BACKGROUND: A review of the nonsteroidal anti-inflammatory drug (NSAID) literature suggested occurrences of low-level incidences of @entity65 in @entity95 fetuses exposed in utero. @entity117 ( @entity117 , @entity1281 ) is a widely used NSAID that irreversibly inhibits @entity70365 . @entity1281 has been studied extensively in @entity35 and has consistently increased low-incidence @entity65 and defects in midline closure. The objectives of the current study were to comprehensively define the developmental toxicology profile of @entity1281 in @entity95 by using a dosing paradigm encompassing the period of organogenesis and to test the hypothesis that maternal @entity344 after repeated dose administrations hampers the detection of low-incidence malformations with @entity1281 in @entity95 by limiting @entity1281 administration to sensitive windows for cardiovascular development and midline closure. METHODS: @entity1281 was administered to pregnant New Zealand White @entity95 from gestation days (GDs) 7 to 19 at dose levels of 125, 250, and 350 mg/kg per day and as single doses of 500, 750, or 1000 mg/kg on GD 9, 10, or 11. Cesarean sections were performed on GD 29, and the fetuses were examined for external, visceral and skeletal development. RESULTS: In the repeated dose study, maternal @entity137 was exhibited in the 250- and 350-mg/kg per day groups by mortality and @entity1907 and body @entity1017 . In the single dose studies, maternal @entity137 was exhibited at all doses by reductions in body @entity1017 and food consumption for 3 days after treatment. Fetal body weight was significantly reduced in the repeated dose study at 350 mg/kg per day. Fetal weights were not affected by single doses of @entity1281 on GD 9, 10, or 11. There were no treatment-related external, @entity600 associated with @entity1281 administration throughout organogenesis or with single doses administered during critical developmental windows. CONCLUSION: These findings supported previous work demonstrating that @entity1281 is not teratogenic in @entity95 , as opposed to @entity35 , even when large doses are administered on single days during specific windows of development.

Comparison of the developmental XXXX of @entity117 in @entity95 when administered throughout organogenesis or during sensitive windows of development.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity117 :: ('MESH:D001241', 'Chemical') :: ['Aspirin', 'acetylsalicylic acid'] @entity95 :: ('9986', 'Species') :: ['rabbits', 'rabbit'] @entity70365 :: ('100009407;100009248;808231;808233', 'Gene') :: ['cyclooxygenases (COXs) 1 and 2'] @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal toxicity'] @entity600 :: ('MESH:D000014', 'Disease') :: ['visceral or skeletal malformations'] @entity1017 :: ('MESH:D015430', 'Disease') :: ['weight gain'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity1281 :: ('CHEBI:15365', 'Chemical') :: ['ASA'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular and midline defects', 'cardiovascular malformations'] @entity1907 :: ('MESH:D014397', 'Disease') :: ['decreased food consumption']
@entity137 :: (MESH:D064420,Disease) :: ['toxicity']
