Emerging Contaminants and Issues of Concern Research Program

新出现的污染物和关注问题研究计划

• 批准号: 10914584
• 负责人: Suzanne Fenton
• 金额: $ 158.5万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10914584
• 关键词: Academy; Acute; Address; Adult; Affect; Agriculture; Alopecia; Area; Biological Assay; Body Weight decreased; California; Cells; Chemicals; Child; Chronic; Chronic Kidney Failure; Clinical; Clothing; Collaborations; Color; Communities; DNA Damage; Data; Development; Diquat; Disasters; Disease; Dyes; Educational workshop; Emergency Situation; Environment; Epithelium; Excretory function; Exposure to; Female; Follow-Up Studies; Food; Formulation; Gastrointestinal tract structure; Goals; Half-Life; Health; Hearing; Heavy Metals; Hematology; Herbicides; Human; Hyperplasia; Industry; Infant; Knowledge; Lead; Legal; Link; Literature; Malignant Neoplasms; Maps; Metabolism; Methods; Micronucleus Tests; Mission; Mothers; Mus; Mutagenicity Tests; Oral; Outcome; Peer Review; Perinatal; Pesticides; Phosphonic Acids; Plasma; Politics; Population; Predisposition; Public Health; Publications; Publishing; Rattus; Reporting; Research; Resources; Rewards; Risk; Scanning; Science; Series; Societies; Sodium; Solvents; Source; Testing; Thallium; Time; Toxic effect; Toxicology; Training; Umbilical Cord Blood; United States National Academy of Sciences; United States National Institutes of Health; Update; Vanadium; Water Pollutants; Work; carcinogenicity; chemical association; cytotoxic; cytotoxicity; design; dietary supplements; drinking water; environmental health disparity; exposed human population; follow-up; genomic signature; genotoxicity; glyphosate; ground water; hazard; immunotoxicity; improved; interest; male; marginalized community; meetings; member; microbial; persistent organic pollutants; placental transfer; programs; rapid technique; response; systematic review; tool; vanadyl sulfate; virtual

The goal of the ECIC research program is to develop strategies to provide high-quality data and knowledge to decision-makers and affected communities in a timely manner to address contemporary public health issues. These strategies include scoping activities to proactively identify environmental conditions that lead to the release of new hazards, increases in exposure to previously contained hazards, increases in environmentally related disease, and gaps in capabilities that, if addressed, would improve response to issues of concern. Emerging contaminant exposures or health conditions are typically highly visible issues that may be affected by outside factors (i.e., political, legal, and societal). While there are challenges in addressing time-sensitive issues of concern, there are also rewards: benefits to public health, the advancement of science, and expansion of collaborations. Our portfolio consists of program projects/activities for developing strategies and interactions with partners on problems related to specific ECIC. Our work in the last year has focused on: 1. Building a stakeholder network and strategies. In addition to connecting with stakeholders of interest by virtual zoom meetings, particularly those stakeholders that may have a vested interest in proactively identifying emerging contaminants or public health issues of concern through horizon scanning, we have further developed inter-agency and inter-divisional relationships on the topics of disaster response (DR2) and drinking water contaminants (National Emerging Contaminants Research Initiative or NECRI). Specifically, our team members have engaged with the weekly inter-agency/grantee DR2 meetings to develop and undertake a rapid scoping and systematic review of the East Palestine train derailment chemicals that is nearing completion. We are participating in the National Academy of Sciences review of these chemicals, and our report will inform the committee. As a follow-up to our involvement in NECRI activities, three ECIC team members are currently attending bi-monthly OSTP-sponsored interagency committee meetings (NTA-EBM or RC teams) to design cross-agency projects driven to assay for emerging contaminants in drinking water. We are also developing methods for rapid systematic review that could potentially be part of the DR2 Resource Portal of tools. The ECIC team developed and chaired a Society of Toxicology 2023 workshop entitled "Scanning the environmental horizon: Developing strategies to proactively identify and address tomorrows emerging issues". Speakers presented their work on mapping PFAS in drinking water, nanoplastic bioactivities, chronic kidney disease of unknown origin, and a rapid response toolbox. The ECIC team will also be sponsoring the DTT Seminar Series speaker from California EPA to hear about recent updates to the Cal EnvironScreen and how it might help to identify communities with potential environmental health disparities. 2. Management of our ECIC project portfolio. Most of our ECIC project portfolio existed prior to our team, so in FY23 we completed a couple of projects listed in the publications section and heard updates on other projects. The project addressing the chemical exposome in cord blood of infants and their mothers in three different regions of NC aims to address the questions of existing environmental health disparities in some communities of NC. The project has made substantial progress and has validated the methods for identifying and quantifying about 60 suspect contaminants in human plasma, including heavy metals, persistent organic pollutants, and some short half-life contaminants. The ECIC research program published work demonstrating excretion of and exposure to vanadium, a contaminant present in food, dietary supplements and drinking water, following perinatal drinking water exposure to vanadyl sulfate and sodium metavanadate in rats and characterized the short-term toxicity of vanadium in drinking water in rats and mice. In follow-up studies published this FY, although these compounds were not found to be mutagenic, oral exposures resulted in hematological effects and epithelial hyperplasia of sections of the gastrointestinal tract in male and female rats and mice. Thallium is a heavy metal, sometimes found in drinking water, and known to induce a broad spectrum of adverse health effects in humans. Initial findings in a perinatal 28d rat study and an adult mouse study confirmed that thallium in drinking water may increase clinical signs of alopecia and decreased body weights in mice and rats and indicated placental transfer of the compound. Glyphosate, a pesticide used in numerous commercial mixtures (or glyphosate-based formulations; GBF) to control weeds, has had mixed findings in terms of genotoxicity, depending on the mixture tested. Therefore, the NTP tested glyphosate, glyphosate isopropylamine (IPA), and (aminomethyl)phosphonic acid (AMPA, a microbial metabolite of glyphosate), 9 high-use agricultural GBFs, 4 residential-use GBFs, and additional herbicides (metolachlor, mesotrione, and diquat dibromide) present in some of the GBFs in bacterial mutagenicity tests, and in human TK6 cells using a micronucleus assay and a multiplexed DNA damage assay. NTP results showed no genotoxicity or notable cytotoxicity for glyphosate or AMPA at concentrations up to 10mM, while all GBFs and herbicides other than glyphosate were cytotoxic, and some showed genotoxic activity. Finally, a series of studies on sulfolane, a solvent used in the petrochemical industry and a groundwater contaminant in areas near refineries, have been published. Following the earlier work on disposition and metabolism of sulfolane in mice and rats, work in FY22 reported the 28-d toxicity studies in three species following oral exposures, and the immunotoxicity outcomes in developmentally exposed rats and in adult-exposed mice. The sulfolane chronic toxicity and carcinogenicity study is going to peer review in FY23. 3. Development of new projects. The ECIC research program has reviewed and facilitated approval of a project evaluating the toxicological effects of bromo-azo dyes (June Dunnick lead), often found in children's clothing and other colored materials, that are suspected of having a link to some cancers. The study will evaluate genomic signatures linked to acute exposure and characterize the genotoxic and immunotoxic effects of three bromo-azo dyes compared to previously studied chemicals that are structurally related. Additionally, the ECIC team reviewed and had approved a Rapid Scoping and Systematic Review of East Palestine chemicals project. Using authoritative sources, recent reviews, and primary literature, the project has developed a list of definitive, possible, and null associations of chemicals involved in the East Palestine, OH train derailment with health outcomes. Additionally, research gaps (e.g., no conclusions or data) were identified. These data will be delivered to the affected community and the National Academies committee as soon as possible. We also plan on developing systematic review methods for disasters or other ECIC issues. Finally, the ECIC team is in the planning stages of a workshop to identify tools used in horizon scanning of emerging contaminants of issues of health concern, and to coordinate inter-agency programs interested in developing further horizon scanning efforts. The workshop is proposed for FY24.

ECIC研究计划的目标是制定战略，及时向决策者和受影响社区提供高质量的数据和知识，以解决当代公共卫生问题。这些战略包括主动确定导致新危害释放、先前遏制危害增加、环境相关疾病增加以及能力差距的环境条件活动，如果解决这些问题，将改善对所关注问题的响应。新出现的污染物暴露或健康状况通常是高度可见的问题，可能会受到外部因素（即政治、法律和社会）的影响。虽然在解决时间敏感问题方面存在挑战，但也有回报：对公共卫生的好处、科学的进步和合作的扩大。我们的产品组合包括针对特定 ECIC 相关问题制定策略以及与合作伙伴互动的计划项目/活动。 去年我们的工作重点是： 1. 建立利益相关者网络和战略。 除了通过虚拟变焦会议与感兴趣的利益相关者建立联系，特别是那些可能对通过地平线扫描主动识别新出现的污染物或关注的公共卫生问题有既得利益的利益相关者外，我们还进一步发展了有关灾害响应（DR2）和饮用水污染物（国家新兴污染物研究计划或NECRI）主题的机构间和部门间关系。具体来说，我们的团队成员参加了每周一次的机构间/受赠者 DR2 会议，以对即将完成的东巴勒斯坦火车脱轨化学品问题进行快速范围界定和系统审查。我们正在参加美国国家科学院对这些化学品的审查，我们的报告将通知委员会。 As a follow-up to our involvement in NECRI activities, three ECIC team members are currently attending bi-monthly OSTP-sponsored interagency committee meetings (NTA-EBM or RC teams) to design cross-agency projects driven to assay for emerging contaminants in drinking water.我们还在开发快速系统审查的方法，这些方法可能成为 DR2 资源门户工具的一部分。 ECIC团队制定并主持了毒理学会2023年研讨会，题为“扫描环境视野：制定策略以主动识别和解决未来新出现的问题”。演讲者介绍了他们在绘制饮用水中的 PFAS、纳米塑料生物活性、来源不明的慢性肾病和快速反应工具箱方面的工作。 ECIC 团队还将赞助加州 EPA 的 DTT 研讨会系列演讲者，了解 Cal EnvironScreen 的最新更新以及它如何帮助识别存在潜在环境健康差异的社区。 2. 信保局项目组合的管理。我们的大多数 ECIC 项目组合在我们的团队之前就已经存在，因此在 2023 财年，我们完成了出版物部分列出的几个项目，并听到了其他项目的最新情况。该项目针对北卡罗来纳州三个不同地区的婴儿及其母亲的脐带血中的化学物质暴露问题，旨在解决北卡罗来纳州某些社区现有的环境健康差异问题。该项目取得了实质性进展，并验证了识别和定量人体血浆中约 60 种可疑污染物的方法，包括重金属、持久性有机污染物和一些短半衰期污染物。 ECIC 研究计划发表的研究成果展示了大鼠围产期饮用水接触硫酸氧钒和偏钒酸钠后，钒（食品、膳食补充剂和饮用水中存在的一种污染物）的排泄和接触情况，并描述了大鼠和小鼠饮用水中钒的短期毒性。在本财年发表的后续研究中，尽管未发现这些化合物具有致突变性，但口服暴露会导致雄性和雌性大鼠和小鼠的血液学影响和胃肠道部分上皮增生。铊是一种重金属，有时存在于饮用水中，已知会对人类产生广泛​​的不利健康影响。围产期 28 天大鼠研究和成年小鼠研究的初步结果证实，饮用水中的铊可能会增加小鼠和大鼠的脱发临床症状并降低体重，并表明该化合物会通过胎盘转移。草甘膦是一种在多种商业混合物（或基于草甘膦的制剂；GBF）中用于控制杂草的农药，根据所测试的混合物，在遗传毒性方面的研究结果不一。因此，NTP 测试了一些产品中存在的草甘膦、草甘膦异丙胺 (IPA) 和（氨甲基）膦酸（AMPA，草甘膦的微生物代谢物）、9 种高用量农用 GBF、4 种住宅用 GBF 以及其他除草剂（异丙甲草胺、甲基磺草酮和敌草快二溴化物）。 使用微核测定和多重 DNA 损伤测定在细菌致突变性测试和人 TK6 细胞中检测 GBF。 NTP结果显示，草甘膦或AMPA在浓度高达10mM时没有遗传毒性或显着的细胞毒性，而除草甘膦以外的所有GBF和除草剂均具有细胞毒性，并且有些显示出遗传毒性活性。最后，一系列关于环丁砜的研究已经发表，环丁砜是一种石化工业使用的溶剂，也是炼油厂附近地区的地下水污染物。继早期对小鼠和大鼠中环丁砜的处置和代谢的研究之后，2022 财年的工作报告了三个物种口服暴露后 28 天的毒性研究，以及发育暴露大鼠和成年暴露小鼠的免疫毒性结果。环丁砜慢性毒性和致癌性研究将于 2023 财年接受同行评审。 3、新项目开发。 ECIC的研究计划已审查并协助批准了一个评估溴偶氮染料（June Dunnick铅）毒理学影响的项目，这种染料经常出现在儿童服装和其他有色材料中，被怀疑与某些癌症有关。该研究将评估与急性暴露相关的基因组特征，并与之前研究的结构相关的化学物质相比，表征三种溴偶氮染料的基因毒性和免疫毒性作用。此外，信保局团队审查并批准了东巴勒斯坦化学品项目的快速范围界定和系统审查。该项目利用权威来源、最近的评论和主要文献，制定了一份与俄亥俄州东巴勒斯坦火车脱轨事件有关的化学物质与健康结果之间明确的、可能的和无效的关联清单。此外，还发现了研究差距（例如，没有结论或数据）。这些数据将尽快交付给受影响的社区和国家科学院委员会。我们还计划针对灾害或其他 ECIC 问题制定系统审查方法。最后，ECIC 团队正处于研讨会的规划阶段，以确定用于对健康问题的新兴污染物进行水平扫描的工具，并协调有兴趣进一步开展水平扫描工作的机构间计划。建议在 2024 财年举办该研讨会。

项目成果

Toxicology and carcinogenesis studies of an isomeric mixture of tris(chloropropyl) phosphate administered in feed to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.

对 Sprague Dawley (Hsd:Sprague Dawley SD) 大鼠和 B6C3F1/N 小鼠饲料中磷酸三(氯丙基)酯异构体混合物的毒理学和致癌作用研究。

• DOI: 10.22427/ntp-tr-602
• 发表时间: 2023
• 期刊: National Toxicology Program technical report series
• 作者: NationalToxicologyProgram

Short-term toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice.

• DOI: 10.1016/j.toxrep.2023.05.003
• 发表时间: 2023
• 期刊: TOXICOLOGY REPORTS
• 作者: Shipkowski, Kelly A;Hubbard, Troy D;Ryan, Kristen;Waidyanatha, Suramya;Cunny, Helen;Shockley, Keith R;Allen, Joshua L;Toy, Heather;Levine, Keith;Harrington, James;Betz, Laura;Sparrow, Barney;Roberts, Georgia K
• 通讯作者: Roberts, Georgia K

Toxicology and carcinogenesis studies of sodium tungstate dihydrate in Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice (drinking water studies).

二水合钨酸钠对 Sprague Dawley (Hsd:Sprague Dawley SD) 大鼠和 B6C3F1/N 小鼠的毒理学和致癌作用研究（饮用水研究）。

• DOI: 10.22427/ntp-tr-599
• 发表时间: 2021
• 期刊: National Toxicology Program technical report series
• 作者: NationalToxicologyProgram

Toxicity studies of select ionic liquids (1-ethyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium chloride, 1-butyl-1-methylpyrrolidinium chloride, and n-butylpyridinium chloride) administered in drinking water to Sprague Dawley (Hsd:Sprague Daw

• DOI: 10.22427/ntp-tox-103
• 发表时间: 2022-05
• 期刊: Toxicity report series

Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water.

• DOI: 10.1016/j.toxlet.2022.03.004
• 发表时间: 2022-05-01
• 期刊: TOXICOLOGY LETTERS
• 影响因子: 3.5
• 作者: Waidyanatha, Suramya;Weber, Frank X.;Fallacara, Dawn M.;Harrington, James M.;Levine, Keith;Robinson, Veronica G.;Sparrow, Barney R.;Stout, Matthew D.;Fernando, Reshan;Hooth, Michelle J.;Xie, Guanhua;Roberts, Georgia K.
• 通讯作者: Roberts, Georgia K.