In a previous paper, we reported that linseed oil heated under the inert gas showed a definite toxicity to mice and the toxic substance was considered to be 9- (2′-
n-propylcyclohexyl) nonanoic acid and/or 8- (2′-
n-butylcyclohexyl) octanoic acid with two double bonds. Moreover, the authors noticed that these cyclic fatty acids (Cy. FA) are carried to the liver after the absorption through the smallintestinal mucosa because those acids were found as the component fatty acids of liver lipids.
To know the degree of toxicity of these Cy. FA, linseed oil was heated under nitrogen gas and non-urea adduct forming fraction (NAFD Fr.) was separated and the 50% lethal dose (LD
50) of this fraction was determined by oral administration. It was found to be 9.84g/kg mouse and 33.35mmol/kg mouse.
In order to clarify the mechanism of acute toxicity of Cy. FA, several organs including the liver, lung, kidney, cerebrum, cerebellum and heart muscle were separated from the animals used for the determination of LD
50 and histopathological examinations were carried out.
Pathological changes were noticed mainly in the liver, lung, kidney and cerebrum. Among these changes, it was recognized that the changes of liver cells such as diffuse fatty degeneration, atrophy and necrosis were regarded only as the direct injurious effect of the Cy. FA. All the other findings were mainly attributed to non-specific circulatory impediment due to the shock that occurred secondary by administration of Cy. FA. In them there were the congestion of the liver and lung, necrosis of nerve cells in the cerebral cortex and degenerative epithelial changes of the distal tubules of the kidney.
These pathological examinations suggested that the acute toxicity of Cy. FA is realized through hepatic insufficiency resulted from toxic hepatocellular injury. Ischemic lesions of several organs caused by concomitant shock was also thought to be responsible for the death of animals.
View full abstract