Print ISSN: 0355-3140 Electronic ISSN: 1795-990X Copyright (c) Scandinavian Journal of Work, Environment & Health

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Original articleScand J Work Environ Health 1976;2(4):240-255 doi:10.5271/sjweh.2805

Behavioral effects of long-term exposure to a mixture oforganic solvents.by Hänninen H, Eskelinen L, Husman K, Nurminen M

Key terms: behavioral effect; exposure; long-term exposure; organicsolvent; solvent; toluene

This article in PubMed: www.ncbi.nlm.nih.gov/pubmed/798266

Scand. j. work environ. & heaUh 4 (1976) 240-255

Behavioral effects of long-term exposureto a mixture of organic solvents

by HELENA HANNINEN, L.Ph., LEENA ESKELINEN, M.A.,KAJ HUSMAN, M.D., and MARKKU NURMINEN, L.Sc.1

HANNINEN, H., ESKELINEN, L., HUSMAN, K. and NURMINEN, M. Behavioraleffects of long-term exposure to a mixture of organic solvents. Scand. j. workenviron. & health (1976) 240-255. The behavioral effects of long-term exposureto a mixture of organic solvents were investigated in a comparison of the test resultsof 100 car painters with those of a reference group. The test battery included testsfor intelligence, memory, psychomotor performances, and personality. In addition tothe comparison of the mean results, two discriminant function analyses were made.In one, only the performance test variables were used, but in the other personalityvariables were also included. The results indicated impairments in psychologicalperformances, as well as personality changes in the ,exposed group. Impairments invisual intelligence and verbal memory and a reduction of emotional reactivity werethe central features of the adverse effects of solvent exposure, but the behavioraldisturbances also involved several other functions, including performance on a verbalintelligence test. The possible role of the differences in the initial intelligence levelswere controlled with a separate comparison of the test results of 33 pairs of exposedand nonexposed subjects who were matched for age and for their intelligence level,measured during the military service. The discriminant function analyses were basedon the results of these matched subgroups and tested in the rest of the material.According to the results the sensitivity of the psychological test methods was high,but the specificity somewhat low, with regard to solvent exposure. The concentrationsof various solvents induded in the exposure of car painters were low, the summatedexposure corresponding to 32 Ofo of the Finnish threshold limit value. The possiblerole of a potentiating effect of the solvent in the development of behavioral distur­bances is discussed.

Key words: solvents, toluene, behavioral effects, long-term exposure.

Many industrial solvents are known tohave neurotoxic effects, and therefore theyare also capable of causing behavioraleffects.

More is known about the effects ofacute solvent exposure on humans thanabout long-term effects. More is alsoknown about the effects of pure expo­sures than about the effects of mixed

1 Institute of Occupational Health, Helsinki,Finland.

Reprint requests to: Ms. Helena Hanninen,Institute of Occupational Health, Haartma­ninkatu 1, FIN-00290 Helsinki 29, Finland.

240

ones, which, however, are a very commonform of occupational hazard.

Toluene, for instance, has been ratherintensively studied by behavioral methodswith regard to both its acute and long­term effects. Exposure to low concentra­tions has not been found to cause changesin performances, but exposure to higherconcentrations affects reaction times andthe speed of perception (13, 26, 27, 37).Moreover, toluene causes changes in sub­jective experiences and feelings (6, 26).

In experimental studies the behavioraleffects of a short exposure to dichloro­methane (35), trichloroethylene (30, 31, 37),

Exposure

TabLe 1. The exposure times of the car paint­ers in Helsinki and of the examined sample.

Solvent concentrations in the air weremeasured in six randomly selected carrepair garages, in which a total of 40 carpainters were employed. On the averagethe car painters used three liters ofpaint and solvent and spray-painted5 m 2 a day.

The paint binders were mainly nitrocel­lulose, alkyd, acrylic, carbamide, or ureth­ane resins. The solv,ents and thinnerswere aromatic hydrocarbons (toluene,

ers in Helsinki (N = 166) by the stratifiedsampling method so that subjects withvarious exposure times would be equallyrepresented. The exposure times of theHelsinki car painters and the examinedsample are presented in table 1. The sub­jects' exposure times varied from 1 to 40years (mean 14.8, SD 8.5); and their age,from 20 to 65 years (mean 35, SD 11).

The nonexposed reference group waschosen from the employees of the FinnishState Railways so that the ages of thesubjects were matched within 1 to 2 years.About half of the group consisted ofengineers and the other half of locomotiveassistants. Noise, vibration, irregular shiftwork, and mental stress are the mostimportant railroad work factors whichmight have had a possible effect on thepsychological functions tested.

Two of the 102 car painters were ex­cluded from the sample because of braindamage of other etiology, and one locomo­tive engineer refused to participate in thepsychological examination. Thus the finalsample consisted of 100 exposed and 101nonexposed subjects.

Car painters Car painters inin Helsinki the sample

Exposure time(years)

methylchloroform (14), methylene chloride(17, 36), styrene (15), and white spirit (16),among others, have also been investigated.Most of these studies have concerned dis­turbances in psychomotor and visual func­tions or disturbances in vigilance.

The documentation of the behavioraleffects of long-term exposure to solvents ismore scanty. There are some resultsindicating that exposure to trichloroethy­lene and other solvents impairs memoryand causes neurotic symptoms (7, 8), thatexposure to styrene causes disturbancesin visuomotor accuracy and psychomotorperformance (18, 23), and that some per­formances of house painters exposed todifferent mixtures of solvents are im­paired (2). In addition widespread dis­turbances in psychological functions havebeen found in workers who are exposedto solvents and have been verified asbeing, or suspected of being, poisoned orwho are considerably exposed at work(22).

Although the results of earlier investi­gations have been somewhat inconsistent,they indicate that solvents affect manypsychological functions simultaneouslyand cause impairment of several per­formances, as well as subjective changes inthe domain of emotions, moods, and feel­ings. Impairment of visual functions andvisual intelligence and changes in the vigi­lance level seem to be the central featuresof the psychological effect of solvents.Results concerning disturbances in psy­chomotor functions or impairments ofverbal intelligence are rarer. Memory andlearning abilities have not been greatlyinvestigated in recent studies, even thoughthe impairment of memory is known to bevery central in the subjective symptoma-tology of exposed subjects. .

This report deals with the psychologicalchanges that occur in car painters exposedto a mixture of organic solvents. Toluenewas the most important component of theexposure in question.

MATERIAL AND METHODS

Subjects

The exposed group consisted of 102 carpainters from 27 car repair garages. Thesample was chosen from all the car paint-

1- 56-10

11-1516-2021-25~26

Total

374445151114

166

212119151113

100

241

xylene), aliphatic hydrocarbons (whitespirit), alcohols (ethanol, isopropanol, buta­nol), esters (ethyl acetate, buthyl acetate,ethyl glycol acetate), ketones (acetone,methyl ethyl ketone, methyl isobutylketone), and terpenes (pinene). The restof the paint was composed of pigmentsand fillers (organic and inorganic dyes,zinc chromates, titanium dioxide, talc),catalysts (phosphoric acid), plasticizers,siccatives, and antiskinning agents.

During spray-painting the paint and thesolvent are nebulized by means of COllll­

pressed air, and the workers are thereforeexposed to vapors and particulate aerosols.In the course of the study the 27 car repairgarages were visited and, in general, thespray-painting of cars took place in effi­ciently ventilated chambers. Duringspraying, which took 1 to 2 h per day, theworkers wore a filter mask. The air ofthe workroom was contaminated by sol­vent vapors and paint dusts from the prim­ing, grinding, and cleaning of surfacesfor painting and occasionally by exhaustgases containing carbon monoxide, nitro­gen oxides, and soot. On the average thecarbon monoxide concentration was low(0-20 ppm).

The median age of the car repair shopswas 15 years, and the ventilation installa­tions were, on the average, about 10 yearsold.

TabLe 2. Mean concentrations of organicsolvents in the breathing zone of 40 carpainters. (Sampling period = 1 h; number ofcar repair garages = 6; number of samples =54)

Mean Percentageconcen- TLyaSolvent tration of the (ppm)

(ppm) TLya

Toluene 30.6 15.3 200Xylene 5.8 5.8 100Buthyl acetate 6.8 4.5 150White spirit 4.9 2.5 200Methyl isobuthyl

ketone 1.7 1.7 100Isopropanol 2.9 0.7 400Ethyl acetate 2.6 0.7 400Acetone 3.1 0.3 1,000Ethanol 2.9 0.3 1,000

Total 31.8

a TLy = threshold limit value.

242

The mean solvent concentrations in theambient air are presented in table 2. Theaverage of the sum of the percentage was31.8 Ofo of the Finnish threshold limit value(TLV) for solvent mixtures. The range ofseparate components was 4 to 212 Ufo of theTLV. The variation, with time, of the 1-haverage concentrations during a workdaywas evaluated by repeated sampling. Theaverage standard deviation of the loga­rithms of the sum of the percentages was0.27.

There were no marked differences inwork conditions and 'Solvent exposuresbetween the six car repair garages sincethe work methods, equipment, and paintsused were essentially the same. Therefore,the six car repair garages were represent­ative of the 27 car repair garages visited.

For the elimination of acute effects thetest battery was always administered atleast 16 h after the cessation of the lastexposure.

Psychological methods

The psychological examination of the sub­jects was performed in conjunction withmedical examinations performed by aneurologist, a neurophysiologist, a neuro­ophthalmologist, and an occupationalhealth physician.

The test battery was chosen accordingto the following principles: (a) the meth­ods should cover a broad range of variouspsychological functions; (b) especiallytasks measuring various aspects of memoryand psychomotor functions should beincluded; (c) the test battery should con­tain tests used previoU'sly in toxicopsy­chological investigations; (d) the testsshould be easy to administer and suitableeven for use in routine health examina­tions of workers exposed to solvents andfield investigations. Hence stationaryequipment was not used, reaction tiImemeasurements being the only exception.

The test battery contained one test forverbal intelligence, three visual tests, fourmemory or learning tasks, four tests ofpsychomotor performances, and the Ror­schach test for measuring personalitychanges.

The psychological tests and variables usedin the statistical analyses

Similarities (Sim) from the WechslerAdult Intelligence Scale (WAIS) (33) wasused for the measurement of verbal intelli­gence and abstraction. There was no timelimit.

Picture Completion (PC) from the WAISwas used for the measurement of visualintelligence and observation. There wasno time limit.

Block Design (BD) from the WAISmeasured visual intelligence and abstrac­tion. Each subtask had a time limit.

Figure Identification (FI) (11) measuredspeed of perception and memory for visualdetails. The time limit was 5 min, andthe number of attempted tasks was usedas the variable for the speed of percep­tions.

Digit Span (DSp) from the WAIS andthe WMS (Wechsler Memory Scale) (32)measured the subjects' memory for digits.As the digits must be recalled both for­wards and backwards, the test demandsattention and concentration.

Logical Memory (LogM) from the WMSmeasured verbal memory. The task(recalling a short story) demands theability to concentrate on spoken verbalmaterial and recall it.

Associate Learning (AssL) from theWMS was used for the measurement ofverbal memory and learning. It consistsof 10 pairs of words to be learned duringthree trials. Before each trial, the wordpairs are read to the subject, and thesubject has to recall the second word whenhe hears the first one.

The Benton test for visual reproduction(Ben repr) was used for the measurementof visual memory (1). In this test thesubject must draw one or three simplefigures after a 10-s presentation. Thetest contained 10 subtasks. The test scorewas the number of correctly drawn fig­ures.

The Benton test for visual retention(Ben ret) was used. After seeing a testdesign containing one or three figures,the subject has to recognize it among fourdifferent designs. The test contains 10subtasks.

The Santa Ana Dexterity Test (12)measures the subjects' psychomotor speed.It demands both eye hand coordination andcoordination between the movements ofthe wrist and fingers. A separate scorewas given for the performance of theright (SA right) and left (SA left) handsand for the coordination of two hands (SAcoo).

Finger tapping measures motor speed.It was performed with a simpJe counter.The subject had to tap it with the thumbas fast as possible. A separate score wasgiven for the performances of the right(FT right) and left (FT left) hands (sum oftappings during four 10-s trials).

Reaction times were measured by reac­tion time measuring equipment construct­ed at the Institute of Occupational Health,Helsinki. In the task the subject reacts tovisual signals by pressing a bar with theright or left hand. The signals are present­ed randomly with 2-, 4-, or 6-s intervals.

The subjects performed simple reaction­time tasks separately with the right (RTright) and left (RT left) hands. The scorewas the cumulative time for 40 reactions.

In the choice reaction time (RT choice)task there are three visual signals, i.e.,three separate lights placed on a panel.The subject has to react to the light on theright side with the right hand, to the lighton the left side with the left hand, and notto react to the light in the middle. Therewere 25 signals in incidental order with2-, 4-, or 6-s intervals. The ordinarytask was preceded by an exercise trial.The score was the cumulative time forreactions in the ordinary task.

In addition the Mira test (20, 25) wasused as a test for psychomotor behaviorand psychomotor ability. The task is todraw a simple pattern without optic con­trol, i.e., without seeing the paper andpencil. In the staircase subtask used thesubjects have to draw stairs first upwardsand then, without looking, continue withdownward stairs so that an angle of 90degrees is formed. The drawing is madeseparately with the right and left hands.The test demands the learning and master­ing of simple motor patterns and thecontrol of hand movements. Two vari­ables were used. One indicated the size ofthe stairs; and the other, the form level ofthe performance. The size of the stairs

243

(Mi size) was measured as the number ofstairs in a distance of 8 em. For the formlevel (Mi form) 1 to 4 points were given,depending on the qualitative aspects of theperformance.

Personality was investigated by theRorschach personaLity test (21). Using itsvariables in statistical analyses is knownto be a problem because of the relativesubjectivity of the scoring and the highintercorrelations between the scores usedin clinical practice. Five variables wereused that had been developed earlier byone of us (H.H) (20). They are supposedto measure adaptability (Ada), emotional­ity (Emo), spontaneity (Spon), rationalself-control (Rat), and originality of per­ception (Orig). In addition three vari­ables were included that were based on thecontent analyses of the answers developedby DeVos (10), namely, hostility (Host),anxiety (Anx), and bodily preoccupation(Bod Pre), and also the number of re­sponses (R), rejections (Rej), and the aver­age latency times (rt) were included asseparate variables.

The Mira test and the Rorschach testwere scored blindly by two independentpsychologists. In cases of divergent scoresa third independent psychologist acted asa referee.

In order to control the possible effects ofdifferences in the initial intelligence levelson the results, we used psychological testresults recorded during the subjects' mili­tary service as the estimation of the initialintelligence levels. All subjects had notbeen tested during their military 'service,however, because the tests were not ad­ministered regularly until after 1958. Itwas, however, possible to form 33 pairsmatched both for age and for the intelli­gence level recorded during military ser­vice, i.e., at the age of about 20 years. Themilitary test battery consisted of threefactor tests measuring different aspects ofintelligence. In our study the total scorewas used. For the car painters this in­telligence score represented in principletheir performance level before exposure,although some of them had been employedin car painting garages already beforetheir military service. The mean exposuretime after the earlier psychological ex­amination for the 33 car painters was 7.4years (± 4.1 SD). The mean age was 27years.

244

Additional data about the subjects weregathered with a questionnaire and a struc­tured interview. One part of the question­naire concerned the subjective symptomsof the subjects. A detailed report on thevalidity of subjective symptoms with re­gard to the effects of solvents will be givenelsewhere. In the present study we com­pared the psychological findings with thefollowing subjective symptom complexes:sleep disturbances, fatigue, disturbances ofmemory and vigilance, absentmindedness,emotional lability, and neurovegetativelability.

StatisticaL methods

The statistica:l analyses of psychologicaldata contained several steps.

First the differences in the mean levelsof the test scores between the age-matchedexposed group and the reference groupwere examined. The same mean levelcomparison was also performed with re­gard to the smaller subgroup of pairs fur­ther matched with respect to initial in­telligence level, as indicated by test re­sults recorded during military service.

In the evaluation of the effect of thepairwise matching procedure, correlationcoefficients for all the contemplated testvariables between the compared groupswere calculated.

When matching resulted in a high posi­tive correlation, a t-test for paired datawas employed; otherwise in the signifi­cance testing the two groups were treatedas stochastically independent series. In thelatter case two different situations wereencountered. In one we could assumethat the population variances were equalin the groups and therefore applied theordinary Student's t-test for the two setsof observations. In the other the variancehomogeneity condition was not obtained,and we applied an approximate t-test, ,ac­cording to Welch (34), which modified thedegrees of freedom of the t-distribution.In both cases a bilateral testing was used.

The norma:lity of the sampling distribu­tion of the psychological test scores wasassessed through visual inspection only.Those data which did not display thecharacteristic features of a normal distri­bution pattern, i.e., symmetrical unimodaldistribution, with few extreme values on

either tail (sigmoid cumulative distribu­tion function) were either discarded ordichotomized and tested by a paired chi­square test for a fourfold table (24).

The linear combination of variables dif­ferentiating best between the exposed andnonexposed subjects was searched forby multiple discriminant analysis accord­ing to the technique reported by Cooleyand Lohnes (9). The analysis was based onthe results of the matched subgroups,which were formed from subject pairsindividually matched with regard to bothintelligence and age.

The solvability of the eigenvector v,which maximizes the mean differencebetween the populations, was assured inthe within-groups or W-metrics by thecondition v'Wv = 1. Since the discriJrninantfunction was not only used for the separa­tion of the two groups, but also for themeasurement of the distance betweenthem, the eigenvectors were normed byletting the length of the vector v equalunity or

,-------Ilvll = 'J V1

2 + vl + V32 = 1.

So that the relative contributions of thetest variables to the discriminant functioncould be found, these normalized vectors

were scaled by multiplying them with thesquare roots of the corresponding diagonalelements of matrix W. The numericalvalues of the discriminant function wer,eobtained from the standardized variahles,i.e., the variables were expressed in astandard measure (zero mean, unit vari­ance), whence also the expected value andthe variance of the total sample discrimi­nant function score equal zero and unity,respectively. In the test for the appli­cability of the discriminant function, dis­criminant score values were calculated forall subjects and used for the assignmentof the subjects to the groups to which theymost probably belonged according to theirtest results.

RESULTS

Differences in performances

Table 3 presents the mean performancesand their standard deviations for bothgroups (with the group sizes N = 100 and101), as well as the probabilities for suchdifferences occurring by chance.

Table 4 presents the data obtained in thecomparison of the pairs matched for initialintelligence and age (N = 33/33).

Table 3. Performance tests: means, standard deviations and significances between the groupmeans (age-matched groups).

Means and standard deviationsTest

Exposed (N = 100) Nonexposed (N = 101)

Significancesof differences

(t-test)

SimPCBDFIDSpLogMAssLBen reprBen retSA rightSA leftSA cooFT rightFT leftRT rightRT leftRT choiceMi sizeMi form

19.4 ± 3.114.9 ± 2.934.6 ± 7.032.0 ± 9.010.6 ± 1.611.7 ± 3.715.3 ± 3.621.1 ± 3.1

8.2 ± 1.544.7 ± 5.742.3 ± 5.429.0 ± 5.4

202.5 ± 29.2186.7 ± 28.512.4 ± 2.912.1 ± 3.0

9.1 ± 1.8

18.8 ± 3.82.2 + 1.0

2.9 ± 2.116.2 ± 2.339.6 ± 5.636.7 ± 9.811.5 ± 1.813.9 ± 3.117.1 ± 2.622.6 ± 2.3

8.7 ± 1.347.5 ± 5.843.6 ± 5.131.5 ± 5.7

209.6 ± 23.8196.4 ± 22.4

11.9 ± 1.411.7 ± 1.4

9.1 ± 1.2

20.3 ± 4.62.0 + 0.8

***************************

**

*

a***

a Paired t-test.* p < 0.05; ** p < 0.01; *** p < 0.001.

245

Table 4. Performance tests: means, standard deviations and significances between the groupmeans (groups matched for age and initial intelligence).

TestMeans and standard deviations

Exposed (N = 33) Nonexposed (N = 33)

Significancesof differences

(t-test)

SimPCBDFIDSpLogM

AssLBen reprBen retSA rightSA leftSA cooFT rightFT leftRT rightRT leftRT choiceMi sizeMi form

a Paired t-test.* p < 0.05; ** P < 0.01.

19.2 ± 2.815.3 ± 2.9

36.1 ± 6.735.9 ± 10.810.8 ± 1.612.6 ± 3.5

15.4 ± 3.321.8 ± 2.7

8.3 ± 1.547.4 ± 4.644.4 ± 4.630.8 ± 5.3

207.3 ± 23.7192.2 ± 22.011.5 ± 1.611.5 ± 1.6

8.6 ± 1.019.6 ± 4.1

1.9 ± 1.0

20.7 ± 2.216.4 ± 1.8

40.8 ± 5.640.6 ± 10.511.8 ± 1.714.2 ± 3.2

17.1 ± 2.822.9 ± 2.2

8.9 ± 1.149.1 ± 6.345.4 ± 4.833.2 ± 5.5

216.4 ± 19.5202.9 ± 19.8

11.6 ± 1.411.4 ± 1.6

8.6 ± 1.321.5 ± 4.8

1.9 ± 0.8

*a

***

**

a*

*

Table 5. Personality variables: means, standard deviations and significances between the groupmeans (age-matched groups).

Means and standard deviations SignificancesVariable of differences

Exposed (N = 100) Nonexposed (N = 101) (t-test)

R 13.6 ± 6.4 13.8 ± 4.5

0.7 ± 1.1 0.4 ± 1.0b

Rej **rt 16.4 ± 8.5 16.5 ± 8.1Ada 11.6 ± 3.1 12.1 ± 3.1Emo 8.8 ± 3.3 10.4 ± 3.2 ***Spon 11.8 ± 2.4 11.9 ± 2.6

8.6 ± 2.8 7.3 ± 2.8a

Rat ***Orig 1.6 ± 1.7 1.5 ± 1.2Host 1.6 ± 1.6 2.4 ± 1.7 ***Anx 3.9 ± 2.0 3.8 ± 2.2

0.4 ± 0.8 0.8 ± 1.1b

Bod Pre *

a Paired t-test.b Paired i L test for dichotomized scores.* p < 0.05; ** P < 0.01; *** P < 0.001.

Fig. 1 illustrates the group differencesby presenting the mean performances ofthe exposed groups (N = 100 and N =33)in standardized scores; the correspondingreference groups are used as a standard inadjustment.

Table 3 shows significant differences inalmost all intellectual performances and

246

memory tasks. The differences in thepsychomotor performances were lessmarked. However, dexterity in the SantaAna test and the size of drawings in theMira test differed significantly betweenthe groups.

For most intelligence and memory vari­ables the comparison between the matched

Fig. 1. Mean performances of the exposedsubjects (N = 100 and N = 33) in standardizedscores. (The corresponding reference groupsare used as the standards.)

Sim

PC

SD

FI

DSp

Log. M.

Ass. L.

Ben. repro

Ben. ret.

SA right

SA coo

FT right

FT left

RT right

RT choice

Mi size

Mi form

e'l'" e ~':~6~ ~amPle

< (JMatched group~__ CN=33J---..-1b

.Ae

\ .le()

~.

-1.0 -0.8 -0.6 -0.4 -0.2 0 +0.2

pairs (N = 33/33) (table 4 and fig. 1)yielded almost the same absolute differ­ences in test scores, although the statisticalsignificances of the differences were lowerdue to the smaller size of the comparedgroups. Except for finger tapping andsize of drawing the differences in thepsychomotor tasks were slight.

Differences in personality

Table 5 presents the mean results andstandard deviations of the Rorschach vari­ables and the statistical significances ofthe differences between the group meanvalues (N = 100/101). Table 6 presentsthe corresponding results obtained in thecomparison of the matched pairs (N =33/33). Fig. 2 illustrates the differencesby presenting the results of the exposedgroups, expressed again with reference tothe means and standard deviations of thecorresponding reference groups.

There were no differences between thegroups with respect to the number ofanswers, or latency times, but there weresignificant differences in emotionality, ra­tional self-control, and hostility, the ex­posed being less prone to emotional reac­tions and expressions of hostility and more

TabZe 6. Personality variables: means, standard deviations and significances between the groupmeans (groups matched for age and initial intelligence).

Means and standard deviationsVariable

Exposed (N = 33) Nonexposed (N = 33)

Significancesof differences

(t-test)

RRejrtAdaEmoSponRatOrigHostAnxBod Pre

12.2 ± 3.70.8 ± 1.2

15.7 ± 7.410.6 ± 2.8

8.3 ± 2.911.3 ± 2.2

8.8 ± 2.41.1 ± 1.31.3 ± 1.63.5 ± 1.60.4 ± 0.8

12.8 ± 4.20.5 ± 1.3

19.1 ± 10.011.6 ± 2.5

9.2 ± 2.511.5 ± 2.9

7.1 ± 2.81.5 ± 1.02.1 ± 1.73.2 ± 2.10.8 ± 1.2

a*

*

NS a

a Paired xZ-test for dichotomized scores.

4

247

-----,._-._..-..

prone to control their thinking and behav­ior. The exposed also rejected cards moreoften.

Differences in the subjective symptoms

Table 7 presents the means and standarddeviations of the subjective symptom com-

R

Rej

rt

Ada

Emo

Spon

Rat

Ori

Host

Anx

Bod Pre

-0.6 -0.4 -0.2 0 +0.2 +0.4 +0.6

• Whole sample(N=l00J

()Matched group(N=33J

Fig. 2. Mean results of the exposed subjects(N = 100 and N = 33) on the Rorschach per­sonality test in standardized scores. (Thecorresponding reference groups are used asthe standards.)

plexes, as revealed by the questionnaire.The number of questions included in thevariables is also indicated in the table.For each question, the subject had tochoose one of the following alternativeanswers: "never," "sometimes," or "often."Each answer was scored with 1, 2 or 3,respectively, and the scores were addedtogether.

The difference between the exposed andnonexposed was the most marked in theamount of disturbances in memory andvigilance and in the amount of absent­mindedness. With respect to sleep distur­bances or neurovegetative lability, therewere no differences between the twogroups.

Discriminant function analyses

Two discrimination analyses were per­formed, based on the data obtained fromthe groups matched for ingelligence (N =33/33). In the first analysis 11 performancevariables were used, namely, the tests forintellectual and visual functions (Sim, PC,BD, FI), the memory tests (DSp, LogM,AssL, Ben repr), and three psychomotorvariables (SA, sum of right and left, RT,sum of right and left, and Mi size).

As the first step the analysis chooses thebest differentiating combination of vari­ables by multivariate tests for the equalityof mean vectors and for the additionalinformation provided by individual vec­tors (28). The obtained combination con­sisted of one visual intelligence test (BD)and two memory tests (AssL and DSp).For the other tests the probability of their

Table 7. Subjective symptom complexes: means, standard deviations and significances betweenthe group means.

Variable

Sleep disturbancesFatigueMemory and vigilanceAbsentmindednessEmotional labilityNeurovegetative lability

Number Means and standard deviations Significancesof items of differences

Exposed Nonexposed(N = 100) (N = 101)

3 5.2 ± 1.5 5.1 ± 1.32 4.1 ± 1.2 3.6 ± 1.0 **5 9.6 ± 2.4 8.4 ± 1.8 ***2 3.3 ± 1.1 2.6 ± 0.7 ***9 15.5 ± 3.9 14.4 ± 3.3 *7 10.2 ± 2.2 9.9 ± 2.2

* p < 0.05; ** P < 0.01; *** P < 0.001.

248

TabLe 9. Results of the second multiple dis­criminant analysis.a

TabLe 8. Results of the first multiple dis­criminant analysis. a

a See the section on statistical methods.b Note: YO.672 + 0.502 + 0.552 = 1.

deviations of the dis-

0.750.600.54

Correlation withthe discriminant

function

-0.57 ± 0.930.57 ± 1.07

F (3, 62) = 7.044P < 0.001

0.670.500.55

Variable Scaled eigenvectorin W-metrics b

Eigenvalue 0.34Wilks' lambda 0.75

Means and standardcriminant function

Exposed groupNonexposed group

BDDSpAssL

adding new information about the groupdifferences to that obtained by these threetests was less than 25 0/0.

Thus in the solution of the discriminantfunction only the three variables mention­ed were needed. Table 8 presents the re­sults of the analysis and the correlations ofthe discriminant function with the sepa­rate variables. The performance on theBlock Design test gets the highest weightin the discrimination between the exposedand nonexposed and also correlates bestwith the discriminant function.

The second analysis included three vari­ables of the Rorschach test (Emo, Rat andHost) in addition to the 11 previouslymentioned performance variables. Vari­ables BD, AssL and DSp were again in­cluded in the best discriminating combina­tion of the variables. In addition the com­bination included two Rorschach variables(Rat and Hos). Table 9 presents the resultof the second analysis and the correlationsof the discriminant function with theseparate variables.

Validation of the discriminant functionsEigenvalue 0.49Wilks' lambda 0.67

F (5, 60) = 5.883P < 0.001

a See the section on statistical methods.

Table 10. Percentages of correct classifications.

Means and standard deviations of the dis­criminant function

Exposed group -0.69 ± 1.0Nonexposed group 0.69 ± 1.0

Variable Scaled eigenvectorin W-metrics

826268

0.660.520.47

-0.470.44

767374

Correlation withthe .discriminant

function

Second discrimi­nant analysis

Non­Exposed exposed

766266

0.540.370.50

-0.380.44

737574

First discrimi­nant analysis

Non­Exposed exposed

3369

100

BDDSpAssLRatHost

Groupsize

The individual probabilities for belongingeither to the exposed or to the nonexposedgroup were calculated for each subject,and the subjects were classified into thegroups to which they most probablybelonged.

Table 10 presents the percentiles of cor­rect classifications separately for the ma­terial used in the discriminant analyses(N = 33/33) and the rest of the material.The percentage of correct classifications inthe material not used in the analyses ex­presses the validity of the discriminantfunction in determining whether a newsubject is affected by solvent exposure.The percentage of correctly classified ex­posed subjects expresses the sensitivity;.and the percentage of correctly classifiednonexposed subjects, the specificity of thediscriminant functions (38).

For both discriminant functions the sen­sitivity was slightly better than the spec­ificity. The personality variables includedin the second analysis slightly increasedthe correct classifications in the materialon which the discrimination was based,but it did not improve the validity withregard to new cases.

249

• Exposed

o Nonexposed

10

%

20

15

\ ro ~ 30 ~ 50 60 ~ ~ 90 ~%PROBABILITY OF BELONGING TO THE EXPOSED GROUP

• Exposed

~ Nonexposed

~,,[ -l~

00 10 20 30 40 50 60 70 80 90 100%PROBABILITY OF BELONGING TO THE EXPOSED GROUP

15

20 -

%

Fig. 3. Percentage distribution of the Bayes'probabilities of belonging to the exposed groupaccording to the first discriminant analysis.

Fig. 4. Percentage distribution of the Bayes'probabilities of belonging to the exposed groupaccording to the second discriminant analysis.

The distributions of the Bayes' probabil­ities of belonging to the exposed groupaccording to the discriminant analysesare presented in fig. 3. Fig. 4 presentsthe corresponding distribution of prob­abilities according to the second analysis.

A comparison of figs. 3 and 4 shows that,although the personality variables includ­ed in the second analysis did not improveits validity in terms of correct classifica­tions, the discriminant function yielded bythe second analysis nevertheless gave asharper differentation between the twogroups. When the probabilities of thesubjects belonging to their proper groupwere calculated according to the first dis­criminant function, the modes of a poste­riori probability distribution were about70 °/0 in both the exposed and nonexposedgroup. When the probabilities were calcu­lated according to the second function,the mode of corresponding probabilitieswas about 80 Ufo in the exposed groupand about 90 Ufo in the nonexposed one.

When the subjects with probabilitiesbetween 50 and 75 were considered bor­derline cases and when only a probabilityof belonging to the exposed group of high­er than 75 0/0 was assumed to indicate abehavioral disturbance peculiar to solventexposure, the prevalences of exposed andnonexposed subjects with behavioral dis­turbances were 35 and 12 %, respectively,according to the first discriminant func­tion, and 44 and 11 %, respectively, ac-

cording to the second discriminant func­tion with the personality variables in­cluded.

When, correspondingly, a probability ofbelonging to the nonexposed group ofhigher than 75 Ufo was assumed to be avalid indicator of undisturbed psychologi­cal functioning, the prevalence of undis­turbed subjects was, according to the firstdiscriminant function, 6 Ufo in the exposedgroup and 25 °/0 in the nonexposed one,the corresponding percentages accordingto the second discriminant function being11 and 40.

DISCUSSION

Comparison of the exposed andnonexposed subjects

We cQIIlpared behavioral features of agroup of car painters with those of a non­exposed group in order to determine thepossible psychological effects caused bythe mixed solvent exposure of car painters.The study concerned subclinical effects oflow levels of exposure, the average levelof the total exposure being only 32 Ufo ofthe Finnish TLV with little variabilitybetween the car painting garages. Thepossibility of higher exposures in the pastcould not be ruled out however.

As the intelligence performances differ-

250

ed considerably between the two examinedgroups, the question arose of whetherthese, and maybe also other differencesbetween the groups, were due to differ­ences in the initial intelligence levels ofthe two groups and not to the effects ofsolvents.

The use of reference groups in behav­ioral studies is always a problem, mainlybecause of the possibility of unequalmotivation among the experimental andreference groups in the test situation andunequal initial levels. Due to the differentselection of employees for different oc­cupations, and even for different plants,the latter problem is hard to avoid inbehavioral studies in industrial epidemi­ology. If the effects are limited to a fewpsychological functions only and the otherfunctions are left intact, the problem canbe solved with the study of the differ­ences in behavioral profiles. When theeffects cover a broad range of functions,the possibility of differences in initiallevels becomes crucial.

In our investigation we decided to useemployees from the Finnish State Rail­ways as reference subjects because theywere willing to accept the psychologicalexamination as a part of their health ex­amination, and they were also motivatedto cooperate in the test situation. Theother advantages of this group as a refer­ence group were its suitable age distribu­tion and its homogeneity with regard tohealth status and work conditions. More­over, the reference subjects lived in thesame geographical area as the car painters.

The role of possible differences in theinitial intelligence levels before the com­mencement of exposure was controlled bypsychological test results recorded duringthe military service of the subjects. In acompar,ison of 33 pairs matched both forintelligence at the age of about 20 years(during military service) and for age, thesame group differences were found asbetween the entire samples. This resultconfirmed that the group difference couldnot be explained by initial differencesbetween the exposed and nonexposedsubjects.

The validity of our results concerningthe group differences is also dependent onthe adequacy of the statistical tests used.There are three assumptions underlyingthe t-test for the equality of the mean val-

ues, namely, normality of the samplingdistributions, homogeneity of variances,and independence of errors in the testscores. Although no exact testing for non­normality was done, in significance teststhe 'stipulation of normality may be re­garded as practically complied with forlarge samples if they pass a symmetry test.The two sets of data had an equal andlarge number of observations (i.e., morethan 30) on all the psychological test vari­ables. As a consequence, only in a few in­stances did the rejection of the variancehomogeneity assumption on the basis of anF-test lead to a differing significance levelin the t-test for mean levels from what anordinary t-test would have yielded. Giventhese conditions, there is both theoretical(4, 5) and empirical (e.g., 3 and referencestherein) evidence to support the notionthat the t-test is a robust test; Le., it isonly inconsequentially affected by a viola­tion of the underlying assumptions.

The paired sample t-test was used whenmatching was not regarded as irrelevant,Le., when it made the responses of thenumbers of pairs correlate positively. Insuch a situation the differences of pairwiseresponses are independent, and the t-testof the differences is often more powerfulthan the ordinary t-test.

The differences between the psycholog­ical performances of the exposed andnonexposed subjects could be confirmedby the t-test when whole samples wereconsidered, but the statistical significancesof the t-test were rather low when thegroups matched for initial intelligencewere considered, not because of smallerdifferences but because of smaner groupsizes. The difference was further con­firmed by a multiple discriminant analysisyielding the maximum separation betweenthe two sets of data; both the Wilks'lambda and the t-test for the differenceof the mean scores of the discriminantfunction reached a level of high statisticalsignificance. The choice of variablessufficient for sigIlJificant separation of thegroups was an additional advantage of theuse of the multiple discriminant analysis.

Moreover, we could test the general­izability of the result and the practicalapplicability, Le., the sensitivity and speci­ficity, of the discriminant scores by usingthe discriminant scores of the subjects notincluded in the analysis to classify them

251

into either the exposed or to the non­exposed group. The number of subjectsclassified into the exposed group wassignificantly higher among the exposedsubjects than among the nonexposed ones.The fact that about 25 Ofo of the exposedsubjects had a higher probability ofbelonging to the nonexposed group was inaccordance with our expectations, since itwas reasonable to assume that only somepart of the car painter group woulddisplay effects of solvent exposure. Thenumber of nonexposed subjects classifiedinto the exposed group was a more seriousdisadvantage; it indicated that the centralnervous system dysfunction measured bythe tests is not very specific for solventexposure and that the psychologicalmethods have a high sensitivity to mildbehavioral disturbances of different ori­gins. However, when only the subjectswith a probability of higher than 75 Ofowere regarded as subjects with centralnervous system dysfunction, the percen­tage of such subjects was reduced to 11 inthe nonexposed group, against 44 in theexposed group. The percentages proba­bly correspond better to the true preva­lences of central nervous system dysfunc­tions in both groups.

The checking of possible etiologic factorscausing behavioral disturbances in thereference group remained outside thescope of this investigation. The earlier­mentioned work loads of the referencesubjects, as well as central nervous systemdysfunctions due, for instance, to a heavyuse of alcohol or some neurological dis­ease, may be possible causes for the dis­turbances.

Nature of the psychological changes

According to our results, visual intelli­gence, as measured by the Block Designtest, and the memory functions, measuredby the verbal memory test, were the mostaffected by solvent exposure. The sensi­tivity of v,isual performances with respectto 10ng-teIiffi exposure to solvents hasbeen proven even in earlier studies (2, 22,23), but in these studies Block Design wasnot the most sensitive visual test. Theperformance on Block Design containsboth an intellectual and a pure visual com­ponent. In addition, the test demands

252

concentration. From our results the mostaffected component cannot be determined.Possibly an impairment of all of themaccounts for the sensitivity of this test tothe exposure of car painters.

Memory disturbances among workersexposed to solvents have also been demon­strated earlier (8), but most recent investi­gations have either omitted the examina­tion of memory functions or failed to showany effect on memory, except on visualmemory. According to our results verbalmemory was more affected than visualmemory. Performance on the verbalmemory tests used in this study dependson the ability to concentrate on spokenverbal material and the ability to keep itin mind. It is possible that the poor per­formance of the car painters was partlydue to distractability and not only to poormemory.

The impairment discovered in the per­formances of the car painters was notrestricted to the four previously mentionedtests. On the contrary, solvent exposureseemed to affect a broad range of mentalfunctions. The impaired functions includ­ed verbal intelligence, which in someearlier studies (2, 19) has been consideredresistant to diffuse central nervous systemdisturbances. As the verbal intelligencewas measured by Similarities only, wecould not determine whether the inferiorresult of the exposed subjects was depen­dent on the impairment of verbal reason­ing, abstraction, or communication. In thistest the subject had to answer spokenquestions, and maybe this property of thetest accounts for the car painters' failureon it. It is possible that a paper and penciltest for verbal intelligence could havegiven a different result concerning theverbal intelligence level of the exposedsubjects.

The psychomotor performances of theexposed subjects indicated moderateclumsiness of hand movements. However,in a cOlffiparison with the effects of carbondisulfide on psychomotor performancesmeasured by the same test methods (19),the retardation of psychomotor speed wasvery slight.

There were no significant differences inthe mean reaction times between theexposed and nonexposed subjects. Toluene,among other solvents, has been shown inearlier studies to increase reaction times

both in acute and long-term exposureswhen concentrations exceed 200 ppm. (13,26, 27, 37). According to our results reac­tion time is not a sensitive measure ofeffects due to low-level solvent exposure,even after long-term exposure.

The psychological syndrome of theexposed subjects also included emotionalchanges. As the measurement and inter­pretation of behavioral features belongingto the domain of moods and emotions isvery problematic, this area of behavior isvery often disregarded in behavioral toxi­cology. It is however important withregard to chemical interventions of thecentral nervous system, as well as withregard to the subjective well-being andsocial abilities of the exposed persons. Forstudying the effects of solvents on person­ality, we used the Rorschach personalitytest, even though we knew the difficultiesinherent in the interpretation of the re­sults.

There are two alternative interpreta­tions to the personality changes indicatedby our results. They can be due to toxiceffects on the brain centers regulatingthe emotional aspects of behavior, or theycan be due to the subjects' emotional ormaybe compensatory reaction to a situa­tion created by impairments in mentalfunctions. For the present we are inclinedto interpret the reduotion of emotionalreactivity and the reduction of aggressions(Hostility) as immediate toxic effects. Theincreased rational control of thinking andbehavior can even reflect increasedpsychological tension induced by a toxiceffect on the central nervous system, butit can also be understood as a compensa­tory feature.

The subjective symptoms that wereincreased in the exposed group corres­ponded to the psychological picture oftoxic effects as described in the precedingtext. According to both, impairment ofmemory and concentration and a relativeinability to keep rapport with the envi­ronment seemed to be central features ofthe effects of solvent exposure.

However, although the differences be­tween the average test perfoI1mances ofthe exposed and nonexposed subjectswere statistically significant, the impair­ments discovered in the exposed group canbe considered rather slight. There weremore poor performances among the ex-

posed subjects than among the nonexposedones, but the individual test results werein general within the limits of normalvariation. This result does not mean thatthe behavioral changes found in this studyare harmless. The practical significanceof mild or moderate memory impairmentor a mild decline of intellectual capacitiesand psychomotor skills, as well as a slightchange in emotional reactivity, is difficultto evaluate, but nevertheless they implyreduced resources to cope with the variousdemands of everyday life.

Some final remarks

There is some toxicological evidence tosupport the conclusion that the effect ofcombined solvent exposure can be morehazardous than the summated effects ofthe components (29). However, very littleis known about the interaction of solvents.In addition very little is known about theaction mechanisms and sites in the centralnervous system.

As the available data concerning centralnervous system effects of the separatesolvents present in the exposure of carpainters is scanty, we cannot know whichof the components is the most responsiblefor the effects indicated by our results.Since impairments appeared in an exten­sive area of psychological functions, acombined effect can be supposed. More­over, the fact that there were measurableeffects seems to indicate a potentiatingeffect of solvents when they are together.The mean concentrations of separate sol­vents were between 0.3 and 15.3 % of thecorresponding TLVs, and it must be con­sidered rather improbable that theselevels would cause measurable adverseeffects when occurring alone, or even iftheir interaction caused a simple summat­ed effect.

The potentiated effect need not necessar­ily be potentiality in a toxicological sense.The impairments in car painters' perform­ances can alternatively be a result ofminor disturbances in several functions,caused by separate components of theexposure. It can be hypothesized thateach one of these disturbances could becompensated for in the test situation, aswell as in everyday life, when occurringalone, but that their combination does not

253

leave many possibilities for compensationand thus causes a potentiated effect onthe behavioral level.

Safe TLV values for mixed exposurescan only be based on thorough toxicologi­cal research on the interactions of theseparate agents. This research shouldalso include research on the interactionof the effects on the behavioral level.Currently the TLVs for mixed exposuresare based on insufficient data. There­fore, periodical health examinations ofpersons working in mixed exposures andepidemiologic research with such workersmust be considered highly important.

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