Neurobehavioral study on the interactive effects of age and solvent exposure.

Initial research revealed interaction effects on health measures between exposure to neurotoxicants and age. Symptom reports of workers were conspicuously increased if high-concentration occupational exposure (e.g. to organic solvents, lead) was combined with age above 54 years. The symptom increase in elderly workers was interpreted as a possible indicator of a biological vulnerable phase or delayed response of former high exposure. A second study of the hypothesized age-exposure interaction was performed with a group of workers who had homogenous exposure to a single organic solvent using a neurobehavioral performance evaluation (the EURO-NES). Workers in the rotogravure printing industry who were exposed to toluene were examined two times with an interval of one year (n =333/278). The sample was stratified by workers with significantly different toluene exposure, printers and end-processing operators, and four age classes (< 31, 31-40, 41-50, > 50). The mean lifetime weighted average exposure (LWAE) varied depending on age classes and years of employment with exposure between 7 and 17 ppm in the operators and between 35 to 62 ppm toluene in the printers. Multivariate analyses revealed a significant performance decrease with age (simple reaction time, symbol digit, switching attention, digit span). Again an interaction between age and exposure was found depending on diverging psychometric performance trends with older age. However, contrary to the hypothesis the group with higher exposures (printers) and older age revealed better performance and less symptoms than the group with lower exposure (end-processing operators). The paradoxical results are explained by differences in the intellectual capability in the oldest strata and a possible reversibility of neurobehavioral effects of former high toluene exposure under the condition of later low exposure. There are no hints of adverse delayed effects of former toluene exposure in a possible vulnerable phase in age over 50 years. The different interaction findings of the initial and present study seem to depend mainly on exposure differences in quality and quantity.

Psychological effects upon exposure to polyhalogenated dibenzodioxins and dibenzofurans.

Thirty workers who had been exposed to combustion products for several years due to testing of flame retarding qualities of building materials and 30 controls from the same facility were investigated. Concentrations found in samples taken from different places of the facility were up to 14,660 microg/kg for polybrominated dibenzofurans and up to 67.1 microg/kg for polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). Physical examination, routine laboratory parameters, and blood fat concentrations of PCDDs and PCDFs revealed normal findings. Neurotoxic symptoms showed a weak tendency of overrepresentation among the exposed workers. The frequency of neurobehavioural symptoms increased significantly with trait anxiety independent of exposure to combustion products.

Association of biochemical and subjective indicators of drinking habits with performance on different neurobehavioral tasks.

The present paper outlines the association of biochemical and subjective indicators of alcohol consumption. Due to its relevance as a potential confounding variable in occupational neurotoxicology, both sources of information about drinking habits were related to neurobehavioral test performance. A sample of 308 rotogravure printers and control subjects from a cross-sectional longitudinal study in various German printing plants was studied. Duration of employment was 4 months to 44 years (mean = 14.9, sd = 9.67). Mean age was 38.4 years (range 21 - 60). From venous blood samples three parameters considered to be sensitive for increased consumption of alcohol were used. They were carbohydrate-deficient transferrin (CDT), gamma glutamyl transferase (GGT), and mean cell volume (MCV). During the medical interview subjects with any chronic liver disease were identified and excluded from data analysis. Additionally, information about weekly consumption of alcohol was assessed and transformed to grams per day (g/d) values. Neurobehavioral testing included simple reaction time (SPES version), switching attention, symbol digit substitution, and digit span (EURONEST version). Additionally, a questionnaire of neurotoxic complaints was administrated. Other covariates, i.e. verbal ability, history of solvent exposure, and age were controlled. GGT and CDT were elevated in 10.5% and 6.6% of the population. 3.5% of the subjects reported daily consumption higher than 60 gram. There were positive correlations of CDT and GGT with the subjective indicator of drinking habits. The magnitude of these relationships were low, but the associations were significant. MCV was not correlated with subjective reports of drinking habits, but it showed convergent correlations with CDT and GGT. Comparison of these two parameters with performance on neurobehavioral tasks yielded only one negative association, i.e. between the memory-loaded tasks factor and GGT. CDT and subjective estimation of alcohol consumption were not related to any cognitive function tested in this study. Especially, the digits-backward task was negatively correlated with increased GGT.

Solvent Exposure, Shiftwork, and Sleep.

The effects of different conditions of occupational exposure to organic solvents on subjective sleep quality were studied with and without shiftwork. Laboratory studies showed that four hours of daytime exposure to ethanol (400, 800 ppm) by inhalation led to blood ethanol levels below 0.01 per thousand and had marginal effects on the following night's sleep. Exposures to acetone (1,000 ppm), ethyl acetate (400 ppm), and a solvent mixture (acetone 500 ppm, ethyl acetate 200 ppm) increased the subjective depth of sleep. In a field study with eight hours of exposure, during three different work shifts, dose-response relationships between acetone concentrations during the shiftwork and the depth of sleep were found. Nevertheless, the solvent-exposed shift workers reported a reduced sleep quality, mainly in connection with daytime sleep, in comparison with non-exposed shift workers. The effects of solvent exposure during shiftwork on sleep varied with time of day of the exposure.

Standardization of a questionnaire for neurotoxic symptoms.

A new version of the "Psychological-Neurological Questionnaire," designed for screening purposes, was investigated concerning its sensitivity to detect early signs of occupational exposure to potential neurotoxicants. A study population of 361 subjects was stratified into four age groups (<34, 35-44, 45-54, and >54 years) and three exposure groups (no, low, and high). According to dose and exposure history, workers exposed to dioxins and furans in combustion products, to volatile organic compounds, and to chromates were classified as low exposure. Workers exposed to alkyl lead, single solvents, and solvent mixtures were classified as high exposure. Only the group with the oldest age and highest exposure could be separated clearly from other groups, indicating an interaction effect between exposure and age. The low-exposure group could not be separated from the nonexposed controls. The most effective discriminators were neurologic symptoms. Psycho- and neurovegetative lability and irritative disturbances contributed less to the differentiation. Gastrointestinal and sleep disorders, as well as alcohol intolerance, showed no differentiation quality. The observed type of interaction effect fits models of delayed neurotoxicity.

In search of dose-response relationships of solvent mixtures to neurobehavioural effects in paint manufacturing and painters.

Four exposure indices for the evaluation of mixtures of solvents are outlined. The hygienic effect is a relative measure depending on the limit values of the single compounds of the mixture. The cumulative lifetime exposure (CE) and the lifetime-weighted average exposure (LWAE) are approaches based on measurements of total hydrocarbons at workplaces in different time periods. Estimations of litres of solvents used per day years (l/d years) are necessary if air monitoring is not available. Five studies on neurobehavioural effects due to solvent mixtures in paint manufacturing are compared as example for dose-response relations. The best prediction of neurobehavioural dose-response relations seems to be possible using CE and LWAE for total hydrocarbon as the exposure index. Moreover, four studies on neurobehavioural effects due to solvent mixtures in paints and glues are compared. These studies indicate that the index l/d years is helpful in predicting neurobehavioural deficits. Of numerous neurobehavioural tests, the test symbol digit substitution shows the most significant dose-response relations in the studies. For symptom questionnaires these relations appear only occasionally. In principle, associations between doses of solvent mixtures in paints and neurobehavioural effects are reproducible to a limited extent.

Neurobehavioral effects of solvents and circadian rhythms.

Two studies on the combined neurobehavioral effects of shiftwork and solvent exposure were performed: two-shift work/mixed solvent exposure and three-shift work/single solvent exposure (acetone). Repeated measurements of exposure, body temperature, well-being, complaints, and performance were taken during each shift and during several shift cycles. The air concentrations of the solvent mixture were clearly below and of acetone were near the occupational exposure limit values. Both the exposure quality and the circadian factor contributed to the stronger adverse effects under the three-shift condition. The results support the view that exposure effects should be studied and evaluated in relation to shift and time.