[Chronic toxicity test of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101) in beagle dogs (author's transl)].

Abstract

Male and female dogs, aged 17--21 months, were administered orall M 73101 (0, 60, 120 and 240 mg/kg/day), a new analgesic and antiinflammatory drug, for 27 weeks, and following recovery test was carried out for 5 weeks. Dead animals were not found throughout the experimental period. Body weight gain, and food and water consumption were not affected due to M 73101 administration. Except for a slight increase of vomitting in the highest dose, there were no abnormal symptoms. Biochemical examination showed the slight increase in serum alkaline phosphatase activity and free cholesterol level. Pathological examination revealed a dose-dependent increase of liver weight and hypertrophy of hepatocytes due to proliferation of smooth endoplasmic reticulum. In addition, mitochondria became irregularly large in the highest dose. There were no abnormal findings in the gastro-intestinal tracts except for an erosion of gastric mucosa, which was noted in a female dog treated 240 mg/kg/day of M 73101. From these results, it was suggested that the maximum non-toxic dose was 60 mg/kg/day or less, and the greatest safety dose was 120 mg/kg/day in beagle dogs.

• Authors: C Onodera, T Hayashi, I Makita, T Hashi, K Takeda, F Ozeki, H Shimazu
• Journal: The Journal of toxicological sciences (J Toxicol Sci) Vol. 4 Issue 3 Pg. 229-53 (Aug 1979) ISSN: 0388-1350 [Print] Japan
• PMID: 317111 (Publication Type: English Abstract, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzymes
• Proteins
• Pyridazines
• emorfazone

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (toxicity)
• Body Weight (drug effects)
• Dogs
• Drinking (drug effects)
• Eating (drug effects)
• Enzymes (blood)
• Female
• Growth (drug effects)
• Male
• Organ Size (drug effects)
• Proteins (metabolism)
• Pyridazines (toxicity)
• Time Factors