RESUMEN
Skin irritation is a key human health endpoint assessed by in vitro and in vivo methods. The OECD TG 404 guideline (in vivo) is based on erythema and oedema translated semi-quantitatively into Draize scores, providing hazard statements for substance classification following EUCLP/UNGHS criteria. Draize scores require quantitation from subjective in vivo observations, to obtain a scoring index, the Primary Irritation Index (PII). However, it is not recognised under REACH due to translating difficulties, notably the cut-off limit for classification and non-inclusion of corrosive effects. The aim of this study was to determine if classification can be driven by just one of the observed effects, erythema only, to create a Simplified Irritation Index (SIISKIN). This simplifies the scoring calculation and reduces subjectivity. A quantitative approach with cut-off limits is thus proposed for classification. Substances can be classified as non-irritant, potentially irritant, irritant, or corrosive. The Simplifed Irritation Index (SIISKIN) is based on validated studies, representing multiple chemical groups. A significant correlation between SIISKIN and the harmonised classification was observed, and a proportionate relationship between the SIISKIN and the corresponding PII. The index proved to be useful in the development of an in silico model.
Asunto(s)
Cáusticos/toxicidad , Simulación por Computador , Irritantes/toxicidad , Pruebas de Irritación de la Piel/métodos , Alternativas a las Pruebas en Animales , Corrosión , Humanos , Piel , Enfermedades de la PielRESUMEN
Eye irritation is a key human health endpoint assessed by in vitro and in vivo methods. One of the commonly used scoring methods to quantify the eye irritation potential of chemicals is the Modified Maximum Average Score (MMAS). It is dependent on the eye irritation effects (e.g. corneal opacity) originally proposed by Draize and then partially adopted by the OECD TG 405. These scores are not always fully reported in regulatory dossiers and lead to several drawbacks, 1) the difficulty to translate MMAS into a classification within the existing EU CLP/UN GHS criteria, 2) the absence of corrosion (serious eye damage), and 3) the dependency on input parameters which are usually not required under the OECD TGs (e.g. eye surface area). This study determined if classification can be driven by a maximum of two observed effects thereby simplifying the scoring calculation. The Simplified Irritation Index (SIIEYE), based only on corneal opacity and conjunctival redness, was developed using validated studies representing multiple chemical groups. A correlation was observed between the MMAS and the SIIEYE allowing harmonisation of the classification for the existing data. This index proved to be useful in the development of in silico model.