THE CHRONIC ORAL TOXICITY OF SODIUM CHLORIDE AT THE RANGE OF THE LD50(0.1L)

Abstract

The chronic toxicity of sodium chloride was studied in young male albino rats given 2.57–6.14 g/kg in water by stomach tube once daily for 100 days or until half the animals had died, whichever occurred first. The LD50(0.1 L) or daily dose which killed 50% of the animals after administration for 100 days, i.e. 1/10 the animal's normal lifespan (0.1 L), was 2.69 ± 0.12 g/kg. It is suggested that the LD50(0.1 L) expressed as a percentage of the acute LD50 would provide a useful index of chronic toxicity; this is termed the C/A LD50(0.1 L) index, C meaning chronic and A acute. The value of this index was 72 for sodium chloride, 62 for benzylpenicillin, and 13 for atropine. Rats which survived doses of the order of the LD50(0.1 L) had no change in food intake but lost some body weight as daily dose increased. They had a dose-dependent polydipsia and polyuria. In the initial month of drug administration the rats developed a slight fever, proteinuria, and alkalinuria, and in the terminal month a slight hypothermia and aciduria, all of which were statistically significant but not dose-dependent. When deaths occurred within the first week or two, they were similar clinically and pathologically to those seen in studies on the acute oral toxicity of sodium chloride. Other deaths followed a period of hypothermic cachexia and were due to bronchopneumonia, associated with hepatitis, nephritis, arteriolitis, and occasionally encephalopathy, and accompanied by degeneration of the thymus, adrenals, and testes. Animals which survived for 100 days had developed a hypertrophied gastrointestinal mucosa but most other organs had lost weight, and there was some arteriolitis, myocarditis, pulmonary edema, and nephritis.