FURTHER DEVELOPMENT OF AN EPIDERM™ IN VITRO SKIN IRRITATION TEST FOR THE GLOBALLY HARMONIZED SYSTEM (GHS-SIT) OF CLASSIFICATION AND LABELING OF CHEMICALS.

Determination of skin irritation potential is an international regulatory requirement to ensure safe handling, packaging, labeling and transport of chemicals and evaluation of cosmetics and household products. Recent REACH legislation and a ban on animal testing for cosmetics have heightened the need for validated in vitro SITs. A UN treaty endorsed by the US, EU, China, Japan, Australia and others has outlined a GHS of Classification and Labeling of Chemicals. The GHS classifies skin irritancy of chemicals into three categories: non-irritant (NI), slight irritant (SI) or irritant (I). The EpiDerm model has been validated for in vitro skin corrosion testing worldwide, and in vitro SIT in the EU in studies sponsored by the European Center for the Validation of Alternative Methods (ECVAM). However, the EU SIT system distinguishes only 2 classifications – skin irritants (R38) and non-irritants (no label), and thus does not satisfy the worldwide GHS SIT system. Therefore, additional efforts are underway to validate an EpiDerm SIT for GHS. Previously reported work utilizing 15 reference chemicals established a preliminary EpiDerm-GHS-SIT prediction model (The Toxicologist, 108(1):379 (2009)). In the current poster we report new results obtained with an expanded set of 36 reference chemicals including 12 from each GHS classification category. Using a tiered strategy with 2 MTT viability assay protocols, SI plus I chemicals were identified with a sensitivity of 75.0% and specificity of 100%. Irritant chemicals were identified with a sensitivity of 91.7% and specificity of 91.7%. Concordance for correct classification of each category was 100.0%, 33.3% and 91.7% for NI, SI and I, respectively. Overall concordance was 75.0%. Two SI were over-predicted as I. One I was under-predicted as SI, and 6 SI were under-predicted as NI. However, 4/6 of the under-predicted chemicals are NI in human patch tests. Interlaboratory transferability of the EpiDerm-GHS-SIT protocols will next be evaluated to form the basis for formal validation studies.

GHS of Classification and Labeling of chemicals, Globally Harmonized System (GHS-SIT), Skin irritant, Skin irritation potential, Skin irritation test

1 ,1,1-trichloroethane , 1-bromopentane , 1-methyl-3-phenyl-piperazine , 10-undecenoic acid , 2 -methyl-5-tert-butylth iophenol , 2-ch loromethyl-4-methoxy-3,5-dimethylpyridine hydrochloride , 2-ethoxyethyl methacrylate , 3,3-dimethyl pentane , Allyl heptanoate , Allyl phenoxyacetate , Benzyl acetate , Benzyl benzoate , Benzyl salicylate , Butyl methacrylate , Capric acid (decanoic acid) , Cinnamaldehyde , Diethyl phthalate , Erucamide , Glycerol , Heptanal , Heptyl butyrate , Hexyl salicylate , Isopropanol , Isopropyl myristate , Isoproyl palmitate , Limonene , Linalool , Linalyl acetate , Methyl laurate , Octanoic acid , Potassium hydroxide (5% aq.) , SOS (5% aq.) , Sodium bicarbonate , Terpinyl acetate , Tetrachloroethylene , Tri-isobutylphosphate