Hayes W C, Cobel-Geard S R, Hanley T R, Murray J S, Freshour N L, Rao K S, John J A
Drug Chem Toxicol. 1981;4(3):283-95. doi: 10.3109/01480548109018135.
Prior to employing the Fischer 344 rat in teratology studies, it was considered necessary to establish the responsiveness of this strain to teratogenic agents. Bred Fischer 344 rats were administered 0, 3.2, 32, or 128 mg/kg/day (approximately 1,000, 10,000, or 40,000 USP units per animal) of vitamin A palmitate by gavage on days 6 through 15 of gestation. Maternal toxicity, as evidenced by decreased body weight gain, and decreased food and water consumption, was observed at the 128 mg/kg/day dose level. This dosage level was embryolethal and teratogenic in the Fischer 344 rat. The incidence of fetal resorptions was statistically significantly increased as compared to controls. Among the surviving fetuses, malformations observed included cleft palate, exencephaly, microphthalmia, anophthalmia, hydronephrosis, brachygnathia, pinna anomalies, and great vessel and heart anomalies. Based on these findings, it is concluded that the Fischer 344 rat responded to a known teratogenic agent and hence is appropriate for use in studies designed to evaluate the teratogenic potential of test agents.
在将Fischer 344大鼠用于致畸学研究之前，认为有必要确定该品系对致畸剂的反应性。在妊娠第6至15天，通过灌胃给繁殖的Fischer 344大鼠每日给予0、3.2、32或128 mg/kg体重的棕榈酸视黄酯（每只动物约1000、10000或40000 USP单位）。在128 mg/kg/天的剂量水平观察到母体毒性，表现为体重增加减少、食物和水摄入量减少。该剂量水平在Fischer 344大鼠中具有胚胎致死性和致畸性。与对照组相比，胎儿吸收的发生率在统计学上显著增加。在存活胎儿中，观察到的畸形包括腭裂、脑膨出、小眼症、无眼症、肾积水、短颌、耳廓异常以及大血管和心脏异常。基于这些发现，得出结论，Fischer 344大鼠对已知致畸剂有反应，因此适用于旨在评估受试物致畸潜力的研究。
