Studies on Brown FK. III. Administration of high doses to rats and mice

Abstract

Acute oral toxicity studies with Brown FK gave LD 50 values greater than 2 g/kg and 8 g/kg in mice and rats respectively. The values for intraperitoneal injection were 1·5–2 g/kg in mice and 0·75–1·15 g/kg in rats. When repeated daily oral doses ranging from 0·1 to 2 g/kg were given to rats, a precipitate weight loss and a vacuolar myopathy of the heart and skeletal muscles accompanied by lipofuscin formation occurred with doses of 0·5 g/kg and over. At the highest dose employed (2 g/kg) there was also hepatic centrilobular necrosis and renal tubular degeneration. Pretreatment with antibiotics reduced the incidence of muscle lesions. Repeated intraperitoneal injection did not have any effect on the heart or skeletal muscle. Only two of the six components of Brown FK, compound I (2,4-diamino-5-( p-sulphophenylazo)toluene) and compound II (1,3-diamino-4-( p-sulphophenylazo)benzene), were found to produce muscle damage after repeated oral doses of 0·5 g/kg. Comparable doses of mixtures containing the other components as well as I or II were considerably less toxic. After daily oral doses of 1 g/kg, muscle lesions were found in rats, rabbits and guinea-pigs, but none were seen in mice or hamsters. The results suggest that the intestinal microflora is responsible for the breakdown of the components of Brown FK to toxic products. Variations between species and between animals of the same species may be due to qualitative and quantitative differences in the intestinal microbial population.