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


VOL.: 26 (1981) (p. 267)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Methotrexate was tested by oral administration in mice and hamsters, by intraperitoneal injection in mice and rats, and by intravenous injection in rats. One study in mice by oral administration reported a high incidence of lung carcinomas, but it did not include matched controls. All other studies failed to reveal a carcinogenic effect, but the significance of several was limited because of deficiencies in experimental design or reporting of data.

Methotrexate can induce teratogenic effects in several species and embrolethality at doses nontoxic to the mother. In monkeys, only embryolethality was observed.

Methotrexate is mutagenic in mice in vivo. In various mammalian cells in culture the drug causes chromosomal aberrations and increases in sister chromatid exchanges. Methotrexate also induces morphological transformation in mouse cells.

5.2 Human data

Methotrexate is an antineoplastic agent that has been commonly used since the early 1950s for the treatment of haematological and solid malignancies and as an immunosuppressive agent in bone-marrow transplantation. It is also used in the treatment of psoriasis.

Methotrexate is a human teratogen which causes a variety of malformations. It causes chromosomal aberrations in bone-marrow cells. No data were available to evaluate the mutagenic potential of this drug.

Methotrexate has been associated in case reports with a variety of subsequent neoplasms. One study of a defined group of patients, in which no expected numbers were presented, produced no suggestion of a cancer excess. The only other epidemiological study showed no excess of cancer in patients treated with methotrexate.

5.3 Evaluation

There was no evidence for the carcinogenicity of methotrexate in rats; its carcinogenicity could not be evaluated in mice and hamsters. The available data from studies in humans were inadequate to evaluate its carcinogenicity.

On the basis of the available data, no evaluation could be made of the carcinogenicity of methotrexate to humans.

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 8 April 1998

    See Also:
       Toxicological Abbreviations
       Methotrexate  (IARC Summary & Evaluation, Supplement7, 1987)