Document a1n1OdJj0QEa2w2Rdee2a3baY

Health Exam Findings Among Individuals Occupationally Exposed to Benzene Jean C. Townsend, M.S.; M. Gerald 011, M.S.; and William A. Fishbeck, M.D. r c We previously conducted a cohort mortality study of 594 individuals occupationally exposed to measured concentrations of benzene. This report presents health examination findings lor a subset of 282 men from the larger group. Although slight decreases in mean total bilirubin and RBC values were detected statistically in comparing the exposed group to controls, these changes were not regarded as clinically significant. N o correlations were found between peripheral blood counts and latency. duration or intensity of benzene exposure. Presently we have no indication from our data of adverse effects of benzene having occurred i n our subset. Variation in latency among individuals and the possibility of subtle changes effecting an eventual pattern contribute to the need for continued surveillance. Eiitvts oi chronic benzene poisoning in man are rrl.itcd prrdominantly to the hematopoietic system oi thc bodv. however. central nervous and gastrointestinal involvement may also oc- Thus, symptoms such as headache. dirzinrss. wcsakneis. fatigue, insomnia. anorexia. nausea or vomiting m.iv or mav not appear in conlunction with blood changes. Vxiation in individu.11 susceptibility is considerable and manliestations of rhronic poisoning hwe not been predictable.' Rtuordvd blotd ahnormdities associated with benzene toxicitv include Ieukrqicwia. thromhocvtopenia. macrocytosis. aplastic. .inrniid and Icc1htmi.i: patholosical eiiectr on the hidnevs and liver ha\e ~ 1 3 0btxm rta- ported.' * Vigliani and Forni' habe suggested t h t 1euhtvni.i a\sociattvd with benzene is frequentlv precedcd bv a hvporrqc*ner,itIVP ,inemla o r pancytopenta or more or less longstanding. H o w w r r . t h w authors reported onc? c a w in which the Irulirmia occurrtd 1-1 years after the initid anc*mlawith app.irc~ntlvnormal hluod counts in the intcrim p w d . A l w (wrtinrnt to thr question oi l.itckrlcv I> evidence ot chromosomal .iherr,itions in circul.ltiny: Ivmphoc.vtr< fwn Dnw Chrmirai V 4 UMh w n D n r ~ ~ whrcl- Ruddnnp \t&nti \ti ~ f l h ~ i i o f persons several years after expmure to benzene and subsequent recovery."' t! Historicallv. the postulated rihtion5hip5 bctween clinical findings and benzene exposure h v e b t r n based on individuds exp o s d t o app,irt-ntlv very high Concentrations oi benzene. The I x k oi long-term rnvironmrntal monitoring has becn evident. and h ~ csontributtd to the diificulty oi extrapohting findings to lower ekposure inttvwtim. The purpows i,i this study wc'rc (1) to examine rrccnt laboratorv and health history data on 282 emplovcw with rcrptm to ofImmcv. duration. currmt intmsity. and cumulativr dose ben- r e n p . and '2' to discuss these iinding as t b v relate to thc mortalitv experience o i the s m e target population. The individuals hid exprrienced potential exposure to benzene rangins from 4 2 ppm time weighted average (TWAl to approximatrly 30 ppm T W A ior an right-hour day for periods of from lebr t h n one yedr to 20 years or more. Environmental Considerations The chemical operations covercd hv thiq investigation were grouped into three production areas: Production Area I: Chlortr benzol. date of operation 1920 to present: Produrtion Area II: Alkvl benzene. date of operation 1935 to presrnt: and. Production A r c u 111: Ethyl rcllulose. date oi opcration 19.36 to present. These process ,ireas were selrxttd br.r,iusc p.ist r x p i w r m in at lrast wvrr.iI lob clasciiications within r w h .irca evccded 2 ppm TWA. R w w c h ,ind dcvc.loprncnt I.ih)r.itoriv5 ,ind cithrr production units with undciind tywscrrc. .it thik comp,inv location were not inrludrd in the btGdV. Benrcwe \vas utilizd SI, .i r.iw m.iteri.il in the i i v t two prtduction units whwas. in ethyl rt*llulow. it \vas rmplovcd JS a solvent. TWA estimates o f bt-nrent-t y o s u r e ior rach job in all production x r a s were b a r d on environnit.n t.11 mcasuremmts. process flow shwts and lob dcccriptionc prwidrd hv indcntrial hvjilcnists and plant oiwrating prrwnnci. Evtw p h wlis evalu.iicui on a yedr-byvex b.iso .mcl ,irsi#ncd to onc ot the iollowing four intenritv c.iteqrics: < 2 ppm T I V A : 2-9 ppm TWA: 10-14ppm TLVA: and 2 5 i R*orintmd from Journal of Occuoaltonal Yedtctne August. 1978 Volume 20. No I OD ~ 4 3 . 5 4 ~ JOU 1078 . ~ I ~ I IIILIVA I 111. I,,iir t ,III~,V,III*\wi*ri-f I i * i i v f n i i i i * f i~r i .ifiv.iiii I * firm k.iinl)liiiq C I i I)rii< I - \ \ lint.\. Thin following matrrials considwed to h t i ~ i w l ~ ~ l1~2 1; t * r.lil#i*s II! i ' x ~ ~ l l ~ i i 1f1i1'11 tLIl1 c n X l \ t l V l 111 I ~ M * ~ l ' t v , r i l I ~ I X I I oli~qi.iiI irnpi)rtancr wwe known to be regularly produc tiiin units priwwt in I'rrxluc ticin Arv.1 11: hrnzcni*. ethylhenzrne. divinvlben- A summarv oi industrial hvsirne monitoring d,lt.\ tor the period ZPIIC. toluene. xvlcne. isopropyl hcnzcne. styrene. diisopropyl 1944 throuqh 1974 IS rcported in d rnort.ilitv study concerning bcnzenr and alphi-methvl styrene. The exposure categorization these production arcas.i2 Table 1 presents the measurements of rule with respect to benzene is summarized for jobs in Production -benzene concentrations in a condensed tormat. Area It in abbreviatcd iorm: High exposure Q5+ ppm TWA) In Production Area I benzene w.is chlorinated to produce Operating and maintenance jobs in the ethylbenzene process mono- and di-chlorobenzenes. in a closed continuous svstem. It prior to 1943.Mtderate exposure (10-24ppm TWA) -Operating was recognized as a potential hazard durinq initial chlorination. jobs. ethylbenzene. 1943 to 1960: maintenance mcchanics. ethyl- Other operations in the plant included the separation oi un- benzene unit, 1943 to 1971: operating and maintenance jobs. -reacted benzene for recvcling and iurther chlorination. Mone. di-, propvl benzene unit. 1943 to 1968.Low exposure (2-9ppm TWAI tri-. and tetra-chlorobenzenes were also iouod routinely in the Operating and maintenance jobs. dehydrogenation unit, 1973 work environment. Benzene concentrations in this work area were below 10 ppm TWA. The rule for categorizing lobs by ex- -posure was as follows: Low exposure (2-9 ppm T W A ) to present: miscellanenus jobs in propyl and ethylbenzene over -varying time periods since 1943.Very low exposure ( < 2 ppm TWAI Clerical and supervisory jobs in all areas, and several -Mechanics. chlorinator operators and still operators in the first operating jobs in dehydrogenation. chlorination cycle. Very low exposure ( < 2 ppm TWAI All Production Area 111 consisted ot a process t b t produced ethyl other lobs in the production area. cellulose resins and a second process where. up until 1968,sheets Historically. less industrial hygiene monitoring for benzene took of ethyl cellulose were iabricated. The resin process began by place beyond the first chlorination cycle because oi the unlikeli- treating cellulose rolls with caustic and reacting the treated hood that exposures would exceed accepted guidelines. In 1973 material with ethvl chloride in the presence of benzene. The exposure intensities of up to 4.6ppm TWA were reported outside product was washcd repeatedly and then dried before packaging. the initial chlorination area (Table 1). It should be noted that these High bcnzrne clcpo~uresoccurred durins sampling and also during estimates were based on measurements taken in new production l a d i n g and unln'iding o i hatch reactors. In the p.ist, exposure in facilities. excess o i 25 ppm TWA did occur tor several jobs within the Production Area II began as a semiplant operation for ethylben- production unit: over the Idst ten years. exposure intcnsitw have zene production. This operation was etpanded in 1937 when not exceeded 10 ppm TLVA. demand for styrene increased. The benzene was alkylated with The highmt cxpowrw t i ) henzrne occurred in th?shwtinq ethylene to produce ethvlbenzene m d diethvlhenzene. In a operation. whw .idlu\tmcntc nn th- casting equipment requirrd second process benzene was .dkvlated with propylene to produce entry into ,in cnclrwd .ired. Surveys in 1953 and 'isain in 1%3 in- isopropvl benzene. After 1943 these processes were located in dicated TWA t'xposurcs t o hmzenr above 2 5 ppm for mcn in diiferent building. Dehvdroqmation. which took place in .i several lob classiric.itirms. The bcnzrnr cxposurr c,~tc~giiriz~ition separate process area. led t o the end products stvrrnc. divinvlhenzene. and alpha-methvl stvrene. As in the first production .ired. the processes were closed rontinuouc svstcms. Potentid ior hishest -rule for the ethvl cellulo~eunit\ is ,is tollows: High exposure (2i+ ppm TLVAI Opr,itinq. maintenance lobs in production ,ind -sheeting until 1965.*Modcrateercposurc (10-14 ppm T W q l L,ib exposures occurred in the benzene unloading areas and during technicians and seltutcd operating jobs until 1%6. Low exposure -Table 1. Summary of Industrial Hygiene Measurements of Benzene Concentrations in Producttan Arras. Job C a t y o f i n Chbroanrcn lob mi S r n l f l e d lobs In tntui db~ryiim and dirlillalmn othn IC& Ill UM A l W bmmtene Alhylatim mcraioo lwoss wmwllm units1 Ycchvllcl faurns umwm w1ts1 O l k r lob, m DrmuRlm uniis EISI Cdlucac lob, m rrvlulwturmg l a m taulotin[ ' W o t n I W A s w e mt esiinuled YeJn 01 Survey iwra 1965 1913 1964 1913 1953 1965 1971 It IWS 1911 12 I565 ign 12 1952 1965 1913 1953 1965 hrnbW of AWJ and 8frlthint Zona S a m p k pn Job 03 -2 5 1823 I1 3 39 5 25 2 36 30 135 35 33 35 :39 13 iF5 12:s b il 25 38 9 con*waIs rnsno'nrq *nrn mhawd m l v m Range 01 Samolrr lppm &nzmal 0 :53 239 162 02 I Ib2 0 .loo 0 56 0 283 0 250 0 283 0 55 0 14 0 >IO0 2 515 I321 IO 931 0 .IO0 E ~ i w u t dTWA h T l &nIM*) < I!03 1 to 6 41 io I < I to4 9 io I I I to 1 4 I io I3 1 IO IO 1 (0 14 I to 5 <1l05 I 1 to 35 5 10 I1 3 io 3 35 I I I O 32 (2-9ppm TWAI -jobs downstream from sections usinp,benzene directlv throughout the time period. and high exposure area iobs -aiter 1965.Very low expowre < 2 ppm TWA1 lobs in produc- tion area removed tiom sections oi the process utilizing benzene (1935tl.Ethvl chloride. ethyl ether. and ethvl alcohol were also present in the work environment on a routine basis in Production Area 111. In all areas. TWAs reflect average exposures for employees on ,i given lob. rather t h n those particular to an individual whose work practices mav differ from the norm. By combinins the environ- mental assessment with complete work historv information for each emplovee. it was possible to determine latencv and duration of exposure and to estimate cumulative dose and intensity or ben- zene exposure. a peared on annual emplovmcnt lists (1938-19701o i thc benzent. work ,irr,is. Thr prmcnt study c o v e r d only those perrons irom thr mortditv cohort who wcve still working f o r the companv JS o i 1%: and who pirticip.ited in thr health exarnindion proqrmn ,iitrr thc*ir iirft hcvwrne mportiri- and prior to March. 1974.Table 2 summarizes the cmployrncmt \tatus o i the original cohort .is of Jmu.irv 1967..ind ,is ot I.inu.irv 1974.and identifies the numher o i tvnplovecs participatinq at l i u s t oncc in the health screening program during this period. Htwlth ex,imin,ition\ were given t o 482 person< i4i"'o o i the origind cohort). Thic c ovw.ige mav be tvpical oi situations whrrc. m.intii.irttiring units d.itr hdck many vcxs and indic,ites .I pottmtwl shortcoming oi crosr-sectional sampling'in occupational settings. Methods Since 1967.a health examination program has heen otiered to all employees at the Midland. Michigan location ot Dow Chemical. U.S.A. The time required for the program to cvcle through the cntire manuiacturing complex IS approximately two years. Data used in the present studv were derived from existins record5 oi health examin,itions conducted during the period February 1967 to March 1974.Although there were modiiications in the questionnaire and in the specific labordtorv test5 periormed over the seven-year period. the basic structure o i the program has remained unchanged. For each benzene exposed emplovre the most recent exam w,is utilized in the .in.ilvsi\ 50 thit possihle latent or chronic effects ot henzene could hc scrcrncd. In 'iddition to relevant health historv queGtions. the following -qumtitative health mc'isurt's were studird: B l o c d rhrmistrirs total bilirubin. cre,itininc. total protein. protein dhumin. prottm -globu!in. blood urrd nitrogcn 'BUN). LDH. .ind SCOT. tirniatoloqv hern,itocrit. hemngh>hin.LVBC. RBC. XlCV. MCH. .ind .\lCHC. A control population ior compcir.iti\c* purp(irc~sW.IS rt+(.ttd usinq a matched pairs dmisn. Over 19.000h t d t h invcwtorv r\.imc were given crnplovees during the pcrind oi studit. A contrcil ior each e x p o c d tvnplovee w.i\ chnwn xcnrdinq to thr iollo\vinS criteria: ( 1 ) The control participated in thr hr'ilth invmtnrv prtb gram durinc the sane month ,is the expo& individual. 121 Thtpairs belonqed to the w n r iivr-year .iqe intcrv.il. (31 Cis.irrttc smoking historv oi thr control aSrcc.d with h i t o i thc cxpoccd in- dividual (current moktvs. < 1 pack ' d ~ 1:+ packs.'d.iv.;: iormcr smohers; and never smrjkedt. 141 Among potrntial control employees. the individu'il whose hire date was nearest the hire date oi the exposed c-mplwre was selrc ted. Individuals in the control population mav have experienced e\posure to a variety o i chemicals cxcIusive of benzene. These exposures would he exprcted to diiicr trom person to person and would also he expcctcd t o pirallcl background exposurt.s o i thc study popul.ition during the years these prrsons were emploved outside o i benzene areas. In addition t o overdl matched pair comparisons. the health mr,isures. exprecscd a~ pair ditierences. were examined in relation to e-timated dose ctrrrcnt r\postrre tndcv highect T\V4 e\posure snd duration o t henzone r\pcicure using a multiple regression approach. The current m d hishest TW 4 exposure intensities were exprmsd in coded form: 0 ior not e\- posed: 1 for < 2 ppm: 2 ior 2-9ppm: 3 tor 10-1-1ppm: and 4 ior 25+ ppm benzene. Estimmd currcwt t ' \ p i \ t i r r intensitic's dt thc time oi examination did not exrctd 10 ppm TLVA i o r ot thr individuals in the studv. Htvn,itnlojiic..il d.it.1 w w h i rornp.ired with laboratory findings reported hv .i noiu htvnic .I( comp.lnv. The cohort for the mortality $tudy includtd all persons who ,ip- -Tab10 2. Employment Slatus and Participation in Hrrlth Exam Program Bctwmn 1967 and March 1974 by Production Area. Benzene Cohort. I Empbrmnt Status and Panabation m tbdth I Numbn 01 Emobrns Produalon I Produnion I Pmduccin -Table 3. Selected Measures of Exposure by Production Area and Level o f Hiqhcst TWA Exposure Intensities. Health Exam Panieiprnts. Total pw Currently ermrcd Past cqmw Production Area I Production Area II Proauctlon h a 111 I 282 50 I I8 2 I66 48 a; 5 75 8 I38 31 I 128 4: 36 22 92 i0 2s I 4 33 IO 10 18 52 58 h I 443 24 25 13 1 -Fin --MOW 20 2 4 1.30 19 3 4 :.38 20 8 I1338 ZI 1 21 : I 5994 I8 9 4 I40 Hlpnert TWA bmzelc c r m v d lor I + months 2S+ DDm 1020 om 4 1 0 om 71 3 5 4. I76 IO S 3s 27 16 85 13 4 25 21 10 31 25 5 8 40 22 6 4.31 -I6 9 4 1-31 sistently ranging from 9,000to 10.3~0preceding the emplovee`s rent? exposure included 34 months in the high category i + 2 5 first exposure to benzene. and extending well beyond his last hcn- ppml. 3 0 0 months in rnnder`itc 110-24ppml. and GO months in zene exposure. low (2-9ppml. He retircd in Fchruary 1974 ,it the +ge of 62 years; A second emplovee had a hematocrit reading of 29% and a one month prior t o this time. hi5 hemrqlohin value was 13.5 g. hemoglobin of 10.2 grams in 1970.with reierral to his tamilv phvsi- hcm.itncrit 4O.l"O..ind WRC 4500.A 1976 report irom his prv- cian. (His record also showed anemm secondary to gastrnintestin`il son,il phwicim indicated this individod to hc in soid health. bleeding when hired in March 19671. Suhsequentlv. he w ~ s Thc sixth perwm was rcivrrtd t o hi> iamtly phvsician in 1971 diagnosed with idiopathic thrombocvtopenia purpur`i. His !oh i)i with .in increased whitc cc4l count. He WAC suhsequimtlv d i q - three months' duration in the benzene area (11;67-2%8)w.iz ncwd with hvpcrtcnsion .ind milrl di,ihcitc.c: the inrrcascd white cl.issiiird as low. and was ludged not to be relattd to the clinical counts wrw prc-rumcd to hr thr r t * w l t \ ni ,I rplcncctomv ptv- condition. fnrmtd on clw rrnpli,ycc .iitrr .in ,iutomcihilc accident in 19W. Multiple resression analvses performed for each lab mmsurc hv regressing the lab response on the iour cnvirrmmen tal v,iri.iblc>< sepdratelv for each production .irpa. and for the pmdtictlon xi*<i\ combined. are summarized in terms oi st.itisticalIv signiiic.int . i ~ r *- Benzene E.pnY)II 0 - - Controls ciations in Table 5 . In this c i n . ~ lth~e~L~ib~rr.sponzc was thc- nh- served reding of the exposed individud lrss hts rnatchrd contrril. None oi the hemtitolcq~caml easures \vwc zignliirantlv cnrrrlatcd with anv environmental variable. The two Iah rnecilcurP\t o r wh1c.h associations were observed in thc totail cohnrt were not correhted with environmental vari.ihlec in mnrp thin onr oi the individual production arecis.In Production Area 11. cumul.itive d r ~ was highly correlated with duration of exposure `r = ,751 ,ind current TWA intensity (r = .49)T.hus. duration ni e\powr(* and current TLVA intensity were individually assoc.iatrd with totd bilirubin. for example. although ncithcr `iddpd signtiic`in tlv t o ttitl regression equation drter cumulative dose h i d been takcn tnro CI.- count. Health history items were utilized tn indicate individuals who may have had pertinent conditions in thc past. The r m w w oi specific medtcal records was undemkcn for persons re<ponding positively to a history ot (1) anemia or blood problems: ( 2 1cancrr or malignant growth: (31 fits, convulsicmz. seizures; or 14) locs oi memory. No results oi interest in rcg.ird to bcnrerir t o i c i t v wcri. found among the latter three health histcirv questions. Six persons in the bcnzene Srnup wporttul .i hlstorv oi .intwisi -or blood problems. Company medical rtyordi on tour < ) I thew showed no evidence of anemia three emplovcer rverc t.iLtng medications ior cardiovascular problems at the tinle oi c\,im. and the fourth h d a hemophiliac condition known to thc conillan\ since 1957. The fifth ernplovee haid a hic:orv oi blmd cotinis which hive iluctuated between normal m d slisht drrrr.isec rlnrv 1951. Hemoqlohrn values have rdnqed from 12.9 g to 15.5 g. hematocrit trom 38.5% to 4696.and WBC from 3.600 to 5.1 50.Thtr 'person began working at our company in 1941.His potential bm- 35 4 0 45 Y) 5s -Fig 1 Ptrcrnr Oistribution of WBC. REC and hematocrit readings for total e i p a v d a d matched control populations. c -Table 4. Comparison of Benzene Exwsed Population with Matched Controls for 17 Selected bborlIOrY TeSlS. 1967.1974 1-1 Promduns ~ (lo Of P8.1 8enrme Croup IY SO1 Control Group I Y + 501 k n m e Group Less Conlroh IY ' SO1 aim CWW:WS T o i d Dmrubm q% Cwaiinin ~ p 0 ro:ai cmtcm q-A Pfoiem aibLmm Pvtem g'oaulm g v h BUY 1;0 LOM umic SCOT units Mmlolc~v Mema'mit 0 H(.mopobin ;m WBC m mm RBC In millions MCV HCW MCHC -255 44 76 ra : 24 01 2 38 IP 4 051 213 I :a 5 13 I19 + 19 01 ?. 24 -Z?4 7 12 : 36 I16 t 39 01 2 SI -224 113 : 5.1 436 f 52 03 2 55 224 '79 : 5h zao L r9 - 01 2 62 :2 4 1 I:? 13 170 4 3 I + 5a 1R7 1671 ?. 31 7 1633 IC1 1 8 L 408 + I89 2 6 3 *_ 9 9 266 : 123 2 2 IS0 -290 4q2 2 30 151 28 - 2 40 217 i5.7 +_ I O I53 2 I O - I + Id 232 1 x 9 5 1410 7030 ? I140 210 2190 -236 495 +_ 31 501 + 35 06 48 If < 051 235 910 1 1 9 0 5 *- 4 7 6 52 236 309 2 1 5 336 .: 1 6 2 20 236 339 Lc. I O 339 I O 0 c_ 1 2 -Table 5. Summary of Statistically Si(ni1icant findings (P 4 05) for Retression of Each bb Test (Matched Pair Oifferencer) on Current TWh Eaposure Intensity Category. Highest TWA Intensity Category. Ouration of Esposure and Estimated Career Dosage fppm Months). Total Population and Each Production Area. 1-1 Frocdur* Enruonnuntal Warubk. CorrtCelon Coefficient and Si#nl*.ncs Lnd relative to the US. white male pnpul,\tir)n w r r p nhrtvvtd with respect to production xe.1 or t!\tini;lted carwr dowge t i i honzent-. The rnortalitv analvsis did direct Our attention to five individu& whose death certlticgiteF contdinid inlormalion oi clinical intcrert -in regard to henrenp toxicity. Two dmth\ were duc to anc.nii.i one person dirvl in 1955 fpcrniciow .inrmi.il. .ind thc sccijnd pcrson died in 1957 1apla.tic 'inernid. Lcukrrnta was indiccitcd on three death certiricates ior persim\ dvinq in 1965. 19iO .ind 1971. respectivelv (one. c a w oi acute y'inuloc vtic and t w n C.ISCI ot myelogenous leukrmim. Detail\ req,irdins these CdSP5 Jre dis- cussed in the mortality article.'> The individual who died most rcccntlv irom 1cukcmi.l h.id p x ticipated in the health cumination prngrmn- 'ind IF inc.ludvd among the 282 person\ in the prrwnt Ftudv. tiis hlriwj cr)unts over a ten-year period. including one ,IS recent as ten months before death. were within norm.il r'inqes. Thus. o u r mpdil-al records did not indicate prim hirtorv oi blood abnormalitic?i typical of leukemia attributable to henrcnr. This health examination studv indicates that readilv dtstrt table latent hematopoietic chdnaes have not n c r - t r r r d in our pnoul,ltron of employees.manv oi whom had pat T W A c.cposures oi 10 ppm or more. The question that rem,iinr unmrrverd i\ w h x i s thc. likelihood that serious health riiects (cuch .IS Icukc-mi.i, will occur in individuals vmrs aitcr henzcnr exposure Jt conwntrationz JS described in this article. particul.irlv when ht~matologictinding\ werr normal during the w a r s oi t.mpL)vrncnt. tic.alth \urvtvll.incc' oi this popuiatirm will be continued and p r r h a p will one dav prrF vide a more driinitivr answer t o thr que-5tirin. L c c