© 1986 Oxford University Press
research-article |
Lack of in Vivo Mutagenicity and Testicular Toxicity of Triamterene in Mice1
Smith Kline and French Laboratories Philadelphia, Pennsylvania 19101 *Pharmakon Research International Inc., Waverly, Pennsylvania 18471
Lack of in Vivo Mutagenicity and Testicular Toxicity of Triamterene in Mice. MANSON, J.M., GUERRIERO, F.J., BROWN, T., AND SAN SEBASTIAN, J. (1986). Fundam. Appl. Toxicol. 7, 533-546. Triamterene (2,4,7-triamino-6-phenylpteridine), a widely used diuretic/antihyper-tensive agent with weak antifolate activity, has been found to be positive in several in vitro assays for mutagenicity. The present studies were undertaken to characterize the potential mutagenic and antifolate activity of triamterene in the bone marrow and testes of mice with in vivo treatment. Triamterene had no clastogenic effects on the bone marrow at 6,16, or 24 hr after a single oral dose of 25, 125, or 250 mg/kg. No alterations in hematopoietic cell maturation characteristic of antifolate action were observed in a dose-range study in which triamterene was orally administered to mice at 5-300 mg/kg/day for 5 days. Triamterene had no adverse effects on mating or fertility and did not induce dominant lethal mutations in the germ cells of male mice when given for 5 days at 5-100 mg/kg/day. Oral exposure to mice under identical conditions had no effect on testicular weight, DNA content, or activity of the de novo pathway for thymidine synthesis from deoxy [6-3H]uridine. The present findings are consistent with an absence of mutagenic effect and antifolate action on the bone marrow and testes with in vivo administration.