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考虑到欧洲食品安全局(European Food Safety Authority,EFSA)科学委员会和科学小组进行风险评估时使用透明、科学、合理方法的需要,EFSA请求科学委员会对基准剂量(benchmark dose,BMD)使用情况的已有资料进行评价,作为对传统使用的未观察到有害作用水平(no observed adverse effect level,NOAEL)方法的替代,并对EFSA是否应该使用BMD方法以及在何种情况下使用此方法较为合适提供建议。同时请求科学委员会就如何使用BMD方法来分析实验研究获得的剂量-反应数据提供指导,并探讨在观察流行病学研究数据处理中使用该方法的可能性。最后,科学委员会还需对用BMD方法确定参考点时是否需要选择恰当的不确定系数提供建议。依惯例,当实验动物数据用于食品中无遗传毒性或无致癌性物质的风险评估时,该物质的临界效应—NOAEL和/或最低可观察到的有害作用水平(lowest observed adverse effect level,LOAEL)形成了推导健康指导值(如每日容许摄入量,ADI)的参考点。此方法仅适应于定性资料分析,而不适应于定量数据的处理。相反,BMD方法拓展了动物实验或观察流行病学研究获得的剂量-反应数据的适用范围,可更好地描述潜在风险的特征并将其量化。尽管EFSA的某些科学小组偶尔也使用BMD方法,但到目前为止,EFSA尚未系统地使用过此方法。此外,也时常收到用于BMD计算的实验数据。EFSA科学委员会在之前的意见中也提到过用BMD方法推导具有遗传毒性和致癌性物质暴露限值的参考点。在对BMD和NOAEL方法推导风险评估参考点的优点和局限性进行比较之后,科学委员会认为:由于BMD方法拓展了可用的剂量-反应数据的使用范围,且对剂量-反应数据中的不确定性进行了量化,因此在推导参考点时,BMD是一种更科学、更先进的方法。作为特定基准反应的结果,用BMD方法推导出的参考点更加一致。目前可用软件进行BMD分析,科学委员会注意到其正在发展,并预期在不远的将来在诸如模型平均化及连续数据分析方面会有重大发展。科学委员会同时认为,当修订毒性试验指南(如OECD指南)时,BMD方法的某些具体方面也应考虑修订。从大量风险评估的平均结果来看,用BMD方法获得的健康指导值,预计与那些用NOAEL方法推导出的指导值一样具有保护性。因此,目前采用的针对不确定系数的默认值仍然是恰当的,不需要设定额外的不确定系数。由于BMD和NOAEL方法的均值具有可比性,因此科学委员会认为没有必要使用BMD方法对以前所做的评估再重复一遍。只有当人类暴露量接近ADI时,才有必要完善以前的风险评估结果,此时BMD方法的应用方具有特殊价值。BMD方法适用于食品中不同类别或来源的所有化学物质,如杀虫剂、食品添加剂或污染物。BMD方法在下列情况下使用具有特殊价值:(1)NOAEL不能确定的情况;(2)在物质既有遗传毒性又有致癌性的情况下,为暴露限值提供参考点;(3)观察流行病学资料中的剂量-反应评估。短期内,应大力提倡EFSA科学小组及单位在上述情况中采用BMD方法。从长远来看,科学委员会预计BMD将作为一种备选方法用于确定参考点,以便推导健康指导值及暴露限值。为此,考虑到该方法的引进和EFSA广泛使用的实际情况,同时认识到它的应用需要专家水平的判断以及建模专业知识等,科学委员会提议,对科学小组和EFSA内部专家提供剂量-反应建模以及软件使用的培训。科学委员会要在此后的两年时间内对BMD方法在EFSA工作中的实施情况、经验及接受程度等进行审查。
Taking into account the need for a transparent, scientific and rational approach to risk assessment by the Scientific Committee and the Scientific Panel of the European Food Safety Authority (EFSA), the EFSA requested that the Scientific Board review the use of benchmark dose (BMD) Information is available as an alternative to the NOAEL method used conventionally, and it is more appropriate to provide recommendations on whether the EFSA should use the BMD method and under what circumstances . The Scientific Council is also requested to provide guidance on how to use the BMD method to analyze dose-response data from experimental studies and to explore the possibility of using the method in observing epidemiological data processing. Finally, the Scientific Committee needs to advise on the need to select the appropriate Uncertainty Factor when determining the reference point using the BMD method. Traditionally, when experimental animal data are used to assess the risk of non-genotoxic or non-carcinogenic substances in foodstuffs, the critical effect of this material, -NOAEL and / or the lowest observed adverse effect level (LOAEL ) Formed the reference point for deriving health guideline values (eg daily allowable intake, ADI). This method is only suitable for qualitative data analysis, but not for quantitative data processing. In contrast, the BMD approach extends the scope of animal experiments or observation of dose-response data from epidemiological studies to better characterize and quantify potential risks. Although some of EFSA’s scientific teams use the BMD method occasionally, so far, EFSA has not systematically used this method. In addition, experimental data for BMD calculations are also received from time to time. In its previous comments, the EFSA Scientific Committee also referred to the use of the BMD method to derive reference points for genotoxic and carcinogenic exposure limits. After comparing the pros and cons of deriving risk assessment reference points for the BMD and NOAEL methods, the Scientific Board considers that since the BMD approach broadens the range of available dose-response data and imposes uncertainties on dose-response data As a result, BMD is a more scientific and advanced method for deriving reference points. As a result of a particular benchmark response, the reference points derived using the BMD method are more consistent. Currently available software is BMD analysis, and the Scientific Committee notes that it is evolving and anticipates significant developments in areas such as model averaging and continuous data analysis in the near future. At the same time, the Science Council believes that when it comes to revising the guidelines for toxicity testing (such as the OECD Guidelines), some specific aspects of the BMD approach should also be considered for revisions. Based on the average results of a large number of risk assessments, the health guidance values obtained using the BMD method are expected to be as protective as those derived from the NOAEL method. Therefore, the default values for the uncertain coefficients that are currently used are still appropriate and do not require the setting of additional uncertainties. Because of the comparability of the means of the BMD and NOAEL methods, the Scientific Board did not consider it necessary to repeat the previous assessment using the BMD method. Only when human exposure approaches ADI is it necessary to refine the previous risk assessment and the application of the BMD method is of special value. The BMD method is suitable for all types of chemicals in different categories or sources in foods, such as pesticides, food additives or contaminants. The BMD method is of special value for use in the following situations: (1) where the NOAEL can not be determined; (2) to provide a reference point for the exposure limit when the substance is both genotoxic and carcinogenic; (3) Dose-response assessment in medical data. In the short term, the EFSA Science Group and its units should strongly advocate the use of BMD in these situations. In the long term, the Scientific Committee expects the BMD to be used as an alternative method for determining reference points to derive health guidance values and exposure limits. To this end, considering the introduction of the method and the widespread use of EFSA, and recognizing that its application requires expert judgment and modeling expertise, the Scientific Committee proposes to provide dose-response to scientific teams and EFSA internal specialists Modeling and software training. The Scientific Board will review the implementation, experience and acceptability of the BMD methodology in EFSA work over the next two years.