Predicting skin sensitisation using a decision tree integrated testing strategy with an in silico model and in chemico/in vitro assays

Regulatory Toxicology and Pharmacology : RTP
Donna S MacmillanChristopher G Barber

Abstract

There is a pressing need for non-animal methods to predict skin sensitisation potential and a number of in chemico and in vitro assays have been designed with this in mind. However, some compounds can fall outside the applicability domain of these in chemico/in vitro assays and may not be predicted accurately. Rule-based in silico models such as Derek Nexus are expert-derived from animal and/or human data and the mechanism-based alert domain can take a number of factors into account (e.g. abiotic/biotic activation). Therefore, Derek Nexus may be able to predict for compounds outside the applicability domain of in chemico/in vitro assays. To this end, an integrated testing strategy (ITS) decision tree using Derek Nexus and a maximum of two assays (from DPRA, KeratinoSens, LuSens, h-CLAT and U-SENS) was developed. Generally, the decision tree improved upon other ITS evaluated in this study with positive and negative predictivity calculated as 86% and 81%, respectively. Our results demonstrate that an ITS using an in silico model such as Derek Nexus with a maximum of two in chemico/in vitro assays can predict the sensitising potential of a number of chemicals, including those outside the applicability domain of existing non-animal...Continue Reading

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Citations

Apr 20, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D UrbischR Landsiedel
Jul 28, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D AsturiolA Worth
Jan 21, 2017·SAR and QSAR in Environmental Research·G R VerheyenS Van Miert
Jan 21, 2017·International Journal of Pharmaceutics·Andreia AlmeidaFrancisca Rodrigues
Apr 8, 2017·Contact Dermatitis·William C DreweRichard V Williams
Mar 10, 2017·Regulatory Toxicology and Pharmacology : RTP·David BasketterIan Kimber
May 12, 2017·Chemical Research in Toxicology·David W RobertsAnne Marie Api
Feb 24, 2018·Critical Reviews in Toxicology·Nicole C KleinstreuerDirk Petersohn
Feb 7, 2018·Expert Opinion on Drug Discovery·Emanuela CorsiniMarc Pallardy
Nov 30, 2018·Critical Reviews in Toxicology·Anke WilmJohannes Kirchmair
Nov 3, 2016·Alternatives to Laboratory Animals : ATLA·Terry W SchultzOvanes G Mekenyan

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