Document MGLdq5qRy0grOBKn7mzYw3nrz

P r e p r i n t No. 56-78 N Presented a t t h e A?! Refining Departzent 43rd Midyear H e e t i n g Toxicity and Worker Health T h u r s d a y , May 11. 1 9 7 8 Toronto, Ontario, Canada American Petroleum Institute 210: L Street. Northwest Since izs ori,-iz?al isolzzi~nf r c n ~ o z d c ntown gas and t h e reccgzizics ~2 i t s e x c e l 2 e r . t s a i v e n t properties i n 5F.s .f i r s t q g a r t s r c2 a aajor ckextizsl 5t hueiA` 1c-9:-zt5h . .c e z . ' ~. : z , *,` 9{ tAc3c2;*- I . b &\ e nzen Over e e has leve d n e velo bill p i e o d n inco ?our.Cs w e r e ; ? r ~ & i ; c s C2 2 t h e u9 - .S. in a n d-.-e ` -2t~ib' similar amounts were m a n u f a c t r e d ir. Ezrose acd Jaczr.. A brief sumnary of t h e neca- bolism, t o x i c effects am2 r e q u l a t o q h i s t o r y i n t h e U . S . will be p r e s e n t e d togecher w i z k soxe c o m e n t s on t h e p r e s e n t OSXA Permanent Standard, Hetabolis m A f t e r inhalation of benzene by a mammal, a b o u t 4 0 % is e l i n i n a t e d unchanged in expire2 a i r . The l i v e r c o n v e r t s t h e r e m a i n d e r t o benzene oxicie. S t 2 s e q u e n t l y , some of t h e benzene oxide c o n v e r t s to ?keno1 5.1 spontaneous r e a r r a n g e n t , sone goes t h r o u g h benzene glycol f o r x a t l o n t o catechol and t r a n s - t r a x muconic a c i d and a t h i r d ? c r r i o n rezcts with g l u t a t h i o n e t o produce phenylaercapturic aciC. The phenol. uz5ercoes c o n f c s z t i o n t o form p h e n y l s u i f a c e s a n d s h e n y l g l u c u r o z i d e s o r goes t k r c c ~ hhyd.roguino1 t o c o n j c q a t i o n am5 elixinat2oa. Nost c a t e c h o l is c c r ; j q a t e d and eliixina- .t e d , small anmats beizg oxidized to h y d = o x y h y d r ~ q u i n o l ( ~ ) * (See F i g u r e 1.) Acute Toxicity As shown i n Fiycre 2, direct s k i n contact d i l a t e s b l o c d vessels, re~!Censand irritates the s k i 3 and removes n a t u r a l f z t . X f this sequence is repeated Lke skin d r i e s , scales and cracks. I n general however, noma1 skin does n o t absorb benzene rapidly. Eye c o n t a c t p r o 2 u c e s siailar i r r - i t a t i o n and i f benzene is n o t removed s e r i o u s t i s s u e injury o c c u r s . Mucous membranes (nose, mouth, t h r o a t , lungs, e t c . ) also are i r r i t a t e d e a s i l y by benzene and t h e l u n 5 may d e v e l o p a chem i c a l pneumonia. Inhalation of hich c c n c c n t r a t i o n s c a u s e s e x h i l a r a t i o n , t h e n d e p r e s s i o n with drcwsizess, f a t i g u e , d i z z i n e s s , headache .. and n a u s e a . Ultimarely u I ? c c n s c i o u s n e s s , c m v u l s i o n s and. d e a t h may occur (1) (See ~ i 5 u r e3 , - 1- .. The incidence of these nar.ifcstz.ticzs is ver:i 2 i f f i c z l t t o d e t e r m i n e , prinarily b e c a u s e inost oi t3.e literature reports r e f e r t o single o r s m a l l grcu?s of p a t i e z t s . IC t h e f e w series where l o n g i t u d i n a l studies of e-zployees ex?osed t o benzene has exceeded two y e s r r s , m o s t h a v e shown a :SE~=ZC:J t o r e t u r n toward no,nal when e x p o s u r e to b e n z e n e ceesee. Scze 2 , a t i e n t s however, did show a p e r s i s t e n t l y 3.cnered ~ 5 i t sc3uii= o r p l a z e l e t count when compared to a c o n t r o l grozlp(3J. C l i n i c a l m a n i f e s t a t i o n s cf 5enzeze iz?dzceC!p a n c y t o p e n i a -g e n e r a l l y tend t o b e rather nonse~eciiiz222 3;resl;;nably r e l a t e d to Enezia easy f a t i g u e , heatiacke, zaltisi?, dizzizess, p a l p i z a ticz and dyspnea 02 exertion (see ?L=:zs 5 1 . Since t h e developa e n t of anemia i s u s u a l l y gzz6usL t,".esa z z y n o t Se r e c o g n i z e 2 u r , t i l L%e hemogloSin has dzopped befszv L2.3 5rzrrs. Where l o w w h i t e blood C O - ; ? ~ cz l c w ? l a t e l e t c o u n t are prornizent, t h e c l i n i c a l ficcixqs znay 5 s zcze d r t z a t i c and sr;ec i f i c . I n f e c t i o n is t h e outs=en6izc f e a t z r e r,f a low w h i t e -ccc..t z p p e a r i n g when counts a r e i n :.?e z m 5 e of 1000 1200 (S-4,200 to 10,000) and may le26 to deatk. Platelet counts 02 30,000 or less (E3-140,OOo to 440,OOCj r a y be z a i f e s t e d by p e t e c h i a e , purpura o r frank blee6izq izrerzsil:? o r e x t e r n a l l y . One of t h e most c o n t r o v e r s i a l q x e s z i o n s r e l a t e d t o t h e hematopoietic e f f e c t of benzefie e x c o s x c is wrhetkez it r e s u l t s .H i s t o r y of t h e E n v i z o n x e n t a l C o r ~ t r o lof Eenzene i n t h e U.S. (See F i g u r e 6 1 The Pre-1976 Experiexe I n t h e U.S. the recc~zi.=:e. n iz t h e e a r l y 1920's t h a t benzefie exFcs:=a ;z=<:z=e ? a n c y c o p e n i a l e d t o sore s t a t e s imposing Iiaiczticns of iC3 ppm ex9osure for an 8 - h o w d a y . I n a f e w states =kis wi?s reduced to 50 ppn and - -- --t h e n 35 2 , ~ n5.1 t h e eazIy 1S.;a's. During t h e var years a Federal "v*ma=--; L--..e aLa.4--a- Sd*.*- r a i s e d t h e l i n i t t o 1 0 0 ppn with adeirional excursions 2ernitted for l i n i t e d p e r i o d s . Sy 1336 $52 r'izst XCGIX TLV of 1 0 0 ppn was e s t a b i i s h e k and SGGZ k s c a z e zot o n l y a country wide standard b u t also a w o r X wida g u i d e l i n e . O v e r t h e n e x t 1 3 yeazs t h e l e v e l was lowered t o 50 ppm (1947) an& t o 35 2 2 ~(194s). Ia 1957 t h e TNA was reduced to 25 793. In 1 9 6 3 t h e 25 ppn l e v e l w a s made a c e i l i n g valLe. ' u ' n t i l March 13, 1 9 7 8 t h e s t a n d a r d was based on ~7 X;SL retorzez2ation adopted i n 1 9 6 9 which established =he l e v e l f o r benzene a t 1 0 ppm on an 8-hour d a i l y Tize Neighted Average (TWA) and a 25 ppn 15 xiz. c e i l h g . T h i s Secame an o f f i c i a l OSKA standard i n Oczober L972. T h i s was again r e c o m e n e e d when t h e 1974 X G S J , - = i t e r l a d o c m e n t was p u S l i s h e d ( 4 ) . T h i s had however, aT: " a c t i o n l e v e l " p r o v i s o which r e q u i r e d certain b i o i a c i c a l n o n i t o r i n g i f t h e employee w a s e q o s e d t o more than h a l f t h e TWA ( o r more t h a n 5 ppm) -3- The Post-1976 On Auyzst 2 5 , 1,676 :;IS3 i s s c ~ , I2 r e v i s e d reccr4:en2at i o n f o r an o c c ~ p a t i s ~a%a--~j-c--.=--- - + a - A n - s f o r j e n z e n e lowering tne l e v e l to I ?yias &te-n.ined 5 y a 2-hour .air sanple collected at one lizer ?er m i , ? u t e ( 5 ) The bases f o r t h i s chan5.e were several epidemiologic stcdies on rthber workers iz t k e Akrcn, G k i o , area and d n w e r of case r e p o r t s fro= Z z m c e , Italy ariC Turkey. A l t h o u g h it was a d q i t t e d t h z r in 2 . z ~ i:n~s t s x e s t h e exposure levels were unl<r,o*mo r , Ff k r ? * m , were high ( s e v e r a l hundred ppm) NIOSa z:oo:z. t k e ~ c s i t i c nA,,h.at t h a t data estE5lisheC benzece as 2 czz=izccen and tkis j u s t i f i e d s e t t i n g t h e exs=osare le-.-el a t t k e loiv'est Z e t e c t a k l e level. On April 2 9 , 1977 OSSA isszeci zn Sserfezcy Temporary Sta of ndar6 Augus ( t 6) whi 1976 c5 bu t f c c E it c e x d ee z3.c ts it s !;Xs: fus t i.rzC er. c c c z xe3d tion z f tio or ns th e W i . m i n e n t danger" catsqory t5e w s z k or' I n f n t e et al. This study.S e c m e a v a i l z 2 l e to C2"% f z m the N I O S i i Division of S u r v e i l l a c c e , 3azar5 Z*.-aiuations and Fie12 S t u d i e s i n early 1977 b u t was n o t ?Slisi?ec! in Lancet u n t i l July 9 , 1977(7). The ,,.,vis reported t h a t s e v e n cases of acute or c h r o n i c qloqe:-ro=?s or monocytic l c u - kemia occurre< i n 7 4 8 vorkers Lx cl p l i o f i l r n o p e r a t i o n in -Akron and St. :.lazy' s r C 3 l 0 , 2urizc 5% ?eriod January 1 1 9 4 0 and J u n e 3 0 , 1 9 4 9 E? incFCence 10 tizies ~ o m a l . p.Ioreover, i t was alle$er! tht t h e exgosure l e v e l s of beazene were below L?c IFnits recc;r??e.n.C.edat the! t i m e of their measurenezc, t k c i z ? E = z t i m b e b g t h a t these levels were t h e Icxess z e p z = e C =c d ~ t e . T h e ETS was prozptly k l c c k e c ? 3~ COL'T: action on t h e part of t h e k p I and a Z*AT~OTof p c z z o L e u ~companies. On May 2 7 , 1977 OSHA i s s u z d E ?zc;ssed. ;ermar.ent standare which in essence re2ezts5 ti=e reculstions of t>e STS ( 8 ) . - -'I azC sit:atiz:s where a Liquid stream contained 1% or less of .fE1 -.5.e-r..z.ee-z=-s= ( t h e lstter exerption would 2 2 : ~ ~e then would drop to proSably 0.1%) The b z s i c p s i t i c n of S i G S X and OSiiX presented, at the hearings may be srz-;.31.,zizec?as follows (see Figures 7 and 8 ) : - -1. Tke svi.c.or,ce f r s n zany case reports and s e v e r a l e p i d e n i o l o q i c s t * * C ; e s zsnfirz-.s the f a c t t h a t b e n z e n e i s a. .le!i:<ezcyen (or a calrcer producing s u s t a n c e for the h e m t o p i e t i c system) 2. I t i s ixipossible to prove t h a t a safe l e v e l of expo- sure exists for any leukemoqen ( c a r c i n o q e n l , hence, eqosares be reduced t o the lowest measurable level. 3. The axi p k resc..ci invc;vee tica cxa. .l f realities zf e 2c. 2ccza-t1riacr.l5 p rogram gzsolin stablis for t h e e iiicta hing thou te th an san at enviro ds of for t h nmenta people e l r.cz.ent at leas-, t h e s e individuals should be exempee f ron co2='tz2I. m&he a??czez$s os' t k e 2,roposed permanent standard offered the f o l l o w i q a s g ~ i i , r . =:s 1. Eenzene %as not been proven to b e a primary carcinoqen a l t 5 o u c h it say be a promoter or co- carcinogen a t l e v e l s w e l l above tke p r e s e n t scandzrd. T h i s i s supported by t h e s p i d m i o l o c i c a l studies of Thorpe (Exxon a f f i l i a t e s in Z U T O ~ S , 1 9 6 1 - 7 0 ) ( 9 ) Lloyd ( I n c i d e n c e of Leukemia i n Coke Over? * - -Lezs) (lo$ and J o y n e r (Shell O i l Compar,y .er.?iayses 'I The Xnfante study when subjected EO -close review also tends t o support t h i s concept t h e accual e.wosure levels averaged over 100 ppm with excur- .sions t h o t ?:rc,ka.bly reached the 1 , 0 0 0 ppm mark on n m e r - ous o c c a s i c n s 2. The concept that t h e r e i s no threshold for a c a r c i n o p n is fallacious. 3 . The OSHA 2roposal does not i d e n t i f y t h e b e n e f i t s , con- sicier r c a s c n a b l e r e g u l a t o r y a l t e r n a t i v e s or adequately assess the economic in?act a s requlred by l a w . -5- .. 1. i? l e v e l of period. 3 . An 0 . 5 ppm z c t i o z LeveL for monitorizs and medical surveillance. m e n t resexzces ctr.nc.: Se j u s t i f i e d CR t h e b a s i s of t h e theoretical szins f c r s s c A e t ~2~s e wholc. .. Refererrces: .GerarZe, H . W . T o x i c o l o q and Biochemist,y of the Aromatic Hydrocarbcns Federa: Iiesister '101. 43, # 2 9 , p . 5918, February 10, 1978. - .L a s k i n P Benzene S T . o a. ce. sicr= G y a l dstei A.?. ,? I 3. A Critical Nonograph. Evaluation of -C r i t e r i a Doc-,-,en=s Zecomendations f o r a Benzene Stmdar6. 1 9 7 4 . UICSS. Revised RecoI;c.ea&ation f o r an Occupational Exposure Standard f o r Eienzene. 1 9 7 6 . N i O S H . -Ezersency ?ez;orary Standard f o r Benzene. 29 A p r i l 1 9 7 7 . OSHA. I n f a n t e , ?.?. e t a i . Leukemia i n Benzene Workers. Lancet, J u l y 9 , 1977; 22. 76-78. Prososed P e z a n e n t Stanciard f o r Benzene. 27 May 1 9 7 7 . CSHA. T h o q e , J . 2 . E g i e d o l o g i c Survey of Leukemia i n Persons P o t e n t i a l l y Z q o s e 6 to Benzene. 3.O.M. 16: 375-382; 1974. (10) L l o y d , J.W. Lonq-Tem Mortality Study of S t e e l Workers Vs. Ressiratory C a n c e r in Coke Plant Workers. J.O.M. 13; -7- .. 3/3/78. To be given at t h e D i v i s i c x of ?c,Zining X e e t i n g at Toronto on May 11, 1978. -8- F i g u r e 1. Metabolism of Benzene. BENZENE--THE CURRENT CONTROVERSY -SKIN Acutm B.nzscw Toxkity YUCUI WIMflRAWES LUNGS Figure 2. Acute Benzene Toxicity. -9- ' .- BENZEri E-1 H E C U33ElYT C0HTR0 V ER SY M 4c - %ximum Jilowblr conccntratwn (Thresho!J Iirnio. CREDIT-FPCV. GERARCE. H W TOXICOLOGY A N 0 BIOCYMISTRY OF AFiOUATlC HYDaOCAAGONS. n -_--Figure 3. Efr'octs Gf Benzene V a p o r on Man. -Figure 4 . C h r c n i c T o x i c i t y Hematopoietic E f f e c t s . - 3.0 - 2' TO ANEMIA 2. TO 2- TO GRANULOCYTOFEWIA THROU8OCYTOPEUIA BENZEXE-THE CURRENT CONTROVERSY . 19203 1910'8 1940 1s42-rs t 946 1917 1wa 1057 1963 1969 1Q72 1S74 lQ76 1S17 Figure 6. E v o l u t i o n of' B e n z m e S t a n d a r d . - 11 - 6ENE.41E--THE CUR R ENT C0N TR 0V E9 SY oppotkrg Podt!ons on 1977 Proposad Standard INDUSTRY 1. B m x m e 1. not 0 Orlmsry carclnogmn. It may Ma momator of co-carclnogm. No c a w o b d o w 10 porn E p 4 d . r m o l ~ yltudr.. d f k o r w . U q d bnd Joynu 2 The *no thrrrno(d'cwopt tor careinopwa hfrlloclaa. a. A numbof of factamcan p r r v m f ca(ICof lnducdon or dolay It. 0.1.Mstabolle block. DNA reprlr. Immuno r o s m r o . de. b. D o u r.lallonenlp ro lafont pnlod. c Domooatra:lon of cocarclnogonlc or pomotor m h J n k m S . ._.- F i g w e s 7 and 8. Opsosing P o s i t i o n s on 1977 Proposed Standar2. - 12 - BEHZENE--iHE C U R R E N T COHTEOVE3SY F i g u r e 5 . C l i n i c a l S i q n s of Eenatotoxiclty. BENZENE-34 E Ct'n"REH7 CONTROVERSY Evdutlon ul Standad Figure 6. Evolution- of 3enzsne Standard. - 11 - . .. BENZENE-THE CURRENT CONTROVERSY Oppamq Pwtbns on 1977 P r o p o r 4 SlanGsrd lNDU8TRY 1. Bomuns IOnot ortmary carcinogen. It m w M s pornotor or co-carcinwen. No c*-I b d o r 10 pem t p l d m o ~ e g yS t W h ol T h o r n . U q d and Joynu 2 The-no thrnho(d'concogt lor c.rctnogens is1.ll.cbur 8. A numbu d toetom can orovont caruzw lnductlonor dduy It. 0.0. Yotabotlc Mock. D N A r w r , ImmuMresoonso. *IC. b. Doso rotattonsklp to Ialont period. e. Domonatrrtlon of cosarclnogonic 01 pomolr muhaniama. " . -- BENZEN E-THE CURRENT CONTROVERSY oppodrq P o J t i m s On ISn Stsndard (CmPd.) 4. Th.uonomie c-uwun .IO kmroolo. F i v e s 7 and 8. Opgosing Positions on 1977 Proposed. Standard. - 12 -