Haemotoxicity of chloramphenicol succinate in the CD-1 mouse and Wistar Hanover rat

Abstract

<jats:p> 1 Chloramphenicol has been widely used in the treatment of serious infections including typhoid fever and meningitis. However, the drug is haemotoxic in man inducing firstly, a reversible, dose-dependent anaemia which develops during treatment, secondly, an often fatal aplastic anaemia with pancytopenia and acellular marrow, and thirdly, leukaemia. 2 We investigated the haemotoxicity of chloramphenicol succinate (CAPS) in female CD-1 mice in repeat dose studies, to compare the response with the reversible anaemia reported in man. Studies in male Wistar Hanover rats were also carried out. 3 CAPS was gavaged daily to mice at dose levels from 800–2000 mg/kg for seven days. Values were significantly reduced for reticulocytes at 1700 and 2000 mg/ kg, and for erythrocytes (RBC), haematocrit (HCT), and haemoglobin (Hb) at 2000 mg/kg. Platelet and white blood cell (WBC) counts were unaffected. 4 Mice were dosed with CAPS at 1400 mg/kg for 10 days and sampled at 1, 4 and 15 days after the last dose. At day 1 post dosing, RBC, HCT and Hb values were significantly reduced, but returned to normal (or above normal) by day 4 or 15. 5 CAPS from 2000–4000 mg/kg was gavaged to rats daily for 19 days. Hb values were significantly lower at 3600 and 4000 mg/kg; reticulocytes were not reduced. WBC and platelet counts, in general, were unaffected. 6 Levels of apoptosis in marrow mononuclear cells were increased in CAPS-treated mice, but not in CAPS-treated rats. Serum biochemistry parameters, in general, showed few changes of toxicological significance. 7 We conclude that the administration of CAPS to CD-1 mice induced haematological changes showing close parallels with the chloramphenicol-induced reversible anaemia seen in man. </jats:p>

Animal Models for Acquired Bone Marrow Failure Syndromes

“…In these animals, there were usually dose-related reductions in reticulocytes, erythrocytes, hematocrit, hemoglobin, CFU-erythroid, and CFU-GM, but these hematological parameters tend to return to normal without intervention. [30][31][32][33][34][35] A significant difference between strains was observed in response to chloramphenicol succinate toxicity. Inbred C3H/He, CBA/Ca, BALB/c, and B6 mice were demonstrated to be much more susceptible to chloramphenicol succinate toxicity than outbred CD1 mice.…”

“…29 More recently, a series of studies failed to produce a chronic aplastic anemia mouse model by using chloramphenicol succinate. [30][31][32][33][34][35] Administration of chloramphenicol succinate at 800 mg/kg to 2000 mg/kg for 7 days to CD1 mice, 31 2000 mg/kg/day for 17 days to BALB/c mice, 32 2000 mg/kg/day to 4000 mg/kg/day for 19 days to Wistar Hanover rats, 31 and 2500 mg/kg/day to 3500 mg/kg/day for 9 days in guinea pigs 35 all induced reversible anemia, but not irreversible aplastic anemia. In these animals, there were usually dose-related reductions in reticulocytes, erythrocytes, hematocrit, hemoglobin, CFU-erythroid, and CFU-GM, but these hematological parameters tend to return to normal without intervention.…”

A new model of busulphan‐induced chronic bone marrow aplasia in the female BALB/c mouse

“…Blood samples and bone marrow suspensions were analysed with a Technicon H*1 hamatology analyser (Bayer Diagnostics UK Ltd, Newbury, Berks) with mouse‐specific software (Technicon, Swords, County Dublin, Eire), as described previously (Turton et al . 1999, 2000).…”

Scientific Opinion on Chloramphenicol in food and feed

“…Turton et al (1999) gavaged CD-1 mice with chloramphenicol succinate at doses from 800 to 2 000 mg/kg b.w. per day for seven days and observed reduction of reticulocytes in the medium-dose group (1 700 mg/kg b.w.…”