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

ANGELICIN AND SOME SYNTHETIC DERIVATIVES

VOL.: 40 (1986) (p. 291)

CAS No.: 523-50-2
Chem. Abstr. Name: 2H-Furo[2,3-h][1]benzopyran-2-one

5. Summary of Data Reported and Evaluation

5.1 Exposure

Angelicin and its methoxy derivatives occur in a number of plants belonging to the Umbelliferae family. These compounds have been tested clinically in combination with ultraviolet A radiation for use in the treatment of psoriasis. Human exposure occurs through contact with or ingestion of the plants in which these compounds occur.

5.2 Experimental data

Angelicin, 5-methylangelicin and 4,5'-dimethylangelicin, with and without ultraviolet A radiation, were tested for skin carcinogenicity in mice by skin application. All compounds produced skin cancers when administered with ultraviolet A radiation but not when given alone. The presence of some linear psoralen impurities in the methylangelicins cannot be excluded and may have influenced the results obtained. The studies were inadequate to evaluate the systemic carcinogenicity of these compounds. No data were available to evaluate the carcinogenicity to experimental animals of 4,4'-dimethylangelicin or 4,4',6-trimethylangelicin.

No data were available to evaluate the reproductive effects or prenatal toxicity of angelicin or its methyl derivatives.

Angelicin, in the presence of ultraviolet A radiation, bound covalently to isolated DNA and to DNA in bacteria, yeast and cultured mammalian cells. In the dark, both positive and negative findings were observed for mutagenicity in bacteria, but angelicin was not mutagenic to yeast. In the presence of ultraviolet A radiation, it was mutagenic to phage, bacteria and yeast. In the presence of ultraviolet A radiation, but not in the dark, it induced sister chromatid exchanges, chromosomal aberrations and micronuclei in mammalian cells in vitro.

5-Methylangelicin bound covalently to isolated DNA in the presence of ultraviolet A radiation. It was mutagenic to bacteria both in the dark and in the presence of ultraviolet A radiation. In combination with ultraviolet A radiation, it induced mutations and sister chromatid exchanges in mammalian cells in vitro.

44'-Dimethylangelicin, in the presence of ultraviolet A radiation, bound covalently to isolated DNA and to DNA in bacteria. In the dark, it was not mutagenic to Salmonella typhimurium. In the presence of ultraviolet A radiation, it was mutagenic to Escherichia coli and induced cytoplastic petite mutations in Saccharomyces cerevisiae.

4,5'-Dimethylangelicin, in the presence of ultraviolet A radiation, bound covalently to isolated DNA and to DNA in cultured mouse tumour cells and was mutagenic to bacteria, yeast and cultured Chinese hamster cells.

4,4',6-Trimethylangelicin, in the presence of ultraviolet A radiation, bound covalently to isolated DNA. In the dark, it was not mutagenic to Salmonella typhimurium. In the presence of ultraviolet A radiation, it was mutagenic to Escherichia coli.

4.3 Human data

No case report or epidemiological study of the carcinogenicity of angelicin or its synthetic methyl derivatives was available to the Working Group.

5.4 Evaluation

There is limited evidence for the carcinogenicity to experimental animals of angelicin, 5-methylangelicin and 4,5'-dimethylangelicin in combination with ultraviolet A radiation. There is inadequate evidence for the carcinogenicity of these compounds to experimental animals in the absence of ultraviolet A radiation.

No data were available to evaluate the carcinogenicity to experimental animals of 4,4'-dimethylangelicin or 4,4',6-trimethylangelicin.

No evaluation could be made of the carcinogenicity of angelicin or its methyl derivatives to humans.

For definition of the italicized terms, see Preamble Evaluation.

Subsequent evaluation: Suppl. 7 (1987) (p. 57: Group 3)

Synonyms


Last updated: 22 April 1998






















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