Health Effects of Lifetime Exposure to Food Contaminants

描述(申请人提供)：只有在潜伏期过后，才能检测到对神经系统的毒性影响，这是由于年龄相关的退化过程导致缺陷暴露的一段时间。这一假设需要很长时间才能在前瞻性研究中进行验证，而且对产前暴露的回顾评估肯定是严重不准确的。这一流行病学难题现在将在法罗群岛得到解决，在那里可以估计出生前暴露于甲基汞(MeHg)，因为甲基汞暴露主要来自摄取鲸鱼肉。当地的鲸鱼群捕获量在岛屿之间和每年都有很大不同，鲸鱼肉的传播一直很困难，直到1950年左右，岛屿之间更先进的运输和冷藏出现了。因此，受试者产前接触甲基汞的潜在风险可以根据出生地点怀孕期间的详细捕鲸数据进行分类。法罗人海鲜摄入量很高，但他们的心血管死亡率仍高于斯堪的纳维亚其他地区，帕金森氏症的发病率约为预期的两倍。因此，我们将研究两个群体，每个群体由大约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。根据性别和年龄匹配，一组的出生地将是有大量鲸鱼的社区，第二组的出生地将是没有鲸鱼的社区。每个受试者在研究时都将大约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分析适当的暴露生物标志物来评估出生后暴露于甲基汞和多氯联苯及相关污染物的情况。此外，还将在血液样本中检测来自海鲜的基本营养物质，如n-3脂肪酸和硒。出生前和/或出生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。这些结果将为发育和出生后暴露于这些神经毒物的长期健康影响提供证据，这些毒物广泛存在于淡水鱼和海产品中，以及伴随而来的基本营养素摄取可能产生的补偿作用。这项研究将为产前接触污染物对健康的不利影响提供独特的证据，因为它们出现在高龄。因此，结果可能提供新的信息，很可能对美国和其他地方的EPA和其他监管机构的预防努力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.