title: A toxicologic evaluation of ethyl fluclozepate (CM 6912).
abstract: This paper presents the results of acute, subacute, and chronic toxicity studies on ethyl fluclozepate (CM 9612). Acute toxicity was studied in rats and mice of both sexes by oral and intraperitoneal routes. This study established the very low toxicity of this compound. The LD0 by the oral route in these two species is at least higher than 4 g/kg, whereas by the intraperitoneal route the compound has a LD50 of 645 mg/kg at the lowest level. The 3- and 6-month subacute and chronic toxicity studies were carried out in baboons and in rats. The only effects observed during these studies were sedation in the baboon, a slight decrease of the heart rate also in baboons (6 months), and the presence of foam cells in rat lungs after only 6 months of treatment. The sedation and the decrease of heart rate are not toxic effects, but rather the consequence of the anxiolytic activity of CM 6912. Pulmonary foam cells occurred in rats only after a long period of treatment (6 months) and at very high dose levels. This lesion was considered evidence of pulmonary phospholipidosis, a change known to occur frequently with compounds of this nature.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005487:Foam Cells / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010215:Papio; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C029617:ethyl loflazepate