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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 50 (1990) (p. 307)

CAS No.: 103-90-2
Chem. Abstr. Name: Acetamide, N-(4-hydroxyphenyl)-

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Paracetamol has been used extensively as an analgesic and antipyretic since 1946.

5.2 Experimental carcinogenicity data

Paracetamol was tested for carcinogenicity by oral administration in mice and rats. In one strain of mice, a significant increase in the incidence of multiple liver carcinomas and adenomas was observed in animals of each sex at a markedly toxic dose; in two studies on another strain, no increase in the incidence of any tumour was observed at a well-tolerated dose that was approximately half that in the preceding study. Administration of paracetamol to two different strains of rats did not increase tumour incidence. In a further strain of rats, the incidence of neoplastic liver nodules was increased in animals of each sex given the higher dose; the combined incidence of bladder papillomas and carcinomas (mostly papillomas) was significantly greater in high-dose male and in low-dose female rats. Although treatment increased the incidence of bladder calculi in treated rats, there was no relationship between the presence of calculi and of either hyperplasia or tumours in the bladder.

Oral administration of paracetamol to rats enhanced the incidence of renal adenomas induced by N-nitrosoethyl-N-hydroxyethylamine.

5.3 Human carcinogenicity data

A positive association between use of paracetamol and cancer of the ureter (but not of other sites in the urinary tract) was observed in an Australian case-control study. None of three other population-based case-control studies showed an association between paracetamol use and cancer in the urinary tract.

5.4 Other relevant data

One study provided no evidence that use of paracetamol in the first trimester of pregnancy is associated with an increase in the incidence of malformations. Paracetamol induced testicular atrophy in rats.

Hepatotoxicity has been reported repeatedly in people taking high doses of paracetamol; chronic alcohol users are particularly sensitive. Paracetamol is metabolized in humans and animals to reactive intermediates that bind to proteins. It is hepatotoxic to experimental animals and causes renal tubular necrosis in rats.

Paracetamol induced chromatid breaks in peripheral human lymphocytes in vivo. It induced aneuploidy in rat embryos treated transplacentally. It gave negative results in the micronucleus test in mice in vivo. It did not induce chromosomal aberrations in bone-marrow cells or spermatocytes of mice.

Paracetamol induced sister chromatid exchange and chromosomal aberrations in Chinese hamster cells, micronuclei in rat kidney cells and chromosomal aberrations in human lymphocytes in vitro. It did not induce point mutations in mouse or Chinese hamster cells. Paracetamol gave positive results in a transformation test in mouse cells in vitro. It induced unscheduled DNA synthesis in mouse and rat cells but not in Chinese or Syrian hamster or guinea-pig cells. Paracetamol did not induce sex-linked recessive lethal mutations in Drosophila and was not mutagenic to Salmonella typhimurium or Escherichia coli.

5.5 Evaluation

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

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

Overall evaluation

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

For definition of the italicized terms, see Preamble Evaluation.

Subsequent evaluation: Vol. 73 (1999)


Last updated: 30 September 1999

    See Also:
       Toxicological Abbreviations