DDT & PBDE exposure, puberty onset and neurodevelopment in Mexican-American girls

描述（由首席研究员提供）：持久性有机污染物（POPs）是一种亲脂性化学物质，可在环境中持续存在，在食物链和人体组织中积累，并可能是内分泌干扰物。2001年，90多个国家签署了《关于持久性有机污染物的斯德哥尔摩公约》，承诺消除对健康造成最大关注的12种持久性有机污染物的使用。使用二氯二苯三氯乙烷（滴滴涕）控制疟疾是一个例外，这种使用在许多发展中国家正在增加。条约未涵盖的新化合物，如多溴联苯醚（PBDE）阻燃剂的使用也在增加。滴滴涕和多溴二苯醚都是动物内分泌干扰物和神经毒物，但对人类的研究有限。近几十年来，女孩（可能还有男孩）进入青春期的年龄有所下降。一种假设是，干扰内分泌的化合物，包括滴滴涕或多溴二苯醚，可能是造成这些趋势的原因。这些污染物还可能危害儿童的认知发展，特别是在产前和青少年时期大脑发育高峰期接触这些污染物。我们建议在加州萨利纳斯山谷的墨西哥裔美国儿童CHAMACOS纵向队列中调查子宫内和9岁时滴滴涕和多溴二苯醚暴露与青春期发病和神经发育的关系。CHAMACOS的孩子出生在2000年和2001年，他们的母亲从最近使用滴滴涕的墨西哥地区移民过来，他们在子宫内接触了相对较高的滴滴涕。在12个月和24个月大时，我们发现与子宫内滴滴涕血液水平相关的认知功能显著的剂量依赖性缺陷。由于他们在加州长大，CHAMACOS的孩子很可能接触到家具和电子产品中使用的多溴二苯醚。随着CHAMACOS女孩接近9岁，我们计划从与原始队列相同的来源人群中招募130名新女孩，将研究范围从170名女孩扩大到300名。在9岁时，我们将采集所有300对母亲/女儿的血样，并测量滴滴涕和多溴二苯醚。我们将构建模型，以140名原始参与者的9年母体水平和产前水平为基础，估计未采取这些措施的人的子宫内滴滴涕和多溴二苯醚水平。我们将评估子宫内（测量或推断）和9岁（测量）滴滴涕/E和多溴二苯醚的血液浓度与9岁、101/2岁或12岁评估的女孩的一般认知、执行、注意力、记忆和社会认知功能的关系，以及与青春期开始的时间和速度的关系，这些都是通过从9岁到12岁每六个月进行一次的临床坦纳检查来评估的。该应用程序利用了参与CHAMACOS纵向队列研究的墨西哥裔美国儿童的丰富数据集，并建议扩展这一独特的队列。我们的目标是解决这些目前使用的化合物对人类健康影响的关键数据缺口，这些化合物对评估其公共卫生成本和效益至关重要，也是国家和国际监管决策所必需的。公共卫生相关性：杀虫剂二氯二苯三氯乙烷（DDT）和工业阻燃剂多溴二苯醚（PBDEs）这两种持久性有机污染物在环境中广泛存在，在人体脂肪组织中积累，并已证明会破坏动物的激素功能和神经发育。很少有研究调查这些化学物质对人类健康的影响。这笔拨款将检查一组从出生前就开始跟踪的青春期前儿童，以确定9岁时收集的儿童血液或怀孕期间收集的母亲血液中的滴滴涕和多溴二苯醚水平是否与9至12岁儿童的青春期年龄提前和神经发育较差有关。

DESCRIPTION (provided by principal investigator): Persistent organic pollutants (POPs) are lipophilic chemicals that persist in the environment, accumulate in the food chain and human tissues, and are likely endocrine disruptors. In 2001, more than 90 countries signed the Stockholm Convention on Persistent Organic Pollutants, committing to eliminate the use of 12 POPs of greatest health concern. An exception was made for use of dichlorodiphenylthrichloroethane (DDT) for malaria control, and this use is increasing in many developing countries. Use of new compounds not covered under the treaty, such as polybrominated diphenyl ether (PBDE) flame retardants, is also increasing. Both DDT and PBDEs are endocrine disruptors and neurotoxicants in animals, but studies in humans are limited. Age at onset of puberty in girls, and possibly boys, has declined in recent decades. One hypothesis is that endocrine-disrupting compounds, including DDT or PBDEs, may be responsible for these trends. These pollutants may also jeopardize children's cognitive development, particularly with exposure during the prenatal and peri-adolescent periods of peak brain growth. We propose to investigate the associations of DDT and PBDE exposure in utero and at age 9 years on pubertal onset and neurodevelopment in the CHAMACOS longitudinal cohort of Mexican-American children in the Salinas Valley, California. The CHAMACOS children, born in 2000 and 2001, received relatively high in utero exposures to DDT from their mothers, who immigrated from areas in Mexico with recent DDT use. At 12 and 24 months of age, we found significant, dose-dependent deficits in cognitive functioning related to in utero DDT blood levels. Through their upbringing in California, CHAMACOS children likely have high exposure to PBDEs used in furniture and electronic products. As CHAMACOS girls approach age 9, we plan to enroll 130 new girls from the same source population as the original cohort, expanding the study from ~170 girls to 300. At the 9-year- old visit, we will collect blood samples from all 300 mother/daughter dyads and measure DDT and PBDEs. We will construct models to estimate in utero levels of DDT and PBDEs in those missing these measures, based on 9-year maternal levels and prenatal levels measured in 140 original participants. We will assess the relationship of in utero (measured or extrapolated) and age 9 (measured) blood concentrations of DDT/E and PBDE with the general cognitive, executive, attention, memory, and social cognition functioning of the girls assessed at ages 9, 101/2, or 12 years and with the timing and tempo of their pubertal onset as assessed by clinical Tanner exams conducted every six months from age 9 to 12 years. This application takes advantage of a rich dataset of Mexican-American children participating in the CHAMACOS longitudinal cohort study and proposes to expand this unique cohort. We aim to address key data gaps on the human health effects of these currently used compounds crucial for assessing their public health costs and benefits and necessary for national and international regulatory decision-making. PUBLIC HEALTH RELEVANCE: Two persistent organic pollutants, the pesticide, dichlorodiphenylthrichloroethane (DDT), and the industrial flame retardants, polybrominated diphenyl ethers (PBDEs), are widespread in the environment, accumulate in human fat tissue, and have been shown to disrupt hormonal function and neurodevelopment in animals. Few studies have examined the health effects of these chemicals in humans. This grant would examine a cohort of pre-adolescent children who have been followed since before birth to determine whether DDT and PBDE levels in children's blood collected at age 9 or in their mother's blood collected during pregnancy are associated with earlier age at puberty and poorer neurodevelopment in the children between ages 9 and 12 years.