Document bOyJrm6LjKjz5QodmqZ61aK1g

API TOXICOLOGICAL REVIEW BENZENE SECOND EDITION, 1960 The information and recommendations contained 51 thk publication have been compiled from sources believed to be rdiable and to represent the k c caurcnc opinion on the subject No wamnty, p r a t c e , or wrescnution is made by the Amcricazl PeuoIeum Institute as to th8 absolute C O r m t D e s t or sullicicllcy of any representation contained in this aud other T o ~ i o g i c aRl eviews, and the Institute luarmesaorupodmyincoMach*onthacwith; nor can it be assumed that dl affappblesafttymclsyrsr are coaa'mai h t h i r a n d o t h e t T o x i c o ~ d ~ t?Cttutothrrotddithli~=ySberrquircdundarprrcicPlPrWaxccp bEaoricwditionsorcirnmprtpnck lheAmaricanPetro~krr$attqassponror ofthis review, aka no poddonas to whuheror not any meLhnd conmiud hmin im covemiby an exiswpuent.nor as to the rrIiditpof any patcat aUq@ to cover any such ii.er6t;l Funhamorr,nothing containuiin this review grants any r:? by implication or otherwise, for the n u d a u m , de,or use in coanccm'nwith rrnymahod, qpmms. or product covered W ltctos Pam% ~ r r v i e w w a s p ~ a r c d a t t h e H v wodt ~Pulbtic Health, Bortw.Mass.. under the direction of Professor Philip Drinker. Aayone defiring to submit additioad information or proposed changes for consideration prior to rrirsuance of this miew it rcqwstcd to d them to the American PeQoIcum Institute. AMERICAN PETROLEUM INSITIXTE 1271 AVemn OF THE &=CAS NEW YORK20, N. Y. i API TOXICOLOGICAL BEYIEW OF B E " E III. Maunfacture, UMS, and P o d l o Sources of Expo#- Benzene is usuaUy m a a u f a d from catalytically 6strucnaalformula: reformed light naphthat from which it is isohtcd by dirtillation or solveat extraction, Bmzenetusuiasadventinmaayappficatioru. It Molecular weight: 78.11 Synonyms: benzol phene is at0 used as acomporruuof some motor fuels and as the raw materialbr tbe mao- of a &os2of syn- thetic chemicals. Examples are: styrene, phenol, anrrinc, DDT, chdon>bcnzcne, cnmcnc, nitmbaulcnt, II. Ropertier and Characterhtics diphenyl, cyclohcxam adipic acid, and detergeats. &cause of its voktility, bcmzne presents a vapor Boiling point =SO.1 C (176.2 F) at 760 mm, Mdthg point ~ 5 . 4C to 5.5 C (41.7 F to 41.9 F). .Vapor pressure =74.6 mm of mercury at 20 C (68 F) .Liquid density =0.899 gper miIlEtcr at 0 C (32 F) Explosive limits =1.4 to 8 per cult Rash point =12 F (closed cup). Refractive index=1.5016 at2OC (68 F). .Specik graviiy =0.8787 at 15C (59 F) ' mg per liter =313 ppm; 1ppm=0.00319 mg per liter. Benzene is a clear, colorless liquid with a charac- hazard. The vapor may arise from numerous handling operations, as wed as from leaks and accidental spills. Skincontactis a possiiility when handling or packaging. IV. Toxicology I Acpts Efibetr Acute benzene poisoning generally results from the - -inhalation of relativdy high concenuations of vapor. Exposmetoair- g~incollantratioruof 19,OOO ppm to 20,OOO ppm (61 to 65 mg per liter of air) mayuusc death within5 to 10 min, whenas con- teristic pleasant odor at low concentrations and a disagreeable odor at higher concentrations. It forms a hi@y flammable and explosive mixture with air at con- centmions of 7,500 ppm (25 mg per liter) are dan- gerom to li5e in 0ne-M to m e hour.* Severe toxic &em m y be causcd by 1-hour exposure to conan- centrationsran- from 1.4 to 8.0 per cent buuene by trations of 1,500 ppm (4.8 mg per liter). Concentra- volume. PIUe berwne burns with a JreIIow, luminouS, tions of 500 ppm (1.6 rng per liter) may lead to symp- smoky tlame and is a &e hazard d e s proper care is toms of iIlness when exposure continues for more than takenin handling and storage. a short time.s Benrene is relatively insoluble in water (0.08 g in 100 mi of water at 22 C ) but is readily misci'ble in all Inhalation of 50 ppm to 150 ppm (0.10 to 0.48 rng m h )o f k o z c e e f o r ~ h o ~ ~ p t e d ~ t b e a d a c h e ~ proportions with alcohol, ether, acetic acid, chloroform, a d Wtd~.T ~ cnd-bload COUU~ de- urbon disuIfidc. cjrbon teaEhloride, and Similar OT- c r e a d , the white-bhd count was unchpngd eXCCpt ~ s o 1 v e n t 3 ,commerc*lnl~ i s p r a c t ' i ~ y n r v e r for mild tympkoqmsis, eosinopenia, and mo zpure and usw,IIy contains varyin3 mounts of xylene, penia. n e ~umin-globulinrario increyed phenoi, and toluene; commsrcid benzene also contains at tower amca~tmionsbut decreyed with highu con- traces of carbon disdde (0.2 to 1.0 per cent), thiophene (0.1 to 0.2 per cent), olehs, naphthalene, and C U I ~ ~ O ~TUlw h r y coproporphyriru i~- crulsw& w h c m the urinary sulfate ntio was de- similar substances. ciemidy, benzcne is the sirapicst of the m d c hydroc;rrbons. It is rclrrtiycly stable but is capable of a variety of subsdartion Zwctiolu such as chlorhrio4 -aimtion, sulfomtioa, and aUryMou. Benzene is an ex- &nt solvent for most organic subsonces. cretmd.' Skin contact will awe dehydration and defatting which may lead to dcrmtitis. Systemic intoxication by cutaneous absorption is unliirely. Dtini;ing knzme causes acute symptoms with IouI cvidcaa of ;~cutcirritation of the mouth, throat, and stomach. A tablespoonful or less of bcnrme when d- Ficurcs rcfcr to BIBLIOGRAPHY on p. 6. I d h3s been knownto Qufo serious collapse. s u b s - 2 BENZENE 3 q-dy, it m y result in bronchitis or pneumonia which is probably caused by benzeneentering the air P~BWFS.' i Acute exposure to benzene exem a toxic action on the maat OCNOUS system. Benzene first behaves as a stimulant--in the d y stages of acutt poisoning, per- sonsshow excitemen& euphoria, hilarity; ttreaquite a d - d d y this changes to weariness, fatigue, and sleepiness, followed by coma and death.' Acute exposure to benzene produces rapidly inmas- ing symptoms of dizziness, cxatation, and pallor, fol- lowed by flushing, wdcncss, headache, b r d h s n c s , CO1IStriCtiOn in the chest, and fear of impending death. V i disturbances,tremors, andmuscularwedmess arc also encountered. The victim may lose conscioumeJs and pass into wmaor may develop acutemania and de- lirium. Convulsions occur frequently. Death may supervene almost at once or several hours to several days following exposu~c.~ Recovery from acute benzene poisoning requires from one to four weeks. Immediately after exposure then are temporary symptoms of chest and head pains, shortness of breath, giddiness, nausea, and loss of ap- petite. Evidence of unsteady gait, nervous irritability, and breathlessness may persist for two or three weeks, whereas cardiac distress and a peculiar yellow pallor to the skin may last for as long as a month. Recovery from acntc poisoning is generally complete after this period, ( although evidences of chronic benzene poisoning may be urcountercdlater., Benzene also sensitizes the heart muscle to the action of epinephrine, so that instant death may occur as a result of ventricular fibrillation.' Musc&ar activity in- creases the rate and severity of acute benzene poisoning. Persons dyingof acute benzene poisoninggcncraIly show absence of clotting of the blood and widespread pe- techial hemorrhages in the brain, pleura, pericardium, Urinary tract, intestinal tract, mucous membranes, and skin. There are no specific lesions of diaglostic im- portancc.9 Local effects from acute exposure are seldom seven. Continued skin contact with benzene results in defatting of the skin and leads to erythema, dry scdiug, and, in some uses. the formation of vcsicut;u papules. Pro- longed esposurc may produce lesions resembling &st- or second-degree burns. It may cause considerable ir- ritation of the eyes or mucous membranes of the nose and throat on contact. Benzene poisoning by skin absorption has received s u n t attention in the literature. The possibiliry of per- cutamus absorption of benzene has been studied in three uses. Immersion of the hands and f o r e m s from ( 25 to 35 min showed no evidence of skin absorptioa1 Unquestionably, small amounts of benzene c i u ~be absorbed through the skin, but it is very doubtful that enough would be absorbed by this route to causc sysremicpoisoning.' b. (=hronia Effsctr Chronic benzene poisoning results from repeated or continuous exposure to relatively low concentrations of bermme vapor. The levei and degree of exposure necessary to produce poisoning vary widely. There are at least two well-authenticated cases of poisoning by np e a t e d exposures to 75 ppmu The toxic action is exerted mainly on the hematopoietic system. It may take months or even yean to show harmful effects. Symptoms may be present over long periods, i.e. headaches, dizincss, fatigue, an ore^, and dyspnea. They may be varied and vague and not obviously connected with benzene poisonin3. During the early stages of poisoning, Heinz bodies may be present in the red-blood cells and a neutropenia is often seen. At this stage the blood uicture may retmnto normal after removal from contact with benzene. As chronic polsorung progresses, nausea and vomiting, burning sensations of the eyes and throat, and hemoxrhagcs from mucous membrana, tongue, and gums become manifest Purpuric spots and ecchymoses may follow the slightest injury, and epistaxis may occur. Menorrhagia, metrorrhagia, and spontaneous abortion may develop in otherwise healthy women. Blood examhation at this point may show leukopenia (below 4,000 white cells), neutropenia, and a severe anemia. Later the platelet count fatl- :: *>-: thrombopenia is marked, The blood condition,at this stage, may have become h v c n i b k The clinical picture of a worker with chronic benzene poisoning at this stage is characteristic-he complains of headaches, giddiness, drowsiness, lassitude, loss of appetite, and nausea with occasionalvomiting. He looks pale; is short of breath; has a rapid pulse, a lowblood pressure, and a mildly elevated temperature. He may also have epistaxis, bleeding from the gums, a purpuric rash, or subconjunctival hem~~hageJT.he condition progmses sbwIy to acute leukopenia ending in fatal aplastic anemia.* Repcated small doses of_ben;tuv:hv mwth c a p~roduce the same tvpe of chronic poisonin3.7 Repeated Contact or benzene with the skin sill cause dehydration and delipidition predisposing to dermatitis. Benzene is relatively insoluble in body fiuids and tissots. Therefore, only small amounts are absorbed by the body. Equiliirium between blood and air is approached withii a few minutes after exposure is begun, and p n c t i d y completeelimination of benzene from the - -.. API TOXICOLOGICAL REVIEW blood accurs withii a few minutes aftcr exposure is tere a t c d . Higher concentrationsof benzene are obtained 4 tissues with a mater fat content, and saturation and elimination arc more graddU Human subjectsinhalcd benzene in concentrations of 340 micrograms per liter of air for 5 hours. Between 33 and 65 per cent of the inhaled benzene was retained (385 mg). During the dcsaturation period 3.8 to 27.8 per cent of retained benzene was excreted through the langs and 0.1 to 0.2 per cent in the urine and other body excrtta. Of the absorbed buuene, 9.7 to 42 per cent was axcreted in tfu urine as phenol, 0 to 5.4 per cent as pytocatechol, and 0.1 to 3.3 per cent zu hydroquinone. Excretion of phenol and pyrocatechoiwas highest during tht fint 24 horn and complete in 48 hours, whereas hydroquinone took more than 48 hours. Excretion of organic sulfates in urine of exposed subjects was in- creased. The opinion was expressed that benzene affects t&e metabolism of proteins, the metabolites of which are excreted in urine as ethereal sulfate^.'^ Benzene is Unique in its myeIotoxicity. It has been shown that the introduction of an akyl p u p into the ammatic ring results in a loss of its myelotoxic property. This diEerence may be a result of the difference in the metabolic pathway. Benzene is mttaboli#d to phenols and quinones which inhtiit c c U produ&on. The in vivo metabolites of alkylbenzenesarc alcoholsand carboxylic acids rcsuitiq from side chain oxidations. These compounds have a Iow-orcicr toxicity and are devoid of spec& ccil destructive effects.a* A variety of reactions may be encountered as the result of the chronic effect of benzene poisoning. ZCiis= little cornlation between the degree and duntion of exposure and the severity or nature of the 6ndings in the blood on microscopic examination.lS They may consist of a reduction in redcell, whitecell, or platelet levelsin any two of these or in aIl three. These changes may develop gadually or suddenly. The blood usudly shows a moderate reduction in red ceiIs (below 3 5 million), white cells (below 4JOO), and pl;rtelets. Blood examinations for evidence of benzene poisoning should consist of a complete study of red, white, and platelet ktions. Progressive c h i m p arc more significvlt than the absolute levels. In anemia caused by benzene, it has been shown that then is a constant increase in serum iron (average increase. 213 micrognms) which is associated with a nduction o trimsferrin (average reduction. 225 micro- -). The iron saturation of transferrin is above normal and is matched by iron saturation of the tissue. The uusc of the disturbance of iron rnet3bOkIl in benzene poisoning is the failure of the marrow to utili= iron zu well as incrwed intake of iron supplied pare n t e d y by transfusion.'* There is some evidence that chronic benzene poisoning produces a bloodclotting defect which is uuscd by functional and morphological as well as a q m u U v e alteration of the piaulets.1~The marrow cclls exhibit a decrease in peroxidare in benrene poisoning, Because benzene inhibits granulocyte maturation, it may act on peroxidase metabolites,or the peroxidase may be used up in detoxifying beIucne.1a The bone manow may be hypoplastic, fairly normal, or hyperplastic in appearance. Abnonnai forms or young cells may abound, and leukemia as a rcsult of chronic benzene txposun has been reported. various individuals diEcr in their bone marrow response to benzene-es with symptoms fairiy soon after exposure usually have fewercells in the marrow, whereas cases developing later arc more apt to have an increased number of cells in the marrow. It is believed that this represents an early weeding out of those who develop hypopIastk changes, rather thana gradual shift from one type of response to the other.'*- 20 In a long-term follow-up of chronic benzene poisonk g 4,538 cases wen studied from 2 to 12 years after assation of work involving exposure. Then has been oulp one fatal casc, six cases involving bone marrow Changes, and one cas8 of Lwpored resistance to in6tc- tiam~ h t ~ t h e n ~ ~ n r c t i c a l ~ ~ n b a t s h o w aegrec!5 of n e w Bennae is eliminated from the body via the lungs and the kidneys. In one study C-14 labeled benzene was given orally to rabbits. In 2 d a y A' per cent of the dose was eliminated in the expired air (43 per cult as unchanged benzene and 1.5 per cent as carbon dioxide), and 35 per cent was eliminated as metabolites in urine (23 per cent as phenol, 4.8 per cent as quinol, 2.2 per cent as catechol, 0.3 per cent as hydroxyquinoi, 0 5 per cent as L-phenylmercapturic acid, and 1.3 per cent as trans-, trans-muconic acid). Five per cent o the administered radioactivity was found in the tissues occcmingmoiniy as metabolites." Certain factors have been noted which influence individuai variation in susceptibility to benzene, Over- weight mdividuds arc more commonly ahtcd," and a low-protein, high-fat, Iow-Vitamin C diet is said to promote the discye. ?he presence of heart or lung dis- ease and liver or kidney damage arc believed to p n dispose to the condition.2L Pregnant women may be more susceptible to benzene poisoning.4 Patholo& ul changes in ovaries. testes, thyroid, and pituitary am ottriiuted to bearcne; and changes in women workers leading to sterility arc emphasizeds ,. S (- I I \ 6 R.com& Lkair Of A w p h r i a The p e d y rccogni-rrd maximum acsqtabie con- c ~ l d fonr benzene vapor is 25 ppm by volume in -ait (0'.08 mg per In G liter c of air) for an 8&0m d d y ex- the &~ - permissible COLL- centration to which workers may be exposed k 31.3 ppm by volume in air (0.1 mg per liter of air).= The Massa- &useas laws have established 25 ppm as a maximum benzene CWccntration.= V. Trartmeat Acute benzene poisoning should be contidend an -acute cmergenrp. Remove the victim from further ex- ponrtt at once and caR a physician immabtdy. The patiat should be kcpt warm and quiet in the recumbent position. If breathing has stopped, artificiat respiration should be started at once. Oxygen should be administered by a q d e d person as long as neceJsary to maintainthe normal color of skin and mucous membranes. Tbis may prevent the development of severe pulmonary edema Stimulants WilI rareiy be necessary when adequate oxygenation is maintained.' Care should be takcn that xcsctrers are not also overcome by vapors. Chronic benzene poisoainq: is extremely refractory to trcamzenf It is most important that the condition be diagnosed d y and the individual withdrawn from furtfrer contact with the hydrocarbon. Btood transfusions arc temporarily useful in combating severe anemia. VI.F tioa The prctmploymcnt examination should include a detai&dhistory,physical examination, chest X-ray,and compIete biood c o u n ~WO&K with organic disease of the heart, lungs, liver, or kidueys should bc elhbi- naad, as should those with a history of urcwus ben- ~~.~intor;ication or evidence os an abnormafty of &e bToodor bloodclotting 4: Paiodicnzlwminations &odd be d out n g ~ - m y , the bqucncy being determined on the basis of the pFobabIe d q m of exposure. The examination shouid indude a brief inadhistory &phytical e x s u b t ion, together with a complete blood study. The presence of p n O~f thc blood h w h imuirerecXamina- tion at l u s t twice at LotcrvaIs of one week and 8 thorough study ot the working conditioor. Unless there 's notice3ble improvement on n-cxamimion, thc worker *odd be withdrawn from finther exposure. The foUowing changes uiI for rc-amnhuion: white- btood count less than 4,000, rcd-blood count less than 4,000,000, hemo@obin less than 12 g per 100 ml (80 per cent), blood phtcku less ttWn 1 ~ , p~er 0 cn mm, dXcmtial count lcss than 50 per cent poiy- mnrp$onudeat leukocytes, and more than a very fcw lmmrfiln blood ccils. l k urine suifate test may be uscd, not as a dkigkoStic test, but as a measure of the dcgm of the cumnt benzene exposure. It das not measure ttre degree of benzene poisoning nor the blood -F prrsent' VIL P r e c a U t i O ~ H ~ a l r W he safety mcasufcs ncoesary for the pnvcntion of knmmc poisoning arc primarily those designed to pn- -the inhalationof benzene vapor. Proper ventitation, local exhaust, and dosed systems should be lued to maintaina concentrationbelow themaximumacceptable concentrationof 25 ppm by volume in air. All apparatus and piping should be inspected regularly and sys- tematicaIIy for Ieakap. When excessive concentrations arc unavoidably encountered in operations such as the draning of tank cars, vats, or storage tanks,air masks and protective clothing should be E~u~oY- ees should be fuilv instructed regarding health hazards w a may be present in the h - & g of benzene and should * ly mmrt any unusual Symptoms or iTincss. CIothing wet with ben&ne &odd be removed Promptly. If the hands an litely to have contact with benzene, impervious gloves or protective creams &odd be pscd Proper ventilation, routine plant inspection, c o n ~ofl benzene air concentration, and periodic medi- cal cxminations am an of the UmoSt i l x l p o ~ ~ The concentration of buuene vapor in tbe airphodd be cnecxcu repany m IucamnS w@xe me pdSiibility os e~xsslvceqosurc maybe mcountena.-'~lllSmapbe done by a vanety ot procRIUES anhng wmch arc the bu- tanone met&od,~ the mdinitrobcnzcne reduction method,* an absorptiornetric method, and a photo- colorimetric dctcm'mltioa The latter method in- volvcs the nitration of benzene with S ~ m o vmix- tnre which fonns mdinilrobanenc. Thir gives a co&r reactha with acetone in altralinc solutions. Under cimilar cwditions toluene gives a faint vioIet color. Based on ttrese photocolMimtaic mahods small qPontititr of benzene ;mdtoIuene can be determined in More d y a silica gel adsorption method has been rrported.*O Aaurafe qtmntitath study of ;rrmotphcrk bemrne as low iu 0.003 mg per ml (0.9 ppm) may be determined by adsorption on acti- voted silica gcf and elution with abtotute alcohol. ThC benzene conrent is then determined spcctrophotomeui- d y accotding to ASTM Desiparion 0 I017: Method - .4 .*.\~ APX TOXICOLOGXCAL REVIEW of Test for B e m e and ToLIcna by Uitraviolcr Spec- tropiroromray. The range of musmmcntis 0.003 m3 1 1.28 mg per liter. 'The m u n yield was approximately I. 'tpercent There am a number of inst~nentton the markcc tatrieh measure hydrocarbon air con- ?lu: pia#nce of more thanone hydrocarbonvapor, however, prodnas erratic results. Ym. BibEogmphy 'E. Browrring, Toxicity of Zndumicrl Orgun& Soivatu9 lnkrrairrl H d t h R a s h Bomd Report No. 80, badon (l937). 'M. G. Jacobs, The &dytiaJ ChaniraJlof ZndvtairJ P O i m N , H e ond solvacrr, 399, *Ptlbh& 5InsNerrYork(l944). * C D. Hod- and H. N. Holmes, Handbook of chmrkar muf Physics, 25th 4 x 4 chemical Rubber Pub- lithtrg Co, C k v e b d (1941). Y. Headersoa and H.W.Haggard, Noxiout Gam and the Principles of Repitmion ZnpUcncing TheirAction, 164, Chemical Catalog Co, New York (1943). m,"M. W.GoidbW "Rcscarcb in Iadusuiai Health in the clhamicnl Brit. 1. Id.Med. 12 1 (19SS). 'Genichi Watanabe, Juu Ysrhioka, Harm Hondo, Muao Muouchi and Takem SpltpIlUchi 3. Sci. Labour (Jopcm) t9 70 (l9S3); &om C k A b . dOJZ (19S4). 'vltbrsshald Limit v8iUes for 19159," Amarc*rrcr o n - f- of Govaznnezml krdrrrrri.l Hyghhts. A M A . Arch I d . E& 20 266 (19S9). (.- 4 J. B. LL&, "OccupationalHaWH;mrdt iotheManu- ctpra of XnsaUickkw S. Afr. Jour. CZin Sd. 3 212 9m. 'J. L Svirbely, R C Dlmn, and W. F. von Oettingen, 'The Acute Toxicity of Vapors of CertainSolvena Contain- ing Appreciable Amounts of Benzene and Toluene,"J. I d Eyg. Toxicol. 25 366 (1943);aud "2hc Chronic Toxicity of Mod- Concentmtions of Benrcne aud Adixmra a Bemzene ami Itr Homoiopues for Rars aud 00s"J. I d Hyg. Toxicot. 26 37 (1944). mG. L Corm urd A. ?vfaltagiioti.*"S&ndy On Trans- cuaaeous Absorpdon of Beuzeae.'' Med. &vom 46 194 (1955): from Chmr A h . , I6232 (19SS). =A& Bow&& a d H,B. Elkin%"chlwic Expasmra to Bmz8ue-I: The Industrial Aspe~6,"1. I d . Hyg. Toxicol. 21 321 (1939). aH. H schnnk, W. P. Yins S. J. Pavec F. A.Patty, and R. tiorr ot R B Sayers, m "ABbodsoprpr-tion. -D * llldEfimba- a d RUMS ot Door EX- pard to 8- Vapor." 3. I n k Byg. T O W . 23 20 (1941). "I. Tebiogu. V. Bagtnn;lrTucron. a d I. Kudrru. a&feaboiisaolf Beazcne in MWL" Qufar Univ. (Pngw), Pfiacovni Lekamvi 4 17s (19S2); han Chent. A b , 4181 (1955). "EL W. Gaydc T O X i C O I O ~ U ISIudiCs ou Ky*bwA M A A& Znd. Ha& I3 468 (19S6). "L A.Erf md C. P. Rhonb,"Ihr,Hanrtological Ef- deca Of POiSOh&" 1. Z n d TO&- Zl 421 (1939). NB. Panis and L Myeo, "Mcubokmr of Iron in E b m p t h k Due to Bcmmk- Mad lovoro 46 325 (HSS); lbom than. A b . , 14996 (HS5). lrG. Saita, E. suarrlli, a d F. Cdaruu. "The Blood Qr#ing-mM~~wMd Lrr#r, 45 313 (1954):fromChan. Ab., l16S2 (19%). uV. Rat0 md G. F.Rpbina, 'gorrs bQnow Peroxidase Bemzene P o i i n Univ. Turin ( M y ) Mtnavo mad &357 (1954);fmm Chmr.A b . , S662 (WS). uT.B. Zvfallory, E. A. Gall. and W.J. Biicklty, "Qromc kposma to Bcmene-III: The Patholoeicpl ResU4" J. Ind. Hyg. Toxiwl. 21 3S6 (1945). mF. H. Htmtet, "Chmnic Exposurr to Benzene-II: Tbe clinical meets," J . Znd. Hyg. Toricol.21 331 (1939). =&rei Rcjsck aad Maria RcJtkova, "Lo03 Term Ob- smmthm of Chmaic b e n e Poisonin3," Acrtx Me& S d IS271 (1955). =D.V. Parke and R T.WiXhms, 3tudies in Detoxia- tiOD 49, Meubolism of B- ct' B a - =e". Bdoeium. J. 54 231 (19S3). *A. F a %e bcntoiitmc p m f d ~ n e iP, ~rase med. 41 6, U9 (1933). *C. E A.W i , 3- of the National slfctg Of -1 h h d # w 1. I d &78. 9 61 (1927). J. L. Gutkrres de Mcr,3tczEV m Labarem cuwd by Benzene and Other Solvents" M t d y scpuridod &qo 31 4 (1954);from Chem. Abm, 13556 (1955). =''.R' W. HOCSCK~O ~ O ~ C"TCO, XMO~ofPSolP k t h 4 11 (1951):from C h a Absu, I1178 (19s). at Mass. Div. of Occup. Ryg. E& Mprfmum Allowable CorrcenaorrO* N (lSS7). moaarpotion and RrolrA Encrdopcdh of Hypimr, Patholop a d sodnl Wetfer, Wamtm* ml Laboroacc, GQBV~1,228 (1930). . .SF. L -ya, B. E. Rcnzi4 rpd S. S G i Dedammraoo of Benzene and ToIueae," N d Zap&& Dnrpropenvvsk. Gosadkzs~Univ. 43 45 (19~3)f;rom Clum.A b , 783 (19s). ~-Perovntm,ecrumirudonof Atmorphclic Beuzaw C m c a w m h by Displncement FoIlowhq Adrorgtioa on sillcr Gd." Brit. J. Znd Med. U 210 (19S6).