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c THE JOURNAL OF IhTDUSTRIAL HYGIEhTE AND TOXICOLOGY .. RECOVERY FOLLOWISC E-;POSURE TO BEXZESE (BESZOL)' LE OS.^^ J. GOLDWATER .LVD ~ L ~ R G A RPE. TEIVKSBURT Departments o j Prevcntiuc illedicinc and Clinical Pathology, and Occupational Discrrse Clinic, Ncto York linivcrsity Collepe o j Afedicinc, Nclo Ymk City TEIE LITER.4TL.E dealing gretted that full details concerning with follow-up studies in non- these cases are not given. fatal cases of benzene poisoning During the early part of 193s a is not very extensive. Erf and Rhoads study of benzene poisoning in the (1) have recently reported on the rotogravure printing industry was course of 9 cases of benzene poisoning undertaken by the Division of In- over periods of from 2 to 5 months dustrial Hygiene of the Xew York folloning cessation of benzene ex- State Department of Labor (3). This posure. These patients d receive_-d study covered 332 persons of whom 130 intensive anti-anemic therapy and all presented suficient-lymarked hemato- but one recovered. In the exTensive logic abnormdity to be considered r e ~ e wuf benzene (benzol) poisoning cases of benzene poisoning. The at- contained in the British Medical Re- mospheric concentration of benzene search CounciI's report on industrid to which the men were exposed varied solvents (2) mention is made of 14 from 11 to 1060 p.p.m. and the dura- workers who were re-esamiued follow tion of exposure from 6 to 60 months. ing removal from or mitigation of benzene esposure. It is to be re- * Received for publication February 21, 1941. before the American Industrid -4 detailed analysis of the blood findings in this investigation has been pubIished eisen-here (4). The use of benzene was discontinued in this industry immediately upon` the dis- BYJriene Association, Pittsburgh, LIay 9, 194. `L -The. term "benzene" is Pmnin..arl .-- -- .-, I he Editors. covery of the e:iitence of 3 hazardous situation in April 193s. T-he present report deals with three sets of folloT-up blood studies. The - 21s JOURS.\L OF ISDrSTRLU IIYGIESE ASD TOSICOLOGT [vu!. .?5, r~).6 first covered 56 workers in one printing ing tlie eiiniiiiation of benzene no great establishment (designated Plant A) 3 difference in rapor concentmtions months after cessation of the benzene could have been espected. The few esposure, the second involved com- air annlpscs made confirmed the es- plete blood examinations on 49 eni- pected findings. It can be st3ted with ployes of a second printing plant reasonable certainty that thc vapor (dcsignnted Plant B) approshntelp concentrntions of the minor constit- 14 months after the use of benzene had uentS of the iiiks were well below the been discontinued. and the third en- levels wliicli might be coiisiciercd tosic. tailed rc-esnniiiution of 10s men from Plant .Iabout 3 years d t t r the original XETHODS studies. :it this time 20 men who had The technics follon.cd in exlmining entered the employ of this company the blood were the same as those fol- during the interim were nlso esaininc>d. l u w d at the tinil. of ttiv oriqin:il cx- Arrangements for re-esamination of nminntion (4) and the counts w r e :ti! the second and third groups a t the done by tlie -amc person who n i d c the Occupationnl Disease Clinic of the Original dcterminatiow. In Plant X Xew Tork University College of Xedi- the first re-csamixiation was limited to cine mere made by the Division of a study of the hernoglobin value, the hdustrial Hygiene of the Sew Tork erythrocyte count and the leucocyte State Department of Labor with the count. For the Plant B group and the cooperation of the employers and the second re-esamination at Plant A, printing pressmen's union repre- hemoglobin, red and white count, dif- senting the workers. ferentid, phtelets, hematocrit and the In evaluating the results of the indices of mean corpuscdar volume, studies reported in this paper it must hemoglobin and hemoglobin concen- be borne in mind that other soh-ents tration were done. As the men re- had been substituted for benzene when ported. they were questioned regarding the use of the latter was discontinued. ,n~nptomsand as to what treatment, The several ink manufacturers from if any, they had received in the interval whom the printing plants under in- between examinations. ,411 but five vestigation obtained their inlis were of the men r h o were re-examined had estremeiy co-opemtive in suppl_ving remained a t work nithout losing axiv iniormation as to the nature of the time. Four of the five r e r e m a y from materials that had been used in place their jobs ior irom 2 to 4 months ant1 of benzene. The great bulk of the the fifth had not returned to work 3t solvent material used consisted of vari- the end of 14 months. ous petroleum naphthas cox-erhg a boiling range of about 150F to 300F. Re-eraminations at Plant A ,D mon!hs In addition, small amounts of some of afrer cessafionof the use of benzene the better known esters and lietones m e n the original survey was begin were used in certain of the ink.. in April 193s it \vas necessary to ex- Mention has aired. been mad&of amine 3 large number of men in a rch- the wide range of \ - q o r conce~trations rively &or: time. ..is a rapid `*srrcc~11- that prevailed duricg the period of ing" niethocl it ivas decided to do ~i benzene esposure. I n s m u c h as no hemoglobin determination and 3 Icuc1'- radical cl:31ig:c\s in vei:tihtion or in cytc count on e w h n.orker a : ~ liitl)r ` operating practice irere msde iollon-- complete ?ti:LIv- rJii t!lo.:e l u i u ~ l1 ' June, JB.$fl RECOVERY AFTER BESZESE ESP0.3VRE 2 19 h a w low valurs in either of thme tests. T.\DLE 1 It subsequently developed that this COVPAR~SOOXF HEIfociLoBxs, ERI-TIIRO- rapid survey method 1~sentirely ~ 1 1 - W E AND LEUCOCYTE\`.<LUES IN PLANT A satisfactory for case &ding (3, 4). IS APRIL 1938 ASD IN JUNE 193s Reexaminations 2 months later were done on 56 individuals and consisted of hernoglobin, erythrocyte and leuco- cyte determinations. The group se- A?= 1038 Numb-\ R JWWZ la6 zjHumheri Hemoglobin lected for re-cuminntion included 17 c s e s which l u d originally bcen con- sidered tlchitcly :hnorrnnl, 1G borderline cases and 23 whose blood pictures had been normal. Because of the Iiniited information obtained a t the i h e of the first esnniii:atiois, only limited conlpnrisons c3u be made. Hemoglobin. 54 cases are mailable 10.0-10.9 11.0-11.9 - 12.0-12.9 .I 13.0-13.3 25 14.0-14.9 1.; 15.U- 1s.!) -,-.- 3 Total.. .. . SI 3.7 12.9 46.3 27.s 5.6 1 1100.0 1 7 16 In LJ 54 1.!I 12.9 33.3 s.2 -1C.7 100.0 for comparison. The frequency distribution of these cases in April 1936 1\lean, 13.54 gm.l.\Ienn, 14.02 gm. St. dev., 1.05 St. dev., 0.653 9s compared nith June 1935 is shown in table 1. It is apparent that there has been an upward shift of the values, lpLyows Erythrocytes but the change is not very striliing. Since relatively few cases had very low hemoglobin d u e s at the time of the original e.&tions, no great im- provement in the group as a whole could have been expected. Erythrocytes. There mere 34 cases 3.0-3.4 1 2.9 2 5.9 3:5-3.9 4 11.8 5 14.7 4 . 0 4 . 4 11 32.4 6 17.6 4.5-4.9 10 29.4 16 47.1 5.06.4 7 20.6 4 11.8 -- -5.5-5.9 1 2.9 1 2.9 ,-* .Total.. . . M 100.0 34 100.0 in which red cell counts were made on both occasions. As shown in table I, mil. RBC 16 of the 34 had reduced eq%hroc:te counts (less than 4.5 million) at the time of the first esaminations and thirteen still had subnormal counts 2 months later. A c t u d y the mean value vas slightly lower at the later date, although the m e r e n c e is quite insignificant. Furthermore, there rere 6 cases in n-hich the second count was lower than the first. Although the comparison has been made on a small group, it seems apparent that it k possible for the erythrocyte count to remain depressed or even 10 conh u e to fall for a period of a t least 2 Leucocytes ~oouwo~ 3- 3.9 4- 4.9 5- 5.9 6- 6.9 7- 7.9 s- s.9 9- 9.9 10-10.9 11-11.9 12-12.9 13-13 .O 4 10 13 9 7 7 2 1 0 0 0 1.9.1 17.8 91 23.2 10 16.2 11 12.5 10 15.5 9 3.6 1 7.1 1 03 00 10 1 Total.. ... 1.6 16.2 17.6 19.5 17.8 16.2 1.6 1.9 5.3 0 1 .s months after cessation of bwzcne cXPo.sure. Leucoytea. The entire group of 56 blood-forming organs caused by ben- cases who were re-e.samined after 2 zene can continue to progress for at months had had leucocyte counts least 2 months after exposure has made at the earlier date. Aq was the cenqed. The possible role of the xiew case with the hemoglobin values, solvents used i u s been mentioned and there had been a slight upward trend, will be discussed briefly later. although a considerable number still Treatmcnf. Some form of nnti- showed subnormal counts (table 1). anemic therapy W:LS takcn by 1'7 of In view of the ivcil known lability of the workers in P1:int A idio were re- the Icucocyte count, cstcrided Cis- es:imined. Of these, 11 had been classified as positive and G as bordcr- ThBLE 2 line. Of the 11 positives, 4 h d be- CO~IPARISOOF SSTATKO.~F CASES i s .\rniL t'ome negatir-e at the enfl of 2 months, 103s ASD IS Jcsr 193d, PL.ur A 3 had c h g c d to borderline and 4 re- Single abnormalities were used M a bwis mained positive. .4t the same time for classification 5 of the 6 borderline cases b c c m e A?- positive. In most instances the trmtment consisted of liver estract given ---- p z r e n t e d y t x o or three times a week, Positive ......... 17 8 4 5 whole iiver in the diet twice a week, Borderiine...... 16 6 7 1 I '* IXepative........ s -I-I-i o d . * - - - . - - . / jg 2 l6 7 14 nnd some concentrated form of the v i e B complex taken M y by mouth. The xnmlber o f ' c ~ e sinvolved \vas not large enough to justify detailed criteria Positive : R.B.C.. ................ .4 million or lesa W.B.C.......................5,000 or less comparison of treated and untreated cases. Actually the proportion of positive and borderline cases who did not receive treatment and showed im- Borderlinc: provement was practically the same P..B.C ...................4.011.50 million as for the treated group. 1T.B.C.. ......................... .5-6,000 Re-ezaminatwns at Plant B 14 months cussion of these h h g s does not seem ajter cessation of the we of ba-ene warranted. Diagnosis. An anaiysis of the dng- nosis of the 36 individuals who mere resxamined a t the end of 2 months is given in table 2. It is apparent that there had been Iittle change when one considers the entire group. It is The group studied consisted of 49 of the 69 printers who were emmined a t the time of the original survey. The candidates for re+xnmination were self-selected in that the sane opportunity for emmination was presented to d the men, to be accepted true that 9 of the 1 i who wete on a purely voluntary basis. That ori,&isll- c l s d i e d as positive had this method of selection resulted in 3 moved into the borderline and nega- truly representative sample is demon- tive groups, but on tne other hand 6 strated in table 3. bordcrline 3nd 9 iiegntil-ec s e s showed X comparison of the original :id definite regression. This furthcr em- follow-up blood studies in the A:? n:.:rl phasizes the point that damage to the n.ho were re-esunined can b e s ~ made' by considering separately the different blood tests. The results are given in table 4. Those individuals who did not report for re-e.samin3tion are omitted from consideration. Hemoglobin. Diminution in hemo- globin values was not n common find- ing 3t the time of the 1933 survey. This being the c s e , no great chance in the hemoglobin picture n-oiild IIC anticipated aftcr cessation of benzene exposure. Inspection of the table reveals that time i n s a slight general -;lift of the h:mo:'ivLi:t \-slues to a OM. ?El 100 CC. 11.0-11.9 12.0-12.9 13.0-13.9 14.0-1: .9 15.0-1:.9 16.0-16.9 TABLE 3 17.0-17.9 DIAGSOSTICCLASSIrlC.\TIOS 1s 103s OF ESTIREPLASTB COMPAREWDITX THAT Total.. ... OF CROUP \\.'RICE CAME FOR RE-EXAYI- NATIOS Positive. ........ Borderline.. .... Kegstive.. ...... Total.. ....... higher level but the mean value increased by only 0.5i gm. Erythrocytes. Diminution of the red cell count vas a prominent feature as the time of the o r i k h l sruclj- with practically one haif of the subjects haiingcounts below 4.5 miliion. Gen- eral improvement in the erythrocyte picture is reflected in the class frequency distributions as %-ellas in the mean values, shoirp in table 4. In spite of the upward trend there isstill an appreciable proportion of the cues (24%) haring counts below 4.5 million 14 months after the temination of benzene esposure. L e w c y l e s . A general improvement total counts was noted in the folloi~--u:,study, as indicated in the table. -4single case i m s found to have 3.0- 3.9 4.0- 4.9 5.0- 5.9 6.0- 6.9 7.0- 7.9 8.0- 8.9 9.0- 9.9 10.o-10.9 11.0-11.9 E.0-12.9 2 5 10 10 10 6 2 1 2 1 -I- Total.. ... 49 4.1 10.2 20.4 20.4 20.4 12.3 4.1 2.0 , 4.1 j 2.0 j 100.0 J I e m 6,349 K.u.c. St. dev.. 1,5SO 2 2 J o t - R S I L OF ISDTSTRIAL HSGIELYE ASD TOSICOLOCY [rol. 23, M. 19 T l B L E 4-Confinued TABLE M o n c i u d c d iNumb-1 Z jh'umk( % N e i n corpuvculnr hemoglobin I% -OM. 10-19 4 8.5 3 6.3 3-29 19 40.4 16 34.0 30-39 19 40.4 23 49.0 40-13 4 5.5 4 8.5 --5J-59 1 ?.? 1 1.? Total..... 47 100.0 r7-1 100.0 Mean, 30.53% Blcm. 31.6% iynplo St. der., SASS, S t . de%..i,.79% 24-?6. 0 0 3 6.5 5-3 9 19.5 13 3 . 3 30-32 33-35 17 12 37.0 20 3.1 * 4135..25 313-33 7 15.1 3 6.5 3941 1 1.2 0 0 ----Total.. ... 46 100.0 4G 100.0 I 'I .\lea%,39.6 .\lead: 31.9 I St. .lev., 3.105 St. dev.. 2.91 --Blood plntelets less than 4,000 white cells, and four more had slightly reduced counts (be- Under 50 50- 99 100-149 150-199 200-249 4 9 15 8 6 6.9 0 20.0 1 33.3 18 17.6 11 13.3 14 0 tween 5,000 and 6,000). The indi- 2.2 40.0 vidual hating the count under 4,OOO 21.5 was the Same one whose erythrocytes 31.1 remained under 4 million, indicating 250-299 2 4.5 1 2.2 that probably he was still suffering 300-349 1 2.2 0 0 from benzene effect 14 months after 7- --Total.. ... 45 100.0 45 100.0 cessation of exposure. Lymphocytes. A relative lympho- Mean, 139,450 cytosis is usually mentioned as an - -pirteieta piateleta St. dev., 69.700 St. dev.. 46,950 Mean cor~usculav~olume important part of the blood picture in chronic benzene poisoning. The goup of workers under discussion may eo. bl 75- 19 so-84 1 0:o 00 be seen (tEble 4)to have had a normal 3 6.7 distribution of lytnphocyre percentages 3 6.7 at the time oi the first e..:unimtion 85- s9 9 20.0 11 24.5 and qain 14 months h e r . This s 9 4 14 31.2 13 25.6 would seem to hciicate that the per- 95- 99 5 11.1 9 a . 0 centage of lymphocytes in the blood is lOO-l(H 1os5-109 110-114 6 5 5 13.3 11.1 11.1 3 2 1 6.7 4.4 of no significance in the diagnosis of 2.2 benzene poisoning or in estimating 115-119 1 2.2 0 0 --- --Totd.... 45 100.0 45 100.0 recoven.. Platelets. -A sigdicant reduction in blood platelets was found in nearly ~~ ~ Jean, 97.62 cu. rIean. 92.61 CI. one-third of the cases in the orighd microns micro= emmination. In the follor-up study, St. der., 6.i4 St. dev., i.6.L a single individual (the same one - June, 19411 RECOVERY AFTER BESZCSE ESPOSrRE 223 mentioned aiJo\-e 3s 11ari11glow red c s e s w r c iurthcr fromor no nearer to 3nd white cell counts) was found to normal when examined 14 months have less than 100.000 plrttelcts. It after cessation of benzene esposure. is apparent from the t3bk that nppreci- Treatrncnf. Only S of the cases able improvement in thc platelet pic- from Plant B who were rr-examined ture had taken place. gave n tiiston. oi having taken treat- Mean Corpuscular I'olume. The ment: two received liver extract par- importance of mncrocytosis as evidence enterally and orally, four took the of benzene poisoning has been pointed estract by mouth only, and two added out in recent publications (3, 4). In u-hole liver to their tlict once a u--rck. tlic prcscnt serics uf c'Lm this liema- tologic abnormality occupicd n prom- 'I'.\BLE 5 inent position, Generally spcaliin;;, Cow2.misos OF STATCSOF CASES IS .\PRIL wssntion of bcnzcne esposure resulted 193s ASD IS JFSE 1939, PLCST13 in a mow ncirly iiornial ceIl size. but even after 14 months an appreciable number of cases stili had abnormally large erythrocytes. The findings are summarized in the table. illean Cotpuscttlar Hemoglobin. The hdings in this test parallel those CIs+ificstionImcd on siwle abnornralities Arm&193s 1 JOWL 1939 BTATVB ' zStraw Toul I P c s t t ~ e ~ ~ ~ ~ ~ ---I- Positive.. ....... ?O .I 15 1 IBorderline...... 7 ?4 Negative.. ...... 2 2 18 for mean corpuscular volume. The resultsare given in table 4 and call for Criteria no particular comment. Diagno&. T h e classification of the 19 cases as t o diagnosis at the time of each e-xamination is shown in table 5. The general improvement in the blood Poaitive: R.B.C.. ................ .4 million or le= W.B.C....................... 5,000 or lm Plates...................... 50,000or less R.B.C..................<A5 million v-ith M.C.V. >loo . pictures naturally resulted in most of the cases falling into the "negative" ;roup after 14months of freedom from benzene exposure. On theother hand it cannot be said that there had been Borderline: R.B.C.. ................ .4.01-$.50 million with normai bI.C.1'. R.B.C............... .:. . . . . . . . . . .54,000 :niversal recovery. Table 5 inciicntes :hat 4 of the 20 cases origically ciiag- Oniy one hsd continued under trezt- losed as positive stiIl remained de&- ment for the entire 14 month period aitely abnormal and four more of this and most had stopped treatment after -up had shon-nonly partial recovery. 2 or 3 months. The one man who h3d Furthermore, there were 2 men? who continued under treatment still hsd were considered to have n o m 1 blood a distinctlr abnormal blood picture Sictures at the time of the original when re-examined.' There r a s no :mninations, whose counts were defi- indication in these 8 cases that the litely abnormsl 14 months later and 2 m r e n-ho had shon-n regression of a 'This is the case referred t o above 3s cser degree. In all. 11 of the 49 haring below 4,lrOO leucocyres and bclow 4.0 million erythrocytes. I I .'I . [: !. ! ,. i:;i .I .I .I 1 -! -. :f >. ii i '1 .: I !1 ' .I I?. I ! trentment taken had modified the poisoning are not likely to manifest c o m e of recovery. themselves by a diminution in hemo- Re-etaniinations at Plant d 24 months aflm cessation of the we of benzene globin content of the blood. Consequently the hemoglobin test cannot be used 3s a criterion in evaluating recovery. All that can be snid con- The group studied consisted of 108 cerning the present series of obsemo- of the 16s men who were esamined a t tions is that 3 years nfter esposure to the time of thc original sunvey. As benzrne had ceased, a single c s e wvas the case with Plant B, the group (0.9%) was found to hare a lorn ~ 1se"ll-selected and was made up of hernoglobin value as compared nith n representative sample of the plant 4.7T0 of subnormal values in 235 cases personnel. Complete blood studics studied at the tinic: of benzene cs- were made in all c s e s a t the time of posure. re-examination, nlthough 3s has been Erythrocytcs. In connection nith stated, only a small p u p had been recovery, BS reflected in the erythro- fully studied in the original survey. cyte picture (table 6), there are two It is felt that the status of the men in features which seem worthy of com- Plnnt A after a 2 year i n t e n d can ment. The fact that six (5.5%) of best be brought out by comparing the the workers in Plant A were found t o results of the 1940 examhtionswith have red cell counts below 4.5 million the 1938 findings inthe entire p u p 2 years after cessation of benzene that had been exposed to benzene in exposure may indicate that recovery all plants, and also by comparing the was incomplete in this small p u p . 1940 results with those of a control In View of the high proportion of re- series of workers who had had no un- duced en.throcyte counts at the time usual occupational exposure. These of the first examination in 193s it comparisons are made in tables 6 and would seem reasonable to use this i. It can be seen that with one or test as a criterion of recovery. A two exceptions there is very dose re- second point of interest in connection semblance between the control group with the red cells is the fact that 23 and the Plant A group in 1940,whereas cases (21.2Y0) had counts above 6 there are striking Werences between million in 1 N O and that 6 of the 23 the controls and the 1938 benzene were &ove 6.5 million. One might group, as has been pointed out in speculate on the possibility of these previous publications (3, 4). The elevated counts being a reflection of hdings d be discussed very briefly. the hyperplastic bone IW which Hemoglobin. As was the case in has been described in connection Plant B, low hemoglobin d u e s were Kith benzene poisoning (1,5). not common at the time of the original Several cases showed an abnom31 studies 3t Plant h in April 1938,,but amount of basophdic stippling and table 6 shows a general increase in the polychromatophilia, but these findir.rs values ~ t ah single case remining could not be correlated with eir1it.r significantly l o r . Experience has high red or r h i t e cell counts. Their shonm that indications of early benzene presence cannot be explained at present TABLE 6 COMPARISOorN BLOOD FISDINGOSF TEE EmmE BESZEXECROVPIN 1038 WITH TaosE OF TILE PLANAT MEN JVEO WERE EXANINEIDS la0 AND WTX A CONTROL CROUP ~~ ..I.-omom. 1938 INo. 9. .wtA. 1040 INo. 95 CO#IT~OLo a o w . 1038 IKO. ~~ am. ?E. 100 cc. Hemoglobin Less than 1 0.4 0 11 .o 11.0-11.9 10 4.3 1 0.9 0 0 -12.0-12.9 9 10.5 3 5.6 7. 2.4 13.0-13.9 95 40.5 34 31.5 25 30.9 14.0-14.9 7s 33.2 32 ' ' YJ.7 40 49.5 35.0-15.9 20 8.6 2s 25.9 11 14.8 16.0-16.9 6 2.5 9 s.3 2 2.4 17.0-17.9 0 0 1 0.9 0 0 I I I 1 I ITotal ..... 23.5 100.0 106 100.0 61 100.0 Mean, 13.S p. St. der., 1.07 Mean, 14.56 gm. St. dev., 1.08 Mean. 14.34 gm. St. dev., 0.79 -on 1.5-1.9 2.0-2.4 2.5-2.9 3.0-3.4 3.5-3.9 4.04.4 4.5-4.9 5.0-5.4 5.5-5.9 6.0-6.4 6.5-6.9 . - e .:. 4,4 Total .... m0O.yID. 3.0- 2.9 3.0- 3.9 4.0- 4.9 5.0- 5.9 6.0- 6.9 7.0- 7.9 8.0- 8.9 9.0- 9.9 Erythrocyten 1 0.6 1 0.6 3 1.9 3 1.9 22 13.9 46 29.0 50 31.4 29 18.2 4 2.5 00 00 00 159 100.0 Mean, 4.46 St. dev., 0.6i 0 0 0 0 0 6 28 33 18 17 5 1 I 108 0 0 0 0 0 5.5 25.9 30.7 16.7 13.7 4.6 0.9 100.0 I Mean, 5.4-4 St. deo., 0.645 ~ Leucocmea 6 1.8 16 4.8 !?6 7.9 55 16.5 5s Ii.5 55 16.5 48 14.6 21 I 7.2 00 1 0.9 3 1.9 9 5.3 13, 11.1 14 13.0 15 13.3 16 14.0 00 00 00 00 00 2 2.4 16 19.6 33 40.6 2s 34.6 2 2.4 00 00 81 ' 100.0 Mean, 5.32 St. der., 0.42 00 00 0- 0 I S.6 Ij 3 . 4 1196 19.s 11 13.6 10 ! 12.4 TEOCSAWDB I i I TABLE "ontinwd DEWZZWC oaour. 1938 xo. I x I i M A . lw 1N ~ . k 1 IC O ~ O eLnour, IS31 No. w I* 10.0-10 9 : ll.o-ll.!l , 12.0-12.3 , 13.0-13.!I 14 11-14 I) 1 15.0 or I more 1 I 1 Leucocyter-Concludcd 2G I 7 . 8 14 13.0 2.1 8 7.4 5 36 2 0.G 0 0 cj I 5.5 I 1109 100.0 iMean, 7.295 St. dcv., 2.36s ?tlc.in, 9 , W St. dev., 2.710 1 I 113 16.1 I3 3.7 1 1.2 1 j 1.2 0 100.0 Mean, 6,153 St. des., 1 . s ~ so 10-19 20-3 30-39 4049 -59 6049 I' Total ..... 10 41 41 15 5 0 112 Lympbocytu 9.9 36.6 36.6 13.4 4.5 0 100.0 4 21 57 24 2 0 ~~ 108 3.7 2 2.4 19.4 10 12.4 52.8 40 49.5 2.2 23 29.3 1.9 5 6.2 0 ,1 1.2 I 100.0 I81 100.0 >lean, 31.79 St. der., 9.66 Mean, 35.0 St. der., 7.9 Mean, 35.25 St. dev., 11.65 ~ raouwDa Less than 50 50- 99 1011-149 1150-199 200-249 SO-199 30G3i9 . I33-399 ! ~otal 12 11.2 33 21.5 31 29.0 20 18.7 12 11.? 5.6 2.8 0 I107 100.0 Xein, 137,620 St.de\-., 13,970 Piatelets 00 7 6.5 27 3.0 29 26.6 19 17.6 14 13.0 10 9.2 2 1.9 1108 100.0 ~~ Mean, 195,250 St. dev., 66,600 00 00 9 1s 11 In, 20 40 8 16 12 12 50 I 100.0 m. c 70- i 4 75- 79 EO- 84 S5- $9 `30- 91 95- 99 100-104 105-109 110-114 ll5-11Y 1 Total.. .. . I Y om 20-23 24-26 27-29 30-32 33-35 36-38 3941 Total ..... % 2+26 27-29 30-32 33-35 36-38 39-41 I Total ..... I Nenn corpurcitl3r volume ~- 1 0.9 9 8.3 2 1 .9 17 15.s 9 8.8 1s 15.7 19 18.5 L1; 25.0 24 dI > . . 2 20 1S.5 15 14.6 10 9.2 16 15.5 1 3 . i S 7.8 2 I .9 w I 6.0 1- 0.n 2 1.9 0 0 103 100.o I08 100.0 Mean, 95.51 St. dev., 9.40 X e m , 6s.14 St.der., S.58 Bfenn corpusculnr hemoglobin 7 9.3 9 12.0 10 25.4 30 26.7 13 17.3 3 4 .O 4 5.3 00 00 00 100.0 Mean, 55.30 St. dev., 7.11 00 12 10.0 31 25.8 40 33.3 21 17.5 11 9.2 5 4.2 1120 100.0 10 9.2 36 33.3 41 38.0 17 15.8 3 2.8 11 0.9 0 10O6 100.0 00 30 41.2 34 46.5 9 12.3 00 00 0 0' j73 100.0 sfe a , 31.6 St. der., 3.76 Mean, 27.66 St. dev., 2.96 Mesn, 9.16 St.dev., 2.02 Nean corpuscular hemoglobin concentration IIII 00 00 2 1.9 11 10.2 40 35.0 72 66.7 53 50.6 24 22.2 9 8.6 1 0.9 I1 0.9 105 100.0 00 1106 100.0 Mean, 33.63 St. dev., 2.07 1 I e q 31.92 St. dev., 1.75 I, I I` 1.2 5 6.1 3 67.9 19 23.6 1 1.2 00 Sl II 100.0 ?dean, 32.02 St. dev., 1.18 .; ]i.. y..,. .... 1 ' I .1 .-,. .*.-..I.; . . . ,.' i ! -! , ; a I :' '1I Jlean Corptasculat Volunrc (M.C.T'.). In the ori-ginal studies in 1938 an increase in the avenge cell size was found counts. It seems worth while point to be B very prominent feature. This ing out that the mean er?.throcj%e determination along with the en-count for the 1i cases showing leuco- throcyte count mas shown to be a cvtosis was 3.91 million while the mean reliable index of early benzene wison- leucocge count for the 33 cwes hming more than 6 million red cells was vealed thzt in most.c s e s the cells were 10?T90. Both of these mean values normal in size, but that in n few inare significantly higher than those for stances macroc_vtosis persisted. The the entire group. The elevation can- fact that the average 31.C.T. of the not be accounted for on the basis of 1940 series is significantly larger than hemoconcentration since the hemato- that of the control p u p suggests crits showed normal cell-plasma ratios. that there had been incomplete r e On the other hand, there was no con- covery as far 3s this abnormality ~ ~ 3 5 stmt elevation in blood platelets in concerned (table 6). these c8ses. nor n-ast.here m increase U e a n Corp~rscular Hernoglobit1 in the percentage of polymorphonu- (J1.C.H.) and X e a n Corpwcitlar Hornclear cells. -4 further point. inviting globin Concentration (M.C.C.). At the i June, IS411 RECOVERY AFTER I~ESZCSC ESPO.S.L-RE 229 time of the o i g h l studies in 103s Plant h h3d many more complaints there was found to be an increse in than those of Plant B (3). This may 3l.C.H. values due mainly to the in- have been related to the generally creased cell size, but ig part to actual higher concentrations of benzene vapor hemoglobin concentration. Inspection in the air of Plant A. When an a t of table 6 reveals a general return to tempt was mnde to correlate sympto- normal of the values in these tests matology with Mood findings it be- with 4 cases showing persistence of a came apparent that there \\*asno rch- high 11.C.H. tionship. 11nny individuals with Scriim Bilirubin. Comparison of nornia.1 blood Iiad nunicrous com- the results obtaind in 1835 with those FI:iiuts, and n i m y \vi til marked hcma- of 19-10 (table T) shows that there h s tologic abwrmality hsd no complaints been little change in the propor:ion whatsoever. In view of the fact that of Imv znd high values. Thcfindincs -the men continued to work in an to indicate that the serum Mi- atmosphere which n'm laden with rubin test cannot be used as a reliable solvent vapors, even though benzcne indes of benzene poisoning or of was no longer present, it is not sur- recovery. prising that a large proportion con- Diagnosis. Inasmuch 3s complete tinued to have the same complaints blood studies were made on only a that they had before benzene was small fraction of the Plant A personnel eliminated. At the time of r e + x d - in 1938,there is no m y of knowing the nation there was no correlation be- number of positive, negative and bor- tween symptoms and blood picture. derline cases at that time. 'zising the New Employes. Mention was made -same criteria that were applied to at the beginning of this paper of the Plant B, (see table 5 ) , the fact that 20 men mho had entered the tions in Plant A in 1940 revealed that employ of Plant X subsequent to the 4 of the 108 cases still remained in the time of the 1938 studies reported for positive group and 8 fell into the examinstion in 1940. The employ- borderline class. These findings sug- ment period for this group varied from gest that damage due to benzene may 5 to 22 months. Two of these men persist for a period of at least 2 years aiter cessation of exposurr?. It is interesting t o note that two of the cases classified as positive in 1940 had been considered normal in 1938 on the basis of 3 white cell count and hemoglobin determination. It is possible that if complete blood studieshad been done at the time of the first & . a tion in 1938,these 2 cases might have had eqthrocyte counts below 4.5 million assucizted. nith mean corpwcuhr volume ralues of more than 100 C U . ~and consequently vere considered abnormal. One case had 3 leucocyte count of 21,000 with a normal diflerentid count and mother had 8n eq-throcyte count of 6.92 million. Otherwise the blood findings in this been found to be abnormal a t that group were entirely within normal time. limiu. Interpretation of these ab- Symptoms. At the time of the normalities \rill be possible only after origind es;lminations the workers in subsequent obsen-ztiors. , - 230 JOIT.S.\L OF ISDL3TRI.lL IIYGIESE ASD TOSICOLOCT [ F O ~ .3,ne?6. COUMEXT The workers in Plant B who n-ere \\-hen an attempt is made to d y s e examined after an i n t e n d of 14 the findings in these follow-up studies it is nt once appuent that the datn are not ILS complete as might be desired. months showed very dccidcd improve- ment, but not universal recovery. Of puticular interest is the fact that 2 In dealing nith groups of printers individuals whose blood m a normal actively engaged in pursuing their trade it is obviously not possible to mnkc the detsilcd observations which at the time of the first examination had distinctly abnormal fiiidirig when re-e.umined. Both c a m eshibited can I)c made on hospitdizcd patients a fall in the rtd cell coiint nnd a eon- or on laboratory animals. The diffi- comitant increase in erytlirocyte size. culties inherent in this type of invcsti- gation no doubt esplain to some de- gree tlie paucity uf reltorts dealing 4 additional cases originally classified m positive still reniained in a definitely abnonnnl state 2nd 1 bordi*rIinc c s e with recoven from benzene pois- oning. In spite of the limitations of the present study there are sevenl findings which throw a certain m o u n t of light on the subject of m v e v following protracted exposure to benzene fumes. In P h t A, where the intend between cessation of benzene exposure and the first re-examination was about 2 months there was practically no change in the status of the p u p studied at the end of this time. The treatment which individuals in group received seemed to have no d e c t in hastening recovery. As a matter of fact, in a number of cases the blood picture was further from normal after 2 months of treatment than it had been at the time benzene exposure ceased and treatment was begun. This finding suggests that the deleterious action of benzene may showed regression. In Plant A, 4 of the 108 men who were re-examined after 2 years showed distinctly abnormal blood pictures and 8 others exhibited abnormalities of a lesser degree. It thus becomes apparent that it is possible for the effects of benzene to persist for a period of at least 2 pears. The cases which shonwi regression after the cessation of exposure are somewhat difficult to esplain. It mould seem that if the solvents which replaced benzene mere responsible for the adverse trend, many more cases mould have been nEected. The much over-worked explanation of "individual susceptibfitf' does not seem adequate. It is unresonable to assume that benzene continued t o act for s period of 2 years after exposure n - s terminated. Until further obserra- tions can be made on this and on similar groups of workers, one can continue to operate for several months only speculate as to why a few cases after the termination of exposure. T h e seem to have retrogressed. possibility of the benzene substitutes contributing to this adverse trend SWARY .ihp CONCLUSIONS cannot be excluded, but seems d- 1. Three sets of follow-up blood tremeiy untiliely in view of subsequent studies were made on mtogmurc events. printers mho had been exposed to benzene. TIic studies wcrc mudc 2, inciiriduab still had distinctly 3b 14 and 24 months, respectively, after normal blood pictures. This indicates cessntion of benzene esposure. that h a p to the blood caused by 2. The studies made on 56 men at benzene may persist for at least 2 the end of 2 months indicated that years folloning cejsation of exposure. tile toxic efiects of benzene may con- 5. Recovery is Iiianifested primarily tinue to act for a period of at least 2 months following the termination of contact. 3. The stiiclies mncle on 49 mcn a t the ciid of 14 months sho\vcd that whilc a large majority of the affected by incrcnse in erythrocyte numbers, decrense in erythrocyte size and increase in blood plntelets. 6. Thc tot21 Icucocyte count and the diffeiwhal fomiula is an unreliable workers had apparently recovered, n indcs of bcnzene poisoning or of ..>mall numbcr had failed to regain o recovery. noriual hcmotologic status. 7. The usual fo:ms of anti-anemic 4. The studies made on 10s men a t therapy seem to have no efiect in the end of 24 months showed that 4 hastening recoven. BIBLIOGRAPHY 1. ERF, L. .L,AID RHOADSC, . P.: The gravure printing industry in Xew York hematological effecb of benzene (ben- City. Tars J., 21, 395 (1939). zol) Poisoniw. Tars J., JI,o1(1939). 4. GOLDWATERL, . J.: Disturbances in the 2. Toxicity of indwtrid organic solventa. blood following esposure to benzol. Medical Rerearch Council, Industrial J. Lab. Clin. Med., 28, 957 (1941). LDResearch H-M* tionery O5ce, London, 1937. 3. CREENBVBO, L,b & m , 1%.R.,CO 5. S&LLORTT,. B., GALL. E. A., AXD - BRICSLEY,W.J.: Chronic exposure to WATEIL, L J., AXD SYITH, A. R.: Ben- benzene (benzol). III. The patho- zene (benzol) poisoning in the mto- logir results. THISJ., 21, 355 (1939).