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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 51 (1991) (p. 421)

CAS No.: 83-67-0
Chem. Abstr. Name: 3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Theobromine is the principal alkaloid of the cacao bean. It is extracted from the bean husks and used in the synthesis of caffeine. It has been used in various pharmaceutical products. Theobromine is consumed in cocoa and chocolate beverages and in arious forms of chocolate-based foods. Theobromine is also present in small amounts in green coffee beans, tea and mate.

Daily per-caput consumption of theobromine in the USA in 1980 from food and beverages was estimated to be 39 mg.

5.2 Experimental carcinogenicity data

No data on the carcinogenicity of theobromine were available.

5.3 Human carcinogenicity data

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

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

5.4 Other relevant data

Oral administration of high doses of theobromine to rats caused severe testicular atrophy, which was largely irreversible. Administration of lower levels for prolonged periods had no significant adverse effect on the testis. Mice, hamsters and dogs were less sensitive than rats or were resistant to the effect of theobromine in causing testicular changes. No adverse reproductive effect was observed in a three-generation study in rats given cocoa powder containing theobromine in their diet. Teratogenic effects were observed in rabbits after gavage but not after dietary administration of theobromine. The signs of developmental toxicity observed at the lowest dose level included decreased fetal body weight and increased skeletal variations in rabbits. No teratogenic effect was seen in rats.

In vivo, theobromine did not induce dominant lethal effects in mice or rats. It induced sister chromatid exchange and micronuclei but not chromosomal aberrations in the bone marrow of Chinese hamsters. In human cells in vitro, theobromine induced sister chromatid exchange and chromosomal breaks. In cultured mammalian cells, it induced gene mutations and sister chromatid exchange but not chromosomal aberrations or cell transformation. In plants, theobromine did not induce chromosomal aberrations. It induced gene mutations in lower eukaryotes and bacteria but gave negative results in the Salmonella/mammalian microsome assay.

5.5 Evaluation

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

There are no data on the carcinogenicity of theobromine in experimental animals.

Overall evaluation

Theobromine 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

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       Toxicological Abbreviations