DECISION TREE FOR OCULAR SAFETY ASSESSMENT OF AGROCHEMICAL FORMULATIONS

RIVERO, MARTIN NICOLAS; LENZE, MARIELA; RESCHINI, AGUSTINA; PINA, JUAN IGNACIO; MARTÍNEZ, ROMINA; WIKINSKI, SILVIA; GUTIÉRREZ, MARÍA LAURA

Barcelona

Congreso; 21st International Congress ESTIV; 2022

European Society of In Vitro Toxicology

For the registration of agrochemical formulations, acute eye toxicity assessment isrequired by regulatory agencies. The Draize rabbit eye test (OECD TG 405) hasworldwide acceptance to assess eye irritation, even it has been increasingly questioned.The test distinguishes four categories considering reversible and non-reversible ocularlesions according to UN GHS Categories 1 (severe eye damage), 2A and 2B (reversibleeye damage) and No Category (minimal effects). Bovine Corneal Opacity andPermeability (BCOP) and Short Time Exposure (STE) are methods for identifying Cat. 1and No Cat. products, according to OECD TG 437 and TG 491 respectively.Histopathological analysis of the corneas, after the BCOP test, is recommended toidentify the depth of the damage as complementary information.As the limitation of these alternative methods is to classify in the middle-rangecategories (2A and 2B), the aim of this work was to create a strategy to identify thesecategories. The STE and BCOP methods were used to test 17 pesticides manufactured byATANOR SCA. These products had been previously classified in categories 1, 2A, 2B or NoCat. using the Draize eye irritation test.By STE test, all formulations were tested at 5 and 0.05%. By the BCOP test, liquidproducts were tested neat and at 10% and solids at 10%. After BCOP, anhistopathological analysis was performed and 3 different models were used to analyse:depth of injury, stromal thickness, and total histopathological damage. Following a 4-stepdecision tree, we obtained the same classification for 14 of the 17 agrochemicals. Ananalysis by category shows: Cat. 1 100% accuracy and specificity; Cat 2A 82.4%accuracy and 86.7% specificity; Cat 2B 88.2% precision and 90.9% specificity and NoCat. 94.1% precision and 100% specificity.Finally, we successfully established an in-house strategy for testing agrochemicals eyeirritation.