Qualitative and quantitative toxicity of single and sequential sublethal doses of 5-fluorouracil in BDF mice

Qualitative and quantitative toxicity studies were conducted in BDF mice after ip injection of 33, 66, 134, and 200 mg/kg of 5-fluorouracil (5-FU) in daily doses for 1, 2, 3, or 4 consecutive days. Groups of five mice from each schedule and dose level provided blood and selected visceral organs for hematologic and histologic evaluation on posttreatment Days 1, 3, 6, 10, 14, and 21. Comparable groups of five mice were blood donors for biochemical evaluation of pooled plasma samples. The results indicated the onset, severity, and duration of injury to target organs and characterized the relationship of sublethal toxicity to drug dose and frequency of administration. Marrow suppression was reflected in peripheral erythropenia, thrombocytopenia, and leukopenia and also in medullary erythropenia and granulocytopenia. A transient elevation of plasma LDH, loss of body weight, and appearance of microscopic lesions of the gastrointestinal mucosae were additional indices of toxicity. The BDF mouse appears to provide a good qualitative and quantitative prediction of 5-FU toxicity, although the mouse apparently is quantitatively more sensitive than man.