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基准剂量(BMD)建模:当前实践、问题与挑战。

Benchmark dose (BMD) modeling: current practice, issues, and challenges.

机构信息

a Risk Science Center , University of Cincinnati , Cincinnati , OH , USA.

b Independent Consultant , Chapel Hill , NC , USA.

出版信息

Crit Rev Toxicol. 2018 May;48(5):387-415. doi: 10.1080/10408444.2018.1430121. Epub 2018 Mar 8.

Abstract

Benchmark dose (BMD) modeling is now the state of the science for determining the point of departure for risk assessment. Key advantages include the fact that the modeling takes account of all of the data for a particular effect from a particular experiment, increased consistency, and better accounting for statistical uncertainties. Despite these strong advantages, disagreements remain as to several specific aspects of the modeling, including differences in the recommendations of the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA). Differences exist in the choice of the benchmark response (BMR) for continuous data, the use of unrestricted models, and the mathematical models used; these can lead to differences in the final BMDL. It is important to take confidence in the model into account in choosing the BMDL, rather than simply choosing the lowest value. The field is moving in the direction of model averaging, which will avoid many of the challenges of choosing a single best model when the underlying biology does not suggest one, but additional research would be useful into methods of incorporating biological considerations into the weights used in the averaging. Additional research is also needed regarding the interplay between the BMR and the UF to ensure appropriate use for studies supporting a lower BMR than default values, such as for epidemiology data. Addressing these issues will aid in harmonizing methods and moving the field of risk assessment forward.

摘要

基准剂量 (BMD) 建模现在是用于确定风险评估起点的科学方法。其主要优点包括:该模型考虑了特定实验中特定效应的所有数据,提高了一致性,并更好地考虑了统计不确定性。尽管具有这些强大的优势,但建模的几个具体方面仍存在分歧,包括美国环境保护署 (USEPA) 和欧洲食品安全局 (EFSA) 的建议存在差异。在连续数据的基准响应 (BMR) 的选择、无限制模型的使用以及所使用的数学模型方面存在差异,这可能导致最终 BMDL 的差异。在选择 BMDL 时,考虑对模型的信心很重要,而不仅仅是选择最低值。该领域正在朝着模型平均的方向发展,这将避免在生物学基础不建议选择单一最佳模型时选择单个最佳模型所面临的许多挑战,但需要进一步研究如何将生物学考虑因素纳入平均使用的权重中。还需要进一步研究 BMR 和 UF 之间的相互作用,以确保在支持比默认值更低的 BMR 的研究中正确使用,例如在流行病学数据中。解决这些问题将有助于协调方法并推动风险评估领域的发展。

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