Birth Defects in Mice Caused by Tap Water

自来水导致小鼠出生缺陷

• 批准号: 7788635
• 负责人: THERESA C HRUBEC
• 金额: $ 22.7万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788635
• 关键词: Affect; Back; Baltimore; Cereals; Cessation of life; Chemicals; Child; Chloramines; Chlorine; Congenital Abnormality; Consumption; Development; Disinfection; District of Columbia; Doctor of Philosophy; Dose; Drosophila genus; Economic Conditions; Embryo; Environmental Risk Factor; Fetal Development; Fetus; Folic Acid; Goals; Guidelines; Health; Human; Human Development; Interdisciplinary Study; Measures; Methods; Michigan; Municipalities; Mus; Neural Tube Defects; New York; North Carolina; Population; Positioning Attribute; Process; Rattus; Research Infrastructure; Risk; Role; Safety; Shipping; Ships; Students; System; Teratogens; Testing; Time; Universities; Virginia; Wages; Water; chlorination; disability; drinking water; fetal; fortification; improved; malformation; meetings; nitrification; pregnant; prevent; public health relevance; water treatment

DESCRIPTION (provided by applicant): Since May of 2006, we have observed neural tube defects (NTDs) in untreated control mice. NTDs are serious birth defects affecting 320,000 children annually resulting in severe disability or death. Most NTDs result from environmental factors altering the development of a genetically susceptible fetus. As such, they can be prevented, for example, folic acid fortification of grains reduced NTDs by 1/3, saving $400 million annually. The cause of the unknown NTDs in mice was localized to municipal tap water. Providing distilled deionized water eliminated NTDs. The malformations reappeared when mice were placed back on tap water from Blacksburg, VA, Washington DC, or Baltimore, MD in a dose dependent manner. The problem appears to be widespread since commercially purchased pregnant mice (shipped after the time of NT closure) from suppliers located in Lansing, MI, Raleigh, NC, Dublin, VA, and Germantown, NY all arrived with NTDs. One feature common to water from these widely varying regions is the water treatment method. Concerns regarding the safety of disinfection by-products (DBPs) recently led the EPA to revise guidelines regulating DBPs. Many utilities began treating with chloramine to meet the new guidelines. Concentrations of known and regulated DBPs have declined, but new DBPs have inadvertently been produced. The goal of this project is to determine the cause of the NTDs in control mice. This project utilizes an established multidisciplinary research team to test the hypothesis that DBPs in tap water are responsible for observed NTDs, and that the teratogen now present in the water resulted from a switch to chloramine treatment. Specific aims to test this hypothesis are to unequivocally establish whether DBPs are responsible for the NTDs in mice and other species, and to systematically characterize and identify the compound or class of compounds in tap water responsible for NTD formation. The results of this study will help determine if there is an increased risk to human health and development. PUBLIC HEALTH RELEVANCE: This study will determine if the malformations observed in mice and Drosophila are caused by ambient disinfection by-products (DBP) present in tap water and also determine if tap water is teratogenic to rats. This study may indicate an increased health risk to humans and is the first step to regulate concentrations of new DBPs. This project will improve local economic conditions directly by employing 2 PhD students, providing significant salary support for a technician and PI and indirectly supporting many other positions within the university infrastructure.

描述（由申请人提供）：自2006年5月以来，我们在未治疗的对照小鼠中观察到神经管缺陷（NTD）。NTD是严重的出生缺陷，每年影响320，000名儿童，导致严重残疾或死亡。大多数NTD是由环境因素改变遗传易感胎儿的发育引起的。因此，它们是可以预防的，例如，谷物的叶酸强化减少了1/3的NTD，每年节省4亿美元。小鼠中未知NTD的原因定位于市政自来水。提供蒸馏去离子水消除NTD。当小鼠以剂量依赖性方式重新饮用来自Blacksburg，VA，华盛顿DC或巴尔的摩，MD的自来水时，畸形再次出现。该问题似乎很普遍，因为从位于密歇根州兰辛、北卡罗来纳州罗利、弗吉尼亚州都柏林和纽约州日耳曼敦的供应商处购买的妊娠小鼠（在NT关闭后运输）均携带NTD。来自这些差异很大的地区的水的一个共同特征是水处理方法。对消毒副产物（DBPs）安全性的担忧最近导致EPA修订了DBPs监管指南。许多公用事业开始用氯胺处理，以满足新的指导方针。已知和受管制的消毒副产物的浓度已经下降，但无意中产生了新的消毒副产物。本项目的目标是确定对照小鼠NTD的原因。该项目利用一个成熟的多学科研究团队来测试这样的假设：自来水中的消毒副产物是观察到的NTD的原因，并且现在水中存在的致畸剂是由于改用氯胺处理而产生的。测试这一假设的具体目的是明确确定DBPs是否是导致小鼠和其他物种NTD的原因，并系统地表征和鉴定自来水中导致NTD形成的化合物或化合物类别。这项研究的结果将有助于确定是否对人类健康和发展的风险增加。 公共卫生关系：本研究将确定在小鼠和果蝇中观察到的畸形是否由自来水中存在的环境消毒副产物（DBP）引起，并确定自来水是否对大鼠具有致畸性。这项研究可能表明对人类的健康风险增加，是调节新DBPs浓度的第一步。该项目将通过雇用2名博士生直接改善当地的经济条件，为技术人员和PI提供重要的工资支持，并间接支持大学基础设施内的许多其他职位。