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[Toxicological studies of a new cephamycin, MT-141. III. Its chronic toxicity in rats]
Abstract:
The chronic toxicity of MT-141 was studied in male and female Wistar rats with 182-time intramuscular injections of 50, 100, 200, 400, 800 and 1,600 mg/kg/day and the following results were obtained. MT-141 at all dosage levels caused no lethal effect on rats. However, it induced local inflammatory changes at the site of injection, such as hemorrhage, infiltration of round cells and fibrosis particularly at high doses. MT-141 at a high dose of 1,600 mg/kg/day decreased the gain of body weights in male rats but not in female rats. MT-141 increased the water intake in male and female rats from 8th day till last day after treatments with the doses more than 800 mg/kg/day. This compound also softened the feces and distended the cecum. MT-141 at the highest dosage level of 1,600 mg/kg/day increased the weight of kidney in male and female rats. Electron-microscopic findings revealed dissociation of basal infolding and dilatation of endoplasmic reticulum in renal epithelial cells of rats treated with the doses more than 800 mg/kg/day. These results suggest that MT-141 may induce renal toxicity in rats at these doses. The administration of MT-141 changed some toxicological parameters in gross and histopathological examinations and analyses of blood, serum and urine. However, the changes were accidental, independent on the dose and within physiological variations. It is concluded from above-mentioned results that the maximal "no effective" dose of MT-141 is 400 mg/kg/day in male and female rats.
Insights
Chronic toxicity studies of MT-141 in rats revealed local inflammatory changes and potential renal toxicity at high doses. The maximal no-observed-adverse-effect level was determined to be 400 mg/kg/day.
Area of Science:
- Toxicology
- Pharmacology
- Animal Studies
Context:
- MT-141 is a compound undergoing toxicological evaluation.
- Chronic toxicity assessment is crucial for understanding potential risks associated with drug or chemical exposure.
- Wistar rats are a common model organism for preclinical toxicity testing.
Purpose:
- To evaluate the chronic toxicity of MT-141 following repeated intramuscular injections in male and female Wistar rats.
- To determine the dose-response relationship and identify potential target organs for MT-141 toxicity.
- To establish the maximal no-observed-adverse-effect level (NOAEL) for MT-141.
Summary:
- MT-141 administration (50-1600 mg/kg/day) induced local inflammatory reactions at injection sites, particularly at higher doses.
- High doses (≥800 mg/kg/day) led to increased water intake, softened feces, cecal distension, and kidney weight increase.
- Renal toxicity was suggested by electron microscopy findings in kidney epithelial cells at doses over 800 mg/kg/day.
- The maximal no-observed-adverse-effect level (NOAEL) for MT-141 was identified as 400 mg/kg/day in both male and female rats.
Impact:
- This study provides critical data on the safety profile of MT-141, informing future research and development.
- Identifies potential target organs (kidneys) and adverse effects associated with chronic MT-141 exposure.
- Establishes a safe dosage threshold (NOAEL) for MT-141, essential for risk assessment and regulatory purposes.