Endocrine disrupting and immune effects of Triclosan in children

描述（由申请人提供）：三氯生是一种广泛使用于肥皂、牙膏和其他个人护理产品中的抗菌剂，75%的美国人体内可检测到三氯生的含量。体外和动物研究表明，三氯生是一种内分泌干扰物。在啮齿动物的研究中，在发育的关键窗口期暴露三氯生会降低甲状腺激素（T4）的水平，增加过敏敏感性和哮喘样反应，降低雄性的睾丸激素，改变雌性的青春期时间。迄今为止，只有少数研究考察了三氯生对人类健康的影响，主要针对学龄儿童和成人。这些研究在一定程度上证实了三氯生对内分泌和免疫系统的影响，但它们没有涉及子宫内接触三氯生的问题——这是内分泌紊乱和免疫发育的关键时期——因此可能低估了三氯生对健康的潜在影响。美国食品和药物管理局（FDA）和环境保护署（EPA）正在着手对三氯生进行全面的监管审查，但由于缺乏人体数据而受到挑战。目前迫切需要进行高质量的独立研究，评估产前和幼儿接触三氯生与随后的健康影响之间的关系。萨利纳斯母婴健康评估中心（CHAMACOS）是一项纵向出生队列研究，收集了300多名儿童从出生前到12岁期间的环境暴露、健康和发育的综合数据。我们建议对CHAMACOS孕妇及其5岁和9岁孩子的尿三氯生浓度进行表征，并检查这种暴露对以下方面的潜在影响：1)孕妇和新生儿的甲状腺激素稳态，2)5岁和7岁儿童的过敏和哮喘症状，以及3)9岁至12岁儿童的青春期时间和性激素水平。我们已经收集了实现这些目标所需的大部分数据，粗略的初步分析表明，在该队列中，三氯生与T4降低和哮喘症状风险增加有关。然而，如果没有专门的资金，完成尿液三氯生测量、获得额外的结果数据和进行复杂的数据分析（控制纵向效应和混淆）所需要的工作是无法完成的。这项研究是探索性的，因为它是第一个关于发育性三氯生暴露的纵向研究；发展性，为未来的深入研究奠定基础；而且风险很高，因为我们希望及时得到结果，为即将出台的政策决策提供信息。凭借丰富的现有数据，该项目可在短短两年内完成，具有很高的监管和科学影响。

DESCRIPTION (provided by applicant): Exposure to triclosan, an antibacterial agent used in soaps, toothpaste, and other personal care products, is widespread, with 75% of Americans having detectable levels in their bodies. In vitro and animal studies show that triclosan is an endocrine disruptor. In rodent studies, triclosan exposure during critical windows of development lowers levels of the thyroid hormone thyroxine (T4), increases allergic sensitivity and asthma-like response, decreases testosterone in males, and alters pubertal timing in females. To date, only a small number of studies have examined health effects of triclosan in humans, focusing on school-age children and adults. These studies provide some confirmation of effects on endocrine and immune systems, but they do not address exposure in utero - a critical period for endocrine disruption and immune development - and thus likely underestimate triclosan's potential health impact. Both the U.S. Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) are embarking on comprehensive regulatory reviews of triclosan, but are challenged by a dearth of human data. High-quality, independent research assessing associations of prenatal and early childhood triclosan exposures with subsequent health effects are urgently needed. The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) is a longitudinal birth cohort study that has gathered comprehensive data on environmental exposures, health, and development in more than 300 children who have participated from before birth through age 12. We propose to characterize urinary triclosan concentrations from CHAMACOS mothers during pregnancy and their children at 5 and 9 years of age and to examine the potential impact of this exposure on: 1) thyroid hormone homeostasis in pregnant women and newborns, 2) allergy and asthma symptoms in children at ages 5 and 7, and 3) timing of puberty and sex hormone levels in children between ages 9 and 12. We have already collected most of the data needed to achieve these aims, and crude, preliminary analyses suggest associations of triclosan with decreased T4 and increased risk of asthma symptoms in this cohort. However, the work needed to finalize urinary triclosan measurements, obtain additional outcome data, and conduct sophisticated data analyses that control for longitudinal effects and confounding cannot be completed without dedicated funding. This study is exploratory, because it is the first longitudinal study of developmental triclosan exposure; developmental, in that it lays groundwork for future in-depth research; and high risk, because we hope to have results in time to inform pending policy decisions. By relying on a rich existing data, this project can be completed in just two years, promising high regulatory and scientific impact.