Neurologic function in children exposed to ambient manganese

接触环境锰的儿童的神经功能

• 批准号: 8274466
• 负责人: Roberto G Lucchini
• 金额: $ 54.69万
• 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/8274466
• 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; Gasoline; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Guidelines; Hair; Haplotypes; Health; Health Policy; Home environment; Impaired cognition; Industry; Ingestion; Inhalation Exposure; 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 deficiency; 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）：新兴证据表明，升高的环境锰（MN）暴露与儿童的认知和行为缺陷有关。然而，到目前为止，对儿童的研究仅专注于通过摄入途径暴露，尽管成年人的职业研究已经确定，通过吸入的MN暴露与通过摄入相比，通过吸入的MN暴露对认知和运动效应的风险更大。我们将评估11-13岁儿童居住在受到当前或过去的Ferroyaly行业影响的地区的11-13岁儿童中的神经发育影响。我们将在意大利布雷斯西亚省的三个特征性的研究地点进行750名儿童，这些儿童在铁合金植物活动的历史上有所不同：1）Bagnolo Mella，这是一个具有活跃的Ferroyaly植物的社区，可产生非常升高的空气MN水平； 2）Valcamonica，由于2001年结束的铁合成植物活动的史，空气MN水平略有升高的区域； 3）Garda Lake，一个具有背景空气MN水平的参考区域，没有铁合金植物活动的历史。该项目将建立在现有的欧盟资助的Phime（易感人群中混合元素暴露的公共卫生影响）研究的基础上，该研究已经检查了来自瓦尔卡马尼卡和加尔达湖的300名儿童；我们建议再注册450次，以实现我们的目标。我们建议的优势是强调环境暴露评估，利用24小时个人空中监视器的机载MN的措施，房屋中的MN水平沉积灰尘，自来水，污垢和详细的食物频率问卷，并与全面的认知，行为性，行为性，行为性，行为性，行为频率。 ，运动和感官评估，以及暴露生物标志物测量（血液，尿液，头发，指甲）和脱落牙齿中的MN，以评估早期生活和累积的终生暴露。初步结果表明，瓦尔卡马尼卡历史悠久的地区居民中运动协调，气味识别和智商的变化与空气MN水平有关。这项研究将提供独特的机会，通过评估三个暴露历史的儿童在不同的发育时间内比较MN的影响1）自出生以来连续高空空降MN暴露（Bagnolo Mella），2）在前3个中接触高空MN水平。 -5年后5年，但降低了当前的暴露（Valcamonica），而3）没有升高的空中MN暴露史（Garda Lake）。我们还将通过铁代谢途径基因中的遗传变异来解决遗传对MN的敏感性的作用。这将是对儿童中MN神经毒性的首次研究，这些儿童受环境MN暴露水平的深刻表征。 公共卫生相关性：拟议的研究将解决我们对儿童环境锰暴露升高所带来的健康风险的显着差距儿童11-13岁。这项研究还将研究遗传多态性如何影响暴露风险。这样的发现肯定会对未来的研究计划和公共政策有很大的影响，该计划旨在最大程度地减少与锰的暴露相关的发病率，尤其是在与铁缺乏，铅暴露和其他协变量有关的情况下。鉴于MMT在汽油中的潜在用途，这项研究还将有助于了解机载锰的潜在风险，这些风险可能通过在全球范围内引入这种基于锰的燃料而增加。这些知识将为全世界儿童接触的适当水平接触的公共卫生政策和准则提供信息。