Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation

Abstract

The Technical Committee of Classification and Labelling dealing with harmonized classification of substances and classification criteria under Directive 67/548/EEC on behalf of the European Commission nominated an expert group on skin sensitization in order to investigate further the possibility for potency consideration of skin sensitizers for future development of the classification criteria. All substances and preparations should be classified on the basis of their intrinsic properties and should be labelled accordingly with the rules set up in the Directive 67/548/EEC. The classification should be the same under their full life cycle and in the case that there is no harmonized classification the substance or preparation should be self-classified by the manufacturer in accordance with the same criteria. The Directive does not apply to certain preparations in the finished state, such as medical products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could be translated into practical thresholds and whether these could be set for both induction and elicitation. Examples are given for substances falling into various potency groups for skin sensitization relating to results from the local lymph node assay, the guinea pig maximization test, the Buehler method and human experience.

Epoxy Resin Monomers with Reduced Skin Sensitizing Potency

“…The new ERMs are classified as moderate skin sensitizers in comparison to DGEBA and DGEBF, which are strong skin sensitizers. 32 To our knowledge, these are the first reported ERMs that are only moderately sensitizing. This is also the first time that a combined medicinal chemistry/toxicology approach has been used to design…”

“…32 For registration in REACH, the LLNA is the preferred method for measuring skin sensitization potential in animals. 36 Polymerization procedure.…”

“…The four new ERMs are classified as moderate sensitizers (EC3>2% w/v) in accordance with regulatory guidelines in comparison to the commercially available monomers DGEBA and DGEBF which are classified as strong sensitizers (0.2<EC3≤2% w/v) ( Figure 2). 32 To establish whether there was a statistically significant difference between the sensitizing potencies of the new ERMs and DGEBA, an extension of the LLNA using non-pooled lymph nodes was applied. This modified method was used in our previous work with epoxy resin analogs as well as in other studies by the group.…”

“…30,31 DGEBA and DGEBF are classified as strong sensitizers in both species according to regulatory guidelines. 32 It would be highly advantageous to replace these strongly sensitizing ERMs with less hazardous alternatives.…”

Effect of Prolonged Repeated Exposure to Formaldehyde Donors with Doses Below the EC3 Value on Draining Lymph Node Responses

“…The quantitative data obtained in the LLNA might be of use as a starting point for the risk assessment of individual chemicals rather then an identification as sensitizer or non-sensitizer (Kimber et al, 2001;Basketter et al, 2005aBasketter et al, , 2005b. This opens the possibility for sensitizers to perform a more in-depth risk assessment to estimate relatively safe exposure levels for ingredients in consumer products.…”