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

GRISEOFULVIN
(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 79 (2001) (p. 291)

CAS No.: 126-07-8
Chem. Abstr. Name: (1S,6R)-7-Chloro-2,4,6-trimethoxy-6-methylspiro[benzofuran-2(3H),1-[2]cyclohexene]-
3,4
-dione

5.  Summary of Data Reported and Evaluation

5.1 Exposure data

Griseofulvin is an antifungal drug given orally for the treatment of dermatophyte and ringworm infections of the scalp, hair, nails and skin. It is also used as an antifungal agent in veterinary medicine.

5.2 Human carcinogenicity data

Griseofulvin was mentioned in the report of a cohort study designed to screen 215 drugs for carcinogenicity. Although an excess of thyroid cancer was reported among users of griseofulvin in a 9-year follow-up, no results for this drug were reported in a 15-year follow-up, implying that no significant association was observed for cancer at any site.

5.3 Animal carcinogenicity data

Griseofulvin was tested by oral administration in two studies in mice and in one study each in rats and hamsters. It produced hepatocellular adenomas and carcinomas in mice and thyroid follicular-cell adenomas and carcinomas in rats. The incidence of tumours was not increased in hamsters.

5.4 Other relevant data

Griseofulvin induces hepatic enlargement and accumulation of protoporphyrin in mice by inhibiting ferrochelatase. Hepatic porphyria is accompanied by cell damage, necrosis and inflammation. Administration of griseofulvin to mice increased P-glycoprotein in hepatic membranes and resulted in the formation of Mallory bodies. Griseofulvin induced the cytochrome P450 (CYP) 2A5 enzyme concentration in mouse liver. These effects may be related to its hepatocarcinogenic effects. Short-term treatment of rats by gavage caused thyroid gland enlargement, decreased serum thyroxine concentrations and increased serum concentrations of thyroid-stimulating hormone. Griseofulvin binds to tubulin, thereby interfering with the normal polymerization of microtubule protein.

Griseofulvin was teratogenic in rats and cats.

No data were available on the genetic and related effects of griseofulvin in humans. Griseofulvin induced sister chromatid exchange in bone-marrow cells and chromosomal aberration in spermatocytes, but it did not cause micronucleus formation or chromosomal aberrations in bone-marrow cells of mice. It induced aneuploidy in vivo and in vitro and micronucleus formation in cells in vitro. Griseofulvin did not induce recombination or mutation in fungi, but it induced DNA damage and somatic mutation or mitotic recombination in insects. Griseofulvin was not mutagenic and did not induce DNA damage in bacteria.

5.5 Evaluation

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

There is sufficient evidence in experimental animals for the carcinogenicity of griseofulvin.

Overall evaluation

Griseofulvin is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluations: Vol. 10 (1976); Suppl. 7 (1987)

Synonyms

  • (2S,4R)-7-Chloro-2,4,6-trimethoxy-4- methylspiro[benzofuran-2(3H),3-cyclohexene]-
    3,6
    -dione
  • (1S-trans)-7-Chloro-2,4,6-trimethoxy-6-methylspiro[benzofuran-2(3H),1-[2]cyclohexene]-
    3,4
    -dione
  • 7-Chloro-2,4,6-trimethoxy-6b-methylspiro[benzofuran-2(3H),1-[2]cyclohexene]-3,4-dione
  • (+)-7-Chloro-4,6-dimethoxycoumaran-3-one-2-spiro-1-(2-methoxy-6-methylcyclohex-2-en-
    4
    -one)
  • (+)-Griseofulvin

  • Last updated: 25 September 2001
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
        See Also:
           Toxicological Abbreviations
           Griseofulvin  (IARC Summary & Evaluation, Supplement7, 1987)
           Griseofulvin  (IARC Summary & Evaluation, Supplement7, 1987)
           Griseofulvin  (IARC Summary & Evaluation, Volume 10, 1976)