While there are many industrial compounds reported to cause olfactory dysfunction, there is little data, either epidemiological or experimental, to support these conclusions. The primary objective of this research is to evaluate the effects of a number of metals and volatile industrial compounds on olfactory function, using an integrated multi-disciplinary approach. While assessment of olfactory function has most often been accomplished usinq detection thresholds, the sensitivity of the olfactory system appears to be so great that only a minimal number of receptors are required to detect an odor. Thus, the system can suffer extensive insult and still be capable of detecting odor stimuli. Whether the system can discriminate between different odors, i.e., whether perception of odor quality is impaired, cannot be determined by measuring detection thresholds alone. Paradigms that assess recognition thresholds (odor discrimination) will be employed to pemit more rigorous examination of the functional status of the system. Since previous research has shown that gross morphological damage correlates poorly with the functional status of the system, at least in terms of detection thresholds, emphasis will be placed on a finer analysis of the ultrastructure of the primary sensory neurons (PSN) remaining after insult. Epithelia and bulbar levels of the putative neurotransmitter/neuromodulator of the olfactory PSN, carnosine, also show little correlation with the functional status of the system after insult. Receptor binding studies will be conducted to determine whether there is a compensatory response, e.g., denervation supersensitivity, or whether the result is due to the functional reserve capacity of the olfactory system. Prior research has focused on the heavy metals, cadmium and nickel; in this protocol , zinc, due to its potent effect on the olfactory mucosa will be evaluated. The effects of both soluble (zinc sulfate) and insoluble (zinc oxide) zinc on olfactory function will be examined within the framework describe above. In additon, a series of volatile vapors and gases widely used in the workplace or found in the environment will be tested for their effects on olfactory function. These include formaldehyde. All of these have been shown to damage the nasal epithelium at low exposure levels. The results obtained under these known exposure conditions with sensitive assessment procedures will provide some of the first experimental data relating exposure to toxic compounds with olfactory dysfunction.
| Sun, T J; Miller, M L; Hastings, L (1996) Effects of inhalation of cadmium on the rat olfactory system: behavior and morphology. Neurotoxicol Teratol 18:89-98 |
| Evans, J E; Miller, M L; Andringa, A et al. (1995) Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system. Toxicol Appl Pharmacol 130:209-20 |
| Szarek, J L; Ramsay, H L; Andringa, A et al. (1995) Time course of airway hyperresponsiveness and remodeling induced by hyperoxia in rats. Am J Physiol 269:L227-33 |
| Pixley, S K; Bage, M; Miller, D et al. (1994) Olfactory neurons in vitro show phenotypic orientation in epithelial spheres. Neuroreport 5:543-8 |
