Document RagnkRnmOnJErvVx16QGJwVBV

, 'I .I. c , - THRESHOLD LlMRT VALUES I I i i A Ni I i i j SURE INDICES 1 1 < Fifih Edition i i I I I ! I ! CINCINNATI. OHIO AMERICAN CONFERENCE OF GOVERNMENTAL I N DUSTRIAL HYGIENI STS INC. c ISBN 0-036712-68-6 c '\ BENZENE CAS: 77-43-2 C,% -TLV-WA, 10 ppm (= 30 mdm3)* Appendix A2 Suspected Human Carcinogen Benzene is a colorless, highly flammable, non-polar liquid, with an odor characteristi; of aromatic hydrocarbons. Its physiochemical properties include: Molecular weight: 78.I 1 Specific gravity: 0.87865 at 20C Melting point: 5S0C Boiling point: 80.I "C Vapor pressure: 75 torr at 2OoC Closed cup flash point: 12"F(- 11.1 "C) It \vas formerly derived almost exclusively by distillation of coal tar, but now comes primarily from petroleum, either by extraction or by dealkylation of toluene. Benzeneis slightlysoluble in water, but soluble in all proportions in alcohol, acetone, and ether. At one time benzene was an important solvent, especially for rubber, as a diluent in lacquers, and paint removers. At present such uses are minimal; most benzene is consumed in the chemical industry, as a raw material for numerousorganic chemicals. It is found in gasoline from trace amounts to as much as 30% concentration in some countries. As an acute poison, benzene produces narcotic effects comparable to those of toluene: it is a more potent narcotic than the alkanes or naphthenesof similar boiling points. But the effect of chronic exposure to this compound i s by far the most serious disease caused by any of the common hydrocarbon solvents. Its action on the bone marrow may result in detectable alterations, and, in some instances, aplastic anemia. The reported LD, orally in young adult rats is 3.8 ml/kg.'" It is unique among hydrocarbonsas a myelotoxicant.t21More than 1-10 fatal cases of benzene poisoning had been recorded prior to 1gjg."l Vigliani and Saita'" listed 26 deaths from chronic benzene poisoningin two provinces in Italy between 1960 and 1963. Eleven of these were diagnosed as leukemia, which may develop several years after cessation of exposure to benzene. Most deaths from benzene have resulted from exposures of the order of 200 ppm or more. In a few instancesconcentrationsof 1000 or even 2000 ppm have been recorded in workplaces where deaths occurred. Some of these are: Legge,"' 210 to 1050 ppm; Greenburg;b' 70 to 1800 ppm, with over half above 200; Bowditch,'" 100 to ZOO+ measured; one leukemia case described by Huntern1and Malloryi" six years after exposure at over 200 ppm; Greenburg""' 25 to 1000 ppm in four rooms; Helmer,'"' 140 to 200 ppm aiter improvements; Savilahti,"" 318, 433 and 470 pprn: Kozlova,'"' 47 to 310 ppm; Vigliani."' 190 io 660 ppm. aitcr four years death irom leukemia; J~zwiak,"'~31 IO 156 ppm; ~ksoy,'"''150 i o 650 ppm, and 210 to 650 ppm,'"'' 26 pdtients with acute leukcrnia or preleukcmia; Ikcda."" 100 to 800 ppni, 7 deaths, ,111 tem,ilcs, 1101le irom Icukemia. IVinslow;"" tiowrvcv, rq)orttd hlootl ch,ingcyj i r i wnrlnr.; \\her(' concc'titr,itions ni I)enrc*nc vapor I)c*low I 00 i)pii \vc're Iountl. Hcimaiin and Ford I"' found onr tlis.iih ,wtl ilirc*el,w>wlih Idor)tl changes where air analysis for benzene showed a concentration of 105 ppm. Wilson*'"' reported three fatal cases in a plant where the average concentration of benzene vapor was 100 ppm. In a fifth room, associated with benzene poisoning, CreenburglO' found 11 to 57 ppm. SO far as can be determined the lowest measured concentration of benzene vapor associated with a fatal case of benzene intoxication (due to aplastic anemia) was the 60 ppm reported by Hardy and Elkins in 1948:"' in a plant where repeated air analyses were made, and a number of other workers showed some blood abnormalities. Blanc*' found little evidence of benzene intoxication in a group ' of 90 workers regularlyexposed to benzene for about 13years. Concentrationswere generally low. but urinary phenol measurements indicated some exposures of the order o i 25 ppm.uJ1A follow-up several yean later showed no evidenceor persistingblooddyscrasias. No cases of leukemia are known to have occurred in this group of workers. Pagnotto et found workers in rubber spreading operations involving naphtha with a relatively high benzenecontent exposed to benzene in concentrations which were for the most part between 6 and 25 ppm. A number of blood studies showed a iew abnormalities but only two were serious 10 warrant special consideration. In one case the possibility of leukemiawas raised, but on being removed from his job and given iron therapy the worker recovered. Because oi several job changes his benzene exposure could not be reliably estimated. The other worker was in a group studied intensively over a period of several years by Pagn0tto.l:" He had a red count below four mil- lion, a hemoglobin below twelve grams and suiiered from nose bleeds. His benzene exposure, as estimated from several urinary phenol determinations, was to about 40 pprn. After his exposureto benzene was terminated, his blood picture gradually returned to normal. The 38 workers in this plant were iollowed up for 15 years after the use of naphtha containingbenzenewas discontinued. None showed any signs ofpermanent blood abnormalities. There were three deaths, none being from leukemia. It was concluded that 25 ppm of benzene vapor is safe for most workers, but that since the margin of safety is small, a TLV of 10 ppm was recommended'*" Elkins"*) in a summary of the iindings in the rubber spreading industry, came to a similar conclusion. These conclusions were consistent with those of FuchstJ"in 1969, who found variations in the blood pictures oi three workers but did not consider that the changes were prowd to result iron1their h n zene exposures ot' 19. 28 x i d -13 ppm. re5pwtively. He ,~lsostated that lie could find no datalin the literature011 prov(yj benzcnewi5olling in coi1CCntrdiiOnS bc'low 1b ppm, iior could tic )ind .1(IV Sovtct report which cited r t w m fordecrcasins ille Kussi,ln h\AC to 6 ppnl. Two investigators haw studtcd the etttyts on r,lts o i p*posures .It relatively low lcvrk oi hwzcne v.ipor tor tN\tendLrl periotis. Dcichmaiiti ('I/I, :"' lollntf 1h.11 .illt'r 5 to 8 \\cy+s 01 j Il()llrg'dJy. tlaydwwk cxpowrc &it4-1 m t l -17 ppni. r.its dcvt*Iopecj.I nroder.ite tlrgrcv oi Ieuho~icni~h . t t l w notic rmtiItPd iron1 1 j IO 31 ppm. N J U ('I ,I/:*' towitl ,Idtw-.ise 111tlw ~ I I W t,lo~)dct-11 COUIIIC01r m ~oIlo\ving7 5 6 Iiotirs 01 i-\powri- .it 5 0 i)Im111 t)c*nrpneon .I .chcd- tile l i t H Iinur4,'(1.iy, 3 d.iwin(& Krtlitct.d . ~ r n o u l i t cot 0 x 1rn the 50 , ... .. white cells, a depression in myelocytic activity, and an increase in -Epidemiologicstudies of workers exposed to measured low con- the relative numbers of red cell precursors in the bone marrow were centrationsof benzenevapor have yielded negative or inconclusive ' also observed. c - There have been numerous reviews of the literature of benzene intoxication. Noteworthy are those of the National Academy of Sciences in 1976"" and the NIOSH criteria document on benzene, published in 1974.'31A1s a result of this extremely thorough review, NIOSH recommended a workplace time-weightedaverage standard results. Thorpe,'H1lafter studying the occurrence of leukemia in a population of 38,000 workers in a variety of European petroleum and petrochemicaloperations, some of whom were exposed at levels of benzene that occasionally reached 20 ppm, over a period of.ten years, found that deaths from leukemia "were not abnormal" for the countries involved (18 VS. 23.23 expected). of 10 ppm, with a ceiling of 25 ppm. Retrospective studies of employees of a large chemical company, In 1976, ho\;;ever, NIOSH issued a revised recommendation for an occupational exposure standard for benzene.'"' The key to this recommendation is the statement in the introduction that "Because it is not at present possible to establish a safe exposure level for a carcinogen, the NIOSHrecommendation is to restrict exposure to very low levels which can still be reliably measured in the workplace." exposed for many years to benzene, mostly at low levels, revealed no excess mortality."'.'" A cohort of 594 workmen were divided into four exposure groups: very low exposures, less than 2 pprn as timeweighted average W A ) ; low exposures, 2-9 ppm; moderate exposures, 9-24 ppm; and high exposures, above 25 ppm. In many areas there was exposure to other chemicals as well as to benzene. The duration oi exposure was also divided into four groups, with 186 workers having in excess of 20 years. A number of references are given, primarily to support the characterization of benzene as a carcinogen (leukemogen). Thus, most relate to leukemia cases associated with heavy benzene exposures, either measured or inferred from association with numerous cases of aplastic anemia or other blood dyscrasias. Others are epidemic- logic studies on cancer in which no evidence of the degree, or even fact, of benzene exposure is cited. Thus, in at least hvo of these papers,"'."' the word "benzene" does not appear. In these and other papers the incidence of various types of cancer, including leukemia, was found to be higher than in the general populationamong certain groups of rubber workers. Monson and Nakanoi3j' found 55 cases of leukemia, vs. 43 expected, among rubber workers. It was noted that benzene has been used extensively in the rubber industry, but is no longer employed, although it is a contaminant of extensively used naphtha solvents. The degree of exposure to benzene in the rubber industry during the first half of the 1940-1950 decade may well have been excessive. Wilsonlzo'has noted deaths and blood abnormalities among workers in the rubber industry during the war years who were exposed, on the average, to concentrations of benzene vapor of 100 ppm. Neither Monson-Nakano or other Of 102 deaths, two were due to anemia, two to leukemia, and one had leukemia as a complication. Of these five cases, only one, an autopsyconfirmed pernicious anemia, involved a previous exposure to benzene of significance, 5520 ppm months. The other anemia death, diagnosed as being of the aplastic type, was of a worker with 453 ppm months of benzene exposure. Two of the leukemia cases involved exposures of 545 and 305 ppm months, respectively, while the third was of a worker with only 18 ppm months benzene exposure. To put these exposure data in perspective, three oi the deceased workers had had exposures to benzene equivalent to 40 years' employment at concentrations slightly above or below 1 ppm; the exposure of the fourth, if spread over 30 years, would have been at a concentration of 0.05 ppm. The predicted deaths from anemia and leukemia were 0.2 and 1, respectively. The iact that, apart from the pernicious anemia death, there appeared to have been no dose-response relationship, which apparently led the authors to the conclusion that "no mortality iindings directly attributable to benzene exposure were observed." authors of similar papers quoted in the NIOSH update mention whether or not aplastic anemia or other blood dyscrasias, apart from leukemia, occurred in the groups of workers that were studied. The NIOSH update mentions the consistent observation oi chromosomal aberrations associated with benzene exposure. but iur- ther comments that the implications oi these iindings with respect Nevertheless. in 1977 OSHA issued an Emergency Temporary Standard (ETSPb'establishing a TWA limit of 1 ppm for benzene vapor. (Enforcement oi this standard was voided by the courts). Much of the evidence substantiatingthis action was the same as that quoted in the NIOSH update. However, one additional paper was cited by infante et al,"" in which nine leukemia deaths were reported from two rubber film casting plants where benzenevapor concentrations allegedly ranged from 0 to 15 ppm. This report was critically examined at the OSHA hearings held during the summer of 1977 on a permanent stagdard, with essentially the same provisions as the ETS. The data on benzene exposure in the two plants in question. especially during the iirst part oi the ten year employment period ( 1 9 ~ t0o 1950) covered by the study, were tourid to be incomplcte, unreliable and contradictory. Even in 1976 J NIOSH report oi one to benzene leukemia are still not clear. The possibility oi a chromosomal instability acting as a stimulus tor a latent leukeme genic virus has been speculated upon:'" This question was dis- cussed at some length at the International Workshop on the Toxicology of Benzene, held in Paris in November 1976. ToughJJi had previously reported that marked aberrations were found only in plants where concentrations of benzene vapor were believed to be between 25 and 250 ppm, and that no signiticant change were observed at 12 ppm. Forni,"" however, stated that there had Iwen ,I few positive, as wrll LIS negative, rrports at levels bet\veen 5 ,ind 25 ppm. Tlic conseiiws of opinion w.is that the signiiicance oi the iinding oi increased cliromosonie abcrraiions ior the occurrence 01 benzene Icukt*nii,i w i s still iiot clew. h.\,iiigcri .ifld PoIIi1iI~;. reported th.it ,iiiionS It.ili,iii *hoe workcrs 4. b .J' c D&owin's report'*" of a case of leukemia following an apparent 14. luzwiak, I.: ,bled. Przemylowa 2 0 ~ 6 7(1969). Ibid. benzeneinduced aplastic anemia contains a discussion which in? 15. Aksoy, M. et al: Brit. I. Ind. Med. 2956 (19721. plies that there is evidence that aplastic anemia per se may lead to teukemia, and that delayed cases of this disease are not confined to aplastic anemia due to benzene. 16. Aksovy, M. et al: Blood 44837 (1974). 17. Ikeda, M.: Poisoning Due to Benzene and its Subsrirutes in lapan. International Workshop on the Toxicology of Benzene, Paris (1976). / \ It is the opinion of the Committee that the characterizationof ben- 18. Winslow, C.E.A.: 1. hd. Hyg. 9:69 (1927). zene as a leukemogen by NIOSH is, in essense, valid, although ben- 1 9 . Heimann, H. and C.B. Ford: NY lnd. H y g . Bull., p. 224 (November zene may be what Truhaut has described as a "secondary 1940). carcinogen."'"' An A2 notation should be applied to benzene in the TLV listings. 2 0 . Wilson, R.H.: 1. Lab. Clin. bled. 271517 (1942). 2 1. Hardy, H.L and H.B. Elkins: 1. hd. Hyg. Jox. 3&196 (1948). On the other hand, the Committee does not agree with the NIOSH recommendation of 1 ppm as an occupational exposure standard, insofar as the TLV can be defined as such a standard. There is little evidence that exposure to benzene at concentrations below 25 pprn causes blood dyscrasias of any kind. Setting the TLV at 10 ppm, as a time-weighted average, provides an added margin oi saiety. 22. Blaney, L:lnd. ,Wed. Surg. 19227 (1950). 2 3 . Walkley, ].E. et al: Am. Ind. Hyg. Assoc. 1. 22362 (1961). 2 4 . Pagnotto, LD. et ai: Ibid.. p. 417. 25. Pagnotto, LD. et al: Benzene Exposure in the Rubber Coating lndus- try: r\ Followup. Presented at the American Industrial HygieneConierence. New Orleans (May 1977). If the standard is to be set at the lowest practicabledetectable limit, 2 6. Elkim, H.B.: Significanceof BenzeneExposureAmong Workers in Rubber it is the opinion of some members of the Committee that a value lower than 1 ppm should be selected. In the absence of interfering Spreading Operations. Presented at the InternationalWorkshop on the Toxicology of Benzene, Paris (1 976). substances benzene vapor can be measuredwith reasonable accuracy 2 7. Fuchs, A.: Documentationof the MAC in Czechoslovakia. Prague(1 969). in concentrations at least as low as 0.1 ppm; in the presenceof certain interferences, it may be difficult to achieve the prescribed accuracy and reliability even at concentrationssomewhat above 1 ppm. Because the effects the TLV is designed to prevent are chronic in nature, a ceilingdesignation is not appropriate. At this time, the Com- 2 8 . Deichmann, W.B. et al: Jox. Appl. Pharm. 5201 (1963). 2 9 . Nau, C.A. et al: Arch Env. Health 12382 (1966). 3 0. National Academy of Sciences: Health Effects of Benzene: A Review . -(1 976). 3 1 NIOSHCriteria for a RecommendedStandard OccupationalExposure mittee also recommends the deletion of the STEL until additional to Benzene (1974). toxicological data and industrial hygiene experience become avail- 3 2. NIOSH: Revised Recommendationfor an Occupational ExposureStan- able to provide better base for quantifying on a toxicological basis dard ior Benzene (August 1976). what the STEL should be. The reader is encouraged to review the section on Excursion Limifs in the Introductionto Chemical Substances of the current TLV booklet for guidance and control of excursions above the TLV-TWA, even when the 8-hour nivA is within the recommended limits. 3 3 . McMichael. A.j. et al: 1. Occup. Med. 16:458 (1974). 3 4 . Andjelkovic, D. et ai: Ibid. 18387 (1976). 35. Monson, R.R. and K.K. Makano: Am. 1. Epidem. 103:284 (1976). 3 6 . OSHA: Emergency Temporary Standard for Occupational Exposure to Benzene. Federal Register 42:22516 (May 3, 1977). ' Other recommendations:ANSI (1969)and Sweden (1975) 10 ppm; 3 7 . Infante, P.F. et al: Leukemia Among Workers Exposed to Benzene. A Czechoslovakia (1969) and East Germany (1973) 16 ppm; USSR manuscript I 1977). (1972) 1.6 ppm; West Germany (1974) no value, treats as carcinogen. 3 8 . Young, R. et ai: Walk Through Survey of Coodyear Tire & Rubber Co., St. Maty's, OH. A manuscript (1977). References 3 9 . Harris, R.L. Ir.: Testimony beiore OSHA hearingson the proposed standards ior occupational exposure to benzene. Washington, DC (August 1 . Kimura et al: Joxicol. Appl. Pharm. /9:699 (1971). 2 . Gerarde, H.W.: J o x i ~ ~ l oagnydBiochemistryof Aromatic Hydrocarbons. Elsevier Publishing Co., New York (1960). 3 . Elkins, H.B.: Chemistry oflndustrial Toxicology, p. 103. Wiley & Sons, New York (1959). 4 . Vigliani, EC. and C. Saita: New Eng. 1. Med. 271:872 (1964). 5 . Legge, T.M.: 1. Ind. Hyg. 1:539 (1920). 6 . Greenburg, L.: U.S. Public Health Reports 41:1357 (1926). 7 . Bowditch, M. and H. Elkins: 1. Ind. H y g . Tox. 21:321 (1939). 8. Hunter, F.T.: /bid.&. 331. 9 . Mailory, T.B. ct ai: hid.. 11. 335. 10 . Greenburg, L. et 51: /hid, 11. N 5 . .1 1 Helmer, K.H.: :\cld ,\led. 5c.trd. IIH:35J (1044). 12. Savilahti, M.: &ch. Ccrvf*rbc./)Jrh.u. (iwwbehvg. I 5:147 (l%6). 19771. .40. Thorpe, 1.1.: 1. Occup. ,\led. 16:375 (1974). 4 1 Ott, M.C. et al: Mortality Among lndividuals Occupationally Exposed to Benzene. A manuscript (1975). 4 2. F i s h k k , W.A.: Testimony beioreOSHA hearingson the proposedstandards ior occupational exposure to benzene. Washington, DC (August 1977). 4 3 . Todaro, G.I. and R.I. Huebner: Proc. Nat. .-\cad. 5~;. 69:ioog (1972). Cited by NIOSH in reterence 31. 4 4 . Tough, 1.M.et ai: Eur. 1. Cancw 6:49 ( 1 ~ 0 ) . -I5 , Forni. A.: Krpon. PfOCCedingS of Inlern.tIiortj/ \y()rk,/lop on the TOXIc o l o ~ y01 litanzcne, Pairis(1976). 4 6 . htaugeri, S. and C. Pollhi: U t w c n r II.itviiop.ithv, C.c/lu/Jr U~mag'. .ml (./iro~rio~omCeli.tngo. Pcr*on.il Kcw.irctlc.,. I / ) ; ( / . 1 7 . DeCot\in, R.L.: /.,.\.A/.A I R j : 7 4 R (l%3). 1 3 . K ~ S ~ O VTJ.A, . and A.P. Volkuva: Gig. h i t . ,!j:?Y (1960). Cilcd IN NIOSH i n rvieriwce !1 , 49. Truhaut. K.: /'roc-crtbn,qrS or Ihr X I frittvr~~tt~onC.t.,ljrIcpr C t ~ l l g r t * ~ ~ . F l t ~ f i ~ cItt .~lIv, t I Y i 4 ) . 52