Brominated Flame Retardants: Multigenerational Endocrine Disruption?

描述（由研究者提供）：在非专业人士和科学界，各种合成化学品在体外和野生动物种群中显示出激素或抗激素特性，通过干扰正常的内分泌功能，对人类健康造成不利影响，这引起了人们的关注。许多结构相似的卤化有机物属于这一类。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，任何与不利健康影响的关联都可能产生深远的公共卫生影响。密歇根多溴联苯队列由4000多名因工业事故而暴露于溴化阻燃剂的人组成，并已成功跟踪了近30年。这个队列提供了一个独特的机会来确定接触卤化有机物是否与内分泌紊乱有关，并评估代际影响。在流行病学的伟大传统中，我们试图从不幸的“自然”实验中学到尽可能多的东西。该应用程序遵循先前由同一研究小组进行的队列成员中内分泌敏感终点的两项研究。在拟议的研究中，我们将重点放在我们发现内分泌紊乱的最大证据的队列成员的后代上。具体目标1继续评估男性子宫内暴露的后果。我们之前发现，高暴露妇女的儿子患泌尿生殖系统疾病的风险增加，生长和青春期发育较慢。特异性目标2针对女性后代的内分泌敏感终点，因为有证据表明，高度暴露的女孩初潮年龄更早，流产风险更高。在专项目标3中，我们试图描述溴化阻燃剂的跨代转移，专项目标4是跨学科方法的探索，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. PUBLIC HEALTH RELEVANCE: Brominated flame retardants are ubiquitous in the modern environment however the consequences of chronic exposure to humans are unclear. Studying the health of the Michigan PBB cohort (who were exposed to brominated flame retardants through an unfortunate industrial accident) and their children provides important information regarding exposure to chemicals that may disrupt the endocrine system across generations. Findings from the study of this unique and dedicated cohort may lead to important information about the health effects of brominated flame retardants and other related chemicals that are still in production today.