For definition of Groups, see Preamble Evaluation.
VOL.: 50 (1990) (p. 123)
Chem. Abstr. Name: 1,1',1''-Phosphinothioylidynetrisaziridine
Thiotepa is a cytostatic agent that has been used in the treatment of malignant lymphomas and solid tumours, in a wide range of doses.
Thiotepa was tested for carcinogenicity by intraperitoneal administration in mice and rats and by intravenous administration in male rats. In mice, it induced an increased incidence of lung tumours and lymphoproliferative malignancies in mice of each sex. In rats, intraperitoneal administration induced an increased incidence of lymphoproliferative malignancies in males and of uterine adenocarcinomas and mammary carcinomas in females. Intravenous administration to male rats induced tumours at a variety of sites.
Several cases of leukaemia following treatment with thiotepa alone have been reported. One case-control study has shown a strong association between risk for leukaemia and treatment with thiotepa.
In one study, there was no evidence that thiotepa therapy adversely affected subsequent fertility in women. Thiotepa is embryotoxic to mice and rats, and embryo- and fetolethality and gross structural abnormalities were induced during organogenesis after single intraperitoneal injections.
Thiotepa is converted to alkylating metabolites in vivo. It suppresses the bone marrow in humans.
In one study, increased frequencies of chromosomal aberrations were observed in peripheral lymphocytes of patients receiving thiotepa.
Thiotepa induced chromosomal aberrations in germ cells, sperm abnormalities and dominant lethal mutation in mice in vivo. It induced micronuclei in the bone marrow of rats and mice, chromosomal aberrations in bone-marrow cells and liver cells of mice and in peripheral lymphocytes of rabbits and rhesus monkeys and sister chromatid exchange in bone-marrow cells of mice in vivo. Thiotepa induced DNA damage in chick embryos. It induced chromosomal aberrations in cloned hamster cells, in Chinese hamster cells and in human cells, sister chromatid exchange in human, mouse, Chinese hamster and rabbit cells, gene mutations in Chinese hamster cells and unscheduled DNA synthesis in human peripheral lymphocytes in vitro. It induced cell transformation in mouse cells. Thiotepa induced sex-linked recessive lethal mutations in Drosophila and sister chromatid exchange and chromosomal aberrations in Vicia faba. It induced gene mutations in Aspergillus nidulans and Salmonella typhimurium.
There is sufficient evidence for the carcinogenicity of thiotepa in humans.
There is sufficient evidence for the carcinogenicity of thiotepa in experimental animals.
Thiotepa is carcinogenic to humans (Group 1).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 9 (1975) (p. 85); Suppl. 7 (1987) (p. 368)
Last updated: 11 November 1997
See Also: Toxicological Abbreviations