Toxicity of Vitamin B 6

Abstract

The existence of vitamin B₆, the rat acrodynia factor was first established by György. 1 The compound has since been isolated 2 , 3 4 , 5 and synthesized. 6 , 7 Sufficient amounts of the synthetic vitamin, 2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine, are now available for the study of the effect of large doses in animals.

The following investigation of the toxicity of the synthetic vitamin B₆ has been carried out on rats, dogs, and monkeys. All animals were maintained on completely adequate diets with the exception of one series of rats which was kept on a modified Sherman-Spohn diet supplemented with 40 micrograms of thiamin and of riboflavin per rat per day. This group developed typical symptoms of rat acrodynia.

The vitamin was administered both as the base and as the hydrochloride. The solutions of the base are neutral in reaction; those of the hydrochloride react acid, the pH of a 20% solution being 2.3.

Acute toxicity following oral and subcutaneous administration was studied in rats, 10 animals being used for each dose level. Doses up to 1 g per kg were tolerated without untoward effects. Higher doses produced rather peculiar toxic symptoms. Twenty-four hours after dosing, the rats showed tonic convulsions, the hind limbs stretched away from the body, the fore limb bent under the body and the paws closed. Between convulsive attacks the animals were able to move slowly and awkwardly and showed marked impairment of the righting reflexes. Animals receiving sublethal doses exhibited these convulsive reactions over a period extending from several days to as much as 3 weeks. With lethal doses the animals died in tonic convulsions within 36 to 72 hours. The L.D. 50∗ following subcutaneous injection was 3.1 g per kg for the free base and 3.7 g per kg for the hydrochloride.