Maternal reproductive effects of oral salicylic acid in Sprague-Dawley rats

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.