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

CHLOROZOTOCIN
(Group 2A)

For definition of Groups, see Preamble Evaluation.

VOL.: 50 (1990) (p. 65)

CAS No.: 54749-90-5
Chem. Abstr. Name: D-Glucose, 2({[(2-chloroethyl)nitrosoamino]carbonyl}-amino)-2-deoxy-

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Chlorozotocin has been used as a cytostatic drug for the treatment of cancers at a variety of sites.

5.2 Experimental carcinogenicity data

Chlorozotocin was tested for carcinogenicity in single experiments in rats by intraperitoneal and intravenous injection. Intraperitoneal administration induced a high incidence of sarcomas and mesotheliomas in the peritoneal cavity in rats of each sex. The study by intravenous administration was inadequate for evaluation.

5.3 Human carcinogenicity data

No data were available to the Working Group.

5.4 Other relevant data

Chlorozotocin alkylates DNA and protein and causes DNA interstrand cross-links. In humans, it induces leukopenia and thrombocytopenia; in animals, it suppresses the bone marrow and affects immune response.

It is hepatotoxic in both humans and experimental animals.

Chlorozotocin induced DNA damage in bone-marrow cells of rats in vivo. It induced DNA damage in human, mouse and Chinese hamster cells in vitro, sister chromatid exchange in mouse and rat cells and gene mutation in Chinese hamster cells. It induced sex-linked recessive lethal mutations in Drosophila and gene conversion in Saccharomyces cerevisiae. Chlorozotocin induced mutations in Salmonella typhimurium.

5.5 Evaluation

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

No data were available from studies in humans on the carcinogenicity of chlorozotocin.

In making the overall evaluation, the Working Group also took note of the following information. Chlorozotocin is an alkylating agent and is structurally related to other chloroethyl nitrosoureas, one of which, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU), is carcinogenic to humans (Group 1) and two of which, bischloroethyl nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), are probably carcinogenic to humans (Group 2A) (IARC, 1987). Chlorozotocin has given consistently positive results in a broad spectrum of assays for genetic and related effects, including those involving mammalian cells.

Overall evaluation

Chlorozotocin is probably carcinogenic to humans (Group 2A).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms


Last updated: 11 November 1997























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