STUDIES TO EVALUATE THE POTENTIAL FOR ENVIRONMENTAL&THERAPEUTIC AGENTS TO INDUCE IMMUNOTOXICITY - In vitro immunomodulation

NIH RePORTER · NIH · N01 · $662,415 · view on reporter.nih.gov ↗

Abstract

In vitro techniques for hazard identification for potential sensitizers have been of increasing importance to the NIEHS and for agency partners conducting risk assessment. A research collaboration agreement with a commercial vendor was established to assess the utility of the GARDair assay to identify respiratory sensitizers. As an extension of the previously reported agency partner studies where >200 chemicals were evaluated using in vitro methods to assess their potential to induce skin sensitization, NIEHS requested nominations from partner agencies to evaluate the use of an in vitro method to evaluate chemicals for their potential to induce allergic responses in the lung. The GARDair assay uses a gene set that has potential for identifying respiratory sensitizers. Agency partners nominated a total of 100 chemicals to be tested, including known respiratory sensitizers as well as chemicals of unknown potential to induce sensitization. Procurement of 100+ chemicals has been completed and laboratory testing is ongoing. To date, 93 chemicals have passed range finder assays, and main runs are complete for 52. Data analysis and classifications have been completed for 24 of the compounds. NIEHS funded contractor participation in validation trials for the Electrophilic Allergen Screening Assay (EASA). This assay uses non-protein/peptide probes in a cell-free assessment to measure the ability of a test substance to “react” with biologically important molecules for the identification of electrophilic allergic contact dermatitis hazards. A NICEATM report has been drafted on the results of the validation trials and has undergone peer review. The final report will be available in FY25. NIEHS is also sponsoring work to establish scientific confidence in a new 3D in vitro tissue model for assessment of the potential for chemicals to induce dermal sensitization. The Epi2SensA assay is a me-too model that will be included in the OECD TG 442D for assessment of keratinocyte activation and will be instrumental in broadening the accessibility of this 3D tissue model outside of Japan where it was originally developed. A study protocol for the method transfer of the Epi2SensA assay to the contractor was finalized and approved in FY24. The work is expected to be completed in FY25.

Key facts

NIH application ID
11142292
Project number
273201400017C-P00023-9999-3
Recipient
BURLESON RESEARCH TECHNOLOGIES, INC.
Principal Investigator
FLORENCE BURLESON
Activity code
N01
Funding institute
NIH
Fiscal year
2024
Award amount
$662,415
Award type
Project period
2014-08-13 → 2024-08-12