Robertson R T, Allen H L, Bokelman D L
Teratology. 1979 Oct;20(2):313-20. doi: 10.1002/tera.1420200215.
Beagle bitches were administered aspirin at either 100 or 400 mg/kg/day between Days 15 and 22 or Days 23 and 30 postmating, and corresponding control groups were dosed with vehicle during one of these same time periods. Maternotoxicity was evident in all dogs dosed with 400 mg/kg/day of aspirin, but no signs of toxicity were observed when 400 mg/kg/day of aspirin was administered from Days 15 to 22 postmating. Teratogenicity, as evidenced by 50% malformation rate, was seen in fetuses from dams treated with 400 mg/kg/day on Days 23 to30 postmating. Observed malformations included, but were not limited to cleft palate,micrognathia, anasarca, cardiovascular malformations, and tial anomalies. No evidence of embryotoxic or teratogenic effects was seen in fetuses from either 100 mg/kg/day dosage level group. Examination of fetuses from 12 untreated litters and 4 vehicle-control litters revealed a very low spontaneous malformation rate confined almost entirely to minor tail abnormalities. These data support use of the dog as an acceptable alternative species in teratogenic screening.
在交配后的第15至22天或第23至30天，给比格犬母犬分别按100或400毫克/千克/天的剂量服用阿司匹林，相应的对照组在这些相同时间段中的一个期间给予赋形剂。所有按400毫克/千克/天剂量服用阿司匹林的犬均出现母体毒性，但在交配后第15至22天给予400毫克/千克/天阿司匹林时未观察到毒性迹象。在交配后第23至30天接受400毫克/千克/天治疗的母犬所产胎儿中，出现了致畸性，畸形率达50%。观察到的畸形包括但不限于腭裂、小颌畸形、全身性水肿、心血管畸形和尾部异常。在100毫克/千克/天剂量组的胎儿中未发现胚胎毒性或致畸作用的证据。对12窝未治疗的幼犬和4窝赋形剂对照幼犬的检查显示，自发畸形率极低，几乎完全局限于轻微的尾部异常。这些数据支持将犬作为致畸性筛查中可接受的替代物种。
