Search

The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Magnetic resonance imaging is a non-invasive method that allows the indirect quantification of manganese (Mn) and iron (Fe) accumulation in the brain due to their paramagnetic features. The WELDOX II study aimed to explore the influence of airborne and systemic exposure to Mn and Fe on the brain deposition using the relaxation rates R1 and R2* as biomarkers of metal accumulation in regions of interest in 161 men, including active and former welders., Material and Methods: We obtained data on the relaxation rates R1 and R2* in regions that included structures within the globus pallidus (GP), substantia nigra (SN), and white matter of the frontal lobe (FL) of both hemispheres, as well as Mn in whole blood (MnB), and serum ferritin (SF). The study subjects, all male, included 48 active and 20 former welders, 41 patients with Parkinson's disease (PD), 13 patients with hemochromatosis (HC), and 39 controls. Respirable Mn and Fe were measured during a working shift for welders. Mixed regression models were applied to estimate the effects of MnB and SF on R1 and R2*. Furthermore, we estimated the influence of airborne Mn and Fe on the relaxation rates in active welders., Results: MnB and SF were significant predictors of R1 but not of R2* in the GP, and were marginally associated with R1 in the SN (SF) and FL (MnB). Being a welder or suffering from PD or HC elicited no additional group effect on R1 or R2* beyond the effects of MnB and SF. In active welders, shift concentrations of respirable Mn>100μg/m 3 were associated with stronger R1 signals in the GP. In addition to the effects of MnB and SF, the welding technique had no further influence on R1., Conclusions: MnB and SF were significant predictors of R1 but not of R2*, indicative of metal accumulation, especially in the GP. Also, high airborne Mn concentration was associated with higher R1 signals in this brain region. The negative results obtained for being a welder or for the techniques with higher exposure to ultrafine particles when the blood-borne concentration was included into the models indicate that airborne exposure to Mn may act mainly through MnB., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Exposure to manganese (Mn) may cause movement disorders, but less is known whether the effects persist after the termination of exposure. This study investigated the association between former exposure to Mn and fine motor deficits in elderly men from an industrial area with steel production., Methods: Data on the occupational history and fine motor tests were obtained from the second follow-up of the prospective Heinz Nixdorf Recall Study (2011-2014). The study population included 1232 men (median age 68 years). Mn in blood (MnB) was determined in archived samples (2000-2003). The association between Mn exposure (working as welder or in other at-risk occupations, cumulative exposure to inhalable Mn, MnB) with various motor functions (errors in line tracing, steadiness, or aiming and tapping hits) was investigated with Poisson and logistic regression, adjusted for iron status and other covariates. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for substantially impaired dexterity (errors >90th percentile, tapping hits <10th percentile)., Results: The median of cumulative exposure to inhalable Mn was 58 µg m-3 years in 322 men who ever worked in at-risk occupations. Although we observed a partly better motor performance of exposed workers at group level, we found fewer tapping hits in men with cumulative Mn exposure >184.8 µg m-3 years (OR 2.15, 95% CI 1.17-3.94). MnB ≥ 15 µg l-1, serum ferritin ≥ 400 µg l-1, and gamma-glutamyl transferase ≥74 U l-1 were associated with a greater number of errors in line tracing., Conclusions: We found evidence that exposure to inhalable Mn may carry a risk for dexterity deficits. Whether these deficits can be exclusively attributed to Mn remains to be elucidated, as airborne Mn is strongly correlated with iron in metal fumes, and high ferritin was also associated with errors in line tracing. Furthermore, hand training effects must be taken into account when testing for fine motor skills., (© The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Aluminum is regularly taken up with the daily diet. It is also used in antiperspirants, as an adjuvant for vaccination, and in desensitization procedures. In this review, we present the scientifically documented harmful effects of aluminum on health and the threshold values associated with them., Methods: This review is based on publications retrieved by a selective search of the PubMed and SCOPUS databases on the topic of aluminum in connection with neurotoxicity, Alzheimer's disease, and breast cancer, as well as on the authors' personal experience in occupational and environmental medicine., Results: The reference values for the internal aluminum load (<15 μg/L in urine, <5 μg/L in serum) are especially likely to be exceeded in persons with occupational exposure. The biological tolerance value for occupational exposure is 50 μg of aluminum per gram of creatinine in the urine. For aluminum welders and workers in the aluminum industry, declining performance in neuropsychological tests (attention, learning, memory) has been found only with aluminum concentrations exceeding 100 μg/g creatinine in the urine; manifest encephalopathy with dementia was not found. Elevated aluminum content has been found in the brains of persons with Alzheimer's disease. It remains unclear whether this is a cause or an effect of the disease. There is conflicting evidence on carcinogenicity. The contention that the use of aluminum-containing antiperspirants promotes breast cancer is not supported by consistent scientific data., Conclusion: The internal aluminum load is measured in terms of the concentration of aluminum in urine and blood. Keeping these concentrations below the tolerance values prevents the development of manifest and subclinical signs of aluminum toxicity. Large-scale epidemiologic studies of the relationship between aluminum-containing antiperspirants and the risk of breast cancer would be desirable.

Manganese (Mn) is an essential trace element with well characterized neurotoxic effects in high concentrations. Neurochemically, the initial neurotoxic effect of Mn is the perturbation of striatal γ-aminobutyric acid levels. Specific tasks for the assessment of cognitive functions subserved by fronto-striatal loops are available as the stop-change task (SCT) assessing control of multi-component behavior and action cascading. In a cross-sectional study, fifty male welders and 28 age-matched controls completed the SCT during a whole day examination. Reaction times, responses accuracy, and event-related potentials (ERPs) from electroencephalogram (EEG) recordings were analyzed. The shift exposure of the welders to respirable Mn was stratified by 20 µg/m 3 in 23 low-exposed (median = 4.7 µg/m 3 ) and 27 high-exposed welders (median = 86.0 µg/m 3 ). Welders graduation was lower and was therefore included in the analyses. The task-related factor (stop-change delay, SCD) modified the responses as expected; however, the lack of an interaction "SCD × group" revealed no differences between welders and controls. EEG data showed that the "SCD" modulated the amplitude of the P3 ERP in controls stronger than in welders. There was no difference between the two groups of welders and no association between airborne or systemic Mn and the P3 ERP. Moreover, the P3 amplitude was smaller in subjects with lower education. These results showed that multitasking performance and cognitive flexibility are not impaired in welders. The electrophysiological results gave a weak hint that relevant neurobiological processes were different in welders as compared to controls but this may be related to lower education.

Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate the influence of former occupational Mn exposure on olfaction within the framework of a prospective cohort study among an elderly German population. Information on job tasks with recognized Mn exposure and data on odor identification assessed with Sniffin' sticks was collected during the second follow-up of the Heinz Nixdorf Recall Study. The study population consisted of 1385 men aged 55-86 years, 354 of whom ever worked in jobs with potential Mn exposure (median 58.3μg/m 3  years, interquartile range 19.0-185μg/m 3  years). Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn determined in blood samples (MnB) archived at baseline, were used to estimate effects of Mn on olfaction. Having ever worked as welder was associated with better olfaction compared to other blue-collar workers without Mn exposure. Blue-collar workers identified less odors in comparison to white-collar workers. Concentrations of previous Mn exposure >185μg/m 3  years or MnB ≥15μg/L were not associated with impaired olfaction. In addition to a strong age effect, participants with lower occupational qualification identified less odors. We found no relevant association of former Mn exposure at relatively low levels with impaired olfaction. Possible neurotoxic Mn effects may not be persistent after cessation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Perceptions that arise from stimulation of olfactory and trigeminal receptors in the nasal cavity guide the evaluation of chemical environment in humans. Strong interindividual differences in these assessments may be attributed to nonsensory factors such as gender, anxiety, and chemical sensitivity. Knowledge regarding the influence of these factors originates mainly from basic odor research using short-term exposure scenarios. In situations with continuous chemical exposures-common in the working environment-their impact is less clear. To investigate their role during the exposure to workplace chemicals, 4-hour experimental exposure studies (total N = 105) using nine different airborne chemicals were summarized. In each study, subjects evaluated a single chemical in a controlled environment by rating five chemosensory perceptions, including odor intensity, disgust, annoyance, pungency, and burning, several times during occupational limit and low exposures. It was investigated whether the effects of trait-like modulators, such as anxiety and self-reported chemical sensitivity, depend on exposure-related factors and gender. Trait-like modulators markedly affected ratings by women, but not men. Highly anxious women reported more intense annoyance and disgust than less anxious women. Stronger self-reported chemical sensitivity was associated with increased ratings of pungency and burning in women exposed to occupational limit concentrations. This study demonstrates that a complex interplay of exposure-related factors, gender, and trait-like individual differences affects perceptual ratings during continuous chemical exposure. It seems necessary to incorporate the assessment of specific as well as general trait-like modulators into future experimental exposure studies.

While the health impact of high exposures to pesticides is acknowledged, the impact of chronic exposures in the absence of acute poisonings is controversial. A systematic analysis of dose-response relationships is still missing. Its absence may provoke alternative explanations for altered performances. Consequently, opportunities for health prevention in the occupational and environmental field may be missed. Objectives were (1) quantification of the neurotoxic impact of pesticides by an analysis of functional alterations in workers measured by neuropsychological performance tests, (2) estimates of dose-response relationships on the basis of exposure duration, and (3) exploration of susceptible subgroups. The meta-analysis employed a random effects model to obtain overall effects for individual performance tests. Twenty-two studies with a total of 1758 exposed and 1260 reference individuals met the inclusion criteria. At least three independent outcomes were available for twenty-six performance variables. Significant performance effects were shown in adults and referred to both cognitive and motor performances. Effect sizes ranging from dRE=-0.14 to dRE=-0.67 showed consistent outcomes for memory and attention. Relationships between effect sizes and exposure duration were indicated for individual performance variables and the total of measured performances. Studies on adolescents had to be analyzed separately due to numerous outliers. The large variation among outcomes hampered the analysis of the susceptibility in this group, while data on female workers was too scant for the analysis. Relationships exist between the impact of pesticides on performances and exposure duration. A change in test paradigms would help to decipher the impact more specifically. The use of biomarkers appropriate for lower exposures would allow a better prevention of neurotoxic effects due to occupational and environmental exposure. Intervention studies in adolescents seem warranted to specify their risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Neurobehavioral studies do not always gain the impact they should have, neither in the scientific nor in the regulatory field of neurotoxicology. Among others, shortcomings and inconsistencies across epidemiological studies may contribute to this situation. Examples were compiled to increase awareness of obstacles for conclusions. Meta-analyses were exploited since they sometimes allow the detection of deficits that are not obvious from individual studies. Exposure assessment, performance measures, and confounding were scrutinized among 98 primary studies included in meta-analyses on mercury, solvents, manganese and pesticides. Inconsistent and hardly comparable markers of exposure were found; figures, units or sampling periods were not always provided. The contribution of test materials to differences in test outcomes across studies could sometimes not be evaluated due to the insufficient description of the employed tests. Hypotheses for the selection of performance variables often remained undisclosed. Matching procedures prevailed with respect to the confounder age; the comparability of groups with respect to intelligence and gender remained more elusive. 8% and 16% of the studies did not even mention confounding from intelligence and gender, respectively. Only one third of the studies provided adjusted means for group comparisons; the proportion was slightly larger for studies published 2000-2010. While 50% of the studies considered confounders for their dose-response assessment, only 29% reported results for the total of test variables. The outlined deficits impede, among others, the assessment of exposure-effect relationships and confounding across studies; thereby they limit the use of the studies for toxicological risk assessment and future prevention. Some shortcomings also impede a deeper insight into the mechanisms of toxicity: tests like the Digit Symbol show that something is affected, but not what is affected. Thorough description of measures employed is among the first consequences from the data. The consideration of mechanistic insights from research on animals and neurobiology may further help to increase the significance of epidemiological studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, "sensory irritation" pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, "tissue irritation" pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, "sensory NOAEChuman" can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an "irritative NOAECanimal." Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acetaldehyde, ammonia, n-butyl acetate, hydrogen sulfide, and 2-ethylhexanol). Thus, extrapolating from animal studies, an iEF of 3 should be applied for local sensory irritants without reliable human data, unless individual data argue for a substance-specific approach.

Introduction: The presence of neuropsychological impairment is a hallmark of chronic solvent-induced encephalopathy (CSE), and using clinical neuropsychological procedures to generate a valid assessment of the condition is crucial for its diagnosis. The goals of this consensus document are to provide updated knowledge of the neuropsychological characteristics of CSE and to provide internationally acceptable guidelines for using neuropsychological assessments in the process of diagnosing patients who are suspected of having CSE., Materials and Methods: A European working group that was composed of experts in the field of the clinical diagnosis of CSE met at several round-table meetings and prepared this report. The first section of the consensus paper addresses a review of the relevant literature that was published between 1985 and March 2012. The second section addresses recommendations for the clinical neuropsychological assessment of patients who are suspected of having CSE., Results: The literature review indicates that the most common neuropsychological impairments in CSE patients are within the domains of attention, particularly the speed of information processing, memory, and motor performance. It appears that the influence of CSE on memory processes mainly involves immediate recall and generally involves verbal, visual and visuospatial material. In the second section, six recommendations are presented regarding important functional domains for the neuropsychological diagnostic process of CSE that relate to the evaluation of neuropsychological impairment, the assessment and evaluation of symptoms, differential diagnostic considerations, the reliability and validity of neuropsychological test results, and the retesting of patients., Discussion and Conclusions: These recommendations will contribute to the improvement of the process for accurately diagnosing CSE, better counselling for CSE patients, the comparability of epidemiological data between countries, and finally, by raising awareness, these recommendations will contribute to combating the adverse health effects of occupational exposure to solvents., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The review aimed at quantifying the evidence of performance effects resulting from occupational exposure to manganese. Epidemiological studies published between 1987 and 2008 were analyzed. The approach was based on the meta-analytical method of effect size estimates and sought to contribute to the following issues: (1) identification of the affected functions; (2) identification of sensitive neuropsychological tests; (3) analyses of exposure-effect relationships. Thirteen studies examining 958 exposed and 815 unexposed workers were included in the meta-analysis. Mean concentrations of inhalable manganese ranged from 0.05 to 1.59 mg/m(3), mean concentrations of manganese in whole blood ranged from 8.1 to 48.4 microg/L. Nineteen neuropsychological performance variables were analyzed as they were included in at least three of the identified studies. Apart from two outcomes, the overall effects displayed a negative impact of manganese on performance. Significant overall effects were obtained for six test variables; their size ranged from d=-0.23 to -0.36. Four of the variables measured motor speed and two of them speed of information processing. The analysis of exposure-effect relationships showed that larger effect sizes were more consistently associated with higher concentrations of inhalable manganese than with manganese in blood. The evidence of cognitive and motor performance effects is in accordance with the knowledge about accumulation of manganese in the basal ganglia and the effect of manganese on the neurotransmitter dopamine. Inconsistencies in the relationship between effect sizes and the biomarker manganese in blood were discussed in the context of results indicating that the biomarker might not be sufficiently meaningful for the neurobehavioral alterations. Simple motor performance tests with a distinct speed component seem to be highly recommendable for further studies, because they seem to be appropriate for measuring manganese-related changes, seem to provide homogenous results and their outcomes show consistent relations to exposure. The rigorous quantitative approach was especially appropriate for revealing exposure-effect relationships, but information about individual cumulative exposure would enhance the potential for risk assessment of manganese.

Objectives: The ototoxicity of occupational exposure to toluene plus noise was investigated in a longitudinal study in rotogravure printing and existing findings in the literature were evaluated., Material and Methods: The study comprised four repeated examinations during 5 years and started with 333 male workers. Lifetime weighted average exposures (LWAE) to toluene and noise were determined from individual work histories and historic recordings; recent individual exposures were measured 10 times during the study (toluene, active sampling; noise, stationary measurements). Auditory thresholds were measured with pure tone audiometry at 0.125, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 kHz., Results: Mean LWAE exposures to toluene and noise were 45+/-17 ppm plus 82+/-7 dB(A) for high toluene exposed and 10+/-7 ppm plus 82+/-4 dB(A) for low toluene exposed subjects, mean current exposures were 26+/-20 ppm plus 81+/-4 dB(A) and 3+/-3 ppm plus 82+/-4 dB(A). Mean exposure duration was 21.3+/-6.5 years for long exposed and 5.9+/-2.2 years for short exposed subjects. Repeated measurement analyses of variance did not reveal effects of toluene intensity, exposure duration and interactions between toluene intensity and noise intensity. Noise intensity [79+/-3 dB(A) vs. 84+/-1 dB(A)] was significant for auditory thresholds. A case concept utilising developments of individual auditory thresholds did not reveal significant toluene effects. Logistic models including age, exposure duration, toluene in ambient air, current noise and either hippuric acid or ortho-cresol (o-cresol) found only age to be significant for elevated OR of high frequency hearing loss., Conclusions: Due to missing toluene effects, it was concluded that the threshold level for developing hearing loss as a result of occupational exposure to toluene plus noise might be above the current limit of 50 ppm toluene.

Aluminum is a metal with known neurotoxic properties which are linked to encephalopathy and neurodegenerative diseases. The objectives of the current meta-analysis study were: (1) to summarize neurobehavioral data obtained by epidemiological studies in occupational settings and (2) to analyze confounding within these data. The meta-analysis was based on estimates of effect sizes. Overall effect sizes were obtained by application of a random effects model. The final sample consisted of nine studies examining 449 exposed and 315 control subjects. The mean urinary aluminum concentrations in the exposed groups ranged from 13 to 133 microg/l. Six neuropsychological tests, which yielded 10 performance variables, were analyzed. Nine overall effect sizes indicated an inferior performance for the exposed group. A significant overall effect size (d(RE)=-0.43) was obtained for the digit symbol test measuring speed-related components of cognitive and motor performance. Moreover, the individual effect sizes obtained for this test suggested an exposure-response relationship. Results obtained from either raw or adjusted mean scores revealed that confounding in the data could not be excluded. The results were compared to studies not included here due to a shortage of required data. Similarities were discussed in terms of sensitivity of the tests for detecting aluminum-related changes in brain function. There was concurring evidence from different studies that urinary Al concentrations below 135 microg/l have an impact on cognitive performance. The significant effect for the digit symbol might be related to its multifaceted character which requires functioning in different components of cognitive and motor performance. This feature could possibly turn the test into a screening instrument for neurobehavioral effects. However, additional studies are necessary to verify and to differentiate the effect of aluminum on cognitive performance. From a neuropsychological perspective, implicit and explicit memory, visuo-spatial and central odor processing should be examined. A measure of verbal intelligence should be included in order to address the influence of confounding. Internationally standardized exposure measures would enhance the comparability of studies.

A human experimental study was carried out with 16 volunteers to examine the elimination of N-methyl-2-pyrrolidone (NMP) after exposure to the solvent under simulated workplace conditions. The NMP concentrations were 10, 40 and 80 mg/m(3) for 2 x 4 h with an exposure-free interval of 30 min. Additionally, a peak exposure scenario (25 mg/m(3) baseline, 160 mg/m(3) peaks for 4 x 15 min, time-weighted average: 72 mg/m(3)) was tested. The influence of physical activity on the uptake and elimination of NMP was studied under otherwise identical exposure conditions but involving moderate workload on a bicycle ergometer (75 W for 6 x 10 min). The peak times and biological half-lives of urinary NMP and its main metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in urine were analysed as well as the interrelationships between exposure and biomarkers. All analytes showed a close correlation between their post-shift peak concentrations and airborne NMP. An exposure to the current German workplace limit value of 80 mg/m(3) under resting conditions resulted in urinary peak concentrations of 2,400 microg/L NMP, 117 mg/g creatinine 5-HNMP and 32 mg/g creatinine 2-HMSI (workload conditions: 3,400 microg/L NMP, 150 mg/g creatinine 5-HNMP, 44 mg/g creatinine 2-HMSI). Moderate workload enhanced the total uptake of NMP by approximately one third. Differences between the estimated and the observed total amount of urinary metabolites point to a significant contribution of dermal absorption on the uptake of NMP. This aspect, together with the influence of physical workload, should be considered for the evaluation of a biological limit value for NMP.

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.

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.

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.

Industrial exposure varies distinctly both between persons and for each person over time. It is often not possible to measure individual exposure repeatedly due to high costs. Therefore, a method for assessment of exposure is needed that accounts for inter- and intraindividual variability. We consider a strategy suggested by Preller et al. (1995, Scandinavian Journal of Work, Environment, and Health 21, 504-512), the idea of which is to predict exposure on several days via a linear model using additional variables as regressors. Those additional variables are easier to obtain than exposure measurements and are assumed to influence exposure. The paper gives a theoretical proof of the use of this method. An example is given using toluene exposure data from a study in a rotogravure printing plant.

Problems related to attentional functions have often been reported within the neurotoxicology of long-term exposure to solvents, but knowledge about neuroanatomical sites involved in this degenerative process is still rare. However, some studies have emphasized the frontal cortex as a region of structural or functional changes in long-term exposed patients or accidental intoxications. Neurobehavioral tests using active switching tasks are widely used to detect frontal lobe dysfunction. Test batteries used in neurotoxicology provide such tasks but standard test interpretations often neglect these aspects. Rotogravure printing workers exclusively exposed to toluene were investigated in a longitudinal study with cross-sectional design. Data from two examination periods are presented. In the first sample 333 male workers were investigated. In the second examination period 278 workers could be retested. The workers differed with respect to level and duration of lifetime exposure to toluene. All subjects completed a neurobehavioral test battery including the task switching attention (EURONES). Different parameters were computed for consecutive trials with constant vs. shifted tasks and repetitions vs. changes of the response direction. In general the expected interaction between the two sequence factors could not be observed. In both examination periods the alternative strategy revealed no marked differences between task/response shifts. Considering the result of previous studies on task/response shifts, the results were highly unexpected. One explanation might be the strong deviations from equality for the relative frequencies of the four sequence conditions, resulting in biased expectancies. These may have superimposed on the basic effects of task shifts. However, in both examination periods weak effects of task shift could be revealed in the subgroup of the long-term exposed workers. In further studies it is necessary to balance conditions more carefully in order to exploit the sensitivity that the measurement of shift costs promises to provide. The exposure-related results of this study support this aspect.

In this study, we analyse the impact of personality factors on the frequency of self-reported symptoms for workers under different exposure conditions. Reported symptoms may depend on the level and type of exposure, as well as on personality factors such as trait anxiety of the worker or his general sensitivity with regard to the environment. The employed data stems from three studies: The first study contains information of 60 workers who suspected to be exposed to polychlorined dibenzodioxins and dibenzofuranes (Lifetime Weighted Average Exposure, LWAE, as an index for contact with the substances). The second study concerns 40 workers who are exposed to different concentrations of solvent mixtures in paint manufacturing (LWAE of total hydrocarbons about 10 ppm). The third study includes repeated measurements of two subgroups of workers from rotogravure printing plants who are exposed to different concentrations of toluene: a "high" exposure group (n = 129, LWAE about 46 ppm, current exposure 25 ppm) and a "low" exposure group (n = 96, LWAE for toluene about 9 ppm, current exposure 3 ppm). Trait anxiety, environmental sensitivity, and self-reported symptoms are measured by validated questionnaires and age as well as verbal intelligence are controlled. To determine the effect of the individual characteristics and the different exposures on self-reported symptoms, frequency analyses and variance analyses are conducted and linear models are fitted. For all analyses, trait anxiety explains the highest share of the variance. If there is no effect of the exposure on the reported symptoms (dioxin and low-level toluene study), trait anxiety seems to have a larger explanatory power in comparison with those studies where the exposure has an effect on the reported symptoms (solvent-mixture and high-level toluene study). Neurotoxicological risk analysis has to account for the detected dependence of self-reported symptoms on personality traits: assessments for elevated symptoms should not only be linked to the intensity of exposure but also related to benchmarks derived from the normal variability of personality factors.