No abstract is available for this article. mehr
Um alle Funktionen dieser Seite zu nutzen, aktivieren Sie bitte die Cookies in Ihrem Browser.
Mit einem my.bionity.com-Account haben Sie immer alles im Überblick - und können sich Ihre eigene Website und Ihren individuellen Newsletter konfigurieren.
Dermal contact with chemicals may lead to an inflammatory reaction known as allergic contact dermatitis. Consequently, it is important to assess new and existing chemicals for their skin sensitizing potential and to mitigate exposure accordingly. There is an urgent need to develop quantitative non‐animal methods to better predict the potency of potential sensitizers, driven largely by European Union (EU) Regulation 1223/2009, which forbids the use of animal tests for cosmetic ingredients sold in the EU. A Nearest Neighbours in silico model was developed using an in‐house dataset of 1096 murine local lymph node (LLNA) studies. The EC3 value (the effective concentration of the test substance producing a threefold increase in the stimulation index compared to controls) of a given chemical was predicted using the weighted average of EC3 values of up to 10 most similar compounds within the same mechanistic space (as defined by activating the same Derek skin sensitization alert). The model was validated using previously unseen internal (n = 45) and external (n = 103) data and accuracy of predictions assessed using a threefold error, fivefold error, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) and Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classifications. In particular, the model predicts the GHS skin sensitization category of compounds well, predicting 64% of chemicals in an external test set within the correct category. Of the remaining chemicals in the previously unseen dataset, 25% were over‐predicted (GHS 1A predicted: GHS 1B experimentally) and 11% were under‐predicted (GHS 1B predicted: GHS 1A experimentally). Copyright © 2017 John Wiley & Sons, Ltd.
|Autoren:||Steven J. Canipa, Martyn L. Chilton, Rachel Hemingway, Donna S. Macmillan, Alun Myden, Jeffrey P. Plante, Rachael E. Tennant, Jonathan D. Vessey, Thomas Steger‐Hartmann, Janet Gould, Jedd Hillegass, Sylvain Etter, Benjamin P. C. Smith, Angela White, Paul Sterchele, Ann De Smedt, Devin O'Brien, Rahul Parakhia|
|Journal:||Journal of Applied Toxicology|
Abstract The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The world‐wide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high ... mehr
Abstract Background Whether morbidity from the 1918‐19 influenza pandemic discriminated by socioeconomic status has remained a subject of debate for 100 years. In lack of data to study this issue recent literature have hypothesized that morbidity was “socially neutral”. Objectives ... mehr