612 IX. CAROTENOIDS AND VITAMINS A 



Moore and Wang"^* that the lower limits of acute toxicity in young rats 

 are within the range of 40,000 to 90,000 I.U., 50,000 I.U. being the average 

 figure when the vitamin is administered parenterally. On the other hand, 

 Rodahl"^^ believes that if no puncture of the blood vessels occurs during 

 the injection of the vitamin A, and hence no fat embolism develops, a 

 single injection of a high-potency concentrate of 1,000,000 I.U. will prc^ 

 duce no effect. 



In the case of orally-administered vitamin A, the lethal dose given in oily 

 solution to rats is reported by v. Drigalski"*^ to be ca. 120,000 I.U. Ro- 

 dahl"^* obtained only a temporary effect in adult rats when the dose was 

 1,600,000 I.U. 



b. Chronic Toxicity in the Rat. (a) The Level of Toxicity in Young Rats. 

 Various investigators have demonstrated that the onset of toxicity in young 

 rats, as evaluated by different symptoms, occurs at ca. 10,000 to 12,500 I.U. 

 per day, and at 20,000 to 25,000 I.U. per day for the lethal dose. ""^ Thus, 

 although Bell et al.^^^'^ were unable to demonstrate toxicity when 13,500 

 I.U. of vitamin A were given daily, Studer^^^^ did report that a change in 

 the blood pattern occurred in the rat after two days when a dosage of 10,000 

 I.U./day was given. Confirmatory e\adence of this latter figure was ob- 

 tained by Rodahl.^^^^ Van Metre"^ noted fractures and disturbances of 

 bone growth in rats which had received 1250 I.U. per g. body weight per 

 day, while Guerrant^^^ noted some delay in the growth of rats given 8,800 

 I.U. of this vitamin per day. When rats received 13,500 I.U. of vitamin 

 A/day, they survived, but growth was arrested and their pelts became 

 coarse. This was defined as a "subtoxic dose."^^°^ On the other hand, more 

 severe symptoms such as loss of weight and skin lesions were shown by 

 Weslaw et aZ.^^^° to occur in young rats, when the vitamin A intake, as Vo- 

 gan or Cresavit, was at a level of 20,000 I.U./day. (Vogan and Cresavit 

 Merck are sesame oil solutions of vitamin A obtamed from A-rich fish liver 

 oils). Harris and Moore^^^^ observed loss of weight, marasmus, lack of 

 appetite, difficulty in walking and sometimes paralysis in rats given 25,000 

 times the minimum dose of vitamin A. According to Wolbach and Bes- 

 ggy^io4o aj^(^ Moore and Wang,'^^" bone fractures occurred within seven to 

 twenty days when young rats were fed 25,000 to 50,000 I.U./day. 



11^5 T. Moore and Y. L. Wang, Biochem. J., 39, 222-228 (1945). 



116S W. V. Drigalski, Klin. Wochschr., 12, 308-309 (1933). 



116' M. E. Bell, E. Gregory, and J. C. Drummond, Z. Vitaminforsch., 2, 161-182 

 (1933). 



1168 T. E. Van Metre, Johns Hopkins Hosp. Bull, 81, 305-311 (1947). 



ii«9L. J. Harris and T. Moore, Biochem. J., 22, 1461-1477 (1928); 23, 1114-1121 

 (1929). 



i"o T. Moore and Y. L. Wang, Biochem. J., 37, viii-ix (1943). 



