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: 8389471
• 负责人: PHILIPPE ADAM GRANDJEAN
• 金额: $ 15.95万
• 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/8389471
• 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; Ecosystem; 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; 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. Public Health Relevance: The investigators will examine immune functions in two birth cohorts in the Faroe Islands and Greenland with elevated exposures to potentially immunotoxic ocean pollutants from seafood intake. As sensitive measures of immune functions, they will assess antibody responses to childhood immunizations, efficiency of vaccinations at adult age, and occurrence of allergy up to adult age, and link them to exposures incurred prenatally or during later life stages. The results will provide new insight needed for the protection of oceans against pollutants and for prevention of adverse effects in seafood-consumers.

描述（由申请人提供） 海鲜是人类接触环境污染物的主要来源，例如甲基汞和亲脂性污染物，包括多氯联苯 (PCB)。 此外，全氟化合物 (PFC) 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中浓度最高。研究人员最近发现，PFC 可能会对人类免疫系统的发育产生不利影响。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。 研究人员现在建议利用法罗群岛和格陵兰岛现有的独特出生群体来扩展这一观察，这些群体海鲜摄入量高，并且传统上食用海洋食物链中较高的海洋哺乳动物。由于可以获得广泛的基线数据，对出生队列（每个人群 250 名受试者）中的免疫功能进行后续检查是可行的，并将涵盖从学龄早期到青年时期关于不同生命阶段（包括子宫内）暴露的结果。 作为主要结果，他们将评估针对儿童免疫接种的血清中特定抗体的浓度。 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（甲型和乙型肝炎）疫苗接种的免疫反应。 他们将记录过敏性疾病的发生情况，并测量总 IgE 和特异性 IgE 的血清浓度，作为与产前和产后暴露相关的可能的免疫毒性结果。 将使用先进的统计模型来确定全氟化碳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。这一新证据对于了解终生接触来自海洋食品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对这些海洋污染物的风险评估具有重要意义。 公共卫生相关性：研究人员将检查法罗群岛和格陵兰岛两个出生队列的免疫功能，这些出生队列因摄入海鲜而暴露于潜在的免疫毒性海洋污染物。 作为免疫功能的敏感指标，他们将评估儿童免疫接种的抗体反应、成年疫苗接种的效率以及成年之前过敏的发生情况，并将它们与产前或生命后期发生的暴露联系起来。研究结果将为保护海洋免受破坏提供所需的新见解 污染物并预防对海鲜消费者的不利影响。