Defined Approaches to Identify Potential Eye Irritants
Potential eye irritants can be identified without animal testing using defined approaches to testing and assessment. A defined approach consists of:
- Input data generated from identified methods.
- A data interpretation procedure (e.g., machine-learning model, flowchart, or decision tree through which the data are evaluated).
NICEATM is collaborating with the PETA International Science Consortium Ltd. (PETA-ISC), EPA, and member companies of the trade association CropLife America to develop an in vitro defined approach for classification of eye irritation potential of agrochemical formulations. This public-private partnership was established as a means to develop confidence in non-animal methods for identifying potential eye irritants and thus encourage adoption and use. Results of Phase 1 of the study were presented in a poster (Choksi et al.) at the 2019 SOT Annual Meeting; results of Phase 2 were described in a poster presentation (Choksi et al.) at the 2020 Annual Meeting of the American Society for Cellular and Computational Toxicology.
Details of the Study
NICEATM initially analyzed data from four in vitro assays paired with in vivo rabbit eye test data to determine if a defined approach using a combination of these assays could assess eye irritation potential. While the results of this analysis indicated that developing such a defined approach was feasible, the data sets were limited in size and a final conclusion could not be made. Therefore, it was determined that additional prospective testing was needed.
Members of the collaboration team designed a three-phase prospective evaluation to (1) assess the applicability of seven in vitro eye irritation/corrosion methods to agrochemical formulations and (2) develop a defined approach for agrochemical formulations testing for prediction of U.S. and international irritancy classifications. The test methods used include:
- Bovine corneal opacity and permeability
- Neutral red release
- Isolated chicken eye
- Porcine cornea reversibility
- EpiOcular EIT
- EpiOcular time-to-toxicity ET50-neat
- EpiOcular time-to-toxicity ET50-dilution
In Phase 1, six formulations were tested in seven eye irritation test methods. All seven methods were used in Phase 2, which evaluated 10 formulations that represented a range of eye irritancy classifications. Phases 1 and 2 are complete, and analysis of the data from these phases will determine the next steps of the study.