Retrospective evaluation of the OECD adopted in vitro skin irritation/corrosion tests for agrochemical formulations

The Draize rabbit skin test is the primary method for assessing skin irritation potential of chemical products despite limited human relevance, reproducibility, and ethical concerns. The Organisation for Economic Co-operation and Development has issued two test guidelines (TGs) that describe the use of in vitro reconstructed human epidermis models to predict skin irritation or corrosion potential. However, these tests have not been explicitly validated for agrochemical formulations. To address this knowledge gap, we conducted a retrospective analysis to evaluate how well the in vitro methods predict in vivo classifications of these products. Of the 187 formulations with in vivo data (TG 404), 162 formulations had corresponding in vitro corrosion and/or irritation data (TG 431 and/or 439). We also evaluated the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) concentration threshold (CT) approach for 186 formulations. Our analyses suggest that the in vitro irritation test (TG 439) and GHS CT approach are highly predictive of formulations that are mildly or non-irritating to skin (i.e., GHS Category 3 or Not Classified). Therefore, these approaches provide an opportunity to reduce animal use for determining skin irritation potential of agrochemical formulations.