Occupational and Environmental Medicine 1996;53:100-105

Short term inhalation exposure to turpentine:toxicokinetics and acute effects in men

Agneta Falk Filipsson

AbstractObjectives-This study describes the toxi-cokinetics, pulmonary function, and sub-jective ratings of discomfort in volunteersexperimentally exposed to turpentinevapour (a mixture of monoterpenes). Theresults were compared with similar expo-sure to single monoterpenes to look in thetoxicokinetics and acute effects for signsof interactions between the monoter-penes.Methods-Eight male volunteers wereexposed to 450 mg/ml turpentine byinhalation (2 h, 50 W) in an exposurechamber.Results-The mean relative uptakes of a-pinene, /3-pinene, and 3-carene were 62%,66%, and 68% respectively, of the amountsupplied. Between 2% and 5 % of the netuptake was excreted unchanged in theexpired air after the end of exposure. Themean blood clearance 21 hours after expo-sure (CL2lh) of a-pinene, f3-pinene and 3-carene, were 0f8, 0 5, and 0 4 l.kg-'.h-1,respectively. The mean half lives (t1,2) ofthe last phase of a-pinene, f-pinene, and3-carene averaged 32, 25, and 42 hours,respectively. The t1,2s agreed with previ-ously calculated half lives from singleexposures. The total blood clearance CL2lhof 3-carene found in this turpentine studywas lower, and CL4h of 3-carene was sig-nificantly lower than the values obtainedfrom similar exposure to pure 3-carene.The subjects attending both exposure toturpentine and to pure a-pinene at 450mg/ml had lower CL4h during the exposureto turpentine, when they experiencedmore discomfort of the throat or the air-ways (F = 5-7, P = 0.048) than duringexposure to control concentrations. Afterexperimental exposure to turpentine anincrease in airway resistance was foundthat differed significantly from results ofexposure to 3-carene at 10 mglm' (P =0-021) or 450 mg/ml (P = 0.047).Conclusions-Toxicokinetics and acuteeffects show small, if any, interactionsbetween a-pinene, f3-pinene, and 3-carene. The subjects experienced discom-

Department of fort in the throat and airways duringToxicology, National exposure to turpentine and airway resis-Institute of tance was increased after the end of expo-S171 84 Solna, Sweden sure.A Falk FilipssonAccepted 26 September 1995 (Occup Environ Med 1996;53:100-105)

Keywords: monoterpenes; toxicokinetics; lung function

Terpenes are naturally occurring in pine treesand certain bushes. An oleoresin is obtained,as a yellow sticky gum, when the trees aretapped. After distillation of the oleoresin avolatile oily fraction, turpentine, is obtained.The main components of turpentine are themonoterpenes: a-pinene, -pinene, and 3-carene. The composition of turpentine varieswith species, location, and season. Mono-terpenes are also present in gases liberatedduring sawing or processing of fresh wood andpose a potential exposure for workers insawmills. Industrial exposures of 39-550mg/m3 have been reported.1 2 For turpentine, amixture of monoterpenes, and for a singlemonoterpene the Swedish occupational expo-sure limit (OEL) value is 150 mg/m3n. At thetime of the exposure the OEL was 450 mg/m3.In rats, terpenes accumulate in peripheral fat,kidneys, and the brain.34 The blood:air parti-tion coefficients are 15, 23, and 32, respec-tively, for a-pinene, /pinene, and 3-carene.Solubility of monoterpenes in human blood ishigh. This should imply a high respiratoryuptake. Solubility in olive oil is also high; theoil:air partition coefficients are 2900, 4300,and 5000, respectively, for a-pinene, ,t-pinene, and 3-carene. This should imply accu-mulation in adipose tissue.5 Respiratory andpercutaneous uptake of terpenes have beenfound in humans.7 Slow metabolism andrenal elimination of monoterpenes were sug-gested after a patient acutely poisoned by pineoil was studied.8 Almost all the scientific litera-ture found on monoterpenes (except for d-limonene) are about occupational exposure to amixture of monoterpenes, but no quantitativestudy of uptake and elimination of a mixturewas found. It is important to study toxicoki-netics and effects of exposure to the differentcomponents in a mixture, firstly as singleexposures to avoid contributions from othersolvents and secondly as multiple exposures tolook for signs of interactive effects between thecomponents. High respiratory uptake of themonoterpenes a-pinene, 3-carene, and d-limonene was found when human volunteerswere exposed to the monoterpenes by inhala-tion.9- 1 The monoterpenes were fairly readilymetabolised and only small percentages of thetotal uptake were eliminated as unchangedmonoterpene through the lungs and even lessin the urine. Up to 4% of the total uptake of a-pinene after human exposure by inhalation

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was eliminated in the urine as cis- and trans-verbenol." Terpenes may irritate the skin andmucous membranes613 and prolonged expo-sure may result in allergic contact dermatitis'4 15or chronic impairment of lung function.2The aim of this study was to elucidate toxi-

cokinetics, pulmonary function, and ratings ofdiscomfort in men experimentally exposed toturpentine and to look for signs in the toxicoki-netics and acute effects of interactionsbetween the monoterpenes.

Materials and methodsSUBJECTSEight healthy men, not occupationallyexposed to solvents, with a mean (range) ageof 28 (18-37) years and weight of 75 (62-83)kg participated in the study. All were non-smokers and they were instructed to refrainfrom alcohol and activities that could causeexposure to organic solvents during the pre-ceding two days and throughout the experi-ment. The study was approved by the regionalethics committee at the Karolinska Institute(Solna, Sweden)

EXPOSURE CONDITIONSThe subjects were exposed to turpentine(Swedish turpentine, Alcro Beckers) for twohours at the Swedish OEL then in force(450 mg/m3 (75 ppm)) during light physicalexercise (50 W on a bicycle ergometer). Theexposure was conducted in an exposure cham-ber as described earlier for 3-carene and d-limonene.'0I A low concentration of 3-carene,10 mg/m3, was used as a control. The controlconcentration was chosen as low as possible sothat no effect was to be expected, but the sub-jects could still smell the solvent. Thus theydid not know what concentration they wereexposed to. The workload 50 W was chosen toimitate the physical activity generally found inlight industries.'617 The solvent concentrationin the air of the chamber was continuouslymonitored at atmospheric pressure by aninfrared spectrophotometer (Miran 80)equipped with a 20 m thermostatically con-trolled (45"C) gas cell. Measurements ofmonoterpenes in the air of the chamber weremade at 3 39 ,um with 3-6 gm as the referencewavelength. The concentration of monoter-penes varied by less than 2% during the twohour exposure of turpentine and less than 3%between different days. The mean tempera-ture in the chamber was 210C and varied byless than 2 50C during a two hour exposure toturpentine and between different days. Earlierexposures to monoterpenes performed in asimilar way were used for comparison betweenmonoterpenes.910

MEASUREMENTS AND ANALYSISAir sampling and analysisAt four regular time intervals during the expo-sure exhaled air was individually collected inpolyester laminated aluminium foil bags(about 20 1) for about four minutes each.Exhaled air samples were also collected afterexposure (5, 15, 25, 85, 150, and 230 minutes

after the end of exposure). The volume of theexpired air was measured with a balancedspirometer and the concentrations of monoter-penes were analysed on a gas chromatograph(Carlo Erba, Fractovap 2350) equipped with aflame ionisation detector and a polar column(Supelcowax 10, 30 m, 0-75 mm inner diame-ter). The injector and detector temperatureswere 200°C and the column temperature was80°C. Nitrogen at a flow rate of 5 ml/min wasused as the carrier gas. The mean value of thefour sampling periods was used to calculatethe total uptake of monoterpenes during theentire exposure period, which was calculatedas the difference between the total amount ofmonoterpenes in inhaled and exhaled air. Thepulmonary ventilation (VE) was measured asthe collected volume of air, corrected to bodytemperature and pressure (BTPS) divided bythe collection time of the volume measured.TheVEBTPS was measured at rest before andafter exposure and at exercise during the expo-sure. Heart rate was continuously recordedduring the exposure with a heart rate meter(Sport tester PE3000, Polar Electro, Finland).

Blood sampling and analysisArterial capillary blood (200 1cl) was collectedfrom a prewarmed fingertip at selected inter-vals during the exposure and up to 21 hoursafter end of exposure, for measurement ofmonoterpenes in blood. Blood sampling dur-ing exposure was taken by the subject holdingout one hand through a closable hole in thewall. Blood samples were collected inheparinised capillary tubes (2 x 100 pl) andtransferred to gas tight head space vials (22-4ml) which were capped immediately withTeflon lined membranes. The samples werekept for 20 minutes at 37°C before analysis.The headspace of the blood samples wasanalysed on a gas chromatograph (PerkinElmer 8700) equipped with a head spaceautosampler (Perkin Elmer HS-101), a polarcolumn (Supelcowax 10, 30 m, 0-75 mm innerdiameter), and a flame ionisation detector.The injector temperature was 170°C and thedetector temperature was 240°C. The initialtemperature of the column was 80°C; aftertwo minutes it was increased by 5°C/min to100°C and then by 250C/min to 2100C.Nitrogen at a flow rate of 5 ml/min was usedas the carrier gas. The concentration ofmonoterpenes in the blood was measured bycomparison with individual standard curvesprepared in the same concentration range byadding monoterpenes to blood samples takenbefore the exposure. The detection limit was0-06 gmol/l, and the relative error of themethod was 4%, based on 10 duplicatesamples within the relevant concentration range.

TOXICOKINETIC CALCULATIONSApparent blood clearance (CL) was calculatedas the quotient between the total uptake(dose) and the area under the blood concen-tration v time curve (AUC), and was adjustedto body weight. To obtain the AUC, areas foreach experiment were calculated by the trape-soidal method from the start of exposure to

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the time the blood samples were taken fourand 21 hours after exposure. Thereafter areas

to infinity were calculated as the quotientbetween the line estimate of the monoterpeneconcentration in blood at four and 21 hoursafter exposure, and the slope was calculated bylinear regression of the log linear blood con-

centration v the time curve of the last phase.The concentrations of turpentine, a-pinene,and 3-carene in blood were measured until21 hours after exposure to 450 mg/M3n. Atlower exposure concentrations of a-pineneand 3-carene the concentration in blood couldonly be detected until four hours after expo-

sure because the blood concentrations of themonoterpenes were low and close to the detec-tion limit. To allow comparisons between dif-ferent exposure concentrations, CL4hs basedon AUCGoh were found; the AUCGh was cal-culated for all exposures of monoterpenes. Inthis case, the last section of the blood concen-

tration time curve is neglected, AUC is under-estimated and clearance thus overestimated.The values that included the last phase ofCL,s are probably more accurate but maystill be somewhat overestimated for the same

reason.

Individual semilogarithmic plots of theelimination from blood v time for monoter-pene concentration were treated by themethod of residuals. Linear phases were dis-tinguished by best fit with the end phase sub-tracted. The slopes of the phases were

calculated by linear regression and convertedinto t12s.The amount of solvent exhaled after the end

of exposure was estimated from the AUC ofconcentration of monoterpenes in expired airv time and multiplied by the ventilation. TheAUC of exhaled air was calculated as

described for the blood samples.

RATINGS OF SYMPTOMS

Before, during, and after each exposure thesubjects rated the level of perceived discomfortin 10 questions. Ratings were performed witha 100 mm visual analogue scale graded fromno effect to almost unbearable.18 The ques-tions included irritative symptoms such as: (a)discomfort in the eyes (burning, irritation, or

running eyes); (b) discomfort in the nose

(burning, irritation, or running nose); (c) dis-comfort in the throat or airways; and symp-

toms related to the central nervous systemsuch as: (d) headache; (e) fatigue; (f) sicknessfeeling; (g) dizziness; (h) intoxication; (i) diffi-culty in breathing; and finally (j) smell of sol-vent.

PULMONARY FUNCTIONPulmonary function was assessed with a con-

stant volume, variable pressure, body plethys-mograph (Jaeger Masterlabbody, Erich JaegerGmbH, Wiirzburg, Germany), equipped witha pneumotachograph system for forced expira-tory volume measurements. The followingvariables were measured: forced expiratoryvolume in one second (FEV,), vital capacity(VC), peak expiratory flow, residual volume,total lung capacity, mean expiratory flow at50% (MEF5O), and airway's resistance. Thesubject confined in the box generates a pres-sure change by volume displacement of severalml during breathing. The aim of this test is a

precise measurement of the volume displace-ment. The breathing frequency was 30 perminute. Airway resistance was measuredbefore spirometry and specific conductancewas calculated from airway resistance and cor-

rected for lung volume. Measurements were

carried out immediately before exposure andbetween 20 and 30 minutes after the end ofexposure. To measure the effect of exposure toturpentine and 3-carene at 450 and 10 mg/M3,the individual differences between values afterand before exposure were divided by the indi-vidual values before exposure and presented as

the means.

STATISTICAL EVALUATIONThe respiratory and toxicokinetic variableswere analysed both with the Wilcoxon signedrank test and Student's t test for paired analysis(two sided test) with Statview 4-02 on an

Apple Macintosh. For comparison betweenexposure to a-pinene and turpentine no statis-tical evaluation was made because four of thesubjects attended both studies whereas theother subjects only participated in one of thestudies. Thus, neither paired nor unpairedanalysis could be made. To investigate thesubjective ratings, given by all the subjects

Table 1 Mean (SD) experimental results ofsome physiological and toxicokinetic vaiablesfrom two hour inhalationexposure to 450 mg/m3 of turpentine during physical exercise at a workload of 50 W (also, results from previous singleexposure to ac-pinene and 3-carena are presented)

a-pinene 3-carenefiPinene

Exposure to Exposure to Exposure to Exposure to Exposure to Exposure to Exposure toturpentine a-pinene' a-pinene' turpentine turpentine 3-carene1' 3-carene'°

Air concentration(mg/M3) 242 (3 3) 455 (5 3) 225 (5-1) 49 (0 67) 157 (2-1) 451 (5 8) 228 (5-8)

Heart rate(beats/min) 89 (10) 88 (9) 87 (10) - - 92 (11) 90 (9)

Pulm ventilation(1/min) 24 (2 8) 26 (4 5) 25 (3 8) - - 23 (1-6) 24 (2-7)

Net uptake(% of total inhaled) 62 (5-3) 58 (5 3) 60 (3 9) 66 (5 8) 68 (7 5) 71 (4-7) 70 (4-4)

Respiratory eliminationt(% of net uptake) 3 8 (1 1) 7-7 (3-1) 5-7 (5-7) 5 0 (5-8) 2 4 (1 5)* 4-8 (1 2) 1 9 (1-5)

Concentrations steady statestates (umol/l) 9 0 (0 75) 19 (3 6) 9-6 (1-9) 2-6 (0.29) 9-9 (0.89) 25 (0 92) 12 (1-4)

*P < 0-05, Student's t test v pure 3-carene (450 mg/M3).tDuring exposure; after exposure; mean from last 30 minutes of exposure.

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12

0E

:I_'a

00

in

G)

a

0.0)0a0

10

8

4

2

-- a-pinenej3-pinene

-r- 3-carene

E~~~~~ ~~~~~~~~~|7- -

-0 1 2 3 4 5 6 12 13 22 23

Time (h)

Concentration of a-pinene, /3-pinene, and 3-carene in arterial capillaty blood during and after exposure (2 h, 50 WU9 toturpentine at a concentration of 450 mg/M3. Mean (SD) of eight subjects are given.

during the exposures, analyses of variance wasperformed with SuperANOVA. The level ofstatistical significance was set to 0-05. Unlessotherwise stated results are presented as mean(SD).

ResultsThe mean total concentration of the monoter-penes in the air of the chamber from all theturpentine exposures was 449 mg/M3, with arelative SD of 1-4%, based on air concentra-tions from four different occasions at eachexposure. Correcting for pulmonary ventila-tion this indicates that the mean amount ofturpentine delivered was 8-5 mmol. Othersubstances in the turpentine were not detectedand, if the assumption is made that the tur-pentine consists of a-pinene, f3-pinene, and 3-carene, the proportions of the vapour wereabout 54%, 11%, and 35%, respectively (table1). The relative net uptakes of the totalinhaled a-pinene, fpinene, and 3-careneaveraged 62%, 66%, and 68% respectively(table 1). Between 2% and 8% of the net

Table 2 Apparent CLs and t,,2s of a-pinene, /3-pinene, and 3-carene from two hourinhalation exposure to 450 mg/M3 of a-pinene, p3-pinene, 3-carene or turpentine duringphysical exercise at a workload of 50 W (mean (SD) from eight subjects are given)

oa-pinene 3-carene/3-pinene

Exposure to Exposure to Exposure to Exposure to Exposure toturpentine a-pinene9 turpentine turpentine 3-carene'0

CLhr (l.kg-I.h-I)t 1-6 (0 3) 1-4 (0-31) 0-8 (0-3) 1-0 (0-2)* 1-3 (0 1)CL2,h,(l.kg- '.h'4) 0-8 (0-09)§ 1.1 (0 20) 0-5 (0-3)§ 0-4 (0 1)§ 0-9 (0 3)t,2 initial (min)4 4-1 (2 8) 4-8 (1-5) 5-3 (3-0) 3-1 (0-7) 4-5 (1-5)t,,, middle (min)4 33-4 (4-1) 38 (8 2) 41 (15) 33 (6 2) 35 (5 7)t,,2 terminal (h)4 32 (18) 12 (4) 25 (18) 42 (23) 30 (22)

*P < 0 05 Student's t test v pure 3-carene exposure.tBased on AUC from values measured up to 4 h after exposure; *based on AUC from valuesmeasured up to 21 h after exposure; four subjects due to analytical problems resulting in prob-lems calculating AUC.

uptake was excreted unchanged in the expiredair after the end of exposure (table 1).Respiratory elimination of 3-carene was signif-icantly higher after exposure to 450 mg/M3 of3-carene than after exposure to turpentine (P- 0-01).During the exposure the arterial blood con-

centration increased rapidly initially and thenlevelled off toward the end of exposure (fig-ure). The decay was similarly rapid and afterthe end of exposure three log linear phasescould be distinguished visually during the timestudied. There was an initial phase (0-15 minafter the end of exposure), a middle phase(16-197 min after the end of exposure) and alast phase (3-3-21-3 h after the end of expo-sure). Table 2 shows the tl2 of the threephases. The t1,2 of the initial and middlephases agreed with earlier results from expo-sure to single monoterpenes whereas the aver-age t1/2 of the last phases of a-pinene and3-carene tended to be higher in this presentstudy (table 2). The CL2lh from blood samplestaken during exposure and until 21 h afterexposure was lower for turpentine exposure(0-4 l.kg- .h1-) than for similar exposure to 3-carene alone (0-9 l.kg-'.h- ), but this differ-ence was not significant (table 2). The CI,from blood samples taken during exposureand until four hours after exposure was signifi-cantly lower (P = 0-02) after multiple expo-sure (1-0 l.kg-'.h-1) than after single exposure(1-3 l.kg-1.h-1). The mean CL4h, however, washigher for turpentine exposure (1-6 l.kg -.h- 1)than for single a-pinene exposure,(1-4 l.kg -.h-) but the subjects who wereattending both exposure conditions showedlower CL4h for a-pinene during exposure toturpentine than during exposure to a-pineneon its own.

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Table 3 Mean (SD) lungfunction variables before exposure and about 30 minutes after two hours inhalation exposureto serpentine at a concentration of 450 mg/M3, during physical exercise at a workload of 50 W (values are of six subjects(seven for 3-carene exposure))

Effect of exposure (change as % of before exposure value)Turpentine

Turpentine 3-Carene 3-CareneBefore exposure After exposure (450 mg/r3) (450 mg/m3)'° (450 mg/m3)10

VC,,. (1) 6-3 (1 0) 6-1 (1-1) -1-8 (2-2) -0-34 (2-1) 0-08 (1 8)FVC (1) 6-3 (1 0) 62 (1-1) -14 (27) -1.1 (20) -1-1 (26)FEVy (1) 5-1 (06) 5.1 (05) 1 7 (42) 24 (32) 25 (2-1)RV (1) 2-1 (0-6) 2 5 (0 5) 28 (32) 20 (21) 26 (19)TLC (1) 8-4 (1-3) 8-5 (1 7) 3-5 (5-6) 3-3 (5 1) 4 7 (3 6)MEFO (1/s) 6-0 (1-5) 6-0 (1-0) 3 0 (7-8) 3-1 (9 9) 4-9 (6-6)PEF (1s) 12-4 (2-0) 12-0 (1-0) -3-8 (8-1) - 1-4 (6-9) 1-7 (10)sGaw (l/kPa.s) 1.9 (0 6) 1.5 (0-3) 17 (74) 36 (100) 57 (120)Raw (kPA.s/1) 0.12 (0 04) 0 15 (0 03) 29 (32) - 5-7 (45)* - 21 (38)*

*P < 0 05 Student's t test, turpentine v 3-carene exposure.FEVy = forced expiratory volume in 1 second; VC = vital capacity; PEF = peak expiratory flow; RV = residual volume; TLC = totallung capacity; MEFfi, = mean expiratory flow at 50% VC; Raw = airway resistance; sGaw = conductance.

During exposure to turpentine the subjectsrated more discomfort of the throat or airways(F = 5 7, P = 0 048) than during exposureto control conditions (10 mg/m3 of 3-carene).The ratings were similar to those (about 5% ofthe scale) for exposure to 450 mg/m3 of 3-carene. The subjects rated more discomfort(about 10% of the scale) when exposed to225 mg/M3 of 3-carene. A small but not signif-icant increase in discomfort of the nose (about5% of the scale) was found during exposure toturpentine compared with control exposures.No significant difference was found in ratingsof symptoms of the central nervous systemafter exposure to turpentine compared withratings during control exposures.

Significant increases in airway resistancewere found after experimental exposure to tur-pentine (table 3) compared with control expo-sures (P = 0-021) or exposure to 450 mg/miof 3-carene (P = 0-047).

DiscussionThe conditions during the exposures to tur-pentine, except for the concentration ofmonoterpenes and the temperature of the airin the chamber, were the same as for earlierexposures to 3-carene'0 and a-pinene.9 All thesubjects who took part in the exposure to tur-pentine were also exposed to 3-carene andfour of them participated in the exposure to a-pinene. The toxicokinetic variables were stud-ied with a non-parametric method (Wilcoxonsign rank test) and a parametric method(Student's t test) to investigate if there wereany differences and thus an uneven distribu-tion. A fairly good agreement was found andtherefore the Student's t test for paired analysis(two sided tests in Statview) was used to com-pare the effects on the toxicokinetics betweenexposures to 3-carene and turpentine.A high net uptake of the monoterpenes was

to be expected from their relatively high solu-bilities in blood5 and above all from earlierexposures to single monoterpenes.9- 'Accordingly the net uptakes of a-pinene, /3-pinene, and 3-carene were high after exposureto turpentine and were in agreement with thenet uptakes during exposure to singlemonoterpenes. The CLlh of 3-carene found inthis turpentine study was lower, and the CL4hof 3-carene was significantly lower, than when

obtained from similar exposure to pure 3-carene. For a-pinene the mean CL4h washigher after exposure to turpentine than aftersingle exposure to a-pinene even although thesubjects who attended both exposure to tur-pentine and to pure a-pinene at 450 mg/M3had lower CL4hs for turpentine. From the highsolubility of terpenes in oil one would expectaccumulation in adipose tissue and thus a longtl/2 in blood. The first and middle phases of thetl/,s of a-pinene and 3-carene were in agree-ment with earlier single exposures. The lastphase of the t,/2s tended to be longer afterexposure to a mixture of terpenes. The con-centration of 3-carene in arterial blood at theend of exposure was higher than the concen-tration of a-pinene, even although the totalinhaled was higher for a-pinene than for 3-carene. Possible explainations are the higherblood solubility of 3-carene,5 resulting in ahigher rate of net uptake and lower respiratoryelimination of 3-carene; the higher fat:bloodpartition coefficient for a-pinene, resulting ina higher distribution rate of a-pinene fromblood to fat and a higher metabolic rate of a-pinene. Respiratory elimination of 3-careneafter exposure to turpentine was about thesame as after exposure to 225 mg/m3 of 3-carene but significantly lower than after expo-sure to 450 mg/m3 of 3-carene (P = 0.01).The mean respiratory elimination of a-pineneafter exposure to turpentine was lower thanthe mean after exposure to single a-pinene.However, it is not possible to compare thegroups as some of the subjects attended bothexposures and some only one of the exposures.

During exposure to turpentine the subjectsexperienced more discomfort of the throat orairways than during control exposures. Theratings were similar to those from exposure to3-carene at the high level.10 Yet, the subjectsrated even more discomfort, about twice asmuch, when exposed to 3-carene at themedium concentration. During exposure to 3-carene the subjects experienced irritation ineyes and nose and their responses to the highconcentration were significantly higher thanresponses during exposure to the medium andlow concentration. The ratings of irritation ofthe eyes, during exposure to turpentine,showed a small increase at the beginning ofthe exposure but 40 minutes later there was nodifference compared with control exposures. A

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small, but not significant, increase in discom-fort of the nose was found, during exposure toturpentine, compared with control exposures.This increase was lower than during exposureto 3-carene at the high concentration buthigher than during exposure at the mediumconcentration. The mean concentration of 3-carene in the turpentine vapour was about onethird of the concentration during high expo-sure to 3-carene. Thus it is possible that theratings of nasal irritation are related to 3-carene. In the ratings of symptoms of the cen-tral nervous system no significant differencewas found between exposure to turpentine andcontrol conditions.

Significant decreases in FEVI, FVC, andMEF50 were found in workers occupationallyexposed to monoterpenes at a mean (range)value of 254 (100-550) mg/M3.2 During exper-imental exposure to a-pinene9 and 3-carene atthe control concentrations there was adecrease in airway resistance compared withbefore exposure. The decrease may have beencaused by exercise rather than by exposure toterpenes. A tendency towards increased airwayresistance was found for 3-carene at the highexposure. During experimental exposure toturpentine an increase in airway resistance wasfound. The differences between exposure toturpentine and 3-carene at high and controlexposures were significant. Thus exposure toturpentine, and possibly 3-carene at high con-centrations, may cause an increase in airwayresistance that is greater than the tendency ofexercise to increase airway lumen.The main purpose of this study was to mea-

sure the toxicokinetics, pulmonary function,and ratings of discomfort in men experimen-tally exposed to turpentine and to look forsigns of interactive effects between the mono-terpenes. Based on comparisons with previousexperiments involving inhalation exposure tomonoterpenes the present study indicates thatthe interactions between toxicokinetics andacute effects of a-pinene, /-pinene, and 3-carene are small, if present at all.

I thank Zhiping Wang for carrying out the pulmonary functionanalysis, Elisabeth Gullstrand, and Lena Emstgird for their

skilful technical assistance, and Agneta L6f, Ewa WigaeusHjelm, and Gunnar Johanson for valuable discussions and crit-icism of the manuscript.

1 Eriksson K, Levin J-O. Identification of cis and trans ver-benol in human urine after occupational exposure to ter-penes. Int Arch Occup Environ Health 1990;62:379-83.

2 Hedenstierna G, Alexandersson R, Wimander K, Rosen G.Exposure to terpenes: effects on pulmonary function. IntArch Occup Environ Health 1983;51:191-8.

3 Savolainen H, Pfaffli P. Effects on longterm turpentineinhalation on rat brain protein metabolism. Chem BiolInteract 1978;21:271-6.

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