Document k6Zmj9XEG8KdpLJ4YV5LZeQxD

t-... __.. ..... .-........ . I WORK LOAD A OF SOLVENTS IN TI$SUES OF MAN XmLtrpnd ~ Unitfor Work Physiolo#y, Depcrrment of OcmpafbmlHeoltJt, National Board of Occupational Safty a d Health. SI71 84 Solna, Sweden ABSTRACT Subjects weH exposed to dwemnt solvenfs in inspiratory air through u breathing valve both at reh clnd duriw physicul exercise on tz bicycle ergometer. The uprake in thtj organism was increased duringphysical work 9compared IOai RSI. The upr k? was 5-6 timeshigher during hcavyphysicd work compared to at restfo id blood easy soluble solvents w h e m s it was only doubledformom insolublesolvenrs. Tho uptake can be estimatedfrom the quotienrbetween [heconcentration inalveolarand inspiratory airand the pulmonary ventilation The concentration in subcutaneous adipose cissue was higher in lean than in obesesubjecrs. Theha&Ige of methylene chloride irr ad@osetissue was ab0ut 8 hr andf i r styrene and xykne about 2-4 days. INTRODUCnON The uptake ofsolvents in the organismofman was measured inasedesof experiments,Thisarticlesummarizes some of the resultswhich were obtained in exposure to totuene. industrial xylene. styfiae. methylene chloride, methylchlotoform, trichloroethylene. butanol and white spirit. In 1975 a review was written of results available at that time.' The present paper wag presented in Stockholm to the International Symposium on 0ccuPat;Onal HealthHazardsEncounteredin Surface Coatingand Handlingofpaintsin the Constmction industry in October of 1979. EXPENMENTAL DESIGN, SUBJECTS AND METHODS The same design ofthe uptake studies was uscd for all solvents. Young, healthy malts were used as subjects. Each subject was exposed during both rest and exercise on a bicycte ergometer. Each period of e * p u r c usuaUy lasted2 hr, 30 min at rest, 30min at awork loadof50 W. 30 min at 100W and another 30 rnh at 150 W. The solvent was given to the subject in the inspiratory air thmgh a breathing valve. The concentration m the air was constant and it was usually kept around the Swedish threshold limit value of the solvent By using the same work loads and exposure time for all solvents bothpulmonary ventilation and blood circdlation could be keptfairly constant during the 30 minute periods of exposurej meaning that the influence ofthe solubility in blood and tissues ofdiffcreni solvents could be nudied The total uptake of the solvent wad continuously measured with the Douglas'bag technique. The cmcenrraliohsof solvents in air, in arterial and venous blood and in some instances in kubcutaneous adipose tissue were measured by different gas chmmatograplfic methods. Further details on the experimental design, analyticalmethods ahd error ofthe methods are given in the differentpart reports.~.~.a-)o I RESULTS AND DISCUSSION Uptake mwaremcnt. Examples of uptakes of methylenechloride.richlore ethylene,industrial xylene &CI! styrene dit1 be presented. In Figure I . the uptake d a subject exposed to methylene chloride is ill~stratedW.~ith increasing work loads,the pulmonary ventilation increased and thereby the given amountof the solvCnt. The pulmonary ventilation was about 6 times higher at 150 W than at rest. The amount taken up was about doubled duringwork comparedtoatrest andof aboutthe same sizeduringthe dthree cycling periods. During the whole period of exposure the percentage uptakedeclinedfrornabout55%atrest,d wnto25% at 150W.Theuptakein twohrin a groupof 5 subjectswas in mead 2.0 g. constituungabout3 1%ofthe inhaled amount of 6.5 g. I JUmg '7 L- -'=ome;m. REST FIGURE I The amount d methylene chloride supplitd and th%up in one subject during cxpoJun.Exposure was performcdwith1. 7 4 0 ~ m J o f m e t h y l c mchlorideduriagrcscandexercise at an intensicy of 50, 100 and IS0W.' (Reptinled by Permission from CRC Press. IBC.) 52 n I was p -d 50. iFigu m e1 :period0 16 during I ' 5denu Iyconstant :rice of the id. d with the merial and issue were tails on the agiven in 7 I aIn Figure 2, the uptake of subject exposed to uichlomethylene is illustrated: The uptake decreased wingthe whole period ofexposure.Itwas about55% duringthe first 30 minude periodat test andit succcsivelydeclined to about 6% duringthe last petiod kt 150 W. It was almost zero ar the end of exposun?. After two hr. the concedtration in the arterial blood of the subject was nearly in eqailibrhrn With the concentration in the alveolar air. The subject was in gaod physical condidonandfairly thin-The supplitdamount in two hr to a group of 5 subjects was in mean 3.9 g. The uptake wa 1.4 g, constituting about 36% of the inhaled amount- -1TT RGUREZ T h c a m o u n c o f t r i c h l o r o a h y l e b s ~ i o d du~pninme-du-e-. Exposure was performed with 1.080 mJm' of trichlorocthyknc durirr?:mrt a d exerokc 1c an intensity of 50. 100 and IS0 W? ( R e p r i n d by Pcmissbn from CRC Pmss. Inc.) In Figure 3. the rnem uptakeofagroupof6subjectsexposedtoindustrial xylene, a mixture ofxylene isomers and ethylbenzene, is illustrated.' T h e uptake rosefFomabout80 mg duringthe restperiod to about390 mgduriogthe last peixodofexercke.Thepercentageuptakewas about6,C% atrestandabout 50% buing !SO W.During the two hr exposure an average of 1.0 g or 59% was taken up of a supplied amount of abaut 1.7 g. FIGURE 3 themean amountofxylcne supplied and raken up in six subjeer$during exmu*. Exposurew s performed with 435 mdm3ofxylcne during rest and exercise atan inmsityaf50. -100 .nd 150 W.' (Reprinted by Permission from CRC Press. Inc.) -. . compared to at rest. For styrene and and xylene the uptake increased 5-6 fold during 150 W as compared to at rest, whereas the uptake for methylene -_ . chloride and trichlotoethylene was onty doubled. The cxpfmation of these findings is that both styrene and xylene are easily soluble,whereas methylene chloride and trichlomthylene are comparatively insoluble in blood and probably also in the tissues. The more soluble the substance is the slowerthe equilibrium is reached between rbe concentration in blood and alveolar air snd between tissues and blood. Especially, in the later part of the exposure the degree of metaboiism also plays a role for the uptake. FIGURE 4 T expos~~rcE.xpc intensit> of 50. I e related. measures inc ' 'T in alveo Therel. fhduptake never miount t the alveolar i estimation w the blood anc the concenu. ambient air. limit values i Gambetale 1 ofthese prob STYRENE 146 mg 95 rng mmg 145 TOTAL 355mg 210 mg 787 mg 489 mg duhgexpun. t an intensityof 50. ;physical work :reased 5-6 fold for methylene nation of these !reasmethylene : h blood and .sthe siowerthe md alveolar air of the expasure I i I 210 -EST- 80 1 210 mg/rn3 FIGURE 4 The mean amount of styrene supplied a d taken up in s m wbjcetr aUN exposure. E x p u r r was performed wirh 210 mglnJof r*.rme mt rad exercise at an intensity of 50. 100 a d 150 W."(Reprinted by Permission rrom CRC Press. InC.1 Alveolar comeatration. When the percentage uptake of the differentsolvents were relatedto the alveolarconccntratimoverthe inspiratoryconcentration,a linear correlation was observed.!.?(Fig 5). The correlation between the two measures indicates that the uptake of agas in the lungs approaches zero atthe same time as the alveolar concentration approaches the concentration in inspiratory air. and that the percentage uptake hereased when the concentra- tion in alveolar air decreases. The relationship between the two variables is natural. The fact that the uptake never reached 100% is due tothe dead space ventilation. Accordingly. the amount taken up of a solventmay be estimated from the concentrationsin the alveolarand inspira?oryair and the pulmonary ventilation. This method of estimation was triedin the field with SUCCCSS.~l- j It should be noted,however, that the cornlation only exists for solvent uptake in the lung capillaries. The uptakein the lungsisdistributedby the blood tothe Mknnttissues and organs. The higher the uptake per unit of time, the higherthe concentration in theblood and thehigherthe conceatrationid differentorgans.Thismeans that the concentration in vital organs variesdespiteitconstantconcentdon in the ambient air- Therefore,what one would like to have is some sort of biological limit values as complementsto the ordinary thmhold limit values- Franccsco Gamberale has worked tower with our group. He made an extensive Sudy dthesc Hewas abletoshowatwhich uptake asigniflcantincnase 146 Work Load and Uprake of solve^^ in 7issues of Man in simple reaction time can be demonstrated for the solvents discussed here. Such values can k used as biological limit values when d i m s $ i q acute effects.' I% uptake 8ot.\ y = -0.86 r79.3; c methylene chloride + trichloroethylene (j aliph. white spirit arom. whire spirit a styrene xylene A toluene I 4 20 I A0 1I 60 80 alv. conc. x io0 imp. COPC. Coateut in oubcoraneoasadiport tissue. Jorgen Engstrijm wrote his thesis on concentrationof solvents in subcutaneous adipose tissue.6 In Figure 6. the concentrationofmethylene chloride in subcutadeousadiposetissue after 1 hr exposure is given.' The concentration was, as a d e , higher in lean than in obese suajects, The concentration did not change significantlyduringtbt first 4 ht afterexposure.T h e concentrationwasmeasured in2 subjects the morning after the exposure and the estimated mean half-life of the concentrations m adipoQctissue was 8 hr. The estimated mean amountofsolventretainedin the totalfat deposits ofthe body was greater in the obese subjects.The estimated total amount of methylene chloride in far stores 4 hr after exposure w a ~ -ally elated tothe estimatedamountofthe body fatexpcpressdin percentof body weight (Fig. 7). FlGURE6 Co subjects(ywp I 12wbjcnsuea gcxercisei 01 iiiscussed'here. iscussiw acute I !ne chloride oethylene jhite spirit yhite spirit 9 :onc.x 700 p. conc. wote his thesis InFigure6, the tissue after I hr in lean than in duringthe tirSt cts the morning ncentrations in t retainedin the .The estimated . exposure was edinperccntof r,.ul*,*,~llr',,.,r*.lI, (yn lo". * Work Load and Uptakeof S o l e in risues of Mrur 147 I II METHYLENE CHLORIDE i6 4 1 Ob I 1 0 M ? =Group1 I 13 M all subjects f MtSEGroupII 1 I1 1 2 34 hours after exposure I ': g. . ,. a 9T 'd T9ts86ST8ZT 01 M I t l E I I O B ATllWH WOW SS:6T L66T-LT-33a -7 Work Load and Uptake of Solvents in Tissues s/Marr 149 1- 0- --1 --2 Figure 10illustratesthe concentrationsin adipose tissue after exposure ID tg,industrialxylene."rhere was nochangein bentrationdutingthefvst24 hr. In a subsequent study the half-life d xyl e h subcutmeous adipose tissue varied between 1 md 5 days." I' Because ofpoorbloodperfusion of adiposetissue, only small amountsor around 1.0%ofthe total uptake were retaidd @ adipose tissue. It is probably Bnoriskofaccumulationofmdylene chlori e inadiposetissue ifthe threshold limit values arenoterccedtd.However, be use ofthe ionghalf-Iifeiaadipose L. tissue of s y r a e and xylene, accumulation can be expected in occupational exposure. in three persons 0ccupationaUy exposed to styrene, the mean -. - codcentrationinadipose tissuewas about 80 times higherthaninambientair-' "here is reason to suspectthat the eliminationafter indusvial c x p w e takes much Ionget than two weeks. What isthe implicationofanaccumuhtionofa solventintbe adiposetissue? It means thatas longas the solvent stays in the adipose tissue, it probably also stays inotherfat-nche tissues. It also means that indirect exposure ofinternal organs suchasthe nervoussystem and the Iivercontinues as long asthe release frem the adipose tissue coutinucs. If the solvent d o r its metabolites a n toxic the effect wili of course be carried on during a longer time, and that is probably associated with a greater risk of development of diseases. i \ \ \ \ \ \ \ ue atterexposure to uringthe first24 hr. e m adipose tiwe --JYm@!-W*g Ql. issue. It is probably issue ifthc threshold !ghalf-lifein adipose ;ted in occupational styrent, the m e a than in ambient &;T raid exposure takes ;htheadiposCtissue? m e , it probably also exposure of internal aslong astheredew r its mMbdifcs are get time, md that is of diseases. / 6T 'd T9P806ST8ZT 01 REFERENCES 1, brandI: Uptake of solvenu in the blood and tissues ofman. A review. Scand J Work Environ & Hcdfrh 1:199, 1975. 2. brandI,Engsmm J. OvrumP.Exposum toxylene and ethylbenzene. I. Uptake. distribution and elimination'inman.Scand J WorkEnuimn & ffealth 4:185. 1978. 3. Astrand I and Gamkrale F: Effects on humans of solvents in the inspiratory air; A method fw cstirnatibn of uptake.Environmenral Res 15:l. 1978. I 4. b a n d I and O m m P Exposure to uichloroethylene: I. Uptake and $stribution in man. Scand J Work Environ & Hedth 4:199, 1976. 5 . Astrandl, OvnunP d C a r l w n A . : Exposuretomethylcne chloride:1. Its concentrationsin dveolar air and blood during rest andexercise and its metabolism.Scarld J Work Enviton & Healdt 1:78. 1975. 6. EngsWm J: Organic solvents inhuman adiposetissue.drbereoch Hulsa 1978:22. Arbetarskyddsverket. Stockholm. 7. Engstr6m J T, xsuand I and Wigaeus E: Exposure to styrene in a polymerization plant. Uptake in thk organism and concentration in subcutaneousadipose tissue. ScandJ Work Environ & Healrh 4524, 1978. 8. Eagstrern J md Bjursuom R: Exposure to methylenechloride. Cofltent in subcutaneousadipuse tissue. ScandJ WorkEnvimn 6r Health 3 215, 1977. 9. Enptrorn J and Bjursvliin R Exposure to xylene and ethylbenzene. 11. Concentration in subcutaneous adipose tissue. ScaltdJ Work Enuiron & Healrh 4:195, 1978. 1 10. EngsatimJ, Bjurstriim R, h n n d 1 .knd O m P: Uprake, distribuuon and eliminationof styreneinman,Ckcentration in subcutaneoustissue. Scad J Work Envimn & Healrh $:315, 1978. 11. En@- J and RiihimikjV:Distridutioa ofm-xylene to subcutanMus adipose tissue in short-term experifnental human exposure. Scund J ?Work Envimn & Hedlrh 5:126. 1 9. 12. GarnbcraleF:Behavioral effects of xposure to solventvapors. Experi- .L, mental and field studies. Arbere och Hiilsa 1975~14.Arbetarskydds- verket, Stocwiolm. 13. h m P, Hultengrea M and Lindqvist 1,Exposure to toluene in a photogravureprinmg plant. Concentration in ambient air and uptakein the body. Scand J Work Environ & Health 4~327,1978. Illustrations are reprinted wirh permission from :Modelling the uptake, metabolism ,and elim-inarionofsome inhaled vapors andgases. Vera FizerovaBergerova(Ed.).Boca Raton: CRC Press.Inc.. 1982.Copyrightthe Chemical Rubber Co.,CRC Press. Inc. RE: I I Pbint! jsprayi: tkeathi LCC. IBeca irehas b. hey. etc iition tc How mtrast tc mly des :imce din8 ex; !Conch d phagc dens d ~ously al lung Ideal posed I( d k d: Not 01 kstos. ists on. onchiti: