Purpose

The National Institute of Environmental Health Sciences (NIEHS) and the NIEHS Division of Translational Toxicology (DTT) seek input on key research areas and knowledge gaps for in vitro inhalation toxicology. Information provided will be used to help inform the use of in vitro lung models such as air-liquid interface (ALI) airway cultures, lung-on-chip microphysiological systems (MPS), and precision-cut lung slices (PCLS) for inhalation toxicology testing, including formulating DTT’s future research objectives and priorities and preparing a roadmap for their potential use in human health risk assessments. This information may also be used to plan a future meeting/workshop in 2024-2025 or other activities related to the application of these in vitro approaches in research. This request for information (RFI) is for planning purposes only and should not be construed as a funding opportunity or grant program. Input from all interested parties is welcome including the lay public, environmental health researchers, health professionals, educators, policy makers, industry, and others.

Information Requested

The DTT requests information on the advancements, challenges, and required research for the development, application, standardization, and validation of in vitro lung models, including ALI airway cultures, lung-on-chip MPS, PCLS, and in vitro exposure systems (e.g., for vapors, gases, aerosols, and particles). Responses to any or all the questions below are invited from interested individuals/groups including, but not limited to, the environmental health research community, health professionals, educators, policy makers, industry, and the public.

  1. Have you used or are you currently using in vitro lung models (preferably together with physiologically relevant in vitro inhalation exposure systems/technologies) for applications to:
    • Inhalation/Respiratory toxicity screening?
    • Chemical-specific mechanistic studies?
    • In vitro to in vivo extrapolation (IVIVE)?
    • And/Or development/validation for regulatory decision-making or risk assessment?
  2. What do you perceive are the most important scientific knowledge gaps underlying the assessment of the effects of inhaled substances (particles, vapors, etc.) on human health when utilizing in vitro lung models?
  3. What do you perceive are the most important current technical challenges and limitations related to using in vitro lung models in research?
  4. Are you aware of any concerted efforts by individuals or groups to utilize in vitro lung models in routine hazard or risk assessment?

All responses to information requested in this RFI are optional. First and last name and email address is primarily collected to submit a response to a Request For Information and any follow up for clarification or program development.  If you do not provide this information, you would not be able to participate in the RFI process.  Providing affiliation is optional.  Collection of this information is authorized under 42 U.S.C. 203, 241, 289l-1 and 44 U.S.C. 3101, and Section 301 and 493 of the Public Health Service Act. The Privacy Act System of Records Notices (SORNs) that cover collection of this information are 09-25-0156 Records of Participants in Programs and Respondents in Surveys Used to Evaluate Programs of the Public Health Service, HHS/PHS/NIH/OD and 09-90-1901 HHS Correspondence, Comment, Customer Service, and Contact List Records.

How to Submit a Response

This survey is closed. Interest in this Request for Information can be directed to William Gwinn, Ph.D., or Kristen Ryan. Ph.D. (contact information is provided below). Thank you.

Background

Experimental studies that evaluate the toxicity and carcinogenicity of inhaled substances are challenging to design and conduct due to the complex methods and systems required to characterize, deliver, and monitor exposures in the laboratory testing environment. Nonetheless, robust hazard characterization is critical to creating safe living and working environments and reducing the disease burden associated with inhalation exposures. DTT has worked to develop scientific and engineering capabilities for the design and application of complex inhalation exposure-generation and monitoring systems for vapors, gases, liquid aerosols, particles, and fibers. As a result, DTT has established robust and unique capabilities to conduct state-of-the-art hazard assessments for inhalation and workplace exposures, enabled by internal resources and external partnerships with federal agencies and contract research laboratories.

The DTT Occupational and Inhalation Exposures (OIE) Program was initiated in 2020 to coordinate research utilizing animal studies and human exposure assessments, and to evaluate the use of new approach methodologies (NAMs) such as human-relevant in vitro lung models (e.g., air-liquid interface (ALI) airway cultures and lung-on-chip MPS) to generate data that can support human health risk assessments. To date, these data from NAMs for inhalation toxicology are not routinely used in risk assessment due to the lack of standardization and validation.

The focus of this RFI is to gather information regarding the use of in vitro lung models in toxicology research. The information gathered through this RFI will be used to guide future research strategies and prepare a roadmap for their potential use in human health risk assessments and may also be used to plan for a meeting/workshop that fosters discussion on the approaches and resources needed to make progress and to identify new scientific opportunities by applying innovative tools to the field of in vitro inhalation toxicology. Additionally, the meeting/workshop should provide opportunities for the development of collaborations and foster multidisciplinary interactions among the scientific community.

For Further Information Contact

Other correspondence regarding this RFI should be directed to either:

William M. Gwinn, Ph.D.
William M. Gwinn, Ph.D.
Biologist
530 Davis Dr
530 Davis Drive (Keystone Bldg)
Durham, NC 27713
Tel 984-287-4216
[email protected]
Kristen Ryan, Ph.D.
Kristen Ryan, Ph.D.
Staff Scientist, Toxicologist
P.O. Box 12233
Mail Drop K2-12
Durham, NC 27709
Tel 984-287-3179
[email protected]