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Many xenobiotics adversely affect the senses of olfaction, gustation, and cochlear-vestibular functions. These toxic effects are not life threatening and frequently considered less important than they actually are to the patient. Because of the lack of standardized diagnostic techniques and normal parameters, such adverse effects may be overlooked and dismissed by healthcare providers, despite significant patient distress and dysfunction. This is particularly true for disorders of olfaction and gustation. This chapter reviews the anatomy and physiology of these senses; describes the effects of xenobiotics on these senses and examines the significant diagnostic information these senses contribute to identifying the presence of xenobiotics. Understanding the effects of xenobiotics on the senses may allow for early detection, which occasionally can be lifesaving.

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Anatomy and Physiology

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Olfactory receptors are bipolar neurons located in the superior nasal turbinates and the adjacent septum. There are 10 to 20 million receptor cells per nasal chamber, and the receptor portion of the cell undergoes continuous renewal from the olfactory epithelium.106,110 Renewed olfactory receptors regenerate neural connections to the olfactory bulb. These olfactory receptor neurons are distinctive in their ability to regenerate.22 The axons of these cells form small bundles that traverse the fenestrations of the cribriform plate of the ethmoid bone to the dura. Within the dura, these bundles form connections with the olfactory bulb from which neural projections then connect to the olfactory cortex. There are extensive interconnections to other parts of the brain, such as the hippocampus, thalamus, hypothalamus, and frontal lobe, suggesting effects on other biologic functions.106 Although primary odor detection is a function of the olfactory nerve (I), some irritant odors, such as ammonia and acetone, are transmitted through the trigeminal nerve (V) and its receptors.40,144

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The actual olfactory receptor sites are structurally similar to the taste receptors of the mouth and the photoreceptors of the retina. The receptor is a single polypeptide chain consisting of approximately 350 amino acids, which folds back and forth on itself to traverse the cellular membrane seven times. The outer end of the polypeptide contains an amine group (N-terminal) and the cytosol end contains a carboxyl group (C-terminal). The transmembranous portions determine the receptor shape and characteristics of the binding site. When a molecule binds to a specific receptor site, the resultant conformational change leads to the activation of the G protein system and calcium and/or sodium channel activation and neurotransmission.72

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Smelling is an extremely sensitive mechanism of detecting xenobiotics. Olfactory receptors can detect the presence of a few molecules of certain xenobiotics with a sensitivity that is superior to some of the most sophisticated laboratory detection instruments.65

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Limitations of the Olfactory Senses

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The sense of smell can be extremely useful as a toxicologic warning system. Human olfaction is a variable trait.5,117,174 For example, 40%–45% of people have specific anosmia (inability or loss ...

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