title: IgG and IgE antibody responses following exposure of Brown Norway rats to trimellitic anhydride: comparison of inhalation and topical exposure.
abstract: A variety of chemicals can cause sensitisation of the respiratory tract and occupational asthma, including certain acid anhydrides, diisocyanates and reactive dyes. As yet, no well-validated methods are available for the toxicological evaluation of the respiratory sensitising potential of chemicals. One approach which has been explored recently is the evaluation of induced IgE responses or cytokine expression patterns in rats or mice following topical exposure to chemical. Thus, it has been demonstrated that topical exposure of rodents to respiratory sensitising chemicals, but not to contact allergens, causes a dose-dependent and time-related increase in the concentration of total IgE. Using the reference respiratory allergen trimellitic anhydride (TMA), we have considered here the influence of route of exposure on the nature of induced immune responses. Specific IgG and IgE antibody responses and changes in total serum concentration of IgE have been measured following exposure of Brown Norway (BN) starin rats to TMA by topical administration or by inhalation. Exposure to TMA by both routes resulted in the stimulation of specific IgG and IgE antibody, although responses were considerably more vigorous after dermal exposure. Topical treatment also provoked marked and sustained increases in total serum IgE levels, whereas exposure via the respiratory tract stimulated a more transient elevation of this immunoglobulin in a minority of animals which reached statistical significance only at the highest dose group. The lesser vigour of the immune response following inhalation exposure is likely to be related to the considerably lower total antigenic dose which is delivered by this route. Nevertheless, these results show that the nature of immune response with respect to antibody isotype profile provoked by topical administration of TMA is qualitatively comparable with that stimulated by inhalation exposure to the same chemical. For the purposes of hazard assessment and identification of potential chemical respiratory allergens as a function of induced changes in serum IgE concentration, however, the evidence is that topical administration of test material is the preferred route of exposure.
authors.affiliation: Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK.
authors.forename: E Vicky
authors.initials: EV
authors.lastname: Warbrick
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
mesh_terms: D000280:Administration, Inhalation; D000287:Administration, Topical; D000336:Aerosols; D000388:Air / Q000032:analysis; D000812:Anhydrides / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008297:Male; D008670:Metals / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011914:Rats, Inbred BN; D012709:Serum Albumin
chemical_list: D000336:Aerosols; D000812:Anhydrides; D007074:Immunoglobulin G; D008670:Metals; D012709:Serum Albumin; D007073:Immunoglobulin E