ABSTRACT
A preliminary dose-range finding study and a 13-week toxicity study were performed in male cynomolgus monkeys with catena-(S)-[mu-[N a-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc] (Z-103, CAS 107667-60-7), a novel anti-peptic ulcer agent, as part of a safety evaluation program. In the preliminary ascending dose study emesis was observed in animals treated at 625 mg/kg and transient reductions in food intake with associated body weight loss in a male treated at 625 or 312.5 mg/kg. Plasma zinc levels were also increased in all animals treated at 625 or 312.5 mg/kg. As a result dosages of 0, 20, 63 and 200 mg/kg/day were selected for the 13-week toxicity study. In this study, treatment-related changes were confined to the 200 mg/kg/day dosage and consisted of emesis, piloerection and transient body weight loss in one animal, increased plasma zinc concentrations, and zinc and copper deposition in the liver and kidneys without any associated morphological change. The no observed effect level was estimated to be 63 mg/kg/day in this study.
Subject(s)
Anti-Ulcer Agents/toxicity , Carnosine/analogs & derivatives , Dipeptides/toxicity , Organometallic Compounds/toxicity , Animals , Body Weight/drug effects , Copper/metabolism , Eating/drug effects , Electrocardiography/drug effects , Eye Diseases/chemically induced , Eye Diseases/pathology , Female , Iron/metabolism , Macaca fascicularis , Male , Piloerection/drug effects , Vomiting/chemically induced , Zinc/metabolism , Zinc CompoundsABSTRACT
Anoura geoffroyi (Chiroptera, Phyllostomidae, Glossophaginae), Geoffroy's hairy-legged long-tongued bat, were collected from September 1984 to August 1985, and these bats were found to breed seasonally in the wild on Trinidad, West Indies, at 10 degrees N latitude. Histological examination of these samples indicated that females became pregnant in July or August, and young were born in late November or early December. The testes and epididymides were small from September to mid-April, increased threefold in weight between mid-April and late May, reached a peak weight in July, and decreased in weight in August. Spermatogenesis occurred throughout the testes of males captured from May to August. In 1990, the timing of parturition in females that gave birth in the laboratory to young conceived in the wild was similar to the timing in the field in 1984-1985. Groups of 10-13 males were subjected in the laboratory to (i) a gradually changing, civil twilight photoperiod that mimicked the natural cycle of annual change at 10 degrees N latitude, (ii) the same gradually changing cycle of photoperiod accelerated to a six-month period, or (iii) a constant photoperiod (light 12:54 h: dark 11:06 h). These treatments began in mid-December, four months before the initiation of testicular recrudescence in the wild. In all three groups, testicular volume remained low until April, and then increased two- to threefold between late April and late June, rising to a peak in July, as occurred in the wild.(ABSTRACT TRUNCATED AT 250 WORDS)
