A key challenge in systematically incorporating mechanistic data into human health assessments is that, compared to studies of apical health endpoints, these data are both more abundant (mechanistic studies routinely outnumber other studies by several orders of magnitude) and more heterogeneous (e.g. different species, test system, tissue, cell type, exposure paradigm, or specific assays performed). A structured decision-making process for organizing, integrating, and weighing mechanistic DNT data for use in human health risk assessments will improve the consistency and efficiency of such evaluations. At the Developmental Neurotoxicology Society (DNTS) 2016 annual meeting, a symposium was held to address the application of existing organizing principles and frameworks for evaluation of mechanistic data relevant to interpreting neurotoxicology data. Speakers identified considerations with potential to advance the use of mechanistic DNT data in risk assessment, including considering the context of each exposure, since epigenetics, tissue type, sex, stress, nutrition and other factors can modify toxicity responses in organisms. It was also suggested that, because behavior is a manifestation of complex nervous system function, the presence and absence of behavioral change itself could be used to organize the interpretation of multiple complex simultaneous mechanistic changes. Several challenges were identified with frameworks and their implementation, and ongoing research to develop these approaches represents an early step toward full evaluation of mechanistic DNT data for assessments.

中文翻译：

---

支持发育神经毒性结果的机械数据评估的潜在框架：研讨会报告。

将机械数据系统地纳入人类健康评估的一个关键挑战是，与顶端健康终点的研究相比，这些数据更加丰富（机械研究通常比其他研究多几个数量级）并且更加异质（例如不同物种、测试系统、组织、细胞类型、暴露范例或进行的特定测定）。用于组织、整合和权衡机械 DNT 数据以用于人类健康风险评估的结构化决策流程将提高此类评估的一致性和效率。在发育神经毒理学会 (DNTS) 2016 年年会上，举行了一次研讨会，讨论现有组织原则和框架在评估与解释神经毒理学数据相关的机制数据方面的应用。发言者指出了在风险评估中可能推进机械 DNT 数据使用的考虑因素，包括考虑每次暴露的背景，因为表观遗传学、组织类型、性别、压力、营养和其他因素可以改变生物体的毒性反应。还有人提出，由于行为是复杂神经系统功能的表现，行为变化本身的存在和不存在可以用来组织对多个复杂的同时发生的机械变化的解释。框架及其实施存在一些挑战，开发这些方法的持续研究代表了全面评估机械 DNT 数据以进行评估的早期步骤。