Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals.
Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological and functional) after inhalation challenge was examined in the present study. In Brown Norway (BN) and Wistar rats, serum IgE concentrations were examined following topical exposure of chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer; dinitrochlorobenzene (DNCB), a dermal sensitizer with no known potential to cause respiratory allergy; and methyl salicylate, a skin irritant devoid of sensitizing properties. Functional and histopathological changes in the respiratory tract were examined after subsequent inhalatory challenge with these chemicals. Of the three tested chemicals, only topical exposure to TMA resulted in a significant increase in total serum IgE concentrations in the high-IgE-responding BN rat. Upon subsequent inhalatory challenge of these rats, TMA induced specific airway reactions which included a sharp decrease in respiratory rate during challenge, followed by an increase in breathing rate with a concomitant decrease in tidal volume 24 and 48 h after inhalatory challenge, and histopathological changes in the larynx and lungs of animals necropsied 48 h after challenge. Interestingly, despite low IgE levels, TMA induced histopathological changes in the larynx and lungs of Wistar rats too. Laryngeal changes were also observed in Wistar rats upon sensitization and challenge with DNCB. These data suggest that increased total serum IgE after topical sensitization is associated with immediate-type specific airway reactivity after inhalation challenge in BN rats and thus may be a valuable parameter in testing for respiratory sensitization potential of LMW compounds. Histopathological examination upon subsequent inhalation challenge of sensitized low-IgE-responders may provide information on other allergic inflammatory airway reactions.
Toxicology Division, TNO Nutrition and Food Research Institute, Zeist, The Netherlands. jarts@voeding.tno.nl
J H
JH
Arts
C F
CF
Kuper
S M
SM
Spoor
N
N
Bloksma
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001835:Body Weight; D001980:Bronchi / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D004137:Dinitrochlorobenzene / Q000009:adverse effects*; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis; D009929:Organ Size; D010796:Phthalic Anhydrides / Q000009:adverse effects*; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D012459:Salicylates / Q000009:adverse effects*
D000485:Allergens; D004137:Dinitrochlorobenzene; D010796:Phthalic Anhydrides; D012459:Salicylates; D007073:Immunoglobulin E; C015559:trimellitic anhydride; C033069:methyl salicylate