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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 50 (1990) (p. 211)

: 67-20-9

Nitrofurantoin monohydrate
: 17140-81-7

Nitrofurantoin sodium salt
: 54-87-5

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Nitrofurantoin has been used since 1972 in the treatment of urinary-tract infections.

5.2 Experimental carcinogenicity data

Nitrofurantoin was tested by oral administration to mice in four studies and to rats in three studies and by transplacental administration to mice in one study. Two of the studies in mice, including the transplacental study, were inadequate for evaluation. In one study in mice, an increase in the incidence of ovarian tubular adenomas and benign mixed tumours was observed. In two studies in other strains of mice, no such increase was observed, although in one study there was an increase in the incidence of malignant lymphomas in males. One study in rats was inadequate for evaluation. A further study in female rats demonstrated an increase in the incidence of mammary fibroadenomas. In the third study in rats, although a few rare tumours were observed, there was no significant increase in the incidence of malignant neoplasms.

5.3 Human carcinogenicity data

In a hypothesis-generating cohort study, use of nitrofurantoin was associated with the occurrence of cancers of the female genital tract and nervous system, but these findings could have been due to chance.

5.4 Other relevant data

Use of nitrofurantoin during pregnancy has not been associated with birth defects. The drug has gonadotoxic effects in male and female rats and mice and teratogenic effects in mice at high doses.

In humans, use of nitrofurantoin has been associated with pulmonary fibrosis, hepatocellular injury, aplastic anaemia and other blood dyscrasias.

Nitrofurantoin gave negative results in the mouse spot test and in the rat micronucleus test. It did not induce chromosomal aberrations in male germ cells or dominant lethal effects in mice. It induced DNA strand breaks in rats and mice and sister chromatid exchange and unscheduled DNA synthesis in bone-marrow cells of mice. Nitrofurantoin induced DNA strand breaks in mouse, rat and human cells in vitro and increased the frequency of sister chromatid exchange in Chinese hamster cells but not in human cells in vitro. Nitrofurantoin induced chromosomal aberrations in Chinese hamster cells but not in human cells in vitro. It did not induce unscheduled DNA synthesis in human fibroblasts or rat hepatocytes in vitro. It induced gene mutations in Chinese hamster cells. Nitrofurantoin gave ambiguous results in Drosophila in the sex-linked recessive lethal test but positive results in the wing spot test. It gave contradictory results in tests for mitotic gene conversion in Saccharomyces cerevisiae. Nitrofurantoin induced differential toxicity in Escherichia coli, Salmonella typhimurium and Bacillus subtilis and mutations in E. coli and S. typhimurium.

5.5 Evaluation

There is inadequate evidence for the carcinogenicity of nitrofurantoin in humans.

There is limited evidence for the carcinogenicity of nitrofurantoin in experimental animals.

For definition of the italicized terms, see Preamble Evaluation.

Overall evaluation

Nitrofurantoin is not classifiable as to its carcinogenicity to humans (Group 3).


Last updated: 11 November 1997

    See Also:
       Toxicological Abbreviations
       Nitrofurantoin (PIM 377)