Model systems and organisms for addressing inter- and intra-species variability in risk assessment.
Model systems and organisms for addressing inter- and intra-species variability in risk assessment.
复制标题
在风险评估中处理物种间和物种内变异的模型系统和生物。
DOI：
10.1016/j.yrtph.2022.105197
复制
发表时间：
2022-07
影响因子：
3.4
通讯作者：
Wright, Fred A.
中科院分区：
文献类型：
--
作者：
Rusyn, Ivan;Chiu, Weihsueh A.;Wright, Fred A.
解决化学品潜在危险影响的物种间和物种内差异仍然是人类健康风险评估中的一项长期挑战，通常通过使用10倍的默认“不确定性”或“安全”因素来试探性地解决。尽管人们早就认识到，特定于化学物质的数据将更好地取代“默认”，但直到最近，才出现了有可能对特定化学物质的毒物动力学和毒物动力学中的种群变异性进行实验量化的实验模型系统和生物体。最明显的进展是使用群体体外人类细胞模型和群体体内小鼠模型。过去10-15年发表的多个案例研究清楚地表明，这些模型可用于得出数据，直接应用于量化危险识别、暴露-反应评估和对传统风险评估毒性步骤的机械性理解的可变性。在这里，我们回顾了最近在风险评估的背景下，利用这些新的基于群体的体外和体内模型来开发适合于目的的方法的努力。我们还描述了扩大基于人口的实验方法应用的关键挑战和机遇。我们的结论是，基于种群的模型现在开始认识到它们在解决物种间和物种内变异性方面长期存在的数据差距方面的潜力。
Addressing inter- and intra-species differences in potential hazardous effects of chemicals remains a long-standing challenge in human health risk assessment that is typically addressed heuristically through use of 10-fold default “uncertainty” or “safety” factors. Although it has long been recognized that chemical-specific data would be preferable to replace the “defaults,” only recently have there emerged experimental model systems and organisms with the potential to experimentally quantify the population variability in both toxicokinetics and toxicodynamics for specific chemicals. Progress is most evident in the use of population in vitro human cell-based models and population in vivo mouse models. Multiple case studies were published in the past 10–15 years that clearly demonstrate the utility of such models to derive data with direct application to quantifying variability at hazard identification, exposure-response assessment, and mechanistic understanding of toxicity steps of traditional risk assessments. Here, we review recent efforts to develop fit-for-purpose approaches utilizing these novel population-based in vitro and in vivo models in the context of risk assessment. We also describe key challenges and opportunities to broadening application of population-based experimental approaches. We conclude that population-based models are now beginning to realize their potential to address long-standing data gaps in inter- and intra-species variability.
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DOI：
10.1080/15287394.2015.958417
发表时间：
2015
期刊：
Journal of toxicology and environmental health. Part A
影响因子：
--
作者：
Yoo HS;Bradford BU;Kosyk O;Shymonyak S;Uehara T;Collins LB;Bodnar WM;Ball LM;Gold A;Rusyn I
通讯作者：
Rusyn I
DOI：
10.1080/15287394.2015.958418
发表时间：
2015
期刊：
Journal of toxicology and environmental health. Part A
影响因子：
--
作者：
Yoo HS;Bradford BU;Kosyk O;Uehara T;Shymonyak S;Collins LB;Bodnar WM;Ball LM;Gold A;Rusyn I
通讯作者：
Rusyn I
影响因子：
2.5
作者：
Churchill, Gary A.;Gatti, Daniel M.;Munger, Steven C.;Svenson, Karen L.
通讯作者：
Svenson, Karen L.
影响因子：
2.2
作者：
Bussiere, Jeanine L.;Martin, Pauline;Horvath, Christopher
通讯作者：
Horvath, Christopher
影响因子：
4.3
作者：
Burnett SD;Blanchette AD;Chiu WA;Rusyn I
通讯作者：
Rusyn I