Human biomonitoring: State of the art
Human biomonitoring: State of the art
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DOI：
10.1016/j.ijheh.2007.01.024
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发表时间：
2007-05-01
影响因子：
6
通讯作者：
Wilhelm, Michael
中科院分区：
文献类型：
--
作者：
Angerer, Juergen;Ewers, Ulrich;Wilhelm, Michael
当今，剂量和生化效应的人体生物监测(HBM)具有巨大的实用价值，为测量人类接触化学物质提供了一种有效和经济的手段。HBM考虑了所有吸收途径和所有相关来源，使其成为风险评估和风险管理的理想工具。HBM可以确定新的化学品暴露、趋势和暴露的变化，确定暴露在一般人群中的分布，确定易受伤害的群体和暴露较高的人群，并确定相对较低支出的特定污染地点的环境风险。此外，HBM方法的灵敏度使阐明污染物的人体代谢和毒性机制成为可能。因此，HBM既是科学家的工具，也是决策者的工具。到目前为止，血液和尿液是被批准最多的基质。可以对大多数化学物质进行HBM，这些物质是世界范围内环境医学讨论的焦点。这尤其适用于金属、多环芳烃、邻苯二甲酸盐、二恶英、杀虫剂，以及芳香胺、全氟化学品、环境烟草烟雾和挥发性有机化合物。蛋白质加合物，特别是Hb加合物，作为DNA加合物的替代品，非常特异和灵敏地测量暴露和生化效应，是一种比测量人体体液中的遗传毒性物质及其代谢物更好的估计癌症风险的手段。使用非常复杂但仍然适用的分析方法，今天常规地测定烷化剂、芳香胺和硝基芳香化合物的HB-加合物。为了扩大生化效应监测的范围，应进一步阐述将裂解和分离加合物蛋白质分子作为样品制备措施的方法。通过这种方式，所有加成部位以及其他蛋白质，如血清白蛋白，都可以用于HBM。DNA加合物表明一种化学物质的突变性以及癌症风险的增加。因此，DNA加合物将是HBM的理想参数。虽然有非常敏感的DNA加合物监测技术，如P32-后标记和免疫学方法，但它们缺乏特异性。为了阐明致癌机制，为了在流行病学研究中具有广泛的适用性和可比性，必须制定严格针对DNA加合物的化学结构的分析方法。然而，目前的分析可能性遇到了它们的边界。在暴露于遗传毒性化学物质的HBM研究中，特别是淋巴细胞DNA链断裂和白细胞中8-羟基-2‘-脱氧鸟苷(8-OHdG)的测量已经变得非常流行。然而，在职业或环境暴露与8-OHdG的诱导或链断裂的形成之间仍然缺乏良好的剂量反应关系，这限制了这些标记的适用性。人口研究中使用的大多数生物标记物都由标准操作程序(SOP)以及内部和外部质量评估计划涵盖。因此，来自全球领先实验室的HBM结果在分析上是可靠的，具有可比性。新出现的与环境相关的物质，如全氟化合物，可以在体液中快速评估，因为对于实验室来说，跟上仪器分析的进展变得越来越困难。尽管如此，达到HBM的最终顶峰将是值得的，因为这是识别和量化人类暴露和风险，阐明毒性影响机制，并最终决定是否必须采取措施减少暴露的唯一途径。没有HBM的风险评估和风险管理导致错误的风险估计，并导致措施不足。在一些国家，如美国和德国，数以千计的居民定期接受关于他们内部暴露于各种环境产生物质的调查。为评价健康管理结果，德国健康管理委员会详细说明了参考值和健康管理价值。(C)2007年爱思唯尔股份有限公司。版权所有。
Human biomonitoring (HBM) of dose and biochemical effect nowadays has tremendous utility providing an efficient and cost effective means of measuring human exposure to chemical substances. HBM considers all routes of uptake and all sources which are relevant making it an ideal instrument for risk assessment and risk management. HBM can identify new chemical exposures, trends and changes in exposure, establish distribution of exposure among the general population, identify vulnerable groups and populations with higher exposures and identify environmental risks at specific contaminated sites with relatively low expenditure. The sensitivity of HBM methods moreover enables the elucidation of human metabolism and toxic mechanisms of the pollutants. So, HBM is a tool for scientists as well as for policy makers. Blood and urine are by far the most approved matrices. HBM can be done for most chemical substances which are in the focus of the worldwide discussion of environmental medicine. This especially applies for metals, PAH, phthalates, dioxins, pesticides, as well as for aromatic amines, perfluorinated chemicals, environmental tobacco smoke and volatile organic compounds. Protein adducts, especially Hb-adducts, as surrogates of DNA adducts measuring exposure as well as biochemical effect very specifically and sensitively are a still better means to estimate cancer risk than measuring genotoxic substances and their metabolites in human body fluids. Using very sophisticated but nevertheless routinely applicable analytical procedures Hb-adducts of alkylating agents, aromatic amines and nitro aromatic compounds are determined routinely today. To extend the spectrum of biochemical effect monitoring further methods should be elaborated which put up with cleavage and separation of the adducted protein molecules as a measure of sample preparation. This way all sites of adduction as well as further proteins, like serum albumin could be used for HBM. DNA-adducts indicate the mutagenicity of a chemical substance as well as an elevated cancer risk. DNA-adducts therefore would be ideal parameters for HBM. Though there are very sensitive techniques for DNA adduct monitoring like P32-postlabelling and immunological methods they lack specificity. For elucidating the mechanism of carcinogenesis and for a broad applicability and comparability in epidemiological studies analytical methods must be elaborated which are strictly specific for the chemical structure of the DNA-adduct. Current analytical possibilities however meet their borders. In HBM studies with exposure to genotoxic chemicals especially the measurement of DNA strand breaks in lymphocytes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in white blood cells has become very popular. However, there is still a lack of well-established dose response relations between occupational or environmental exposures and the induction of 8-OHdG or formation of strand breaks which limits the applicability of these markers. Most of the biomarkers used in population studies are covered by standard operating procedures (SOPs) as well as by internal and external quality assessment schemes. Therefore, HBM results from the leading laboratories worldwide are analytically reliable and comparable. Newly upcoming substances of environmental relevance like perfluorinated compounds can rapidly be assessed in body fluids because there are very getting more and more difficult for the laboratories to keep up with a progress in instrumental analyses.In spite of this it will pay to reach the ultimate summit of HBM because it is the nly way to identify and quantify human exposure and risk, elucidate the mechanism of toxic effects and to ultimately decide if measures have to be taken to reduce exposure. Risk assessment and risk management without HBM lead to wrong risk estimates and cause inadequate measures. In some countries like in USA and in Germany, thousands of inhabitants are regularly investigated with respect to their internal exposure-to a broad range of environmentally occurring substances. For the evaluation of HBM results the German HBM Commission elaborates reference- and HBM-values. (C) 2007 Elsevier GmbH. All rights reserved.