2-YEAR TOXICITY STUDY ON COUMARIN IN THE BABOON

Groups of male baboons were fed 0 (control), 2·5, 7·5, 22·5 or 67·5 mg coumarin/kg/day for between 16 and 24 months. No adverse effect was found on histological examination of a wide variety of tissues or in the biochemical or histochemical examinations of the liver. Ultrastructural examination of the liver revealed dilatation of the endoplasmic reticulum, a finding consistent with the early stages of intracellular oedema in hepatocytes, in three of the four animals fed 67·5 mg coumarin/kg/day, and a significant increase in liver weight expressed relative to body weight was recorded in this group. The dilatation was first evident after 10 months and showed an increase in severity and extent at 16 months and 2 yr. This finding indicates a no-effect level of 22·5 mg/kg/day. However, if conventional histological evidence alone were considered, 67·5 mg/kg/day would constitute the no-effect level. © 1979.