Studies on Brown FK. V. short-term feeding studies in the rat and pig

Brown FK was administered to rats at dietary levels of 0.0 (control), 0.001, 0.01, 0.1 and 1.0% for up to 21 wk and to miniature pigs in daily doses of 0, 100, 250 and 500 mg/kg for 24 wk. No effect was observed in either species with respect to growth rate, food consumption, organ weights or liver and kidney function. Apart from the observations described below, no histopathological changes were seen in any organs of the rats or pigs and no significant haematological abnormality was noted in either species. In rats, lipofuscin deposits were observed in the heart, skeletal muscle, kidney tubules, liver parenchymal cells and Kupffer cells at the 1.0% dietary level, in females at 13 wk and in both sexes at 21 wk. At this dietary level, one male showed myocardial changes similar in every respect to those seen following repeated daily administration of Brown FK by stomach tube and reported in paper III of this series (Grasso, Gaunt, Hall, Golberg & Batstone, Fd Cosmet. Toxicol. 1968, 6, 1). After 150 days' treatment, lipofuscin deposits were seen in renal tubular cells also at the 0.01 and 0.1% dietary levels. Deposition of lipofuscin was the principal change observed in pigs. It affected mainly the liver, in which it was observed in both males and females at all dosage levels of Brown FK and was accompanied by increased lysosomal enzyme activity, more marked at the higher dose levels. Lipofuscin was seen also in the heart in males, and here it was associated with an increased acid-phosphatase activity. It was not detectable in the heart in females. Lipofuscin was also present in the kidneys of both sexes, at the highest dose level in females and at all levels in males.