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

Autor: Chilton ML; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK. Electronic address: martyn.chilton@lhasalimited.org., Api AM; Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, USA., Foster RS; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK., Gerberick GF; GF3 Consultancy, LLC, West Chester, OH, USA., Lavelle M; Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, USA., Macmillan DS; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK., Na M; Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, USA., O'Brien D; Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, USA., O'Leary-Steele C; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK., Patel M; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK., Ponting DJ; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK., Roberts DW; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK., Safford RJ; B-Safe Toxicology Consulting, 31 Hayway, Rushden, Northants, NN10 6AG, UK., Tennant RE; Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2022 Aug; Vol. 133, pp. 105200. Date of Electronic Publication: 2022 Jun 01.
DOI: 10.1016/j.yrtph.2022.105200
Abstrakt: 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/cm 2 (based on 79 sensitisers), a reactive (non-HPC) DST of 73 μg/cm 2 (based on 331 sensitisers) and an HPC DST of 1.0 μg/cm 2 (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.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: