Development and evaluation of integrated testing strategies for eye irritation evaluation of agrochemical products
NICEATM, PETA Science Consortium International e.V., EPA, and CropLife America member companies are collaborating to develop an in vitro defined approach for hazard classifications of eye irritation potential of agrochemical formulations. A three-phased prospective evaluation was designed to (1) assess the applicability of seven in vitro eye irritation/corrosion protocols to agrochemical formulations and (2) develop defined approaches (DAs) for agrochemical formulations testing for prediction of U.S. and international irritancy classifications. Agrochemical formulations were selected for prospective testing based on availability of historical rabbit test data, to represent common agrochemical formulation types, and to span the full range of ocular irritation hazard. Test methods were included based on their relevance to mechanisms of human eye irritation, and the results were assessed to determine which methods should advance to potential incorporation in a DA. Twenty-nine formulations were tested in up to five methods: bovine corneal opacity and permeability, EpiOcular, SkinEthic time-to-toxicity for liquids, in vitro depth of injury, and EyeIRR-IS.
In a project led by PETA Science Consortium International, two DAs were developed to predict eye irritation potential in the context of the EPA pesticide classification system (van der Zalm et al. 2023). Predictions derived using the DAs were assessed using orthogonal validation and weight-of-evidence, rather than direct concordance analysis with the historical in vivo rabbit eye data. Both DAs were demonstrated to be as or more fit-for-purpose, reliable, and relevant than the in vivo rabbit eye test.
A separate project led by NICEATM focused on predicting eye irritation potential based on the GHS classification system. A preliminary analysis of alignment across the five in vitro methods and historical rabbit test data was conducted to determine consensus predictions for each formulation. Four methods were then used in the development of four DAs to predict GHS classifications. All four proposed DAs may have high utility for predicting eye irritation classification of agrochemical formulations, as the hazard labeling associated with the predictions are as or more protective of human health compared with the in vivo rabbit test. Furthermore, using the consensus prediction as the reference standard, some standalone in vitro methods can predict the human eye irritation hazard of agrochemical formulations as well as or better than the rabbit test. Results of the study will be described in a poster at the 2024 annual meeting of the Society of Toxicology (Daniel et al., Ocular Toxicology session) and in a paper to be submitted for publication in 2024.