Integration of in vivo and in vitro approaches to characterize the toxicity of Antalarmin, a corticotropin-releasing hormone receptor antagonist.

Non-clinical studies were conducted to evaluate the toxicity of Antalarmin, a corticotropin-releasing hormone type 1 receptor antagonist being developed for therapy of stress-related pathologies. Antalarmin was not genotoxic in bacterial mutagenesis assays, mammalian cell mutagenesis assays, or in vivo DNA damage assays. In a 14-day range-finding study in rats, Antalarmin doses >or=500 mg/kg/day (3,000 mg/m(2)/day) induced mortality.

Oncogenicity evaluations of chemopreventive soy components in p53((+/-)) (p53 knockout) mice.

Epidemiologic data suggest that soy consumption may protect against cancer induction in several tissues in humans. Although the soy components responsible for this activity remain unidentified, isoflavones (e.g.

Modulation of hepatic and renal drug metabolizing enzyme activities in rats by subchronic administration of farnesol.

Farnesol demonstrates antitumor activity in several animal models for human cancer and was being considered for development as a cancer chemopreventive agent. This study was performed to characterize the effects of minimally toxic doses of farnesol on the activity of phase I and II drug metabolizing enzymes. CD((R)) rats (20/sex/group) received daily gavage exposure to farnesol doses of 0, 500, or 1000 mg/kg/day for 28 days; 10 rats/sex/group were necropsied at the termination of farnesol exposure; remaining animals were necropsied after a 28-day recovery period.

Resveratrol-associated renal toxicity.

Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks.

Reproductive toxicity assessment of chronic dietary exposure to soy isoflavones in male rats.

Epidemiologic and experimental data suggest that consumption of diets that are rich in isoflavones may decrease cancer risk in the breast, prostate, and other tissues. Isoflavones such as genistein and daidzein are structurally similar to endogenous estrogens, and demonstrate both estrogenic and weak anti-estrogenic activities; these activities may underlie the impaired fertility and reproductive tract disorders reported in animals exposed to high doses of isoflavones. To identify possible effects of isoflavones on male fertility, we evaluated reproductive parameters in Wistar-Unilever rats receiving dietary exposure to PTI G-2535, a characterized mixture of soy-derived isoflavones containing 45% genistein, 23% daidzein, and 4% glycitein.

Toxicologic evaluation of humectants added to cigarette tobacco: 13-week smoke inhalation study of glycerin and propylene glycol in Fischer 344 rats.

Glycerin (CAS no. 56-81-5) and propylene glycol (CAS no. 57-55-6) are commonly used as humectant ingredients in manufactured cigarettes to control and maintain the moisture content of the cut tobacco filler.

Preclinical toxicity studies of kahalalide F, a new anticancer agent: single and multiple dosing regimens in the rat.

Purpose: Kahalalide F (KF) is a new anticancer agent currently in clinical trials for solid tumors, including prostate cancer. During the preclinical development of this drug, the studies reported here were conducted to determine the acute and multiple dose toxicities of KF when administered intravenously (i.v.