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ICCVAM Biennial Report 2020-2021

Biennial Progress Report 2020-2021 Interagency Coordinating Committee on the Validation of Alternative Methods

Variability Analysis of Human Skin Sensitization Data to Use in Establishing Confidence for Alternative Methods

Because humans are the primary subject of interest for regulatory safety testing, it is advantageous to have human reference data available for evaluation of NAMs for assessing chemical safety. Scientists with CPSC, FDA, and NIEHS and collaborators compiled such a data set for human skin sensitization potential by collecting data from the scientific literature for human predictive patch tests that used the human maximization or human repeated insult patch test protocols. They then assessed the variability of these data to determine the potential impact on concordance with NAMs. The data collection identified 2,255 tests that were deemed to be sufficiently reliable for the analysis, including reports for 232 substances with at least two test results. The substances included anilines, amines, aldehydes, esters, and other chemical classes. For 68 substances, all tests were positive (at least one sensitized subject in a study); for 126 substances, all tests were negative (no sensitized subjects); and for the remaining 38 substances, both positive and negative results were obtained. None of the protocol variables such as test type, skin patch size, sample size, or dose applied were associated with high or low variability. There was also no detected association with variability for any of the 10 physicochemical properties examined. The effect of variation in vehicle used could not be analyzed because the majority of tests used a single vehicle. Future work will examine the variability of potency estimates, measured as the dose per skin area that sensitizes one subject. This characterization provides context for defining benchmarks for the evaluation of NAMs for skin sensitization assessments. A poster describing the data set (Strickland et al.) will be presented at the 2022 annual meeting of the Society of Toxicology.