HYPERVITAMINOSIS A 613 



(6) Age as a Factor in Toxicity. Hypervitaminosis A is produced with a 

 much lower dosage in young rats than in older animals. Thus, amounts as 

 high as 26,500 I.U./day'^o^ or 30,000 I.U./day'^a were not toxic in adult 

 rats, but reduced the metabolic rate.^^^ This is nearly twice the level 

 which is considered to be toxic in yomig rats. Inasmuch as the feeding of 

 50,000 I.U./day does brmg on definite hypervitaminotic symptoms (fatal 

 uterine hemorrhage) in the older animals, ^^^^ Nieman and Klein Obbink^^"® 

 consider that chronic oral toxicity begins at 25,000 I.U./day, and that the 

 lethal dose is ca. 50,000 I.U./day in adult rats. 



(c) Relative Toxicity When Vitamin A Is Administered Orally or Paren- 

 terally to Rats. The toxic dosage of vitamin A is apparently approxi- 

 mately the same when given subcutaneously as when administered orally. 

 Although Chauchard"''^ observed a reduction in nerve and muscle chro- 

 naxia and an excitation of the nervous system when only 3,500 I.U. of vita- 

 min A daily (two drops of a solution containing 120,000 I.U. per c.c.) were 

 injected subcutaneously, Weslaw et aZ.^"" stated that the lethal dosage of 

 \'itamui A is lower for subcutaneous than for oral administration. Bone 

 fractures appeared after rats had been injected daily for two weeks mth 

 25,000 I.U. of vitamin A; moreover, Poumeau-Delille^^^" observed a lethal 

 effect in rats following the daily administration of 100,000 I.U. to 400,000 

 I.U. subcutaneously for two weeks. Nieman and Klein Obbink"'*^ are of 

 the opmion that there is no great difference in toxicity between oral and 

 subcutaneous administration. However, Rodahl"'^ reported that larger 

 doses of vitamin A are required to produce equal intoxication when the 

 subcutaneous route is employed than when the vitamin is administered 

 orally. 



{d) Toxicity in Animals Other Than the Rat. The amount of vitamin A 

 required to produce toxic effects in animals other than the rat is to a great 

 extent in proportion to body weight. Thus, in the case of the mouse, Moll 

 and co-workers^^^'^'^^^^ observed a toxic effect when 4500 I.U. of vitamin A 

 (as Vogan) were given per day, while Ypsilanti^"- reported that adult mice 

 succumbed after 1.5 weeks when ca. 11,000 I.U. of vitamin A were injected 

 daily. This establishes the effective quantity of vitamin A to produce 

 toxicity in mice as about one-fourth that of rats. 



In the case of cats and rabbits, naturallj^, much larger amounts of vita- 

 min A can be tolerated. Moll and associates' ^^-'^^'^ stated that as much as 

 2,000,000 to 6,000,000 I.U. of vitamin A could be administered to animals 

 of these species without ill effects. Howe^•er, Wendt and Schroeder^^^' 



"" P. Chauchard, Compt. rend. soc. bioL, 137, 429-4.30 (1943). 



"" H. Ypsilanti, Klin. Wochschr., 14, 90-91 (1935). 



1173 H. Wendt and H. Schioeder, Z. Vitaminforsch., 4, 206-212 (1935). 



