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


VOL.: 24 (1980) (p. 135)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Phenacetin alone was tested in three studies in rats by oral administration and in combination with aspirin and caffeine in one study in mice and in one in rats by oral administration. In one study in rats, phenacetin alone induced benign and malignant tumours of the urinary tract and of the nasal cavity in males. When given in combination with aspirin and caffeine to rats or mice, no significant association was found between the administration of the mixture and the incidence of tumours. Phenacetin alone enhanced the urinary bladder carcinogenesis of N-nitrosobutyl-N-(4-hydroxybutyl)amine in rats.

Phenacetin is mutagenic to Salmonella typhimurium in the presence of a hamster liver microsome preparation, and it produces chromosome aberrations in Chinese hamster fibroblasts in vitro. No mutagenic effects were detected in Drosophila melanogaster or in mice in vivo, or in bacterial test systems when rat or mouse liver microsome preparations were used.

No teratogenic effects were found in rats, although embryotoxicity was observed.

N-Hydroxyphenacetin, a minor metabolite of phenacetin in humans, was tested by oral administration in male rats: it induced hepatocellular carcinomas.

N-Hydroxyphenacetin is mutagenic to Salmonella typhimurium in the presence of a rat liver microsome preparation.

5.2 Human data

Phenacetin is used extensively as a mild analgesic. Its use in certain countries has been restricted.

There are many case reports of renal pelvic cancer associated with abuse of analgesic mixtures containing phenacetin. In addition, an increased incidence of renal pelvic cancer has been reported in a population with a high prevalence of analgesic abuse; analgesic abuse has been reported to be more common in patients with renal pelvic cancer than in those with other urinary-tract neoplasms; and in one small follow-up study, renal pelvic cancer developed nine times more frequently in patients with analgesic nephropathy than in those with other chronic renal disease. One small case-control study showed no evidence of the association, although the prevalence of prior analgesic abuse was very low. Cases of other urinary-tract tumours have also been reported in association with analgesic abuse, but analytical studies have been inconclusive.

Two studies of pregnant women exposed to phenacetin alone or in combination with other drugs failed to find evidence of an increased rate of malformations in the offspring.

5.3 Evaluation

There is limited evidence that phenacetin and N-hydroxyphenacetin, a metabolite, are carcinogenic in experimental animals.

There is limited evidence that abuse of analgesic mixtures containing phenacetin causes cancer of the renal pelvis in humans. It is not possible to specify what component(s) of the analgesic mixtures may be responsible for this effect. There is insufficient evidence to link analgesic abuse with other tumours of the human urinary tract.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 13 (1977)

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 7 April 1998

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       Toxicological Abbreviations