ASSESSMENT OF CHEMICALS FOR THEIR POTENTIAL TO INDUCE RESPIRATORY ALLERGY IN GUINEA-PIGS - A COMPARISON OF DIFFERENT ROUTES OF INDUCTION AND CONFOUNDING EFFECTS DUE TO PULMONARY HYPERREACTIVITY
J. Pauluhn, ASSESSMENT OF CHEMICALS FOR THEIR POTENTIAL TO INDUCE RESPIRATORY ALLERGY IN GUINEA-PIGS - A COMPARISON OF DIFFERENT ROUTES OF INDUCTION AND CONFOUNDING EFFECTS DUE TO PULMONARY HYPERREACTIVITY, Toxicology in vitro, 8(5), 1994, pp. 981-985
Guinea pigs were sensitized either to selected low molecular weight ch
emicals known to induce respiratory allergy in humans, trimellitic anh
ydride (TMA), toluene diisocyanate (TDI), or diphenylmethane-4,4'-diis
ocyanate (MDI), or to ovalbumin (OA) as a positive control. In most in
stances, sensitization was induced either by repeated intradermal inje
ctions or by a single brief (IS-min) high-concentration inhalation exp
osure. For TMA the repeated high dose intradermal injection regimen wa
s compared with a single low dose intradermal injection regimen. Addit
ionally, the effectiveness of the single 15-min induction protocol was
compared with that of five consecutive inhalation exposures each of 3
hr/day. Animals were challenged 2-3 wk later by exposure to the subst
ance used for induction, either as the free chemical or as a hapten-pr
otein conjugate, and with increasing concentrations of acetylcholine (
ACh). Challenge with the parental or conjugated hapten was used to ass
ess compound-specific immediate onset respiratory hyperreactivity, whi
le ACh challenges were used to identify non-specific airway hyperreact
ivity. After intradermal sensitization with either MDI or TMA guinea p
igs challenged with the corresponding hapten-protein conjugate showed
a moderate incidence of immediate-type respiratory responses. However,
the highest incidence of unequivocal allergic responses was evident f
rom challenge with the hapten rather than with the protein conjugate,
although these responses were only elicited with slightly irritant con
centrations. After challenge with irritant concentrations of TDI, anim
als sensitized intradermally did not experience characteristic changes
in respiratory patterns. On challenge with Ach and the TDI-protein co
njugate these same animals showed an increased airway hyperresponsiven
ess although characteristic stereotypic breathing patterns, as observe
d in sensitized animals challenged with TMA, TMA-protein conjugate, or
OA, were not detected. Comparison of the intradermal and inhalation i
nduction regimens indicated that prior encounters with irritant hapten
s by inhalation reduces the concentration required to elicit airway hy
perresponsiveness. This finding supports the conclusion that in animal
s sensitized and challenged by inhalation, irritant respiratory respon
ses may be misconstrued as immediate-onset allergic responses. It appe
ared that the low dose single intradermal injection protocol is more e
ffective in sensitizing guinea pigs than the high dose repeated inject
ion protocol.