This article was downloaded by: [UQ Library] On: 04 February 2015, At: 02:15 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Electroencephalographic Findings during Experimental Human Exposure to m-Xylene a
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Anna Maria Seppäläinen M.D. , Arto Laine M.D. , Tapani Salmi M.D. , Elvi a
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Verkkala M.D. , Vesa Riihimäki M.D. & Ritva Luukkonen Sc.D. a
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Department of Neurology , University of Helsinki , Helsinki, Finland
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Institute of Occupational Health , Helsinki, Finland Published online: 03 Aug 2010.
To cite this article: Anna Maria Seppäläinen M.D. , Arto Laine M.D. , Tapani Salmi M.D. , Elvi Verkkala M.D. , Vesa Riihimäki M.D. & Ritva Luukkonen Sc.D. (1991) Electroencephalographic Findings during Experimental Human Exposure to m-Xylene, Archives of Environmental Health: An International Journal, 46:1, 16-24, DOI: 10.1080/00039896.1991.9937424 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937424
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Electroencephalographic Findings during
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Experimental Human Exposure to m-Xylene
A N N A M A RI A SEPPALAINEN, M.D. Department of Neurology University of Helsinki Helsinki, Finland A R T 0 LAINE, M.D. Institute of Occupational Health Helsinki, Finland TAPANI SALMI, M.D. ELVl VERKKALA, M.D. Department of Neiirology University of Helsinki Helsinki, Finland VESA RIIHIMAKI, M.D. RITVA LUUKKONEN, k.D. Institute of Occupational Health Helsinki, Finland
ABSTRACT. Aromatic hydrocarbon solvents, used widely in industry, cause central nervous system symptoms in exposed workers. Acute effects of m-xylene were studied in nine voluntary subjects exposed experimentally to stable or varying concentrations of m-xylene at rest or while exercising. Each subject participated in four exposure and two control sessions in a singleblind fashion. The time-weighted average (TWA) m-xylene concentration was always 200 parts per million (ppm) (8.2 pmolll) during the 4-h exposure period, complying to a TWA of 4.1 pmolll . 8 h, which i s equivalent to the hygienic limit allowed i n work situations. The short-term peak concentrations were 400 ppm or less. Electraencephalography was recorded at the beginning of exposure, during exposure, and after exposure was stopped. Eighteen 60-s EEC samples for each subject on each experimental day were analyzed automatically. Exercise increased theta percentage and delta power and percentage; these changes were more prominent in the control session without exposure. Exposure increased the dominant alpha frequency and alpha percentage during the early phase of exposure and also counteracted the effects of exercise. The effects of short-term m-xylene exposure on EEC were minor, and no deleterious effects were noted. Perhaps alpha activation is indicative of stimulating and excitatory effects induced by m-xylene exposure, which has been noted heretofore in the absorption phase of alcohol intake.
EXPOSURE TO VARIOUS aromatic hydrocarbon solvents, e.g., toluene, xylene, ethylbenzene, and styrene, occurs at the work place. Xylene i s used widely in solvent mixtures in paints, varnishes, glues, and print16
ing inks; in the rubber and leather industry; and in histological laboratories. Pure xylene isomers are used as raw materials in the manufacture of polymers.' Metaxylene (rn-xylene), which is the predominant xylene Archives of EnvironmentalHealth
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isomer, has aroused interest as a model chemical in toxicokinetic studies and in experimental human neurobehavioral research. High concentrations of aromatic hydrocarbons may cause central nervous system depression and even death. At lower concentrations, exposed workers have complained of mild irritation, headache, drowsiness, dizziness, and nausea during daily e ~ p o s u r e . ~ In* field ~ studies, impairments in neurobehavioral performance tests have been reported, even though the average exposure has been at or near the hygienic limit values.'6 Human experimental studies with m-xylene have shown that relative low solvent levels (i.e., 100-400 parts per million [ppm]) may cause slightly impaired neurobehavioral Short-term exposure to fluctuating air concentrations of m-xylene may cause more pronounced effects during peak concentrations with concomitant high uptake rates than the same average exposure to a constant concentration." Physical activity and heavy work may enhance the central nervous system effects by increasing xylene absorption.'^^ The aim of this study was to describe and determine possible electroencephalographic (EEG) effects induced by varying m-xylene exposures during short periods at rest and combined with exercise. The time-weighted average (TWA) concentration during the different exposures was 8.2 pmol/l, and it was within those limits allowed in work situations in Finland (TWA for 8 h: 4.1 pmolll). Because quantitative computer analysis of EEG samples may detect features not readily identified visually," EEGs were submitted to spectral analysis off-line.
Subjects and methods Subjects. Nine male students (age 19-22 y, height 182-187 cm, weight 72-80 kg) who had no occupational exposure to organic solvents volunteered to participate in this study. All subjects were deemed healthy after a thorough medical examination that preceded the experiment. They had no history of neurologic, psychiatric, or other chronic diseases, and no abnormal signs were detected in their general physical and neurological examinations. No abnormalities were o b served in their EEGs, chest X-rays, or a cardiac function test (i.e., electrocardiography at rest and during sub maximal ergometer exercise). Clinical chemical investigations (i.e., hemoglobin; white cell count; serum ASAT, ALAT, and creatinine; urine albumin; glucose; and sediment) were within reference limits. General physical and chemical examinations were repeated after the exposure period on the last experimental day, and no significant changes were noted. All subjects reported social use of alcohol. Exposures. All procedures were conducted in accordance with the World Medical Association's ethical principles (Declaration of Helsinki, rev. Tokyo 1975). The study was approved by the Ethics Committee of the institute of Occupational Health, Helsinki. The voluntary (paid) subjects were informed about the experiment, average exposure levels, and methods used. The sequence of the exposures was not revealed (singleblind experiment). Informed consent was obtained Januaylkbruary1991 [Vol. 46 (NO.l)]
from every subject prior to commencement of the study. Exposures to m-xylene (laboratory grade, Merck, FRG) were conducted in a 15-m' exposure chamber, three glass walls of which faced a large room where usually two or three persons worked. The solvent concentration, temperature, and humidity in the chamber were controlled automatically.12 The concentration of m-xylene in the chamber air was always kept within 5 ppm of the desired value, and it was monitored continuously with an infrared analyzer (Miran lA, Wilks Scientific Corporation, USA) and controlled automatically with a Eurotherm 070 industrial processor (Eurotherm Ltd, UK). The ambient temperature was kept at 23 f 2 O C . In all test situations, a small amount of peppermint oil vapor was used to mask the presence or a b sence of solvent. None of the subjects used any drugs during the experimental period. Each subject was instructed to a b stain from alcohol and drug use during the evenings preceding the experimental days. Venous blood samples drawn on the morning of each experimental day showed no signs of alcohol in any of the subjects. The subjects were divided into three subgroups, each containing three subjects. Only one subgroup was in the exposure chamber at any time. An exception was on 1 d when a subject was absent because he had a common cold. The sequence of the experimental exposure situations was balanced over the groups. The experiments were si ngle-blind with cross-over design, and the subjects acted as their own controls. The experiments were conducted during consecutive weeks. Sometimes an exposure day followed a control day to insure that the time interval was always at least 5 d. On each experimental day, the subjects arrived at 8 A.M. for baseline tests. Exposure of the first subjects commenced at 9 A.M., after which the two other sub jects entered the chamber at 20-min intervals (Fig. 1). Each subject remained continuously in the chamber for 3 h. The three subjects left the chamber for a 40-min
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Fig. 1. Exposure of subject no. 1 and exposure patterns under different experimental conditions. Area surrounded by doffed line shows exposure type with a stable concentration of 200 ppm (8.2 pmoVI). S b a M areas indicate exposure type combined with 2Gmin peak concentrations of m-xylene up to 400 ppm (16.4 pmoUI) at the beginning of the morning and afternoon sessions. E I timing of physical exercise and EEC I timing of EEC recordings. During different exposures, the time-weighted average concentration of m-xyhe was 200 ppm (8.2 pmolll).
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break, during which a standardized meal was served. A smaller meal wa!, served before exposure and once during the morning session to eliminate changes in blood glucose concentration. After the break, subjects entered the chamber, one at the time, at 20-min intervals for an additional 40 min. According to the experimental design, each group was exposed on 2 separate d to a constant concentration of 8.2 pmol/l (870 mg/m3 = 200 ppm) of m-xylene in the air. On 2 other exposure d, the baseline concentration of m-xylenle was 5.2 pmolll (550 rng/m3 = 135 ppm) combined with a 20-min peak concentration of 16.4 pmolll (1 740 mg/m3 = 400 ppm) at the beginning of the morning and afternoon sessions. The subjects were either sedentary or exercised at 100 W for 10 min at the beginning of each session during both exposure types (Fig. 1). The various exposure situations are as follows: 200 R = exposure to a stable 200-ppm level of m-xylene while subjects were at rest; 200 E = exposure to a stable 200-ppm level of m-xylene with a 10-min exercise period at the beginning of the morning and afternoon sessions; 400 P + R = exposure to m-xylene, including peak exposure periods of 400 ppm, while the subjects were at rest; and 400 P+E = exposure to m-xylene, including peak exposure periods of 400 ppm, combined wilth exercise. Moreover, 2 corttrol d were included in the experiment. The days’ ekents were similar to that of exposure days, but absent m-xylene exposure: 1 d the subjects exercised (control E) and 1 d they rested (control R). Electroencephalographic recordings. EEG recordings were taken with glued-on electrodes using a scalpto-scalp montage F4C4, C4-02, F3-C3, and C3-01 with an Elema Mingograph on paper. The cables were fixed with gauze to avoid movement artifacts. The amplified EEG was recorded simultaneously on tape with a Racal 4D four-channel instrumentation tape recorder (frequency band DC to 30 Hz). The EEG was recorded for the first 18 min in the exposure chamber and included the total period of 10 min with exercise and 3-4 min after exercise ended. The afternoon exposure commenced with a similar EEG recording. In addition, the EEG was recorded for 5 min on two occasions in the chamber, i.e., 1 and 2 h after the subject had entered the chamber. The last 5 m i n EEG recording of the day occurred 45 min after the afternoon exposure had ceased. The morning and afternoon exposure sessions started with a similar 18-min recording, even when no exercise was performed. The subjects always sat on the bicycle ergometer, fitted with a special backrest during the recordings, and had their eyes closed. The timing of the EEG recordings during the exposures are presented in Figure 1. The paper recordings were checked visually, and 1-min periods with the least artifacts were chosen for computer analysis. The periods chosen were: (1) before exercise; (2) 1 min after starting exercise; (3) 3 min after starting exercise; (4) 5 min after starting exercise; (5) 9 min after starting exercise; (6,)2 min after exercise stopped; (7) and (8) during a 5-min recording 1 h after exposure started; (9. and 10.) during a 5-min recording 2 h after 18
exposure started; (11.-16.) in the afternoon, during which recordings (1.) through (6.) were repeated; and (17. and 18.) during a 5-min recording taken 45 min after exposure ceased. Computer analysis of the 18-min recordings was completed at the same time points for subjects who exercised and for those who did not. The computer analysis was performed off-line in 5-s epochs, and a compressed analysis was based on 12 epochs (60 s). The analysis provided the percentage of delta (1-3.9 cps, frequencies lower than 1.0 cps were omitted), theta (4-7.9 cps), alpha (8-13 cps), and beta (13.1-25 cps) activity; the dominant (mode) frequency in each band; and an absolute power in each band. Collection and analysis of blood samples. A teflon catheter was inserted into an antecubital vein prior to the exposure, and venous blood samples were drawn for m-xylene measurements during the exposure and after the subjects had left the chamber. Blood samples were collected at specified time intervals following the EEG recordings. Venous blood concentrations of m-xylene were analyzed by gas chromatography.” Statistical analysis. Statistical analysis was performed using either t tests or two-way analysis of variance (ANOVA). In the statistical analysis of the data, the means of the subjects on each analysis point were accounted for. Results in the exposure situations were first compared with results obtained on the equivalent control day, i.e., results of an exposure day with exercise were compared with the control day with exercise, and those of a sedentary exposure were compared with results of a sedentary control day. Student’s t test for matched pairs was used in that statistical analysis. This was done for all variables and situations. The two-way ANOVA was then applied when examining the effects of exercise, exposure, and their interaction with the EEG data for the time point in question. This was done for only those variables and situations where it was supposed that the null hypothesis could be rejected based on the t test results. Because comparisons were always done for control days with similar time schedules, a pre-exposure EEG recording each monring was considered unnecessary.
Results The dominant frequency of the alpha activity measured with the centro-occipital leads fluctuated during the day (Fig. 2). During the first minute of exercise in the morning, a rise in the alpha frequency for 0.3 c/s occurred when exposure to the stable and peak concentrations occurred. No such early rise occurred on the control days; the dominant frequency remained at 9.85 c/s. This difference was statistically significant @ < .05, t test) when 200 E and 400 P+E were compared with control E. In the samples that followed during the first 20 experimental min, an increase in the alpha frequency was noted in all situations. In the recordings made later in the morning session, the alpha frequency tended to stay at a higher level during m-xylene exposure than on the control days. For the recording made 45 min after exercise ceased, the alpha frequenArchives of Environmental Health
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Fig. 2. Variations of dominant alpha frequency (mean of 9 subjects) in the centroacipital leads during various exposures to m-xylene. 400 P + E = exposure to 400 pprn peaks combined with exercise, 200 E = exposure to stable concentration of 200 ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = control session at rest.
cy was higher during exposure (p < .01 for 200 E and p < .05 for 400 P+E, t test) than on the corresponding control day. During the beginning of the afternoon session, the alpha frequency was higher in exposure than in control situations (p < .05 for the first recording and p = .06 at 8 min from restart of exposure, ANOVA). In the peak exposures (400 R and 400 E), an early rise of the alpha frequency was again noted (for 0.25 and 0.35 ds, respectively), but the resulting dominant frequency did not differ significantly from the others. The alpha frequency stayed higher during m-xylene exposure, but it differed significantly from the corresponding control day only at the end of the exercise @ < .05 for 200 E and p < .005 for 400 P+ E, t test). After exposure ceased in the afternoon, the alpha frequency dropped toward the same level in each situation. In the centro-occipital leads, the percentage of alpha activity decreased immediately after exercise commenced, but rose to a higher level during exposure situations with exercise (Fig. 3). Analysis of variance indicated that the change in alpha percentage was related to exercise during the first minutes of both the morning and afternoon sessions (p < .001 and < .05 at 3 min after exercise started, respectively). At the end of the exercise periods, these effects appeared to be related to solvent exposure; at 9 min after exercise started (or 14 min after exposure commenced), the alpha percentage was higher when exposure occurred (p < .01, ANOVA) during both the morning and afternoon sesJanuary/February 1991 [Vol. 46 (No. l)]
sions. After 2 h exposure in the morning, the alpha percentage was correlated to either solvent exposure @ < .05,ANOVA) or interaction of exposure and exercise @ < .05,ANOVA). When considering only exposures combined with exercise versus the control day, the clearest differences were noted 2 h after exposure started (p < .005,t test) and, if exposed to the peak concentration, at the end of the afternoon exercise period (p < .05,t test). In the frontocentral leads, the theta percentage rose at the beginning of exercise in the morning and afternoon (Fig. 4). This was correlated to exercise @ < .05, ANOVA, at 3 min after exercise started), but the theta percentage for 200 E was often lower than that for control E. For all afternoon recordings, the theta percentage was statistically significantly @ < .05-.005,t test) lower for 200 E than for control E. At and following cessation of exercise, the theta percentage dropped; the drop was more acute when accompanied by exposure. In the afternoon at 14 min after restarting the exposure (and the last minute of exercise), the theta percentage was significantly lower during m-xylene exposure @ < .01, ANOVA). Similarly, in the centrooccipital leads the theta percentage was lower during exposure, both in the morning and in the afternoon at recordings 14 min after exposure started @ < .01 and p < .02,respectively, ANOVA). The same was noted 30 rnin after cessation of exposure @ < .05,ANOVA). In the centro-occipital leads, exercise was not significantly correlated to the theta percentage. 19
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Fig. 4. Variations of theta percentage (mean of 9 subjects) in the frontecentral leads during various exposures to m-xylene. 400 P + E = exposure to 400 ppm peaks combined with exercise, 200 E = exposure to stable concentration of 200 ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = contml session at rest.
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When stable and fluctuating exposure types were combined with ergometer exercise in the beginning of the sessions, the blood m-xylene concentration reached the maximum in 15 min-at the time point when the exercise stopped (Fig. 6). The highest blood m-xylene concentration during the morning session was 43 14 pmol/l in 200 E and 72 f 14 pmolll in 400 P+E. These levels were about 2.5 times higher than in corresponding exposures at rest, which were 17 5 pmol/l in 200 R and 27 f 6 pmol/l in 400 P + R. The blood m-xylene concentration declined rapidly after exposure periods with exercise; consequently, after a 60-min exposure, the concentration range of m-xylene for all exposures was 24-34 pmolll. During the afternoon sessions, the blood m-xylene concentration was 10-30% higher than during the first 40 min of the corresponding morning sessions. There were no marked differences between different exposure patterns in the post-exposure concentrations.
In the centro-occipital leads, the absolute delta power increased during exercise, especially for 400 E and control E (Fig. 5). The difference, when compared with sedentary situations, was statistically significant @ < .05, ANOVA) at 9 min after exercise started. The highest delta power was noted in control E during the last minute of exercise when exposure decreased the delta power (p = 0.52,ANOVA). At that time, the delta percentage was significantly lower when accompanied by exposure (p = .02,ANOVA). After exercise ceased, the delta power clearly decreased. In the fronto-central leads, delta activity (and theta activity) often increased during exercise, and 400 ppm P + R showed similar trends. Beta activity in the frontal and occipital areas varied slightly during the study, but no relevant relationships between exposure and exercise paradigms and beta activity were detected. m-Xylene in venous blood. The time course of m-xylene concentration in venous blood was different in the varying exposure types. There was a continuous build-up of m-xylene concentration in 200 R, followed by a leveling off to 31 7 pmol/l toward the end of the morning session (Fig. 6). In exposure 400 P+R, the blood m-xylene concentration rose more rapidly at the beginning of the morning session and reached about 40% higher levels than in 200 R, but then declined slightly after the baseline concentration in the chamber decreased toward the end of the morning session.
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Discussion Although EEG can be analyzed quantitatively with computer techniques-and these techniques have been widely applied to pharmacologic drug studies in humans and animals-quantitative EEG studies are scarce concerning chemicals in the ~ o r k p l a c e . 'More~ over, no quantitative EEG studies during combined sol-
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Fig. 5. Variations of ddta power (mean of 9 subjects) in the centrooccipital leads during various exposures to mxylene. 400 P + E = exposure to 400 ppm peaks combined with exercise, 200 E = exposure to stable concentration of Mo ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = control session at rest.
January/February1991 [Vol. 46 (No. l)]
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vent exposure and exercise have come to our attention. We report results from an exposure chamber study designed to examine central nervous system effects related to rapid environmental changes during single-day m-xylene exposure using quantitated EEG. The exposure fadors are relevant because they are common in the workplace. Physical exercise has been suggested as a provocative method to enhance EEG signs of cerebrovascular disorder, and, indeed, a prolonged decrease of alpha frequency after physical exercise was shown in 5 of 10 patients with a history of cerebrovascular accident and among 3 of 10 normal subjects who were older than 50 y.I4 Conversely, normal young subjects usually showed an increase in alpha frequency after exercise, as did 6 of 10 older control:; and some patients. In the present study, exercise, which increased ventilation and perfusion but did not cause actual hyperventilation, induced changes in the EEG. Theta percentage in the frontal areas increased during exercise and decreased shoirtly after exercise stopped. Similarly, absolute delta power and delta percentage increased during exercise. Frequencies less than 1 cps were omitted from analysis; therefore, brain activity was measured rather than movement or other artifacts with our well-secured electrodes. Changes in theta and delta activity were more prominent in the control and peak exposure situations; at the end of the exercise period, exposure appeared to attenuate these EEG ef22
fects. In fact, exposure seemed to account for the lowering of the theta percentage close to the end of exercise and at the moment when the highest blood m-xylene concentrations occurred. Similar effects were noted for sedentary situations. Exposure during the early phase in the morning increased the alpha activity, and higher alpha frequencies were also noted 1 h after initiating exposure in sedentary and exercise conditions. Similar higher alpha frequencies were noted in exposure paradigms at the end of the afternoon exposure. Changes resulting primarily from m-xylene exposure were minor, which indicates slight alpha activation (i.e., increased percentage and higher frequencies of alpha) toward later phases of exposure. These effects are diametric to those of ethanol, which decreases the alpha frequen~y.'~-'~ Smoking tobacco prior to or during alcohol consumption counteracted this alcohol effect on the EEG." An alcohol dosage of approximately 0.3 mllkg increased alpha abundance,Ig which is similar to the increased alpha percentage in the present study. A biphasic effect of alcohol on the alpha activity has also been reported: during the absorption phase, alpha activity increased as was accompanied by a concomitant decrease in delta and theta activity, whereas in the elimination phase, alpha activity decreased." Alpha activity increased during transient episodes of ethanol-induced euphoria." In a previous study, where the exposure patterns to m-xylene were different and Archives of Environmental Health
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visually analyzed EEGs were recorded 20 min after physical exercise, an increase in occipital slow transients was noted in a few subjects while being exposed to varying concentrations of m-xylene.’ The exposure situations in that study differed greatly from the present study; therefore, direct comparisons are not possible. Trichloroethylene, another industrial solvent, has induced similar effects as reported in our study for m-xylene. During exposure of 20 volunteers to 95 ppm of trichloroethylene, the alpha percentage (as measured with recording lengths with alpha activity) increased significantly from the pre-exposure level after 1 and 2 h of exposure.22When paper recordings taken before and after trichloroethylene exposure for 4 h were compared,23no statistically significant differences emerged for the alpha amplitude, the mean alpha frequency, or in the percentage time alpha. Three of six healthy workers who had long-term occupational exposure to trichloroethylene experienced activated alpha activity during a workshift when occupational exposure to trichloroethylene occurred. Trichloroethylene concentrations in blood (2.6-3.25 pg/ml) were high among those with alpha activation; however, the workers with no detectable change in their EEG had lower trichloroethylene concentrations in their blood and atmospheric air.22During a 4.5-h exposure to 3.2 mmol/m3 of toluene only or in combination with 15 mmollkg of ethanol, no changes were found in the EEGs of 12 male volunteers when EEGs were subjected to spectral analysis.24 Toluene, however, produced symptoms such as headache, local irritation, and a mildly depressed heart rate and ethanolimpaired performance in two of four performance tests and effected an increased heart rate. Long-term effects of solvents on EEG may be similar to effects observed in the present acute exposure. Automatized EEG frequency analysis in exposure-free situation has revealed that the EEGs of car and industrial painters occupationally exposed to solvents have higher alpha powers, smaller alpha band widths, lower delta powers, and larger delta band widths than do the EEGs of their referents. The painters were exposed to solvent levels that were approximately 30% of the contemporary hygienic limit values. However, no statistically significant differences were found between the two groups.25When the EEGs from a group of 32 men with clinically diagnosed chronic toxic encephalopathy after long-term occupational solvent exposure were submitted to power spectrum analysis, the absolute power within each frequency range was much higher than that among a control group of 50 men who had not solvent exposure in the workplace.26 Spectral analysis of EEGs among 50 workers exposed to solvents during paint production showed significant differences when compared with 50 pairwise matched referents employed in a sugar refinery.*’ The power of beta activity was greater among the exposed subjects. No relevant changes in beta activity were noted in the present experimental study. Because exercise clearly induced EEG changes in the present study, and some of those were counteracted by m-xylene exposure, one wonders about the contribuJanuary/February1991 [Vol. 46 (No. l)]
tion of mild physical stress and chemical exposure. The present study did not analyze individual results, and the individual effects may vary in type and degree. No deleterious effects of exposure could be detected during this type of m-xylene exposure. However, the effects of xylene during long-term occupational exposure and among elderly workers may be different. Thus, no direct conclusions can be drawn concerning possible effects of long-term xylene exposure on the EEG. EEG effects similar to those reported in our study, i.e., increased alpha activity and decreased theta and delta activity, have been observed during the alcohol absorption phase and have been attributed to the stimulating or excitatory effects of alcohol.20Thus, the minor differences between exposure and control conditions in our study probably suggest stimulating or excitatory effects of low-level, short-term exposure to m-xylene. Alternatively, the increased alpha percentage could be associated with a more relaxed state of the subjects; this could indicate that sedative effects of m-xylene counteract the alerting effect of physical exercise. Because the alpha percentage decreased during exposure absent exercise and because the alpha frequency increased during exposure, it is probable that m-xylene stimulates these effects during exposure.
********** This study was supported, in part, by Finnish Work Environment Fund, Helsinki. Submitted for publication February 24, 1990; revised; accepted for publication June 18, 1990. Requests for reprints should be sent to: A. M. Sepplainen, Division of Clinical Neurophysiology, Department of Neurology, University of Helsinki, Haartmaninkatu4, SF-00290 Helsinki, Finland.
********** References 1. National Institute for Occupational Safety and Health (NIOSH). Criteria for a recommended standard: occupational exposure to xylene. Cincinnati, OH: U S . Department of Commerce. National technical information services; 1975. 2. Browning E. Toxicity and metabolism of industrial solvents. Amsterdam: Elsevier; 1965. 3. Longley, EO, Jones AT, Welch R, Lomaev 0. Two acute toluene episodes in merchant ships. Arch Environ Health 1%7;14 481-87. 4. Camberale F, Lisper HO, Anshelm Olson 8. The effect of styrene vapour on the reaction time of workers in the plastic boat industry. in: M Horwath, Ed., Adverse effects of environmental chemical and psychotropic drugs. Vol. 2. Amsterdam: Elsevier, 1976; pp. 135-48. 5. Cherry N, Venables H, Waldron HA. The acute behavioural effects of solvent exposure. J Soc Occup Med 1983;33:13-18. 6. Anshelm Olson B. Effects of organic solvent on behavioral performance of workers in the paint industry. Neurobehav Toxicol Teratol 1982;4703-08. 7. Canberale F, Annwall C, Hultengren M. Exposure to xylene and ethylbenzene. 111. Effects on central nervous functions. Scand J Work Environ Health 1978;4204-11. 8. Savolainen K, Riihimaki V, Linnoila, M. Effects of short-term xylene exposure on psychophysiological functions in man. Int Arch Occup Environ Health 197944:201-11. 9. Savolainen K, Riihimaki V, Sepplainen AM, Linnoila MG. Effects of short-term m-xylene exposure and physical exercise on the central nervous system. Int Arch Occup Environ Health 1980;45: 105-21. 10. Riihimaki V, Savolainen K. Human exposure to m-xylene.
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Kinetics and acute effects on the central nervous system. Ann OCHyg 1980;23:411-422. Richards JE, Parmelee AH Jr, Beckwith L. Spectral analysis of infant EEC and behavioral outcome at age five. Electroencephalogy Clin Neurophysiol 1986;64:1-11. Riihimaki V, Pfaffli .'F Percutaneous absorption of solvent vapours in man. Scand J Work Environ Health 1978;473-85. Benignus VA. EEG as cross species indicator of neurotoxicity. Neurobehav Toxicol Teratol 1984;6:473-83. Kamp A, Troost 1. EEG signs of cerebrovascular disorder, using physical exercise as a provocative method. Electroencephalogr Clin Neurophysiol 1978;45:295-98. Kalant H. Effects of ethanol on the nervous system. In: J TremoliPres, Ed. Alcohols and derivatives (International Encyclopedia of Pharrnacology and Therapeutics, Section 20, Vol. 1) Oxford: Pergamon, 1970; pp. 189-236. Lehtinen I, Lang AH, Jantti V, et al. Ethanol-induced disturbance in human arousal mechanism. Psychopharmacol 1981;73: CUP
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223-29. 17. Zilm DH. Ethanol-induced spontaneous and evoked EEG, heart rate, and respiration rate changes in man. Clin Toxicol 1981; 18:549-63. 18. Knott VJ, Venables PH. EEC alpha correlates of alcohol consumption in smokers and nonsmokers: effects of smoking and smoking deprivation. J Stud Alcohol 1979;40:247-57. 19. Docter RF, Naitoh f', Smith JC. Electroencephalographic changes and vigilance behavior during experimentally induced intoxication with alcoholic
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Electroencephalographic Findings during Experimental Human Exposure to m-Xylene a
b
a
Anna Maria Seppäläinen M.D. , Arto Laine M.D. , Tapani Salmi M.D. , Elvi a
b
Verkkala M.D. , Vesa Riihimäki M.D. & Ritva Luukkonen Sc.D. a
b
Department of Neurology , University of Helsinki , Helsinki, Finland
b
Institute of Occupational Health , Helsinki, Finland Published online: 03 Aug 2010.
To cite this article: Anna Maria Seppäläinen M.D. , Arto Laine M.D. , Tapani Salmi M.D. , Elvi Verkkala M.D. , Vesa Riihimäki M.D. & Ritva Luukkonen Sc.D. (1991) Electroencephalographic Findings during Experimental Human Exposure to m-Xylene, Archives of Environmental Health: An International Journal, 46:1, 16-24, DOI: 10.1080/00039896.1991.9937424 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937424
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Electroencephalographic Findings during
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Experimental Human Exposure to m-Xylene
A N N A M A RI A SEPPALAINEN, M.D. Department of Neurology University of Helsinki Helsinki, Finland A R T 0 LAINE, M.D. Institute of Occupational Health Helsinki, Finland TAPANI SALMI, M.D. ELVl VERKKALA, M.D. Department of Neiirology University of Helsinki Helsinki, Finland VESA RIIHIMAKI, M.D. RITVA LUUKKONEN, k.D. Institute of Occupational Health Helsinki, Finland
ABSTRACT. Aromatic hydrocarbon solvents, used widely in industry, cause central nervous system symptoms in exposed workers. Acute effects of m-xylene were studied in nine voluntary subjects exposed experimentally to stable or varying concentrations of m-xylene at rest or while exercising. Each subject participated in four exposure and two control sessions in a singleblind fashion. The time-weighted average (TWA) m-xylene concentration was always 200 parts per million (ppm) (8.2 pmolll) during the 4-h exposure period, complying to a TWA of 4.1 pmolll . 8 h, which i s equivalent to the hygienic limit allowed i n work situations. The short-term peak concentrations were 400 ppm or less. Electraencephalography was recorded at the beginning of exposure, during exposure, and after exposure was stopped. Eighteen 60-s EEC samples for each subject on each experimental day were analyzed automatically. Exercise increased theta percentage and delta power and percentage; these changes were more prominent in the control session without exposure. Exposure increased the dominant alpha frequency and alpha percentage during the early phase of exposure and also counteracted the effects of exercise. The effects of short-term m-xylene exposure on EEC were minor, and no deleterious effects were noted. Perhaps alpha activation is indicative of stimulating and excitatory effects induced by m-xylene exposure, which has been noted heretofore in the absorption phase of alcohol intake.
EXPOSURE TO VARIOUS aromatic hydrocarbon solvents, e.g., toluene, xylene, ethylbenzene, and styrene, occurs at the work place. Xylene i s used widely in solvent mixtures in paints, varnishes, glues, and print16
ing inks; in the rubber and leather industry; and in histological laboratories. Pure xylene isomers are used as raw materials in the manufacture of polymers.' Metaxylene (rn-xylene), which is the predominant xylene Archives of EnvironmentalHealth
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isomer, has aroused interest as a model chemical in toxicokinetic studies and in experimental human neurobehavioral research. High concentrations of aromatic hydrocarbons may cause central nervous system depression and even death. At lower concentrations, exposed workers have complained of mild irritation, headache, drowsiness, dizziness, and nausea during daily e ~ p o s u r e . ~ In* field ~ studies, impairments in neurobehavioral performance tests have been reported, even though the average exposure has been at or near the hygienic limit values.'6 Human experimental studies with m-xylene have shown that relative low solvent levels (i.e., 100-400 parts per million [ppm]) may cause slightly impaired neurobehavioral Short-term exposure to fluctuating air concentrations of m-xylene may cause more pronounced effects during peak concentrations with concomitant high uptake rates than the same average exposure to a constant concentration." Physical activity and heavy work may enhance the central nervous system effects by increasing xylene absorption.'^^ The aim of this study was to describe and determine possible electroencephalographic (EEG) effects induced by varying m-xylene exposures during short periods at rest and combined with exercise. The time-weighted average (TWA) concentration during the different exposures was 8.2 pmol/l, and it was within those limits allowed in work situations in Finland (TWA for 8 h: 4.1 pmolll). Because quantitative computer analysis of EEG samples may detect features not readily identified visually," EEGs were submitted to spectral analysis off-line.
Subjects and methods Subjects. Nine male students (age 19-22 y, height 182-187 cm, weight 72-80 kg) who had no occupational exposure to organic solvents volunteered to participate in this study. All subjects were deemed healthy after a thorough medical examination that preceded the experiment. They had no history of neurologic, psychiatric, or other chronic diseases, and no abnormal signs were detected in their general physical and neurological examinations. No abnormalities were o b served in their EEGs, chest X-rays, or a cardiac function test (i.e., electrocardiography at rest and during sub maximal ergometer exercise). Clinical chemical investigations (i.e., hemoglobin; white cell count; serum ASAT, ALAT, and creatinine; urine albumin; glucose; and sediment) were within reference limits. General physical and chemical examinations were repeated after the exposure period on the last experimental day, and no significant changes were noted. All subjects reported social use of alcohol. Exposures. All procedures were conducted in accordance with the World Medical Association's ethical principles (Declaration of Helsinki, rev. Tokyo 1975). The study was approved by the Ethics Committee of the institute of Occupational Health, Helsinki. The voluntary (paid) subjects were informed about the experiment, average exposure levels, and methods used. The sequence of the exposures was not revealed (singleblind experiment). Informed consent was obtained Januaylkbruary1991 [Vol. 46 (NO.l)]
from every subject prior to commencement of the study. Exposures to m-xylene (laboratory grade, Merck, FRG) were conducted in a 15-m' exposure chamber, three glass walls of which faced a large room where usually two or three persons worked. The solvent concentration, temperature, and humidity in the chamber were controlled automatically.12 The concentration of m-xylene in the chamber air was always kept within 5 ppm of the desired value, and it was monitored continuously with an infrared analyzer (Miran lA, Wilks Scientific Corporation, USA) and controlled automatically with a Eurotherm 070 industrial processor (Eurotherm Ltd, UK). The ambient temperature was kept at 23 f 2 O C . In all test situations, a small amount of peppermint oil vapor was used to mask the presence or a b sence of solvent. None of the subjects used any drugs during the experimental period. Each subject was instructed to a b stain from alcohol and drug use during the evenings preceding the experimental days. Venous blood samples drawn on the morning of each experimental day showed no signs of alcohol in any of the subjects. The subjects were divided into three subgroups, each containing three subjects. Only one subgroup was in the exposure chamber at any time. An exception was on 1 d when a subject was absent because he had a common cold. The sequence of the experimental exposure situations was balanced over the groups. The experiments were si ngle-blind with cross-over design, and the subjects acted as their own controls. The experiments were conducted during consecutive weeks. Sometimes an exposure day followed a control day to insure that the time interval was always at least 5 d. On each experimental day, the subjects arrived at 8 A.M. for baseline tests. Exposure of the first subjects commenced at 9 A.M., after which the two other sub jects entered the chamber at 20-min intervals (Fig. 1). Each subject remained continuously in the chamber for 3 h. The three subjects left the chamber for a 40-min
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Fig. 1. Exposure of subject no. 1 and exposure patterns under different experimental conditions. Area surrounded by doffed line shows exposure type with a stable concentration of 200 ppm (8.2 pmoVI). S b a M areas indicate exposure type combined with 2Gmin peak concentrations of m-xylene up to 400 ppm (16.4 pmoUI) at the beginning of the morning and afternoon sessions. E I timing of physical exercise and EEC I timing of EEC recordings. During different exposures, the time-weighted average concentration of m-xyhe was 200 ppm (8.2 pmolll).
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break, during which a standardized meal was served. A smaller meal wa!, served before exposure and once during the morning session to eliminate changes in blood glucose concentration. After the break, subjects entered the chamber, one at the time, at 20-min intervals for an additional 40 min. According to the experimental design, each group was exposed on 2 separate d to a constant concentration of 8.2 pmol/l (870 mg/m3 = 200 ppm) of m-xylene in the air. On 2 other exposure d, the baseline concentration of m-xylenle was 5.2 pmolll (550 rng/m3 = 135 ppm) combined with a 20-min peak concentration of 16.4 pmolll (1 740 mg/m3 = 400 ppm) at the beginning of the morning and afternoon sessions. The subjects were either sedentary or exercised at 100 W for 10 min at the beginning of each session during both exposure types (Fig. 1). The various exposure situations are as follows: 200 R = exposure to a stable 200-ppm level of m-xylene while subjects were at rest; 200 E = exposure to a stable 200-ppm level of m-xylene with a 10-min exercise period at the beginning of the morning and afternoon sessions; 400 P + R = exposure to m-xylene, including peak exposure periods of 400 ppm, while the subjects were at rest; and 400 P+E = exposure to m-xylene, including peak exposure periods of 400 ppm, combined wilth exercise. Moreover, 2 corttrol d were included in the experiment. The days’ ekents were similar to that of exposure days, but absent m-xylene exposure: 1 d the subjects exercised (control E) and 1 d they rested (control R). Electroencephalographic recordings. EEG recordings were taken with glued-on electrodes using a scalpto-scalp montage F4C4, C4-02, F3-C3, and C3-01 with an Elema Mingograph on paper. The cables were fixed with gauze to avoid movement artifacts. The amplified EEG was recorded simultaneously on tape with a Racal 4D four-channel instrumentation tape recorder (frequency band DC to 30 Hz). The EEG was recorded for the first 18 min in the exposure chamber and included the total period of 10 min with exercise and 3-4 min after exercise ended. The afternoon exposure commenced with a similar EEG recording. In addition, the EEG was recorded for 5 min on two occasions in the chamber, i.e., 1 and 2 h after the subject had entered the chamber. The last 5 m i n EEG recording of the day occurred 45 min after the afternoon exposure had ceased. The morning and afternoon exposure sessions started with a similar 18-min recording, even when no exercise was performed. The subjects always sat on the bicycle ergometer, fitted with a special backrest during the recordings, and had their eyes closed. The timing of the EEG recordings during the exposures are presented in Figure 1. The paper recordings were checked visually, and 1-min periods with the least artifacts were chosen for computer analysis. The periods chosen were: (1) before exercise; (2) 1 min after starting exercise; (3) 3 min after starting exercise; (4) 5 min after starting exercise; (5) 9 min after starting exercise; (6,)2 min after exercise stopped; (7) and (8) during a 5-min recording 1 h after exposure started; (9. and 10.) during a 5-min recording 2 h after 18
exposure started; (11.-16.) in the afternoon, during which recordings (1.) through (6.) were repeated; and (17. and 18.) during a 5-min recording taken 45 min after exposure ceased. Computer analysis of the 18-min recordings was completed at the same time points for subjects who exercised and for those who did not. The computer analysis was performed off-line in 5-s epochs, and a compressed analysis was based on 12 epochs (60 s). The analysis provided the percentage of delta (1-3.9 cps, frequencies lower than 1.0 cps were omitted), theta (4-7.9 cps), alpha (8-13 cps), and beta (13.1-25 cps) activity; the dominant (mode) frequency in each band; and an absolute power in each band. Collection and analysis of blood samples. A teflon catheter was inserted into an antecubital vein prior to the exposure, and venous blood samples were drawn for m-xylene measurements during the exposure and after the subjects had left the chamber. Blood samples were collected at specified time intervals following the EEG recordings. Venous blood concentrations of m-xylene were analyzed by gas chromatography.” Statistical analysis. Statistical analysis was performed using either t tests or two-way analysis of variance (ANOVA). In the statistical analysis of the data, the means of the subjects on each analysis point were accounted for. Results in the exposure situations were first compared with results obtained on the equivalent control day, i.e., results of an exposure day with exercise were compared with the control day with exercise, and those of a sedentary exposure were compared with results of a sedentary control day. Student’s t test for matched pairs was used in that statistical analysis. This was done for all variables and situations. The two-way ANOVA was then applied when examining the effects of exercise, exposure, and their interaction with the EEG data for the time point in question. This was done for only those variables and situations where it was supposed that the null hypothesis could be rejected based on the t test results. Because comparisons were always done for control days with similar time schedules, a pre-exposure EEG recording each monring was considered unnecessary.
Results The dominant frequency of the alpha activity measured with the centro-occipital leads fluctuated during the day (Fig. 2). During the first minute of exercise in the morning, a rise in the alpha frequency for 0.3 c/s occurred when exposure to the stable and peak concentrations occurred. No such early rise occurred on the control days; the dominant frequency remained at 9.85 c/s. This difference was statistically significant @ < .05, t test) when 200 E and 400 P+E were compared with control E. In the samples that followed during the first 20 experimental min, an increase in the alpha frequency was noted in all situations. In the recordings made later in the morning session, the alpha frequency tended to stay at a higher level during m-xylene exposure than on the control days. For the recording made 45 min after exercise ceased, the alpha frequenArchives of Environmental Health
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Fig. 2. Variations of dominant alpha frequency (mean of 9 subjects) in the centroacipital leads during various exposures to m-xylene. 400 P + E = exposure to 400 pprn peaks combined with exercise, 200 E = exposure to stable concentration of 200 ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = control session at rest.
cy was higher during exposure (p < .01 for 200 E and p < .05 for 400 P+E, t test) than on the corresponding control day. During the beginning of the afternoon session, the alpha frequency was higher in exposure than in control situations (p < .05 for the first recording and p = .06 at 8 min from restart of exposure, ANOVA). In the peak exposures (400 R and 400 E), an early rise of the alpha frequency was again noted (for 0.25 and 0.35 ds, respectively), but the resulting dominant frequency did not differ significantly from the others. The alpha frequency stayed higher during m-xylene exposure, but it differed significantly from the corresponding control day only at the end of the exercise @ < .05 for 200 E and p < .005 for 400 P+ E, t test). After exposure ceased in the afternoon, the alpha frequency dropped toward the same level in each situation. In the centro-occipital leads, the percentage of alpha activity decreased immediately after exercise commenced, but rose to a higher level during exposure situations with exercise (Fig. 3). Analysis of variance indicated that the change in alpha percentage was related to exercise during the first minutes of both the morning and afternoon sessions (p < .001 and < .05 at 3 min after exercise started, respectively). At the end of the exercise periods, these effects appeared to be related to solvent exposure; at 9 min after exercise started (or 14 min after exposure commenced), the alpha percentage was higher when exposure occurred (p < .01, ANOVA) during both the morning and afternoon sesJanuary/February 1991 [Vol. 46 (No. l)]
sions. After 2 h exposure in the morning, the alpha percentage was correlated to either solvent exposure @ < .05,ANOVA) or interaction of exposure and exercise @ < .05,ANOVA). When considering only exposures combined with exercise versus the control day, the clearest differences were noted 2 h after exposure started (p < .005,t test) and, if exposed to the peak concentration, at the end of the afternoon exercise period (p < .05,t test). In the frontocentral leads, the theta percentage rose at the beginning of exercise in the morning and afternoon (Fig. 4). This was correlated to exercise @ < .05, ANOVA, at 3 min after exercise started), but the theta percentage for 200 E was often lower than that for control E. For all afternoon recordings, the theta percentage was statistically significantly @ < .05-.005,t test) lower for 200 E than for control E. At and following cessation of exercise, the theta percentage dropped; the drop was more acute when accompanied by exposure. In the afternoon at 14 min after restarting the exposure (and the last minute of exercise), the theta percentage was significantly lower during m-xylene exposure @ < .01, ANOVA). Similarly, in the centrooccipital leads the theta percentage was lower during exposure, both in the morning and in the afternoon at recordings 14 min after exposure started @ < .01 and p < .02,respectively, ANOVA). The same was noted 30 rnin after cessation of exposure @ < .05,ANOVA). In the centro-occipital leads, exercise was not significantly correlated to the theta percentage. 19
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Fig. 4. Variations of theta percentage (mean of 9 subjects) in the frontecentral leads during various exposures to m-xylene. 400 P + E = exposure to 400 ppm peaks combined with exercise, 200 E = exposure to stable concentration of 200 ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = contml session at rest.
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When stable and fluctuating exposure types were combined with ergometer exercise in the beginning of the sessions, the blood m-xylene concentration reached the maximum in 15 min-at the time point when the exercise stopped (Fig. 6). The highest blood m-xylene concentration during the morning session was 43 14 pmol/l in 200 E and 72 f 14 pmolll in 400 P+E. These levels were about 2.5 times higher than in corresponding exposures at rest, which were 17 5 pmol/l in 200 R and 27 f 6 pmol/l in 400 P + R. The blood m-xylene concentration declined rapidly after exposure periods with exercise; consequently, after a 60-min exposure, the concentration range of m-xylene for all exposures was 24-34 pmolll. During the afternoon sessions, the blood m-xylene concentration was 10-30% higher than during the first 40 min of the corresponding morning sessions. There were no marked differences between different exposure patterns in the post-exposure concentrations.
In the centro-occipital leads, the absolute delta power increased during exercise, especially for 400 E and control E (Fig. 5). The difference, when compared with sedentary situations, was statistically significant @ < .05, ANOVA) at 9 min after exercise started. The highest delta power was noted in control E during the last minute of exercise when exposure decreased the delta power (p = 0.52,ANOVA). At that time, the delta percentage was significantly lower when accompanied by exposure (p = .02,ANOVA). After exercise ceased, the delta power clearly decreased. In the fronto-central leads, delta activity (and theta activity) often increased during exercise, and 400 ppm P + R showed similar trends. Beta activity in the frontal and occipital areas varied slightly during the study, but no relevant relationships between exposure and exercise paradigms and beta activity were detected. m-Xylene in venous blood. The time course of m-xylene concentration in venous blood was different in the varying exposure types. There was a continuous build-up of m-xylene concentration in 200 R, followed by a leveling off to 31 7 pmol/l toward the end of the morning session (Fig. 6). In exposure 400 P+R, the blood m-xylene concentration rose more rapidly at the beginning of the morning session and reached about 40% higher levels than in 200 R, but then declined slightly after the baseline concentration in the chamber decreased toward the end of the morning session.
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Discussion Although EEG can be analyzed quantitatively with computer techniques-and these techniques have been widely applied to pharmacologic drug studies in humans and animals-quantitative EEG studies are scarce concerning chemicals in the ~ o r k p l a c e . 'More~ over, no quantitative EEG studies during combined sol-
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January/February1991 [Vol. 46 (No. l)]
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Fig. 6. Mean blood levels (9 subjects) of mxylene during various exposure models. Venous concentrations are given for the morning (0-180 min) and afternoon (220-260 min) exposure sessions and post-exposure (290 min). 400 P + E = exposure to 400 ppm peaks combined with exercise, 200 E = exposure to stable concentration of 200 ppm combined with exercise, control E = control session with exercise, 400 P + R = exposure to 400 ppm peaks at rest, 200 R = exposure to stable concentration of 200 ppm at rest, and control R = control session at rest.
vent exposure and exercise have come to our attention. We report results from an exposure chamber study designed to examine central nervous system effects related to rapid environmental changes during single-day m-xylene exposure using quantitated EEG. The exposure fadors are relevant because they are common in the workplace. Physical exercise has been suggested as a provocative method to enhance EEG signs of cerebrovascular disorder, and, indeed, a prolonged decrease of alpha frequency after physical exercise was shown in 5 of 10 patients with a history of cerebrovascular accident and among 3 of 10 normal subjects who were older than 50 y.I4 Conversely, normal young subjects usually showed an increase in alpha frequency after exercise, as did 6 of 10 older control:; and some patients. In the present study, exercise, which increased ventilation and perfusion but did not cause actual hyperventilation, induced changes in the EEG. Theta percentage in the frontal areas increased during exercise and decreased shoirtly after exercise stopped. Similarly, absolute delta power and delta percentage increased during exercise. Frequencies less than 1 cps were omitted from analysis; therefore, brain activity was measured rather than movement or other artifacts with our well-secured electrodes. Changes in theta and delta activity were more prominent in the control and peak exposure situations; at the end of the exercise period, exposure appeared to attenuate these EEG ef22
fects. In fact, exposure seemed to account for the lowering of the theta percentage close to the end of exercise and at the moment when the highest blood m-xylene concentrations occurred. Similar effects were noted for sedentary situations. Exposure during the early phase in the morning increased the alpha activity, and higher alpha frequencies were also noted 1 h after initiating exposure in sedentary and exercise conditions. Similar higher alpha frequencies were noted in exposure paradigms at the end of the afternoon exposure. Changes resulting primarily from m-xylene exposure were minor, which indicates slight alpha activation (i.e., increased percentage and higher frequencies of alpha) toward later phases of exposure. These effects are diametric to those of ethanol, which decreases the alpha frequen~y.'~-'~ Smoking tobacco prior to or during alcohol consumption counteracted this alcohol effect on the EEG." An alcohol dosage of approximately 0.3 mllkg increased alpha abundance,Ig which is similar to the increased alpha percentage in the present study. A biphasic effect of alcohol on the alpha activity has also been reported: during the absorption phase, alpha activity increased as was accompanied by a concomitant decrease in delta and theta activity, whereas in the elimination phase, alpha activity decreased." Alpha activity increased during transient episodes of ethanol-induced euphoria." In a previous study, where the exposure patterns to m-xylene were different and Archives of Environmental Health
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visually analyzed EEGs were recorded 20 min after physical exercise, an increase in occipital slow transients was noted in a few subjects while being exposed to varying concentrations of m-xylene.’ The exposure situations in that study differed greatly from the present study; therefore, direct comparisons are not possible. Trichloroethylene, another industrial solvent, has induced similar effects as reported in our study for m-xylene. During exposure of 20 volunteers to 95 ppm of trichloroethylene, the alpha percentage (as measured with recording lengths with alpha activity) increased significantly from the pre-exposure level after 1 and 2 h of exposure.22When paper recordings taken before and after trichloroethylene exposure for 4 h were compared,23no statistically significant differences emerged for the alpha amplitude, the mean alpha frequency, or in the percentage time alpha. Three of six healthy workers who had long-term occupational exposure to trichloroethylene experienced activated alpha activity during a workshift when occupational exposure to trichloroethylene occurred. Trichloroethylene concentrations in blood (2.6-3.25 pg/ml) were high among those with alpha activation; however, the workers with no detectable change in their EEG had lower trichloroethylene concentrations in their blood and atmospheric air.22During a 4.5-h exposure to 3.2 mmol/m3 of toluene only or in combination with 15 mmollkg of ethanol, no changes were found in the EEGs of 12 male volunteers when EEGs were subjected to spectral analysis.24 Toluene, however, produced symptoms such as headache, local irritation, and a mildly depressed heart rate and ethanolimpaired performance in two of four performance tests and effected an increased heart rate. Long-term effects of solvents on EEG may be similar to effects observed in the present acute exposure. Automatized EEG frequency analysis in exposure-free situation has revealed that the EEGs of car and industrial painters occupationally exposed to solvents have higher alpha powers, smaller alpha band widths, lower delta powers, and larger delta band widths than do the EEGs of their referents. The painters were exposed to solvent levels that were approximately 30% of the contemporary hygienic limit values. However, no statistically significant differences were found between the two groups.25When the EEGs from a group of 32 men with clinically diagnosed chronic toxic encephalopathy after long-term occupational solvent exposure were submitted to power spectrum analysis, the absolute power within each frequency range was much higher than that among a control group of 50 men who had not solvent exposure in the workplace.26 Spectral analysis of EEGs among 50 workers exposed to solvents during paint production showed significant differences when compared with 50 pairwise matched referents employed in a sugar refinery.*’ The power of beta activity was greater among the exposed subjects. No relevant changes in beta activity were noted in the present experimental study. Because exercise clearly induced EEG changes in the present study, and some of those were counteracted by m-xylene exposure, one wonders about the contribuJanuary/February1991 [Vol. 46 (No. l)]
tion of mild physical stress and chemical exposure. The present study did not analyze individual results, and the individual effects may vary in type and degree. No deleterious effects of exposure could be detected during this type of m-xylene exposure. However, the effects of xylene during long-term occupational exposure and among elderly workers may be different. Thus, no direct conclusions can be drawn concerning possible effects of long-term xylene exposure on the EEG. EEG effects similar to those reported in our study, i.e., increased alpha activity and decreased theta and delta activity, have been observed during the alcohol absorption phase and have been attributed to the stimulating or excitatory effects of alcohol.20Thus, the minor differences between exposure and control conditions in our study probably suggest stimulating or excitatory effects of low-level, short-term exposure to m-xylene. Alternatively, the increased alpha percentage could be associated with a more relaxed state of the subjects; this could indicate that sedative effects of m-xylene counteract the alerting effect of physical exercise. Because the alpha percentage decreased during exposure absent exercise and because the alpha frequency increased during exposure, it is probable that m-xylene stimulates these effects during exposure.
********** This study was supported, in part, by Finnish Work Environment Fund, Helsinki. Submitted for publication February 24, 1990; revised; accepted for publication June 18, 1990. Requests for reprints should be sent to: A. M. Sepplainen, Division of Clinical Neurophysiology, Department of Neurology, University of Helsinki, Haartmaninkatu4, SF-00290 Helsinki, Finland.
********** References 1. National Institute for Occupational Safety and Health (NIOSH). Criteria for a recommended standard: occupational exposure to xylene. Cincinnati, OH: U S . Department of Commerce. National technical information services; 1975. 2. Browning E. Toxicity and metabolism of industrial solvents. Amsterdam: Elsevier; 1965. 3. Longley, EO, Jones AT, Welch R, Lomaev 0. Two acute toluene episodes in merchant ships. Arch Environ Health 1%7;14 481-87. 4. Camberale F, Lisper HO, Anshelm Olson 8. The effect of styrene vapour on the reaction time of workers in the plastic boat industry. in: M Horwath, Ed., Adverse effects of environmental chemical and psychotropic drugs. Vol. 2. Amsterdam: Elsevier, 1976; pp. 135-48. 5. Cherry N, Venables H, Waldron HA. The acute behavioural effects of solvent exposure. J Soc Occup Med 1983;33:13-18. 6. Anshelm Olson B. Effects of organic solvent on behavioral performance of workers in the paint industry. Neurobehav Toxicol Teratol 1982;4703-08. 7. Canberale F, Annwall C, Hultengren M. Exposure to xylene and ethylbenzene. 111. Effects on central nervous functions. Scand J Work Environ Health 1978;4204-11. 8. Savolainen K, Riihimaki V, Linnoila, M. Effects of short-term xylene exposure on psychophysiological functions in man. Int Arch Occup Environ Health 197944:201-11. 9. Savolainen K, Riihimaki V, Sepplainen AM, Linnoila MG. Effects of short-term m-xylene exposure and physical exercise on the central nervous system. Int Arch Occup Environ Health 1980;45: 105-21. 10. Riihimaki V, Savolainen K. Human exposure to m-xylene.
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223-29. 17. Zilm DH. Ethanol-induced spontaneous and evoked EEG, heart rate, and respiration rate changes in man. Clin Toxicol 1981; 18:549-63. 18. Knott VJ, Venables PH. EEC alpha correlates of alcohol consumption in smokers and nonsmokers: effects of smoking and smoking deprivation. J Stud Alcohol 1979;40:247-57. 19. Docter RF, Naitoh f', Smith JC. Electroencephalographic changes and vigilance behavior during experimentally induced intoxication with alcoholic
