7. Análisis e interpretación de resultados 91
7.2 Los foros 105
7.2.2 Usos de los foros 115
The trigeminal system mediates a variety of protective reflex responses to potentially life-threatening chemical irritants. Sensory irritation is related to chemical reactivity. For an irritant gas or vapour, one speaks of the substance’s warning properties, or its ability to produce immediate upper respiratory irritation. Such irritation triggers protective physiologic reflexes, alerts the exposed individual to danger, and initiates escape behaviour. For a given degree of chemical reactivity, the warning
properties of a gas or vapor tend to correlate with its water solubility. Examples of irritants that have good warning properties, i.e. high water solubility, are ammonia and sulfur dioxide. Alarie uses the term sensory irritant or upper-respiratory tract irritant to denote irritant gases or vapors that have good warning properties.
The irritation effect of gases and vapof) is believed to be caused by their direct interaction with one or more receptors on trigeminal nerve endings in the cornea and nasal mucosa. The chemosensitive trigeminal nerves are C-fibres and possibly also ôA- fibres. They are part of the somatic sensory system, which conveys peripheral impulses to the central nervous system. Stimulation of the trigeminal nerve endings results in a stinging sensation, which can increase to a burning and painful sensation.
Unlike olfaction, which relies upon stimulation of hundreds of types of receptors to give the spectrum of odor quality, chemesthesis for nonreactive VOCs appears to rely upon stimulation of a very small variety. Indeed, one type of broadly tuned receptor may transduce the majority of VOCs, except for some special molecules, such as nicotine. One YOG might accordingly behave like another with respect to its dose- response ,i.e. psychometric, function.
2.1.2.1. Bio-Assavs for Nasal Pungencv
Two main bio-assays have been developed for nasal pungency. First, there is the mouse bio-assays developed by Alarie, which is now a ASTM standard method. In this assay a stream of air carrying a constant concentration of VOC is passed over the head of a mouse for 10-15 min, and the reduction in respiratory rate is obtained using a plethysmograph.^® The VOC concentration in ppm that causes a 50% reduction rate is taken as the bio-assay endpoint, and denoted as RD5 0. Values for some 150 VOCs have been listed in recent reviews. Secondly, there is the measurement of nasal pungency thresholds in humans in which the VOC is administered as a short ‘sniff lasting a few seconds.^'^^ The threshold is taken as the lowest concentration in ppm the subject can
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detect; these thresholds are denoted as NPT. Cain and Cometto-Muniz have measured nasal pungency thresholds in persons lacking a functional sense of smell, viz. anosmies, for whom odor does not interfere. Values of NPT for 50 VOCs have been recently listed.
Some observations have indicated that normosmics could localise the nostril stimulated by a chemical only when it triggered chemesthesis. Fortunately, the concentration at which a person can localise the nostril coincides almost exactly with the concentration for chemesthetic detection. This approach produces sensory data for chemesthetic detection free of olfactory sensations.
The negative mucosal potential seems to offer an objective measure of sensory irritation. Pungency stimulation can elicit a surface potential from the nasal respiratory mucosa. Because of its predominant negative peak, with amplitude up to hundreds of microvolts, the response has become known as the negative mucosal potential. Recorded from a limited region of the septum, the signal represents most likely the aggregate receptor potential of many thousands of free nerve endings of the stimulation. Kobal and colleagues ruled out various epiphenomenal sources, such as blood flow, olfaction, and activity from sympathetic fibers. The finding that the NMP correlates closely with feelings of irritation, expressed in ratings of magnitude, argues for a trigeminal source.^^
2.1.2.2. Bio-assavs for Eve Irritation
Two approaches have been used to determine eye irritation thresholds. First, the rabbit eye irritation test developed by Draize, Woodard and Calvery^^ is still regarded as the accepted standard for assessing eye irritation hazard. In the Draize test the substance under study is applied to the eye of a living rabbit. The effects of the substances on the cornea, iris and conjunctivae are graded on individual scales and given weighted scores. The final eye irritation score is the sum of the weighted scores for the cornea, iris and conjunctivae. Data from the rabbit eye irritation test have been acceptable for assessing the hazard of chemical irritation to the eye because of two assumptions: (1) substances that are irritant to the rabbit eye are also irritant to the human eye because the mechanisms which operate in rabbit eye irritation also generally operate in human irritation; (2) the rabbit eye test is thought to overestimate the human hazard and so provide a margin of safety to protect human health. Eye irritation in humans, BIT in ppm, have been gathered for 17 VOCs. Noteworthy, the human and animal differ in an important way.^'^^ The human data came from vapor phase stimulation with various VOCs, whereas the animal data came from direct application of VOCs as bulk liquid.