A Note on Bactericides in Solutions for Injection

Abstract

ONE of the methods described in the British Pharmacopeia for sterilising aqueous solutions is " heating with a bactericide." The bactericides recommended are 0.2 per cent. solution of chlorocresol (p-chloro-mcresol) or 0.002 per cent. solution of phenylmercuric nitrate. Davis and Davison' have shown by means of the filtration sterility test that relatively low concentrations of bacterial spores may survive after heating with 0.2 per cent. solution of chlorocresol. In the discussion on this paper, Hartley2 pointed out that chlorocresol in concentrations of 0.2 per cent. or less was inadequate for sterilisation and asked the authors to suggest a more suitable concentration.Wien3 determined the chronic toxicity of 0.25 per cent. solution of chlorocresol and of 0.002 per cent. solution of phenylmercuric nitrate by experiments on rabbits. The purpose of the experiments described in this paper was to determine the chronic toxicity of higher concentrations so that if the present concentrations are found inadequate, appfopriatc concentrations may be recommended. CHLOROCRLSOLIn the following experiments 0.4 per cent solution in distilled water, prepared by dissolving in hot water and cooling to room temperature, was used. The experiment was made on two rabbits. Each received daily 5 ml. of the 0.4 per cent solution subcutaneously. A third rabbit used as control received daily 5 ml. of distilled water subcutaneously. The urine was examined every other day by qualitative tests for albumen and blood.Once a week the urine was examined for deposit of epithelial cells or casts.All the results were negative. The blood was examined once a week and no pathological abnormalities were found in the red or white cell counts. The variations in the white cell count were the same as in the control animal. Values are given for each week in Table I. The appearance of the rabbits remained normal in every way. There was no diarrhm except in the case of the control rabbit which recovered in a day with careful feeding.Histological examination of tissues. The liver and kidneys were examined. Sections were stained with eosin. Microscopic examination showed that all the specimens were normal. The skin at the site of injection showed no degenerative changes.Eflect of intracisternal injection on the presure und cell content of the cerebrospinal fluid. The general experimental procedure was similar to that described in the literature (Bedford3p4). 1 ml. of 4 per cent. solution was introduced into the cisterna magna of three dogs. The animals, after recovery from the amsthetic, were allowed to survive for 6 hours. The results are shown in Table 111. 101Chronic Toxicity as determined by experiments on rabbits.