Analyses of volatile organic compounds from human skin.

BACKGROUND: Human skin emits a variety of volatile metabolites, many of them odorous. Much previous work has focused upon chemical structure and biogenesis of metabolites produced in the axillae (underarms), which are a primary source of human body odour. Nonaxillary skin also harbours volatile metabolites, possibly with different biological origins than axillary odorants. OBJECTIVES: To take inventory of the volatile organic compounds (VOCs) from the upper back and forearm skin, and assess their relative quantitative variation across 25 healthy subjects. METHODS: Two complementary sampling techniques were used to obtain comprehensive VOC profiles, viz., solid-phase microextraction and solvent extraction. Analyses were performed using both gas chromatography/mass spectrometry and gas chromatography with flame photometric detection. RESULTS: Nearly 100 compounds were identified, some of which varied with age. The VOC profiles of the upper back and forearm within a subject were, for the most part, similar, although there were notable differences. CONCLUSIONS: The natural variation in nonaxillary skin odorants described in this study provides a baseline of compounds we have identified from both endogenous and exogenous sources. Although complex, the profiles of volatile constituents suggest that the two body locations share a considerable number of compounds, but both quantitative and qualitative differences are present. In addition, quantitative changes due to ageing are also present. These data may provide future investigators of skin VOCs with a baseline against which any abnormalities can be viewed in searching for biomarkers of skin diseases.

Left-handers have a lower prevalence of arthritis and ulcer.

In a very large study (N = 1,247,344), left-handedness showed no association with allergies overall (and an inconsistent association with individual allergies), but there was strong evidence that left-handers had lower rates of arthritis and ulcer--Arthritis: Odds-ratio (OR) = 0.942, 95% CI 0.922-0.962; Ulcer: OR = 0.920, 95% CI 0.896-0.944.

Odorant exposure increases olfactory sensitivity: olfactory epithelium is implicated.

Exposure-induced shifts in sensitivity to odors may involve peripheral and/or central components of the olfactory system. The ability to disconnect the olfactory epithelium from the bulbs provides a unique opportunity to examine how odorant exposure affects each component. In one experiment, odor thresholds were established for either amyl acetate or androstenone. The mice were then exposed for 10 days to the same test odorant for which a threshold was obtained. After exposure, sensitivity to the odorant increased relative to preexposure levels. The mice then underwent bilateral olfactory nerve transection (BNX). When both groups of mice were tested 45-50 days after recovery from surgery and return of olfactory function, increased sensitivity to the exposed odorant persisted; however, 121-203 days after surgery, sensitivity returned to preexposure levels. Another experiment was similar to the first except that mice were exposed to an odorant, either amyl acetate or androstenone, for 10 days beginning 1 day after BNX or sham surgery. When the mice were tested 45-50 days after surgery, sensitivity to the exposed odorant was increased relative to preexposure levels, whereas sensitivity to the nonexposed odorant remained at preexposure levels. Although further work is needed to determine the precise mechanism(s) underlying shifts in sensitivity to odors, these studies provide additional evidence for peripheral involvement in exposure-induced sensitization to odorants and demonstrate the remarkable capacity of the olfactory system to maintain or even regain sensitivity after injury.

Amelioration of odorous components in spent mushroom compost.

Volatile sulfur compounds, as well as other volatiles found in the headspace above spent mushroom compost (SMC), were analyzed by gas chromatography and mass spectrometry. Data from these techniques as well as organoleptic evaluation of both the SMC and the chromatographic eluant indicated that the volatile sulfur compounds and cresol were important odorous components in SMC; cresol was reported as a musty, cattle-feces aroma. Samples consisted of headspaces from untreated SMC as well as SMC stirred with 1% (by weight) powered activated carbon (PAC). SMC stirred with and without PAC reduced headspace volatile concentrations, but the stirred with added PAC further decreased concentrations of important malodorants such as volatile sulfur compounds and cresol.

Spatiotemporal masking in pure olfaction.

In olfaction, it is not possible to determine which nostril is being stimulated, i.e., lateralize, when a pure olfactory substance, e.g., phenylethyl alcohol or vanillin, is administered into one nostril, and, simultaneously, an odorless, solvent blank into the contralateral nostril. We subjected volunteers to extensive training, with feedback on each trial, in an attempt to determine whether it was possible, in these well-trained subjects, to overcome this apparent impossibility. We failed to obtain any evidence to support the notion that a pure olfactory stimulus could be lateralized when the odorant and blank were presented simultaneously. The task, however, became simple when the odorant and the blank entered each nostril sequentially. We investigated, using a two-channel olfactometer, temporal parameters that enabled such discrimination. We controlled the duration of odorant and blank air puffs, as well as their mutual timing, to determine the threshold stimulus onset-disparity, i.e., the interval between stimulus onset and blank onset, that resulted in an inability to lateralize. Latencies shorter than the threshold interval would be perceived as simultaneous stimulation. We determined that the onset interval was between 200 and 400 ms, depending on the duration of the stimuli (a shorter interval was noted for stimuli of 150-ms duration relative to 300- and 450-ms stimuli). This was also true when two odorants were applied, rather than an odorant and a blank, and the subject was instructed to focus on the sequence of odorant delivery and side of stimulation. The temporal onset threshold was the same for lateralization and for order of stimulation. Whether the olfactory system per se mediates this discrimination or whether inputs from olfaction and chemesthesis, via trigeminal free nerve endings stimulated by air-stream onset, combine to allow this discrimination has yet to be determined.

FOS immunoreactivity after exposure to conspecific or heterospecific urine: where are chemosensory cues sorted?

Female prairie voles (Microtus ochrogaster) typically require an intact vomeronasal system and exposure to a chemical signal found in urine from male prairie voles to induce uterine growth necessary for reproduction. Urine from male mice (Mus musculus) does not contain an effective cue for activation of female vole reproduction: after 4 days of exposure to stimuli, voles exposed to urine from female or water had still uteri whereas voles exposed to urine from male voles had large uteri. The initial response to urine from male voles included neuronal activity in the vomeronasal system as indicated by FOS immunocytochemistry. Stimuli (urine from a male vole or a male mouse, or water) were painted on the nose of naive female voles 1 h before sacrifice. Female voles exposed to urine from male voles had more FOS-immunoreactive cells in the accessory olfactory bulb than voles exposed to mouse urine or to water. We conclude that exposure to urine from male voles stimulates the vomeronasal pathway (as measured by FOS immunoreactivity) and induces uterine growth in female voles, whereas exposure to urine from male mice (or water) does not. This suggests that some degree of functional specificity of the clinical cue is determined at or before the accessory olfactory bulb, perhaps in the expression of specific receptors within the vomeronasal organ, rather than entirely within the central nervous system.

Acetone odor and irritation thresholds obtained from acetone-exposed factory workers and from control (occupationally unexposed) subjects.

Sensitivity of olfaction (smell) and chemesthesis (irritation) was evaluated for 2-propanone (acetone) and 1-butanol in acetone-exposed workers (AEW; N = 32) during a workday and unexposed subjects (microES; N = 32). Irritation sensitivity was assessed using a method that relies on the ability of individuals to localize irritants on the body. When a volatile compound is inhaled into one nostril and air into the other, the stimulated side can be determined (lateralized) only after the concentration reaches a level that stimulates the trigeminal nerve (irritation); compounds stimulating olfaction alone cannot be lateralized. Intranasal lateralization thresholds offer an objective measure of sensory irritation elicited by volatile compounds. Test results indicated that neither olfactory nor lateralization thresholds for butanol differed between AEW and microES. Olfactory thresholds to acetone in AEW (855 ppm) were elevated relative to those of microES (41 ppm), as were lateralization thresholds (36,669 ppm and 15,758 ppm, respectively). Within AEW, level of occupational exposure was not correlated with thresholds. Other measures revealed that microES used more irritation descriptors than did AEW on trials where the acetone concentration was below the lateralization threshold. This is noteworthy because microES received lower concentrations of acetone to evaluate than did AEW. These results suggest that exposures to acetone induce changes in acetone sensitivity that are specific to acetone. The acetone concentrations eliciting sensory irritation using the lateralization technique were all well above current occupational exposure standards. The current study indicates that acetone is a weak sensory irritant and that sensory adaptation is an important factor affecting its overall irritancy.

Perceived odor, irritation, and health symptoms following short-term exposure to acetone.

The subjectivity of irritancy judgments can bias attempts to establish exposure guidelines that protect individuals from the sensory irritation produced by volatile chemicals. At low to moderate chemical concentrations, naive and occupationally exposed individuals often show considerable variation in the reported levels of perceived irritation. Such variation could result from differences in exposure history, differences in the perceived odor of a chemical, or differences in generalized response tendencies to report irritation, or response bias. Thus, experimental evaluation of sensory irritancy must dissociate sensory irritation from response bias. To this end, judgments of perceived irritation from 800 ppm acetone were obtained from acetone-exposed workers and age- and gender-matched naive controls. To assess the role of response bias during exposure to odorants, subjects were also exposed to phenylethyl alcohol (PEA), an odorant that does not produce sensory irritation. Following exposure, subjects completed a subjective symptom survey that included symptoms that have been associated with long-term solvent exposures and symptoms that have not. Acetone-exposed workers and naive controls reported large differences in the perceived intensity of odor and irritation from acetone, yet no differences in the perception of PEA. However, for both groups, the most significant factors mediating reported irritancy and health symptoms from acetone were the perceived intensity of its odor and an individual's bias to report irritation from PEA. The perception of odor intensity and degree of response bias will differ between and within groups of exposed and naive individuals; hence, an assessment of the influence of these factors in experimental and workplace studies of chemical irritancy is warranted.

The influence of cognitive bias on the perceived odor, irritation and health symptoms from chemical exposure.

OBJECTIVE: Responses to volatile chemicals are often subjective and variable, both over time and across individuals. Although variability can derive from differences in individual olfactory sensitivity, the response to a chemical stimulus is also influenced by the complex environment surrounding the exposure, which can include the perceiver's cognitive state. To explore the role of cognitive bias in chemical exposures, we evaluated whether information about the consequences of exposure to acetone could influence ratings of odor and irritation during exposure and/or the frequency or intensity of reported health symptoms following exposure. METHODS: Ninety adults (mean age 33.7, range 25-64) with no history of occupational exposure to solvents, were exposed to 800 ppm acetone in a chamber for 20 min. To control for non-specific responses to the odor of acetone, the subjects were also exposed for 20 min to 200 ppm phenylethyl alcohol (PEA), a non-irritant volatile chemical that produces a distinct odor but does not elicit irritation in the vapor phase. Subjects were assigned to one of three groups (n = 30/group); each group was given either a positive, negative or neutral bias towards the consequences of exposure to the chemicals in the study. During exposure, subjects rated the intensity of odor and irritation; following exposure, they completed symptom questionnaires. RESULTS: During the 20-min exposure to acetone, the positive bias group exhibited the most adaptation to its odor and the lowest perceived irritation; following exposure they reported the fewest health symptoms. In contrast, the negative bias group rated higher levels of odor intensity and, on average, reported the most over-all irritation; following exposure they reported significantly more health symptoms than the other groups, None of the demographic variables studied (e.g., age, gender, race, smoking status) were predictive of the response to odor or irritation. The perceived irritancy of acetone was well predicted by a linear combination of the perceived odor of acetone and perceived irritation for PEA (the nonirritant), r2 = 0.73. CONCLUSIONS: The results provide strong evidence that both the perceived odor and cognitive expectations about a chemical can significantly affect how individuals respond to it. Moreover, because naive control subjects appear to exhibit extreme variation in their cognitive evaluations of chemical effects, there may be limited value in using non-exposed controls to assess the irritancy of chemicals for worker populations.

The nature and duration of adaptation following long-term odor exposure.

Any individual living or working in an odorous environment can experience changes in odor perception, some of which are long lasting. Often, these individuals report a significant reduction in the perception of an odor following long-term exposure to that odor (adaptation). Yet, most experimental analyses of olfactory adaptation use brief odorant exposures which may not typify real-world experiences. Using a procedure combining long-term odor exposure in a naturalistic setting with psychophysical tests in the laboratory, we present evidence to show that reduced odor intensity following long-term exposure is accompanied by odorant-specific shifts in threshold. Subjects were exposed continuously to one of two odorants while in their home for a period of 2 weeks. Exposure produced an odorant-specific reduction in sensitivity and perceived intensity compared with preexposure baselines: Detection thresholds for the adapting odorant were elevated following exposure and perceived intensity ratings for weak concentrations were reduced. For most individuals, reduced sensitivity to the test odorant was still evident up to 2 weeks following the last exposure. The persistence of the change, as evidenced by the duration of recovery from adaptation, distinguishes this phenomenon from the adaptation seen following shorter exposures and highlights the need for the study of exposure durations that are more similar to real-world exposures.

The role of perceptual and structural similarity in cross-adaptation.

Cross-adaptation, the decrease in sensitivity to one odorant following exposure to a different odorant, is affected by odorant similarity, both perceptual and structural, but the precise relationship is obscure. The present series of studies was designed to explore various aspects of perceptual and structural similarity as they relate to cross-adaptation. In Experiment 1, cross-adaptation was assessed between androstenone and five odorants that share a common urinous note with androstenone, but retain unique perceptual characteristics; only the compound judged most perceptually similar to androstenone cross-adapted it. In Experiment 2, odorants both perceptually and structurally similar (androstenone and androstanone) displayed significant, mutual cross-adaptation. Furthermore, magnitude estimates for androstanone were significantly reduced following exposure to 3-methylidene-5 alpha-androstane (3M5A), a structurally similar, perceptually odorless compound. This finding appears to be the first demonstration that an odorless compound can affect, via cross-adaptation, the perception of an odorous compound. Finally, in Experiment 3, significant, asymmetric cross-adaptation was observed between compounds that are perceptually and structurally dissimilar (4-cyclohexylcyclohexanone [4-CHCH] and androstenone). These findings indicate that the role of similarity in cross-adaptation is difficult to quantify and emphasize the numerous odorant characteristics that can affect cross-adaptation.

An ephemeral pheromone of female house mice: perception via the main and accessory olfactory systems.

Two experiments examined the chemosensory modalities by which males detect an ephemeral sex pheromone in the freshly voided urine of female mice. Experiment 1 examined the interaction of deafferenting the accessory olfactory system (vomeronasal organ removal) and subsequent sexual experience upon ultrasonic vocalizations by male mice to freshly voided female urine. In general, sexually experienced males vocalized substantially more than sexually naive males. In addition, males possessing a vomeronasal organ vocalized slightly more than those without. Nonetheless, a functioning vomeronasal organ clearly was not essential for vocalizing to fresh female urine. Experiment 2 examined the effects of deafferenting the main olfactory system (ZnSO4 nasal irrigation) and/or the accessory olfactory system (vomeronasal removal) in sexually experienced males. Males with both olfactory systems functioning vocalized at high levels to fresh urine, while males with only one functioning system vocalized at intermediate levels. Males with neither system functioning did not vocalize at all to fresh urine. In contrast, when female mice themselves served as stimuli, all groups of males vocalized at high levels. We conclude that adult male mice can detect the ephemeral pheromone via either the main olfactory system or the accessory olfactory system. However, vocalizations to the female herself can be mediated by other sensory systems as well.

Chemosensory function and diet in HIV-infected patients.

Alterations of chemosensory function have been noted in human immunodeficiency virus (HIV)-infected patients, but their frequency, severity, and relationship to diet have not been adequately assessed. Odor and taste identification tests and a taste-intensity scaling task were administered to 25 men who were HIV-infected but otherwise healthy. Responses were compared to those of 49 comparably aged male control subjects. Dietary information was obtained by questionnaire. Although 72% of HIV-infected patients reported some chemosensory alteration, no significant differences in taste identification ability or intensity ratings were observed between patients and controls. Twelve percent of patients had poor odor identification scores, but the group mean was similar to that of controls. Neither measured nor self-reported sensory indices were significantly related to any variable of health (e.g., HIV helper cell (CD4) count, body weight, or body composition), treatment, or diet.

Cross-adaptation of sweaty-smelling 3-methyl-2-hexenoic acid by a structurally-similar, pleasant-smelling odorant.

Cross-adaptation has been interpreted as a measure of the degree to which odors share common sensory channels. How structural similarity, in the absence of perceptual similarity, influences cross-adaptation is unknown. The present study assessed cross-adaptation by structurally similar, but perceptually different, odorants. Magnitude estimates for a 10:1 mixture of (E)- and (Z)-3-methyl-2-hexenoic acid (3M2H), a principal component of human underarm odor, decreased following adaptation to a mixture of (E)- and (Z)-ethyl esters of 3M2H (EE3M2H), which possess a pleasant, fruity odor. Cross-adaptation was asymmetric; adaptation to 3M2H did not significantly affect the perceived intensity of EE3M2H. By contrast, there was no significant cross-adaptation between 3M2H and the fruity-smelling ethyl esters of its homologues, 3-methyl-2-octenoic acid (EE3M20) and 3-methyl-2-pentenoic acid (EE3M2P). Similarity ratings revealed no differences among the three ethyl esters in their perceptual similarity to 3M2H (i.e. all were rated equally dissimilar to 3M2H). Molecular modeling studies revealed no difference in the charge distribution of these molecules. Rather, differences in the shape and size of the hydrophobic part of the molecule may determine the extent of cross-adaptation. These results demonstrate that structurally-similar, yet perceptually-distinct, odorants may cross-adapt and suggest that the extent of cross-adaptation may be affected by the degree of structural, as well as perceptual, similarity.

Age-dependent responses to chemosensory cues mediating kin recognition in dogs (Canis familiaris)

During individually administered 5-min tests conducted in a neutral cage, four age groups (n = 10 males and 10 females per group) of purebred beagles reacted to bedding from their home cage vs. bedding from another litter of the same age. The 20-24-day-old males and females preferred (p < 0.05) home cage bedding over strange cage bedding. Those aged 31-36 days or 66-72 days showed no reliable preference for either type of bedding. Among pups aged 52-56 days, the males preferred (p < 0.05) strange cage bedding, but the females showed no reliable preference. Chemosensory cues are sufficient as mediators of kin recognition in beagles, but their reactions to such cues vary with age-dependent factors, some stemming from changes in the strength of the mother-litter bond. The dogs providing the two types of bedding lived in the same room and on the same diet. Therefore, kin recognition could not have been mediated by different chemosensory cues produced by variations in these environmental factors.

Induction of olfactory receptor sensitivity in mice.

Repeated exposure to olfactory ligands (odorants) increased peripheral olfactory sensitivity in mice. For two unrelated ligands, androstenone and isovaleric acid, induction of olfactory sensitivity was odorant-specific and occurred only in inbred strains that initially had low sensitivity to the exposure odorant. These data demonstrate stimulus-induced plasticity in a sensory receptor cell, suggesting a form of stimulus-controlled gene expression. Induction with two unrelated odorants implies that olfactory induction is a general phenomenon that may occur in a large fraction of the human population.

Life span changes in the verbal categorization of odors.

An odor description task was used to explore age-related change in odor perception based on 1.19 million U.S. and Canadian respondents (ages 10-90 years) to the National Geographic Smell Survey. Respondents sampled six microencapsulated odorants and selected 1 of 11 descriptors to characterize each smell. Four odors were characterized by strong consensus endorsement of a single descriptor. This consensus weakened with advancing age, and nonmodal descriptors were endorsed more frequently. Nonmodal responses were neither randomly selected, nor systematically biased across odors. Rather, they showed odor-specific patterns of change. Together, these results suggest a marked change in odor categorization across the life span. Odor descriptor profiles were used to generate age-specific multidimensional scaling maps. Stimulus configurations were stable from the third through fifth decades. Those from the sixth through ninth decades showed major displacements for two odors, and suggest that the sweet dimension of odor quality may be particularly variable with maturation.

The effects of aging on the human sense of smell and its relationship to food choice.

Olfaction plays a significant role in the perception of foods. For the most part, taste is limited to sweet, sour, bitter, and salty. The sensory experiences during consumption of complex foods and drinks cannot be constructed from these units. Indeed, much of the taste of a meal derives from olfactory stimulation. Hence, factors that influence olfactory perception should affect treatment of food-related odors. This article initially reviews previously published observations on the effects of age on olfaction and food preferences and then presents the results of original analyses of data derived from a substantial database formed as a result of the National Geographic Smell Survey. Included in the Survey form were topics relevant to the present article. They include the following question: Would you eat something that smelled like this? Two of the odors in the Survey were food related and two were fragrance related. Hence, in addition, we assessed responses to the following question: Would you apply something that smelled like this to your body? Answers were affected in part by the age and gender of the respondent and by the perceived pleasantness and intensity of the odor.

Hand preference and age in the United States.

A survey of 1,177,507 U.S. men and women between the ages of 10 and 86 included questions regarding hand preference for writing and throwing. Three effects were observed. Individuals with at least some left motoric bias comprised a smaller percent of the population with advancing age. This finding provides large-scale confirmation of a previously described phenomenon. Among sinistrals, concordance for writing and throwing was 2.2 times as prevalent as left-writing with right-throwing, and 4.1 times as prevalent as right-writing with left-throwing. These sinistral subpopulations displayed distinct and stable prevalence prior to age 50 and changing patterns of prevalence subsequent to age 50. The results confirm a decrease with age in the prevalence of sinistrality, but indicate that age-specific rates of mixed- and left-handedness are distinct. The implications for hypotheses regarding age-related change in the prevalence of sinistrality are discussed.