DESIGN AND EVALUATION OF AN OLFACTOMETER FOR THE ASSESSMENT OF 3-METHYLINDOLE-INDUCED HYPOSMIA

Few studies objectively evaluate olfactory function in animals followi ng exposure to chemicals that induce nasal toxicity. An olfactometer c apable of generating a reproducible olfactory stimulus and measuring a n odorant-cued behavioral response was developed for rats from a comme rcially available two-way shuttle box. The box was modified to deliver the test odorant, acetaldehyde, to either of two chambers separated b y a physical barrier consisting of a downward-directed airwall sandwic hed between two exhaust panels. Male Fisher 344 rats were trained with either a coupled odorant- or tone-cued active avoidance paradigm in o rder to compare auditory-cued versus olfactory-cued learning and memor y. Odorant-cued animals had faster acquisition and longer retention of the avoidance behavior than tone-cued animals. Animals given the mode l olfactory toxicant 3-methylindole (3-MI, 400 mg/kg, ip) had reduced odorant-cued avoidance, while no effect on tone-cued behavior was obse rved. In a follow-up study, additional odorant-trained rats were dosed with 0, 100, 200, or 300 mg/kg of 3-MI ip and olfactory function reas sessed 6 days later. Histopathologic evidence of moderate to severe ol factory epithelial damage was observed in all rats 7 days after 3-MI a dministration. Only the highest 3-MI dose (300 mg/kg) was associated w ith a significant reduction in odor-cued avoidance behavior as compare d to that seen in control. These results indicate that use of this olf actometer can provide a functional assessment of chemically induced ol factory toxicity and complements more routine nasal pathology. (C) 199 6 Society of Toxicology