Alternative Methods for Acute Inhalation Toxicity
NICEATM and the PETA International Science Consortium (PISC) presented a webinar series on Alternative Approaches for Acute Inhalation Toxicity to Address Global Regulatory and Non-regulatory Data Requirements. Webinar presenters reviewed regulatory guidelines relevant to assessing inhalation toxicity hazard potential and alternative approaches for identifying chemicals likely to cause acute systemic toxicity via inhalation, and identified mechanisms of acute toxicity that may constitute key events in adverse outcome pathways for acute inhalation toxicity. The webinar series steering committee was comprised of members from government and nongovernment stakeholder organizations including NICEATM, PISC, The Dow Chemical Company, Simulations Plus, Inc., the Netherlands Organisation for Applied Scientific Research, and the U.S. Environmental Protection Agency (EPA).
Following the webinar series, experts from industry, government, academia, and nongovernmental organizations convened at the National Institutes of Health in September 2016 to discuss their experiences using alternative approaches for acute inhalation toxicity testing and, building upon those approaches, how to develop strategies that regulatory agencies will accept. Participants made four key recommendations:
- Develop a database of existing acute systemic toxicity data
- Prepare a state-of-the-science review on mechanisms and assays for acute inhalation toxicity
- Develop an in silico decision tree
- Optimize in vitro assays and standardized protocols that can be used across laboratories
Working groups were formed and tasked with follow-up actions directed towards implementing each of these recommendations. A follow-up meeting will be convened in late 2017 or 2018 to discuss progress, identify outstanding issues, and define action plans to continue progress towards implementation.
In Vitro Testing Strategies to Assess Inhalation Toxicity of Nanomaterials
NICEATM is collaborating with PISC, EPA, and industry scientists to support a workgroup focused on inhalation toxicity. The workgroup met February 24-25, 2015, at EPA in Washington to define specifications for the development and evaluation of an in vitro system to assess inhalation toxicity of multiwalled carbon nanotubes. The recommended system would include different lung cells co-cultured at an air-liquid interface and consider relevant human dosimetry and nanomaterial lifecycle transformations. PISC used these recommendations for a subsequent request for proposals for funding to develop an appropriate testing system; funding was awarded in September 2015. Presentations from the meeting and a list of publications developed by meeting participants are available on the PISC website.
This activity followed a NICEATM request for information (79 FR 35176, June 19, 2014) on devices and/or technologies currently used for identifying potential inhalation hazards.