Studies on the Teratogenicity of Furylfuramide in Fetuses and Offspring of Rats in Relation to Fetal Distribution

Developmental Toxicity of Aspirin Prenatally Given to Rats: Assessment in Sic: Wistar‐KY Rats

“…This study was designed to examine the effects of aspirin on Slc: Wistar-KY rat dams and fetuses and most of our results obtained would support the views of the earlier reports (Kimmel et al, 1971;Tanaka et al, 1973;Warkany and Takacs, 1959). Suppression of maternal weight gain, decreased food consumption during the treatment, decreased fetal weight, higher incidence of dead or resorbed fetuses and increased skeletal defects were observed as added proof in our experiment.…”

“…Recently, Mitala et al (1984) reported that SD rat fetuses exposed to aspirin in utero showed an accessory skull bone, which was not confirmed in S1c:Wistar-KY rats of the present study. Tanaka et al (1973) reported aspirin teratogenesis in Wistar rats given on days 8 to 14 of gestation. To elucidate the causes of such strain differences on aspirin teratogenesis, studies on pharmacokinetics and susceptibility of embryonic tissues might be essential.…”

Safety Assessment of Salicylic Acid, Butyloctyl Salicylate, Calcium Salicylate, C12–15 Alkyl Salicylate, Capryloyl Salicylic Acid, Hexyldodecyl Salicylate, Isocetyl Salicylate, Isodecyl Salicylate, Magnesium Salicylate, MEA-Salicylate, Ethylhexyl Salicylate, Potassium Salicylate, Methyl Salicylate, Myristyl Salicylate, Sodium Salicylate, TEA-Salicylate, and Tridecyl Salicylate

“…The thyroid weight of male offspring from the 75-mg/kg group was significantly increased and the adrenal gland weight of male offspring from the 150-mg/kg group was significantly decreased compared to controls. The incidences of external organ, internal organ, and skeletal anomalies in offspring were 0%, 5.0%, and 0%, respectively, for the 75-mg/kg group and 13.7%, 17.2%, and 79.2%, respectively, for the 150mg/kg group (Tanaka et al 1973b). Waltman et al (1973) studied the effects of anti-inflammatory drugs on parturition parameters in the rat.…”

“…No maternal toxicity and no changes in reproductive parameters or malformations were seen; positive controls had 100% incidence of total resorptions Infurna et al 1990 LVG hamsters 350 or 525 mg/100 g Methyl Salicylate was applied to the back of each animal at 7 days 9 h, and the skin was washed 2 h after dosing; fetuses were recovered on d 9 of gestation Neural tube defects were seen in 6% and 53% of the low-and high-dose litters, respectively Overman and White 1983 Oral exposure to: Salicylic Acid 20 Wistar rats/group 0.06%, 0.1%, 0.2%, or 0.4% in feed Animals were fed test diets on GDs 8-14; 15 animals/group were killed on GD 20; 5 animals/group delivered Maternal mortality was 0%; neonatal mortality was 71% in the 0.4% group; significant reproductive effects were seen in the 0.4% group; skeletal anomalies were seen in the 0.2% group; only one dam gave birth to live neonates in the 0.4% group and skeletal anomalies were seen in 0.2% neonates Tanaka et al 1973a 20 Wistar rats/group 75, 150, or 300 mg/kg Animals were dosed orally once daily on GDs 8-14; 15 animals/group were killed on GD 20; 5 animals/group delivered 3 dams of the 300-mg/kg group died; fetal mortality was 26% and 100% in the 150and 300-mg/kg groups; significant reproductive effects were seen in 150-mg/kg fetuses and neonates Tanaka et al 1973b 10 Sprague-Dawley (SD) rats/group 10 mg/kg Animals were dosed twice daily on GD 20 and 21 The mean gestation period was increased Waltman et al 1973 Sodium Salicylate NZW rabbits 100 mg/kg Animals were dosed on GDs 4-7 and killed on GD 8 or 28 The preimplantation ratio and average litter size were not affected; teratogenic effects were not induced Fabro et al 1984 (Continued on next page) Embryotoxicity was seen at 400 mg/kg; fetal mortality was 2% and 50% in the 200-and 400-mg/kg groups; fetal body weight index was significantly decreased in the 400-mg/kg group; some developmental anomalies were seen in both groups, and dose-related decreases in organ weights were observed Kavlock et al 1982 5-16 SD rats 250-450 mg/kg Animals were dosed IP with [10][11][11][12][11][12][13] and killed on GD 20 Maternal toxicity was observed; fetal weight was significantly decreased (dose dependent); malformations were observed in fetuses of groups dosed with ≥350 mg/kg on GD 11 and ≥300 mg/kg on >1 day; incidence of resorptions was significant in the 400 mg/kg gp dosed on GD 11; kidney development was affected …”

“…Fetal and amniotic fluid concentrations were relatively lower than those observed in maternal organs (13.86 µg/g in the fetus and 12.35 µg/ml in the amniotic fluid). Tanaka et al (1973b) determined the Salicylic Acid concentration in maternal organs and in fetuses. Five gravid Wistar rats were given 150 mg/kg Salicylic Acid orally once daily on days 8 to 14 of gestation or given one dose on day 14 of gestation.…”