Development of the SkinEthic HCE Time-to-Toxicity test method for identifying liquid chemicals not requiring classification and labelling and liquids inducing serious eye damage and eye irritation.

This study describes the development of a Time-to-Toxicity approach for liquids (TTL) based on the SkinEthic™ HCE tissue construct, capable to distinguish chemicals that do not require classification for serious eye damage/eye irritation (No Cat.) from chemicals that require classification for eye irritation (Cat. 2), and serious eye damage (Cat. 1). Briefly, the Time-to-Toxicity of 56 liquids was evaluated by exposing SkinEthic™ HCE tissue constructs to the test chemical for three different time periods (5-min, 16-min, and 120-min). Based on the viability observed for the different exposure periods, a classification was assigned. The within laboratory reproducibility in terms of concordance in classifications (3 UN GHS categories), based on a set of 50 liquids, was 80.0%. Furthermore, 84.3% Cat. 1 (N = 17), 79.4% Cat. 2 (N = 21) and 72.2% No Cat. (N = 18) were correctly identified with the SkinEthic™ HCE TTL test method. This study provides evidence that the SkinEthic™ HCE Time-to-Toxicity method (multiple exposure times) is capable of distinguishing Cat. 2 liquids from Cat. 1 liquids. This is an advantage compared to the SkinEthic™ HCE EITL method (single exposure time) that can distinguish No Cat. chemicals from chemicals that do require classification and labelling for eye irritation/serious eye damage (Cat. 2/Cat. 1).