For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 370)
CAS No.:
Chem. Abstr. Name: 5-[Bis(2-chloroethyl)amino]-2,4(1H,3H)pyrimidinedione
A. Evidence for carcinogenicity to humans (inadequate)
No epidemiological study of uracil mustard as a single agent was available to the Working Group. Occasional case reports of treatment with uracil mustard, especially in the presence of concurrent therapy with other putative carcinogens, such as ionizing radiation, alkylating agents and other potent oncotherapeutic drugs, do not constitute evidence of carcinogenesis [ref: 1-5].
B. Evidence for carcinogenicity to animals (sufficient)
Intraperitoneal administration of uracil mustard to mice of three strains induced lung adenomas and adenocarcinomas in a dose-dependent incidence; in one of the strains, liver, ovarian and lymphatic tumours were also observed. In rats, intraperitoneal administration induced peritoneal sarcomas and lymphomas and tumours in the pancreas, ovary and mammary gland [ref: 6].
C. Other relevant data
Uracil mustard is an alkylating agent [ref: 7]. No data were available on its genetic and related effects in humans.
Uracil mustard did not induce dominant lethal mutations in mice in one study using low doses. It induced mutation in mouse lymphoma cells in vitro, aneuploidy and sex-linked recessive lethal mutations in Drosophila and mitotic recombination in yeast. It caused DNA damage and was mutagenic in bacteria [ref: 7].
Overall evaluation
Uracil mustard is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluation: Vol. 9 (1975)
References
1. Reimer, R.R., Hoover, R., Fraumeni, J.F., Jr & Young, R.C. (1977) Acute leukemia after alkylating-agent therapy of ovarian cancer. New Engl. J. Med., 297, 177-181
2. Zarrabi, M.H. & Rosner, F. (1979) Acute myeloblastic leukemia following treatment for non-hematopoietic cancers. Report of 19 cases and review of the literature. Am. J. Hematol., 7, 357-367
3. McKenna, R.W., Parkin, J.L., Foucar, K. & Brunning, R.D. (1981) Ultrastructural characteristics of therapy-related acute nonlymphocytic leukemia: evidence for a panmyelosis. Cancer, 48, 725-737
4. Rosner, F. (1976) Acute leukemia as a delayed consequence of cancer chemotherapy. Cancer, 37, 1033-1036
5. Zarrabi, M.H. (1980) Association of non-Hodgkin's lymphoma (NHL) and second neoplasms. Semin. Oncol., 7, 340-351
6. IARC Monographs, 9, 235-241, 1975
7. IARC Monographs, Suppl. 6, 558-560, 1987
Synonyms
See Also:
Toxicological Abbreviations
Uracil Mustard (IARC Summary & Evaluation, Volume 9, 1975)