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     

Indoor air pollutants in office environments: Assessment of comfort,health, and performance

Concentrations of volatile organic compounds (VOCs) in office environments are generally too low to cause sensory irritation in the eyes and airways on the basis of estimated thresholds for sensory irritation. Furthermore, effects in the lungs, e.g. inflammatory effects, have not been substantiated at indoor relevant concentrations. Some VOCs, including formaldehyde, in combination may under certain environmental and occupational conditions result in reported sensory irritation. The odour thresholds of several VOCs are low enough to influence the perceived air quality that result in a number of acute effects from reported sensory irritation in eyes and airways and deterioration of performance. The odour perception (air quality) depends on a number of factors that may influence the odour impact. There is neither clear indication that office dust particles may cause sensory effects, even not particles spiked with glucans, aldehydes or phthalates, nor lung effects; some inflammatory effects may be observed among asthmatics. Ozone-initiated terpene reaction products may be of concern in ozone-enriched environments (≥0.1 mg/m³) and elevated limonene concentrations, partly due to the production of formaldehyde. Ambient particles may cause cardio-pulmonary effects, especially in susceptible people (e.g. elderly and sick people); even, short-term effects, e.g. from traffic emission and candle smoke may possibly have modulating and delayed effects on the heart, but otherwise adverse effects in the airways and lung functions have not been observed. Secondary organic aerosols generated in indoor ozone-initiated terpene reactions appear not to cause adverse effects in the airways; rather the gaseous products are relevant. Combined exposure to particles and ozone may evoke effects in subgroups of asthmatics.     

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.     

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.     

Irritation of the human eye mucous membrane caused by airborne pollutants

OBJECTIVES: The purpose of this study was to investigate the different irritative effects of carbon dioxide and n-butanol exposure on the ocular mucous membrane. MATERIAL AND METHODS: Provocation by the gases was at the same sensory level, which was 50% of maximum on a linear scale. The experiment was performed on nine healthy subjects with the aim of identifying the relationship between eye irritation and the human physiological response to this irritation. A goggle exposure system, invented at the Department of Occupational and Environmental Medicine, Aarhus University, was used for the experiment. The exposures lasted for 30 min each. RESULTS: There were no changes in tear film stability and conjunctival corrosion (lissamine staining) after carbon dioxide and n-butanol exposures leading to 50% sensory eye irritation. However, the study showed a delayed inflammatory response after carbon dioxide exposure when compared with clean air. The significant change was seen for tear fluid neutrophilic granulocytes 22 h after carbon dioxide (CO(2)) exposure only. CONCLUSIONS: It is concluded that the type of exposure made no difference to the elicited physiological responses and that tear film stability and epithelium damage were not affected by sensory irritation itself.     

Volatile organic compounds: do they present a risk to our health?

Indoor air quality has been recognised as a significant health, environment, and economic issue in many countries. Research findings have demonstrated that some air pollutants occur more frequently and at a higher concentration in indoor air than in outdoor air, including volatile organic compounds (VOCs). In this context, the indoor environment can be of crucial importance because modem society spends most of their time indoors, and exposure to VOCs may result in a spectrum of illnesses ranging from mild, such as irritation, to very severe effects, including cancer. These effects have been seen at very low levels of exposure in many epidemiological studies. In this review, we discuss the nature of the VOCs that are ubiquitous in indoor environment and the evidence for adverse health effects associated with exposure to some of these compounds.     

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.     

Sensitivity of the eyes to airborne irritant stimuli: influence of individual characteristics.

The purpose of this study was to measure trigeminal sensitivity of the eyes to irritative exposures and to examine the influence of individual characteristics, e.g., gender, age, and smoking, on this sensitivity. During an experimental study, 158 of 2,025 randomly selected volunteers were examined for sensory irritation threshold in the eyes to carbon dioxide (CO2). Eyes were exposed to progressive concentrations of CO2 (10, 20, 40, 80, and 160 ml/l), until the subject claimed a distinct irritation. Each exposure level lasted 2 min. A special exposure mask system was used for eyes-only exposure. No significant dependence of gender or smoking was found, but subjects who were less than 40 y of age were more sensitive than were the elderly subjects. Subjects who reported frequent "sick building syndrome" irritation symptoms had lower thresholds (i.e., higher sensitivity). The CO2 threshold was related to skin irritation sensitivity, i.e., response to lactic acid smeared on the cheek, and there were indications that occupational stress was associated with low thresholds. Studies of irritation to n-decane indicate that the CO2 threshold may be an important factor in the prediction of individual sensitivity to irritation from airborne pollutants. The CO2 threshold of the eyes may be of value in the evaluation of hypersensitivity to indoor air pollution. Furthermore, the threshold may be used to assess important relationships between the different trigeminal innervated areas, e.g., skin and eyes. Finally, the method has the advantage of avoiding interference from olfactory stimulation.     

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.     

Trigeminal and olfactory sensitivity: comparison of modalities and methods of measurement

Objective: The principal objective was to chart sensitivity for human nasal irritation by alternative psychophysical methods, namely, a common detection procedure versus a nasal lateralization procedure that required the subject to indicate whether a vapor had stimulated the left or right nostril. This objective relates to the broader issues as to (a) whether subjects with normal olfaction (normosmics) can yield, through novel methodology, an index of sensitivity to nasal irritation comparable with that obtained from subjects without olfaction (anosmics) and (b) whether both types of subjects have similar irritation sensitivity in general. This study sought to gauge interconvertability both between types of subjects and between modes of stimulus presentation for irritative and, where appropriate, olfactory stimulation. Methods: Static dilution series of four n-aliphatic alcohols, chosen to represent volatile organic compounds (VOCs), provided the source of calibrated olfactory and irritative vapors emitted from their squeezable containers into the nose or eye either by a mechanical device or by hand. Standard psychophysical methodology (forced-choice; ascending strength of stimulation) served to chart detection thresholds for irritation and odor and an analogous procedure served to chart the threshold for localization of stimulation. Results: Within the limits of resolution, detection thresholds and nasal localization thresholds yielded comparable indices of the potency of the VOCs to evoke nasal irritation. The thresholds agreed well with those for detection of eye irritation, though only the eyes proved to be capable of detecting irritation from 1-octanol. The method of emitting the stimulus had little material effect on measures of either irritative or olfactory detection. Conclusions: The threshold for nasal localization offers a suitable way to measure nasal irritation in normosmic persons. Olfactory stimulation does not interfere with the measure since subjects cannot localize on that basis. Anosmic and normosmic persons have comparable sensitivity to nasal and ocular irritation. If anosmic persons have any lower sensitivity, as sometimes claimed, it would seem to have only trivial consequences for estimates of the irritative potency of VOCs. Received: 10 April 1997 / Accepted: 10 July 1997     

Unmetabolized VOCs in urine as biomarkers of low level exposure in indoor environments

This study aimed to test the possible use of unmetabolized volatile organic compounds (VOCs) in urine as biomarkers of low-level indoor environmental exposure. Twenty-four subjects in 13 dwellings in a prefecture of Japan participated in this study. Air samples of the breathing zone were collected in the living room and bedroom, along with spot urine samples (before bedtime and first morning voids). Toluene, ethylbenzene, xylene isomers, styrene and p-dichlorobenzene in the air and urine samples were measured by gas chromatography/mass spectrometry. For the 21 subjects without solvent exposure at work, there were significant correlations between the time-weighted average air concentrations in the bedroom and morning urinary concentrations for toluene, o-xylene, total xylene and p-dichlorobenzene (correlation coefficients of 0.54, 0.61, 0.56 and 0.84, respectively). Multiple linear regression analysis showed only air VOCs in the bedroom influenced the morning urinary VOC concentrations. We concluded that unmetabolized VOCs in the urine can provide a reliable biological indicator for air VOC exposures in non-occupational environments.     

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.     

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.     

Exposure of humans to a volatile organic mixture. III. Inflammatory response.

A set of symptoms has been described during the past two decades that has been called the "sick building syndrome." These symptoms include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that the volatile organic compounds (VOCs) present in synthetic materials used in homes and office buildings contribute to these symptoms. However, there have been very few studies in which humans have been exposed to known amounts of VOCs under carefully controlled conditions. In this study, 14 subjects were exposed to a mixture of VOCs (25 mg/m3 total hydrocarbon) that is representative of what is found in new homes and office buildings. Because irritations of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, we used nasal lavage to monitor neutrophil (PMN) influx into the nasal passages following exposure to VOCs. There were statistically significant increases in PMNs, both immediately after a 4-h exposure to VOCs and 18 h later.     

Psychophysical sensory examination in individuals with a history of methylmercury exposure

Paresthesias are the first symptom that people report following toxic doses of methylmercury. The authors conducted a psychophysical study of tactile sensation to evaluate the somatosensory abilities of subjects living in a methylmercury-polluted area around Minamata City, Japan. The authors examined control subjects and methylmercury-exposed subjects with and without numbness. A history of methylmercury exposure was taken and a neurological examination performed. Aluminum-oxide abrasive papers were used as stimuli in a psychophysical sensory examination of fine-surface-texture discrimination. Difference thresholds from 3 microm were calculated by the two-alternative, forced-choice technique. Difference thresholds in control subjects were also calculated for comparison. The difference threshold was 6.3 microm in exposed subjects with sensory symptoms, 4.9 microm in exposed subjects without sensory symptoms, and 2.7 microm in control subjects. Acuity of fine-surface-texture discrimination was disturbed not only in subjects with clinical complaints of hand numbness, but also in subjects without hand numbness who lived in the district where methylmercury exposure occurred. Sensory testing using a psychophysical test of fine-surface-texture discrimination in this population suggests that the number of individuals affected by methylmercury exposure in the polluted area was greater than previously reported.     

Changes in eye blink frequency as a measure of trigeminal stimulation by exposure to limonene oxidation products,isoprene oxidation products and nitrate radicals

Objectives To measure eye blink frequency as a measure of trigeminal stimulation of the eye. Human subjects were exposed to oxidation mixtures representative of reactive indoor pollutants and clean air, from which relative changes in blink frequencies were measured.Method Male subjects (n=8) were exposed for 20 min to limonene oxidation products (LOPs), isoprene oxidation products (IOPs), nitrate radicals (NO₃), their residual reactants, and clean air at 20% relative humidity. A baseline blink frequency was measured prior to and following each exposure (2×8 min). The subjects were exposed locally in the non-dominant eye and single blind in random order. Blinking was video-recorded and evaluated for full sessions of 36 min while the subjects viewed an educational film. The initial terpene concentrations were one to two orders of magnitude higher than mean indoor concentrations.Results The mean blink frequency increased significantly during subjects exposure to gas-phase oxidation products at lower part-per-billion (ppb) levels of LOPs, 42% (P<0.0001) and NO₃, 21% (P<0.022), compared with that at baseline. Neither the residual reactants nor clean air changed the blink frequency significantly. The findings coincided with qualitative reporting of weak eye irritation symptoms.Conclusions Changes in blink frequency appear to be a promising measure of trigeminal stimulation from exposure to eye irritants in ppb levels. Gaseous products of limonene and ozone, and reactive radicals may cause eye irritation indoors.     

Reactions of healthy persons and persons suffering from allergic rhinitis when exposed to office dust

OBJECTIVES: Reactions to airborne office dust among healthy subjects and subjects suffering from allergic rhinitis were investigated. METHODS: Twelve healthy and 11 subjects suffering from allergic rhinitis were exposed to clean air [17 (SD 2) microg/m3] and office dust [439 (SD 68) microg/m3] for 245 minutes. The effect measurements included subjective sensations (questionnaire and potentiometer ratings), mood scale, peak flow, bronchial provocation with histamine using forced expiratory volume in 1 second as the effect measure, nasal mucosal swelling, tear film stability, epithelial damage, foam formation in the eye canthus, threshold for eye irritation with carbon dioxide, eye redness, cellular content of conjunctival fluid, and an addition test for distraction. As many investigations were made and as many statistical analyses (including subgroup analyses) were carried out, the risk of mass significance appeared. This problem was dealt with using the Bonferroni correction for multiple significance tests. RESULTS: The mean ratings of the potentiometer were higher (the subjects showed more irritation) during the dust exposure. The objective investigations showed only indications of effects of dust exposure, and some of the indications were in biologically unexplainable directions. No difference in the reactions to dust was observed between the healthy subjects and the subjects suffering from allergic rhinitis. CONCLUSIONS: Dust does not seem to have objective or subjective effects on humans, as only indications of dust effects were found. Subjects suffering from allergic rhinitis do not appear to be a risk group in relation to dust exposure.     

Airway symptoms among house painters in relation to exposure to volatile organic compounds (VOCS)—a longitudinal study

The increased use of water-based paint (WBP) for indoor application during the last decade has drastically changed the exposure conditions for Swedish house painters. WBP has a lower emission of volatile organic compounds (VOCs) than solvent-based paint (SBP), but contains more reactive compounds, such as biocides, glycol ethers, and other high molecular solvents. The aim of this study was to compare the incidence of airway symptoms and self-reported asthma in house painters with a different degree of use of WBP and SBP. The incidence of seven general airway symptoms, and three work-related symptoms, was analysed by means of a self-administered questionnaire, in a cohort of 207 house painters followed from 1989 to 1992. Different airway symptoms were compared with clinical information obtained by a methacholine challenge test and dynamic spirometry in a selected subgroup of 44 painters. Information on the degree of use of SBP and WBP was used to estimate the total exposure to volatile organic compounds (TVOC) for each individual. In total, 175 men in the cohort worked as painters during the study period. No increase of asthma or respiratory symptoms was observed among those 50 painters with a pure exposure to WBP (estimated TVOC 1–3mgm⁻³). Most painters (N = 125) had a mixed exposure to SBP and WBP, the main source of the TVOC being the limited use of SBP. WBP was perceived as less irritative than SBP, but complaints on airway irritation from WBP increased during the study period. The most pronounced increase of airway irritation in relation to both SBP and WBP, was observed among those 35 painters with the highest solvent exposure (estimated TVOC 100–380 mgm⁻³). An increase of respiratory symptom index and shortness of breath, in relation to estimated TVOC exposure was also observed. Selection effects were detected. Painters leaving their job during the study period had more non-specific hyper-reactivity symptoms, and more airway irritation from WBP-as compared to painters remaining at their occupation. Our study indicates that VOC emissions from SBPs may contribute to the development of respiratory symptoms and airway irritation. We found no increase of respiratory symptoms among painters exposed only to WBPs. There were, however, indications that VOC exposure from WBPs may cause airway irritation in some subjects. Because of selection effects, cross-sectional studies on respiratory symptoms in relation to occupational exposure to paint emissions may be inconclusive.     

Sensory eye irritation in humans exposed to mixtures of volatile organic compounds

Eight subjects participated in a controlled eyes-only exposure study of human sensory irritation in ocular mucosal tissue. The authors investigated dose-response properties and the additive effects of three mixtures of volatile organic compounds. The dose-response relationships for these mixtures showed increases in response intensity as concentration increased. Replication of exposure did not result in significantly different dose- response relationships. Moreover, the result implied that components of the three mixtures interacted additively to produce ocular irritation, a result referred to as simple agonism. Finally, the authors addressed the comparability of two methods to measure sensory irritation intensity (visual analogue scale and a comparative scale). The results indicated that the two rating methods produced highly comparable results.