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Assessing Experimental Uncertainty in Defined Approaches: Borderline Ranges for In Chemico and In Vitro Skin Sensitization Methods Determined from Ring Trial Data

Assessing Experimental Uncertainty in Defined Approaches: Borderline Ranges for In Chemico and In... Introduction: Prediction models of most toxicological assays translate continuous data to binary classifications (“positive” or “negative”) using cutoff values. Mostly these cutoffs do not consider data variability. Some OECD test guidelines, however, provide a range close to the cutoff. If a test result is in this range, a repetition of the test is proposed. Yet, these ranges were based on few data and not systematically derived.Materials and Methods: In the present study, we determined the borderline ranges from multilaboratory ring trial studies for five nonanimal methods addressing skin sensitization: Direct Peptide Reactivity Assay (OECD TG 442C), KeratinoSens® and LuSens (OECD TG 442D), and human cell line activation test (OECD TG 442E) as well as the kinetic direct peptide reactivity assay (update of OECD TG 442C).Results: We used a uniform statistical approach based on the log median absolute deviation. Implementing the proposed borderline ranges helps to assess certainty of both individual test results and of combinations of multiple data sources in a defined approach (DA) or an integrated approach.Conclusion: The OECD guideline on DAs for skin sensitization provides the first regulatory application of borderline ranges to the “2 out of 3” DA. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied In Vitro Toxicology Mary Ann Liebert

Assessing Experimental Uncertainty in Defined Approaches: Borderline Ranges for In Chemico and In Vitro Skin Sensitization Methods Determined from Ring Trial Data

Assessing Experimental Uncertainty in Defined Approaches: Borderline Ranges for In Chemico and In Vitro Skin Sensitization Methods Determined from Ring Trial Data

Applied In Vitro Toxicology , Volume 7 (3): 10 – Sep 1, 2021

Abstract

Introduction: Prediction models of most toxicological assays translate continuous data to binary classifications (“positive” or “negative”) using cutoff values. Mostly these cutoffs do not consider data variability. Some OECD test guidelines, however, provide a range close to the cutoff. If a test result is in this range, a repetition of the test is proposed. Yet, these ranges were based on few data and not systematically derived.Materials and Methods: In the present study, we determined the borderline ranges from multilaboratory ring trial studies for five nonanimal methods addressing skin sensitization: Direct Peptide Reactivity Assay (OECD TG 442C), KeratinoSens® and LuSens (OECD TG 442D), and human cell line activation test (OECD TG 442E) as well as the kinetic direct peptide reactivity assay (update of OECD TG 442C).Results: We used a uniform statistical approach based on the log median absolute deviation. Implementing the proposed borderline ranges helps to assess certainty of both individual test results and of combinations of multiple data sources in a defined approach (DA) or an integrated approach.Conclusion: The OECD guideline on DAs for skin sensitization provides the first regulatory application of borderline ranges to the “2 out of 3” DA.

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Publisher
Mary Ann Liebert
Copyright
© Susanne N. Kolle et al., 2021; Published by Mary Ann Liebert, Inc.
ISSN
2332-1512
eISSN
2332-1539
DOI
10.1089/aivt.2021.0003
Publisher site
See Article on Publisher Site

Abstract

Introduction: Prediction models of most toxicological assays translate continuous data to binary classifications (“positive” or “negative”) using cutoff values. Mostly these cutoffs do not consider data variability. Some OECD test guidelines, however, provide a range close to the cutoff. If a test result is in this range, a repetition of the test is proposed. Yet, these ranges were based on few data and not systematically derived.Materials and Methods: In the present study, we determined the borderline ranges from multilaboratory ring trial studies for five nonanimal methods addressing skin sensitization: Direct Peptide Reactivity Assay (OECD TG 442C), KeratinoSens® and LuSens (OECD TG 442D), and human cell line activation test (OECD TG 442E) as well as the kinetic direct peptide reactivity assay (update of OECD TG 442C).Results: We used a uniform statistical approach based on the log median absolute deviation. Implementing the proposed borderline ranges helps to assess certainty of both individual test results and of combinations of multiple data sources in a defined approach (DA) or an integrated approach.Conclusion: The OECD guideline on DAs for skin sensitization provides the first regulatory application of borderline ranges to the “2 out of 3” DA.

Journal

Applied In Vitro ToxicologyMary Ann Liebert

Published: Sep 1, 2021

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