Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid.

Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important in human brain and retina development, and there is growing evidence showing the importance of these fatty acids in infant nutrition. Triglyceride oils, highly enriched in ARA (ARASCO) and DHA (DHASCO), were evaluated using very high dose acute (20 g/kg) and 4-wk subchronic gavage feedings in weanling Sprague-Dawley rats. The combination of these oils, Formulaid, was also tested in the 4-wk subchronic study, ARASCO, DHASCO and Formulaid were found to have a no-observable-adverse-effect level of more than 2.5 g/ kg/day, 1.25 g/kg/day and 3.75 g/kg/day, respectively. This represents a 50-fold safety margin over the intended use of Formulaid in infant formula. Survival, clinical signs, body weight gain, food consumption, haematology, clinical chemistry and histopathological evaluations failed to show any significant differences in animals administered ARASCO, DHASCO or Formulaid compared with that in control animals administered equal amounts of high oleic sunflower oil. The bioavailability of ARASCO, DHASCO and Formulaid was verified by increases in DHA and ARA levels in heart and liver tissues in these animals. Because these oils are enriched in only a single bioactive fatty acid, and they have been shown to be safe, they may offer a new source of these fatty acids in speciality foods such as infant formula.

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations.

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.

Anterior corneal dystrophy of American Dutch belted rabbits: biomicroscopic and histopathologic findings.

Spontaneously occurring anterior corneal opacities were present in related, juvenile American Dutch belted rabbits. Slit lamp biomicroscopy revealed focal opacities of epithelium, basement membrane, and subepithelial corneal stroma. Lesions were characterized histologically by thin and disorganized surface epithelium, thickened and intensely staining epithelial basement membrane, fimbriated and irregular basement membrane-stromal juncture, and disorganized subepithelial stroma. Biomicroscopic and histopathologic features of anterior corneal dystrophy of American Dutch belted rabbits appear similar to those of human anterior corneal dystrophies.

Toxicity studies on the radioprotective agent WR-2721 in CDF1 mice and beagle dogs.

WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is used extensively to protect normal cells during the irradiation of neoplastic cells. Dose levels for human radiotherapy are based on results obtained from laboratory animal lethality and toxicity studies. WR-2721 was administered intravenously to CDF1 mice and beagle dogs. Single dose lethality studies in mice showed the average 1/10 of the lethal dose, the median lethal dose and 9/10 the lethal dose to be 508 (1523 mg/m2), 589 (1766 mg/m2), and 682 mg/kg (2047 mg/m2), respectively. The lethal dose for female mice was lower than that for males. The 1/10 lethal dose in mice was slightly toxic to dogs; 1/10 of that dose was nontoxic. The lethal dose for dogs (6000 mg/m2) was higher than that for mice (2000 mg/m2). Clinical signs of toxicosis in the single-dose mouse toxicity study were evident in the 1st week following treatment and declined during the recovery period; signs of toxicosis were transient in dogs. Acute drug-induced pathologic changes included elevated BUN and SGOT levels, lymphoid necrosis, and renal tubular degeneration in mice. These changes were evident in the 1st week following treatment, but had dissipated by study termination. Generalized vascular changes (congestion, hemorrhage, and edema) and renal tubular degeneration occurred in treated dogs that had died or were killed moribund 7 days postinjection. These findings indicate sex-dependent and interspecies variation in the toxicity of WR-2721 with acute, but reversible, pathologic changes.