Bladder cancer documentation of causes: multilingual questionnaire, 'bladder cancer doc'.

There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

Odor thresholds and breathing changes of human volunteers as consequences of sulphur dioxide exposure considering individual factors.

OBJECTIVES: Though sulfur dioxide (SO(2)) is used widely at workplaces, itseffects on humans are not known. Thresholds are reported without reference to gender or age and occupational exposure limits are basedon effects on lung functioning,although localized effects in the upper airways can be expected.This study's aim is to determine thresholds with respect to age and gender and suggests a new approach to risk assessment using breathing reflexes presumably triggered by trigeminal receptors in the upper airways. METHODS: Odor thresholds were determined by the ascending method of limits in groups stratified by age and gender.Subjects rated intensities of different olfactory and trigeminal perceptions at different concentrations of SO(2). During the presentation of the concentrations, breathing movements were measured by respiratory inductive plethysmography. RESULTS: Neither age nor gender effects were observed for odor threshold. Only ratings of nasal irritation were influenced bygender. A benchmark dose analysis on relative respiratory depth revealed a 10%-deviation from baseline at about 25.27 mg/m(3). CONCLUSION: The proposed new approach to risk assessment appearsto be sustainable. We discuss whether a 10%-deviation of breathingdepth is relevant.

Sensory and pulmonary effects of acute exposure to sulfur dioxide (SO2).

BACKGROUND: Exposure to sulfur dioxide (SO(2)) affects large populations worldwide. Pulmonary effects have been reported at concentrations relevant in the general (<0.5 ppm) and working environment (>0.5 ppm). SO(2) is an irritant but the existing studies often emphasize only pulmonary effects and no clear dose-response relationship has yet been described. OBJECTIVES: Using a multi-level, multi-method approach, odor annoyance, sensory irritation and pulmonary effects of SO(2) were to be investigated in an experimental exposure study. METHODS: Eye blink frequency, rhinomanometry, spirometry and symptom ratings of acute health effects were assessed before, during, and after the exposures. Each session lasted 4h and concentrations of 0.5, 1, and 2 ppm were investigated and compared to a control condition using clean air. Sixteen human volunteers (8 females/8 males) participated and during exposure light physical exercise was simulated with bicycle ergometry. RESULTS: Eye blink frequency, nasal airflow, and lung function were not affected by the acute SO(2) exposure investigated. These physiological responses to moderate SO(2) exposures were not significantly affected by gender. Regarding subjectively measured chemosensory sensations, only odor annoyance ratings increased in a dose-dependent manner, but the average magnitudes were labeled weak to moderate. CONCLUSIONS: In healthy volunteers, without hyperresponsiveness to SO(2), no dose-dependent effects of acute SO(2) exposures up to 2 ppm could be measured. Due to olfactory perceptions subjects were aware of the different SO(2) exposures but the associated annoyance was relatively low.

Neurobehavioral effects during exposures to propionic acid--an indicator of chemosensory distraction?

The chemosensory effects of propionic acid (PA) in humans have not been conclusively studied and there is no established occupational exposure limit (OEL) in Germany. In addition to sensory irritation caused by PA, it was hypothesized that the annoying odor of PA might interfere with the performance results. There were 23 consenting healthy participants (12 female, 11 male) in the group studied. They were exposed for 4 h to PA in concentrations of 0.3, 5 and 10 ppm in a cross-over design. During these exposures, performance was recorded with four cognitive tests measuring response-inhibition, working memory, set-shifting, and divided attention. Odor annoyance, other chemosensory sensations, and acute symptoms were assessed before, during, and after exposure with standardized rating scales. Moderate odor annoyance and weak sensory irritation were reported during 5 and 10 ppm exposure conditions. The different levels of exposure to PA had no impact upon the results of three out of the four behavioral tests. The difficulties of the task were reflected in the results. However in the fourth, which was the response-inhibition task, there was significant increase in the error rates which corresponded to the exposure levels. Results from previous experiments suggested high odor annoyance at the investigated concentrations. Our findings showed that odor annoyance and reported sensory irritations were low. In conclusion, the hypothesis of a distractive effect due to the malodor of PA could not be confirmed. Only in concentrations as high as 10 ppm acute PA exposure affected the response accuracy of one of the four neurobehavioral task. For other more annoying substances, a neurobehavioral effect influenced by an indirect mechanism of resources competition is still conceivable.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

OBJECTIVES: This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. METHODS: The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. RESULTS: The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. CONCLUSIONS: The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

Evaluation of ethyl acetate on three dimensions: investigation of behavioral, physiological and psychological indicators of adverse chemosensory effects.

A variety of national occupational exposure limits for ethyl acetate exist based on different studies, mostly relying on subjective evaluations of ethyl acetate as an irritant. Only one study also used physiological methods with inconsistent results in subjective and objective data. The present study was designed to investigate ethyl acetate on three different dimensions: behavioral, physiological and psychological indicators of adverse chemosensory effects were investigated during acute exposures to different concentrations of ethyl acetate. Twenty-four subjects were challenged with ethyl acetate in three exposure patterns (2 ppm, 400 ppm, 400 ppm including peaks of 800 ppm). While the odor intensity is rated "strong", trigeminal perceptions were rated less than "moderate". The absence of substantial trigeminal ratings was supported by physiological data. There was neither an effect of concentration on blinking frequency nor on nasal resistance which both are indicators of irritation. Furthermore, there are no effects of ethyl acetate concentration on behavioral measures indicating no olfactory or trigeminally mediated disturbance of cognitive processing. In conclusion, the results of this multilevel approach revealed no adverse chemosensory effects at ethyl acetate concentrations as recommended by the German MAK-value.

Odor annoyance of environmental chemicals: sensory and cognitive influences.

In low concentrations, environment pollutants like volatile organic compounds (VOCs) may be perceived via olfaction. Modulators of odor-mediated health effects include age, gender, or personality traits related to chemical sensitivity. Severe multi-organ symptoms in response to odors also characterize a syndrome referred to as idiopathic environmental intolerance (IEI). One prominent feature of IEI is self-reported odor hypersensitivity that is usually not accompanied by enhanced olfactory functioning. The impact of interindividual differences in olfactory functioning on chemosensory perceptions is sparsely investigated, and therefore this study addressed the influences of different types of modulators, including olfactory functioning. In a psychophysical scaling experiment, an age-stratified sample of 44 males and females was examined. After controlled application of nine concentrations of six chemicals by flow-olfactometry, the participants rated four olfactory and nine trigeminal perceptions. Weak effects were found for gender and age, as well as some modulating effects of self-reported chemical sensitivity and odor discrimination ability. For chemical sensitivity, the results were as expected: Subjects with higher sensitivity reported stronger perceptions. The individual odor threshold (n-butanol) exerted no influence on the subjects' ratings of olfactory and trigeminal perceptions. Surprisingly, above-average odor discrimination ability was associated with lower ratings of odor intensity and nausea. This particular aspect of olfactory functioning might be a reflection of a more objective odor evaluation model buffering emotional responses to environmental odors.

Chemosensory effects during acute exposure to N-methyl-2-pyrrolidone (NMP).

Organic solvents are still essential in many industrial applications. To improve safety and health in the working environment lower occupational thresholds limits have been established and less toxic substitutes were introduced. N-Methyl-2-pyrrolidone (NMP) is a versatile solvent that is used as a substitute for dichloromethane in paint strippers. Due to conflicting results, there is a debate whether NMP causes irritations of the upper airways/eyes or not. In a human experimental study we examined the chemosensory effects of NMP under controlled conditions. Fifteen healthy males were investigated in a cross-over study. NMP vapor concentrations were 10, 40 and 80 mg/m(3) for 2 x 4h with an exposure-free lunch break of 30 min. To maximize chemosensory effects a peak exposure scenario (25mg/m(3) baseline, 160 mg/m(3) peaks 4 x 15 min, time-weighted average: 72 mg/m(3)) was tested. The four different conditions were conducted with and without moderate physical workload. Chemosensory effects were measured physiologically by anterior rhinomanometry, eye blink rate and breathing frequency. Subjectively, ratings of acute health symptoms and intensity of olfactory and trigeminal sensations were collected repeatedly throughout the exposures. All physiological variables were unaffected by the different NMP concentrations and even the peak exposures were non-effective on these measures. Olfactory mediated health symptoms increased dose-dependently. For these symptoms a strong adaptation was observable, especially during the first 4h of the exposures. Other acute symptoms were not significantly affected. Comparable to the symptoms, only olfactory sensations increased dose-dependently. Trigeminal sensations (e.g. eye and nose irritations) were evaluated as being barely detectable during the different exposures, only during 160 mg/m(3) exposure peak weak and transient eye irritation were reported. The results clearly suggest that NMP concentrations of up to 160 mg/m(3) caused no adverse sensory irritation or undue annoyance.

From neurotoxic to chemosensory effects: new insights on acute solvent neurotoxicity exemplified by acute effects of 2-ethylhexanol.

Historically, acute solvent neurotoxicity was strongly related to reversible narcotic states that could be detected by neurobehavioral tests (e.g., simple reaction time). Nowadays, the occupational exposure to chemicals is markedly reduced and the avoidance of chemosensory effects is more important for the regulation of solvents. Exemplarily, this study examines if the chemosensory perception of 2-ethylhexanol is capable to distract performance in demanding neurobehavioral tasks. In two experiments three time-weighted average concentrations of 2-ethylhexanol (C(TWA): 1.5, 10, and 20 ppm) were investigated. In experiment A (n=24) variable concentrations over time (4h) were used, experiment B (n=22) investigated constant concentrations. The experiments were conducted in a 29 m3 exposure laboratory. Cross-over designs with randomized sequences of exposures were used. Among the 46 male participants 19 subjects reported enhanced chemical sensitivity; the other 27 subjects did not show this personality feature. During the exposure periods neurobehavioral tests were presented twice (beginning; end), the intensity of chemosensory perceptions were rated thrice. The intensity of chemosensory perceptions showed a clear dose-dependency. Subjects' performance in the vigilance test was not affected by the different exposures. Moreover, the results of neurobehavioral tests measuring executive function were neither affected by the C(TWA) concentration nor by the exposure peaks. With increasing C(TWA), a subgroup of the chemically sensitive subjects showed deteriorated accuracy in a divided attention task. Especially the 20 ppm conditions were very annoying. Only during the constant 10 ppm condition the time courses of the annoyance and nasal irritation ratings indicated some adaptation. In general, with the applied neurobehavioral tests distractive effects of acute 2-ethylhexanol exposures up to 20 ppm could not be confirmed. In sensitive groups such distractive effects of irritating solvents might be conceivable and moreover, in cooperation with researchers from cognitive neuroscience more sensitive functions and tests should be developed and incorporated.

From chemosensory thresholds to whole body exposures-experimental approaches evaluating chemosensory effects of chemicals.

OBJECTIVES: To ensure safety and health the avoidance of adverse chemosensory effects is essential at workplaces where volatile chemicals are used. The present study describes psychophysical approaches that provide information for the evaluation of such effects. METHODS: By means of a modified staircase procedure the odor (OT) and irritation thresholds (IT) of 15 irritants were determined. These basic chemosensory properties, confining the chemosensory effect range, were investigated in a random sample of 144 persons stratified for gender and age. Those irritants exhibiting high chemosensory potency were selected for the second psychophysical part of the study. Forty-eight persons, again stratified for gender and age, rated the intensity of 13 trigeminal and olfactory perceptions elicited by nine ascending concentrations of the irritants, ranging from the odor to the irritation threshold of the respective substances. RESULTS: Across the investigated chemicals the transition from concentrations eliciting pure olfactory stimulation (OT) to trigeminal stimulation (IT) differed markedly. The carboxylic acids yielded narrow ranges from odor to irritation thresholds, while for the amines (cyclohexylamine, dimethylamine, and trimethylamine) and the esters (ethyl formate and ethyl acetate) these ranges were somewhat wider. The two chemosensory thresholds of ethyl acrylate and ammonia were farthest from each other. Gender and age had only weak impact on the chemosensory thresholds. At present, the results of the intensity ratings could be given for six substances. Among them, the rated pungency for cyclohexylamine, formic acid, and ethyl acetate increased strongest across the nine applied concentrations. CONCLUSIONS: By means of these psychophysical approaches a diverse class of chemicals can be described and compared with respect to their chemosensory potency. This information can be used twofold (a) for the evaluation of existing studies reporting sensory irritations and (b) for the design of experimental exposure studies.

Eye blinks as indicator for sensory irritation during constant and peak exposures to 2-ethylhexanol.

Two experiments were performed to re-evaluate the sensory irritating properties of 2-ethylhexanol in relation to dose and time and to examine the usability of electromyographic eye blink recordings as indicator of sensory irritation. Mean exposure levels of 1.5, 10 and 20ppm were realized in experimental models simulating either constant or variable 4h exposure. Each study was carried out with two subject samples, healthy young men with self-reported multiple chemical sensitivity (sMCS) and age matched controls. Although 2-ethylhexanol exposure was below the occupational threshold limit value of 50ppm, the study revealed strong dose-response relationships between airborne solvent concentrations and blink rates. During 40ppm peak exposures the blink rate increased threefold. In the course of 4h, exposure blink rates increased significantly showing no adaptation. Subjects with sMCS revealed, with one exception at start of exposure, no significantly higher blink rates than controls. The results indicate that the irritative potential of 2-ethylhexanol is higher than commonly expected. In both exposure scenarios with either constant or peak exposures, electromyographic eye blink recordings were an appropriate method for the examination of acute sensory irritations in time.

An integrative approach considering acute symptoms and intensity ratings of chemosensory sensations during experimental exposures.

Even at low concentrations airborne chemicals can excite olfactory and trigeminal receptors and inform the organism about the presence of airborne chemicals. Acutely, malodors or sensory irritations might trigger symptoms (e.g., bad air quality, eye irritations) and in the long-run functional impairment of chemoreception might occur. In humans, knowledge about short-term adaptational processes and effects of exposure peaks on these systems is limited. Therefore, two different experiments with human volunteers were conducted. In experiment A exposures (4h) with fluctuating concentrations of 2-ethylhexanol (1.5, 10, 20ppm C(TWA)) were investigated, experiment B used similar but constant vapor concentrations. Olfactory- and trigeminal-mediated symptoms and intensities of odor, eye, and nasal irritations were recorded. All measures showed a dose-dependent response and peak exposure effects. In the course of the 4h exposures solely olfactory symptoms decreased. Nasal irritations remained nearly unchanged across the 4h, eye irritations slightly increased. Inter-individual differences related to the personality trait of self-reported chemical sensitivity had only minor effects on chemosensory symptoms in experiment B and no effect on intensity ratings in both experiments. Chemosensory effects seem to be amplified by exposure peaks and less adaptive than assumed.

Changes of neurobehavioral and sensory functions due to toluene exposure below 50ppm?

Data of a follow up study with four examinations were summarized by odds ratio statistics in order to scrutinize the results of the earlier studies with cross sectional approaches. For a "high"- (n=106) and a "low"-exposed group (references, n=86) current toluene exposures of 26ppm versus 3ppm and lifetime weighted average exposures of 45ppm versus 9ppm were ascertained. As measures of sensory functions vibration thresholds, colour discrimination, and auditory thresholds were used. Measures of psychological performances were attention (symbol-digit substitution, switching attention, simple reaction), memory (digit span forward, delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board). Additionally, the frequency of diseases and symptoms were ascertained. By odds ratio statistics including relevant cofactors no significant increase of "cases with impaired functions" among the high-exposed workers was found. Evidence for neurobehavioral effects due to long-term toluene exposure below 50ppm was not established.

Neurobehavioral effects of experimental exposures to low levels of styrene.

Two experimental studies were conducted with the intention to simulate exposure characteristics of work places with styrene exposure and to investigate the risk for neurobehavioral impairments. In experiment I 16 volunteers (8 in the morning, 8 in the afternoon) were exposed to 0.5 and 20 ppm styrene on a constant level for 3h. In experiment II 24 volunteers (12 in the morning, 12 in the afternoon) were exposed for 4h to 0.5 and 20 ppm styrene on a constant level as well as to a changing exposure between 0.5 and 40 ppm with a TWA of 14 ppm. Simple reaction, choice reaction, attention, acute symptoms, and ratings for well-being were measured. Exposure related performance effects could not be detected. However, 6h time change resulted in delayed choice reactions in the morning hours. Analysing acute symptoms and the state of well-being the impact of styrene did not reach adverse extents of impaired well-being.

Colour vision and occupational toluene exposure: results of repeated examinations.

Potential effects of human occupational exposures to toluene on colour vision were investigated in a follow-up study over 4 years with three repeated examinations. Colour vision was measured with the Lanthony desaturated colour vision test D-15d, and the colour confusion index (CCI) was calculated. The mean current exposures were 26+/-21 ppm for printers (high toluene level) and 3+/-4 ppm for end-processors (low toluene level). The mean exposure durations were 23+/-6 years for "long-time exposed" and 7+/-2 years for "short-time exposed" subjects. Repeated analyses (n=162) and multiple regressions (maximum available n=267) did not reveal significant effects of toluene with respect to intensity or duration of current or long-term exposure. Age and occupational qualification were significantly associated with CCI in both kinds of analysis, whereas alcohol consumption (carbohydrate-deficient transferrin, CDT) and smoking habits (cigarettes per day) were not. It is concluded that current industrial exposure limits of toluene provide sufficient protection against possible disturbance of colour vision.

Toluene exposure below 50 ppm and cognitive function: a follow-up study with four repeated measurements in rotogravure printing plants.

OBJECTIVE: There are findings of cross-sectional studies on slight cognitive effects due to toluene exposure below 50 ppm. The critical points of the earlier studies will be scrutinised by a follow-up study with four examinations in 5 years. METHODS: Employees from 14 magazine rotary printing plants were classified into groups of "high" (printing area) vs "low" (end-processing) and "short" vs "long" exposure. The sample size of 333 in examination 1 decreased to 216 in examination 4. A repeated-measurement design could be applied for 192 persons. Current exposure was measured by personal air sampling (n=2,521). Data for past exposure (lifetime weighted average exposure, LWAE) were based on job exposure matrices. High-exposure and low-exposure groups were characterised by 26 ppm vs 3 ppm (current exposure) and 45 ppm vs 9 ppm (LWAE). For long-exposure and short-exposure groups 21 vs 6 years were ascertained. Attention (symbol digit substitution, switching attention, simple reaction), memory (digit span forward and backwards, immediate and delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board) were measured as dependent variables. RESULTS: Separate stepwise regressions for examinations 1 to 4, which included the co-variables age, level of education, carbohydrate-deficient transferrin as an alcohol marker, and trait anxiety as personality characteristic, did not exhibit remarkable exposure impacts on the performance variables. Repeated-measures analyses of covariance, which included all examination periods, also did not exhibit significant impacts of LWAE or current exposure on the functions measured. Age and education were the dominant factors for the variability of the data. Additionally, carbohydrate-deficient transferrin and trait anxiety showed sporadic impacts on the test results. CONCLUSION: Evidence for psychological performance effects due to long-term toluene exposure below 50 ppm could not be proved.

Breathing and heart rate during experimental solvent exposure of young adults with self-reported multiple chemical sensitivity (sMCS).

This paper deals with the assumption that young adults with self-reported multiple chemical sensitivity (sMCS) show a heightened sensitivity of autonomic functions during experimental solvent exposure. Male sMCS-subjects were selected (out of n=274) on the base of a German questionnaire on chemical and environmental sensitivity (CGES). Two independent experiments were carried out, each with 12 sMCS-subjects and 12 age-matched control-subjects. In experiment I two concentrations of the solvents ethyl benzene (10 and 98 ppm) and 2-butanone (10 and 189 ppm) were used. Experiment II investigated 2-propanol (35 and 190 ppm) and 1-octanol (0.1 and 6.4 ppm). The low concentrations correspond nearly to the olfactory thresholds while the high concentrations correspond to the German occupational threshold limit values (MAC). The exposure duration under each condition was 4h. The sequence of the four exposure conditions was random including intervals of at least 2 days without exposure. During the exposure physiological changes of breathing rate and heart rate were recorded. Two 30 min intervals with a sedentary position of the subjects at the beginning and end of exposure were chosen for analyses. Neither in experiment I nor in experiment II significant specific reactions to the type or level of the exposures were found. The autonomic functions in both experiments revealed alterations within the exposure sessions. The heart rate in experiment II and the breathing rate in both experiments decreased significantly during the analyzed 30 min intervals. Furthermore, in both experiments the heart rates decreased significantly from beginning to end of exposure. Only in experiment I the mean breathing rate of sMCS-subjects was generally higher compared to the control-subjects. Regarding the assumption of a heightened sensitivity of sMCS-subjects the two experiments yielded controversial results. Thus, the hypothesis of stronger responses of autonomic functions of sMCS-subjects provoked by various exposure scenarios remains open.

Intranasal effects in chemically sensitive volunteers: an experimental exposure study.

During inhalational exposure to irritants stimulation of the trigeminal nerve endings in the nasal mucosa or other biochemical mechanisms might initiate inflammatory processes. Increased sensitivity of this physiological system in response to chemical stimulation is postulated in subjects reporting chemical intolerance. In the present study 12 subjects reporting chemical sensitivity and 12 controls were exposed to different concentrations of the industrial solvents ethyl benzene and methyl ethyl ketone (MEK). Concentrations of various inflammatory biomarkers, namely eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin 1ß (IL-lß), substance P (SP), and neurokinin A (NKA) were measured in nasal secretion after exposures. Before, during, and after the exposures subjects rated the severity of nasal irritations. The biomarker concentrations and reported irritations were not affected by the exposures. Regardless of substance and concentration sensitive subjects reported more nasal irritations. In conclusion, the investigated substances might possess weaker potency to elicit intranasal irritative effects than postulated.

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.

Time courses of sensory irritations due to 2-butanone and ethyl benzene exposure: influences of self-reported multiple chemical sensitivity (sMCS).

The individually different effects of exposure to comparable levels of chemicals might be partly explained by dissimilar response sensitivity towards chemicals. Multiple chemical sensitivity (MCS) might be the clinical endpoint of this altered sensitivity. Concerning a subclinical range of chemical sensitivity, 'challenge studies' with people reporting chemical sensitivity are needed to improve the knowledge about such differences. The chemical and general environmental sensitivity questionnaire (CGES) is a standardized screening tool for the selection of this group. In the present study 24 healthy male volunteers, half of them classified as sMCS-subjects, were experimentally exposed to 2-butanone and ethyl benzene at different levels (TLV-level vs. odor threshold). The strength of self-reported sensory irritations (nasal and ocular) and symptoms of bad smell were assessed, prior, during, and after the 4 hours of exposure. The time courses of sensory irritations were affected by sMCS. Across all exposure periods sMCS-subjects showed increasing symptom scores while control-subjects did not. Symptoms of bad smell were affected by three exposure-related factors (substance, level, duration) without any additional influence from the sMCS factor. Starting from these results it could be concluded that the time-depending influence of reported chemical sensitivity is most prominent for subjective data of sensory irritations.