Health Effects of Lifetime Exposure to Food Contaminants

描述（由申请方提供）：对神经系统的毒性作用只有在潜伏期后才可检测到，此时由于年龄相关的退行性过程，缺陷变得暴露。这一假设需要很长时间才能在前瞻性研究中得到验证，而对产前暴露的回顾性评估必然是严重不准确的。这一流行病学难题现在将在法罗群岛得到解决，在那里可以估计产前接触甲基汞的情况，因为甲基汞接触主要来自摄入鲸鱼肉。当地的鲸群捕获量在岛屿之间和每年之间都有很大的差异，鲸鱼肉的传播一直很困难，直到1950年左右，当岛屿之间更先进的运输和冷藏变得可用时。因此，受试者产前接触甲基汞的可能性可以根据出生地怀孕期间的详细捕鲸数据进行分类。法罗群岛的海鲜摄入量非常高，但他们的心血管死亡率仍然高于斯堪的纳维亚半岛的其他地方，帕金森病的发病率大约是预期的两倍。因此，我们将研究两组，每组约有250名男性和女性，他们都出生在1935年左右，当时鲸鱼捕获量的变化最大。根据性别和年龄匹配，一组的出生地将是鲸鱼数量最多的社区，第二组的出生地将是没有鲸鱼的社区。每例受试者在研究时年龄约为70岁，将接受一系列神经行为和心血管功能测试。将通过详细的调查问卷和适当的接触生物标志物分析，评估出生后接触甲基汞、多氯联苯和相关污染物的情况。此外，海产品中的必需营养素，如n-3脂肪酸和硒也将在血液样本中进行测量。产前和/或产后神经毒物暴露的影响将在包括结构方程模型的统计分析中进行混杂控制后确定。这些结果将提供证据，说明发育和出生后接触这些广泛存在于淡水鱼和海产品中的神经毒物对健康的长期影响，以及同时摄入必需营养素可能产生的补偿效应。这项研究将提供独特的证据，产前污染物暴露的不良健康影响，因为他们出现在一个先进的年龄。因此，这些结果可能提供新的信息，很可能对美国环保署和其他监管机构的预防工作和标准制定产生影响。

DESCRIPTION (provided by applicant): 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.