Evaluation of the effects of subchronic oral administration of n-butyl maleate in Sprague-Dawley rats.

n-Butyl maleate, also referred to as monobutyl maleate, is an ester of maleic acid, which is used as a counterion in the pharmaceutical industry. While substantial published data exist on short-term treatment, maleic acid-induced renal toxicity in the rat, no toxicity data are available on the monobutyl ester. This study evaluated the oral subchronic nephrotoxicity potential of n-butyl maleate administered to Sprague-Dawley rats (10/males and females/group) at doses of 0 (vehicle control), 10, 30, or 60 mg/kg/d for 2 wk. Statistically significant elevations in organ weights were noted in males at 60 mg/kg/d and included: (a) increases in absolute heart, kidney, and liver weights; (b) increased liver to body weight ratios; and (c) increased heart, kidney, liver, spleen, and epididymides to brain weight ratios. In females, statistically significant increases in organ weights were limited to increases in adrenal to brain weights at > or = 10 mg/kg/d, kidney to brain weights at > or = 30 mg/kg/d, and kidney to body weight and liver to brain weight ratios at 60 mg/kg/d. There were no macroscopic or microscopic pathology changes observed in any of the tissues examined. Importantly, light microscopic examination of the kidney was unremarkable at the end of the 2-wk dosing period with n-butyl maleate. Although lacking a histopathological correlate, resultant increases in organ weights at 60 mg/kg/d might be considered indicative of an adverse effect. However, renal perturbation induced by n-butyl maleate was mild in comparison to maleic acid-induced renal toxicity, which manifested as impaired tubular resorption and necrosis of the proximal tubules at doses > or = 60 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for the study was 30 mg/kg/d.

90-day oral (gavage) study in rats with galactooligosaccharides syrup.

A 90-day oral (gavage) study was conducted in male and female Sprague Dawley rats to investigate the safety of Vivinal galactooligosaccharides (GOS) syrup at 2500 or 5000 mg/kg bw/day. A reference control containing fructooligosaccharides (FOS) was used to match the oligosaccharide and digestible sugars in the test material (approximately 45% and 30%, respectively) and to assess if these had an impact on food consumption. Measurements included clinical observations, body weights, food consumption, hematology, clotting parameters, blood chemistries, urinalysis, ophthalmologic examinations, gross necropsies, organ weights, and histological examinations. There were no effects of feeding GOS syrup at either concentration on any parameter except food consumption. Statistically significant decreases (7-13%) in food consumption were seen in both sexes in the GOS syrup-treated animals at 5000 mg/kg bw/day and animals treated with the FOS control when compared to the reverse osmosis deionized (RODI) water controls. Based on the lack of toxicological effects in the study, the NOAEL for Vivinal GOS syrup is 5000 mg/kg bw/day when administered by gavage for 90 consecutive days.