Paternal Residential Exposure to Unconventional Oil and Gas Drilling (UOG)

父亲住宅暴露于非常规石油和天然气钻探 (UOG)

• 批准号: 10162589
• 负责人: Chung-Ho Lin
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-11 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10162589
• 关键词: Address; Adult; Adverse effects; Affect; Age; Air Pollution; American; Androgen Receptor; Area; Benzene; Biological Markers; Characteristics; Chemical Exposure; Chemicals; Child Health; Chromosomes; Confounding Factors (Epidemiology); Congenital Abnormality; Cotinine; Creatinine; DNA; DNA Fragmentation; Data; Defect; Dermal; Dose; Embryonic and Fetal Development; Endocrine Disruptors; Endocrine disruption; Endocrine system; Environment; Epigenetic Process; Exposure to; FDA approved; Female; Fertility; Future; Gases; General Population; Gonadal Steroid Hormones; Health; Health Personnel; Home; Hormone use; Hormones; Hour; Human; Human Cell Line; Impairment; In Vitro; Industry; Infant; Infertility; Ingestion; Inhalation; Laboratories; Life Style; Location; Mass Spectrum Analysis; Maternal Exposure; Measures; Modeling; Monitor; Morphology; Mothers; Mus; Natural Gas; Newborn Infant; Occupational; Occupational Exposure; Oils; Outcome; Participant; Paternal Exposure; Persons; Pesticides; Petroleum; Pilot Projects; Policy Maker; Population; Pregnancy Outcome; Pregnancy loss; Production; Pump; Questionnaires; Reporting; Reproduction; Reproductive Health; Reproductive system; Research; Resolution; Rodent; Sampling; Seminal fluid; Site; Smoking; Source; Specimen; Sperm Count Procedure; Sperm Motility; Spermatogenesis; Steroids; Surface; Telephone; Testing; Time; Toxic effect; Toxicant exposure; Urine; Water; Woman; Work; biomarker identification; chemical association; chemical release; demographics; drinking water; epidemiology study; exposed human population; exposure route; ground water; histone methylation; hydraulic fracturing; hypothalamic pituitary gonadal axis; male; man; men; metabolomics; muconic acid; offspring; operation; prenatal exposure; programs; recruit; remediation; reproductive; reproductive hormone; reproductive outcome; sperm cell; sperm quality; steroid hormone; systematic review; toxicant; urinary; volunteer; wasting; water quality

Unconventional oil and natural gas (UOG) extraction combines directional drilling and hydraulic fracturing or “fracking.” Over 1000 UOG chemicals (UOGCs) are used across the industry, and the waste water contains an additional 599 chemicals. Hundreds of these are known or suspected endocrine disrupting chemicals (EDCs). UOG operations cause air pollution and contamination of surface and ground water, exposing nearby humans by inhalation, dermal contact, and/or ingestion. Approximately 18 million Americans (5% of the population) live within 1 mile of a UOG site. Robust studies have reported birth defects in newborns with mothers residing near UOG activities, but failed to separate maternal and paternal exposure. A systematic review found only six high quality articles evaluating male occupational exposure to petroleum operations; none included exposure to UOG. Recent work has highlighted the importance of paternal exposures not only to fertility but also to pregnancy outcomes and offspring health. Environmentally relevant concentrations of chemicals detected in surface and ground water near UOG sites acted as EDCs in a human cell line in vitro, in adult female mice, and in prenatally exposed male and female mice. This prior work suggests the potential for adverse reproductive outcomes in humans exposed to UOGCs, and serves as the rationale for the hypothesis: residential proximity of men to UOG operations is associated with urinary biomarkers of exposure, disruption of reproductive hormones, decreased sperm production, and damage to sperm chromosomes. In a pilot study, UOGCs were elevated in the urine of residentially exposed humans. For example, trans,trans-muconic acid (ttMA), a benzene metabolite, was detected at levels almost 5 times higher than seen in the general population, and higher than prior reports for occupational petroleum exposure. In this proposed study, 240 men of reproductive age will be recruited, half in areas rich in UOG operations (< 5 miles) and half in nearby areas devoid of these activities (> 25 miles). Participants will collect urine and semen, and will complete questionnaires to assess demographics and exposures. Urine will be evaluated for UOGCs, their metabolites and reproductive hormones using high-resolution mass spectrometry. Participants will measure sperm motility using an FDA-approved phone app, and sperm count, morphology, DNA integrity and histone methylation will be measured in the laboratory. Outcomes: UOGC levels, hormone levels, and sperm measures, adjusted for questionnaire-derived factors, will be compared between exposed and unexposed men. Exposure will be calculated from home and work addresses, time spent at each location, and geocoded UOG well locations using inverse distance weighted well counts. Multivariable models will evaluate relationships between exposure and outcomes, adjusting for confounding variables. Completion of the proposed study will dramatically increase the understanding of UOGC exposure and male reproductive health; and will inform both healthcare providers and the UOG industry residential exposure and toxicity.

非常规石油和天然气 (UOG) 开采结合了定向钻井和水力压裂或 整个行业使用了 1000 多种 UOG 化学品 (UOGC)，废水中含有 另外 599 种化学物质中有数百种是已知或可疑的内分泌干扰化学物质 (EDC)。 UOG 作业造成空气污染以及地表水和地下水污染，使附近的人类暴露在外 大约有 1800 万美国人（占人口的 5%）通过吸入、皮肤接触和/或摄入。 居住在 UOG 站点 1 英里范围内的稳健研究报告了母亲的新生儿存在出生缺陷的情况。 居住在 UOG 活动场所附近，但未能区分母亲和父亲的接触情况。 只有六篇评估男性职业接触石油作业的高质量文章；没有一篇纳入其中 最近的研究强调了父亲暴露不仅对生育能力而且对生育能力的重要性。 还影响妊娠结局和后代健康。 在 UOG 站点附近的地表水和地下水中检测到的在体外、成人细胞中充当 EDC 雌性小鼠以及产前暴露的雄性和雌性小鼠的这项先前的工作表明了潜在的可能性。 暴露于 UOGC 的人类出现不良生殖结果，并作为该假设的基本原理： 男性居住地与 UOG 手术地点的接近程度与暴露的尿液生物标志物有关， 生殖激素紊乱、精子生成减少以及精子受损 在一项初步研究中，居住在暴露环境中的人的尿液中 UOGC 含量升高。 例如，反式，反式粘康酸 (ttMA)（一种苯代谢物）的检测水平几乎高出 5 倍 高于一般人群，也高于之前关于职业石油暴露的报告。 在这项拟议的研究中，将招募 240 名育龄男性，其中一半来自 UOG 手术丰富的地区（< 5 英里），一半在没有这些活动的附近地区（> 25 英里），参与者将收集尿液和精液， 并将完成问卷调查以评估人口统计数据和暴露情况，并评估尿液中的 UOGCs， 参与者将使用高分辨率质谱分析其代谢物和生殖激素。 使用 FDA 批准的手机应用程序测量精子活力，以及精子数量、形态、DNA 完整性和 组蛋白甲基化将在实验室进行测量：UOGC 水平、激素水平和精子。 根据调查问卷得出的因素进行调整后，将在暴露和未暴露之间进行比较 男性的暴露程度将根据家庭地址和工作地址、在每个地点花费的时间以及地理编码来计算。 将使用反距离加权多变量模型评估 UOG 井位置。 完成 拟议的研究将极大地增加对 UOGC 暴露和男性生殖健康的了解； 并将告知医疗保健提供者和 UOG 行业住宅暴露和毒性。