North Colin M, Ezendam Janine, Hotchkiss Jon A, Maier Curtis, Aoyama Kohji, Enoch Steve, Goetz Amber, Graham Cynthia, Kimber Ian, Karjalainen Antti, Pauluhn Juergen, Roggen Erwin L, Selgrade MaryJane, Tarlo Susan M, Chen Connie L
ExxonMobil Biomedical Sciences, Inc., Annandale, NJ, USA.
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Regul Toxicol Pharmacol. 2016 Oct;80:295-309. doi: 10.1016/j.yrtph.2016.06.006. Epub 2016 Jul 7.
Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, -omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non-immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment.
呼吸道致敏可能会对健康产生重大的急性和慢性影响。虽然某些化学物质引起呼吸道致敏已得到广泛认可，但目前尚无经过验证的用于识别和表征该危害的标准方法或框架。举办了一次关于呼吸道致敏评估的研讨会，以讨论呼吸道致敏剂危害识别和表征的科学现状，确定有助于开发经过验证的标准方法和框架的信息，并考虑监管和实际风险管理需求。与会者就主要的Th2免疫机制以及呼吸道致敏的几个步骤达成了共识。呼吸道致敏和皮肤致敏中一些重叠的细胞事件已得到充分了解，但完整的机制仍不清楚。会上认可了皮肤致敏测试非动物方法的进展，包括体外系统、组学、计算机模拟分析和结构分析等。应对诱导期和激发期仍然具有挑战性。与会者指出，缺乏统一的剂量指标增加了跨暴露解释剂量学的难度。确定了一些研究需求，包括一份商定的呼吸道致敏剂和其他哮喘原清单，区分免疫介导机制与非免疫机制产生的不良反应。关于未来测试策略的讨论出现了一些主题，特别是需要一个分层框架进行呼吸道致敏剂评估。本次研讨会为迈向证据权重评估奠定了基础。
