The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.
Pesticides are biologically active substances that are significant environmental contaminants. Only a few of the many pesticides have been subjected to short- or long-term carcinogenicity tests. To date, 16 of them have been identified as hepatocarcinogenic agents in animals, usually mice. However, their cancer-inducing effect in humans has not been completely proved. The use of short-term screening tests (first of all the Salmonella-microsome test) for routine screening of pesticides on a large scale is highly recommended. The herbicide 2,4,5-trichlorophenoxyethanol (TCPE) containing different amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was tested for carcinogenicity in Swiss mice. TCPE enhanced liver tumors in males but TCDD did not affect liver tumor incidence. The occurrence of liver tumors was shown to be dose-dependent. There was no correlation between the results of in vivo carcinogenicity studies and the induction of aryl hydrocarbon hydroxylase and biphenyl 2-hydroxylase activities.
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