572 NIACIN 



effect on toxicity. Brazda and Coulson^ found the following LDso's in rats 

 given the following compounds subcutaneously (grams per kilogram) : nico- 

 tinic acid 5.0, trigonelline 5.0, nicotinamide 1.68, N^-methylnicotinamide 

 2.4, N,N-diethylmcotinamide (coramine) 0.24, coramine methochloride 

 1.90, pyridine 1.00, and pyridine methochloride 0.28. Nicotinamide, cora- 

 mine, and their N^-methyl derivatives caused paralysis of the respiratory 

 centers. Pyridine and its methyl derivative caused deep anesthesia. Karasek 

 and coworkers* reported considerably lower LDso's for nicotinic acid in 

 mice (1.8 g. per kilogram) than those recorded above. They also found that 

 as little as 0.4 g. per kilogram caused preglomerular, corticomedullary, and 

 interstitial hemorrhages in rats. Unna,^ on the other hand, fed 1.0 g. per 

 kilogram of sodium nicotinate daily for 40 days to rats and observed no 

 effect on growth or on tissue histology. Chen and associates^ found no 

 abnormalities in mice injected with 0.5 g. per kilogram daily for four weeks. 

 McCrea^ gave 0.05 to 0.2 g. of nicotinic acid to rats intraperitoneally for 

 24 days with no ill effects. Unna^ suggested that the toxic effect of nico- 

 tinic acid and its amide may be due, at least in part, to simple osmotic 

 effects, since the same volumes of a solution of sodium chloride equimolec- 

 ular to the sodium nicotinate solutions caused some deaths in their animals. 



2. Dogs 



Dogs tolerated up to 2 g. of sodium nicotinate per kilogram of body 

 weight orally for 35 to 63 days without toxicity .^ Chen and associates^ gave 

 dogs 1 g. of nicotinic acid per day orally for eight weeks with no toxic 

 symptoms, although 2 g. per dog per day produced marked toxic symptoms 

 in 11 to 20 days. 



3. Other Species 



Chickens tolerated sodium nicotinate up to 2 g. per kilogram of body 

 weight orally each day for periods as long as two months.- The minimum 

 lethal dose of sodium nicotinate by injection into guinea pigs was 3.5 g. 

 per kilogram. Rabbits tolerated 0.02 to 0.06 g. per kilogram per day for 

 ten days.^ As much as 5.4 g. of nicotinic acid per day has been given orally 

 to man with no harmful effects.^ Hawker^ reported a 20% increase in 

 ovary weight and a decrease in pituitary gland weight of virgin guinea 

 pigs receiving nicotinic acid in amounts up to 150 mg. daily. This report 

 must be accepted with reservations because of the very small number of 

 animals used. 



6 F. Karasek, O. Poupa, and V. Jelinek, Minerva med. 39, 28 (1948) [C. A. 43, 6291 

 (1949)]. 



6 F. D. McCrea, /. Pharmacol. Exptl. Therap. 63, 25 (1938). 



7 C. M. Kurtz, O. S. Orth, and G. Sepulveda, Wisconsin Med. J. 44, 761 (1945). 



8 R. W. Hawker, Med. J. Australia I, 872 (1946). 



