Improving predictive capacity of the Amino acid Derivative Reactivity Assay test method for skin sensitization potential with an optimal molar concentration of test chemical solution. Issue 2 (30th October 2020)

• Record Type: Journal Article
• Authors: Imamura, Mika; Wanibuchi, Sayaka; Yamamoto, Yusuke; Kojima, Hajime; Ono, Atsushi; Kasahara, Toshihiko; Fujita, Masaharu
• Is Part Of: Journal of applied toxicology. Volume 41:Issue 2(2021)
• Page Start: 303
• Page End: 329
• Publication Date: 2020-10-30
• Subjects: ADRA‐FL -- ADRA‐UV -- Amino acid Derivative Reactivity Assay (ADRA) -- in chemico -- molar concentration -- optimal concentration -- predictive accuracy -- skin sensitization; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4082
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: The Amino acid Derivative Reactivity Assay (ADRA) is a convenient and effective in chemico test method for assessing covalent binding of test chemicals with protein‐derived nucleophilic reagents as a means of predicting skin sensitization potential. Although the original molar‐concentration approach to ADRA testing was not suitable for testing multiconstituent substances of an unknown composition, a weight‐concentration approach that is suitable for such substances was developed, which also led to the realization that test chemical solutions prepared to molar concentrations higher than the original 1 mM would reduce false negative results as well as enhance predictive capacity. The present study determined an optimal molar‐concentration that achieves even higher predictive capacity than the original ADRA. Eight chemicals that were false negatives when tested with 1 mM test chemical solutions were retested with test chemical solutions between 2 and 5 mM, which showed 4 mM to be the optimal molar‐concentration for ADRA testing. When 82 chemicals used in the original development were retested with 4 mM test chemical solutions, false negative results were reduced by four. When an additional 85 chemicals used to evaluate the weight‐concentration approach to ADRA were retested, the results essentially replicated those obtained with 0.5 mg/ml test chemical solutions and gave 10 fewer false negatives than original ADRA with 1 mM solutions. A comparison of these results for 136 chemicals showed that ADRA testing with 4 mM solutions achieved a four percentage point improvement in accuracy over original ADRA and a two percentage point improvement over DPRA testing. Abstract : The Amino acid Derivative Reactivity Assay (ADRA) is a convenient and effective in chemico test method as a means of predicting skin sensitization potential. The present study determined an optimal molar concentration that achieves even higher predictive capacity than the original ADRA test method. A comparison of these results for 136 chemicals showed that ADRA testing with optimal molar concentration achieved a four percentage point improvement in accuracy over with the original method.