Abstract
Introduction: The amino acid derivative reactivity assay (ADRA) is a novel in chemico alternative to animal testing for assessment of skin sensitization potential. The conventional ADRA protocol stipulates that test chemical solutions should be prepared to a specific molar concentration, allowing only for use of test chemicals with known molecular weights. Since many potential test substances are prepared by weight concentration or contain multiple unknown chemicals, this study was conducted to verify if it is possible to accurately assess the sensitization potential of test chemical solutions prepared at a specific weight concentration. Methods: (1) Test chemical solutions for 82 chemicals were prepared at four different weight concentrations. Results were evaluated for agreement with in vivo results. (2) A liquid mixture comprising ten different non-sensitizers was prepared at 1 mg/mL. Ten different sensitizers of varying sensitization potencies were added individually to this mixture. The resulting pseudobinary mixtures were tested to confirm that the sensitizers could be detected. Results: (1) The accuracies for test chemical solutions prepared at 0.5 and 0.2 mg/mL were 87.8% and 86.6%, respectively, which were roughly equivalent to the accuracy of 86.6% achieved with a solution prepared at the conventional molar concentration of 1 mM. In contrast, the accuracies for solutions prepared at 0.1 and 0.05 mg/mL were 82.9% and 74.4%, respectively, both of which were lower than that obtained with the conventional method. (2) Sensitizers added to the liquid mixture at 0.5 mg/mL were all correctly detected. Discussion: Preparing test chemical solutions at a weight concentration of 0.5 mg/mL decreased false negatives and increased false positives while improving prediction accuracy, which suggests that the sensitization potential of mixtures can also be assessed with this method.
| Original language | English |
|---|---|
| Pages (from-to) | 67-79 |
| Number of pages | 13 |
| Journal | Journal of Pharmacological and Toxicological Methods |
| Volume | 97 |
| DOIs | |
| Publication status | Published - May 1 2019 |
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Keywords
- ADRA
- DPRA
- In chemico
- Key event
- Methods
- Protein reactivity assay
- Skin sensitisation
- Weight concentration
ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Expanding the applicability of the amino acid derivative reactivity assay : Determining a weight for preparation of test chemical solutions that yield a predictive capacity identical to the conventional method using molar concentration and demonstrating the capacity to detect sensitizers in liquid mixtures. / Yamamoto, Yusuke; Fujita, Masaru; Wanibuchi, Sayaka; Katsuoka, Yasuhiro; Ono, Atsushi; Kasahara, Toshihiko.
In: Journal of Pharmacological and Toxicological Methods, Vol. 97, 01.05.2019, p. 67-79.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expanding the applicability of the amino acid derivative reactivity assay
T2 - Determining a weight for preparation of test chemical solutions that yield a predictive capacity identical to the conventional method using molar concentration and demonstrating the capacity to detect sensitizers in liquid mixtures
AU - Yamamoto, Yusuke
AU - Fujita, Masaru
AU - Wanibuchi, Sayaka
AU - Katsuoka, Yasuhiro
AU - Ono, Atsushi
AU - Kasahara, Toshihiko
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Introduction: The amino acid derivative reactivity assay (ADRA) is a novel in chemico alternative to animal testing for assessment of skin sensitization potential. The conventional ADRA protocol stipulates that test chemical solutions should be prepared to a specific molar concentration, allowing only for use of test chemicals with known molecular weights. Since many potential test substances are prepared by weight concentration or contain multiple unknown chemicals, this study was conducted to verify if it is possible to accurately assess the sensitization potential of test chemical solutions prepared at a specific weight concentration. Methods: (1) Test chemical solutions for 82 chemicals were prepared at four different weight concentrations. Results were evaluated for agreement with in vivo results. (2) A liquid mixture comprising ten different non-sensitizers was prepared at 1 mg/mL. Ten different sensitizers of varying sensitization potencies were added individually to this mixture. The resulting pseudobinary mixtures were tested to confirm that the sensitizers could be detected. Results: (1) The accuracies for test chemical solutions prepared at 0.5 and 0.2 mg/mL were 87.8% and 86.6%, respectively, which were roughly equivalent to the accuracy of 86.6% achieved with a solution prepared at the conventional molar concentration of 1 mM. In contrast, the accuracies for solutions prepared at 0.1 and 0.05 mg/mL were 82.9% and 74.4%, respectively, both of which were lower than that obtained with the conventional method. (2) Sensitizers added to the liquid mixture at 0.5 mg/mL were all correctly detected. Discussion: Preparing test chemical solutions at a weight concentration of 0.5 mg/mL decreased false negatives and increased false positives while improving prediction accuracy, which suggests that the sensitization potential of mixtures can also be assessed with this method.
AB - Introduction: The amino acid derivative reactivity assay (ADRA) is a novel in chemico alternative to animal testing for assessment of skin sensitization potential. The conventional ADRA protocol stipulates that test chemical solutions should be prepared to a specific molar concentration, allowing only for use of test chemicals with known molecular weights. Since many potential test substances are prepared by weight concentration or contain multiple unknown chemicals, this study was conducted to verify if it is possible to accurately assess the sensitization potential of test chemical solutions prepared at a specific weight concentration. Methods: (1) Test chemical solutions for 82 chemicals were prepared at four different weight concentrations. Results were evaluated for agreement with in vivo results. (2) A liquid mixture comprising ten different non-sensitizers was prepared at 1 mg/mL. Ten different sensitizers of varying sensitization potencies were added individually to this mixture. The resulting pseudobinary mixtures were tested to confirm that the sensitizers could be detected. Results: (1) The accuracies for test chemical solutions prepared at 0.5 and 0.2 mg/mL were 87.8% and 86.6%, respectively, which were roughly equivalent to the accuracy of 86.6% achieved with a solution prepared at the conventional molar concentration of 1 mM. In contrast, the accuracies for solutions prepared at 0.1 and 0.05 mg/mL were 82.9% and 74.4%, respectively, both of which were lower than that obtained with the conventional method. (2) Sensitizers added to the liquid mixture at 0.5 mg/mL were all correctly detected. Discussion: Preparing test chemical solutions at a weight concentration of 0.5 mg/mL decreased false negatives and increased false positives while improving prediction accuracy, which suggests that the sensitization potential of mixtures can also be assessed with this method.
KW - ADRA
KW - DPRA
KW - In chemico
KW - Key event
KW - Methods
KW - Protein reactivity assay
KW - Skin sensitisation
KW - Weight concentration
UR - http://www.scopus.com/inward/record.url?scp=85064084656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064084656&partnerID=8YFLogxK
U2 - 10.1016/j.vascn.2019.01.001
DO - 10.1016/j.vascn.2019.01.001
M3 - Article
VL - 97
SP - 67
EP - 79
JO - Journal of Pharmacological and Toxicological Methods
JF - Journal of Pharmacological and Toxicological Methods
SN - 1056-8719
ER -