A ninety-day feeding, subchronic toxicity study of oligo-N-acetylglucosamine in Fischer 344 rats.

Oligo-N-acetylglucosamine (OAG) is a hydrolyzed derivative of chitin that has been used as a sweetener in foods. Since, no information has been published about the safety of OAG, a 90-day feeding study was conducted, using F344 Fischer rats of both sexes, to characterize and evaluate the toxicity of OAG, and the results of the study are presented here. Dietary levels of 0% (control), 0.2%, 1%, and 5% OAG did not change any measurements in ophthalmological examinations, clinical signs, body weights, food consumption, hematology, blood biochemistry, urinalysis, necropsies, organ weights or histological examinations. The sole finding, which could not be clarified to be attributed to OAG or not, was a decrease in the relative weight of the submaxillary gland to body weight in the male animals given the 5% OAG diet. Although no lesions were found in either gross or histological examination in the present study, further studies using OAG levels higher than 5% might provide a clue to the mechanisms underlying the decreased organ weight observed here. Taken together, under the conditions in the present study, the No Observed Adverse Effect Level (NOAEL) for males was found to be 1% (0.641 g/kg/day); and that for females, 5% (3.64 /kg/day) or more, based on the lack of toxicological effects.

A 90-day ad libitum administration toxicity study of oligoglucosamine in F344 rats.

A 90-day ad libitum administration toxicity study of oligoglucosamine (OG) was carried out using F344 rats of both sexes. The animals were divided into four groups of 20 animals each, 10 of each sex, and fed a diet containing 0, 0.04, 0.2 or 1.0 (w/w)% OG. During the administration period, no animals of either sex died or exhibited abnormal signs in the 0.04% OG and 0.2% OG groups. In the 1% OG group, in both sexes, erythema and swelling of the snout and forelimbs and loss of fur in the forelimbs were observed. On macroscopic observation, emaciation, swelling of the snout, auricles and forelimbs and alopecia of the forelimbs were also observed in 2-3 males of the 1% OG group. It was suggested that these topical abnormalities might be due to dermal responses to OG adhering to the skin and fur, which are easily soiled with saliva during grooming. In the animals of the 1% OG group, food consumption decreased, resulting in body weight gain being suppressed. This was found concomitantly with the abnormal findings mentioned above. Thus, feeding difficulties due to the topical lesions on the snout and forelimbs were thought to affect body weight. In hematology, platelet count, lymphocyte count and differential neutrophil count increased in males of the 1% OG group. These changes might be related to the dermal inflammation. Abnormalities in urinalysis and blood chemistry, as well as a small thymus, small spleen, dark spots or areas on the glandular stomach mucosa, pale Harderian glands and small testes in histopathology, were also observed in males in the 1% OG group. Whether or not all these changes were related only to the malnutrition remains to be elucidated. From these results, OG gave rise to no adverse effects in rats up to the dose level of 0.2 (w/w)%. Thus, the no observed adverse effect level was determined to be 0.2 (w/w)% for rats of either sex (124.0mg/kg/day in males, 142.0mg/kg/day in females).

Screening of toxicological properties of 4-methylbenzoic acid by oral administration to rats.

Oral toxicity of 4-methylbenzoic acid in male and female Sprague-Dawley rats was profiled through a twenty-eight-day repeated dose toxicity study (the 28-day study) and a screening test for reproductive/developmental toxicities (the reproduction/developmental study) conducted under Organisation for Economic Co-operation and Development (OECD) test guidelines. Daily administration of 4-methylbenzoic acid, at a dose level of 0, 100, 300 or 1,000 mg/kg, did not show any adverse effect on reproductive organs of animals in the 28-day study. In the reproductive/developmental study, however, 1,000 mg/kg/day of the compound reduced epididymal weights and increased incidence of cauda epididymal oligo/azoospermia. While the compound did not affect estrous cycle or mating performances, 1,000 mg/kg of the compound reduced fertility. Furthermore, 300 mg/kg or more of the compound increased pre-implantation loss, which resulted in a decrease in the number of offspring, and reduced body weight gain of the dams during the latter period of gestation. From these results, the no-observed-effect-level (NOEL) for reproductive/developmental toxicities is considered to be 100 mg/kg, whereas 1,000 mg/kg did not show any effect on neonates. In the 28-day study, NOEL is considered to be 300 mg/kg for male and female rats, since 1,000 mg/kg of the compound caused, in both sexes, a few minor changes, such as temporal salivation, a slight increase in food consumption and a moderate increase in blood aspartate aminotransferase (AST) activity. Thus, 4-methylbenzoic acid has the potential for reproductive toxicity, with diverse adverse effects on the epididymis, after repeated administration, observed in the two studies.