Document r9zrKmJo4Er9pz35NjkD99yq

Human Exposure to 1,1,1 -Tricliloroclliauc Vapor: Relationship of Expired Air and Blood Concentrations to Exposure4 and ToxicilvW RICHARD D. STEWART*, M.D.. HAROLD II. GAY. M.D., DUNCAN S. ERLEY, iM.S.. CARL L. HAKE, Ph.D., and ARNOLD W. SCHAFFER, ILS. Mcdictil l)<pnrtmvnl, Chrinirnl I'lii/mrs Jirxriirrh Lolmmtori/. mol IIuwIiiiiiii'iiI Lahoniturt/, The Dow I'haiiirol ('ompmiii, M iillmol, Mnltii/mi A study of root rolled human exposures to 1 ,1,1-t rieliloroet li;me v.-ijior has revealed ti prolonged exponenti;d "deeav curve" when the eoneetitrulion in the pnstexpnsure e\])ired ;ur is plotted against hours after ex|)osure. 'Flu- iiiea-ureiiient \\n- predictable enough to allow a reasonable estimation of the magnitude of exposure. Chemical, physiological, and clinical laboraton studies were carried out and cortelated with the vapor exposures. The determination of urinary urobilinogen proved to he the most sensitive tc-t of liver stress produced h\ markedlv exce,--i\e exposures to 1,1, J-triciiloroethane. Data from this ntudv 'support 500 ppm as a satisfactory tJmndioW tmwr hw tths compound. Introduction It i- the purpo-c nf this ]).-tper to report a sene- of aeiiie h 11111 a 11 exposures to 1,1,1-tri- THE probability of human exposure to the ehloroet liaue x ;i[mr in which these obstacles were vapors of 1,1.1-t rieliloroet bane i- increasin'; studied. Yoluiiteet' were expo-ed in a eliamber rapidly as tins compound sain- popularity as ain which the concent rat inn ol 1 ,1,1-t richloro- solvent in cold degreasing application- Because etliane vapoi was eont rolled by simultaneous of its low toxicity, it- use as a solvent m several a l lim~] iherie alia.lv scs. ('nncellt ration of 1 lie other applications, c.r/., agricultural chemical', elieinieal in the Blood was determined by infrared hair sprays, and dry cleanin';, is also being in speetroinel i le methods de-enlied prev musly.1, = vestigated. Tims, the physician, the industrial while post expo'll re ex|iired air eoiirenl rat loll was hygienist, and the toxicologist will be called deieriiiined direelh through the use of an in- njion to evaluate acute and chronic exposures to ftared 'peelronieter einpluvuig a long path- 1 ,1,1-trichlnroctItalic vapor in an increasingly length ga- cell. Blood and expired air eoneen- large segment of ihc population. I rat ions were t lien eorrelaled with the inagiulilde A major ob-taele which has prevented ac of the exposure and with the plivsiologiea! ef curate evaluation of the significance of exposures fects of the I , 1 ,1-1 rieliloroetliano. to 1,1, l-trirliloroothane vapor has been the lack of a practical method to identify and measure the concentration of the compound m the blood or expired air of the exposed individual. This has prevented a correlation of the blood or ex pired air concentration with the magnitude of exposure. A second obstacle lias been the lack of a reliable means of determining the magnitude of an accidental exposure alter it lias occurred, Experimental Procedure A series ol timed human exposures to known concent ration- of 1 ,1 ,1 -t rieliloroet hane vapor was rolidiic.led The fust two exposures to be de scribed, Experiments 1 ;md 1', were to atmos pheric concentration' of odd ppm. During 1 lio next expo-lire, which was lo an aimo-pherie eoiieeiii rat ion approaching 11)1)0 ppm, subjects Pi<w*n!ftl nt th< Twfntv-M'conrl Anoint Mont mu of thr AnifM-inm ImlnMnot llvinenr A-sopintmo. IVtuiit. Mirlncan, April 1901. * Present nrltlie-, p"p:n Mnrnt of Intom-i] Mrnhemi', Vni- were removed troni the expo-ore chamber at three lime-interval- The-e giuup- will be discU'-ed a- Experiment - !!, 4, and o. The above Aersilv of Mirlncoti MMirfil ('enter. Ann Arbor, Mirlimnn. concent ration- wen- elio-eu beeail-e of t lie studies SL 036802 art a 1-tri- neous ' the rarcd n was in in pat hincennitude lal ef- known vapor be dontmosng the =pheric ubjects iber at be disabove studies Industrial II jigicuc Journal 47.; of Toikol.-on, ft al.f wliich indicated that tlie aimosphcric concentration of ], 1,1-tnehloroethane for daily exposures of 7 to S hours dura tion should not exceed 5(10 ppm, and that con centrations approaching 1000 ppm would have anesthetic effects. In a final exposure, Experi ment 0, the atmospheric concentration was in creased rapidly until anesthetic levels were readied. Table I outlines the tune and decree of ex]insure for the experiments in this series. Material 1,'xed The 1,1,1-trichloroethane (CIIXThi Used in this scries of experiments was the inhibited prod uct, commercially available Chlnrothene' sol vent. Chlorothene solvent ha- the following composition: 94 to 97C ] ,1 J-trichloroelhane, 2.4 to 3 .OH dioxnne, 0.12 in O.dH butanol, and small amounts of ethylene dichloride, water and other materials. The acute toxicity and the vapor pressure of Chlorothene have been shown to be essentially identical with those of 1,1,1triohloroetbane.'1 The latter designation will gen erally be used throughout tins paper since infra red analysis specifically identifies this chemical in the composition. Exposure Chamber An interior room, measuring IT X 12' X 7'2" high, served as the exposure chamber. The room had a continuous positive air supply. After the subjects were seated in the closed room, Chloro thene was poured into a fiat, partially covered dish. A pedestal fan was used to blow air across the dish and circulate the vapors throughout the room. As seen in Table 1, it was possible to keep the atmospheric concentration of the 1,1,1trichloroethane within the room relatively con stant by regulating the exposed surface area of the material in the dish, Anohjsis of Exposure Atmosphere The atmospheric concentration of 1,1,1trichloroethane m Experiment 0 was determined by absorption of known volumes of air on silica gel.r' In the exposure to atmospheric concen trations just over 000 ppm, three monitoring method- were simultaneously employed; two l)ow-modified Davis llalide Meters," a PcrkinElmer Model 120; infrared spectrometer equipped with a 10-meter path-length gas cell, and a ] irueger (las Detector Kit,* At the lowest, level of exposure, 500 ppm, one Dow-modified Davis Halide meter was u-ed to monitor the at mosphere m Experiment 2. while in Experiment 1 both the Halide Meter and the infrared spec trometer were used. Tmu.u I Human Exposure to 1,1 ,1-Trichloroetlinnc Vapor 1 -% 1 (`one dura z e-- 1 tptipomn * * i" 'r -- XL ~ -- 5E UJ " ] ft 500 (DuunndtmUrT.uniio.iul '' h\|M>-.urc i PI mi' k.inw AfU*r Kcat lunu C1 om i-nlr.it inn ippm* /inn (;i\ ei;m(> of inrl (mils) I7n (1 >JU IK 1 l:t- Inlrt ,V!1 flrifittrdj) .105 575 501-055 2 6 500 s 1st, I'll! f 1 )p \ is 1 In 120 (ill) lltltD A A 1000 5 7:t '155 (iiMTunr nf 11 If't lit '(Is) !>7X (I >:i \ is I Inliiln H55-1075 * 11 !TU (Huvi-s llalnli1 7 to 10'in * 1? > 'h>l (I llfl,'Ht>t| l 750-1075 '50 fltrawr) t a HKKi 5 . 'Ml) of Stunt1 hr r i H't )i< mIn > K\P. :t 5 3 11)1)1) 5 _ itnostlidir 15 2u 11 000 l:i\<*rnit` nf liil'l limN) Sal lit' MS I'Ap, 3 15 1 13*0 (*i)|nt *,.|) 11-2050'' 'Ti) Krimimc*p-\\fcrotjmghtsi'dtuntiVDiTi iiljlrhrKnliirmnnll.Mluh'. Wit! the exception ol the Draegar Detector Kit which was u-ed in the chamber, air from the chamber wa~ -.unpled b\ the u-e ol probes of sarun lulling -U.-Jiended to head height at the center of the room. These probes were passed under the door to the continuous monitoring devices out-ide. The Halide Meter and the in frared sped remoter were coupled to recorders which provided a continuous record of the con centration. Tlte-e machine- were calibrated again-t known concent lations of 1.1,1-triclilorocthane. M the higher concentration of 1 , 1 ,1-1 richlornet ha tie. the bine gla-s filter of the llalide Meter required frei|uent cleaning, there fore two motei- were used. A- seen in Table I, Experiment 3, the data obtained from each of the three monitoring techniques showed re markably close agreement. The time-weighted average from each method wa- therefore u=ed, when more than one monitoring device was SL 036803 ii,'0(1, to ciilculuto ;m overall average for the respective exjioriiiiont. Subjects Healthy male volunteer- from The Dow Chemical Comp,'my, ranging in ago from .SO to 00 years were selected for tlie exposure studios. Eaeli subject had received a complete preeinployment history and physical examination, chest x-ray and, in some cases, lumbar spine xray, complete blood count (O.R.C.I, urinalysis, and orthorator eye examination. Each subject had then been followed by the Medical Depart ment with periodic history and physical examina tions, which included chest x-ray, C.B.C., urinal ysis, orthorater cheek, .and, ill recent years, timed vital capacity and audiometric examination. Only one subject had an abnormal physical finding. The 00-year old male had a liver palpable 4 cm below the right costal margin, but there was no history of liver disease, and liver function tests were within the normal range. Several of the same subjects participated in all of these exposures. No subject participated in any exposure who had had a known ex posure to any chlorinated hydrocarbon within the previous six days. I'recxposure and l'ostexposure Data Immediately before each exposure the fol lowing clinical data and laboratory samples were obtained from each subject: blood pressure, expirogram (timed vital capacityl, serum fur glutamic oxaloacetic transaminase (SGO-T) and urine for urinary urobilinogen. Rroexpo.-ure blood, urine and expired air samples were analyzed for ], 1,Dtrichloroethane for control purposes. A complete urinalysis was obtained both before and after several of the exposures A 15-minute phenolsulfonphthalein (P.S.Pl de termination was done before and after Experi ment 2. Table II lists the pre- and postexposiire data obtained. During the exposures serial urine and blood samples were obtained for analysis of 1,1,1trichloroethane. Subjective responses were noted. Romberg and heel-to-loe tests were performed at 15-minute intervals by tho-e in Experiments 1, '!, 4 and 5. Following the exposures, serial samples of blood, urine, and expired air were analyzed for 1,1,1-trichlornelhanr. Proexpusuro laboratory tests were repeated at appropriate intervals (sec Table III. Expirograms and blood pressures were obtained within 5 to 1(1 minutes following the exposures in which these wen1 studied. Anali/xis of lilood, ( nnv. and Expired Air far 1.1, l-Tnrldoro< thane Venous blood wa- obtained through an in dwelling siliconized 211-guuge needle equipped with a siliconized slylet Two ml of blood were added to a 4-ml ahuumnm-capped. glass \ial containing 2 ml of carbon bisulfide and one drop of O.X,Tb heparin solution. The sample wagently agitated by end-over-end inversion for 5 minutes. The solvent was withdrawn and analyzed for 1,1,1-trichlorocthane in a double beam infrared spectrometer/'" This method for determining organic compounds in biological fluids has been described previouslv in detail.1,8 Voided urine samples were analyzed m a similar manner. The minimal amount of the compound detectable in blood .and urine by tins solvent extraction technique was 1 ppm with an ac curacy of 1 ppm. Expired air samples were collected in six-lilei volume saran bags. The bagged air was allowed to flow into the evacuated ten-meter path-length gas cell, and was scanned on ihe uppropri.at" spectrometer. The absorbance at !l.2,u was meas ured to determine Ihe concent rat ion of 1,1,1tricliloroetliane. The minimal amount of the compound detectable in expired air was 0 5 ppm w it h an accuracy of t*- (1.1 ppm. Results Experiment l.aim ppm. 7S minutes Six subject- were expu-ed to 1 , 1 . 1-tl'ichloroethane at 500 ppm (the Threshold Emm lccommended by the American Conference of Govern mental Industrial Ilygienisi,-) for 7s minnies. From a subject i\c standpoint, no significant untoward effect- were noted. Three of six -ob jects noted a slight eye irritation which rapidly disappeared. There wa- no dizziness noted: balance and coordination were unaffected, l'rea in I postexposiire clinical laboratory data, listed previously, were normal with the exception of subject 5 who exhibited a trace of albumin and o-d red blood cells per high power field (liBC/ IIPFl in the 20-hour postexposiire urine, 'file relation-hip of this observation to the exposure w as quest loliablc Analvsis of serial hi..... -ample- obtained dur ing the expo-ille iiwealcd that the average concentrations of 1 ,1 ,1-trichloroetbane ill the blond at '>(), 00 and 75 minutes after the start of the exposure were all between and 4 ppm, with a range of 1 5 to 0.5 ppm. Twenty-five min utes after cessation of exposure, the compound wa- just detectable in the blood of 4 of the 0 SL 036804 i\,.,, Sin. lA| XI" t'A |',*1 '.111 IM Min I XI 11 hilli miii< ll]l In wa- ' ctliah tec! i a; Tin low 111 pap,a t lirou air c. mum all <>i po-tc Wit ho: m vst, 1061 xpired Air jor hrough an in;edle equipp'd of blood were ped, glass vial e and one drop e sample was 1 inversion for vithdrawn and ne in a double his method for s in biological ously in detail.1'1 tyzed in a similar of the compound by this solvent nm with an ac- cted in six-liter air was allowed >ter path-lensth he appropriate 9.2/i was nieasation of ] ,1,1amount of the air was 0.5 ppm 1,1,1-trichloroId Limit rccotnence of Governior 7S minutes. no significant hree of six stibn which rapidly azziness noted: unaffected. Prctory data, listed he exception of of albumin and ver field (RBC/ sure urine. The to the exposure es obtained durat the average roethane in the s after the start n 3 and 4 ppm, Twenty-five min, the compound id of 4 of the 0 Industrial Hygiene Journal Tmii.I. II 1,1.1-r 'riehlornel linin' Pre anti !'tl.slex|msiuc Da la Subjet 1 ........ .................. ............. Nonniil Value Experiment l 500 ppin, 78 min. I 4 5 fi * ti Experiment 2 4% ppm, 180 min Experiment 3 055 ppm, 73 min 1 2 ft fi 8 10 ft (1 H StiO T -- ' _>o hr. 7 (In j- i Post Post *- Urinary Urobilinogen j L'rinfih .)*. IS min l* S,l, j i i ,i lir. 211 hr ! r th, ' i reesiM-Kiiic JO In PO'.l('\1t*'.UK' -t Pifn- , 20 hr T1 Post Post I'lisl 1 - , injure 1 exposure 1- Mb, Mil n> ' All. Mu'rn 6-40 1-40 or lo** I 22 ! 1,1 12 1 11) l:lo 1 1-10 | net 0 ft KIM ' him' peg peg j(7renter limn 25':;, i nog 11 14 111 M 1.10 ; mu, nog m*C nee nue RH(' ] 1ft o 1,1 1.10 1-10 i 1-1,1 peg , rare K 1M4 t rare 3 fi u hc ' Ifi ' 10 12 1 HI M0 1 1.10 > H`K 1 2 MU' Peg mre MU' Ifi : Ifi II 1.10 M0 j MO 1 Peg rnte 11 Bf' Peg nrr MU' 12 i Ui ,4 t` 10 MU , 1.10 ' ]1 UeC i neg peg Peg i j 20 ! 20 20 ; is ifi : Ifi 23 20 20 i IK 21 i 14 110 16 1.10 in 1:10 IK l.to Ifi 1-10 M0 1.10 ! mn i M0 1 HI MO : mo ' M0 1 M0 ! 1:10 1.10 ' i i ir; :,s'; :il. 5^7 w;. j 4-r; | 44^; 20'7 : 21^ j Ifi IK ir> Mo 10 Ifi 12 l.lo IK Hi IS 1 111 l:ln ' mo ; 110 i l: to l.lo | 1-30 ; peg peg H eg o 2 MU* neg peg Peg nm- HIK' peg peg Peg Peg : j Experiment 1 910 ppm, 35 mill Experiment 5 900 ppm. 20 min. 4 1 i ' Ifi fi 1 1' Hi 1 |H JK Ifi M0 2 i; 1ft 14 ! Mo 7 is 20 37 , 1' Hi " ifi IK 20 1 10 - l.to 1 10 1 1' 10 1, 10 peg mie MU' Meg peg peg rate KMC Peg Peg Mo Mo 1.10 M0 1 lo : l.lo m-g peg peg l-nr MM Peg peg peg peg Peg Peg peg Peg Experiment fi 0-2650 ppm. 15 min. ' ___________ __ . 1 14 Ifi 15 , Mo i:tt4n 1:10 1, lo ` neg Ifi , 15 1ft 1 in M0 1 ' 10 peg . :l ID 11 , Ifi . I 10 Mi 10 l.lo 1 111 Peg 4 14 ! 14 IK 1 in . M0 1:10 1,10 m*u ft 14 N ; 1 lo ! 1 1:10 mo peg fi 1ft 15 i 10 , 1 lo , 1:10 1. 10 peg 1 14 Ifi 20 l:lo I 40 1:10 1 20 peg lieg neg mg peg Peg Peg peg peg peg Peg PC peg peg mu* KIM ' rare K IM' Peg peg o 2 KMC t-ft MU1 ! subjects. TTine s;mi] les taken during expo-ure indicated thai -nine 'ample- po--ibly eomaitieil up to 2 p]mi 1,1.1-tnehlurnethane, uhile nolle ua= detected m one -ample. The -ample- ob tained 15 minute,- alter expo-tire revaled the presence of a trace .-1111011111 of 1,1. l-tnchloroellinne in 2 of the li samples, while none was de tected in the other four. The expired air concentrations' of 1,1,1-triehloroethane, plotted versus time obtained fol lowing the exposuie, are graphed on log-log paper in Figure 1. A free-hand curve was drawn (hrough points' representing the average expired air concent rat ion.-. Knell point, with it.- maximuni and minimum, represents the average of all of the available samples at that given time postexpo-urc. T he number of .-ample- was never less than 4, and wa- u-iially fi. Points plotted without maximum and minimum 'designations n-pre- (Ilf i nr h \ii 11 ia .-.-ini jih - t 'uneeni rat inns al of -en-itivit v, 0 5 ppm. lirperimt nt A JJtt: ppm, 1st; ninuitr* Six -ubjeeis weie exposed to the Threshold Limit recommended for 1 ,1.1-tnrhlorocthanc lor approximately 3 hours (l.Mi minutes). From a subjective standpoint, no untoward effects wen noied No e\ e irritation or dizziuc.-- occurred Balance and coordination were unaffected. Preaud po-iexposure clinical data, listed in Tabic 11, were normal. Analyses for I , I . I-t rirhlnl'uef llano in the blood and urine during and I'ollouing exposure were inaccurate because the samples were procI's.-ed in 1 lie exposure chamber, allowing contami nation of the carbon disulfide used for extrac tion. fn all other experiments, transfer of the \ J SL 036805 206 1 utjust, 1961 HOURS AFTER EXPOSURE FigvhK 1. 1,1,l-Trieliloroetlinne Expired Air Coneeiiliafinii. Humans were exposed to Atmospheric concentrations of 500 ppm for 7S mmnli's (Exp. 1) and 100 ppm for ISO minutes (Exp. 2). extractant was done outside the exposure chamber. The average concentrations of 1,1,1-triehloroethanc in the expired air following exposure are also plotted in graph form in Figure 1. Due to leakage from unsealed bags, many sam ples did not contain siitlieient air for analysis after holding overnight. Therefore there were only three times at whirl) five or more samples obtained simultaneously could bo analyzed. The averages of these arc designated with a maxi mum and minimum. Individual values arc de noted without a maximum and minimum. A free-hand curve was drawn between the points representing average values. E.rpenincnts 3, 4 nd 5: OvO to 933 ppm jar 73, 33 mnl 30 minutes Three subject-' were expo-ed to 055 ppm of 1,1,1-trirhlornotliatio vapor for 7.1 minutes, two subjects to dill ppm for do minutes and three subjects to 1)110 pjiin for 20 minutes The sub jective ami phv.-iulogie.'d response- are recorded ill Table 111. Within thiee minute,- following the conclusion of the exposures no subject experi enced anv difficult! in performing a normal Hmuberg test. No difficulty in performing simple menial ealeulation- was experienced, neither were there any untoward elieels such as malaise, headache, or nausea noted following these ex posures. Tile concentrations of 1 ,1 ,1-triehloroethane in 1 he lilood during the exposure to 11.55 ppm for 7d nmiiiie- were as follow,-: ] ppm at 15 minutes, 2-4 ppm at d(l minute-, and 7-10 ppm at 05 minute- idler ihe ,-ian of the exposure. None of 1 lie chemical could In* delected in the blood sam ples taken dll minutes after the end of the ex posure. In the groups exposed to 010 ppm and SL 036806 lion dill,, w,t~ pn-u lie I' liemen mg ' drh . I lie etlli. I'i dal Hi I exp' had :d I' ellal -no A1 llllli lepi IW n ("li I nth. loilL li.ah' 11 a i w .1 4' oh-" 'INI oi , cell low Clll I lee, "In. I'olt no4t lie 11 e. e ID" me all m to -ltCB and three The sub recorded owing the :t experia normal mg simple ither were i malaise, these ex- t- t -V imethane Sfpn for (Saiautcs, fimjt 65 '- None of lood-sami{ the exppm and Industrial llpi/ienc Journal POO j)pin, in which exposures wore of shorter duration, a Minilar rise in blood concentration was noted while the .subjects were in the ex posure chamber. The concentration of 1,1,1trichloroethane in the urine at 45 minutes after the start of the exposure was 1-`J ppm in Experi ment !. Samples obtained seven minutes follow ing exposure did not contain the compound in detectable amounts. In the shorter experiments the compound was not detected in the urine either during the exposure to postexposuro. J're- and postexposuro clinical laboratory data obtained from the three groups are li-ted in Table 11. One subject who had n 20-minute exposure to an average concentration of *.*tIt) ppm had an elevated urinary urobilinogen 7 days after exposure. The remainder of the clinical laboratory data was normal. There also was no change in the timed vital capacity or blood pres sure values. Average concentrations of 1,1 ,1-t richloroeth.one in the expired air following these ex posures are plotted versus hours after exposure in Figure 2. Each point with its maximum and minimum, plotted for Experiments d and 5 represents the average of 5 values. The upper two points of those plotted for Experiment 4 each represent the average of 2 values and 1 lit' others a single value. Experiment G. i> to Ju-V) ppm, to minutes Seven subjects were exposed to a constantly increasing atmospheric concentration of 1,1,1trichloroethnnc. When two of the .-object' no longer were able to stand, the experiment was halted. This occurred at a peak vapor concen tration of 2650 ppm. The total time of exposure was 15 minutes. The subjective and physiological responses observed during this exposure are recorded in Table 15'. Within the first five minute interval following the exposure all subjects had fullyregained their sense of equilibrium. No naii-ea or vomiting occurred. J( required marked con centration during the fir.-t fifteen minutes fol lowing ex]insure to perforin simple mental cal culations accurately The five subjects who had become lightheaded staled that tl)e\ didn't `Teel normal" until approximately- three hours following the exposure. They defined this ab normal feeling as '-malai-e." The concent ration of 1 ,1,1-trichloroet h.ane in the blood II minute' following expo-urn was 5 I ppm, while 2d minute' following exposure the compound wa- qtie-i numbly detectable 111 blood (05-1 ppm I. Erine, eolleeied 15 minute' follow ing expo-lire, did not cool,-nil measurable amounts of 1 ,1 ,1-tnchloroethane. Tam i: 111 Subjective and Physiological Hespon"es to 1,1.1 -Triehim net liane \ apor ('oncent rations of !I0I) to 11X10 ppm As <*i;uw ('oiuenh.ihon DIM) |ipm fur itiinuh'H (.'1 Miltji'i't1*} (i:w 5> ri'.ii|\< |{| iiiiliiM'u III 1 `.iihjrcl, (iii'ulrt I'f- fnil lri|tiiti'i| lu |KMruiin ii imnnul Hmu- l'iir in 2 suh.iiq'i- ;iflfr 10 imnuti'H of i*\- jMiMiir llt't'l tu-tup sMilkuii: rioimiil. Two `\|u,rn`ru,oi.l tiluiVi' 000 |>j>m light hoadclnoNs OH) ppm fm ;i immitt's (2 (K\p. 4 t (ilctilrl 11 u `Ii t :i I ('Hull n-i|iuir(l ti ipi't fm m ii Muitn:il [{('iiitx'iL' lo-l tilft'i 10 inllliltro of i' \pMHijji \H iii inc sstilkini; p*'i- funut`>l s\pU, < hw* suUjC'i oNps'in-nvt'il pof^i^tf'ht lightlic.iilrilni'^H iiliuvo 0(H) |ip)n, Ufll p|Mn fur 7.< | imniili's (if subjrelsl | (I ap. ;{) j incnt ll flTull l'('(|l|ilrt| In pt'ifnrm iv nuiiiKil liniiiht'iL' iM nfhT 10 minuti*-* of r\j*uiim' Afttw If) initiulrH uf o\p*niiv opr Kubjfvl l|,`*il mil'iislt'inls pnxihsr Ibtlnlu'TK ll*`pl in-tun walking pi'iFoMimm) wHI by all 11 ii mm '\posm`(\ N-i light liemli'iiiif--; " Mih) f\\c irritutinn wtii noted l\ all subjects when \apnr mneentralmtis in we ahuM' PHtO ppm. I* re- and post expo-lire clinical laboratory data are li'ied in Table JI. Two laboratory findings of que-tionable significance were noted following the exposure. Two 'objects had positive urinary urobilinogen 1:641), noted to lie present .-even hours post ex|insure A repeat urobilinogen test twenty hours po-texposure was negative for all subject.- hive subject- were noted to have from 1 to 2 I'HC 11 PI' on a centrifuged urine sample, obtained -IXty minutes po.-lexposure, wllereallo led blood cell,- had been delected prior to expo-tiro It i- to be remembered that dioxalle (the inhibitor) m -iillirieiil concentration is a renal toxin No change occurred in the timed vital capacities or blood pie-sure measurements. 'flie mean and the range of the expired air coneenl ra I ions of 1 , I . I-I richloroet liane follow ing exposure are graphed on log-log paper hi Fig ure d. Discussion It was noted alter the first exposure to 1,1,1triehlurnei liane at its Thte-hold |.mill that this compound was delectable in the expired air lor many hours after expo-ure. From the work of Make, el nl.'" it wa- known that the rat ex pire- unchanged allno-l all ol an intraperiloneal dn~e of 1 , 1 , I-iiichloroeiliane-t Therefore it wa- not -iirpri-mg that the compound could be delected ill human ex j u I e, 1 all after an expo.-llte. Howe\er, it wa- not predictable that it would lit' 036807 Sb V J 2~>S August, 1961 h- FifirHE 2, 1,1.1-Trirhloroe!lame Expired An- Concentration. Humans wimc exposed id atmospheric concentrations of 955 ppm for 73 minutes (Exp. 3). 910 ppm for 35 minutes (Exp. 4), and 900 ppm for 20 minutes (Exp. 5), detected more than 20 hours 'after an exposure to approximately 500 ppm, the-recommended Threshold Limit. When this long expiration lime was found, it suggested that the measurement of the compound in t he post exposure expired air might be helpful in estimating the magnitude of the exposure. It was found that the most significant manner in which the concentration of 1,1,1-t ricliloroethane in the expired air could be compared to ihe time after exposure (decay curve 1 was bv plotting these points on log-log graph paper. From the plot of these points in Figure 1, it can be seen that the decay curve is almost a straight line and it can therefore be concluded that the expiration of 1 ,1, l-tnchloroelhane has jm jn_ verse exponential relationship to time after cxpo-ure. Figure 1 al~n demonstrates another im portant point. From a comparison of the Iwo decay curves alter 7*- and ISO-minute ex posures to 500 ppm, it can be scon that the dura tion of exposure has a direct bearing on the conrentration of 1,1, l-triehloroet hane in Ihe expired air, especially during the early hours after exposure. It was of interest to further determine the offer I of the iongth of exposure on the expired air decay curve. Figure 2, in which the decay curies for 20-, .35-, ami 73-minute ex posures to 1,1 , l-trieliloroetliane concentrations of just over 00(1 ppm are plotted, shows that though the two nines from the 20- and 55lninute exposures contain considerable overla]!, the 73-minute exposure gives a much higher curie. This would aFti indicate that the tleeay curves are .-rn-itne lo length of exposure dif ferentials at higher exposure eoncenlrations. Figure -I demon-lrate,- ihe effect of exposure SL 036808 Industrial Hygiene Journal 2:,9 IVTable Subjective and Physiological Hesponses to a Constantly Increasing 1,1,1-TricliIoroetlinne Vapor Concentration Over a Period of Fifteen Minutes Concentration (pi"") Response* to Kxposurc 0-1000 1000-L100 Increasing uwurctiOM of a slightly sweet, not nnplensnnt tulur, Mild eye irntntmn noted in ti of 7 subjects. 1000^2000 0 of 7 subjects awure of throat irritation. 2000 1 subject \cry lightheaded. 2050 2 subjects unable t> stand. ^ snbjepis \ cry hghlheadfMl, but able to statnl, 2 subjects were not lightheaded, and one of these was able to demonstrate a normal Romberg test. concentration upon ihe decay curve when the tunc of I'xpo'iirc i- held constant. Points from Experiments 1 anil d arc plotted for compari son. it can be seen that for the fust 2 to 5 hours nil it exposure there was no overlapping of points from the expo-tire- to 5(10 and 055 ppm of ci|ual duration. More Ilian -I hours after exposure, there was some overlapping of points, with the probability becoming greater as time after ex posure inereaseil. From this limited data, it appears that a valid eonelnsion as to the atmo-pherie exposure concent ration of 1,1,1-triehloroet.liane can lie drawn from the decay curve after an exposure if the duration of exposure is known. Many more experiments of dillermg duration and concent rations would have.to be earned out in order to determine a tamily of curves. However, from the data in this paper, one could conclude with reasonable accuracy whether a person had been exposed to 500 or 000 ppm, if the dura- D to .ites mute cxthe dura.i the con- in the rly hours determine e on the which the tinute exentrations hows that - and 35ible overitch higher the decay losure dil ations, f exposure Kuu'iik 3. 1,1,1-Trichloroclliane Expired Air Concentration. Unmans were exposed to a rising concent ml ion, 0 to 2050 ppm, of 1,1,1-triohloiocthane for 15 minutes (Exp. 6). JtiQ Auyust, 1001 Fiourf. 4. 1,1,1-Tnrlilomethnne Expired Air Concentr.-< 1 ion. Compaii-oii of exposure' of nearly eipial length; 500 ppm for 7S minutes (Exp 1) and 055 ppm for 7,'l mmoles ( Exp. ;{). tion of exjxisure vvn- nliotit 70 minute#. It may be possible to obtain a family of curve# which would be applicable to liiiman exposure# by exposing animal# for various periods of time to several concentrations of 1,1,1-trichlorocthane. Inirared analysis of the po-texpo-ure expired air for measuring 1,1 ,1 -I richloroet hane proved to be an efficient method for three reasons. First, it provided an absolute, (|iiuntitati\e idcnlifieution of 1 ,1, l-lriehlorootiiane vapor. Second, it was rapid One minute was rei|iiired to obtain the air sample while five minutes were rc<|tiircd for the analysis. Third, it was sensitive In (1.5 (1,1 ppm of 1 ,1 , l-i riehloroet hane in air, allow ing the detection of the compound mam hour'' alter the cxpo-nre occurred Tin- infrared method has proton u-oful for the analysis ol other chlorinated hydrocarbons in the expired air," as well a- for other volatile compounds possessing 'trong absorption in the infrared.'1 file concentration of I , 1 ,1-I riehloroet hane in the blood was determined lit measuring the change m the infrared -poetrum at the wave length where this eliemir.il i- known to have strong absorption Though the result' obtained indicated a positive relationship between the concent ration ol I , I , 1-l rirhlomel hane in the blood and the concent rat inn III the atmosphere, the concent rat ions m the blood were at -ncli a low level that the results were not ol 'igmlieallee loi predicting expO'itte ri mrcu I rn I inn-, neither were tlirv high enough in give ;m infrnied spec trum which could posit iv elv be identified as licit of 1 ,1 ,1-t riehloroet hane. From the results in, i ol r lion over piolt 1 rieli ol I! nth erci, I riel i vnlio Ti 1,I.i expo Tin k liudn I e\ei i lle-ll ciden llio-i nielli ill'll ' ll.-er o a rn Ti llies, liver ellloi aiie-i rail', Tran III tv sure erl a i ever. ] ii i'ii: com | odlca trat in the n by Ik Sumrr \ mg m of ill, and i expo, I.I ! profi, rone, , VVM' of ). bons in volatile i in the hane in ing the le wave to have ibtaincd een the in the osphere, such a lificanee neither ed spec ified as : results Industrial Hygiene Journal Mil of the exposure to near ane.-lhetie concent ra "dera\ curve" was predictable enough to allow' tions, it would appear that the blood of a person a reasonable estimation of the magnitude of ex overcome by 1,1,1-trichloroethane vapor would posure, 0.5 to 3 hours after the exposure had probably attain the 10-15 ppm concentration occurred. Therefore, llie analysis of po-texposure necessary for a positive identification of 1,1,1- expired air allowed a posiibo identification of the trirhloroethane by its infrared spectrum. The re compound, and provided data with which the sults of the urine analyses verify the experiments magnitude of the cxpo'iiro might be estimated. of Hake, et al " in which it was found that only Chemical, physiological, and clinical labora trace amounts of 1,1,1-trichloroethane are ex tory studios were carried out and correlated creted in the urine. Urinary analysis for 1,1,1- with the vapor expn-ures, The determination of trieldoroethanc by infrared was of no practical the concentration of urinary urobilinogen proved value. to be the most sensitive test of liver stress pro The subjective and physiological responses to duced In markedlv excessive exposures to 1,1,1- 1,1,1-trichloroethane vapor noted during the-e triehloruelhane. The laboratory studies and sub exposures agree closely with those reported by jective responses which were noted lend further Torkelson, et nl.1 There was a rapid onset of assurance that 500 ppm is a'satislaclory thresh lightheadedness at atmospheric concentrations old limit for this compound. exceeding 900 ppin. Hence, in order to have a desirable margin of safety for prevention of ac Acknowledgments cidental injury due to lightlicadeduess, the atmo.'pheric concentration in the working environ ment should not exceed 500 ppm. The eye irritation experienced by 1,1,]-trir,hloroethane users is too mild to be relied upon as a good warning property of excessive exposure. The authors express their sincere appreciation to the volunteers who joined them in the expo sure chamber: 1). L. Cassidav, K, U. Garfield, H. Martin,!1!. H. Ode, V. K. itowe, E. Murrav, and T. Wright. The help of .1. E. I'eter.-on, B. II. The laboratory data obtained indicate that these acute exposures produced no significant liver damage. The data adds support to previous Blake, D. Leaven-, ('. Licht, and (,'. Layne in preparing and analyzing the samples is grate fully acknowledged. studies which have indicated that 1,1,1-tri- chloroethane in high concentration acls as an References anesthetic agent and has only slight capacity to cause reversible injury to liver or kidneys.3,11 Transient elevation of the urinary urobilinogen in two subjects following the anesthetic expo sure suggests that 1,1, l-tnchloroethane does ex ert an adverse effect upon liver function. How ever, none of the other liver function tests employed showed any change following the ex posures. If a subject is clironicallv exposed to this com] ion ml it would seem advantageous to peri odically check hi- urinary urobilinogen concen tration for this laboratory test has proven to be the most, sensitive index to liver stress produced by this type of compound.11 It I).yL Stmcaht. D, S. Joins. 1'. Jt Toiim.i.son, and r L, : I'o'tuxp.i'Uif Anniy'i4- of Orenmc Com* pounds id jin* Him id !v :i Jtapid lnhniod Teoliniquo XafuH is; 102 <,lu|\, 10,'!!l. 2 Smmal'j, H. IX. 'I If, It'itki 1 mi\, 1.. Ham, ash IX S. Kin t \ * InititiPi) An 11 \ 'iv of ('biI'mii Toti.ichlin nlo jijhI Ktlmiml in HI..ml J. Lnh ('Int. Mol. ': 14S (July, I `Mill I . 3. Tohm.lson, T, If,, 1' Oiis, IX I). Mt Cm uktu;, axi> K. IfnUl,- 'I'liMrily of 1 .1 ,1 - Tliclilni not lump ft* ]c- tfiinniiul liv Xnlii.uioi'v \uimrtl- ami Unman SulijurlH, Im, hid Ht/0. lx,sue1, ,/ }u 333 Idi'l, lll.'iS), 4. ItouXtoii'd Tmdoinnik of Tim Umv (Tumiral Company. Composition protortod ly V.S. Indent \o. 2.^11.232. 5. rLTKHSMN. J E , II, It, Ilmi.r, am> J). ,1, Schnt.ideh : Tin1 AtialvM- of An foi llalnid'imlpd Ilvdrnrnrhon Con- 1anmi}tnf*t hv Moan** ol Adsorption on Silica Gel. Am. hid. II i/t). .l.ixo/'. (J'ttitt /? 420 H>o<\ 193i>1. Summary 6. Scji\i JT.it A 3V, \sn II it llmii:' Nino Ymix' E\ponrneo \\ nli Tho Dim- IJalido .Motor. Aw. hid. Jlyg. A series of six controlled human exposures to 1,1,1-trichloroethane taper was conducted. Us .Ifltfir. J ,!J' 03 (Apnl 10(il), 7 IVikm-l'/hnoi fViipninium, Noivnlk. Connootiont, fk Thaojjoi (i.T-dotocfoi Mnr|p| l|l 3(, DiaoL'or Coiporahon, ing infrared spedrometric method', the presence of the compound in blood during the exposureand the concentration of the compound in the expired air after the expo-ure,- were determined, 1 ,1,1-Triehloroethane was observed to give a 132 Talk \\i*m|p Sti \ow Vnik J'X X, 3" 0 IIhimiimi |,, . II 1>. lit hi , \s p X Wun.iir* Im- I'lnu'd < ipiir.il Null Jnhaiod SpoctroplniinnuTOi, J. Opt, Sue . 1 //* ,jx"; 3f` (103m )0. II i: C, J,., 'J' If, \\ im.iim i;, D, X. ltmn i: rsnv, \\n i/ K 1111\\ i; '111 r* Moi il.tilisin ol 1,1,1 - Ti M'liloioot linnr prolonged exponential ``decay curve'1 when itconcentration in the post exposure expired air wu- plotted versus hour- po-texpO'iire. This liv Mio Ital, 1,1/ I \ nl), l nlimnim ii/nt Iloilfh ; 3(11 < Amr, JOOd i. n. Sti.wmu. It. T>., If II. Cm, IX s. Etiuv C L, Ham;, ash A, \V, Suniiii: Hunmn Exposure to ToMflchloro- 2 Amjittili UNil pthvJew* \ ;j>m . JtolntmiHtij* <if K\j>Ufi Air ntnl IUcvhI f'onrenirrttmn'* lo K\|io-um* niul Toxicity. AM.I Arrh, Km irttnim ntnl //* nt/h 1. 51(5 (Mm, IMlt, Stk^aht, It, R, H H. <iO. l>. S, Kiii.kt. L, IIxkr, ami J. E, l*KTi-;itsf>\ . JluiiKin ExpOMHf' lo ('nibon *JVtr:i- chlorale V.-ipor. ot JCxpiictl Air Cimmi- trnlion lo K>piMiie mill Tnxicitv. J, (Jcrupohtvwf Mhl,, to be piiblmlietl. 13, Kiu.n. 1> S.. )! u <;. r. iii'io, AM* U D. Stkwaiit: lnlinim1 An;ilysi> mi fitIimim,1 m the K\piie<l Air. Martu- M'tjpi in )*reji;U!i4iMti 4, Aihm-, K. M,, II (\ M'iNciit V. K. vm* D. R f It I sit ' \;l|'M|' m| 1 1 1 "I f M'h)/>rol bfme I.MfMhxl- chloi nbii m) l)i']nmiju*l lo lixpmnicnt'* mi Idlnr:i- }f<m.tmy Anminb Arrl, /n-/ Urnijnitnnnil ,Utv/. 1: n:> <Mt, im>. ]',\l>l\TION KtAMUHI) ANEW AMERICAN STANDARD -peedying imninuim rei|iiirenicni, lor tin- pro tection of worker, from ovcrexpo.-urc to radiation Mini radioactive dtl-ls ntnl ga>cin the uranium mining ntnl milling industry lms hcen approved by Ihe American Standards Association. This publication American Stumlnnl Ilailiatian I'mhrhim in Lranhun Mines anil Mills (('nnrenlriitnrs) AN.i-i'JUO covers the mining, Irnnspoi Img and refining of ores to produce uranium concent ltd es suitable for the feed material., of production plants. Suggesting procedures for the proper fonlrol of the environment and examination of worker, with a view toward protection from radiation, ihe stand ard is intended to serve ns a snide for manuseinont and regulatory agencies having res[Kmsibility in this field of activity. In addition to offering definitions of till terms used, the standard specifies maximum permi'sible doses from external radiation, permissible concentration, of radioisotope, in air, hazards, manasemeni respoii'ibihly, meilieal supervi,ion, protective measures and ei|m))meut, and transportation ot ore-. A fivepart appendix, though not a part of the ,tandard, deal- with suggested procedure- for measuring external radiation and atmospheric concentration, of radon daughter.-, lor obtaining breath radon sample.-, for surveys of uranium concentrating mill,, and the ventilalion of uranium mine,. Twenty-one organizations including the Atomic Industrial I'orum, Inc., and the National Safety Cpimeil, administrative spon.-ors, are represented on the ASA sec tional committee which developed ihc.standurd. I'arlieipatmg lor ihe govermoeol are the I', S. Atomic Energy Commission, l'. S. Department of l.ahor, Ihireau of Labor Standards, C. S, Public Health Service, and National ihireau of Standards. Copie, of the standard, XiM-lddO. which ,<>11 lor Si'.iK) each. are a\ailahh' from the ASA, Department I'll `JU, 10 East 40th St reel. New York 10, New York. SL 036812