RETROSPECTIVE ANALYSIS OF THE EPIDERM 3-MINUTE PREDICTION MODEL FOR ASSESSMENT OF GHS SKIN CORROSION PACKING GROUP SUB-CATEGORY 1A.

OECD has adopted several ECVAM-validated reconstructed human skin models (EpiDerm and EPISKIN/SkinEthic) for testing skin corrosion as OECD TG 431(1). However, OECD TG 431 does not satisfy international (GHS) labeling guidelines for transport of dangerous goods. GHS package labeling guidelines utilize 3 corrosion sub-categories (1A: very dangerous, 1B: medium danger, and 1C: minor danger). Labeling a chemical as sub-category 1A has important consequences, including very small volume package limits for air transport, prohibition from passenger aircraft, protective storage conditions, costly containers, and low market acceptance. Animal tests are still utilized for assessing the 1A label requirement. An in vitro method that discriminates 1A from 1B/1C classes will therefore have a substantial impact on reducing animal tests for this purpose. The current poster evaluates data obtained with the EpiDerm model for the ability to discriminate between GHS 1A and 1B/1C classes. Data obtained for 49 chemicals tested during the ECVAM Phase I validation study (2), plus 17 additional previously tested chemicals (3), were retrospectively analyzed based on the MTT viability assay (50% viability cutoff) and the 3-minute exposure period. The combined set of test articles includes 15 1A, 25 1B/1C, and 26 non-corrosive chemicals. The 3 min prediction model is shown to produce a sensitivity of 93% (14/15) and overall specificity of 77% (39/51) for predicting sub-category 1A. Testing of additional chemicals (ECVAM Phase III validation study) indicates that data correction for direct MTT-reducing chemicals is important. Adoption of the 3-min EpiDerm prediction model would lead to significant reduction in animal use for corrosion sub-group package labeling.

3 corrosion sub-categories, Corrosive (1B/1C), Direct MTT reduction test, EpiDerm, Freeze-killed tissues, GHS package labeling, MTT reducers, OECD TG 431, Retrospective analysis, Severely corrosive (1A), Skin corrosion

1-(2-Aminoethyl)piperazine, 1,2-Diaminopropane , 1,9-Decadiene, 2,4-Xylidine, 2-Hydroxyisobutyric acid , 2-Methylbutyric acid, 2-tert-butyl phenol , 4-(Methylthio)-benzaldehyde, 4-Amino benzenesulphonic acid , 4-Amino-1,2,4-triazol, 55/45 Octanoic/decanoic acid, 65/35 Octanoic/decanoic acid , 8N KOH, Acetic acid, Acrylic acid, Allyl bromide, Benzalkonium chloride, Boron trifluoride, Bromoacetic acid, Butyl carbamate, Butyric acid, Carvacrol, Chromium trioxide, Cyclohexylamine, Dichloracetyl chloride, Dimethyldipropylenetriamine, E4, Eugenol, Formic acid, Glyoxylic acid, Hexanoic acid, Hydrochloric acid (14.4%), Iron(III) chloride, Isostearic acid, Lactic acid, Lauric acid, L-Glutamic acid hydrochloride, Methacrolein, Methyl 2,2- dimethylpropanoate, Methylphosphonic acid bis(oxiranylmethyl) ester, N-(2-Methylphenyl)imido-dicarbonimidic acid, N,N-Dimethylisopropyleneamine, n-Heptylamine , Octanoic acid, o-Methoxyphenol (guaiacol), Oxalic acid, Phenethyl bromide, Phenol, Phosphoric acid, Phosphorus pentachloride, Phosphorus tribromide, Polysolvan, Potassium hydroxide (10%), Potassium hydroxide (5%), Propionic acid, SDS 20%, Silver nitrate, Sodium bisulphate, Sodium bisulphate monohydrate, Sodium Carbonate 50 %, Sodium disilicate, Sodium undecylenate (33%), Sulphamic acid, Sulphuric acid (10%), Tetrachloroethylene, α-Ketoglutaric acid