohort of 1,022 children born in 1986-1987. Detailed information was collected at the time of birth and during the course of follow-up at ages 7 and 14 years. Our previous research efforts have emphasized impacts during childhood and adolescence caused by developmental exposures to methylmercury as a possible paradigm for developmental neurotoxicant effects. The intention is now to complete the follow-up by examining the cohort members as young adults to determine the possible persistence of mercury-associated deficits in neuropsychological and cardiovascular functions, and the impact on educational achievements and overall health. The specific aims of this project are therefore to determine if methylmercury-associated cognitive deficits affect educational achievements, including high- school diploma and college (bachelor) studies; to examine cohort members at age 21 years to determine cardiovascular functions that may be affected by methylmercury exposure; to carry out analysis for PCBs in banked umbilical cord blood from cohort members, and to determine selenium intake from analysis of blood samples; and to assess genotypes for relevant genes that may affect methylmercury toxicokinetics or defense mechanisms against peroxidation processes that may be initiated by methylmercury exposure.