Document wD4gGx5vdgZ9EO5R9OwvqLDNQ

I Experience in industry over the last haifcentury suggests that long-tern exposure t o nign wnccntrailons of benzene in the air in the workplace is associated with the oc. urrence of various blood dyscrasias. including leukemia. I t hc\s htcn stated thai no basis exists for the determmation of a dose-response tel.iiisnsh:p fix the Icukcmogenic anion of benzene. A critical revnew of ._ t_h_e lit- erd!urc. however. rtveltls first, that more cas& Occtir-at- higher-Zncentrations (Ilardy and Elkins. 19% shbncnbcrger. 1963;Vigiqni. 1976);,second. that the miutncc drops when the lcvcl of exposure is rtdurkd (Yllner. 1976;lktd&T976- - Ahsoy, 1980): ZndT--th-ir_d and most importantly, tl(at,no c-ase-s of benzene-induced Leukcmi& have been reported in workers exposed to conccntrationsthat-did not exceed 100 01.. 1979). and- ps - s i b l y IS0 ppm (Jandl. -- 1977% Aksoy. 1977; Pagnotto er Tncre a r t some Haws in the reports which suggest an association between an r x e s z incidence of Ieukcmia in workers and exposure to low leveb of benzene. In i h r context oi this presentation. it i s not possibie LO go into detail criticiung those feu r e p n s which do suggest such an association and to which reference has re- peJiedly been made. Thiscntiquc has been given elsewhere (Lamm and--Tabe- nhaw, 1977; Jandl. _1- 97-7b; VanXaallc, 2-939).A very rdevant comment. however, should be repeated here. The authors of t h e papers suggesting such an association related the reported effects or responses to an at-times-broad range of concentrations. recmied mtermittcntly, to wbich the subjects had been exposed. With res- to the concentration at the upper end of the range. this is probably justified. T'he obwved effects are known to be associated with exposures a t high levels. An eniirely different situation. however, exists with regard to the concentrations at the loucr end of the range. These were measured at different tima. Becaw of the r fluctuating Ievcls in a "range of concentrations" there w e n probably occasions when even lower concentrations could have been recorded. In tbe practice of in- e ' Piper prelcnied in pan at tbc Workshop m Bcarcoc-Intuprrulwro of Data ud Evdrulptr of Current K n o w d g c . June 10-11. 1980, V m 67 68 H.G. S V A N RAAL'E I du\rrid msdrrinc and environmental hcalth, the lower pin1 of an exposure range I \ practicdl~31ways m o . Thus, the conccntrations at t h e lowcr end of a range as uc!l ;IS thc w d 1 c . d "mean concentrailon" become mcaninglcss in dosc-response rclJrrondup a In thcu: C I X L I ~ S ~ ~ ~ C tChSe. only meaningful relationships are ( I ) an obssmcd cffea at a defined upper concentration and. (1)a no-dc.tt/no-rcsponsc level k i o w a defined upper concentration. BeJring these comments in mind. particularly point (2). a critical evaluation of the literature reveals the facts as depicted in Table 1. A i lower conccntralions no cascs of effects have been described or reported that can wiiiistand thc rcid lest of cntlcai validity. BENZENE AND THE GENERAL PUBLIC T u r n i n g mu' to the possibility of a leukemia hazard to memben'of the general public frorc exposure to benzene in community air, the following established facts arc rcievant: ( 1) 'NoCIKS in worken- have been reponed to have occurred at levels of exposure -.- ~c_IOW_. 100 ppm. -- . ~ TABLE 2 S,ORWAY--CASOL!~ECOWL'MmOh, NUMBER OF DEATHS FROM LEUKEMIA 12 Y A N D MORTAUW RATE FROM LEUKEMIA 12 YEARS LATER W hrU. Ytir Cirrolinc rmrurnptm (ions- 10') Number of duths from lculrcmis I2 y u r s kicr M o r t d ~ i yrmtc from leukemia per 1OO.ooO I2 years h e r 1950 I952 19.54 I95h I95N 1% I962 1964 322 363 404 IS3 311 MU 487 a06 298 302 322 354 337 350 340 341 8.3 8.2 8.6 9.9 a.9 a.7 a.5 :.5 BENZENE IN WORKPUCE AIR 69 . FIG. I . Annual gasoline consurnptlon from 1950 10 I964 and W n u m k of yeJ- h e r . 1962 IO 1976. In N o m y . 0 d k u b u 12 /- I 70 H.C. S V A N RMLTE . TABLEk - THE N ~ E R U ~ ~ D S - G A S O L I M C O N N Y P T I OANND MORTAL^^ ROYIsuxul: TOTAL NUMBEUOF CASESA N D NUMBER OF CASESIN MENONLY 1955 i I957 * * 1959 1961 loa? I961 fY M 888 977 1112 1315 1427 1541 I778 930 PMI 819 912 91 I 912 920 53I aa 440 520 538 522 518 (2) Exposure of the gccerai public occurs at concentrations a i least two to three ordcrh 01` ni;r;r?itud:: lower than have been recorded [or industrial sttu3tions. Mea- sured concentrations of benzene in community air were reponed to range from 0.5 io 16.3 ppb. Thus. in a Frankfurt residential art3 outside traffic arteria values of 2 62-10.3 ppb were measured ( Batelk Institute, 1976); in an urban area in Berlin Dahkm. 0 . 7 9 - 4 3 8 ppb (Lahman cc af.;.1978); and in a rural residential and ind~strialarea. 3.Oii-9.24 ppb (Frohne and Knappc. 1975). These levels are very si~:iilarto those rcpmed from the United States, v i r . 0.49- 12 ppb in 18 cities and t o u p and 0.49-2 ppb in rural areas (American Petroleum Insiiiuic, 19715). an abcrage of I5 ppb with peaks up to 57 in the Los Angel= Basin (Lonneman cr 41.. 1965). and an average of 13 ppb in Toronto (Pilar and Gradon. 1973). This com- p2rt.s favorably to levels reponed by Robinson er af. (1973) from air in the Amazon Basin: up to I4 p ~ b . ( 3 ) Expcriencc from Europe shows that the incidence of leukemia docs not increase with incre3sing emissions of benzene in community air. Yur I953 1956 1957 1958 I959 I960 IWI 1%1 1963 I964 TABLE 3b T H E NETHERLANDS-STANDARDIZEMDORTAUYT RATES CdUK oonsumption (tons. IO') 88s 989 977 1037 Ill2 121s 131s 1427 I541 1778 Standrrdizrd monality raic from kukcmu pa Ioo.ooO ~ 7. I 7. I 6.5 6.I 5.8 6.7 6.3 6.2 60 6.0 SLlndarditcd m r i r t y rate from kutcmir per 1oO.ooO males ~- ~~ E. I 1.3 7.3 7.2 6.3 7.7 7.3 7.5 7.2 7.0 BENZENE IN WORKPLACE AIR 71 . .. I IC, J i . Annd.11 pik-Itnc consumption from 1955 io 1964 and total number d d u t h r from kukcmu 1: b u r s h e r . 1967 I.) 1376. in n e ?dclhcrl-ancls. ~ I G3b. S t x d r r d i t c d monrlity rzks for The Netherlands. U'hcr. f;lr-r~3cIilngregulations are being discussed. it would seem reasonablevpsrt from 3 consderation of assumptions and. at times. acrobatic extrapolationsto take a sober 1 0 4 ax facts and figures for what has actually occurred in real life. GASOLIS E CO\SL;MPTION. MORTALITY RATES. A N D INCIDENCE OF LLUKEMIA IN THREE EUROPEAN COUNTRIES There IS no doubt t h x the greatest single contribution to the pmcncc and con- centr;itlon of benzene in community air-certainly in Europc-comen from the t m x d a c ~ u : c . trxspon. storage. and use of motor gasoline. A n imestigdtion h_a_3 _be.en carried out of the consumplion of motor gasoline and ' i t s k n z r : n r ^ i o n h t in t h r e t EurZviin countries togeihFwiih- the nb%&-rGf-&L G I I ~de+aths and the yncidencc o f k u k t m i a over a-pcridof years. Since bcntcne- induced leukemia may have a latency period of 5 to IS years, the consumption of gssolinc has becn conelated with the Occurrence of leukemia 5, I f and, in one c . ..-.. H.G. S VAN RAALTE :- I I ,# I m3b! (057 im tmi r s y RU RU Fs. 4. Annual gasdine conrumption from I955 to I964 and t a d aumbcr d d t r h fnm k u h k for mdes only. 12 years later. 1967 to 1976. in Tbc NetherlrndL case. IS Y C ~ Kliter. The countries involved am Norway, The Netheriands. and Denmark. All three countries have an cxallent National Bureau of Statistics which registers both movements in commerce of goods such as gasoline and causes of death from diseases such as leukemia. TABLE 4. DENMARK- ACUTEN O N L Y W H ~LCEUKEMIA(ANLL): TOTAL NUMBEOFR- IhCIDENCE ?ER 1 ~ A N D G. ASOL~INECONSUMmON 15 Y E U S PIEWOWSLY W i namu~rnp~la Told CLICI rIKldenc+ (tans- ICP) Ycrr d ANLL pcr 1oo.ooo 15mprrnoucrty I968 I969 1970 I971 1972 1973 I974 1975 1976 I67 I82 I S8 I as I 16 153 I45 15s 133 3.4 3.6 3.7 3.8 3.7 3.0 2.9 3.I 26 614 652 690 723 756 790 IS2 910 979 BENZENE IN W O R K P U C E M R TABLE 4b DENMARK-TOTAL NUMBEROF U E S OF L-t& I5 YURS PREV-Y AND GNSCUJNLCOW- 73 YCU -I968 1969 ' 1070.: I971 1972 1973 I914 1975 I976 Total d kukemia 487 523 484 539 506 44 467 492 439 614 652 690 723 756 790 852 910 979 1. rVorway' Table 2 3nd Fig. I show the annual gasoline consumption (tons- 10') from 1950 to 1364 and the total n u m k r of cases of leukernla 12 years later, Le., from 1962 to 1976. 74 H.G. S VAN W E , Since the population of Norway increased considerably during t h e period which would affect the number of cascs of leukemia from other causes. the incidence of leuhernia per 100,OOO population was a h tabuiated and this is also shown in Table 2 and Fig. 2. 2. :Verhcrlands' Table 3a and Fig. 3a show t h e total annual gasoiine consumption (tons. 10') from 1955 to 1964 and the mortality from leukemia expressed as the total number of cases 12 years later. i.e.. from 1967 to 1976. Since men would probably bc mote heavily exposed than women. a similar investigation was carried out for males only (Fig.4). There is no correlation. The standardized mortality rates have decreased (see Table 3b and Fig. 3b). 3. Denmark4 Denmark has a very sophisticated canccr registry which enabled tabulation of the icutc nonlymphocytic leukemia (ANLL) cases separately. It is this type of lcuicrnis which particularly h a s been associated with exposure lo benzene. Tables 4a and b and Figs. Sa and b and 6 show thc number ofcases as well as the incidence .'of A K L L per 100,OOO population, together with the gasoline consumption 15 y u n previousiy 'From: A a o n p w r (1978): OECD Suiuiics: urd hidB-u From: Danlsb tnnitutc of Petroleum; Ckmmtvn (1979). 'Table 4b ud Fig. 5b show J1a s a d k u k c m v Statiakq -V - c c1 BENZENE IN WORKPUCE AIR - TABLE 5 DENMARK-TOTALNUMBEORF C m OF ANLL XNM G A ~ ~ L I NCOENSUMmON 1s Y U I S hEW-Y e ONLY AND Yur 1948 1969 1970 1971 1972 1973 I974 1975 1976 Number of M d ANLL in mm 84 103 91 91 IO2 80 72 82 63 Gudmcaonurrnpum (tmn. I@) 1s yun prm-b 614 652 690 723 7% 790 152 910 979 75 Table 5 and Fig. 7 show the total number of cases of ANLL in males only and the total gasoiine consumption 15 yeark previously. The benrtne content of motor gasoline in all t h r u countria gradually increased from an average of 1.5% in the midfifties to 3-3.58 (range 2 4 % ) in the sixties and seventies. For Denmark (Ciemmcscn, 1979) the absolute number of UKS of A N L L remained constant dunng and after the war. Goti. deputy director of NCI. emphasizes "the distinction between the przctical I and the theoretical" ( 1980). JIICabove figures tend to confirm this and wouid lead to rhc concIu_si_on t - h at idcidcnce of Ieukcmia. at low c o n c c n t r a ~ L ~ &-----n---z c n ef i i - i litt-fe--or-_n_o -ef-f-ec-t-on the -- - - - - TUTIL OF USES Q c r u r u ; ' . ~ -- ~ ~ ~ ~ - L T U P U K Y T CLN m A L WOclNf 1- d 75 T C q mVIWSLI 1 I t I 76 H.G. S VAN RAALTE REFERENCES .. *. t. . . --- , *I. . .. ' 4' 1\ . c .