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Chilton, ML, Api, AM, Foster, RS, Gerberick, GF, Lavelle, M, Macmillan, DS, Na, M, O'Brien, D, O'Leary-Steele, C, Patel, M, Ponting, DJ, Roberts, DW, Safford, RJ and Tennant, RE (2022) Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system. Regulatory Toxicology and Pharmacology, 133. p. 105200. ISSN 0273-2300
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Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
The Dermal Sensitisation Thresholds (DST) are Thresholds of Toxicological Concern, which can be used to justify exposure-based waiving when conducting a skin sensitisation risk assessment. This study aimed to update the published DST values by expanding the size of the Local Lymph Node Assay dataset upon which they are based, whilst assigning chemical reactivity using an in silico expert system (Derek Nexus). The potency values within the expanded dataset fitted a similar gamma distribution to that observed for the original dataset. Derek Nexus was used to classify the sensitisation activity of the 1152 chemicals in the expanded dataset and to predict which chemicals belonged to a High Potency Category (HPC). This two-step classification led to three updated thresholds: a non-reactive DST of 710 μg/cm2 (based on 79 sensitisers), a reactive (non-HPC) DST of 73 μg/cm2 (based on 331 sensitisers) and an HPC DST of 1.0 μg/cm2 (based on 146 sensitisers). Despite the dataset containing twice as many sensitisers, these values are similar to the previously published thresholds, highlighting their robustness and increasing confidence in their use. By classifying reactivity in silico the updated DSTs can be applied within a skin sensitisation risk assessment in a reproducible, scalable and accessible manner.
| Item Type: | Article |
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| Uncontrolled Keywords: | Derek Nexus; Dermal Sensitisation Threshold (DST); Exposure-based waiving; In silico expert system; Quantitative Risk Assessment (QRA); Skin sensitisation; Threshold of Toxicological Concern (TTC); 1115 Pharmacology and Pharmaceutical Sciences; Toxicology |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RA Public aspects of medicine > RA1190 Toxicology. Poisions R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Elsevier |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 01 Aug 2022 09:02 |
| Last Modified: | 01 Aug 2022 09:02 |
| DOI or ID number: | 10.1016/j.yrtph.2022.105200 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/17313 |
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