PDF(Pubmed)
Abstract：
Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents.
The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.
A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.
KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.
The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.
A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.
KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.
摘要：
关键特征(KCs)，赋予潜在危险的药剂或暴露的性质，已开发用于致癌物和其他有毒物质类别。KC已用于系统评估危害，并确定限制筛查和风险评估的测定和数据空白。药物和职业或环境试剂调节免疫功能的许多机制已得到充分认可。因此,KC可被鉴定为免疫活性物质,并用于改进免疫调节剂的危害评估。
目标是产生基于共识的科学证据，描述已知引起免疫毒性和潜在应用的试剂的KCs。例如用于测量KCs的测定法。
一个由18名不同专业的专家组成的委员会确定了10种免疫毒性剂，即,1）共价结合蛋白质形成新的抗原，2）影响抗原加工和呈递，3）改变免疫细胞信号，4）改变免疫细胞增殖，5）改变细胞分化，6）改变免疫细胞-细胞通讯，7）改变特定细胞类型的效应子功能，8）改变免疫细胞运输，9）改变细胞死亡过程，和10)破坏免疫耐受。该小组考虑了这些KCs如何影响免疫过程并导致超敏反应，不适当的增强，免疫抑制,或自身免疫。
KCs可用于改善通过一种或多种机制鉴定引起免疫毒性的药物的努力，开发更好的测试和生物标志物方法来评估免疫毒性，并能够更全面和机械地了解暴露对免疫系统的不利影响。https://doi.org/10.1289/EHP10800.
目标是产生基于共识的科学证据，描述已知引起免疫毒性和潜在应用的试剂的KCs。
一个由18名不同专业的专家组成的委员会确定了10种免疫毒性剂，
KCs可用于改善通过一种或多种机制鉴定引起免疫毒性的药物的努力，
