Respiratory sensitization and allergy: current research approaches and needs.
There are currently no accepted regulatory models for assessing the potential of a substance to cause respiratory sensitization and allergy. In contrast, a number of models exist for the assessment of contact sensitization and allergic contact dermatitis (ACD). Research indicates that respiratory sensitizers may be identified through contact sensitization assays such as the local lymph node assay, although only a small subset of the compounds that yield positive results in these assays are actually respiratory sensitizers. Due to the increasing health concerns associated with occupational asthma and the impending directives on the regulation of respiratory sensitizers and allergens, an approach which can identify these compounds and distinguish them from contact sensitizers is required. This report discusses some of the important contrasts between respiratory allergy and ACD, and highlights several prominent in vivo, in vitro and in silico approaches that are being applied or could be further developed to identify compounds capable of causing respiratory allergy. Although a number of animal models have been used for researching respiratory sensitization and allergy, protocols and endpoints for these approaches are often inconsistent, costly and difficult to reproduce, thereby limiting meaningful comparisons of data between laboratories and development of a consensus approach. A number of emerging in vitro and in silico models show promise for use in the characterization of contact sensitization potential and should be further explored for their ability to identify and differentiate contact and respiratory sensitizers. Ultimately, the development of a consistent, accurate and cost-effective model will likely incorporate a number of these approaches and will require effective communication, collaboration and consensus among all stakeholders.
Boverhof
Darrell R
DR
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland MI 48674, USA. RBoverhof@dow.com
Billington
Richard
R
Gollapudi
B Bhaskar
BB
Hotchkiss
John A
JA
Krieger
Shannon M
SM
Poole
Alan
A
Wiescinski
Connie M
CM
Woolhiser
Michael R
MR
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D051381:Rats; D012130:Respiratory Hypersensitivity / Q000276:immunology*
D000485:Allergens; D007371:Interferon-gamma