Predicting skin sensitisation potential of organic compounds based on toxicity enhancement to Tetrahymena pyriformis, fathead minnow, and Daphnia magna

Skin sensitisation is an important occupational health problem and immunotoxicity endpoint. Considering animal welfare and time and cost savings, many alternative approaches, such as those conducted in vitro, in silico, and in chemo, have been proposed and applied to predict skin sensitisation of compounds. Toxicologically, sensitisers can elicit excess toxicity at greater levels than non-sensitizers due to their capacity to react with proteins/peptides. Based on this understanding, calculated toxicity enhancements (Te) of 65 organic compounds from three in vitro bioassays, i.e. 48-hr ciliate (Tetrahymena pyriformis) growth inhibition, and both 96-hr fathead minnow and 48-hr Daphnia magna acute lethal toxicities, were employed to qualitatively and quantitatively predict skin sensitisation potencies of the test agents. The sensitivity, specificity, and accuracy reaching 80% strongly suggested toxicity enhancement was an excellent parameter for predicting skin sensitisation. Linear regressions of skin sensitization against toxicity enhancement were fitted for each bioassay, and they were improved after the sensitisers were categorised into different reaction mechanistic domains, which, in decreasing order of contribution from Te to sensitisation, were SNAr?>?SN1?>?MA. These results indicated that toxicity bioassays are useful tools and that Te could be a useful parameter that might be applied to predict skin sensitisation.

Authors: Zhang W, Chen L, Yao L. ; Full Source: Journal of Immunotoxicology. 2018 Dec;15(1):82-89. doi: 10.1080/1547691X.2018.1465144.

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