. Brit. J. industr. Med., 28, 296-302. Haematological effects of chronic benzene poisoning in 217 workers. A haematological study consisting of the determination of RBC, WBC, PCV, platelets, and differential counts was carried out, together with bone marrow puncture and haemoglobin analyses in appropriate cases, on a control population of 100 normal people and on 217 male labourers, 95% of whom worked with solvents containing benzene in small shops manufacturing shoes under unhygienic conditions. The concentration of benzene in the workplaces ranged between 30 and 210 p.p.m., and the period of exposure between 3 months and 17 years.In 51 of the 217 workers (23 50%) haematological abnormalities attributable to chronic benzene poisoning were detected. Thus, leucopenia was present in 9 70 %, thrombocytopenia in 1-84%, leucopenia associated with thrombocytopenia in 4-6%, pancytopenia in 2-76%, acquired pseudo-Pelger-Huet anomaly in 0-46%, lymphocytosis in 0-46 %, giant platelets in 0-46%, eosinophilia in 2-30%, basophilia in 0-46%, and eosinophilia associated with basophilia in 0*46% (the maximum normal levels for eosinophils and basophils were 8% and 2 % respectively).Acquired pseudo-Pelger-Huet anomaly was detected in a worker with heterozygous betathalassaemia (HbA2 4-1 % and HbF 8-7%) in whom the only effect of benzene was on the leucocyte nuclei, all other haematological values being within normal limits. On the other hand, in 33-1 % of the workers the haemoglobin was less than 12 g/100 ml and in 32-7% the PCV was less than 40 % with the MCV ranging between 86 and 96 ,um3. In none of them did MCV exceed 100 ,um3. Thirty-on-per cent. of these anaemic workers were treated with adequate doses of oral iron, which resulted, in all cases, in a complete disappearance of the anaemia. Therefore, it is difficult to attribute this anaemia to the effect of benzene alone.Thus it is concluded that benzene exerts its harmful effect, primarily on the leucocytes, with eosinophilia and basophilia as inconstant findings, secondarily on the platelets causing thrombocytopenia, and finally on all three series giving rise to pancytopenia.

There is no doubt about the leukemogenic effect of benzene in man. The evidence is as follows: (1) The incidence of leukemia in shoeworkers exposed to benzene in a period of 8 years in Istanbul was 13.6/100,000, which is significantly higher than that for leukemia in the general population. (2) Following the phase-out of benzene in Istanbul, the number of leukemic workers decreased and none were reported in the subsequent 3 years. (3) The development of leukemia in pancytopenic patients with benzene exposure was observed in 13 out of 51 patients. (4) The differences in the distribution of the types of leukemia in individuals exposed and in nonexposed groups were as follows: acute leukemia 96.1% in the former group, and 46% in the latter group. The high percentages of acute erythroleukemia and preleukemia were other interesting findings in the exposed group. (5) Two cases of leukemia were observed in a 6-year period at a tire cord manufacturing plant with 550 workers. At one location in the plant the concentration of benzene measured by gas chromatography was nearly 110 ppm. Additionally, we have studied 12 cases of malignant lymphoma, four cases of multiple myeloma, and six cases of lung cancer, all of whom were chronically exposed to benzene. The possible role of benzene in the etiology of these malignancies is discussed.

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The distribution of various types of leukemia due to chronic exposure to benzene is described in a series comprising 34 cases. The incidence of leukemia among 31 shoe-workers was 13.5/100,000. Acute myeloblastic leukemia was the most frequent type, followed by preleukemia, acute erythroleukemia and acute lymphoblastic leukemia. The extreme rarity of chronic myeloid leukemia was a noteworthy finding. The differences and similarities between the distribution of various types of leukemia in different series of patients with chronic exposure to benzene and ionizing radiation are discussed.

The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic 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 study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of our series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic 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 may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.

From 1967 to September 1973, 26 patients with acute leukemia or preleukemia were seen in Istanbul among 28,500 shoeworkers exposed chronically to benzene. The incidence of leukemia among these workers was 13/100,000, which is a marked and statistically significant increase over that for leukemia in the general population and provides cogent evidence for the clinical impression of a leukemogenic effect of benzene in man.

Today there seems to be sufficient data to incriminate benzene as a potent carcinogenic agent causing leukemia, malignant lymphoma, multiple myeloma and lung cancer, as well as numerous disorders of the bone marrow depression. Other factors (such as genetic and individual susceptibility) may have a role in the development of these different types of malignancies and hematologic disorders. In this paper, data concerning all these problems are presented and discussed.