Modelling and measurement of Cd exposure and pathology in human volunteers living in proximity to a smelter source

对居住在冶炼厂附近的人类志愿者的镉暴露和病理学进行建模和测量

• 批准号: NE/E00895X/1
• 负责人: David Spurgeon
• 金额: $ 5.59万
• 依托单位: NERC CEH (Up to 30.11.2019)
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FE00895X%2F1
• 关键词: Modelling; measurement; Cd; exposure; pathology

Exposure of people (and environmental species) to heavy metal (e.g. cadmium, lead, mercury, copper) pollution in air, water, soil and food can cause a range of health problems. Examples of diseases associated with exposure to metal pollution are known from many parts of the world, including mercury poisoning through eating contaminated fish in Japan and poisoning by the metalloid element arsenic of many thousands of people that drank waters from contaminated wells in Bangladesh and India. Closer to home in the UK, lead was widely implicated in a range of developmental impairments occurring in children living close to busy roads who were regularly subjected to exhaust smoke from cars using the old type of leaded petrol. Because it is not well excreted from the body after ingestion, the common environmental pollutant cadmium is one metal that has been implicated in as causing of human health problems in populations living close to industrial sources. The fact that this metal tends to accumulate in the kidney makes this organ particularly sensitive to cadmium toxicity. In this exploratory project, we bring together expertise from environmental science, medicine and epidemiology and fundamental biochemistry to investigate whether and to what extent exposure to cadmium causes kidney disease. The study is focused on the area around the town of Avonmouth on the Severn Estuary near Bristol which was until recently home to one of the world's largest cadmium/lead/zinc smelters. During the active life of the plant (1928-2003), significant quantities of cadmium and other metals (including Pb, Hg and Zn) were released, contaminating the environment and exposing local residents (~50,000 people live within 5 km of the smelter). The countryside around the smelter is known to be badly contaminated with these metals and studies of their impacts on plants and animal have revealed toxic effects at locations many kilometers from the factory. Surprisingly, however, the impacts on the toxic metals on the human population are not well understood. To address this, this study will provide information on the effects of metal pollution at Avonmouth on local residents. The information gathered will be beneficial for assessing the wider effects of the cadmium pollution that is still occurring in many parts of the UK (particularly urban areas) on people's health and wellbeing. Our approach to assessing the potential for toxic effects on people in the area polluted by the smelter are to: - measure the amount of cadmium in aerial dust, soil and home grown vegetables that represent the main routes of human exposure; - use these measurements of cadmium concentration as input to existing human environmental exposure assessment methods that are used by regulatory agencies to predict cadmium exposure at contaminated sites and validate these assessments by comparing exposure predictions to measured cadmium concentrations in urine collected (in an existing project) from 200 human volunteers from known postcode locations at Avonmouth; - measuring the concentrations of the small molecules produced by normal metabolism that are present in human urine (e.g. amino acid, sugars, components of DNA and RNA) samples collected from the 200 volunteers and comparing these results to existing information on renal toxicity to establish how cadmium exposure affects kidney health for persons living in postcodes in the Avonmouth area with high, moderate and low levels of cadmium present in air, water, soil and home grown food. By funding this project, NERC would be making an investment in research that addresses fundamental issues in environment and human health research (the link between the amount of a pollutant in the environment, the amount entering the human body and the ultimate toxic effect) and would generate novel data, on human samples, cross-referenced to existing toxicity and geographical pollutant data at a real site.

在空气，水，土壤和食物中，人（和环境物种）暴露于重金属（例如镉，铅，汞，铜）污染可能会导致一系列健康问题。来自世界许多地方的疾病例子是与金属污染相关的疾病，包括通过在日本吃污染的鱼来中毒，以及数千人在孟加拉国和印度污染水域喝水的金属元素砷中毒。在英国更靠近家中，铅在靠近繁忙的道路的儿童中广泛牵涉到一系列发育障碍，他们经常使用旧类型的有铅汽油的汽车从汽车中遇到烟气。由于摄入后它没有从身体中排出，因此普通的环境污染物镉是一种金属，它被牵涉到造成人类健康问题的人群中，这是靠近工业来源的人群。这种金属倾向于在肾脏中积聚的事实使该器官对镉毒性特别敏感。在这个探索性项目中，我们将环境科学，医学和流行病学和基本生物化学的专业知识汇集在一起​​，以研究是否以及在何种程度上暴露于镉会引起肾脏疾病。这项研究集中在布里斯托尔附近的塞文河口埃文茅斯镇周围的地区，直到最近才是世界上最大的镉/铅/锌冶炼厂之一。在该工厂的活跃寿命（1928-2003）期间，释放了大量数量的镉和其他金属（包括PB，HG和Zn），污染了环境并暴露了当地居民（约50,000人居住在冶炼厂5公里以内） 。众所周知，冶炼厂周围的乡村受到这些金属的严重污染，并且对它们对植物和动物的影响的研究揭示了距工厂许多公里的地方的有毒作用。然而，令人惊讶的是，对有毒金属对人类人口的影响尚不清楚。为了解决这个问题，这项研究将提供有关金属污染对雅芳茅斯对当地居民的影响的信息。收集的信息将有益于评估英国许多地区（尤其是城市地区）对人们的健康和福祉的镉污染的更广泛影响。我们评估对冶炼厂污染地区有毒影响潜力的潜在影响的方法的方法是： - 测量代表人类暴露的主要途径的空中灰尘，土壤和家庭种植的蔬菜中的镉量； - 使用这些测量镉浓度作为对现有的人类环境暴露评估方法的输入，该方法被监管机构使用，以预测受污染部位处的镉暴露，并通过将暴露预测与所测量的镉浓度进行比较，以验证这些评估。来自雅芳县已知邮政编码位置的200名人类志愿者。 - 测量由正常代谢产生的小分子的浓度，这些分子存在于人类尿液（例如氨基酸，糖，DNA和RNA的成分）中，这些分子是从200名志愿者那里收集的，并将这些结果与现有的有关肾脏毒性的信息进行比较镉暴露会影响居住在雅芳茅斯地区邮政编码的人的肾脏健康，而空气，水，土壤和家庭种植的食物中存在高，中和低水平的镉。通过为该项目提供资金，NERC将对研究环境和人类健康研究基本问题的研究进行投资（环境中污染物的数量之间的联系，进入人体的数量和最终的毒性效应之间的联系）将在人类样品上生成新的数据，与真实部位的现有毒性和地理污染物数据交叉引用。

项目成果

Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population.

• DOI: 10.1186/1741-7015-10-61
• 发表时间: 2012-06-19
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Ellis JK;Athersuch TJ;Thomas LD;Teichert F;Pérez-Trujillo M;Svendsen C;Spurgeon DJ;Singh R;Järup L;Bundy JG;Keun HC
• 通讯作者: Keun HC

Variance and covariance heterogeneity analysis for detection of metabolites associated with cadmium exposure.

用于检测与镉暴露相关的代谢物的方差和协方差异质性分析。

• DOI: 10.1515/sagmb-2013-0041
• 发表时间: 2014
• 期刊: Statistical applications in genetics and molecular biology
• 影响因子: 0.9
• 作者: Salamanca BV