Health Effects of Lifetime Exposure to Food Contaminants

描述（由申请人提供）：对神经系统的毒性作用可能只有在潜在的一段时间后才会被检测到，当缺陷因年龄相关的退行性过程而暴露时。这一假设需要很长时间才能在前瞻性研究中得到验证，而且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，在法罗群岛可以估计出产前甲基汞（MeHg）暴露情况，因为甲基汞暴露主要来自摄入鲸鱼肉。各岛屿之间和每年的当地鲸荚捕获量都有很大差异，直到1950年左右，岛屿之间有了更先进的运输和冷藏设备，鲸鱼肉的传播才变得困难。因此，可以根据出生地点怀孕期间的详细捕鲸数据对受试者在产前可能暴露于甲基汞进行分类。法罗人的海鲜摄入量非常高，但他们的心血管疾病死亡率仍高于斯堪的纳维亚其他地区，帕金森病的发病率约为预期的两倍。因此，我们将研究两组，每组由大约250名男性和女性组成，他们都出生在1935年左右，当时鲸鱼捕获量的变化最大。根据性别和年龄的匹配，一组出生的地方将是有大量鲸鱼的社区，而第二组出生的地方将是没有鲸鱼的社区。每位受试者在研究时大约70岁，并将接受一系列神经行为和心血管功能测试。将通过详细的问卷调查和适当的暴露生物标志物分析来评估出生后甲基汞和多氯联苯及相关污染物的暴露情况。此外，血液样本中还将检测海鲜中的必需营养素，如n-3脂肪酸和硒。产前和/或产后神经毒物暴露的影响将在统计分析中包括结构方程模型的混杂控制后确定。这些结果将为发育和出生后暴露于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代偿作用提供证据。这项研究将提供独特的证据，对不利的健康影响产前污染物暴露，因为他们出现在高龄。因此，研究结果可能会提供新的信息，这些信息很可能会对美国和其他地方的环境保护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.