cytellin and 3-chlorocholest-5-ene

3 beta-Chlorosteroids, such as cholesteryl beta-chloride and sitosteryl beta-chloride, are formed during the production of protein hydrolysates, which are useful flavour enhancers. These chlorinated steroids may also attract attention as environmental contaminants if they are released from liquid crystal display devices. The effects of orally administered 3 beta-chlorosteroids were tested in female NMRI mice. The animals were fed cholesteryl beta-chloride or sitosteryl beta-chloride at doses of 1 mg and 10 mg/animal/day, that is, 33 mg and 330 mg/body weight/day, over a period of 3 months. Feed intake, body weight and organ weights of the animals, as well as concentration of 3 beta-chlorosteroids in faeces and various organs and tissues showed that cholesteryl beta-chloride and sitosteryl beta-chloride are not acutely toxic compounds. However, chronic toxicity cannot be excluded because small amounts of 3 beta-chlorosteroids, in particular cholesteryl beta-chloride, were absorbed by the intestinal tract and accumulated in adipose tissue. Histopathological examination of sections of organs and tissues showed no indication of irreversible cell damage in the stomach, duodenum, liver, kidneys and spleen caused by the chlorinated steroids.

Topics: Absorption; Adipose Tissue; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Chemical and Drug Induced Liver Injury; Cholestenes; Duodenum; Female; Food Contamination; Hyperplasia; Hypertrophy; Intestinal Absorption; Liver; Liver Diseases; Lung Diseases; Mice; Sitosterols; Stomach

A method for the analysis of 3 beta-chloro steroids by high-performance liquid chromatography is described. These compounds are known to occur in commercial protein hydrolysates. The gastro-intestinal absorption, distribution and metabolism of chlorinated steroids were studied after their intragastric application to mice. At 2 hr after stomach intubation of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro-[4-14C]stigmast-5-ene, large proportions of radioactivity had passed through the small intestine and were found to be concentrated in the contents of the caecum and colon. Very small amounts of 3 beta-chlorocholest-5-ene were absorbed by the intestinal mucosa and distributed to organs and tissues outside the alimentary canal, whereas intestinal permeability of 3 beta-chlorostigmast-5-ene was negligible. After administration of labelled 3 beta-chlorocholest-5-ene, the highest value of radioactivity, 120 Bq/g tissue, outside the intestinal tract was detected in liver. Altogether, less than 0.5% of the total radioactivity applied to the animals was found to be transported through the intestinal wall and less than 0.5% of the total radioactivity was detected in various metabolites. In general, 3 beta-chlorostigmast-5-ene was transported in smaller proportions and metabolized to a lesser extent than the corresponding cholesterol derivative. Moreover, metabolites of the two radioactive substrates formed by enzymatic attack of enteric micro-organisms were not detected in the contents of the caecum and colon. It appears that 3 beta-chlorinated steroids are fairly stable products that are metabolized poorly both by the cells of the intestinal mucosa and by enteric micro-organisms of mice.

Topics: Animals; Cholestenes; Chromatography, High Pressure Liquid; Feces; Female; Glycine max; Intestinal Absorption; Intubation, Gastrointestinal; Lipids; Mice; Sitosterols; Steroids, Chlorinated; Tissue Distribution