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

描述(由首席研究人员提供)：持久性有机污染物(POPs)是一种亲脂性化学物质，持续存在于环境中，在食物链和人体组织中积累，很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》，承诺消除对健康影响最大的12种持久性有机污染物的使用。使用二氯二苯基三氯乙烷(DDT)控制疟疾是一个例外，在许多发展中国家，这种使用正在增加。条约没有涵盖的新化合物的使用也在增加，如多溴二苯醚(PBDE)阻燃剂。DDT和PBDEs都是动物的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，女孩青春期开始的年龄有所下降，男孩可能也是如此。一种假设是，包括DDT或PBDEs在内的内分泌干扰化合物可能是这些趋势的原因。这些污染物还可能危害儿童的认知发展，特别是在胎儿期和青春期大脑发育高峰期。我们建议在加州萨利纳斯河谷的CHAMACOS纵向队列中，研究子宫内和9岁时接触DDT和PBDE与青春期开始和神经发育的关系。出生于2000年和2001年的CHAMACOS儿童在子宫内从母亲那里获得了相对较高的DDT暴露，这些母亲是从最近使用DDT的墨西哥地区移民来的。在12个月和24个月大时，我们发现了与子宫内DDT血液水平相关的显著的、剂量依赖性的认知功能缺陷。由于在加利福尼亚州长大，CHAMACOS儿童可能会高度接触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口中招募130名新女孩，将研究范围从约170名女孩扩大到300名。在9岁的探视中，我们将收集所有300名母女二人组的血液样本，并测量DDT和PBDEs。我们将构建模型，根据140名原始参与者的9年母亲水平和产前水平，估计那些缺少这些指标的人的子宫内DDT和PBDEs水平。我们将评估DDT/E和PBDE的宫内(测量或外推)和9岁(测量)血液浓度与9岁、101/2或12岁女孩的一般认知、执行、注意力、记忆和社会认知功能的关系，以及与她们青春期开始的时间和节奏的关系，这是通过从9岁到12岁每六个月进行一次临床Tanner检查来评估的。该应用程序利用了参加CHAMACOS纵向队列研究的墨西哥裔美国儿童的丰富数据集，并建议扩大这一独特的队列。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差距，这些化合物对评估其公共健康成本和好处至关重要，对于国家和国际监管决策是必要的。

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.