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: 10394972
• 负责人: Aimin Chen
• 金额: $ 63.61万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394972
• 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.

项目摘要 毒理学和流行病学研究表明多溴二苯基的发育神经毒性 Ethers（PBDES），一组在美国和其他地方广泛使用的火焰阻燃剂（FRS）。随着循环 自2004年以来，市场上的PBDES，包括有机磷酸盐阻燃剂（OPFRS）的更换FRS（OPFRS） 和新颖的溴化阻燃剂（NBFR）越来越多地添加到消费产品中以满足 可燃性要求。 Tris（1,3-二氯2-丙酰基）磷酸盐（TDCPP）和Firemaster®550（FM 550）为 最常用的替换FRS。 TDCPP，也称为“氯化tris”，曾经是OPFR 在1970年代还增加了儿童睡衣，但由于毒性问题而被删除。 Triphenyl磷酸盐（TPP）和各种TPP类似物是FM 550中的OPFR成分，而2-乙基己基 - 2,3,4,5-四苯甲酸酯（TBB）和BIS（2-乙基己基）-2,3,4,5-四邻苯二酚（TBPH）是NBFR 据报道，FM 550中的组件。TDCPP，TPP和FM 550可改变甲状腺果实水平，降低 神经元的生存力和复制，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，我们的差距很大 了解他们在人类中的发育神经毒性。我们建议检查发展 OPFR和NBFR的神经毒性使用基于辛辛那提的健康结果和衡量标准 环境（家庭）研究，现有的出生队列，由410名儿童从产前到12岁，与 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对OPFR和NBFR的暴露是 与：1）在母体，绳索和儿童血清样品中改变甲状腺激素水平； 2） 儿童认知功能降低； 3）较贫穷的儿童神经行为功能； 4）对大脑的不利影响 结构，组织和功能通过神经成像在12岁时确定。拟议的研究将是 第一个在儿童中全面研究OPFR和NBFR的发育神经毒性。 针对神经内分泌学，神经行为和神经影像学方面的大脑发育方面高度高度 这项投资的创新。这些发现对科学界和政策制定者至关重要 评估当前使用替代FRS对发育大脑的潜在影响。这项研究很高 与美国国立卫生研究院的任务相关，以确定破坏大脑的潜在化学暴露 开发并提供关键数据以告知预防策略。

项目成果

Prenatal Exposure to Perfluoroalkyl Substances: Infant Birth Weight and Early Life Growth.

• DOI: 10.1097/ee9.0000000000000010
• 发表时间: 2018-06-01
• 期刊: Environmental epidemiology (Philadelphia, Pa.)
• 作者: Shoaff, Jessica;Papandonatos, George D;Braun, Joseph M
• 通讯作者: Braun, Joseph M

Chemical mixture exposures during pregnancy and cognitive abilities in school-aged children.

• DOI: 10.1016/j.envres.2021.111027
• 发表时间: 2021-06
• 期刊: ENVIRONMENTAL RESEARCH
• 影响因子: 8.3
• 作者: Kalloo, Geetika;Wellenius, Gregory A.;McCandless, Lawrence;Calafat, Antonia M.;Sjodin, Andreas;Sullivan, Adam J.;Romano, Megan E.;Karagas, Margaret R.;Chen, Aimin;Yolton, Kimberly;Lanphear, Bruce P.;Braun, Joseph M.
• 通讯作者: Braun, Joseph M.

Gestational and childhood exposure to phthalates and child behavior.

• DOI: 10.1016/j.envint.2020.106036
• 发表时间: 2020-11
• 期刊: Environment international
• 影响因子: 11.8
• 作者: Li N;Papandonatos GD;Calafat AM;Yolton K;Lanphear BP;Chen A;Braun JM
• 通讯作者: Braun JM

Variability and predictors of serum perfluoroalkyl substance concentrations during pregnancy and early childhood.

• DOI: 10.1016/j.envres.2018.04.033
• 发表时间: 2018-08
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Kingsley SL;Eliot MN;Kelsey KT;Calafat AM;Ehrlich S;Lanphear BP;Chen A;Braun JM
• 通讯作者: Braun JM