Environmental Health Perspectives Vol. 82, pp. 193-197, 1989



# Hematotoxicity and 

# Carcinogenicity of 

# Benzene

by Muzaffer 

# Aksoy*

The hematotoxicity ofbenzene exposure has beenwell known fora century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical andhematologic picture ofaplastic anemiaresulting from benzene exposure is not different from classical aplastic anemia; in some cases, mildbilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases ofaplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome

was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic studyproving the leukemogenicity ofbenzene was performedbetween 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemiawas 13.59 per 100,000, which is a significant inorease over that of leukemia in the general population. Following the prohibition anddiscontinuation ofthe use ofbenzene in Istanbul, there was a strikingdecrease in the number of leukemic shoe workers in Istanbul. In 23.7% ofour series, consisting of 59 leukemic patients withbenzene exposure, there was aprecedingpancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of our series showed the findings of acute leukemia. The possible factors that
maydetermine the types of leukemia inbenzene toxicity are discussed. Thepossible role ofbenzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.



## Introduction

The hematotoxicity of chronic benzene poisoning has beenwell known fornearly a century. The effects ofbenzene include leukocytopenia, thrombocytopenia, anemia, transitory leukocytosis, lymphopenia, rarely lymphocytosis, very rarelypseudo-Pelger Huet anomaly changes in the leukocyte osmotic resistance, decreasedphagocytic function ofgranulocytes, reduced glucogen content and inhibited activity ofperoxidase ofneutrophils, an increase in the acid phosphatase and 

### P-glucoronidase activity of the neutrophils, and a decrease of alkaline phosphatase, myeloperoxidase and lipid content of the neutrophils (1). In addition, in chronic benzene toxicity a decrease of the Ea and E18 rosetts (T cells) was noted (1). Furthermore,

an increase of leukoagglutinins was demonstrated in the

sera of some workers exposed chronically to benzene. (1). An increase of eosinophils, basophils, and monocytes in chronic benzene toxicity is amatter ofdiscussion (1). This problem, particularly concerning monocytes, deserves further investigation with modern techniques. In chronic benzene toxicity, some other qualitative abnormalities, such as the presence ofgiantplatelets, has been found (1).

*The Scientific and Technical Research Council ofTurkey, Research Institute for Basic Sciences, Department of Biology, Gebze, Kocaeli,

Tur key. 

### According to 

### Craveri, the

### hemorrhagic effects ofchronic benzene 

### toxicity are not 

### solelydue to 

### thrombocytopenia but are 

### also 

### due to 

### increased 

### fibrinolytic activity (2).



## Aplastic Anemia or 

## Pancytopenia 

## Resulting from 

## Chronic Benzene 

## Exposure

The 

### clinical andhematologic picture ofbenzene-induced 

### aplastic anemiawhich 

### is characterizedby

### pancytopenia, is not 

### different from that 

### ofclassical aplastic anemia idio

### pathic or 

### because of 

### different chemicals or 

### other agents 

### (1). In some cases 

### of benzene-induced aplastic anemia, 

### there are 

### characteristics that are 

### absent when this 

### hematologic disorder is caused 

### by other agents, 

### such as 

### mild bilirubinemia, changes in osmotic fragility, short

### ened 

### erythrocyte survival time, increased serum lactic 

### dehydrogenase activity, increased 

### fecal urobilinogen, and 

### mild reticulocytosis (1). These findings are the result of

a

### hemolytic component in 

### aplastic anemia due to 

### chronic benzene exposure. 

### Additionally, in some cases 

### of 

### benzene-mediated aplastic anemia, absolute 

### and relative 

### lymphocytosis are absent (1). In otherwords, in addition
to 

### aplastic anemia 

### resulting from other causes, 

### absolute 

### lymphopenia ispresent in 

### this hematologic disorder due to 

### chronic benzene exposure.M. AKSOY



### On the 

### other

### hand, although there are no symptoms 

### and 

### findings relating to the nervous system in aplastic ane

### mia, idiopathic or because of different agents, in some
cases of

### aplastic anemia resulting from chronic exposure to 

### benzene, there are some 

### findings relating to the nervous system 

### (3). 

### Although as early as 1967 Truhaut has 

### indicated in

### his reports on

### benzene thepossibility oflongterm

### effects ofthis chemical agent on the nervous 

### system such as 

### polyneuritis of the lower extremities, there are very 

### few reports on this subject (3,4). Baslo and Aksoy 

### performedneurological, electromyographical, andmotor 

### conduction velocity examinations in six patients with 

### aplastic anemia and two 

### patients with 

### preleukemia caused by chronic exposure to benzene (3). In addition, sensory conductionvelocities weremeasured in threepa

### tients. 

### Neurological abnormalities such as 

### global atrophy 

### and 

### decreased sensory 

### vibration of lower extremities (in

one 

### case), 

### distal latency lengthening of

### median nerve (in

one case), 

### decrease in the sensory 

### conduction velocities of the 

### lower extremities 

### (in one 

### case) were 

### found 

### (3). There was a certain 

### relationship between 

### the presence 

### of 

### neurological abnormalities 

### and the 

### period of the exposure. The 

### findings of bone marrow 

### examination in 

### chronic benzene 

### toxicity are 

### extremely variable. The 

### picture i-anges 

### from complete 

### aplasia to

### highlyhyperplastic bone

marrow. In some

### patients, thebone marrow 

### is 

### fullyacel

### lular in 

### the 

### terminal stage 

### (1). 

### According to 

### Mallory et 

### al. the effects ofbenzene on the

### bone marrow

### will vary

### with the 

### individual and are 

### independent of the 

### length of exposure 

### (5). More than one type 

### offoci canbe 

### encountered in 

### the bone marrow. 

### Using 

### 3H-methylthymidine autoradi

### ography, Moeschlin and 

### Speck studied the

### bone marrow 

### ofanimals

### poisoned

### bybenzene 

### and

### foundthat the results 

### varied from animal to 

### animal: 4 very 

### hypoplastic, 6 

### hypoplastic, 5 

### normocellular, and 4 

### hypercellular 

### (6). No 

### correlation was 

### found between 

### cellularity of the bone

marrow 

### and duration of exposure to 

### benzene. A

### follow-up 

### studywas

### performed in 44

### pancytopenic pa

### tients with 

### chronic benzene 

### toxicity (7). 

### Only 21 

### patients had 

### hypocellular bone marrow. It was 

### normocellular in 13 

### patients and

### hypercellular in 8. 

### Contrary to 

### the 

### flndings of

### peripheral 

### blood, therewas a

### relationshipbetween the types 

### of 

### cellularity of the bone marrow 

### and the outcome, 

### including the 

### development of leukemia. 

### Out of 21 

### patients with

### hypocellularbonemarrow, 11 

### died 

### (52.4%), and in 5

### patients (23.8%) leukemia 

### developed later. 

### Contrary to 

### this, only 1 out 

### of 13 

### (7.7%) 

### pancytopenicpatients withnormocellularbone marrow

### died. 

### On the other

### hand, 4 out 

### of8

### patientswith

### hypercellularbone marrowrecov

### ered 

### completely 

### (50%). Two 

### died from the 

### complications of

### aplastic anemia. In 1 

### of the 

### remaining 2, leukemia de

### veloped and in the 

### second 8 years 

### after 

### complete recovery, 

### the occurrence 

### of

### myeloid

### metaplasia was 

### the cause 

### of death. 

### Ultrastructural studies in 4

### patients with

### aplastic ane

### mia 

### and

### leukocytopenia were

### performedby

### Erbengi and 

### Aksoy (8). 

### Electronmicroscopic 

### findings were 

### in accor

### dance 

### with the 

### changes in the 

### bone marrow 

### observed

### by light 

### microscopy. 

### Additionally, there was an 

### increase in 

### plasma cells with maturation arrest in the 

### later 

### phases ofthe erythroid series. 

### Ultrastructural studies 

### shed some 

### light on 

### phagocytic activity of 

### the reticulum cells. 

### This 

### study showed a 

### hyperactivation in the bone marrow of

one case 

### anda

### depression in the 

### erythroid elements inthe 

### secondpatient. These different findings maygive the impression that the effect ofbenzene on the bone marrow may 

### change from 

### patient to 

### patient.


## Benzene-Hepatitis-Aplastic Anemia 

## Syndrome

The 

### occurrence of aplastic 

### anemia in 

### chronic benzene 

### toxicity may be accelerated 

### by the occurrence of viral 

### hepatitis. 

### Recently we have 

### observed a severe case of aplastic anemia 

### associated with chronic 

### benzene toxicity 10 

### months after the 

### appearance of 

### hepatitis B. The 

### propositus was a 32-year-old 

### technician working in a 

### petroleum plant (1). A 

### sample of the product disclosed 2.2% benzene. Twoyears ago he had

### hepatitis B foraduration of 1 month. At 

### that time he was not anemic and there was no 

### leukocytopenia or 

### hemorrhagic diathesis. 

### Approximately 10 months later the 

### signs of

### aplastic anemia 

### appeared. He 

### had severe 

### pancytopenia. The bone

marrow was very 

### hypocellular, and the 

### findings were consistent with the 

### diagnosis of severe 

### aplastic anemia. The tests 

### for 

### hepatitis B-virus antigens determined by ELISA showed that 

### anti-HBs, 

### anti-HBe, and anti-HBc

were 

### positive. The clinical 

### and

### hematologicpicture ofthe 

### patient was similar to those of

### chloramphenicol-hepatitisaplastic anemia 

### syndrome first 

### described

### by Hodgkinson 

### (9). 

### Following the failure of

### oxymetholon 

### therapy, a trial 

### with 

### anti-lymphocytic serum, 

### the 

### patient's clinical and 

### hematological picture 

### improved considerably. He is in 

### remission at 

### the present. We call this 

### syndrome 

### "benzene-hepatitis-aplastic anemia 

### syndrome"(1).



### Benzene and 

## Malignancies

Benzene is a 

### suspected 

### leukemogenic and carcinogenic agent 

### since the 

### first 

### description ofa case 

### of

### leukemiaby Le Noire 

### and 

### Claude in 1897 

### (10). 

### Recently, Maltoni 

### and Scarnato showed in rats andmice that oral 

### intake of

### high doses of

### benzene causes 

### malignancies in 

### several tissues 

### (11). 

### Anyagent 

### toxic to

### pluropotent stem

### cells can cause
an 

### alteration in two 

### important capabilities of the 

### colony 

### formingcells 

### (12): self-renewal anddifferentiation toproduce a 

### variety of 

### lineage restricted 

### progenitor cells, in 

### other

### words, the 

### long-termmaintenance of 

### self-renewal and 

### differentiation. 

### Anyblock or 

### disturbance in 

### these ca

### pabilities will cause 

### either

### aplastic anemia 

### (ablock in 

### selfrenewal) or 

### leukemia (a block in 

### differentiation). There

### fore, benzene as a 

### toxic agent 

### for stem 

### cells, may cause 

### aplastic anemia or leukemia. 

### Although there were numerous case reports 

### showing the

### possible role ofbenzene in the 

### development ofleuke

### mia, the 

### first 

### epidemiologic study on 

### this 

### problem ap

### peared in 1974 

### (13). From 1967 to 

### September 1973, 26pa

### tients with leukemia or

### pre-leukemia were seen among 194HEMATOTOXICITYAND CARCINOGENICITY OF BENZENE

Table 1. Annual number of leukemic shoe workers in Istanbul

between 1967 and 1978.

Year No. of leukemic shoe workers
1967 1 1968 1 1969 3 1970 4 1971 6 1972 5 1973 7 1974 4 1975 3 1976 0 1977 0 1978 0



### 28,500 

### shoe-slipper and handbag

### workers chronically ex

### posed to 

### benzene in Istanbul. At that time, the concen

### tration of

### benzene was 

### found to reach amaximum of 210 to 650ppm

### duringworkinghours in

### workplaces. The content 

### ofbenzene in 

### adhesives and 

### thinners was between 9% 

### and 88% 

### (7,14). Of these leukemic workers, 17 were 

### investigated at the 

### Second Internal 

### Clinic of Istanbul 

### Medical School. The 

### remaining 9 

### leukemic workers were 

### studied in

### other

### hospitals in 

### Istanbul. As explained in this 

### study, anotherworkerwith acute 

### lymphoblastic leukemia resulting frombenzene exposure was not included in this 

### series because his profession was 

### different. In 1974, the 

### number of the 

### leukemic shoe workers in Istanbul in

### creased to 31 

### (15). Thus the 

### incidence of leukemia among 

### them was 13.59 per 100,000, 

### which is a 

### markedly and 

### statistically significant increase over 

### that of

### leukemia in 

### general 

### population, 6 per 100,000. In

### Turkey, accordingto the official YearBookofHealth 

### Statistics, the 

### incidence ofleukemia isbetween 2.25 

### and 2.80 per 

### 100,000 

### (16). As can 

### be seen 

### from Table 1, the 

### peak incidence among 

### shoe

### workers in 

### Istanbul occurred between 1971 

### and 1973 

### (17). Itwas 21.7 per 100,000. The number of leukemic shoe workers in Istanbul started to 

### decrease after the 

### prohibition and 

### discontinuation of the

use 

### of benzene since 1969 

### (17). The number 

### of new 

### leu

### kemic shoe

### workers has 

### decreased in 1974 to 1975 to the 

### level of 1969 to 

### 1970, 

### and none were recorded in 

### subsequent 3 years. 

### But between 1979 

### and 1987, we 

### observed 22 new cases 

### of leukemia 

### associated with 

### chronic exposure to

### benzene. 

### Only 3 ofthemwere 

### shoe

### workers liv

### ing in Istanbul. The 

### decline in the annual occurrence 

### of leukemia in 

### the series of shoe 

### workers in 

### Istanbul may be attributed to the prohibition and gradual discontinuation ofbenzene in

### this city starting in 1969. On the other hand, the reappearance of leukemia after 1979 in Istanbul and other Turkish cities maybe attributed either to the variation in 

### the interval between the occurrence of leukemia and exposure or the continued use ofmaterials containing benzene (17). The evidence for the use of benzene in Istanbul and other cities of Turkey following the prohibition of this chemical is shown in the following study (18). To illustrate the etiologic role of drugs and chemicals in the development ofaplastic anemia, we analyzed 108 cases of aplastic anemia among 3175 hematologic patients during a 10-year period (1973-1982) in the hematology section of the Istanbul Medical School (18). In 25 (23.1%) of the

cases, benzene was responsible for the development of aplastic anemia. On the other hand, a recent study performed in the period between 1983 and 1985 in Istanbul and Izmit showed that despite the considerable decrease in the content ofbenzene in most of the materials, they

were still abovepermissible limits (19). During the study mentioned above we have encountered 2 cases of acute leukemia in a modern tire cord fabric in Izmit (19). Approximately 550 workers were employed. The working conditions were good and properly ventilated. The concentration of benzene in one part of the plant was 110

ppm, and in one solvent used in the auxillary repair shop the benzene content was nearly 5%. The incidence of leukemia was 60.6 per 100,000 in a period of 6 years. 

### Development of 

### Leukemia in 

### Pancytopenic Patients with Chronic Benzene 

### Toxicity

In our series comprising 59 leukemicpatients withbenzene exposure, aprecedingpancytopenicperiod was present in 14 leukemic patients (23.7%) (20). The interval between the onset oftheprecedingpancytopenicperiod and that of leukemia varied between 6 months and 6 years. Furthermore, in a follow-up study in 44 pancytopenic patients with chronic benzene toxicity, leukemia developed in 6 (13.6%) and myeloid metaplasia in 1 (2.8%) (7).



### Familial Connection and Individual 

### Susceptibility

As canbe seen from Table 2, in 6 leukemic patients associated with chronic benzene exposure, in our series, a

Table 2. Genetic relationship between eight leukemic patients with chronic exposure to benzene or colchicine and saccharin.

Case no. Age Duration of exposure, years Occupation Type of leukemia Genetic relationship
1 43 6 Shoe worker AML Paternal uncle of case 2 2 24 4 Shoe worker AML Nephew of case 1 3 36 7 Shoe worker AML Maternal cousin of case 4 4 48 3 Painter AML Maternal cousin of case 3 5 36 15 Shoe worker Erythroblastic leukemia Son of case 6 6a 65 35 Shoe worker Unidentified type of leukemia Father of case 5 7 43 2 Owner of a Chronic lymphoid leukemia Son of case 8 wallpaper and printing shop 8b 77 10-20 tablets daily Stationer Chronic lymphoid leukemia Father of case 7 "This case was not included in our series of leukemia because he was not studied before his death. bUsed colchicine and saccharin. 195M. AKSOY



### familial connection was established 

### (1,15,21).* Two were
an 

### uncle and his 

### nephew, and 2 were cousins (15). The 

### father of the fifth leukemic 

### patient, a 65-year-old shoe 

### worker 

### with a 

### long

### history ofbenzene exposure, died in

a 

### hospital with the 

### diagnosis of myelosclerosis, but re

### evaluation ofthe case report showed that thispatient had acute 

### leukemia ofanunidentified type (15). The father of 

### the seventhpatient 

### with chronic 

### benzene exposure also 

### had the same 

### hematologic malignancyassociatedwith the

use 

### ofcolchicine and/or saccharin (21). These 6 leukemic 

### patients among the 

### first- and second-degree relatives con

### stituted 10.2% of 

### the leukemic patients with chronic exposure to

### benzene.* In these 6 

### patients including case 7, 

### the 

### development of leukemia possibly resulted from 

### simultaneous presence 

### ofgenetic determinants, in addi

### tion to 

### benzene as an extraneous or 

### environmental factor. 

### This suggestion 

### is in accordance with the view that 

### leukemiamaybe 

### causedbythe 

### combination ofvarious in

### trinsic and 

### extrinsic factors (22). On the otherhand, family susceptibility in the development ofvarious disorders 

### of

### chronic benzene toxicity suggested bynumerous inves

### tigators were 

### evident in our 

### studies concerningbenzene 

### toxicity (1,17).



## Types of Leukemia 

### in Chronic Benzene 

## Toxicity

It is 

### evident from the 

### literature that there is a 

### significant 

### difference in 

### the 

### distribution of 

### leukemia types 

### caused 

### by benzene exposure 

### (1,15,20,23). In one group, acute types 

### of

### leukemia, mostlymyeloblastic or 

### erythro

### blastic, 

### predominate, and in the other chronic 

### leukemia, 

### myeloid and 

### lymphoid take themost 

### important 

### place. Al

### though in our 

### series, acute 

### leukemiawas 

### 89.8%, thepercentage 

### ofchronic types 

### comprisingmyeloid, lymphoid, and

### hairy cell 

### leukemia was 

### 10.2% 

### (20). 

### Considering these facts we have 

### tried to 

### explain the 

### possible 

### factors that may 

### determine the types 

### of

### leukemia in chronic

### benzene 

### toxicity (23). 

### One factormay

### be 

### the

### differences in

### the content 

### ofbenzene 

### in 

### the material used. 

### The benzene content 

### of the 

### adhesives and

### thinnersused

### byworkers

### withacute 

### leukemia in our 

### series was very

### high 

### (13,15,17,23). In contrast, 

### itwas very 

### low (2.8%) ina

### workerwith chronic 

### lymphoid leukemia 

### (23). 

### Second, the 

### adhesives and thinners that

were 

### used

### by

### nearlyall the

### workerswith acute 

### leukemia contained 

### onlybenzene 

### (13,15,23). 

### Contrary to 

### this, the 

### solvent 

### used 

### by a 

### worker with chronic 

### lymphoid leukemia 

### had a 

### low 

### level of

### benzene and a

### highpercentage 

### of 

### toluene 

### (23). Third, the great

### majority ofthe 

### individuals with acute 

### leukemia in the 

### series was 

### exposed to 

### high concentration of benzene 

### ranging between 150 

### and 210 ppm

### duringall

### workinghours 

### (13,15,23). Contrary to 

### this, 5 out 

### of 6

### patients with chronic 

### leukemia, 2 

### with chronic myeloid, 2 

### with 

### chronic 

### lymphoid, and one

### with

### hairycell

*Cases 6 and 8 were not included in this series because one (case 6)

was studied in anotherhospital and the second (case 8) was not exposed to benzene (15,21). 

### leukemiawere exposed tobenzene 

### intermittentlyand

### for

a 

### short time 

### during the dailywork. Fourth, 

### the possible role 

### ofgenetic 

### factors may 

### help to 

### explain the 

### development 

### of

### different types of 

### leukemia. As can

### be seen from 

### Table 2, 6

### patients in 3 

### families

### had acute types 

### ofleukemia. In the 

### fourth family, 

### despite different extraneous 

### factors such as chronic benzene exposure 

### and the use 

### of colchicine and/or 

### saccharin, the same type 

### of leukemia, 

### namely chronic 

### lymphoid, 

### developed at 

### different ages 

### (21).



### Benzene, 

## Malignant 

## Lymphoma, Multiple Myeloma, and 

## Lung Cancer
There are a 

### few 

### investigations that suggest a

### possible role 

### of

### benzene in 

### the etiology of

### malignant lymphoma, 

### multiplemyeloma, and 

### lung cancer. 

### In 

### 1961, Wirtschafter and 

### Bichell showed that 

### tissue responses 

### could be observed in 

### lymph

### nodes, 

### spleen, 

### thymus, andbonemarrow 

### of the rat 

### after a 

### single 

### injection of 

### benzene 

### (24). Re

### cently, Irons et 

### al. 

### showed that the effects ofbenzene ad

### ministration in mice on 

### lymphocyte function are at 

### the 

### doses of

### the 

### compound that

### produce little orno measura

### ble 

### differences in the 

### number of

### circulating cells 

### (25). In 

### 1974, we 

### described 6 cases 

### of 

### Hodgkin's disease with 

### chronic exposure to 

### benzene 

### (26). Despite the lack of 

### statistical data, we 

### suggested 

### that chronic exposure to benzene 

### might 

### play a 

### role in 

### the 

### development of 

### Hodgkin's disease. In the last 

### fewyears we 

### have 

### studied 7 more cases 

### of 

### different types 

### of

### malignant lymphomawithbenzene exposure 

### (1,17,19). In 

### 1979, Vianna 

### and Polan

### performed a 

### comparative 

### study on 

### the 

### mortality rates 

### of different types 

### of

### malignant 

### lymphoma among

### workers 

### exposed to 

### benzene 

### (2?). According to 

### the 

### investigators, theirresults

are 

### consistent 

### with the

### possibilitythat chronic exposure to 

### benzene 

### might be 

### important in the 

### etiology of

### malignant 

### lymphoma. A recent 

### study of

### Norseth et 

### al. 

### is also in 

### favor ofthis 

### assumption (28). 

### Furthermore, there are 

### several studies 

### showinga

### high

### mortalityrate 

### fromdifferent types 

### of 

### malignant 

### lymphoma among 

### pathologists, chemists, andpersons 

### handling chemicals 

### containingbenzene 

### (29).



## Multiple 

## Myeloma

As 

### early as 

### 1970, 

### Torres et 

### al. 

### reported 2 cases 

### ofmul

### tiple myeloma with chronic 

### benzene exposure 

### (30). In 1980 and 1984, we 

### described 4 cases 

### ofmultiple

### myeloma with 

### chronicbenzene exposure 

### (31,32). Only one 

### ofthese 

### patients had a 

### short 

### period of 

### pancytopenia with 

### hypoplastic bone marrow. 

### The mean exposure 

### time to 

### benzene was 

### longer than that of cases 

### of leukemia and 

### malignant lymphoma: 18 years 

### in the 

### former and 10.5 

### in the latter 

### (1). In an 

### epidemiologic assessment 

### study of 

### Rinsky et 

### al. in 

### 1987, there was a 

### statistically significant increase 

### in deaths from 

### leukemia and

### multiple 

### myeloma 

### (33). 196HEMATOTOXICITYAND CARCINOGENICITY OF BENZENE 197



### Lung Cancer

In 1976, we considered 5 individuals with lung cancer 

### associated with chronic benzene exposure and suggested 

### that there is a causal relationship between this chemical 

### and 

### lung cancer 

### (34). In our 

### series ofmalignancies result

### ing from chronic exposure to benzene, there are 7 cases 

### of lung cancer (1,17). Only 3 showed mild hematologic findings of chronic benzene toxicity. Because benzene 

### available in

### Turkeydidnot contain

### benzo[alpyrene determined by ultraviolet spectrophotometry, lung cancer in 

### these 7 

### patients cannot 

### be attributed to this carcinogenic agent (1,7). Benzene ismainlyabsorbedviathe lungs, and 

### about 40% 

### of

### the absorbedportion is exhaledunchanged 

### (35). After 24 hr, a small percentage ofbenzene can still be 

### detected in the expired air (35). Therefore, a carcino

### genic effect of benzene in the lung is possible. Because

our 

### patients were 

### also smokers, a contributory role of 

### smoking in the 

### development of lung cancer is possible.

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