Local lymph node activation and IgE responses in brown Norway and Wistar rats after dermal application of sensitizing and non-sensitizing chemicals.
The local lymph node assay (LLNA) and the IgE test in the mouse are proposed models for predictive recognition of low molecular weight chemicals causing IgE-mediated allergic airway reactions in man. Since rats are commonly used in routine toxicity studies and a previous study (Arts et al. (1996) Food Chem. Toxicol. 34, 55-62) has shown that several rat strains were found appropriate for the LLNA, the suitability of the rat for the IgE test was examined in the present study. Serum IgE concentrations were examined following topical exposure of Brown Norway (BN) and Wistar rats to each of four chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer, dinitrochlorobenzene (DNCB), a dermal sensitizer with no or limited potential to cause respiratory allergy; formaldehyde (FA), a skin irritant and dermal sensitizer with equivocal evidence for respiratory sensitizing potential; methyl salicylate (MS), a skin irritant devoid of sensitizing properties. Of the four tested chemicals, only exposure to TMA resulted in a significant increase in serum IgE concentration and this response was only evoked in the high-IgE-responding BN rat. The latter two chemicals were also tested for lymph node activation, in casu the ear-draining lymph nodes. FA caused a dose-dependent activation of the draining lymph nodes whereas MS was inactive. The results as obtained with TMA, DNCB and MS in the rat are in agreement with human data. The results with FA though, indicate the need for further studies of chemicals that have both irritant and sensitizing properties at about similar concentrations or may act through non-IgE-mediated immune mechanisms.
Arts
J H
JH
TNO Nutrition and Food Research Institute, Toxicology Division, Zeist, The Netherlands.
Dröge
S C
SC
Spanhaak
S
S
Bloksma
N
N
Penninks
A H
AH
Kuper
C F
CF
D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000008:administration & dosage / Q000633:toxicity*; D012882:Skin Tests
D000485:Allergens; D004137:Dinitrochlorobenzene; D010796:Phthalic Anhydrides; D012459:Salicylates; D005557:Formaldehyde; D007073:Immunoglobulin E; C015559:trimellitic anhydride; C033069:methyl salicylate