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Biomedical subjects

Andreas Seeber

Publications and source records attributed to Andreas Seeber.

15 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↗

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↗

Impairments of colour vision induced by organic solvents: a meta-analysis study.

The impairment of colour discrimination induced by occupational exposure to toluene, styrene and mixtures of organic solvents is reviewed and analysed using a meta-analytical approach. Thirty-nine studies were surveyed covering a wide range of exposure conditions. Those studies using the Lanthony Panel D-15 desaturated test (D-15d) were further considered. From these for 15 samples data on colour discrimination ability (Colour Confusion Index, CCI) and exposure levels were provided, required for the meta-analysis. In accordance with previously reported higher CCI values for the exposed groups, the computations yielded positive effect sizes for 13 of the 15 samples, indicating that in the great majority of the studies the exposed groups showed inferior colour discrimination. However, the meta-analysis showed great variation in effect sizes across the studies. Possible reasons for inconsistency among the reported findings are discussed. These pertain to exposure-related parameters, as well as to confounders such as conditions of test administration and characteristics of subject samples. Those factors vary considerably among the studies and might have greatly contributed to divergence in measured colour vision capacity, thereby obscuring consistent effects of organic solvents on colour discrimination.

Color Perception↗

Neurobehavioural test results and exposure to inorganic mercury: in search of dose-response relations.

The aim of the analysis was, in general, to find a way to summarise results of studies in search of exposure-response relationships and, in particular, to ask whether an exposure-response relationship can be ascertained for neurobehavioural studies on occupational mercury exposure. Eighteen studies dealing with human mercury exposure and examining 1,106 exposed and 1,105 control subjects were included in the analysis. Effect sizes were calculated for each of the single neuropsychological test results on cognitive and motor performance and were considered in relation to mean current concentrations of exposure. The total of effect sizes demonstrated a correlation to exposure in the range of r=0.50. Additional analyses showed that the influence of mercury on psychological functions was different and that results on motor performance compared with memory and attention revealed the greatest impairment in mercury-exposed workers. Implications for the reversibility of impairments could be discussed because three of the studies examined subjects whose exposure had ceased. Besides the usefulness of the approach, it became obvious that the available 18 studies are a small sample, even when non-dimensional effect-sizes are used; hence, not all psychological domains covered by tests could be analysed.

Attention↗

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↗

Occupational toluene exposure and auditory function: results from a follow-up study.

The ototoxicity of occupational exposure to toluene below 50 p.p.m. was investigated in a longitudinal study over 5 yr with four repeated examinations starting with 333 male workers from rotogravure printing plants. Past lifetime weighted average exposures (LWAE) to toluene and noise were determined from individual work histories; recent individual exposures were measured 10 times during the study (toluene, active sampling; noise, stationary measurements). The auditory thresholds were measured with pure tone audiometry. The mean LWAE exposures to toluene and noise were 45 +/- 17 p.p.m. plus 82 +/- 7 dB(A) for printers (high toluene intensity) and 10 +/- 7 p.p.m. plus 82 +/- 4 dB(A) for end-processors (low toluene intensity). The mean current exposures to toluene and noise during the study were 26 +/- 20 p.p.m. plus 81 +/- 4 dB(A) for printers and 3 +/- 3 p.p.m. plus 82 +/- 4 dB(A) for end-processors. Repeated measurement analyses (grouping factors: toluene intensity, exposure duration and noise intensity) and logistic regressions did not reveal significant effects of toluene intensity, of exposure duration and of interactions between toluene intensity and noise intensity. The stratification dependent on noise intensity itself [79 +/- 3 versus 84 +/- 1 dB(A)] was significantly associated with the auditory thresholds. Regarding the missing toluene effects, it was concluded that the threshold level for developing a hearing loss as a result of occupational toluene exposure might be above the actual limit of 50 p.p.m.

Follow-Up Studies↗

Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol.

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

2-Propanol↗

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↗

A meta-analysis for neurobehavioural results due to occupational mercury exposure.

A meta-analysis for neurobehavioural test results of subjects occupationally exposed to mercury was carried out in order to find general tendencies and express possible deficits numerically. Out of 44 studies investigating neurobehavioural functions of occupationally exposed individuals, 12 studies provided the data required and were included in the analysis. In all, 14 neuropsychological tests with 20 different tasks were analysed. The results related to 686 exposed and 579 control subjects. Nine significant performance effects were shown for mean urinary concentrations between 18 and 34 microg Hg/g creatinine. The effects sizes (D(W+)) referred to attention (D(W+)=-0.40 and -0.46), memory (D(W+)=-0.38 and -0.40), construction (D(W+)=-0.20) and motor performance (D(W+)=-0.24, -0.40, -0.44 and -0.47). Additionally there was evidence for a dose-response relationship of effect sizes, if all test results were taken into account. Whether the effect sizes could be subject to overestimation was discussed, but there were no reasons for such an assumption. The results can be used as suggestions for new discussions about threshold limit values.

Cognition↗

A summary of two meta-analyses on neurobehavioural effects due to occupational lead exposure.

The conclusions from published results about neurotoxic effects of inorganic lead exposures <700 microg lead/l blood are contradictory at present. Effects measured by neurobehavioural methods are evaluated differently as far as recommendations for a Biological Exposure Index (BEI) of occupational lead exposure are concerned. Arguments against the German BEI of 400 microg/l were put forward in new publications, and discussion of the issues is the aim of this article. It summarizes two different meta-analytical reviews on neurobehavioural effects in order to show the main tendencies of 24 selected publications on the matter. Calculations on effect sizes are compiled for 12 tests analysed in two meta-analyses and of ten tests analysed in one of the meta-analyses. The survey of six tests of learning and memory gives hints on impairments measured with two tests, covering Logical Memory and Visual Reproduction. The survey of seven tests of attention and visuospatial information processing describes impairments in four tests, namely Simple Reaction, Attention Test d2, Block Design, and Picture Completion. The survey of four tests for psychomotor functions shows impairments for three tests, namely Santa Ana, Grooved Pegboard, and Eye-hand Coordination. These test results provide evidence for subtle deficits being associated with average blood lead levels between 370 and 520 microg/l. In evaluating the adversity of such effects it is concluded that the results of both meta-analytical reviews support the recommendation for the German BEI.

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↗