血液制品中残留辛酸/根的急性毒性试验

Acute toxicity of caprylic acid/caprylate residues in blood products

目的探讨酸性条件下血液制品中残留辛酸/根的急性毒性。方法配制辛酸浓度分别为0.25、2.5和10 mg/ml的10%静注人免疫球蛋白(pH 4)溶液,另设阴性对照组(0.9%NaCl),经尾静脉注射SD大鼠,每只大鼠等容量注射,注射剂量为4.5 ml/只。每天观察1次大鼠的形态外观、四肢活动和行为方式,并记录大鼠摄食量,共14 d;给药后第3、7、14天称量大鼠体重,计算体重增长率;给药后第14天解剖所有动物,观察内脏器官病变情况。结果辛酸浓度为10 mg/ml时,大鼠出现了明显的应激反应、血尿和行为特征的改变,体重增长率明显降低(P<0.01),解剖后发现有较明显的肺部病变;辛酸浓度为0.25和2.5 mg/ml时,未表现出明显的应激反应和行为特征异常,解剖观察均与阴性对照组无明显差异。结论 10%静注人免疫球蛋白(pH 4)溶液中辛酸/根浓度为2.5 mg/ml时不会对大鼠造成急性毒性,为酸性条件下血液制品中辛酸/根残留的安全性评价提供了实验数据,也为后期制定10%静注人免疫球蛋白(pH 4)中残留辛酸/根的限量标准提供了参考。

Objective To investigate the acute toxicity of caprylic acid/caprylate residues in blood products under acidic condition. Methods The 10% intravenous immunoglobulin （IVIG）（pH 4） solution at caprylate concentrations of 0. 25, 2. 5 and 10 mg/ml were prepared and injected i. v. into SD rats, 4. 5 ml for each, using 0. 9% sodium chloride solution as negative control. The rats were observed for physical and mental features, activity of limbs and behavioral pattern, and recorded for food intake, once a day for 14 d. The rats were weighed on days 3, 7 and 14 after injection, based on which the increasing rate of bodyweight was calculated. All the rats were dissected on day 14 after injection, and observed for pathological change of organs. Results Obvious stress reaction, hemuresis and change of behavioral pattern were observed in the rats injected with IVIG at a caprylate concentration of 10 mg/ml, while the increasing rate of bodyweight decreased signi-ficanfly （P 〈 0. 01 ）, and obviously pathological change was observed in lung. However, when the caplylate concentrations were 0. 25 and 2. 5 mg/ml, no obvious stress reaction or normal behavior was observed, the and result of pathological examination showed no significant difference with that in negative control group. Conclusion The caprylic acid/caprylate residues at a concentration of 2. 5 mg/ml in 10% IVIG （pH 4） caused no acute toxicity in rats, which provided an experimental basis for evaluation of safety of caprylic acid / caprylate residues in blood products at acidic condition, and a reference for determination of quantitative limit of caprylic acid/caprylate residues in 10% WIG （pH 4）.