Effects on mouse embryos of in utero exposure to saccharin: teratogenic and chromosome effects

Abstract

For teratogenesis studies, pregnant ICR albino mice were administered saccharin by three routes and at three different doses by each route as follows: Intraperitoneal injection of 500, 1,000, or 2,000 mg/kg saccharin on day 10 of gestation; intragastric tube delivery of 5, 10, or 25 mg/kg/day of saccharin on days 5-15 of gestation; and as drinking water containing a 5, 10, or 20% solution of saccharin from day 0 through day 17. Appropriate controls were used for each set. No increase in either resorptions or malformations was found in mouse embryos whose dams had received saccharin by any of the three routes. For chromosome studies, saccharin was administered IP to pregnant ICR albino mice on day 10 of gestation as either a 1,000 mg/kg or 2,000 mg/kg dose. To demonstrate sister chromatid exchanges (SCE), bromodeoxyuridine was administered as 16 consecutive half-hourly doses of 25 mg/kg during the 8 h prior to saccharin injection. In addition, one group received two doses of BrdU and 2,000 mg/kg saccharin 8 h apart to demonstrate SCE frequency following exposure to saccharin for two cell cycles. The mice were given colchicine (4 mg/kg) 6 h after the final injection and killed 2 h later. Embryonic cell suspensions and metaphase spreads were prepared by routine methods. Metaphase spreads were examined for breaks or gaps (after Giemsa staining), for G-banding (using the ASG technique), for C-banding (using Giemsa staining after exposure to 0.07 N NaOH and incubation in 2 X SSC at 60 degrees C), and for SCE by the Hoechst-Giemsa method. Fifty metaphase spreads were counted for each experimental condition.(ABSTRACT TRUNCATED AT 250 WORDS)