Immunotoxicity in Humans with Lifetime Exposure to Ocean Pullutants

终生接触海洋污染物的人类的免疫毒性

• 批准号: 8707457
• 负责人: PHILIPPE ADAM GRANDJEAN
• 金额: $ 13.86万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707457
• 关键词: Achievement; Adult; Adverse effects; Affect; Age; Allergic Disease; Antibodies; Antibody Formation; Antigens; Attention; Benchmarking; Biological Markers; Birth; Chemicals; Child; Childhood; Communities; Complex; Consumption; Data; Development; Developmental Process; Diet; Diet Habits; Dietary intake; Dioxins; Diphtheria; Disease; Dose; Elderly; Environmental Exposure; Environmental Pollutants; Epidemiology; Exposure to; Faeroe Islands; Fishes; Food; Food Chain; Greenland; Guidelines; Harvest; Health; Hepatitis A; Hepatitis B; Human; Hypersensitivity; IgE; Immune; Immune response; Immune system; Immunization; Immunology; Individual; Intake; Isomerism; Life; Link; Literature; Mammals; Marines; Measures; Mediating; Mercury; Methylmercury Compounds; Oceans; Organ; Organism; Outcome; Polychlorinated Biphenyls; Population; Pregnancy; Prevention; Prospective Studies; Relative (related person); Research; Research Personnel; Risk; Risk Assessment; Sampling; School-Age Population; Seafood; Serum; Source; Spleen; Staging; Statistical Models; Systems Development; Testing; Tetanus; Thymus Gland; Time; Toxic Environmental Substances; Toxicity Tests; Toxicology; Vaccination; Vaccine Antigen; Vaccines; Vulnerable Populations; Weight; aged; cohort; exposed human population; follow-up; immune function; immunotoxicity; insight; lead immunotoxic effect; mature animal; ocean ecosystems; pollutant; postnatal; prenatal; prenatal exposure; prospective; public health relevance; pup; reproductive; response; standardize guidelines; young adult

DESCRIPTION (provided by applicant) Seafood is a main source of human exposure to environmental pollutants, such as methyl mercury and lipophilic contaminants, including polychlorinated biphenyls (PCBs). In addition perfluorinated compounds (PFCs) biomagnify in ocean food chains, with the highest concentrations in marine mammals at high trophic levels. The investigators recently discovered that PFCs may adversely impact on human immune system development. Thus, in Faroese children, elevated PFC exposures were associated with reduced humoral immune response to routine childhood immunizations. The investigators now propose to extend this observation by utilizing existing and unique birth cohorts of Faroese and Greenlanders with high levels of seafood intake and traditional consumption of marine mammals high in ocean food chains. Due to the availability of extensive baseline data, follow-up examination of immune functions in the birth cohorts (250 subjects from each population) is feasible and will encompass outcomes at early school age through to young adult age in regard to exposures at different life stages, including intrauterine. As the main outcome, they will assess concentrations of specific antibodies in serum in response to childhood immunizations. The investigators will also determine the immune response in adults aged 28 to a booster dose (diphtheria and tetanus) and to vaccination with new antigens (hepatitis A and B). They will record the occurrence of allergic diseases and measure serum concentrations of total and specific IgE as possible immunotoxicity outcomes associated with prenatal and postnatal exposures. Advanced statistical models will be used to determine the relative contributions by PFCs and other ocean pollutants at different developmental stages and calculate benchmark dose levels for use in risk assessment. This new evidence will be of substantial importance for the understanding of immunotoxicity in humans with lifetime exposure to PFCs and other immunotoxic pollutants from marine food and for the risk assessment of these ocean pollutants.

描述（由申请人提供） 海产品是人类接触环境污染物的主要来源，如甲基汞和包括多氯联苯在内的亲脂性污染物。 此外，全氟化合物在海洋食物链中具有生物放大作用，在高营养级的海洋哺乳动物体内浓度最高。研究人员最近发现，PFC可能对人体免疫系统发育产生不利影响。因此，在法罗群岛儿童中，PFC暴露水平升高与常规儿童免疫接种的体液免疫反应降低有关。 研究人员现在建议通过利用法罗群岛和格陵兰岛现有的和独特的出生队列来扩展这一观察，这些群体具有高水平的海鲜摄入量和海洋食物链中海洋哺乳动物的传统消费。由于可获得广泛的基线数据，对出生队列（每个人群250例受试者）的免疫功能进行随访检查是可行的，并将涵盖从学龄早期到年轻成人年龄的不同生命阶段（包括宫内）暴露的结局。 作为主要结果，他们将评估儿童免疫接种后血清中特异性抗体的浓度。 研究人员还将确定28岁成年人对加强剂量（白喉和破伤风）和新抗原（甲型肝炎和B）疫苗接种的免疫反应。 他们将记录过敏性疾病的发生，并测量血清总IgE和特异性IgE浓度，作为与产前和产后暴露相关的可能免疫毒性结果。 将使用先进的统计模型来确定全氟化学品和其他海洋污染物在不同发展阶段的相对贡献，并计算用于风险评估的基准剂量水平。这一新的证据对于了解终生暴露于海洋食品中的全氟化碳和其他免疫毒性污染物的人类的免疫毒性以及这些海洋污染物的风险评估具有重要意义。