Comparative Studies on Toxicity of a New Streptomycin and Streptomycin Sulfate. ∗

Abstract

Investigators at the Northern Regional Research Laboratory of the U. S. Department of Agriculture have recently reported the isolation in pure state of a new antibiotic, hydroxystreptomycin. It is produced by an organism, isolated from Japanese soil, which they believe to be different from other streptomycin-producing strains. The new species has been designated as Streptomyces griseocarneus n. sp. On the basis of degradation experiments, Benedict et al.( 1 ) have assumed that the new antibiotic differs from streptomycin only in having a hydroxy group in place of one of the hydrogens of the streptose methyl group. Accordingly, they have assigned the name “hydroxystreptomycin” to the new member of the streptomycin series.

One mg analytically pure hydroxystreptomycin trihydrochloride, when assayed against Bacillus subtilis, NRRL B-765 (ATCC 6633), was found to be equivalent to 784 jug of streptomycin base. The hydroxystreptomycin trihydrochloride used in these studies was prepared in the Northern Regional Research Laboratory and assayed 596 μg/mg (76% pure). The streptomycin sulfate assayed equivalent to 621 μg of pure free base per mg and was 78% pure.†

In the present studies we have compared the acute toxicity of hydroxystreptomycin trihydrochloride against the toxicity of streptomycin sulfate in white mice by subcutaneous administration. Both samples of streptomycin were dissolved in glass distilled water just before use, and the pH of each solution was measured with a glass electrode. The pH of a 10% solution of hydroxystreptomycin trihydrochloride was 7.1; that of a 10% solution of streptomycin sulfate was 4.8, which was adjusted to 6.2 with solid sodium bicarbonate. At least 10 mice (sexes equally divided) were used at each dosage level in determining the toxicity of the 2 streptomycins. For hydroxystreptomycin trihydrochloride, 46 mice were used and for streptomycin sulfate, 60 mice were used. The approximate LD₅₀, as determined by Trevan's method, was found to be as follows: for hydroxystreptomycin trihydrochloride, 865 mg/kg; and for streptomycin sulfate, 970 mg/kg.