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


VOL.: 26 (1981) (p. 47)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Azathioprine was tested by intraperitoneal, subcutaneous and/or intramuscular administration in mice and by oral and intraperitoneal administration in rats. Suggestive evidence was obtained for the induction of lymphomas after intraperitoneal, subcutaneous or intramuscular injection in mice and for ear-duct carcinomas in rats after oral administration. Because of limitations in design and reporting, however, the results were considered to be inconclusive.

Studies in which azathioprine was tested in combination with other agents were inadequate for evaluation.

Azathioprine is embryolethal at doses nontoxic to the mother and can induce a variety of severe teratogenic effects in several animal species. It is mutagenic in bacteria and yeast in vitro and in Drosophila melanogaster and mice in vivo. At high concentrations, the drug is clastogenic to human lymphocytes in vitro.

5.2 Human data

Azathioprine has been widely used since the 1970s to prevent rejection following organ transplantation. It is also used to treat a variety of autoimmune diseases.

Use of azathioprine during pregnancy may reduce birth weight significantly. The data were insufficient to evaluate the teratogenic potential of this drug to humans. Azathioprine produces chromosomal abnormalities and increases in sister chromatid exchanges in the peripheral lymphocytes of non-cancer patients. No data were available to evaluate the mutagenic potential of this drug to humans.

There is evidence that azathioprine, often combined with prednisone, is associated with an increased incidence of non-Hodgkin's lymphoma, squamous-cell cancers of the skin, hepato-biliary carcinomas, mesenchymal tumours, and perhaps certain other rare neoplasms. The risk of non-Hodgkin's lymphoma is higher in organ transplant recipients; the presence of the graft may make some contribution to this increased incidence.

5.3 Evaluation

There is limited evidence for the carcinogenicity of azathioprine in mice and rats. There is sufficient evidence that azathioprine is carcinogenic in humans.

For definition of the italicized terms, see Preamble Evaluation.

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 8 April 1998

    See Also:
       Toxicological Abbreviations
       Azathioprine (PIM 053)
       Azathioprine  (IARC Summary & Evaluation, Supplement7, 1987)