An assessment of chloramphenicol and thiamphenicol in the induction of aplastic anaemia in the BALB/c mouse

The potential of the antibiotics chloramphenicol succinate (CAPS) and thiam phenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was in vestigated. CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, dail y by gavage, for 17 days. At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for hac haematolog ical examination and haematopoietic stern cell assays. Both CAPS and TAP in duced significant reductions in red blood cell count, haematocrit and haemo globin values at day 1 post dosing; counts of colony-forming units-erythroi d and colony-forming units-granulocyte-macrophage were similarly significan tly decreased at this time. All these reduced parameters returned to,toward s normal at days 13 and 22, At days 41, 98 and 179, results for all haemato logical values and stem cell assays in both CAPS- and TAP-treated mice comp ared with the controls; there mns no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as wou ld be expected in a developing or overt bone marrow aplasia. We therefore c onsider that the administration of CAPS and TAP,,which have been associated with the development of aplastic anaemia in man, induce a reversible anaem ia, but not a chronic bone marrow aplasia, when given at haemotoxic dose le vels for 17 days in the BALB/c mouse. (C) 2000 Elsevier Science Ltd. All ri ghts Reserved.