Academic Journal

Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system

التفاصيل البيبلوغرافية
العنوان: Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system
المؤلفون: 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, Tennant, RE
بيانات النشر: Elsevier
سنة النشر: 2022
المجموعة: Liverpool John Moores University: LJMU Research Online
مصطلحات موضوعية: QH301 Biology, RA1190 Toxicology. Poisions, RS Pharmacy and materia medica
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: text
اللغة: English
Relation: https://researchonline.ljmu.ac.uk/id/eprint/17313/1/Updating%20the%20Dermal%20Sensitisation%20Thresholds%20using%20an%20expanded%20dataset%20and%20an%20in%20silico%20expert%20system.pdf; 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
DOI: 10.1016/j.yrtph.2022.105200
الاتاحة: http://researchonline.ljmu.ac.uk/id/eprint/17313/
https://researchonline.ljmu.ac.uk/id/eprint/17313/1/Updating%20the%20Dermal%20Sensitisation%20Thresholds%20using%20an%20expanded%20dataset%20and%20an%20in%20silico%20expert%20system.pdf
https://doi.org/10.1016/j.yrtph.2022.105200
Rights: cc_by
رقم الانضمام: edsbas.5C6C4FB4
قاعدة البيانات: BASE
الوصف
DOI:10.1016/j.yrtph.2022.105200