International Agency for Research on Cancer (IARC) - Summaries & Evaluations


VOL.: 29 (1982) (p. 93)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Benzene has been tested in rats by intragastric administration and inhalation exposure, and in mice by skin application, inhalation exposure and subcutaneous injection. Oral administration to rats resulted in an increase in the incidence of Zymbal-gland carcinomas. Anaemia, lymphocytopenia and bone-marrow hyperplasia and an increased incidence of lymphoid tumours occurred in male mice exposed by inhalation to benzene; in similar inhalation studies with another strain of mice and with rats there was no evidence of a leukaemic response. Experiments involving skin application or subcutaneous injection of benzene did not produce evidence of carcinogenicity, but most of these experiments were inadequate.

Benzene does not induce specific gene mutations in bacterial systems or in Drosophila melanogaster. A single report showed no evidence for the induction of point mutation in mammalian cells; however, benzene induced cytogenic abnormalities (chromosomal aberrations and sister chromatid exchanges) in mammalian cells in vitro.

The micronucleus test in mice and rats has been consistently positive. Numerous studies have shown that benzene exposure of experimental animals in vivo leads to the induction of chromosomal aberrations in the bone-marrow cells.

Exposure to benzene may damage the testis. Evidence from most studies in mice, rats, guinea-pigs and rabbits suggests that benzene is not teratogenic at doses that are fetotoxic and embryolethal.

5.2 Human data

Workers and the general public are exposed to benzene as a result of a variety of activities in which it is processed, generated or used. Major contributors to benzene emissions into air include: (1) gasoline production, storage, transport, vending and combustion; (2) production of other chemicals from benzene; and (3) indirect production of benzene (e.g., in coke ovens). The last is the major source of benzene emissions into water.

Chronic human exposure to benzene results in leucopenia, thrombocytopenia, anaemia or combinations of these. At early stages of such blood dyscrasias, these effects appear to be reversible. Exposure to high doses for longer periods of time may lead to pancytopenia, which results from aplasia of the bone marrow and is considered to be an irreversible stage of the disease.

Benzene crosses the human placenta. There is a clear correlation between exposure to benzene and the appearance of chromosomal aberrations in the bone marrow and peripheral lymphocytes of individuals exposed to high levels of benzene (> 100 ppm). Such levels of exposure usually lead to clinical symptoms of benzene-induced blood dyscrasias. These aberrations may persist for many years after exposure and after manifestations of haematotoxicity. The results are not so clear with lower levels (< 100 ppm). Although aberrations have been reported following chronic exposures to as little as 10 ppm, this has not been a consistent finding. Environmental factors and exposure to other agents may have interacted with benzene in these studies of low exposure.

Many case reports and case series have described the association of leukaemia with exposure to benzene, either alone or in combination with other chemicals. Most cases were acute myelogenous leukaemia, although some were monocytic, erythroblastic or lymphocytic; and some lymphomas have been noted.

Two follow-up studies showed high incidences of leukaemia among individuals ascertained as cases of benzene haemopathy.

A series of epidemiological studies, both cohort and case-control, showed statistically significant associations between leukaemia (predominantly myelogenous) and occupational exposure to benzene and benzene-containing solvents. These results were replicated in a number of countries and different industries. In the epidemiological studies of people exposed primarily to benzene, statistically significant excesses of leukaemia were observed.

5.3 Evaluation

There is limited evidence that benzene is carcinogenic in experimental animals.

It is established that human exposure to commercial benzene or benzene-containing mixtures can cause damage to the haematopoietic system, including pancytopenia. The relationship between benzene exposure and the development of acute myelogenous leukaemia has been established in epidemiological studies.

Reports linking exposure to benzene with other malignancies were considered to be inadequate for evaluation.

There is sufficient evidence that benzene is carcinogenic to man.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 7 (1974)

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 9 April 1998

    See Also:
       Toxicological Abbreviations
       Benzene (EHC 150, 1993)
       Benzene (ICSC)
       BENZENE (JECFA Evaluation)
       Benzene (PIM 063)