Assessment of Early Life PFAS Exposure in Perinatal Biospecimens, Infant Formula, and Breastmilk.

项目摘要(摘要) 全氟和多氟烷基物质(PFAS)由于其对环境的影响，是一个公共卫生问题 持久性、人体内较长的生物半衰期以及相关的健康影响。在怀孕期间接触全氟辛烷磺酸， 婴儿期和儿童期与低出生体重、先兆子痫、甲状腺功能减退、疫苗接种减少有关 反应和代谢变化。逐步淘汰传统的全氟辛酸，最突出的是全氟辛酸 和(全氟辛烷磺酸)和全氟辛烷磺酸(全氟辛烷磺酸)，已导致未被研究的全氟辛烷磺酸的生产增加， 其含有较短的C-F链长或分支结构。然而，可获得的信息有限 关于这些未得到充分研究的全氟辛烷磺酸的暴露程度和毒性。因此，迫切需要 了解未得到充分研究或替代的全氟辛烷磺酸对全氟辛烷磺酸总暴露的贡献。这项提议将 填补人类在发育敏感期暴露于研究不足的全氟辛烷磺酸的知识空白 在两个队列中使用目标和非目标分析方法相结合的方法对生活进行评估。中心假说 我们的总体目标将通过追求两个具体目标来实现：(1)确定 母体血清、胎盘和脐带中EOF、遗留PFAS和未被研究的PFAS之间的关系 血液样本和(2)对母乳和配方奶中的EOF、遗留的PFAS和未被研究的PFAS水平进行量化 并确定它们对婴儿血清EOF、遗留PFAS和未被研究的PFAS水平的贡献。 表征未被充分研究的暴露程度，更换全氟辛烷磺酸是风险中的一个关键需求 评估过程，并将有助于指导今后的研究，以挑选候选的全氟辛烷磺酸进行审查。 此外，了解牛奶和配方奶粉对婴儿PFAS身体负担的影响有助于了解 暴露人群的母乳喂养指导。这一职业发展奖将延长应聘者的 在环境工程和环境分析化学方面的培训和研究经验 提供专家指导和保护时间，以便1)在流行病学研究设计中获得经验学习 和化学品暴露研究，2)发展非定向全氟辛烷磺酸分析的专业知识，3)熟练掌握 高级统计数据分析，以及4)培养专业和领导技能。她的主要导师Dr。 约瑟夫·布劳恩(流行病学，化学暴露)和她的指导团队成员克里斯特尔·波利特博士 (非定向PFAS分析)和Shelley Liu博士(统计)将为候选人提供所需的指导 建立一个富有成效的独立研究计划。这将通过实践培训来实现， 包括课程、会议、资助发展、科学交流和职业发展技能。 在成功完成这笔赠款的培训部分后，预计曼兹博士将取得成功 作为一名独立研究员，并准备建立一个由R01资助的研究计划。

Project Summary (Abstract) Per- and polyfluorinated alkyl substances (PFAS) are a public health concern given their environmental persistence, long biological half-life in humans, and related health effects. Exposure to PFAS during gestation, infancy, and childhood is associated with low birth weight, preeclampsia, hypothyroidism, reduced vaccine response, and metabolic alterations. The phase out of legacy PFAS, most prominently perfluorooctanoic acid and (PFOA) and perfluorooctane sulfonate (PFOS), has led to increased manufacturing of understudied PFAS, which contain shorter C-F chain lengths or branched structures. However, limited information is available regarding the extent of exposure and toxicity of these understudied PFAS. Thus, there is a critical need to understand the contribution of understudied, or replacement, PFAS to total PFAS exposure. This proposal will fill gaps in our knowledge of human exposure to understudied PFAS during developmentally sensitive periods of life using a combination of targeted and untargeted analytical methods in two cohorts. The central hypothesis will be tested and our overall objectives will be accomplished by pursuing two specific aims: (1) Characterize the relations of EOF, legacy PFAS, and understudied PFAS within and between maternal serum, placenta, and cord blood samples and (2) Quantify EOF, legacy PFAS, and understudied PFAS levels in breastmilk and formula and determine their contribution to infant serum EOF, legacy PFAS and understudied PFAS levels. Characterizing the magnitude of exposure to understudied, replacement PFAS is a critical need in the risk assessment process and will help guide future studies in the selection of candidate PFAS to examine. Furthermore, understanding how milk and formula contribute to infant PFAS body burden can help inform breastfeeding guidance in exposed populations. This career development award will extend the candidate’s prior training and research experience in environmental engineering and environmental analytical chemistry by providing expert mentoring and protected time to 1) gain experiential learning in study design for epidemiological and chemical exposure research, 2) develop expertise in untargeted PFAS analysis, 3) acquire proficiency in advanced statistical data analysis, and 4) develop professional and leadership skills. Her primary mentor Dr. Joseph Braun (epidemiology, chemical exposure), along with members of her mentoring team Dr. Krystal Pollitt (untargeted PFAS analysis) and Dr. Shelley Liu (statistics), will provide the needed mentoring for the candidate to establish a productive independent research program. This will be achieved through hands-on training that includes coursework, conferences, grant development, scientific communication, and career development skills. Upon successful completion of the training portion of this grant, it is expected that Dr. Manz will be successful as an independent investigator and prepared to establish a R01 funded research program.