Neurologic function in children exposed to ambient manganese

接触环境锰的儿童的神经功能

• 批准号: 7950317
• 负责人: Roberto G Lucchini
• 金额: $ 59.39万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950317
• 关键词: 13 year old; Ablation; Address; Adult; Age; Air; Animals; Area; Behavioral; Biological; Biological Markers; Birth; Blood; Breathing; Chemicals; Child; Child Support; Childhood; Cognitive; Communities; Coupled; Critical Pathways; Databases; Dental Enamel; Dentin; Deposition; Development; Dose; Dust; Elements; Enrollment; Environmental Exposure; Epidemiology; Exposure to; Fingers; Food; Frequencies; Funding; Future; Gasoline; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Guidelines; Hair; Haplotypes; Health; Health Policy; Home environment; Impaired cognition; Industry; Ingestion; Inhalation Exposure; Iron; Italy; Knowledge; Lasers; Lead; Life; Link; Literature; Manganese; Measurable; Measures; Metabolism; Modeling; Monitor; Morbidity - disease rate; Motor; Nail plate; Nebraska; Nervous System Physiology; Occupational; Occupational Exposure; Odors; Oral; Outcome; Pathway interactions; Performance; Plants; Population; Population Study; Principal Investigator; Province; Public Health; Public Policy; Questionnaires; Reaction Time; Recording of previous events; Research; Risk; Role; Route; Sensory; Single Nucleotide Polymorphism; Site; Soil; Testing; Time; Tooth structure; Tremor; Urine; Water; Work; air monitoring; base; behavioral health; cohort; critical period; deciduous tooth; design; early childhood; early life exposure; genetic variant; iron metabolism; lead exposure; neurodevelopment; neurotoxic; neurotoxicity; neurotoxicology; operation; performance tests; population based; postnatal; prenatal; programs; public health relevance; residence

DESCRIPTION (provided by applicant): Emerging evidence demonstrates that elevated environmental manganese (Mn) exposure is associated with cognitive and behavioral deficits in children. However, up to now, studies in children have only been focused on exposure via ingestion pathways, although occupational research in adults has established that Mn exposure via inhalation poses a more significant risk for cognitive and motor effects than exposure via ingestion. We will assess the neurodevelopmental effects of airborne Mn exposure in 11-13 year old children living in areas impacted by current or past ferroalloy industries. We will examine 750 children across three well- characterized study sites in the province of Brescia, Italy, that differ in history of ferroalloy plant activity: 1) Bagnolo Mella, a community with an active ferroalloy plant that produces very elevated air Mn levels; 2) Valcamonica, a region with slightly elevated air Mn levels due to a history of ferroalloy plant activity that ended in 2001, and; 3) Garda Lake, a reference region with background air Mn levels and no history of ferroalloy plant activity. The project will build upon the existing EU-funded PHIME (Public Health Impact of Mixed element Exposure in susceptible populations) study that has already examined a total of 300 children from Valcamonica and Garda Lake; we propose to enroll 450 more to achieve our aims. A strength of our proposal is the emphasis on environmental exposure assessment, utilizing measures of airborne Mn with 24 hr personal air monitors, Mn levels in home deposited dust, tap water, soil, and a detailed food frequency questionnaire, coupled with comprehensive cognitive, behavioral, motor, and sensory assessments, along with exposure biomarker measures (blood, urine, hair, nails) and Mn in shed deciduous teeth to assess early life and cumulative lifetime exposures. Preliminary results show changes in motor-coordination, odor identification and IQ among the residents in the historically exposed area of Valcamonica are associated with air Mn levels. This study will offer the unique opportunity to compare effects of Mn at distinct developmental time periods by evaluating children with three exposure histories 1) continuous high airborne Mn exposure since birth (Bagnolo Mella), 2) exposure to high air Mn levels over the first 3 - 5 postnatal years, but reduced current exposure (Valcamonica), and 3) no history of elevated airborne Mn exposure (Garda Lake). We will also address the role of genetic susceptibility to Mn via genetic variation in iron metabolism pathways genes. This will be the first study on Mn neurotoxicity in children supported by a profound characterization of environmental Mn exposure levels. PUBLIC HEALTH RELEVANCE: The proposed studies will address a significant gap in our understanding of the health risks posed by elevated environmental manganese exposure in children by defining in detail the link between early life or continuous exposure and cognitive, behavioral, motor, and sensory deficits in children age 11-13 years. This research will also investigate how genetic polymorphisms influence exposure risk. Such findings will surely be powerful influences on future research initiatives and public policy directed at minimizing the morbidity associated with manganese exposure, especially when associated with iron deficiency, lead exposure and other covariates. Given the potential use of MMT in gasoline, this study will also contribute to understanding the potential risk from airborne manganese that may be increased by the introduction of this manganese-based fuel worldwide. This knowledge will inform public health policies and guidelines on suitable levels of manganese exposure to children worldwide.

描述（由申请人提供）：新出现的证据表明，环境锰 (Mn) 暴露水平升高与儿童的认知和行为缺陷有关。然而，到目前为止，对儿童的研究仅集中于通过摄入途径接触锰，尽管对成人的职业研究已经证实，通过吸入接触锰对认知和运动影响的风险比通过摄入途径接触锰的风险更大。我们将评估生活在受当前或过去铁合金行业影响的地区的 11-13 岁儿童接触空气中的锰对神经发育的影响。我们将对意大利布雷西亚省三个特征明确的研究地点的 750 名儿童进行检查，这些地点的铁合金工厂活动历史不同：1) Bagnolo Mella，一个拥有活跃铁合金工厂的社区，该工厂产生的空气中锰含量非常高； 2) Valcamonica，由于铁合金工厂活动于 2001 年结束，该地区空气中锰含量略有升高； 3) 加尔达湖，一个具有背景空气锰水平且没有铁合金工厂活动历史的参考区域。该项目将建立在欧盟资助的现有 PHIME（易感人群混合元素暴露的公共健康影响）研究的基础上，该研究已经对来自瓦尔卡莫尼卡和加尔达湖的总共 300 名儿童进行了检查；我们建议再招收 450 名学生以实现我们的目标。我们建议的优势在于强调环境暴露评估，利用 24 小时个人空气监测仪测量空气中的锰含量、家庭沉积灰尘、自来水、土壤中的锰含量以及详细的食物频率调查问卷，再加上全面的认知、行为、运动和感觉评估，以及暴露生物标志物测量（血液、尿液、头发、指甲）和脱落乳牙中的锰，以评估生命早期和累积的终生暴露。初步结果显示，Valcamonica 历史暴露地区居民的运动协调性、气味识别和智商的变化与空气中的锰水平有关。这项研究将提供独特的机会，通过评估具有三种暴露史的儿童来比较锰在不同发育时期的影响：1）自出生以来连续高空气中锰暴露（Bagnolo Mella），2）在前 3 年内暴露于高空气锰水平- 出生后 5 年，但当前暴露量减少 (Valcamonica)，并且 3) 没有空气中锰暴露量升高的历史 (Garda Lake)。我们还将通过铁代谢途径基因的遗传变异来探讨对锰的遗传易感性的作用。这将是第一项关于儿童锰神经毒性的研究，得到了环境锰暴露水平的深刻表征的支持。 公共健康相关性：拟议的研究将通过详细定义生命早期或持续接触与儿童认知、行为、运动和感觉缺陷之间的联系，解决我们对儿童环境锰暴露增加所造成的健康风险的理解上的重大差距。 11-13 岁的儿童。这项研究还将调查遗传多态性如何影响暴露风险。这些发现肯定会对未来的研究计划和公共政策产生重大影响，这些研究计划和公共政策旨在最大限度地减少与锰接触相关的发病率，特别是与缺铁、铅接触和其他协变量相关时。鉴于 MMT 在汽油中的潜在用途，这项研究还将有助于了解空气中锰的潜在风险，这种风险可能会因在全球范围内引入这种锰基燃料而增加。这些知识将为公共卫生政策和指南提供有关全球儿童锰接触适当水平的信息。