Alternative approaches to the identification and characterization of chemical allergens.
Chemical allergy can take a variety of forms, those of greatest importance in an occupational setting being skin sensitization resulting in allergic contact dermatitis and sensitization of the respiratory tract associated with asthma and other symptoms. In both cases there is a need for predictive test methods that allow the accurate identification of sensitizing chemicals. Well characterized methods are available for skin sensitization testing, and although to date no tests for respiratory sensitization have been formally validated, progress has been made in defining suitable animal models. In recent years there have been significant advances in our understanding of the cellular and molecular mechanisms through which allergic sensitization to chemicals is induced and regulated. Such progress provides us now with new opportunities to consider alternative approaches to sensitization testing, including the design of in vitro test methods. The greatest investment has been in exploring novel methods for the identification of contact sensitizers and it is upon this aspect of chemical allergy that this article is focused. Described here are some of the general requirements of in vitro test methods for skin sensitization, and progress that has been made in developing suitable approaches with particular emphasis on the utility of dendritic cell culture systems.
Kimber
I
I
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. ian.kimber@syngenta.com
Pichowski
J S
JS
Betts
C J
CJ
Cumberbatch
M
M
Basketter
D A
DA
Dearman
R J
RJ
D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000826:Animal Testing Alternatives; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D009783:Dermatitis, Occupational / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012882:Skin Tests / Q000379:methods*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D000485:Allergens; D007375:Interleukin-1; D012333:RNA, Messenger; D012967:Sodium Dodecyl Sulfate; D004139:Dinitrofluorobenzene