Allergic contact dermatitis (ACD) is a cell-mediated immune response to sma
ll molecular weight chemicals that contact and penetrate the skin. There ar
e a variety of characteristics that determine whether a chemical can functi
on as a contact sensitizer (or allergen) including the ability to penetrate
into the skin, react with protein and be recognized as antigenic by immune
cells. The ultimate challenge for developing non-animal test methods for s
kin sensitization testing will be applying our mechanistic understanding of
ACD to the design of predictive in vitro alternative test methods. Specifi
cally, the in vitro approach should be designed so that a chemical's potent
ial to penetrate the skin, react with protein/peptide (biotransformation ma
y be required) and initiate an antigen-specific immune response is incorpor
ated in the test methods developed. In this review, we have focused on cell
ular-based assays that have been developed or proposed far assessing a chem
ical's skin sensitization potential in vitro. All of the promising leads to
date are based on observations made from in vivo studies conducted in anim
als and humans, and therefore have a strong mechanistic foundation. However
, it remains to be demonstrated whether a single in vitro test, or several
in vitro tests in combination, which model the critical steps in sensitizat
ion, can replace animal experiments for predicting contact allergic reactio
ns in humans. Regardless, the future looks promising with continued develop
ment of our understanding of the chemical and biological aspects of allergi
c contact dermatitis, and most importantly, with the application of genomic
s/proteomics to this field on the immediate horizon. (C) 2001 Elsevier Scie
nce Ltd. All rights reserved.