Kai Savolainen

Effects of short-term m-xylene exposure and physical exercise on the central nervous system.

SummaryEight male volunteers were exposed on 5 consecutive days and 1 day after the weekend to m-xylene vapour at either a constant (Study I) or a periodically varying (Study Il) concentration of 3.7–8.2 μmol/1(90–200 ppm, time-weighted average). The effects of the exposure on psychophysiological functions, such as reaction time, manual coordination and body balance, and EEG were studied. The same tests were completed on 2 non-exposure days for control purposes in both studies, in which physical exercise of 10O W was included.An inhalation exposure to m-xylene already at a concentration of 3.7 μmol/1 (90 ppm) had acute deleterious effects on the above mentioned psychophysiological functions of non-adapted subjects. EEG indicated lowered vigilance during exposure to varying concentrations with peak exposures of 8.2 μmol/l. Slight exercise, especially at the beginning of the exposure, seemed to antagonize the effects of xylene, particularly when the concentration fluctuated. Tolerance against the observed effects developed over one working week, but some effects were again discernible in the following week. A dose-response relationship between blood m-xylene concentrations and the effects of m-xylene was not found. This was probably due to tolerance.

Immediate effects of m-xylene on the human central nervous system.

Male volunteers were exposed to m-xylene vapour for 4 h a day either sedentary or with a period of 10 min exercise twice a day with stable (8.2 mumol/l) m-xylene concentrations or fluctuating concentrations with peaks (16.4 mumol/l). The TWA concentration was always the same (8.2 mumol/l). The body balance of the subjects was clearly impaired in the anteroposterior (a-p) direction, especially with their eyes closed during the peaks at rest, whereas it was improved when exercise was included in spite of the higher blood m-xylene concentrations. When on the contrary, the situation was reversed in the lateral direction. Complex audiomotor reactions were impaired after the peaks combined with exercise, whereas changes in simple reaction times were similar in pattern to those found for body balance in the a-p direction. The results suggest a complex interaction between physiological factors and m-xylene and development of adaptation or tolerance during the exposure.

Acute effects of 1,1,1-trichloroethane inhalation on the human central nervous system

The object of this study was to examine the immediate nervous effects of variable 1,1,1-trichloroethane (TCE) exposure combined with physical exercise. The effects on the quantitative electroencephalography (EEG), visual evoked potentials (VEP) and body sway were analyzed. Nine male volunteers were exposed to either a stable or a fluctuating exposure pattern with the same time-weighted average concentration of 200 ppm (8.1 μmol/l). In both cases, the subjects engaged in physical exercise during the exposures. Exercise alone induced an increase in the dominant alpha frequency in the EEG and, after an initial drop, an increase in the alpha percentage with a concomitant decrease in theta, whereas delta and beta bands remained unaffected. By contrast, exposure to TCE and exercise did not affect the alpha, theta or delta activities but induced changes in beta during the morning recordings at peak exposure to TCE. The body sway tended to decrease slightly during the fluctuating TCE exposure, and the later peaks in VEPs showed slight prolongations. Overall, no deleterious effects of exposure were noted.

Acute effects of m-xylene inhalation on body sway, reaction times, and sleep in man.

SummaryNine male volunteers were exposed to either a constant or a fluctuating exposure pattern of m-xylene with a time-weighted average exposure concentration of 200 ppm in both cases. The subjects remained sedentary throughout the exposure, or the exercised at 100W for 10 min at the beginning of the morning and the afternoon sessions. In another experiment, 12 sedentary male volunteers were exposed to a fixed 200 ppm of m-xylene. The effects of m-xylene on body sway, reaction time performance, and overnight sleep were measured. Body balance was stabilized after exposure to the peaks of 400 ppm of m-xylene in both sedentary and exercising subjects. Simple visual reaction times were prolonged after the peak exposures at rest whereas auditive choise reaction times were prolonged after peaks combined with exercise. Exposure to m-xylene at a constant level of 200 ppm did not affect the ratio of “active” to “quite” sleep in the volunteers as measured with the static charge sensitive bed recording, but decreased slightly the number of body movements in bed. On the next morning no changes were found in body sway and reaction time performance as compared to the morning before exposure.

Short-Term Exposure of Human Subjects to m-Xylene and 1,1,1-Trichloroethane

Inhalation exposure of male volunteers to m-xylene (8.2 mumol/l, 200 ppm) and 1,1,1-trichloroethane (TCE) (8.2 and 16.4 mumol/l, 200 and 400 ppm), as well as to a combination of TCE (16.4 mumol/l) and xylene (8.2 mumol/l), induced only slight changes in psychophysiological functions such as body sway and reaction time. Exposure to the 8.2 mumol/l concentration of xylene or TCE tended to improve the performances, whereas TCE exposure at 16.4 mumol/l alone or in combination with xylene tended to have an opposite effect. The results thus suggest a biphasic acute effect of TCE on the central nervous system (CNS) and reveal that xylene and TCE together exhibit neither kinetic interaction nor synergistic nor antagonistic acute effects on the CNS functions studied.

The Effect of Some Dithiocarbamates, Disulfiram and 2,5-Hexanedione on the Cytoskeleton of Neuronal Cells in Vivo and in Vitro

Dithiocarbamates are widely used fungicides because of their low toxicity to mammalian species and because of their rather rapid biodegradation in the soil and by plants. Their fungicidal action is based on interference with the citric acid cycle of several fungi (Schlagbauer and Schlagbauer, 1972). Several dithiocarbamates show neurotoxic effects in central and peripheral nervous system (Seppalainen and Linnoila, 1976; Freudenthal et al., 1977; Chernoff et al., 1979), but the mechanisms of the neurotoxicity of dithiocarbamates are largely unexplained.

Actions and interactions of cinnarizine and phenylpropanolamine on human psychomotor performance

Abstract This placebo-controlled, double-blind, crossover study was conducted to evaluate the actions and interactions of cinnarizine and a centrally acting sympathomimetic agent on human psychomotor performance. Twelve healthy men received single doses of 10 mg of cinnarizine (C), 50 mg of phenylpropanolamine (P50), the combinations of 10 mg of cinnarizine with 25 mg (CP25) or 50 mg (CP50) of phenylpropanolamine, and respective placebos, in balanced order at 1-week intervals. Digit symbol substitution, tapping, flicker fusion, tracking, choice reactions, and body balance tests were administered before drug intake (between 4 and 5 pm) and 1, 2, and 3 hours posttreatment. Two-way analysis of variance and paired t test were used to analyze the drug-induced changes from baseline. No significant drug-induced impairment of coordination or reaction skills were found. Compared with placebo, CP50 improved digit symbol substitution at 2 hours and impaired the flicker fusion threshold at 3 hours. The sagittal body sway was reduced by P50 (at 1 hour) and by CP50 (at 1 and 2 hours). We conclude that the mild sedation produced by cinnarizine is counteracted by the doses of the stimulant used. A potential therapeutic interaction of cinnarizine and phenylpropanolamine is likely.