Developmental neurotoxicity of organophosphate and novel brominated flame retardants in children

有机磷酸酯和新型溴化阻燃剂对儿童的发育神经毒性

• 批准号: 10247374
• 负责人: Aimin Chen
• 金额: $ 71.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-19 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247374
• 关键词: 12 year old; Address; Affect; Anatomy; Attention deficit hyperactivity disorder; Behavior; Birth; Brain; Brain imaging; Carpet; Chemical Exposure; Child; Childhood; Cognition; Cohort Studies; Communities; DNA Methylation; Data; Development; Electronics; Embryonic Development; Environment; Estrogen Antagonists; Exposure to; Flame Retardants; Gene Expression; Health; Home; Human; In Vitro; Investigation; Language; Measures; Mediating; Memory; Mission; Modality; Neuronal Differentiation; Neurons; Neurotoxins; Organophosphates; Outcome; Outcome Measure; Pentas; Persons; Phase; Policy Maker; Pregnancy; Pregnant Women; Prevention strategy; Problem behavior; Public Health; Regulation; Reporting; Research; Sampling; Scientist; Serum; Structure; Symptoms; Telomere-Binding Proteins; Testing; Textiles; Thyroid Hormones; Thyrotropin; Thyroxine; Toxic effect; Toxicology; Triiodothyronine; United States National Institutes of Health; Urine; analog; androgenic; base; behavior test; cognitive ability; cognitive function; cognitive testing; cohort; consumer product; developmental neurotoxicity; early adolescence; environmental chemical; epidemiology study; executive function; experimental study; exposure pathway; follow-up; in vivo; innovation; inorganic phosphate; neural network; neurobehavior; neurobehavioral; neurochemistry; neuroimaging; neurotoxicity; novel; polybrominated diphenyl ether; polyurethane foam; postnatal; prenatal; skills; white matter

Project Summary Toxicological and epidemiologic studies have shown developmental neurotoxicity of polybrominated diphenyl ethers (PBDEs), a group of flame retardants (FRs) widely used in the U.S. and elsewhere. With the phase-out of PBDEs from the market since 2004, replacement FRs, including organophosphate flame retardants (OPFRs) and novel brominated flame retardants (NBFRs), are increasingly added to consumer products to meet flammability requirement. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and Firemaster® 550 (FM 550) are the most commonly used replacement FRs. TDCPP, also referred to as “chlorinated tris”, is an OPFR once added to children’s sleepwear in the 1970s but later removed because of toxicity concerns. Triphenylphosphate (TPP) and various TPP analogs are OPFR components in FM 550, while 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) are NBFR components in FM 550. TDCPP, TPP and FM 550 have been reported to alter thyroid hormone levels, reduce neuronal viability and replication, alter neuronal differentiation, cause abnormal embryogenesis and development, affect neurobehavior, and change gene expression levels and DNA methylation in experimental studies. Compared with experimental study evidence of OPFRs and NBFRs, there are significant gaps in our understanding of their developmental neurotoxicity in humans. We propose to examine developmental neurotoxicity of OPFRs and NBFRs using the Cincinnati-based Health Outcomes and Measures of the Environment (HOME) Study, an existing birth cohort of 410 children from prenatal to 12 years of age, with prenatal and postnatal exposure assessment, thyroid hormones, cognitive and behavioral tests, and neuroimaging data. We hypothesize that prenatal and postnatal exposures to OPFRs and NBFRs are associated with: 1) altered thyroid hormone levels in maternal, cord, and childhood serum samples; 2) decreased child cognitive function; 3) poorer child neurobehavioral functioning; and 4) adverse impact on brain structure, organization, and function identified by neuroimaging at age 12 years. The proposed research will be the first to comprehensively study developmental neurotoxicity of both OPFRs and NBFRs in children. Addressing neuroendocrinological, neurobehavioral, and neuroimaging aspects of brain development is highly innovative for this investigation. The findings will be of critical value to scientific community and policy makers evaluating potential impact of current-use replacement FRs on developing brain. The research is highly relevant to the National Institutes of Health mission to identify potential chemical exposures that disrupt brain development and provide critical data to inform prevention strategies.

项目概要 毒理学和流行病学研究表明多溴联苯具有发育神经毒性 醚类 (PBDE) 是一组在美国和其他地方广泛使用的阻燃剂 (FR)。随着逐步淘汰 自 2004 年以来市场上 PBDE 的数量、替代 FR，包括有机磷酸酯阻燃剂 (OPFR) 和新型溴化阻燃剂 (NBFR) 越来越多地添加到消费品中，以满足 可燃性要求。磷酸三(1,3-二氯-2-丙基)酯 (TDCPP) 和 Firemaster® 550 (FM 550) 最常用的替代 FR。 TDCPP，也称为“氯化三羟甲基氨基甲烷”，是一种 OPFR 20 世纪 70 年代，它被添加到儿童睡衣中，但后来由于毒性问题而被移除。 磷酸三苯酯 (TPP) 和各种 TPP 类似物是 FM 550 中的 OPFR 成分，而 2-乙基己基- 2,3,4,5-四溴苯甲酸酯 (TBB) 和双(2-乙基己基)-2,3,4,5-四溴邻苯二甲酸酯 (TBPH) 属于 NBFR FM 550 中的成分。据报道，TDCPP、TPP 和 FM 550 可以改变甲状腺激素水平，降低 神经元活力和复制，改变神经元分化，导致异常胚胎发生和 发育、影响神经行为、改变实验中的基因表达水平和 DNA 甲基化 研究。与 OPFR 和 NBFR 的实验研究证据相比，我们的研究存在显着差距 了解它们对人类的发育神经毒性。我们建议检查发育 使用基于辛辛那提的健康结果和措施评估 OPFR 和 NBFR 的神经毒性 环境（家庭）研究，现有出生队列，包括 410 名从产前到 12 岁的儿童，其中 产前和产后暴露评估、甲状腺激素、认知和行为测试，以及 神经影像数据。我们假设产前和产后暴露于 OPFR 和 NBFR 与以下因素相关：1) 母体、脐带和儿童血清样本中甲状腺激素水平的改变； 2） 儿童认知功能下降； 3）儿童神经行为功能较差； 4）对大脑的不利影响 12 岁时通过神经影像学确定结构、组织和功能。拟议的研究将是 第一个全面研究 OPFR 和 NBFR 对儿童的发育神经毒性。 解决大脑发育的神经内分泌学、神经行为学和神经影像学方面的问题非常重要 本次调查具有创新性。研究结果对科学界和政策制定者具有至关重要的价值 评估当前使用的替代 FR 对发育中的大脑的潜在影响。该研究具有很高的 与美国国立卫生研究院的使命相关，即识别破坏大脑的潜在化学物质暴露 开发并提供关键数据来为预防策略提供信息。