Quantifying human susceptibility to contact sensitization; risk assessments now and in the future


  • Conflicts of interest: An educational grant was received from Unilever plc to support some of the work described herein.

Peter S. Friedmann
Emeritus Professor of Dermatology
Dermatopharmacology Unit
Level F South Block (mail point 825)
Southampton University Hospital NHS Trust
Tremona Road
SO16 6YD
Tel: 02380-796148
Fax: 02380-704183
e-mail: psf@soton.ac.uk


Assessment and quantification of the risk that a chemical will induce allergic contact sensitization presently depend heavily on background data from animal tests. Following the banning of animal testing of chemicals used in cosmetics and personal products in Europe after 2013, alternative approaches will be required. The chemical properties likely to make a given compound a sensitizer can be determined in vitro with reasonable certainty, but confirmation that it is a sensitizer comes only from in vivo exposure to it. Assessment of the sensitization risks involves consideration of how much of the compound will be applied to skin, for how long, and at which sites. However, the in vivo interactions of the chemical with the skin, with regard to its permeability, and biochemical and immune defences, cannot be predicted from a theoretical position. The xenobiotic-metabolizing enzymes and antioxidant defences may degrade chemicals or may generate potentially immunogenic haptens. Many factors can modify the skin and the immune response, including sex, race, age, genetic programming of epidermal permeability, and/or antioxidant and drug-metabolizing pathways. The only certain way to evaluate whether a chemical will sensitize is in vivo exposure, and the nature of the hazard is revealed by determination of the dose–response relationship. This review shows there is still a serious gap in our understanding of the biological factors and variables involved in conferring resistance or susceptibility to the development of allergic sensitization by chemicals. We are not yet in a position to predict sensitization by chemicals from a theoretical starting point.