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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结