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.     

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.     

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.     

Acute sensory irritation from exposure to isopropanol (2-propanol) at TLV in workers and controls: objective versus subjective effects

OBJECTIVES: Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and na?ve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. METHODS: Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. RESULTS: Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as 'weak' on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. CONCLUSIONS: The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.     

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.     

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.     

Exposure study to examine chemosensory effects of formaldehyde on hyposensitive and hypersensitive males

Objective

Main objective of this study was to examine the chemosensory effects of formaldehyde on hyposensitive and hypersensitive males at concentrations relevant to the workplace. Attention focused on objective effects on and subjective symptoms of the mucous membranes of the eyes, the nose, the upper respiratory tract and olfactory function.

Methods

Forty-one male volunteers were exposed for 5 days (4 h per day) in a randomised schedule to the control condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to 0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8 ppm, respectively. Peak exposures were carried out four times a day over a 15-min period of time. Subjective pain perception induced by nasal application of carbon dioxide served as indicator for sensitivity to sensory nasal irritation. The following parameters were examined before and after exposure: subjective rating of symptoms and complaints (Swedish Performance Evaluation System), conjunctival redness, eye-blinking frequency, self-reported tear film break-up time and nasal flow rates. In addition, the influence of personality factors on the volunteer’s subjective scoring was examined (Positive And Negative Affect Schedule).

Results

Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min caused no significant sensory irritation of the measured conjunctival and nasal parameters. No differences between hypo- and hypersensitive subjects were seen. Nevertheless, statistically significant differences were noted for olfactory symptoms, especially for the ‘perception of impure air’. These subjective complaints were more pronounced in hypersensitive subjects.

Conclusions

Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects related to irritation, and no differences between hypo- and hypersensitive subjects were observed.     

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     

Sensory and cognitive effects of acute exposure to hydrogen sulfide

Background

Some epidemiologic studies have reported compromised cognitive and sensory performance among individuals exposed to low concentrations of hydrogen sulfide (H₂S).

Objectives

We hypothesized a dose–response increase in symptom severity and reduction in sensory and cognitive performance in response to controlled H₂S exposures.

Methods

In separate exposure sessions administered in random order over three consecutive weeks, 74 healthy subjects [35 females, 39 males; mean age (± SD) = 24.7 ± 4.2; mean years of education = 16.5 ± 2.4], were exposed to 0.05, 0.5, and 5 ppm H₂S. During each exposure session, subjects completed ratings and tests before H₂S exposure (baseline) and during the final hour of the 2-hr exposure period.

Results

Dose–response reduction in air quality and increases in ratings of odor intensity, irritation, and unpleasantness were observed. Total symptom severity was not significantly elevated across any exposure condition, but anxiety symptoms were significantly greater in the 5-ppm than in the 0.05-ppm condition. No dose–response effect was observed for sensory or cognitive measures. Verbal learning was compromised during each exposure condition.

Conclusions

Although some symptoms increased with exposure, the magnitude of these changes was relatively minor. Increased anxiety was significantly related to ratings of irritation due to odor. Whether the effect on verbal learning represents a threshold effect of H₂S or an effect due to fatigue across exposure requires further investigation. These acute effects in a healthy sample cannot be directly generalized to communities where individuals have other health conditions and concomitant exposures.     

Time course of sensory eye irritation in humans exposed to N-butanol and 1-octene

In this study, we investigated the time course effect of sensory eye irritation in 16 subjects exposed (i.e., eye only) to n-butanol and 1-octene. Half the subjects were exposed to n-butanol, and the remaining subjects were exposed to 1-octene. Each subject was studied on 5 different days; during each day each subject was exposed in three runs (i.e., run 1, run 2, and run 3) to a constant concentration of either n-butanol or 1-octene. We performed run 1 and run 3, both of which lasted 15 min each, to evaluate persistence in "sensitization." We performed run 2, which lasted 60 min, to study the time course of sensory irritation. Ratings of ocular irritation intensity were obtained continuously during all three runs. The exposure concentrations for n-butanol were 0 mg/m3, 300 mg/m3, 900 mg/m3, and 3 000 mg/m3, and the exposure concentrations for 1-octene were 0 mg/m3, 6 000 mg/m3, 10 400 mg/m3, and 18 000 mg/m3. During run 2, we observed a slight increase in perceived eye irritation intensity for the lower concentrations of 1-octene and for all exposure concentrations of n-butanol. However, the threshold for irritation was clearly exceeded for only the 1-octene 10 400-mg/m3 and 18 000-mg/m3 exposures. During these two exposures, the response increased 10-fold following 20-40 min of exposure during run 2, after which the response remained constant. We investigated the existence of persistence in "sensitization" by comparing intensity of responses between run 1 and run 3. Persistence in "sensitization" was apparent for only the 1-octene exposure.     

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     

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.     

An experimental study on irritation and annoyance due to passive smoking

Forty subjects were exposed to cigarette smoke produced by a smoking machine in a climatic chamber. The degree of air pollution due to cigarette smoke corresponded to 2.5 and 1.3 ppm delta CO. The concentrations of particulate matter, NO and NO2, were measured. The effects on subjective irritation, annoyance and eye blinking rate were determined. All measured effects increased with increasing smoke concentration as well as with exposure duration. Based on these effects, a tolerable limit in the range between 1.5 and 2.0 ppm delta CO is proposed.     

Passive smoking: Irritating effects of the total smoke and the gas phase

Summary In a ventilated climatic chamber 32 subjects (in groups of two or three) were exposed in one experiment to the total sidestream smoke of cigarettes and in another experiment to the gas phase of cigarette smoke, which was obtained by filtering out the particulate matter. The degree of air pollution corresponded to 10 ppm CO in both experiments. The concentrations of the particulate matter, CO, NO, NO₂ and HCHO were recorded. With a questionnaire, we determined the degree of annoyance and of subjective irritations of the eyes, nose and throat; eye blink rate was measured, as an objective indicator of eye irritation.Both exposures of air pollution produced nearly the same degree of annoyance, which indicates that the gas phase is to a large extent responsible for the annoyance due to cigarette smoke. On the other hand the objective and subjective eye irritation was very much lower with the gas phase than with the total smoke. This indicates that the particulate phase is to a very large extent responsible for the irritating effects.     

Airway sensitivity of asthmatics to sulfur dioxide

The purpose of this study was to describe for asthmatic subjects the distribution of individual bronchial sensitivity to sulfur dioxide (SO2). Subjects were nonsmoking male asthmatics (n = 27) who were sensitive to inhaled methacholine. None of the subjects used corticosteroids or cromolyn sodium. Oral medications were withheld for 48 hr, inhaled medications for 12 hr prior to all testing. Each subject participated in four separate randomly ordered 10 min exposures to 0.00, 0.25, 0.50 and 1.00 ppm SO2 at 26 degrees C, 70% relative humidity. During exposures, subjects breathed naturally and performed moderate exercise (VE, normalized for body surface area = 21 1/m2 X min). Before and 3 min after exposure, specific airway resistance (SRaw) was measured by body plethysmography. Those subjects whose SRaw was not doubled by exposure to 1.00 ppm were also exposed to 2.00 ppm SO2. Dose response curves (relative change in SRaw, corrected for change in clean air vs SO2 concentration) were constructed for each subject. Bronchial sensitivity to SO2 [PC(SO2)], defined as the concentration of SO2 which provoked an increase in SRaw 100% greater than the response to clean air, was determined. Substantial variability in sensitivity was observed: for 23 subjects, PC(SO2) ranged between 0.28 and 1.90 ppm, while for the remaining 4 subjects, it was greater than 2.00 ppm SO2. The median PC(SO2) was 0.75 ppm SO2, and 6 subjects had a PC(SO2) of less than 0.50 ppm. PC(SO2) was not related (r = 0.31) to airway sensitivity to methacholine.     

Psychophysiological functions of subjects with self-reported multiple chemical sensitivity (sMCS) during experimental solvent exposure

The study examined the assumption of a higher sensitivity of autonomic functions of subjects with self-reported multiple chemical sensitivity (sMCS) during environmental exposure. The hypothesis was tested in a laboratory study with standardized exposures. Twelve healthy male subjects (26.4 +/- 5.4 y) with and 12 male control subjects (25.7 +/- 3.8 y) without self-reported multiple chemical sensitivity (sMCS), selected by a questionnaire, were included in the experimental study. At four different days the subjects were exposed in a random order to solvents for four hours: 10 ppm or 98 ppm ethyl benzene, 10 ppm or 189 ppm 2-butanone. Heart rate and breathing rate were analysed for two 30-minutes periods of vigilance testing at the beginning and end of exposure. In sMCS-subjects both functions were elevated at the beginning of the testing periods with a tendency to decrease over the 30-minutes periods. Control subjects revealed a relatively constant level (breathing rate) and a small increase (heart rate) during the periods. These group differences were obvious for all experimental conditions across substances and levels of exposures. Furthermore, the mean of the breathing rate of sMCS-subjects was generally higher compared to the control subjects. While the assumption of a generally altered sensitivity of autonomic functions of sMCS-subjects to environmental changes seems to be supported, no specific reactions to the type or level of the chemical exposure were found.     

Sensory irritating potency of some microbial volatile organic compounds (MVOCs) and a mixture of five MVOCs.

The authors investigated the ability/potencies of 3 microbial volatile organic compounds and a mixture of 5 microbial volatile organic compounds to cause eye and upper respiratory tract irritation (i.e., sensory irritation), with an animal bioassay. The authors estimated potencies by determining the concentration capable of decreasing the respiratory frequency of mice by 50% (i.e., the RD50 value). The RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 182 mg/m3 (35 ppm), 1359 mg/m3 (256 ppm), and 17586 mg/m3 (3360 ppm), respectively. Recommended indoor air levels calculated from the individual RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 100, 1000, and 13000 microg/m3, respectively-values considerably higher than the reported measured indoor air levels for these compounds. The RD50 value for a mixture of 5 microbial volatile organic compounds was also determined and found to be 3.6 times lower than estimated from the fractional concentrations and the respective RD50s of the individual components. The data support the conclusion that a variety of microbial volatile organic compounds may have some synergistic effects for the sensory irritation response, which constrains the interpretation and application of recommended indoor air levels of individual microbial volatile organic compounds. The results also showed that if a particular component of a mixture was much more potent than the other components, it may dominate the sensory irritation effect. With respect to irritation symptoms reported in moldy houses, the results of this study indicate that the contribution of microbial volatile organic compounds to these symptoms seems less than previously supposed.     

Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students

We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma.     

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     

Toxic Pollutants,Science, and Corporate Influence

Groups of male Swiss-Webster mice were exposed to concentrations of chlorine varying from 0.7 to 38.4 ppm and to concentrations of hydrogen chloride varying from 40 to 943 ppm. The total exposure time to both gases was 10 minutes. Dose-response curves were plotted for both chlorine and hydrogen chloride, using the percentage decrease in respiratory rate during each exposure as the response reflecting sensory irritation of the upper respiratory tract. The results showed chlorine to be 33.0 times more irritating than hydrogen chloride, with 95% confidence limits of 18.6 and 57.1. Guidelines for obtaining a range of acceptable threshold limit values (TLV) based on sensory irritation of the upper respiratory tract are discussed. It was concluded that the current TLV of 1 ppm for chlorine is the upper acceptable limit, and that the established TLV of 5 ppm for hydrogen chloride lies at the lower limit of the predicted range. The mechanism of chlorine’s and hydrogen chloride’s sensory irritation may be explained by their reaction with various functional groups in the membranes of the trigeminal nerve endings lining the nasal mucosa.