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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 51 (1991) (p. 391)

CAS No.: 58-55-9
Chem. Abstr. Name: 3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Theophylline is found in black tea and to a lesser extent in green coffee, cocoa cotyledon and dried mate. Theophylline is synthesized on an industrial scale and is used principally in pharmaceutical preparations.

Per-caput daily intake of theophylline from black tea in the USA has been estimated to be 0.14 mg.

5.2 Experimental carcinogenicity data

No data on the carcinogenicity of theophylline were available.

In the one adequate study, theophylline applied to the skin of female mice induced a significantly smaller number of ultraviolet light-induced tumours than in controls.

5.3 Human carcinogenicity data

No data were available to the Working Group to evaluate the carcinogenicity of theophylline per se.

For descriptions of studies on methylxanthines, see the monograph on caffeine.

5.4 Other relevant data

Limited data on mothers taking theophylline during pregnancy showed no excess in the frequency of malformations in their offspring.

Theophylline given by gavage at high doses decreased testicular weight in rats and mice, but there was no change in semen characteristics. Administration of theophylline in the diet at dose levels that were mildly toxic to adults caused decreased numbers of litters per breeding pair, decreased live litter size, an increased number of resorptions and decreased neonatal weight. Abnormal sperm were observed in rats but not in mice at high dose levels.

Theophylline induced sister chromatid exchange in Chinese hamsters in vivo but did not induce dominant lethal mutations in mice or chromosomal aberrations in the bone marrow of rats. Theophylline gave negative results in a host-mediated assay with Salmonella typhimurium in mice. In cultured human cells, theophylline induced sister chromatid exchange and chromosomal breaks but not micronuclei or chromosomal aberrations. It induced sister chromatid exchange and chromosomal aberrations but not micronuclei or gene mutation in animal cells in vitro. Results on the induction of chromosomal aberrations in plants are equivocal. In lower eukaryotes, it induced gene mutations. Theophylline gave negative results in the Salmonella/mammalian microsome assay but induced mutation in other bacteria.

5.5 Evaluation

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

There is inadequate evidence for the carcinogenicity in experimental animals of theophylline.

Overall evaluation

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

For definition of the italicized terms, see Preamble Evaluation.


Last updated: 17 November 1997

    See Also:
       Toxicological Abbreviations
       Theophylline (ICSC)