The Vitamin B 12 - binding Systems of Isolated Intestine of the Rat

1. The fate in the rabbit of the following compounds has been investigated: benzohydrazide and its p-chloro, p-methyl and nand p-hydroxy derivatives; 1-acetyl-2-mand -p-hydroxybenxoylhydrazines and their anhydrides; 2-mand -phydroxyphenyl-5-methyl-1-oxa-3:4-diazoles. 2. Benzohydrazide, p-chlorobenzohydrazide and p-methylbenzohydrazide were lethal to rabbits in oral doses of just over 100 mg./kg. and were metabolized to the corresponding hippuric acids, which were isolated from the urine. Hydroxylation of the benzene ring and acetylation of the hydrazide group were not detected. 3. p-Hydroxybenzohydrazide and its acetyl derivative and I-acetyl-2-p-hydroxybenzoylhydrazinewere relativelynon-toxic andwere metabolized by direct conjugation with glucuronic and sulphuric acids. 4. m-Hydroxybenzohydrazide was intermediate in toxicity between benzohydrazide and phydroxybenzohydrazide, and was metabolized mainly by direct conjugation but partly by hydrolysis to m-hydroxybenzoic acid. 5. 2-mand -p-Hydroxyphenyl-5-methyl-oxa3:4-diazoles were relatively non-toxic and were metabolized by direct conjugation mainly with glucuronic acid. 6. It is suggested that the toxicity of benzohydrazide and its p-chloro and p-methyl derivatives is due to release of hydrazine in vivo.