Induction of respiratory hypersensitivity to diphenylmethane-4,4'-diisocyanate (MDI) in guinea pigs. Influence of route of exposure.
The induction of respiratory sensitization in guinea pigs to diphenylmethane-4,4'-diisocyanate (MDI), a known human respiratory allergen, has been investigated and different routes of exposure compared. Guinea pigs were exposed to MDI by i.d. injection, by topical application or by inhalation. Pulmonary hypersensitivity was measured subsequently as a function of changes in respiratory rate following challenge with atmospheres containing MDI. In addition, contact hypersensitivity was measured by topical challenge and antibody responses evaluated by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). Attempts to sensitize guinea pigs by inhalation exposure to MDI were unsuccessful. Antibody responses and contact sensitization were both infrequent and low grade, and no animals exhibited pulmonary responses following challenge with atmospheric MDI. In contrast, sensitization by either i.d. injection or topical application of MDI induced antibody responses in the majority of animals. Moreover, a proportion of animals in each case exhibited pulmonary responses following subsequent inhalation challenge. These data indicate that the route of exposure influences markedly the effectiveness of sensitization to respiratory allergens such as MDI and that skin contact may be an important cause of occupational respiratory allergy.
Rattray
N J
NJ
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Botham
P A
PA
Hext
P M
PM
Woodcock
D R
DR
Fielding
I
I
Dearman
R J
RJ
Kimber
I
I
D000280:Administration, Inhalation; D000287:Administration, Topical; D000818:Animals; D004333:Drug Administration Routes; D005260:Female; D006168:Guinea Pigs; D007271:Injections, Intradermal; D017953:Isocyanates / Q000008:administration & dosage* / Q000009:adverse effects*; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D001559:Benzhydryl Compounds
D017953:Isocyanates; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds