Birth Defects in Mice Caused by Tap Water

自来水导致小鼠出生缺陷

• 批准号: 8004103
• 负责人: THERESA C HRUBEC
• 金额: $ 18.45万
• 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 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8004103
• 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，我们在未经治疗的对照小鼠中观察到神经管缺陷（NTD）。 NTD 是一种严重的出生缺陷，每年影响 320,000 名儿童，导致严重残疾或死亡。大多数 NTD 是由改变遗传易感胎儿发育的环境因素引起的。因此，它们是可以预防的，例如，谷物中的叶酸强化可将 NTD 减少 1/3，每年节省 4 亿美元。小鼠中未知 NTD 的病因被定位于市政自来水。提供蒸馏去离子水可消除 NTD。当小鼠以剂量依赖性方式重新饮用来自弗吉尼亚州布莱克斯堡、华盛顿特区或马里兰州巴尔的摩的自来水时，畸形再次出现。这个问题似乎很普遍，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商业购买的怀孕小鼠（在 NT 关闭后发货）抵达时都带有 NTD。这些不同地区的水的一个共同特征是水处理方法。最近，出于对消毒副产品 (DBP) 安全性的担忧，美国环保局 (EPA) 修订了 DBP 监管指南。许多公用事业公司开始使用氯胺进行处理，以满足新的指导方针。已知和受监管的 DBP 浓度有所下降，但新的 DBP 却在无意中产生。该项目的目标是确定对照小鼠 NTD 的病因。该项目利用一个已建立的多学科研究团队来检验以下假设：自来水中的 DBP 是观察到的 NTD 的原因，而水中现在存在的致畸剂是改用氯胺处理造成的。检验这一假设的具体目的是明确确定 DBP 是否与小鼠和其他物种的 NTD 相关，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人类健康和发展的风险是否增加。 公共健康相关性：本研究将确定在小鼠和果蝇中观察到的畸形是否是由自来水中存在的环境消毒副产物 (DBP) 引起的，并确定自来水是否对大鼠有致畸作用。这项研究可能表明人类健康风险增加，并且是调节新 DBP 浓度的第一步。该项目将通过雇用 2 名博士生、为技术人员和 PI 提供大量薪资支持以及间接支持大学基础设施内的许多其他职位，直接改善当地经济状况。

项目成果

Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents.

• DOI: 10.1002/bdr2.1064
• 发表时间: 2017-08-15
• 期刊: Birth defects research
• 影响因子: 2.1
• 作者: Hrubec TC;Melin VE;Shea CS;Ferguson EE;Garofola C;Repine CM;Chapman TW;Patel HR;Razvi RM;Sugrue JE;Potineni H;Magnin-Bissel G;Hunt PA
• 通讯作者: Hunt PA

Drinking water treatment is not associated with an observed increase in neural tube defects in mice.

饮用水处理与观察到的小鼠神经管缺陷增加无关。

• DOI: 10.1007/s10661-014-3652-6
• 发表时间: 2014
• 期刊: Environmental monitoring and assessment
• 影响因子: 3
• 作者: Melin,VanessaE;Johnstone,DavidW;Etzkorn,FeliciaA;Hrubec,TerryC
• 通讯作者: Hrubec,TerryC