RESUMEN
One hundred and ninety three odor detection thresholds, ODTs, obtained by Nagata using the Japanese triangular bag method can be correlated as log (1/ODT) by a linear equation with R(2) = 0.748 and a standard deviation, SD, of 0.830 log units; the latter may be compared with our estimate of 0.66 log units for the self-consistency of Nagata's data. Aldehydes, acids, unsaturated esters, and mercaptans were included in the equation through indicator variables that took into account the higher potency of these compounds. The ODTs obtained by Cometto-Muñiz and Cain, by Cometto-Muñiz and Abraham, and by Hellman and Small could be put on the same scale as those of Nagata to yield a linear equation for 353 ODTs with R(2) = 0.759 and SD = 0.819 log units. The compound descriptors are available for several thousand compounds, and can be calculated from structure, so that further ODT values on the Nagata scale can be predicted for a host of volatile or semivolatile compounds.
Asunto(s)
Algoritmos , Odorantes , Umbral Sensorial/fisiología , Humanos , Modelos Biológicos , Compuestos Orgánicos Volátiles/químicaRESUMEN
An unpublished laboratory study by Russell and Rush (1996) showed that human subjects sense the presence of methyl isothiocyanate (MITC) via the eyes at concentrations as low as hundreds of ppb in air, with dependence upon duration of exposure. The longer the stimulation, the lower the concentrations sensed. Application of benchmark concentration (BMC10) modeling indicated a best estimate of 330 ppb by the end of 4h. With a confidence limit (BMCL) applied, the level dropped to 220 ppb, when employing a probit model. Receptors known as TRPA1 ion channels present in trigeminal and associated peripheral afferent nerves have shown particular sensitivity to isothiocyanates. Sensitivity to these electrophiles, which occur naturally in plants (e.g., capers and mustard greens), most likely derives from a mechanism of reversible covalent bonding. Such sensing can provide warning of potential damage rather than actual damage itself. Based upon its reputation as a lachrymator, Russell and Rush assumed that the eyes would sense MITC, before the upper airways, so gathered no data from the airways, except for odor. Field results from spills and results of acute exposures to animals covered in Dourson et al. (2010) add pertinent information on the matter.
Asunto(s)
Contaminantes Atmosféricos/química , Herbicidas/química , Isotiocianatos/química , Umbral Sensorial , Adolescente , Adulto , Anciano , Canales de Calcio/metabolismo , Ojo/metabolismo , Femenino , Humanos , Irritantes/química , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Proteínas del Tejido Nervioso/metabolismo , Odorantes , Proyectos de Investigación , Olfato , Canal Catiónico TRPA1 , Factores de Tiempo , Canales de Potencial de Receptor Transitorio/metabolismo , Adulto JovenRESUMEN
Data on human odor thresholds show disparities huge enough to marginalize olfactory psychophysics and delegitimize importation of its data into other areas. Variation of orders of magnitude from study to study, much of it systematic, threatens meaningful comparisons with animal species, comparison between in vivo with in vitro studies, the search for molecular determinants of potency, and use of olfactory information for environmental or public health policy. On the premise that good experimental results will flow from use of good tools, this report describes a vapor delivery system and its peripherals that instantiate good tools. The vapor delivery device 8 (VDD8) provides flexibility in range of delivered concentrations, offers definable stability of delivery, accommodates solvent-free delivery below a part per trillion, gives a realistic interface with subjects, has accessible and replaceable components, and adapts to a variety of psychophysical methodologies. The device serves most often for measurement of absolute sensitivity, where its design encourages collection of thousands of judgments per day from subjects tested simultaneously. The results have shown humans to be more sensitive and less variable than has previous testing. The VDD8 can also serve for measurement of differential sensitivity, discrimination of quality, and perception of mixtures and masking. The exposition seeks to transmit general lessons while it proffers some specifics of design to reproduce features of the device in a new or existing system. The principles can apply to devices for animal testing.
Asunto(s)
Odorantes , Olfato/fisiología , Humanos , Psicofísica , Compuestos Orgánicos Volátiles/farmacologíaRESUMEN
A large amount of data on the biological and toxicological activity of gases and vapors has been collected from the literature. Processes include sensory irritation thresholds, the Alarie mouse test, inhalation anesthesia, etc. It is shown that a single equation using only five descriptors (properties of the gases and vapors) plus a set of indicator variables for the given processes can correlate 643 biological and non-lethal toxicological activities of 'non-reactive' compounds with a standard deviation of 0.36 log unit. The equation is scaled to sensory irritation thresholds obtained by the procedure of Cometto-Muñiz, and Cain provides a general equation for the prediction of sensory irritation thresholds in man. It is suggested that differences in biological/toxicological activity arise primarily from transport from the gas phase to a receptor phase or area, except for odor detection thresholds where interaction with a receptor(s) is important.
Asunto(s)
Gases/toxicidad , Modelos Biológicos , Compuestos Orgánicos Volátiles/toxicidad , Animales , Oftalmopatías/inducido químicamente , HumanosRESUMEN
Using air-dilution olfactometry, we measured concentration-response functions for the odor detection of the homologous esters ethyl, butyl, hexyl, and octyl acetate. Stimuli were delivered by means of an 8-station vapor delivery device (VDD-8) specifically designed to capture odor detection performance by humans under environmentally realistic conditions. Groups of 16-17 (half female) normosmic (i.e., having a normal olfaction) non-smokers (ages 18-38) were tested intensively. The method involved a three-alternative forced-choice procedure against carbon-filtered air, with an ascending concentration approach. Delivered concentrations were confirmed by gas chromatography before and during actual testing. A sigmoid (logistic) model provided an excellent fit to the odor detection functions both at the group and individual levels. Odor detection thresholds (ODTs) (defined as the half-way point between chance and perfect detection) decreased from ethyl (245 ppb by volume), to butyl (4.3 ppb), to hexyl acetate (2.9 ppb), and increased for octyl acetate (20 ppb). Interindividual threshold variability was near one and always below two orders of magnitude. The steepness of the functions increased slightly but significantly with carbon chain length. The outcome showed that the present thresholds lie at the very low end of those previously reported, but share with them a similar relative trend across n-acetates. On this basis, we suggest that a recent quantitative structure-activity relationship (QSAR) for ODTs can be applied to these and additional optimized data, and used to describe and predict not just ODTs but the complete underlying psychometric odor functions.
Asunto(s)
Acetatos/administración & dosificación , Umbral Diferencial/fisiología , Detección de Señal Psicológica , Olfato/fisiología , Acetatos/clasificación , Adulto , Aerosoles , Umbral Diferencial/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Modelos Biológicos , Psicometría , Valores de Referencia , Olfato/efectos de los fármacos , Volatilización , Adulto JovenRESUMEN
Descriptors have been determined for four inorganic mercury(II) species and for seventeen organic mercury(II) species, using experimental literature data. These descriptors can then be used in equations that we have already set out in order to estimate a large number of physicochemical properties. These include the water to octanol partition coefficient and the gas to water partition coefficient. For the organic mercury(II) species, including dimethylmercury and the methylmercury(II) halides, the latter has been estimated over the temperature range 273-373 K.
Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/química , Compuestos de Mercurio/química , Compuestos Organomercuriales/química , Solubilidad , Solventes/químicaRESUMEN
OBJECTIVES: (1) To assess the relation between occupationally relevant exposures to dust of boric acid and magnitude of feel in the eye, nose, and throat during activity (pedaling) equal to light industrial work. (2) To compare feel from the dust of boric acid with that of the alkaline dusts calcium oxide and sodium tetraborate pentahydrate (sodium borate). (3) To chart how magnitude of feel changes with time in exposures up to 3/4 h. METHODS: Twelve subjects, six males and six females, participated in duplicate sessions of exposure to 2.5, 5, and 10 mg m(-3) of boric acid, 10 mg m(-3) of sodium borate, 2.5 mg m(-3) of calcium oxide presented as calcium oxide alone or diluted with hydrated calcium sulfate, and 0 mg m(-3) (blank). Exposures occurred in a plastic dome suspended over the head and closed around the neck with rubber dam. Measurements pre- and post-exposure included nasal secretion and nasal resistance. Measurements during exposure included rated magnitude of feel in the eye, nose, and throat, and respiration (Respitrace System). Six concentrations of carbon dioxide ranging from just below detectable to sharply stinging gave subjects references for their ratings. RESULTS: In general, feel increased for periods up to half an hour, then either declined or held at a plateau. Each material had a temporal signature. The nose led with the highest feel, followed by the throat, then the eyes. This hierarchy proved weakest for boric acid; at one level of exposure, magnitude in the throat overtook that in the nose. Accompanying measures implied that change of feel with time occurred neither because of an increase in dilution of the dissolved dusts in newly secreted mucus nor an increase of consequence in nasal resistance. Most likely, sensory adaptation determined the change. Boric acid of 10 mg m(-3) fell slightly and insignificantly below 10 mg m(-3) sodium borate in feel. Boric acid, though, showed a relatively flat dose-response relationship, i.e., a change in level caused little change in feel. CONCLUSIONS: The time-constant for feel from dusts lies on the order of tens of minutes. A flat concentration-response function for boric acid and a notable response from the throat suggests that perceived dryness, not mediated by acidity but perhaps by osmotic pressure, may account for the feel evoked at levels of exposure at or below 10 mg m(-3). More acidic dusts that could actually change nasal pH may trigger sensations differently.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Boratos/efectos adversos , Ácidos Bóricos/efectos adversos , Compuestos de Calcio/efectos adversos , Exposición Profesional/efectos adversos , Óxidos/efectos adversos , Adolescente , Adulto , Boratos/administración & dosificación , Ácidos Bóricos/administración & dosificación , Compuestos de Calcio/administración & dosificación , Polvo , Oído Interno/fisiopatología , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Nariz/fisiopatología , Óxidos/administración & dosificación , Faringe/fisiopatologíaRESUMEN
We have applied a quantitative structure-activity relationship (QSAR) approach to analyze the chemical parameters that determine the relative sensitivity of olfaction and nasal chemesthesis to a common set of volatile organic compounds (VOCs). We used previously reported data on odor detection thresholds (ODTs) and nasal pungency thresholds (NPTs) from 64 VOCs belonging to 7 chemical series (acetate esters, carboxylic acids, alcohols, aliphatic aldehydes, alkylbenzenes, ketones, and terpenes). The analysis tested whether NPTs could be used to separate out "selective" chemosensory effects (i.e., those resting on the transfer of VOCs from the gas phase to the receptor phase) from "specific" chemosensory effects in ODTs. Previous work showed that selective effects overwhelmingly dominate chemesthetic potency whereas both selective and specific effects control olfactory potency. We conclude that it is indeed possible to use NPTs to separate out selective from specific effects in ODTs. Among the series studied, aldehydes and acids, except for formic acid, show clear specific effects in their olfactory potency. Furthermore, for VOCs whose odor potency rests mainly on selective effects, we have developed a QSAR equation that can predict their ODTs based on their NPTs.
Asunto(s)
Mucosa Nasal/fisiología , Neuronas Receptoras Olfatorias/fisiología , Relación Estructura-Actividad Cuantitativa , Umbral Sensorial/fisiología , Nervio Trigémino/fisiología , Alcoholes/química , Aldehídos/química , Algoritmos , Derivados del Benceno/química , Ésteres/química , Ácidos Grasos Volátiles/química , Humanos , Hidrocarburos Acíclicos/química , Cetonas/química , Odorantes , Transición de Fase , Olfato/fisiología , Terpenos/químicaRESUMEN
We measured the concentration-detection (i.e., psychometric) functions for the eye irritation evoked by three homologous n-alcohols (1-nonanol, 1-decanol and 1-undecanol) and two homologous acetates (nonyl and decyl acetate). A vapor delivery device based on a dynamic dilution of stimuli in nitrogen served to present various concentrations of each compound, including the undiluted vapor, to the subjects (n >or= 26). Delivered concentrations were quantified by gas chromatography. Detection probability (P) was assessed via a three-alternative, forced-choice procedure and quantified on a scale ranging from P = 0.0 (chance detection) to P = 1.0 (perfect detection). Flow rate to the eye equaled 2.5 l/min and time of exposure was 6 s. The functions for 1-undecanol and decyl acetate plateaued at P approximately 0.5 and P approximately 0.25, respectively, such that further increases in concentration failed to increase detection notably. Thus, both series reached a break point, or cut-off, in the detection of ocular irritation. The present outcome provides additional evidence that the cut-off does not rest on the low vapor concentration of the homolog but, more likely, on the homolog exceeding a critical molecular dimension(s), which prevents it from interacting effectively with the appropriate receptors.
Asunto(s)
Acetatos/farmacología , Alcoholes/farmacología , Ojo/efectos de los fármacos , Irritantes/farmacología , Acetatos/administración & dosificación , Acetatos/análisis , Adolescente , Adulto , Alcoholes/administración & dosificación , Alcoholes/análisis , Cromatografía de Gases , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Ojo/química , Femenino , Gases , Humanos , Irritantes/administración & dosificación , Masculino , Persona de Mediana Edad , Estimulación QuímicaRESUMEN
OBJECTIVES: Assessment of olfactory and chemesthetic sensitivity (feel, sensory irritation) to vapor of glutaraldehyde in young adult females. For chemesthetic sensitivity, assessment included the variable of duration, with focus on whether concentrations initially too low to evoke feel in the eye or upper airway might do so in exposures up to 15 min. METHODS: Experiment 1 probed sensitivity with forced-choice testing of detection over ranges of concentrations appropriate to three endpoints: odor, feel in the eye, and feel in the nose. A subject participated in hours of testing per endpoint to yield enough data to erect a psychometric (concentration-response) function. Exposure in Experiment 1 entailed use of a vapor-delivery system that stimulated sites of interest separately. Exposure in Experiment 2 occurred in the ambient environment of a chamber, with the sites stimulated simultaneously. In that case, subjects rated confidence by the minute that they felt the presence of vapor in the eyes, nose, and throat during exposures of 15 minutes to 35, 50, 75, and 100 ppb, a blank, and an odor control of mild heptane. RESULTS: In Experiment 1, the typical subject achieved 50% detection (threshold) of odor at 0.3 ppb. The typical subject achieved 50% detection of feel in the eye and nose at 390 and 470 ppb, respectively. Psychometric functions for feel showed much sharper dependence on concentration than those for odor. In Experiment 2, confidence in detection of feel migrated progressively away from no-with certainty toward the zone of uncertainty, with bigger change when the exposures contained any glutaraldehyde. The ratings of confidence failed, however, to show distinguish among these concentrations. CONCLUSIONS: Glutaraldehyde has much higher odor potency than previously thought. Its green-apple odor should signal presence of the vapor at levels more than a 100-fold below any that might evoke sensory irritation in brief exposures. Exposures that start decidedly below irritating (100 ppb and below) seem unlikely to turn irritating over time. Although the effects from these concentrations differentiated themselves from those of air and an odor control, they exhibited none of the concentration dependence seen for sensations of feel. They seemed likely driven by the penetrating odor of glutaraldehyde.
Asunto(s)
Contaminación del Aire/análisis , Desinfectantes/toxicidad , Glutaral/toxicidad , Cavidad Nasal/efectos de los fármacos , Fenómenos Fisiológicos Oculares/efectos de los fármacos , Odorantes , Faringe/efectos de los fármacos , Umbral Sensorial/fisiología , Olfato/efectos de los fármacos , Adolescente , Adulto , Contaminación del Aire/efectos adversos , Análisis de Varianza , Femenino , Humanos , Exposición por Inhalación , Psicometría , Percepción Espacial , Factores de TiempoRESUMEN
In Experiment 1, subjects sought to localize the nostril stimulated, left or right, in tests with nine esters (acetates, propionates, and butyrates) at concentrations meant to trigger chemesthesis (pungency, irritation). The task produced psychometric functions for chemesthetic detection unconfounded by olfactory sensations. The functions indicated a sharp transition from no detection to perfect detection, rather uniform across the esters, which themselves varied in potency by two log units. The correlation between the thresholds for the eight materials that yielded thresholds and predictions from a published linear free energy relationship (LFER) equaled 0.99. In Experiment 2, amplitude of the negative mucosal potential (NMP) was recorded from the septum. The resulting functions also increased with concentration sharply. Against a criterion amplitude of the NMP, thresholds measured in the first experiment (and predictions from the LFER) correlated 0.99. The NMP seems to offer an adequate objective measure of sensory irritation. The LFER, although effective predictively, could stand to have a parameter to anticipate that molecules beyond a certain size fail to trigger irritation. In the present case, a cut-off of chemesthetic potency occurred between butyl butyrate and hexyl butyrate for the group of subjects, with some variation of the boundary among individuals.
Asunto(s)
Odorantes , Olfato/fisiología , Adolescente , Adulto , Fenómenos Químicos , Química Física , Cromatografía de Gases , Ésteres/química , Ésteres/farmacología , Femenino , Humanos , Masculino , Potenciales de la Membrana/fisiología , Psicometría , Relación Estructura-Actividad Cuantitativa , Umbral Sensorial/fisiología , Estimulación QuímicaRESUMEN
In a series of experiments, we looked at a "cutoff" effect for the detection of eye irritation from neat vapors of homologous n-alkylbenzenes and 2-ketones. Stimuli comprised pentyl, hexyl, and heptyl benzene, 2-dodecanone, and 2-tridecanone, presented to each eye at 4 and 8 l/min for 6 sec, using a three-alternative forced-choice procedure against blanks. Detection probability corrected for chance (i.e., detectability) decreased with carbon chain length such that heptyl benzene and 2-tridecanone were virtually undetectable, irrespective of flow rate to the eye. Heating both stimuli sources to 37 degrees C (body temperature) from 23 degrees C (room temperature) increased vapor concentration by 5.0 and 6.9 times, respectively, for heptyl benzene and 2-tridecanone. Still, both chemicals failed to show increased detection for 13 of the 21 participants. In addition, plots of experimentally measured and calculated eye irritation thresholds as a function of carbon chain length for each series indicated that, based on the trend, the concentration of the two cutoff homologs at 37 degrees C should have been high enough to allow detection. Taken together, the results suggest that these cutoffs rest on limitations related to the dimension of the molecules rather than on limitations related to their vapor concentration. For example, the stimulus molecule could exceed the size that allows it to fit into the receptor pocket of a receptive protein. Plots of calculated molecular dimensions across homologous alkylbenzenes, from ethyl to dodecylbenzene, and across 2-ketones, from 2-octanone to 2-octadecanone, provided additional support to the above conclusion.
Asunto(s)
Derivados del Benceno/toxicidad , Ojo/efectos de los fármacos , Irritantes/toxicidad , Cetonas/toxicidad , Adolescente , Adulto , Femenino , Humanos , Masculino , Peso Molecular , Temperatura , VolatilizaciónRESUMEN
Previous research showed a cut-off along homologous volatile organic compounds (VOCs) in their ability to produce acute human mucosal irritation. The present study sought to specify the particular cut-off homolog for sensory eye irritation in an acetate and n-alcohol series. A 1900-ml glass vessel system and a three-alternative forced-choice procedure served to test nonyl, decyl, and dodecyl acetate, and 1-nonanol, 1-decanol, and 1-undecanol. Flowrate to the eye ranged from 2 to 8 L/min and time of exposure from 3 to 24 s. Decyl acetate and 1-undecanol were the shortest homologs that failed to produce eye irritation under all conditions, producing a cut-off effect. Increasing the vapor concentration of decyl acetate and 1-undecanol by 3 and 8 times, respectively, via heating them to 37 degrees C made either or both VOCs detectable to only half of the 12 subjects tested, even though the higher vapor concentration was well above a predicted eye irritation threshold. When eye irritation thresholds for homologous acetates and n-alcohols were plotted as a function of the longest unfolded length of the molecule, the values for decyl acetate and 1-undecanol fell within a restricted range of 18 to 19 A. The outcome suggests that the basis for the cut-off is biological, that is, the molecule lacks a key size or structure to trigger transduction, rather than physical, that is, the vapor concentration is too low to precipitate detection.
Asunto(s)
Oftalmopatías/inducido químicamente , Irritantes/toxicidad , Pruebas de Toxicidad/métodos , Acetatos/toxicidad , Adulto , Alcoholes/toxicidad , Algoritmos , Ésteres/toxicidad , Femenino , Humanos , Masculino , Concentración Máxima Admisible , Persona de Mediana Edad , Relación Estructura-Actividad , TemperaturaRESUMEN
We explored the influence of methodological and chemical parameters on the detection of nasal chemesthesis (i.e., trigeminal stimulation) evoked by volatile organic compounds (VOCs). To avoid odor biases, chemesthesis was probed via nasal pungency detection in anosmics and via nasal localization (i.e., lateralization) in normosmics, in both cases using forced-choice procedures. In the experiments with anosmics, 12 neat VOCs were selected based on previous reports of lack of chemesthetic response. Although none of the VOCs reached 100% detection, detectability and confidence of detection were higher when using a glass vessel system adapted with nosepieces to fit the nostrils tightly than when using wide-mouth glass jars. Half the stimuli were detected well above chance and half were not. When the latter were tested again after being heated to 37 degrees C, that is, body temperature (from room temperature, 23 degrees C), to increase their vapor concentration, only one, octane, significantly increased its detectability. Chemesthesis gauged with normosmics mirrored that with anosmics. Gas chromatography measurements showed that, even at 23 degrees C, the saturated vapor concentrations of the undetected stimuli, except vanillin, were well above the respective calculated nasal pungency threshold (NPT) from an equation that, in the past, had accurately described and predicted NPTs. We conclude that, except for octane and perhaps vanillin, the failure of the other four VOCs to precipitate nasal chemesthesis rests on a chemical-structural limitation, for example, the molecules lack a key property to fit a receptor pocket, rather than on a concentration limitation, for example, the vapor concentration is too low to reach a threshold value.
Asunto(s)
Cavidad Nasal/efectos de los fármacos , Trastornos del Olfato/fisiopatología , Compuestos Orgánicos/farmacología , Nervio Trigémino/química , Nervio Trigémino/fisiología , Adulto , Anciano , Femenino , Calor , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal/química , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/etiología , Umbral Sensorial , Estimulación Química , Nervio Trigémino/efectos de los fármacos , VolatilizaciónRESUMEN
The investigation explored the olfactory detectability of two chemically and structurally similar esters, ethyl propanoate and ethyl heptanoate, presented singly and in mixtures. Initially, we measured concentration-detection (i.e., psychometric) functions for the odor of ethyl propanoate and ethyl heptanoate presented singly. Using this information, we prepared binary mixtures of the two chemicals in varying complementary proportions and, also, selected concentrations of the single compounds, such that, if a rule of response-addition (i.e., independence of detection) were to hold, the stimuli (mixed and single) should approximate equal detection. Next, we measured the actual detectability of these stimuli within the same experiment. The results were analyzed in terms of response-addition (or -additivity) and of dose-addition (or -additivity). The outcome revealed that at low levels of detectability the mixtures approximate response-addition, that is, independence of detection, whereas at high levels of detectability they approximate dose-addition. In the light of previous findings for the olfactory detection of the more dissimilar chemical pairs 1-butanol/2-heptanone and butyl acetate/toluene, we conclude that the described outcome generalizes across a variety of chemical pairs.
Asunto(s)
Atención , Aprendizaje Discriminativo , Heptanoatos , Odorantes , Propionatos , Olfato , Adolescente , Adulto , Mezclas Complejas , Relación Dosis-Respuesta a Droga , Femenino , Generalización Psicológica , Humanos , Masculino , Persona de Mediana Edad , Umbral SensorialRESUMEN
Occupational exposure limits (OELs) for irritant dusts have had no quantifiable bases. This study (1) charted chemosensory feel, denoted chemesthesis here, to dusts of calcium oxide (1 to 5 mg/m(3)), sodium tetraborate pentahydrate [sodium borate] (5 to 40 mg/m(3)), and calcium sulfate (10 to 40 mg/m(3)); (2) examined correlates of the chemesthetic sensations; and (3) sought to illuminate the basis for potency. Twelve screened men exercised against a light load while they breathed air in a dome fed with controlled levels of dust for 20 min. Measured parameters included nasal resistance, nasal secretion, minute ventilation, heart rate, blood oxygenation, mucociliary transport time, and chemesthetic magnitude, calibrated to pungency of carbon dioxide. Subjects registered time-dependent feel from exposures principally in the nose, secondarily in the throat, and hardly in the eyes. Calcium oxide had the greatest potency, followed by sodium borate, with calcium sulfate a distant third. Of the physiological parameters, amount of secretion showed the best association with chemesthetic potency. That measure, as well as mucociliary transport time and minute ventilation, went into calculation of mass of dust dissolved into mucus. The calculations indicated that the two alkaline dusts increased in equal molar amounts with time. At equal molar concentrations, they had, to a first approximation, equal chemesthetic magnitude. On the basis of mass concentration in air or dissolved into mucus, calcium oxide and sodium borate differed in potency by a factor just above five, equal to the difference in their molecular weights. This relationship could inform the setting of OELs for a critical effect of irritation.
Asunto(s)
Boratos/efectos adversos , Boratos/análisis , Compuestos de Calcio/efectos adversos , Compuestos de Calcio/análisis , Sulfato de Calcio/efectos adversos , Sulfato de Calcio/análisis , Polvo , Exposición por Inhalación , Exposición Profesional , Óxidos/efectos adversos , Óxidos/análisis , Percepción , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Humanos , Irritantes/análisis , Irritantes/farmacología , Masculino , VentilaciónRESUMEN
A series of experiments probed into the degree of chemosensory detection additivity exhibited by mixtures of ethyl propanoate and heptanoate in terms of their trigeminal detectability via nasal pungency (i.e., irritation) and eye irritation. Nasal pungency was tested in subjects lacking a functional sense of smell (i.e., anosmics) to avoid olfactory biases. First, we built concentration-detection functions for each chemical and sensory endpoint. Second, we used the data from the functions to prepare mixtures of the two compounds in complementary proportions, and suitable single-chemical standards, all of which should be equally detectable under a rule of complete additivity, i.e., independence of detection. Third, we compared the experimentally obtained detectability with that expected under such rule. The outcome revealed that, at a low detectability level (but still above chance), the mixtures showed complete additivity for both trigeminal endpoints. At a high detectability level (but below perfect detection), the mixtures showed complete additivity for nasal pungency but less than complete additivity for eye irritation. In the context of previous studies, the results consolidate a picture of higher degree of detection additivity at perithreshold levels in trigeminal than in olfactory chemoreception. The outcome presents another line of evidence suggesting broader chemical tuning in chemesthesis compared to olfaction.
Asunto(s)
Células Quimiorreceptoras/fisiopatología , Trastornos del Olfato/fisiopatología , Nervio Trigémino/fisiopatología , Adulto , Estudios de Casos y Controles , Combinación de Medicamentos , Ojo/efectos de los fármacos , Femenino , Heptanoatos/farmacología , Humanos , Irritantes/farmacología , Masculino , Persona de Mediana Edad , Cavidad Nasal/efectos de los fármacos , Concentración Osmolar , Propionatos/farmacología , Psicometría , VolatilizaciónRESUMEN
UNLABELLED: We have measured complete concentration-detection (i.e., psychometric or detectability) functions to study the olfactory and ocular/nasal chemesthetic (a term that includes sensory irritation) impact of VOCs presented singly and in various binary mixtures. Such functions provide considerably more information than that provided by measuring only a "threshold". The outcome for single VOCs confirmed the much higher absolute sensitivity of olfaction compared to chemesthesis, but also demonstrated that the detection of ocular and nasal sensory irritation increases as a function of vapor concentration at a much higher rate than that for the detection of odor. The outcome for the binary mixtures revealed that, for both olfaction and chemesthesis, complete additivity of detection of individual components held at relatively low levels of detectability but broke down at higher levels. The breakdown for odor detection, compared to that for sensory irritation detection, was, first, more extensive, and, second, dependent to a larger extent on the degree of structural and chemical similarity/dissimilarity between the mixed VOCs. PRACTICAL IMPLICATIONS: Concentration-detection functions for the chemesthetic and olfactory detectability of VOCs have shown that, even when nasal pungency and eye irritation begin to be evoked at concentrations orders of magnitude larger than those evoking odor, they sharply increase in detectability to become clearly noticeable. In contrast, odor detectability increases with concentration at a much lower rate. As a result, any fixed reduction (e.g., 10-times) in the concentration of a VOC will reduce detectability of sensory irritation much more dramatically than detectability of odor, within their respective ranges. Concentration-detection functions are particularly informative when employed to probe into the rules of dose- and response-additivity in mixtures. Our results for olfaction, and to a lesser extent for chemesthesis, indicate that additivity of detection of individual VOCs in mixtures is level-dependent: as detectability increases, the degree of additivity decreases. This suggests that a substantial improvement of perceived air quality could follow from control of just the few dominating chemosensory sources.
Asunto(s)
Contaminación del Aire Interior/análisis , Monitoreo del Ambiente/métodos , Odorantes/análisis , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos Orgánicos/análisis , Sensibilidad y Especificidad , Olfato , VolatilizaciónRESUMEN
Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.