For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 222)
Chem. Abstr. Name: 1(2H)-Phthalazinone hydrazone
Chem. Abstr. Name: 1(2H)-Phthalazinone hydrazone, monohydrochloride
A. Evidence for carcinogenicity to humans (inadequate)
Two studies suggest an association between exposure to hydralazine and cancer. One was confined to patients with and without signs of toxicity due to hydralazine, and potential confounding factors were not controlled for. The other involved a small number of subjects exposed to hydralazine, but the possibility of selection bias could not be excluded [ref: 1]. However, a study of 3988 participants in a hypertensive detection and follow-up programme suggested no increased risk for cancer at all sites from use of hydralazine. A logistic regression estimate of cancer risk after controlling for age, sex, race, smoking behaviour and concomitant drug therapy was 0.89 (95% confidence interval, 0.45-1.8). It was noted that this estimate of no excess risk was restricted to a hypertensive population over 40 years of age, exposed to hydralazine for various periods (none longer than five years) [ref: 2]. Another study involving women with breast cancer also showed no increased risk with use of hydralazine (relative risk, 0.9; 0.5-1.7) [ref: 3].
B. Evidence for carcinogenicity to animals (limited)
Hydralazine hydrochloride was tested in one experiment in mice by oral administration. A significant increase in the incidence of lung tumours was reported [ref: 1].
C. Other relevant data
No data were available on the genetic and related effects of hydralazine in humans.
In a single limited study, hydralazine did not induce DNA damage in animals treated in vivo. It induced sister chromatid exchanges in human lymphocytes in vitro, whereas assays for chromosomal aberrations in rodent cells in vitro were inconclusive. Hydralazine induced unscheduled DNA synthesis in rat and rabbit hepatocytes in vitro and induced mutation and DNA damage in bacteria [ref: 4].
Hydralazine is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluation: Vol. 24 (1980)
1. IARC Monographs, 24, 85-100, 1980
2. Rogers, A.S. (1984) Hydralazine: an estimate of cancer risk in a hypertensive program (Abstract). Diss. Abstr. int., 44, 2123
3. Kaufman, D.W., Kelly, J.P., Rosenberg, L., Stolley, P.D., Schottenfeld, D. & Shapiro, S. (1987) Hydralazine and breast cancer. J. natl Cancer Inst., 78, 243-246
4. IARC Monographs, Suppl. 6, 338-340, 1987
Synonyms for Hydralazine
See Also: Toxicological Abbreviations Hydralazine (PIM 264)