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LRI-B14: Skin Sensitisation – Chemical Applicability Domain of the Local Lymph Node Assay (LLNA) – Deadline: 1 September 2013

Background

Since the publication of the OECD AOP for skin sensitisation, there have been even greater efforts to anchor the development and evaluation of assays to key events within the AOP. Much of that type of evaluation is likely to use the LLNA as its benchmark. Whilst the LLNA has been through an extensive validation phase relative to the incumbent assay of the time, the GPMT, to date there has been no systematic evaluation of the chemical applicability domain of the LLNA, i.e. an exercise to define in chemical terms which classes of chemicals are well predicted, which are liable to be wrongly predicted and which are unpredictable by this in vivo method. This is particularly critical when considering the outcomes of new in vitro test methods in order to be able to discriminate whether the result is reasonable or whether the outcome is impacted by uncertainty in the LLNA which is used as a basis of comparison.

Objectives

From a scientific perspective, the applicability domain should be defined in terms of the chemicals that were used in the validation exercise: compounds whose chemical properties were not represented in the validation set are outside the applicability domain. The project's objectives are to:

  1. Identify and evaluate existing QSARs/SARs that have been developed on the basis of guinea pig data and compare the trends to those in the LLNA.

2. Characterise quantitatively the mechanistic domains that have been already established qualitatively.

3. Review how well the known bio-activation processes are represented in the LLNA and the GP are aligned.

4. Evaluate the range of key physicochemical properties are covered by the LLNA: hydrophobicity values as modelled by LogKow, and size as quantified by covered by the MW and volatility as modelled by vapour pressure.

5. Compare and contrast the physchem characteristics and the mechanistic domains of the chemicals included in the in vitro validation sets against the LLNA data available.

Scope

The scope will be limited by the available data that can be readily found in the peer reviewed literature. The ECHA REACH website will be utilised as an additional resource of information.

Related links

Download here the full version of the RfP LRI-B14.

Timing: 9-12 months

LRI funding: €50.000 - 60.000

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