Hapten–protein binding: from theory to practical application in the in vitro prediction of skin sensitization

Abstract

In view of the forthcoming European Union ban on in vivo testing of cosmetic and toiletry ingredients, following the publication of the 7th amendment to the Cosmetics Directive, the search for practical, alternative, non-animal approaches is gathering pace. For the end-point of skin sensitization, the ultimate goal, i.e. the development and validation of alternative in vitro/in silico assays by 2013, may be achieved through a better understanding of the skin sensitization process on the cellular and molecular levels. One of the key molecular events in skin sensitization is protein haptenation, i.e. the chemical modification of self-skin protein(s) thus forming macromolecular immunogens. This concept is widely accepted and in theory can be used to explain the sensitizing capacity of many known skin sensitizers. Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. In this review, we consider some of the theoretical aspects of protein haptenation, how mechanisms of protein haptenation can be investigated experimentally and how we can use such knowledge in the development of novel, alternative approaches for predicting skin sensitization potential in the future.

Idiosyncratic Adverse Drug Reactions: Current Concepts

“…Subsequently, researchers in the field of contact allergy have shown that the reactivity of a chemical and its ability to bind covalently to protein is indisputably linked to the activation of immune cells and sensitizing potential (Meschkat et al, 2001a,b;Alvarez-Sanchez et al, 2003). In fact, these observations have resulted in the development and use of chemical reactivity measurements for the predictive identification of skin sensitizing chemicals (Divkovic et al, 2005;Gerberick et al, 2007Gerberick et al, , 2008. The development of sophisticated protein mass spectrometry methods to measure the binding of sensitizing chemicals to protein has greatly assisted analysis of chemical protein interactions (Jenkins et al, 2008).…”

Analogues of the Epoxy Resin Monomer Diglycidyl Ether of Bisphenol F: Effects on Contact Allergenic Potency and Cytotoxicity

“…Reactive amino acid residues that play a role in skin sensitization include cysteines (thiol), lysines (amino) and to a lesser extent arginines, histidines, methionines and tyrosines. 45 It has been previously demonstrated that the epoxy reactive diluent PGE reacts selectively with the thiol residue of a model peptide. 23 We firstly investigated the reactivity of DGEBF and compound 2 with a cysteine derivative (N-acetyl-L-cysteine methyl ester, N-ACME).…”

Identification of PDL-1 as a novel biomarker of sensitizer exposure in dendritic-like cells

“…A European Union ban on in vivo testing of cosmetic and toiletry ingredients will be enforced in 2013, therefore, there is a need to develop novel and accurate alternative methods for assessing hazard risks and potential potencies of sensitizing chemicals (Divkovic et al, 2005). Several contact sensitizers, known to cause hypersensitivity responses, have been shown to directly induce DC maturation in vitro (Arrighi et al, 2001) (Coutant et al, 1999).…”