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Biomedical subjects

Ernst Kiesswetter

Publications and source records attributed to Ernst Kiesswetter.

11 recordsLinked to original sources

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.

Adult↗

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.

Adolescent↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Air Pollutants, Occupational↗

Is multiple chemical sensitivity a clinically defined entity?

In 1996 a WHO/IPCS Workshop has suggested to use as an appropriate descriptor of MCS the broader term "Idiopathic Environmental Intolerances (IEI)", in order to incorporate "a number of disorders sharing similar symptomatologies". Research was strongly encouraged. The following points have been put forward as a precondition to define MCS as a clinical entity: (a) establishment of diagnostic criteria, (b) identification of pathogenic mechanisms, together with, (c) an explanation of relationship between exposures and symptoms. Against this background, progress made in the fields of sensory physiology and neurobehaviour research must be debated. In particular, recent results on processing of cognitive stimuli have to be considered. IEI/MCS patients exhibited differences vs. controls in their reactions to intranasal challenge, consistent with changes in cognitive processing of suprathreshold chemosensory information. Trait anxiety and focus of attention have clearly been identified as major components in eliciting neurobehavioural MCS symptoms. Hence, the question as to whether MCS should be regarded as a clinically defined entity remains controversial, but important progress can be noticed in elucidating and defining the nature of this phenomenon, by a combined effort of several disciplines (toxicology and behavioural toxicology, psychology and psychophysiology, and clinical medicine). The new situation will call for a re-evaluation of traditional positions.

Cognition↗

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.

Adult↗

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.

Adult↗

Nasal function in self-reported chemically intolerant individuals.

Nasal function has not yet been investigated under controlled exposures in individuals with self-reported Multiple Chemical Sensitivity (sMCS). Therefore, anterior rhinomanometry and acoustic rhinometry were applied in 12 individuals with sMCS, and 12 age-matched controls. The sMCS individuals and controls were selected on the basis of a standardized questionnaire. Controlled 4-hr exposures to ethylbenzene and 2-butanone were performed during 4 sessions. Exposures were close to the current German threshold limit values, and they approximated odor thresholds. Subjects with sMCS had a significant decrease in the flow value in anterior rhinomanometry, independent of substance and doses, compared with controls. This result suggests somatic reactions to the exposure. The result must be confirmed in additional studies, and pathophysiological examinations must be performed. For these investigations, anterior rhinomanometry was usable, but acoustic rhinometry can be recommended only after sufficient standardization has occurred. Furthermore, biochemical parameters of nasal mucosa must be considered.

Administration, Intranasal↗