Davis D P, Daston G P, Odio M R, York R G, Kraus A L
The Procter and Gamble Company, Cincinnati, OH 45241, USA.
Toxicol Lett. 1996 Mar;84(3):135-41. doi: 10.1016/0378-4274(95)03538-9.
Clinical and experimental evidence indicates that exposure to relative ly large doses of acetylsalicylic acid (ASA) prolongs parturition. However, little is known about the dose-response relationship for salicylate-related effects on labor and gestation. As well, the relative potency of salicylic acid (SA) as compared with ASA for these reproductive effects has not been well investigated. This study was designed to define a dose-response relationship for salicylic acid (SA) effects on labor and gestation times in Sprague-Dawley rats. Pregnant females received oral doses of 20,80, or 200 mg/kg/day sodium salicylate, or 260 mg/kg/day acetylsalicylic acid (ASA), as a positive control, on days 15 through 21 of gestation (sperm positive = day 0). Onset of labor was followed in each animal beginning on day 21 of gestation. The data failed to demonstrate a substantial potency difference between ASA and SA but some differences in toxicity were observed. Relative to controls, gestation times were unaffected by SA. SA treatment resulted in a dose-related trend towards increased duration of labor which was statistically significant at 200 mg/kg/day of SA. ASA treatment of pregnant females resulted in both prolonged labor and gestation times. Both the highest administered dose of SA and ASA treatment contributed to increased maternal peripartum death. Overall, the study confirms a dose-response relationship for SA-induced maternal reproductive effects and supports a no observable effect level (NOEL) for this compound of 80 mg/kg/day for adverse effects on parturition.
临床和实验证据表明，接触相对大剂量的乙酰水杨酸（ASA）会延长分娩时间。然而，关于水杨酸盐对分娩和妊娠影响的剂量反应关系，人们了解甚少。同样，水杨酸（SA）与ASA相比对这些生殖效应的相对效力尚未得到充分研究。本研究旨在确定水杨酸（SA）对Sprague-Dawley大鼠分娩和妊娠时间影响的剂量反应关系。在妊娠第15天至21天（精子阳性=第0天），怀孕雌性大鼠口服20、80或200mg/kg/天的水杨酸钠，或260mg/kg/天的乙酰水杨酸（ASA）作为阳性对照。从妊娠第21天开始观察每只动物的分娩开始情况。数据未能证明ASA和SA之间存在实质性的效力差异，但观察到了一些毒性差异。相对于对照组，SA对妊娠时间没有影响。SA治疗导致分娩时间呈剂量相关趋势增加，在200mg/kg/天的SA剂量下具有统计学意义。对怀孕雌性大鼠进行ASA治疗会导致分娩时间和妊娠时间延长。SA和ASA治疗的最高给药剂量都会导致产妇围产期死亡增加。总体而言，该研究证实了SA诱导的母体生殖效应的剂量反应关系，并支持该化合物对分娩产生不良影响的无观察到有害作用水平（NOEL）为80mg/kg/天。
