Objective To assess the 4-week (28-day) toxicity of chloramphenicol (CAP) by oral administration in rats and obtain safety evaluation parameters.
Methods Healthy Wistar rats (n=80, sex ratio=1:1) were randomly divided into one control group (5 g/L sodium carboxymethyl cellulose) and three exposure groups (high, medium, and low dose groups administered with 60, 30, and 7.5 mg/kg CAP, with 20 rats for each group, respectively), with 20 rats for each group. All rats were orally administered daily for 28 consecutive days. Body weight, hematological indicators, and organ coefficient were recorded, the bone marrow smear and pathological changes of organ tissues were examined.
Results Compared with the control group, in the high dose group, male rats' body weight growth were inhibited after two weeks (P < 0.05), both male and female rats showed reduced mean corpuscular volume, total protein, and albumin (P < 0.05), and male rats' brain organ coefficient and male and female rats' kidney organ coefficients were increased; in the medium dose group, both female and male rats' showed reduced mean corpuscular volume, total protein, and albumin (P < 0.05), and male rats' kidney organ coefficient was increased (P < 0.05); no obvious changes were observed in the low dose group. The no-observed-adverse-effect level (NOAEL) of CAP was 7.5 mg/kg, the benchmark dose was 1.284 mg/kg, and the benchmark dose lower confidence limit was 0.804 mg/kg under the current experiment conditions. The acceptable daily intake of CAP for human was 8.04 μg/kg.
Conclusion CAP poses greater toxicity to male rats than to female rats. The study provides important data for the formulation of daily safety limits and risk assessment of CAP.
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