Brominated Flame Retardants: Multigenerational Endocrine Disruption?

描述(由研究人员提供)：外行人和科学界已经提出了担忧，即各种在体外和野生动物种群中表现出荷尔蒙或抗荷尔蒙特性的合成化学品正在通过干扰正常的内分泌功能而对人类造成不利的健康影响。一些结构相似的卤代有机物属于这一类。由于这些化学物质在环境中广泛存在，并在人类和动物组织中积累，任何与有害健康影响的联系都可能对公共卫生产生深远的影响。密歇根州PBB队列由4000多名因工业事故而接触溴化阻燃剂的个人组成，并已成功跟踪调查了近30年。这一队列提供了一个独特的机会来确定接触卤代有机物是否与内分泌紊乱有关，并评估这种影响在几代人中的影响。在流行病学的伟大传统中，我们试图从一个不幸的“自然”实验中学到尽可能多的东西。这项申请是在同一研究团队之前对队列成员中的内分泌敏感终点进行的两项研究之后进行的。在拟议的研究中，我们将重点放在队列成员的后代上，在那里我们发现了内分泌干扰的最大证据。具体目标1继续我们对男性宫内暴露后果的评估。我们之前发现，高度暴露的女性的儿子经历了生殖泌尿系统疾病的风险增加，生长和青春期发育缓慢。具体目标2针对女性后代中对内分泌敏感的终点，此前有证据表明，接触高风险的女孩月经初潮年龄较早，流产风险增加。在具体目标3中，我们试图表征溴化阻燃剂的跨代转移，而具体目标4是探索跨学科方法，以了解多代内分泌干扰和基因/环境相互作用的生物学机制。

DESCRIPTION (provided by investigator): Concerns have been raised in the lay and scientific communities that various synthetic chemicals showing hormonal or anti-hormonal properties in vitro and in wildlife populations are causing adverse health effects in humans by interfering with normal endocrine function. A number of the structurally similar halogenated organics belong to this category. Because these chemicals are widespread in the environment and accumulate in human and animal tissues, any associations with adverse health effects could have far reaching public health implications. The Michigan PBB cohort consists of over 4,000 individuals exposed to brominated flame retardants as the result of an industrial accident and has been successfully followed for nearly thirty years. This cohort presents a unique opportunity to determine whether exposure to halogenated organics is associated with endocrine disruption and to evaluate the impact across generations. In the grand tradition of epidemiology we seek to learn as much as we can from an unfortunate "natural" experiment. This applications follows two previous studies of endocrine sensitive endpoints among cohort members conducted by the same team of investigators. In the proposed study we focus on the offspring of cohort members where we have found the greatest evidence of endocrine disruption. Specific Aim 1 continues our assessment of the consequences of in utero exposure among males. We previously found that sons of highly exposed women experienced an increased risk of genitourinary conditions and slower growth and pubertal development. Specific Aim 2 addresses endocrine-sensitive endpoints among female offspring following evidence that highly exposed girls have an earlier age at menarche and an increased risk of miscarriages. In Specific Aim 3 we seek to characterize the cross-generational transfer of brominated flame retardants and Specific Aim 4 is an exploration of interdisciplinary approaches to understand biological mechanisms of multi-generational endocrine disruption and gene/environmental interactions.