Expansion of the applicability domain for highly volatile substances on the Short Time Exposure test method and the predictive performance in assessing eye irritation potential

Abstract

The Short Time Exposure (STE) test method is an in vitro method for assessing the eye irritation potential of chemicals and is used to classify the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 1 and No Category (NC). The method has been adopted by the Organisation for Economic Co-operation and Development (OECD) as test guideline (TG) 491 since 2015. While this method can be used to classify GHS NC, it is not suitable for testing highly volatile substances and solids other than surfactants. Here we evaluated highly volatile substances to expand the applicability domain. According to TG 491, acetone, ethanol, iso-propanol, and methyl acetate as highly volatile substances resulted in false negatives. Saline was selected as a solvent of these false negatives. In this study, mineral oil was used as the solvent, because these false negatives were amphiphilic. Based on this change, four highly volatile substances were correctly evaluated. The predictive performance for classifying GHS NC was then verified using a substance dataset constructed in reference to the Draize eye test Reference Database and STE Summary Review Document. The accuracy and false-negative rate were 86.6% (194/224) and 3.8% (3/80), respectively. Collectively, the applicability domain was expanded by changing the solvent to mineral oil for highly volatile substances, and the predictive performance for the new applicability domain including highly volatile substances was excellent. The STE test method is suitable to classify GHS NC, indicating its applicability as a test method in a bottom-up approach.

Evaluation of MTT reducers and strongly colored substances in the Short Time Exposure test method for assessing eye irritation potential

“…As a result, we obtained cell viabilities of 31% at 5% dilution and 18.7% at 0.05% dilution. These cell viabilities did not show dose dependence, which was also not reported except for this substance in previous STE test data (Abo et al, 2018). When we performed an additional confirmation experiment using GC-FID, this substance was detected at 0.524 mg in wells exposed to 5% dilution but was not detected in wells exposed to 0.5% dilution (Table 6).…”

Test No. 491: Short Time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage

“…It is recommended that SIRC cells are obtained from a well-qualified cell bank, such as American Type Culture Collection CCL60. ©OECD 2020 15.…”

“…measured vapour pressure > 6kPa) and solid substances other than surfactants are excluded from the dataset, the overall accuracy ©OECD 2020 improves to 90% (92/102), the false negative rate to 2% (1/54), and the false positive to 19% (9/48) (7). Further work demonstrated that highly volatile substances can be correctly tested when using mineral oil instead of saline as a solvent (15). The accuracy of the STE test for highly volatile substances (i.e.…”

Sanitizer aerosol-driven ocular surface disease (SADOSD)—A COVID-19 repercussion?

“…[ 4 ] There are several in-vivo and in-vitro studies on the toxicity of these products. [ 5 ] Of particular interest is the Draize rabbit eye and skin irritancy tests, which evaluated the in-vivo irritation potential of these products on the skin and eye. Another important finding was that the eye is more sensitive to the toxic/allergic effects of ABHRs than the skin.…”