Developmental neurotoxicity evaluation of acrylamide in Sprague-Dawley rats.

Based on the literature to-date, the potential of acrylamide (ACRL) to cause developmental neurotoxicity in laboratory animals has not been assessed. We examined this potential in Sprague-Dawley rats using a study design similar to that proposed by the USEPA. Dosages of 0 (deionized water), 5, 10, 15, or 20 mg/kg/day were administered at 5 ml/kg by oral gavage from gestational day 6 to lactational day 10 to groups of 12 mated females each.

Selection of food allotment for New Zealand white rabbits in developmental toxicity studies.

In three initial studies, female rabbits were fed 125, 150, or 230 g of Purina Certified Rabbit Chow No. 5322 ("regular" chow) per day or 150 g/day of Purina Certified High Fiber Rabbit Chow ("high fiber" chow) for at least 5 weeks prior to artificial insemination and until Day 28 of gestation when fetuses were removed and examined. Animals allotted 230 g/day of regular chow ate approximately 180 g/day and gained more weight than the 150 g/day group until Day 14 of gestation after which food consumption declined and body weight decreased.

Toxicity of the HMG-coenzyme A reductase inhibitor, lovastatin, to rabbits.

Lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, has been shown to be highly effective in lowering serum cholesterol in animals and humans and thus represents a promising approach to the treatment and prevention of cardiovascular disease. During the preclinical safety assessment of lovastatin, oral doses that were tolerated by dogs, rats and mice were found to be lethal to rabbits in subacute studies. Postmortem findings in rabbits consisted of centrilobular hepatic necrosis, frequently accompanied by renal tubular necrosis and occasionally gallbladder necrosis.