Perceived odor and irritation of isopropanol: a comparison between naïve controls and occupationally exposed workers

OBJECTIVES: To assess sensory irritation levels from isopropanol (IPA) unconfounded by subjective evaluations of odor for comparison against the recommended exposure limits (400 ppm threshold limit value (TLV); American Conference of Governmental Industrial Hygienists). METHOD: The lateralization method was used to assess intra-nasal irritation thresholds for IPA, while odor detection thresholds were also measured. Thresholds for 1-butanol and phenyl ethyl alcohol (PEA) were obtained as positive and negative irritant controls. To compare potency and hedonic characteristics, subjects provided subjective ratings of odor, irritation and annoyance intensity for three concentrations of each chemical. Workers occupationally exposed to IPA ( n=26) were compared with previously unexposed controls ( n=26). RESULTS: The (geometric) mean odor detection threshold for IPA was slightly higher among exposed workers than controls (39 ppm vs. 11 ppm). Lateralization thresholds measuring intra-nasal irritation were elevated when compared with controls (6,083 ppm in exposed workers vs. 3,361 ppm in na?ve controls), with a significantly higher proportion of phlebotomists being unable to lateralize the maximum concentration regarded as safe, than controls. Calculations of the 6th percentile for lateralization thresholds revealed that 95% of the sample did not experience sensory irritation below 512 ppm. Thus, while odor detection thresholds were well below the current recommended exposure limits, the irritation thresholds were well above these values. The odor, irritation and annoyance from IPA was perceived, on average, as between weak and almost strong, from lowest to highest concentration. CONCLUSIONS: The results indicate that current exposure guidelines would be adequately protective of the acute adverse effect of nasal sensory irritation, as operationally defined by the intra-nasal lateralization threshold. Exposures to higher concentrations should perhaps be evaluated on the basis of existing knowledge about systemic, rather than local (e.g., irritation), toxic effects. IPA appears to be a weak sensory irritant and occupational exposure to IPA appears to elicit small changes in sensitivity that do not generalize to other odorants (e.g., PEA and 1-butanol) and are likely to be reversible.     

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. Am. J. Ind. Med. 31:558–569, 1997. © 1997 Wiley-Liss, Inc.     

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 nonirritant 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 overall 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 the perceived irritation from PEA (the nonirritant), r ²=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. Received: 7 May 1996/Accepted: 20 September 1996     

Odor frequency and odor annoyance Part II: dose–response associations and their modification by hedonic tone

Objective Risk-assessment for environmental odors and the development of an appropriate guideline for protection against undue odor annoyance have long been hampered by the difficulties of assessing odor exposure and community annoyance responses. In recent years, however, dose–response associations between frequency of odor events and odor annoyance level in the affected population were established. However, the influence of hedonic tone (pleasantness–unpleasantness) and perceived odor strength (intensity) on the degree of odor annoyance have long been neglected in such studies and accompanying guidelines. In order to close this gap a pertinent field study was conducted in the vicinity of six odor emitting plants, two with pleasant (sweets production, rusk bakery), with neutral (textile production, seed oil production), and with presumably unpleasant odor emissions (fat refinery, cast iron production). Methods A standardized sensory method was developed (described in Part I in the accompanying paper) to quantify intensity and hedonic tone within the assessment of odor exposure by systematic field inspection with trained observers. Additionally, exposure-information, the degree of annoyance, and the frequency of general health complaints and irritation symptoms were collected from the exposed residents through direct interviews. Multiple logistic regression analysis was used to establish dose–response associations between odor frequency, intensity and hedonic tone as independent variables and annoyance or symptom reporting as the dependent variable. Results It is shown that exposure-annoyance as well as exposure–symptom associations are strongly influenced by odor hedonic. Whereas pleasant odors induced little to no annoyance, both neutral and unpleasant ones did. Additional inclusion of odor intensity did not improve the prediction of odor annoyance. Frequency of reported symptoms was found to be exclusively mediated by annoyance. The results are discussed in terms of environmental stress emphasizing the WHO-definition of health. Conclusions Based on these findings the existing German guideline against undue odor annoyance was modified. Parts of these findings were presented at the 15th Congress of the European Chemoreception Research Organization in Erlangen (2002), at the 43rd Congress of the German Society of Psychology in Berlin (2002), and at the at the 9th Meeting of the International Neurotoxicology Association in Dresden (2003).     

Cytological changes and conjunctival hyperemia in relation to sensory eye irritation

In general, irritation is a physiological response to a chemical or physical stimulus involving objective changes (e.g., local redness and edema) and subjective sensations (e.g., pruritus and pain). The perception of an irritating stimulus in the eyes and the upper airways is called sensory irritation. Sensory irritation is a prevalent symptom in relation to complaints about indoor air quality. The intensity of perceived sensory irritation in humans has mainly been evaluated using psychophysical methods. However, perceived sensory irritation is dependent on the subject expressing the symptoms; that is, it is a subjective measure. This is a problem in assessment of irritation effects from air pollution or other factors, since the expression of the irritation symptoms may be biased by, for example, interaction with other people and odors. The subjectivity of the measures is an important complication in several studies dealing with problems regarding indoor air quality. The bias problems make it important to complement the psychophysical measurements of sensory irritation with objective assessments of irritation. In addition, only little is known about the association between sensory irritation and possible physiological/pathological changes in the mucosal membranes in relation to studies of indoor air. Two studies (study 1 and study 2) were conducted to investigate changes in conjunctival hyperemia and conjunctival fluid cytology for subjects exposed to volatile organic compounds (VOCs) in their eyes only. Eight subjects participated in study 1. Each subject was exposed to three different mixtures of VOCs. A total of 16 subjects participated in study 2. Half of the subjects were exposed to 1-octene and the other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were taken and conjunctival fluid was sampled before and after exposure. Moreover, the perceived irritation intensities were registered continuously during exposure. Overall, perceived irritation intensity and conjunctival hyperemia increased with increasing exposure concentrations, whereas cytological changes in the conjunctival fluid samples did not seem to be related to exposure concentration, perceived irritation, or changes in conjunctival hyperemia. Received: 4 April 1997 / Accepted: 25 September 1997     

Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol

OBJECTIVES: The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. METHODS: In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. RESULTS: At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. CONCLUSIONS: Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.     

Annoyance and performance of three environmentally intolerant groups during experimental challenge with chemical odors

OBJECTIVES: This study investigated exposure- and subject-related determinants of annoyance and performance during the chemical odor provocation of healthy persons with self-reported environmental annoyance. METHODS: Persons with self-reported annoyance attributed to (i) chemicals or smells (smell-annoyed, SA, N=29), (ii) electrical equipment (electrically annoyed, EA, N= 16), and (iii) both smells and electricity (generally annoyed, GA, N=39) were, together with referents (N=54), challenged with n-butyl acetate in an exposure chamber at levels far below the threshold values for neurotoxic effects and trigeminal irritation. A sequence of three air concentrations, 0.37, 1.5, and 6 ppm (1.8, 7.1, and 28 mg/m3) was used, counterbalanced within groups, together with intermittent periods of room air between each exposure level. The response measures comprised ratings of annoyance and smell intensity and reaction-time tests. RESULTS: Only the GA group showed clearly elevated ratings of smell annoyance, mucous membrane irritation, and fatigue, as well as longer reaction times, compared with the referents, in response to the challenge. No group difference was found for the smell-intensity ratings. During intermittent periods without exposure, only the GA group maintained higher ratings for mucous membrane irritation and fatigue. Reaction time and all the rating dimensions showed a positive relationship with momentary n-butyl acetate concentration, while cumulative exposure had a more limited impact on the ratings and reaction time. A suggestion effect by the chamber environment before exposure could not be demonstrated. CONCLUSIONS: The results suggest that self-reported annoyance generalized to both electrical equipment and smells is a better predictor of chemical intolerance than self-reported annoyance to smells only.     

Integration in human eye irritation

 Today it is widely known and accepted that indoor air pollution can affect health. To ensure a healthy indoor climate through source control it is necessary to be able to predict how much of a source can be introduced into a building without unacceptable health and comfort effects. This paper describes a study of human eye irritation, which is part of a research program aimed at developing the use of sensory reference scaling in source characterization. In reference scaling the sensory eye irritation caused by exposure to polluted air is measured in terms of a concentration of a reference gas causing equivalent eye irritation intensity. The purpose of this study, therefore, was to estimate a possible difference in the magnitude of perceived sensory irritation between unilateral and bilateral exposure of human eyes. In each of four runs ten subjects were exposed to five progressive concentrations of CO₂. In two of the runs the subjects were exposed unilaterally and in the other two runs the subjects were exposed bilaterally. In an analysis of variance no significant difference was found between unilateral and bilateral exposures. As expected, the intensity of the perceived irritation increased significantly with increasing exposure level. The sensitivity decreased slightly but significantly following previous exposures. These results enable us to develop a model for source characterization in which sensory eye irritation is measured by reference scaling. The use of reference scaling has the advantage that an otherwise subjective response (perceived irritation intensity) becomes less biased. Received: 5 February 1996/Accepted: 2 May 1996     

Odor, irritation and perception of health risk

OBJECTIVES: Understanding the potential for volatile chemicals to elicit chemosensory irritation in the upper respiratory tract is critical to setting occupational exposure limits that are protective of comfort and well-being for the majority of workers. However, the determination of irritant potency for any volatile chemical has been limited by the lack of reliable and non-invasive assays for studying sensory irritation in humans and a failure to appreciate the many non-sensory factors that can influence the reactions to an odor or an irritant in the workplace. METHODS: This paper reviews the issues involved in distinguishing and measuring sensations of odor and irritation from volatile chemicals, and describes recent developments in psychophysical methods for evaluating chemical irritancy in humans, and discusses some of the many non-sensory factors such as exposure history, attitudes and expectations and personality variables that can significantly alter the perception of odor, irritation and health risk following exposure to a volatile chemical. RESULTS: The availability of safe, non-invasive assays to measure directly odor and irritant responses in the species of interest, humans, can both simplify and improve accuracy in the process of developing appropriate occupational exposure guidelines. CONCLUSIONS: Objective measures of irritation onset obtained in conjunction with subjective responses can lend valuable input to the decision process for determining occupational exposure limits but should always account for other factors (e.g., cognitive or emotional) that may be modulating the subjective response.     

1998 equivalence of sensory responses to single and mixed volatile organic compounds at equimolar concentrations.

Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance.     

Does seasonal allergic rhinitis increase sensitivity to ammonia exposure?

Allergic inflammation in the upper airways represents a wide-spread health issue: Little is known about whether it increases sensitivity to airborne chemicals thereby challenging established exposure limits that neglect such differences in susceptibility. To investigate the role of pre-existing allergic inflammation, 19 subjects with seasonal allergic rhinitis (SAR) and 18 control subjects with low risk of sensitization were exposed for 4 h to ammonia in two concentrations (cross-over design): 2.5 ppm (odor threshold) and 0–40 ppm (occupational exposure limit: 20 ppm TWA). Prior to the whole-body exposure, it was confirmed that subjects with SAR showed persistent inflammation outside the pollen season as indicated by increased exhaled nitric oxide and total immunoglobulin E in serum compared to controls. Despite concentration-dependent increases in chemosensory perceptions and acute symptoms, SAR status did not modulate subjective effects of exposure. Moreover, SAR status did not affect the investigated physiological endpoints of sensory irritation: While eye-blink recordings confirmed weak ocular irritation properties of ammonia at 0–40 ppm, this effect was not enhanced in SAR subjects compared to controls. Irrespective of SAR status, exposure to 0–40 ppm ammonia did not result in a cortisol stress response, objective nasal obstruction as measured with anterior active rhinomanometry, or an inflammatory response as indexed by substance P, tumor-necrosis-factor α, and high-mobility-group protein 1 in nasal lavage fluid. At least for the malodorous compound ammonia, these results do not support the hypothesis that SAR enhances chemosensory effects in response to local irritants. Before generalizing this finding, more compounds as well as sensitization to perennial allergens need to be investigated.     

Olfactory sensitivity in medical laboratory workers occupationally exposed to organic solvent mixtures

BACKGROUND: Published epidemiological information relating the effects of occupational exposure to organic solvents (OS) to olfaction is limited. AIMS: The objectives of this pilot study were to measure the chemosensory abilities of medical laboratory employees occupationally exposed to OS mixtures, to compare these with control workers employed within the same occupational setting and to correlate chemosensory performance with OS exposure history and with employees' hedonic (pleasantness) perceptions about workplace OS odors. METHODS: Twenty-four medical laboratory employees (OS-exposed technicians plus control workers minimally exposed to OS) completed a health-related questionnaire, a test of pyridine odor detection threshold, along with a gustatory detection threshold test involving aqueous quinine solutions. Estimates of cumulative hours of OS exposure (CSI) were calculated from self-reports. RESULTS: OS-exposed laboratory technicians detected weaker concentrations of pyridine odor. Positive correlations were detected between CSI estimates to both pyridine detection and the degree that participants reported that OS odors were present in the workplace. However, no association was detected between pyridine detection and how unpleasant workplace OS odors were perceived. The OS-exposed participants were able to detect weaker concentrations of quinine. Compared to controls, OS-exposed workers complained more of experiencing several symptoms while working, including headaches, nasal irritation and mild cognitive impairment. CONCLUSIONS: The results of this cross-sectional pilot study indicated that, compared to controls, medical laboratory technicians exposed to low-level OS mixtures displayed evidence of elevated olfactory sensitivity (hyperosmia) to pyridine odor. The relation of this study's results to chemical intolerance warrants further investigation.     

Exposure of humans to a volatile organic mixture. II. Sensory.

Time-course functions for symptoms of the sick building syndrome were derived from 66 healthy males who, during separate sessions, were exposed to clean air and to a volatile organic compound (VOC) mixture. The mixture contained 22 VOCs (25 mg/m3 total concentration) commonly found airborne in new or recently renovated buildings. Subjects rated the intensity of perceived irritation, odor, and other variables before, and twice during, 2.75-h exposure periods. Eye and throat irritation, headache, and drowsiness increased or showed no evidence of adaptation during exposure, whereas odor intensity decreased by 30%. These results indicate that irritation intensity and other symptoms are not related in any simple way to odor intensity, which suggests that the symptoms may not be a psychosomatic response to the detection of an aversive odor. Instead, subthreshold levels of VOCs may interact additively or hyperadditively and stimulate trigeminal nerve receptors. Also, air quality ratings improved by 18% during exposure, which suggests that both odor and irritation intensity may influence assessments of air quality.     

Occupational exposure to solvent mixtures: effects on health and metabolism.

Exposure monitoring by personal diffusive samplers, biological monitoring of toluene exposure by urinary hippuric acid determination, haematology, serum biochemistry for liver function, and a subjective symptom survey by questionnaire were conducted on 303 male solvent workers. They were exposed to a mixture of solvents including toluene (geometric mean 18 ppm), methyl ethyl ketone (MEK; 16 ppm), isopropyl alcohol (IPA; 7 ppm), and ethyl acetate (9 ppm). The intensity was mostly below unity using the additiveness formula based on current Japanese occupational exposure limits, but more than eight times unity at the maximum. The results were compared with the findings in 135 non-exposed male workers of similar ages. Haematology and liver function tests did not show any exposure related abnormality, and subjective symptoms were mostly related to central nervous system depression and local irritation. Further analysis suggested that the irritation effects were not related to exposure to MEK. Analysis of the relation between toluene exposure and hippuric acid excretion in urine showed that there was no metabolic interaction between MEK and toluene, or between IPA and toluene. Overall, therefore, it is concluded that there was no sign or symptom detected to suggest anything other than toluene toxicity, that there was no evidence to indicate any modification of toluene toxicity or metabolism due to coexposure, and that the additiveness assumption is reasonable for risk assessment for the combination of solvents under these exposure conditions.     

Psychological reactions related to chemosensory irritation

OBJECTIVES: For risk assessments of solvents the knowledge on chemosensory irritation effects is important, but the methodological base for that is incomplete. The psychological approach measuring chemosensory irritations leans on perceived symptoms and self-reported changes of well being. Characteristics assessing the validity of such psychological approaches are presented. METHODS: The article is based on 14 experimental inhalation studies with (mostly) 4-h exposures to acetone, 2-butanone, ethanol, ethyl acetate, ethyl benzene, iso-propanol, 1-octanol, and styrene. The profiles of exposure include constant and changing concentrations using the range of the German maximum concentrations at the workplace (MAK) list. Irritations (eyes and nose), olfactory symptoms (odour), and annoyance are the dependent variables measured by ratings. Young and healthy subjects ( n=160), - partially, subjects with self-reported odour sensitivity (measured by items from the questionnaire on chemical and general environmental sensitivity) - were investigated. RESULTS: The reliability of ratings is sufficient. Dose-response relationships for perceived odour and annoyance are stronger than those for irritations. A ranked order of the size of effect (related to the values before exposure) for the substances investigated shows correspondence between odour and annoyance; that for irritation differs. Within the limits of the MAK list, perceived irritations are not correlated to annoyance, whereas perceived bad smell correlates significantly to annoyance. Reversibility of the self-reported effects to approximately the pre-exposure level can be shown 1 h after cessation of the experimental exposure for the "normal" subjects. Influences of trait anxiety and chemical sensitivity on reports of annoyance, bad odour or irritation are only weak. CONCLUSION: The psychological approach of repeated measurements for self-reported irritation includes distinctive advantages compared with other methods, the simple and repeated availability during exposure, the sufficient reliability and dose-response relationship, and the comparability between substances by means of effect size. The extension of the concept of "chemosensory irritations" on reports for annoyance and bad smell can be recommended.     

Possible mechanisms of formaldehyde-induced discomfort in the upper airways.

Occupational exposure to formaldehyde often causes nasal discomfort. The objective of this study was to determine whether chronic exposure to formaldehyde causes annoying symptoms by direct irritation and whether it affects all exposed people (through hyperreactivity in atopic persons, through formaldehyde-induced hyperreactivity also in nonatopic persons, or through an immunologically mediated, immediate type 1 reaction to formaldehyde itself). It was found that about 50% of the studied population of 66 workers occupationally exposed to formaldehyde during formaldehyde production experienced nasal discomfort through hyperreactivity. Atopics were not significantly overrepresented among the persons with occupational nasal symptoms. Two workers with isolated occupational nasal discomfort, and sensitized by long-term inhalation, had a positive radioallergosorbent test for formaldehyde. The conclusion was reached that exposure to formaldehyde should be minimized as much as possible for all people, not only for atopic persons.     

Olfactory function in workers exposed to styrene in the reinforced-plastics industry

BACKGROUND: Impairment of olfactory function in humans has been associated with occupational exposure to volatile chemicals. To investigate whether exposure to styrene was associated with olfactory impairment, olfactory function was examined in workers with a minimum of 4 years exposure to styrene in the reinforced-plastics industry (current mean exposure: 26 ppm, range: 10-60 ppm; historic mean dose: 156 ppm-years, range: 13.8-328 ppm-years) and in a group of age- and gender-matched, unexposed controls. METHODS: Olfactory function was assessed using a standardized battery that included tests of threshold sensitivity for phenylethyl alcohol (PEA), odor identification ability, and retronasal odor perception. Odor detection thresholds for styrene were also obtained as a measure of specific adaptation to the work environment. RESULTS: No differences were observed between exposed workers and controls on tests of olfactory function. Elevation of styrene odor detection thresholds among exposed workers indicated exposure-induced adaptation. CONCLUSIONS: The present study found no evidence among a cross-section of reinforced-plastics industry workers that current or historical exposure to styrene was associated with impairment of olfactory function. Taken together with anatomical differences between rodent and human airways and the lack of evidence for styrene metabolism in human nasal tissue, the results strongly suggest that at these concentrations, styrene is not an olfactory toxicant in humans.     

Annoyance and performance during the experimental chemical challenge of subjects with multiple chemical sensitivity

OBJECTIVES: This study explored the subjective reactions and psychological test performance of smell-intolerant subjects during consecutive challenges to chemicals with contrasting neurotoxic properties. METHODS: Women with symptoms compatible with multiple chemical sensitivity (N=10) and healthy referents (N=20) were individually challenged in an exposure chamber. All the subjects attended two separate 2-hour sessions of exposure to n-butyl acetate and toluene, in counterbalanced sequence. After an initial phase without exposure, air concentrations were increased in steps ranging from 3.6 to 57 mg/m3 for n-butyl acetate and from 11 to 180 mg/m3 for toluene. The response measures comprised ratings of annoyance and smell intensity and also neurobehavioral test performance. RESULTS: Both groups showed an increase in annoyance ratings and a decrease in test performance in the initial unexposed chamber phase and also in the first phase of the chemical exposure, these results indicating slight immediate expectancy or "suggestion" effects. During the six chamber phases, the ratings of mucous membrane irritation and fatigue showed a steeper increase in the group with multiple chemical sensitivity than among the referents, while the ratings of smell intensity and smell annoyance were similar in the two groups. A reduction in test performance was observed during the chamber phases, particularly in the group with multiple chemical sensitivity. No relation was found between the ratings or performance and chemical substance. CONCLUSIONS: Stronger immediate expectancy or "suggestion" reactions than normal did not characterize the group with multiple chemical sensitivity. This group showed a stronger than normal gradual build-up of fatigue, mucous membrane irritation, and reduced performance during chemical exposure. The results offer the most support to an irritative basis for multiple chemical sensitivity.     

Local effects in the respiratory tract: relevance of subjectively measured irritation for setting occupational exposure limits

OBJECTIVES: Chemosensory effects of stimulation by a chemical can either be irritating (trigeminal stimulation) or odorous (olfactory stimulation) or both. For odorous irritants, a clear-cut distinction between odour and irritation is difficult to make. The differences in the lowest concentration found to be irritating to the respiratory tract in humans when compared to experimental animals has brought much debate in the process of setting occupational exposure limits (OELs) for such chemicals. In this paper it will be discussed as to how far subjectively measured sensory irritation threshold levels can be used to establish OELs. METHODS: Data on respiratory irritation of four odorous irritants were retrieved from public literature and discussed, viz. acetone, formaldehyde, furfural and sulphur dioxide. RESULTS: Objective measures of irritation yielded results that differed from subjective evaluations. Important factors modulating the reported levels of irritation and health symptoms include the perception of odour intensity, exposure history and the individual's bias to report irritation on the basis of his/her prejudice or knowledge of the compound. CONCLUSIONS: Subjective measures alone are less appropriate for establishing sensory irritation thresholds of odorous irritants and are, therefore, less suitable to establish OELs without supporting evidence. Objectively measured irritation in humans, the Alarie assay (an experimental animal test assessing the concentration that results in a 50% reduction of the breathing frequency) and repeated exposure studies in animals may be of help to study objective irritation. If subjective measurements are used to study sensory irritation, the study design should at least include: measurement of both incidence and severity determined at several concentrations, an appropriate (0 ppm) control condition, preferably a non-irritant odorant control exposure, validated questionnaires and correct concentration measurements.     

The role of odor and irritation, as well as risk perception, in the setting of occupational exposure limits

Objective: This paper reviews current research regarding the relationship between odor perception or irritation and setting an occupational exposure limit (OEL). Special focus was directed at those settings where a small fraction of persons report unacceptable responses to concentrations well below the OEL. Methods: We evaluated the published literature on the topic of irritation and olfactory response to exposure to industrial chemicals. More than a dozen researchers have been active in this area over the past 10 years. Results: It was found that for some chemicals, even when one maintains airborne concentrations below a particular OEL, this level of exposure may not be adequate to prevent all persons from reporting an appreciable adverse response. In some cases, worker’s pre-existing belief systems about the source of an odor may be sufficient to require that they have not be exposed to any detectable concentration. In addition, detection of odors by workers may tap into the person’s aversion to odors, in general. In both situations, it is often necessary to address these specific issues through risk communication and dealing directly with risk perception. Conclusions: For practical reasons, the current objective of organizations charged with setting OELs for chemicals is to identify concentrations that do not cause irritation or widespread reports of unpleasant sensory stimulation in the vast majority of workers (e.g., about 80–95%).