PubMed Health⌕ Search

Biomedical subjects

C B McCullough

Publications and source records attributed to C B McCullough.

6 recordsLinked to original sources
PubMed1992

Preclinical safety evaluation of dilevalol (SCH 19927), an antihypertensive agent, in the rat.

Dilevalol (SCH 19927) is an antihypertensive agent with direct vasodilating properties due to beta 2-adrenergic receptor agonist activity and nonselective beta-receptor blocking activity. In acute (single dose) oral and parenteral studies a low order of toxicity was observed. Clinical signs observed at the higher doses included salivation, prostration, tremors, and convulsions. In multidose oral studies dilevalol produced an increase in mean absolute and/or relative heart weights observed as early as 1 month in the high-dose (300 mg/kg) rats and at all dose levels (35, 90, 220 mg/kg) in rats treated for 1 year. There were no microscopic changes that could be associated with the change in heart weight. Intraalveolar macrophages were observed in the lung tissue of rats treated for 3 months or 1 year with an increase in relative lung weights noted in the high-dose (220 mg/kg) group treated for 1 year. In a 2-year rat study, no evidence of oncogenicity was observed. On the basis of these studies, dilevalol has a low order of toxicity and lacks oncogenic potential in the rat.

Animals↗
PubMedDate not supplied

Toxicologic and carcinogenic evaluation of Fenvalerate in the B6C3F1 mouse.

Groups of 50 male and 50 female B6C3F1 mice were fed dietary concentrations of 10, 50, 250 or 1250 ppm Fenvalerate for 2 years. Two groups of control mice, 50 per sex per group, received basal diet only. Mortality was increased and body weight was significantly decreased in male and female mice in the 1250 ppm treatment group. Mean body weight of female mice in the 250 ppm group was also generally lower than controls after the 60th week of feeding. Decreased albumin and increased glutamic oxaloacetic transaminase levels in mice fed 1250 ppm Fenvalerate were the only effects observed in the hematology and serum chemistry parameters examined. The only treatment related non-neoplastic pathologic effect observed in the study was multifocal microgranulomata in lymph nodes, liver and spleen of 1250 ppm male mice and 250 and 1250 ppm female mice. Less severe microgranulomatous changes were present in mesenteric lymph nodes of 50 and 250 ppm male mice. No statistically significant differences were observed in either the number or type of neoplasms in mice fed Fenvalerate diets when compared to concurrent controls. Thus, Fenvalerate was found not to be carcinogenic in B6C3F1 mice under the conditions of the test.

Animals↗
PubMedDate not supplied

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment.

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.

Animals↗