DOC 046 – Potency Values from the Local Lymph Node Essay: Application to classification, labelling and risk assessment

DOC 046 : Potency Values from the Local Lymph Node Assay: Application to Classification, Labelling and Risk Assessment | December 2008

In this ECETOC Document, the use of potency values derived from local lymph node assay (LLNA) data has been considered to address the following terms of reference:

• Determine whether an EC3 potency value can be used as a cut-off criterion for the classification and labelling of both substances and preparations;
• Evaluate LLNA data in risk assessment approaches for skin sensitisation and, by taking into account potency considerations, provide a rationale for using concentration responses and corresponding no-effect concentrations.

The following recommendations have been made:

• Although the Task Force was of the view that skin sensitising chemicals having high EC3 values may represent only relatively low risks for human health, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling of substances as R43;
• Reviews have been conducted of: 1) previous ECETOC Task Force recommendations for the use of four categories for characterising contact allergens and preparations as a function of skin sensitising potency, and 2) proposals for categorisation according to potency that have been made since then.  The conclusion drawn from those analyses was that the most appropriate, science-based scheme for classification of contact allergens according to relative potency is one in which four sub-categories are identified.  It was proposed that these categories should be termed ?extreme?, ?strong?, ?moderate? and ?weak? to reflect differing skin sensitisation potency based on derived EC3 values.  The recommendations made by the previous Task Force have been endorsed (ECETOC, 2003 a,b);
• Quantitative risk assessment approaches describe the relationship between the calculated exposure to a sensitising chemical and the acceptable exposure level.  Because proliferation of cells in draining lymph nodes is related causally and quantitatively to the extent to which skin sensitisation will be acquired (potency), LLNA EC3 values are well suited to, and recommended for, determination of a no expected sensitisation induction level (NESIL) that represents the first step in the quantitative risk assessment process.
  These recommendations regarding the use of potency considerations derived from LLNA data effectively move the LLNA from the realm of hazard identification to a key component of the development of accurate risk assessments, which can be used as a sound scientific basis for classification and labelling.