ベンフレセートの毒性試験の概要
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概要
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Technical benfuresate was of very low acute oral and dermal and low acute inhalational toxicity to rodents. Repeat dose studies in the rat, mouse and dog showed the material to be well tolerated with the maximally tolerated doses of 318, 561 and 400 mg/kg/day, respectively. Histopathology showed the kidney to be the main target organ in all three species. The principal findings in the kidney, found following subchronic exposure in the rat and following subchronic/chronic exposure in the mouse and dog were papillary necrosis and dilatation and/or degeneration of the proximal tubules (and collecting ducts in rats). These findings were associated with elevated kidney weights in the rat and dog, pyelonephritis in the mouse and dog and interstitial nephritis in the rat and dog. The liver was also a target organ at dose levels above the MTD in the rat and mouse as indicated by swelling of the periportal hepatocytes and centrilobular enlargement, respectively. There was no evidence of oncogenicity in the mouse or rat and the NOEL in the most sensitive species, the rat, was 3 mg/kg/day. Technical benfuresate was non-genotoxic, non-irritant, had no effect on reproduction or fertility and was not a skin sensitiser. The compound was rapidly and completely absorbed. Tissue residues were low and declined rapidly. The highest levels were found in the kidney and fat after 6 hr. Metabolism of the compound in the rat was rapid and complete as was elimination, which was predominantly via the urine. The compound showed weak pharmacological effects on the nervous system following oral administration and the circulatory and respiratory systems, but only after intravenous dosage. The acute toxicity of metabolites, process intermediates and formulations of benfuresate were low. It is concluded therefore that under the recommended conditions of use both technical benfuresate and formulations are unlikely to present hazard to operators or the public who may consume negligible residues from treated produce.
- 日本農薬学会の論文
- 1995-05-20
日本農薬学会 | 論文
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