Characterizing Local Acute Irritation Properties of Captan and Folpet with New Approach Methods

Introduction: The current toxicological registration package for the contact fungicides Captan and Folpet relies exclusively on animal tests for acute endpoints. The actives rapidly degrade and are not systemically available in toxicologically relevant amounts, which may pose challenges in in vitro scenarios. Materials and Methods: To investigate the predictiveness of New Approach Methods (NAMs) for Captan and Folpet hazard assessments, a set of 18 in vitro studies was conducted, comprising eye and skin irritation and skin sensitization assays compliant with Organisation for Economic Co-operation and Development (OECD) test guidelines. Further performed were GARD®skin sensitization assays and rat EpiAirway™ acute airway toxicity assays, the latter with single and repeated exposure. The results were compared against publicly available and confidential information from the legacy vertebrate dataset for each fungicide, and also against current European health classifications and the proposed revision of these classifications. Results: The NAM data package appropriately identifies Captan and Folpet as contact irritants with predicted effects in eyes and the respiratory system and identifies the skin sensitization properties correctly for each fungicide. However, the assays under-classify eye irritation hazard, compared with animal data. Discussion and Conclusion: The results may indicate species sensitivity differences, which are plausible owing to morphological tissue differences. Hence, the suitability of animal test data for the assessment of human irritation risk from Captan and Folpet may be questioned as being overly protective.