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Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 2. The biological variability of the murine Local Lymph Node Assay (LLNA) for skin sensitisation.

Abstract
The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory toxicology test for skin sensitisation, quantifying potency as the EC3, the concentration of chemical giving a threefold increase in thymidine uptake in the local lymph node. Existing LLNA data can, along with clinical data, provide useful comparator information on the potency of sensitisers. Understanding of the biological variability of data from LLNA studies is important for those developing non-animal based risk assessment approaches for skin allergy. Here an existing set of 94 EC3 values for 12 chemicals, all tested at least three times in the same vehicle have been analysed by calculating standard deviations (SD) for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values are within a factor of 2, comparable to those for physico-chemical measurements such as partition coefficients and solubility. The residual SDs of Quantitative Mechanistic Models (QMMs) based on physical organic chemistry parameters are similar to the overall SD of the LLNA, indicating that QMMs of this type are unlikely to be bettered for predictive accuracy.
AuthorsDavid W Roberts, Anne Marie Api, Aynur O Aptula
JournalRegulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 80 Pg. 255-9 (Oct 2016) ISSN: 1096-0295 [Electronic] Netherlands
PMID27470439 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2016 Elsevier Inc. All rights reserved.
Chemical References
  • Irritants
Topics
  • Administration, Cutaneous
  • Animals
  • Data Mining
  • Databases, Factual
  • Dermatitis, Allergic Contact (etiology, immunology)
  • Dose-Response Relationship, Drug
  • Humans
  • Irritants (chemistry, metabolism, toxicity)
  • Local Lymph Node Assay
  • Lymph Nodes (drug effects, pathology)
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Reproducibility of Results
  • Skin (drug effects, immunology, metabolism)
  • Skin Absorption
  • Species Specificity
  • Structure-Activity Relationship

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