The sinuses, a connected system of hollow cavities in the skull lined with mucosa tissue that has a thin layer of mucus, may help humidify air in the nasal cavity. In 2015, a $15-million grant by the National Science Foundation kicked off further research into how animals, including humans, locate the source of an odor, such as food . The research focuses on how odors move in the landscape and how animals use spatial and temporal cues to move toward a target. The research is just one part of the federal BRAIN Initiative that studies olfaction as a window into understanding the brain, because olfaction is considered the most primal pathway to understanding brain evolution. At present, such information is not available for e-nose development. The olfactory epithelium contains three types of cells: olfactory receptor neurons, their precursors and supportive cells. The cilia are constantly exposed to the nasal environment and are continually replaced, even their basal cells, possibly indicating frequent damage. A layer of mucus 10 to 40 µm thick coats the mucosa epithelium, and odorants must pass into this layer to interact with the sensory neurons through a series of poorly understood “perireceptor” events . Each sensory neuron, covered in cilia, trim tray projects down from the olfactory epithelium into the mucosa.These proteins thread back and forth across the outer membrane of the cilia and interact with odorants. Various theories have been put forward on how exactly odorants interact with the proteins, and this remains an area of research.
Receptor cells of the same type are randomly distributed in the nasal mucosa but converge on the same glomerulus. Each type of neuron frequently responds to more than one odorant, even from different chemical classes, so the overall odor signal must be integrated by the olfactory bulb . Integration includes both olfactory and trigeminal signals, and workers often report odor and irritation as a combined, singular perception . The olfactory bulb also receives information from other areas of the brain to filter out background odors and enhance perception. Fascinatingly, none of the physical stimuli themselves ever reach the brain. Instead, a host of proteins transduces captured molecules into a small change in voltage that can be deciphered by the brain . The unpleasant and pleasant aspects of mixtures are represented separately in the brain . Human sensitivity to odorants ranges across several orders of magnitude . Around 1 ppt appears to be a theoretical limit for sensitivity, and many odorants are not perceived until above 1,000 ppm. The major components of air are not sensed at all . Carbon dioxide is an interesting chemical because it is odorless at ambient concentrations yet selectively triggers only the trigeminal neurons and not the olfactory neurons when it reaches 200-fold above background levels . Describing multiple odor notes in mixtures is challenging. Fewer than 15% of the people tested could only identify one of the odorants present in a mixture, and identification of 3 to 4 components was the limit for trained experts . Even 90% of wine judges were unable to reproduce their scores . General variability in odor perception is high. Factors include age, sex, lifestyle, prior exposures, culture and health status . Approximately 3% of Americans have minimal or no sense of smell .Prolonged or repeated exposure to an odor can lead to a decreased response , which has the benefit of allowing a baseline reset in preparation for a new stimulus . Habituation happens as quickly as 2.5 second and is accompanied by decreased transduction by the neurons after 4 seconds . A growing field of research throughout public health is the microbiome, the microflora that contribute to gut, mouth and skin health. The nasal cavity, too, hosts microbes that contribute to normal functioning .
Some microbes themselves emit odorants and can decrease the host’s sensitivity . Attempts to reverse engineer an odor based on the molecular properties of the odorant have been successful. Algorithms were able to predict the odor note of a given odorant based on its chemoinformatic features for 8 descriptors out of 19 total . Researchers using systems biology and computational techniques mapped odors to specific proteins on olfactory receptor neurons, which was dubbed the “odorome” . Risk assessment for estimating the non-sensory health risks of airborne chemicals has a large body of guidance and case studies. The primary focus of this paper is on the sensory health effects of odors that integrate both trigeminal response and olfactory response . In general, the olfactory pathway iscapable of informing the organism about the presence of an odorant while the trigeminal pathway helps inform the organisms about the risk of health hazards and injury .Cognitive bias plays a role in odor responses . Odors trigger memories of previous experiences and are influenced by the power of suggestion. If given a prior warning that an odor is harmful, increased irritation was reported. Fewer symptoms were reported if told the odor was healthful. Even when no odor was administered, suggestion that there was a harmful odor led to symptoms. Prior experience with an odor introduces bias, too. Emotional baseline is also a factor . Sensitization to an odorant occurs when an acute exposure triggers subsequent, more-severe responses, often at lower concentrations . Desensitization can occur when chronic exposure to an odorant increases the concentration required to trigger a response. For example, workers who are habituated and desensitized to an odorant may be baffled by neighborhood complaints . Due to the availability of human data, other animal data were not considered in the hazard identification. Further, humans have a smaller area of nasal olfactory epithelium than rodents, which makes humans more vulnerable to loss, and respiration rates are quite different . Only one experimental study of a typical, complex environmental odor and health effects was found , which included both physical effects and mood . Out of the dozens of parameters evaluated, only headaches,eye irritation and nausea symptoms were elevated among those exposed for one hour as compared to controls . The epidemiology evidence, however, indicated the full range of adverse effects from odor exposure .
Such symptoms were self-reported, which means they may include bias. The distance from facility, an objective measure, contrarily did not predict the frequency of symptoms. Interestingly,ebb and flow the relationship between odor exposure and health symptoms appeared to be greatly influenced by odor hedonic tone, perhaps more so than odor intensity. The debate whether the purely odor-related symptoms are psychological or have an actual underlying physical cause is ongoing. In the same issue of Archives of Environmental Health in 1992, two opposing perspectives were presented. Shusterman concluded that the evidence of health effects was lacking beyond odors’ ability to inflict annoyance. In the editorial immediately after his article, Ziem and David off countered that odor, and chemical sensitivity in general, may well be based on underlying physiological responses, as was often found in the case of sick building syndrome. Both agreed that better ways to determine the impact of odors were needed, and well-controlled prospective case-control studies would be especially welcome. The psychological symptoms of odor exposure include tension, nervousness, anger, frustration, embarrassment, depression, fatigue, confusion, frustration, annoyance, and general stress . Odor frequency, odor intensity and feeling their concerns are not being heard all contribute to annoyance, which leads to stress. Health worries contribute as well. See Table 4.2.Changes in odor-induced frontal lobe activity has been linked to changes in mood, drowsiness, and alertness . Unfortunately, the studies of this connection were few and additional research in this area is needed. Odor-induced brain activity is complex, involving more than 30 different regions. Exposure to malodor led to inability to focus on a task . Other studies reviewed found, however, that odors have no effect on task performance, so they concluded that the impact of odors on task performance may be odorant-specific. Increased prevalence of gastrointestinal symptoms were observed as a function of proximity to a wastewater treatment plant in Poland . The symptoms were correlated with both odors and microbiological pollutants and could not be disentangled to single out odors as the primary agent. Similarly, the negative effects of traffic noise and odor on residents in Windsor, Ontario, Canada, had a strong covariance between these two parameters and could not be differentiated .Some odorants and some co-pollutants within odors are considered hazardous air pollutants because they cause other adverse effects beyond smell and irritation.
Air that contains odorants also is known to contain odorless co-pollutants such as particulate matter and endotoxins . There was a positive correlation between the presence of odors and the prevalence of self-reported health symptoms, such as headache and nausea, when communities near hazardous waste sites were compared . However, more serious health outcomes – cancers, mortality and birth defects – were not higher compared to the control sites .Dose-response relationships for odors aim to link the percentage of people experiencing adverse effects, such as odor annoyance and irritation, to the level of exposure. For toxic chemicals, adverse effects increase as exposure increases. Odors, however, can be more inconsistent. For example, hydrogen sulfide loses its characteristic “rotten egg” odor note as the concentration increases, leading to harmful levels going unnoticed .The major goal of both risk assessment and odor assessment is to verify that exposures are below the thresholds of concern . For conventional risk assessment, the thresholds are health-based, often extrapolated from animal studies, and typically incorporate large margins of safety due to crude extrapolations and uncertainties. For odor assessment, achieving odorless air is the goal, yet due to the “lack of severity” of the effect, the acceptable limit is often set well above the odor-detection threshold. Given the wide variability in human response to odor, this approach is perilous, but a point of departure is needed, nonetheless. The amount of dilution required to achieve odorless air delivers a crude point of departure but should acknowledge the large error and be presented with only one significant figure in the final results. Thresholds for odorants typically vary by several orders of magnitude, especially the ODTC50 . Further, reliable methods may not have been used, and results for odor detection and odor recognition are sometimes mixed up. Within a controlled setting, two approaches to sensory testing of dilutions by panelists are used. One is the Odor Profile Method , which uses sugar solutions for calibration, and the other uses odor disappearance upon sufficient dilution. Both rely on dilution equipment, typically a dynamic dilution olfactometer that delivers sampled air diluted with odorless air to a nose port where the dilution is smelled by the panelist. Concentrations are presented in ascending order to avoid desensitization and anticipation bias. Statistics are then used on the panelists’ results to determine the ODTC50 for the odorant or mixture tested. For a single odorant, OPM is used to assign an odor note and intensity to each dilution. The Weber-Fechner law is applied, meaning that the logarithm of the concentration is taken and then the intensity results are fit to a line through linear regression. Extrapolation to intensity score 1 yields the ODTC50 value. Each odorant can have a vastly different slope. For example, a 200-fold change in concentrations of 1-propanol and n-amyl buterate caused a 15-fold and 0.5- fold change in odor intensity, respectively . For mixtures , the ODTC50 can be determined by forced choice, typically “triangle,” methods using the same dynamic dilution equipment . While inhaling at the nose port, the panelist rotates between three choices and then selects which is the diluted sample. A point estimate is generated rather than a curve, and no odor description is gathered. ASTM Method E679-04 has been used to determine the ODTC50 values for a range of odorants . Such methods have been used in the drinking water industry to set ODTC50 values for methyl tertiary butyl ether and improvements to ASTM Method E679-04 have been suggested for drinking water . In Europe, under EN 13725, the final dataset typically only includes the data for the four or more panelists whose results are the most consistent with the overall panel’s geometric mean value. Also, panelists may be presented with 2 samples instead of 3.