Quantification of the borderline range and implications for evaluating non-animal testing methods' precision.

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Quantification of the borderline range and implications for evaluating non-animal testing methods' precision.

ALTEX. 2017 Feb 23;:

Authors: Leontaridou M, Urbisch D, Kolle SN, Ott K, Mulliner DS, Gabbert S, Landsiedel R

Abstract
Testing methods to assess the skin sensitisation potential of a substance usually use threshold criteria to dichotomise continuous experimental read-outs into yes/no conclusions. The threshold criteria are prescribed in the respective OECD test guidelines and the conclusion is used for regulatory hazard assessment, i.e. classification and labelling of the substance. We can identify a borderline range (BR) around the classification threshold within which test results are non-conclusive due to a testing method's biological and technical variability. We quantify BRs in the prediction models of the non-animal testing methods DPRA, LuSens and h-CLAT, and of the animal test LLNA, respectively. Depending on the size of the BR we find that between 6% and 28% of the substances in the sets tested with these methods were considered borderline. If the results of individual non-animal test methods are combined into integrated testing strategies (ITS), borderline test results of individual tests can also affect the overall assessment of the skin sensitisation potential of the testing strategy. This was analysed for the '2-out-of-3' ITS: Four out of 40 substances (10%) were considered borderline. Based on our findings we propose expanding the standard binary classification of substances into 'positive'/'negative' or 'hazardous'/'non-hazardous' by adding a 'borderline' or 'non-conclusive' alert for cases where test results fall within the borderline range.

PMID: 28230889 [PubMed - as supplied by publisher]

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