TTC原则在食品毒理学安全性评价中的应用

据估算，目前自然界存在10万多种天然化合物以及500多种人造化合物，人体暴露于如此众多的化学物质环境中，对人类的健康安全构成巨大威胁。如果按照传统毒理学安全性评价原则，需要对每个化合物进行逐一的动物毒性试验，这显然要耗费大量的时间、人力和物力资源。相反，毒理学关注阈值（TTC原则）反映了结构上类似的化学物质的安全暴露水平阈值。当对食品中含有的化合物进行毒理学安全性评价时，依据TTC原则就能够排除针对低浓度、无健康危害的化学物质开展的动物毒性试验，避免了资源的浪费和大量实验动物的使用，保障了实验动物的福利。现对TTC原则在食品毒理学安全性评价中的应用做一综述。     

毒理学中心法则的重新审视——毒物兴奋性剂量－反应关系及其对毒理学发展的影响

剂量 反应关系是毒理学的重要概念 ,一直用于对化学品、药物、物理等有害因素进行毒性预测和外推 ,公共卫生管理部门以此为基础进行有害因素的危险度评价 ,并制定相应的管理法规和控制措施。最近毒理学界提出了一种新的剂量 反应关系模型 ,即毒物兴奋效应模型 ,对过去公认的阈值模型和线性非阈值模型提出了挑战。本文对毒物兴奋效应模型的概念及其在环境、医学、公共卫生领域产生的影响及引起的讨论作一介绍     

化学品毒理学安全性评价面临的问题及动物实验替代方法研究的机遇和现状

随着化学品的种类和数量逐年增加,其损害人类健康和污染环境的潜在危险性越来越突出.对化学品进行毒理学安全性评价是化学品安全管理的前提.由于国际范围内对化学品安全管理的加强以及对化学品登记资料要求的提高,需要开展大量的化学品毒理学评价工作.本文将主要论述由此而引起的诸如动物权益保护等方面的问题以及由此带来的动物实验替代方法研究的机遇.     

081 毒理学中心法则的重新审视--毒物兴奋性剂量-反应关系及其对毒理学发展的影响

剂量-反应关系是毒理学的重要概念,一直用于对化学品、药物、物理等有害因索进行毒性预测和外推,公共卫生管理部门以此为基础进行有害因索的危险度评价,并制定相应的管理法规和控制措施.最近毒理学界提出了一种新的剂量-反应关系模型,即毒物兴奋效应模型,对过去公认的阈值模型和线性非阈值模型提出了挑战.本文对毒物兴奋效应模型的概念及其在环境、医学、公共卫生领域产生的影响及引起的讨论作一介绍.     

毒理学关注阈值方法在农药活性成分转化产物慢性膳食风险评估中的应用

目的 以氨基甲酸酯类农药抗蚜威为模式化学物,建立可用于农药活性成分转化产物的慢性膳食暴露评估方法.方法 建立基于Cramer结构分类的毒理学关注阈值(TTC)决策树方法,利用Lazar软件对7种抗蚜威活性成分转化产物(R34836、R34885、R35140、R31805、R34865、R16210和R16192)的遗传毒性进行预测.利用2002年中国居民营养与健康状况调查数据和2011年全国污染物监测网中抗蚜威活性成分残留的监测数据,估计我国全人群以及不同年龄组人群抗蚜威活性成分转化产物的慢性膳食暴露,并按照TTC决策树方法对其进行风险评估.结果 在抗蚜威活性成分转化产物的慢性膳食暴露中,2～6岁年龄段的均值和高端(第97.5百分位数,P97.5)暴露量均最高,7种转化产物即R34836、R34885、R35140、R31805、R34865、R16210和R16192的平均暴露量分别为0.0290、0.0207、0.0015、0.0320、0.0005、0.6918和0.1274 μg/kg,高端暴露量分别为0.0817、0.0581、0.0042、0.0900、0.0014、1.9459和0.3585 μg/kg.其中又以转化产物R16210的慢性暴露最大,分别为0.6918、1.9459μg/kg,分别占TTC阈值的46.12％和129.73％.结论 TTC决策树方法是一种有效的风险评估工具,可用于农药活性成分转化产物的优先筛选和初步评估.     

简易快速推算有害物质近似的最高容许浓度的方法(一)

根据联合国环境规划署下设的“潜在有毒化学品国际登记中心”的估计,当今在全世界已知的化学品超过500万种,其中常用的约有60,000种,同时每年约有近1,000种新化学物质投入市场,致使环境中存在着为数众多的各种潜在的有毒化学品,它们污染环境、影响人体健康。在上述化学品中只有少数是经过充分的预防毒理学评价和进行过对人群健康影响的流行病学调查。在我国《工     

医疗器械免疫毒理学试验原则与方法——介绍ISO/TS 10993-20:2005

医疗器械和材料的某些成分和降解产物可能会使人体免疫系统产生免疫应答(免疫毒性),因此医疗器械和材料对人体免疫系统的影响已引起越来越多的关注。ISO/TC194目前正在制定ISO/TS10993-20《医疗器械生物学评价第20部分:医疗器械免疫毒理学试验原则与方法》,标准给出了医疗器械对免疫系统不良作用方面的评价与试验指南。本文将系统介绍ISO/TS10993-20:2005,并给出免疫毒理学实验设计等相关信息。     

二苯甲酮类紫外吸收剂人体暴露的研究进展

二苯甲酮类紫外吸收剂广泛应用于具有防晒功能的化妆品、塑料包装材料和农用化学品中,可通过饮食、呼吸和皮肤接触等途径进入人体。最新毒理学研究表明,二苯甲酮类紫外吸收剂具有明显的遗传毒性、生殖毒性、内分泌干扰效应及雌激素活性,已成为环境科学、毒理学和医学领域新的研究热点。该文综述了国内外关于二苯甲酮类紫外吸收剂的毒理学、人体暴露以及分析方法的研究进展,为我国开展相关研究提供参考。     

世界卫生组织欧洲区域办公室卫生毒理学出版物介绍

评价化学品对人体健康及周围环境的影响,是世界卫生组织活动的一个重要方面。自从1979年起,与其他国际机构(国际劳工组织——ILO,联合国环境规划机构——UNEP,潜在有毒物质的国际登记机构——IRPTC)一起实施化学品的国际安全规划。根据化学品国际安全规划的一系列任务,赋予世界卫生组织欧洲区域办公室的工作为国际合作与协调,该区域办公室在1979年第29次会议上确定其工作为四个基本方面:1、干部培养,包括培养医学毒理学工作     

国外“预防毒理学”文献资料源概述(四)

二世界环境环境管理与卫生环境致突变,环境污染,环境研究二环境科学与技术.环境毒理学与化学 试验性的肺的研究 食品与化学品毒理学 食品与化妆品毒理学二食品、药品、化妆品法学杂志 基础及应用毒理学 人体和实验毒理学,体外毒理学 吸入毒理学,国际临床药理学、治疗和毒理 学杂志,国际环境分析化学杂志药理学,免疫学一科学情报研究所科学图表美利坚学院的毒理学杂志分析毒理学杂志应用毒理学杂志,生物化学毒理学杂志环境病理学和毒理学杂志Environment Internatfonal·Pergamon Press,HeadingtonH让1 Hall,ox为rd 0X3 OBW,U .K.Envjr…     

Food and Drug Administration: approach to evaluating neurotoxicity

One of the primary features of the mission of the Food and Drug Administration is to assure with reasonable certainty that no harm will result from the intended use of chemicals added to food. In carrying out this mission the FDA uses a structured process to assess the safety of each food chemical. The detailed mechanics of this process are described in an FDA document entitled "Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Use in Food" (Food and Drug Administration, 1982). Central to its evaluation the FDA requires a collective set of information, including estimates of the anticipated human exposure to the food chemical and a broad-based toxicological profile. Certainly, any adverse effect observed in the nervous system is recognized as an important element in the determination of chemical safety and follow-up information which would enable an assessment of such an effect to be included in the toxicological profile. The agency's current approach to evaluating neurotoxicity should be viewed within the context of its overall strategy for the safety assessment of food chemicals. Four basic premises underlie the FDA's approach to safety assessment.     

Sicherheitsfaktoren in der Risikobewertung von Chemikalien

Risk assessment of chemicals is based on data from experimental exposure of animals. Departing from the dose/concentration at which no toxic effects have been observed in animals (no observed adverse effect level, NOAEL), the dose/exposure in humans that will not result in toxic effects is derived by extrapolation done in two steps.Step one is the extrapolation from animal to man and, traditionally, a safety factor of 10 is used to account for differences in toxicokinetics and in toxicodynamics.Likewise, a safety factor of 10 is used in step two, which takes differences into account between the “median” human and the whole population including the sensitive subpopulation.There is increasing awareness that substance-specific factors should be used if data exist.Some regulators apply additional factors to account for uncertainty in the data and model uncertainties. The concept of safety factors is used to derive “safe” levels of exposure or “safe” doses.Application of the margin of safety (MOS) approach is different in which the distance is evaluated between a relevant level of toxicity (NOAEL) in animals and the level of exposure in humans.This approach is used when,e.g., food contamination with levels higher than safe levels have been found.The MOS approach is also used in chemical risk assessment. As the public often does not understand the assumptions behind safe levels, lay people associate levels higher than the safe levels with acute health risks.     

On-farm contamination of animals with chemical contaminants

Food products should not contain unsafe levels of chemical contaminants. However, it is not possible to monitor each and every one of the many thousands of chemicals that are used in our advanced societies. Chemical contaminants in foodstuffs of animal origin may be classified into three categories: natural contaminants (e.g. mycotoxins), environmental contaminants linked to industrialisation and/or urbanisation (e.g. dioxins and dioxin-like compounds) and authorised chemical products (e.g. residues of veterinary medical products). Chemical hazards may contaminate foodstuffs of animal origin all the way from farm to fork. Contamination may occur in any of the different production systems, and it is difficult to make comparisons between production systems (e.g. extensive versus intensive farming systems) with regard to food safety. Even when we take into account the latest analytical methods, which can detect ever-smaller quantities of residues, the relative importance of chemical contaminants seems to have declined during recent decades due to improvements in information and prevention. Nonetheless, individual incidents can never be ruled out and may have serious economic, health or social repercussions. Particular attention must be paid to chemical hazards, in order to reduce as much as possible the risks to livestock and to the consumer. Continued monitoring and periodic reassessment of risks posed by these contaminants (at the national level) are needed to detect or anticipate new problems, so that appropriate actions can be taken in the interest of public health. More attention should be paid to the production of detailed information, especially with regard to background data (e.g. the objectives of the monitoring, sampling methods, chemicals to be analysed, analytical methods, detection limits, raw data and specified units), in order to obtain a better basis for risk assessment. Such risk assessment provides control authorities with an effective tool for the exchange of information and measures to be taken to ensure food safety.     

Chemical compound safety: typology of competency accreditation for assay centers and analytical laboratories

The use of chemicals warrants many benefits on which modern society is entirely dependent. On the other hand, the lack of reliable information about the impact of the use of chemicals raises increasing concern. In order to guarantee the safety of chemicals it is mandatory to proceed to risk assessment, which in turn consists of hazard evaluation and exposure estimation. These activities are strictly dependent upon the availability of reliable data and information, produced by, e.g., test facilities, test laboratories and clinical laboratories, the specific competence of which has been properly recognised. All this applies in the pre-marketing phase as well as during the use of chemical substances. In this latter phase it is necessary to carry out an appropriate monitoring of environment, food and, in specific situations, human beings (biological monitoring). In the field of chemical safety, standards, legal instruments and operative instruments are nowadays available. These tools make it possible to assess both the quality of data and the competence of the entities involved in the production of the data themselves.     

2000-2009年中国食品化学污染物监测概况与分析

目的了解中国食品安全状况以及为食品安全监管政策的制定提供科学数据。方法通过食品化学污染物监测计划制定、工作手册编制、技术培训、质量控制考核、数据收集、审核与统计等措施与步骤在中国部分地区开展监测工作。结果连续10年在16个省市共累计监测了14大类食品和129项化学指标,建立了105万多个监测数据的数据库;监测结果显示中国食品安全形势总体稳定并保持向好趋势,但也存在一些食品安全问题;监测数据已被用于食品安全预警、监管、风险评估和标准制定。结论 10年监测掌握了监测食品中化合物的污染水平及其动态趋势,为政策法规的制定提供了科学数据,为覆盖全国的食品污染物监测奠定了基础。     

毒作用模式和有害结局路径的关系及其在风险评估中的应用

风险评估方法是保障人类健康和环境安全的必要技术手段。基于动物实验获取毒性数据的传统风险评估,由于动物实验通量低、周期长、成本高和高剂量外推至人类暴露剂量的不确定性等问题,难以满足大量化学品亟需开展风险评估的需求。毒作用模式(MOA)和有害结局路径(AOP)风险评估框架的提出为我们开发新型、高效的评价方法指明了方向。本综述介绍了MOA和AOP的基本概念、内容以及两者之间的关系,并以丙烯酰胺(AA)为例,简述MOA/AOP框架在化学物风险评估中的具体应用,以期为更好运用MOA/AOP框架进行化学物风险评估提供理论指导。     

Tales of acute risk assessment: health effects made out of whole cloth

BACKGROUND: Risk assessment utilizes human and animal studies and mathematical models to arrive at threshold exposures for toxic effects of various chemicals. In 1995 the Environmental Protection Agency (EPA) formed an acute risk assessment committee to assist in the planning for worst case chemical releases. The National Advisory Committee for Acute Exposure Guideline Levels (AEGL) examines the toxicological properties and studies of each chemical and then recommends appropriate levels. For the majority of chemicals, the committee relies on animal data (where the most data exists) supplemented with a limited number of human studies. In some cases, human studies are relied on to derive AEGL values. METHODS: In the published levels for hydrogen cyanide (HCN), the AEGL committee used five human studies and a "weight-of-the-evidence" approach. A number of these studies did not investigate adverse health effects, however, the AEGL committee used these studies as evidence that no health effect occurred. In addition, a number of other errors in conflict with well accepted principles of industrial hygiene were made. CONCLUSION: In order to adequately evaluate human studies, risk assessment committees must be composed of a balance of professionals with a wide variety of expertise, including epidemiology and industrial hygiene.     

The relationship of bioaccumulative chemicals in water and sediment to residues in fish: a visualization approach

A visualization approach is developed and presented for depicting and interpreting bioaccumulation relationships and data (i.e., bioaccumulation factors [BAFs], biota-sediment accumulation factors [BSAFs], and chemical residues in fish) using water-sediment chemical concentration XY plots. The approach is based on five basic parameters that affect bioaccumulation of nonionic organic chemicals: The distribution of chemical between sediment and water, the hydrophobicity of the compound (expressed as the n-octanol/water partition coefficient, K(OW)), the relationship of food chains to water and sediment, the length of the food chains, and the degree to which the chemical is metabolized. The visualization approach using water-sediment XY plots captures and visually presents the existing bioaccumulation knowledge in a form that is readily understandable from chemical, biological, and ecological aspects and, therefore, useful in the assessment, communication, and management of risk for persistent bioaccumulative toxicants.     

Accreditation of analytical laboratories and proficiency testing: experiences from Thailand on the issues of pesticide analysis.

Thailand, the economic growth of which largely depends on agriculture-based industry, recognizes the importance of international standards for harmonization of international food trade and for protection of human health from chemicals used as food additives or those present as contaminants. Pesticides which are widely used in Thailand are the anticholinesterase pesticides, pyrethroids, coumarin derivatives, bipyridinium salts, and to some extent organochlorine compounds such as DDT in malaria control. Proficiency testing and accreditation of laboratories are recognized as effective means to ensure quality and validity of data and to enable adequate risk assessment of pesticide residues in food, work environment and environment in general. The paper is a synthesis of relevant local reviews and in-depth interviews with experts in the area of pesticide laboratory accreditation and proficiency testing. The paper refers to other schemes for quality assurance such as ISO guide 25, ISO 9000, and ISO 14000, and addresses future prospects of ongoing activities such as accreditation of inspection bodies in the area of industrial chemicals and occupational safety and health.     

How university researchers can contribute to farm-to-table risk assessments: Listeria monocytogenes as an example

As a part of the Sanitary and Phytosanitary (SPS) agreement, the World Trade Organization requires that member countries establish SPS measures on the basis of an appropriate risk assessment. In addition, many governments use risk assessment in their management of food safety. Consequently, a number of risk assessments for different foodborne pathogens have been conducted. Risk assessments have also been successfully used as a research tool. While, historically, risk assessments are typically initiated by government agencies, university-based researchers are increasingly becoming involved in risk assessments. The purpose of this article is to illustrate the role that university researchers can play in the development and refinement of food safety risk assessments, including possible roles in (1) de novo development or refinement of risk assessment (including farm-to-table risk assessment), (2) data collection supporting risk assessments, and (3) development of new methodological techniques. Transmission of the foodborne pathogen Listeria monocytogenes through the food production chain and risk assessments addressing transmission of this pathogen are used as an example to highlight the roles of university researchers in food safety risk assessments.