首页|1,2-丙二醇的急性毒性、短期毒性和溶血试验

1,2-丙二醇的急性毒性、短期毒性和溶血试验

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目的 为1,2-丙二醇(PG)的临床应用提供毒理学依据。方法 将60只ICR小鼠随机分为对照组(等量氯化钠注射液)和8 750,9 475,10 250,11 100,12 000 mg/kg PG剂量组,均单次尾静脉注射相应药物,观察中毒反应和死亡情况,计算半数致死量(LD50)。将80只Wistar大鼠分为对照组(等量氯化钠注射液),高、中、低剂量组(6 666,3 333,1 666 mg/kg PG),均连续腹腔注射相应药物16 d,观察大鼠的一般状态和测定其体质量,结束后检测血常规、血生化指标,计算脏器系数,并进行组织病理学检查。采用肉眼观察法和分光光度计法考察PG的体外溶血性,并计算溶血率。结果 给药后,小鼠毒性反应主要表现为抽搐、四肢强直、呼吸困难、小便失禁,剂量越大反应越明显。PG对小鼠的LD。为10483 mg/kg。与对照组比较,高剂量组雄性大鼠的血清丙氨酸氨基转移酶、肌酐和雌性大鼠的血清尿酸均显著升高(P<0。05),雌性大鼠的肝脏、肺脏系数均显著升高(P<0。05),雌性大鼠胃系数显著降低(P<0。05)。组织病理学检查结果显示,高剂量组大鼠肝脏、肾脏未见明显的组织学改变。25%PG溶液管未见溶血现象发生;50%,75%,100%PG溶液管均观察到上层偏红色,温育时间越长,浓度越高,颜色越深,溶血率均高于5%。结论 PG对小鼠的LD50值较高,且未对大鼠产生明显毒性作用,PG安全剂量高。但PG存在一定溶血风险,需控制临床用药速度和时间,以保证用药安全。
Acute Toxicity,Short-Term Toxicity and Hemolysis Test of 1,2-Propanediol
Objective To provide toxicological evidence for the clinical application of 1,2-propanediol(PG).Methods A total of 60 ICR mice were randomly divided into the control group(equal volume of Sodium Chloride Injection)and PG dose groups(8 750,9 475,10 250,11 100,and 12 000 mg/kg),the corresponding drugs were injected into the tail vein once,and toxic reactions and mortality were observed.The LD50 was calculated.Eighty Wistar rats were divided into the control group(equal volume of Sodium Chloride Injection),high-,medium-,and low-dose groups(6 666,3 333,1 666 mg/kg of PG),and they were continuously injected with the corresponding drugs intraperitoneally for 16 d.The general condition of the rats was observed and their body mass was measured.After the end of the experiment,the blood routine and biochemical indicators were detected,organ coefficients were calculated,and histopathological examination was performed.The in vitro hemolysis of PG was investigated by visual observation and spectrophotometry,and the hemolysis rate was calculated.Results After the administration,the toxic reactions in mice mainly manifested as convulsions,limb rigidity,difficulty breathing,and urinary incontinence,with more pronounced reactions at higher doses.The LD50 of PG for mice was 10 483 mg/kg.Compared with those in the control group,the serum alanine aminotransferase and creatinine of female rats,and serum uric acid of male rats in the high-dose group increased significantly(P<0 05),the liver and lung coefficients of female rats in the high-dose group increased significantly(P<0.05),while the stomach coefficient of female rats in the high-dose group decreased significantly(P<0.05).The histopathological examination results showed no significant histological changes in the liver and kidneys of rats in the high-dose group.No hemolysis was observed in the 25%PG solution tube,while the upper layer of the 50%,75%,and 100%PG solution tubes was slightly red.The longer the incubation time,the higher the concentration,and the darker the color.The hemolysis rate was all higher than 5%.Conclusion PG has a high LD50 value in mice and does not have a significant toxic effect on rats,indicating a high safe dose of PG.However,there is a certain risk of hemolysis in PG,and it is necessary to control the clinical medication speed and time to ensure the safety of medication.

1,2-propanediolacute toxicity testshort-term toxicity testhemolysis test

刘书显、陈彤、阮健、丁波

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山东省烟台市食品药品检验检测中心,山东烟台 264670

1,2-丙二醇 急性毒性试验 短期毒性试验 溶血试验

2024

中国药业
重庆市食品药品监督管理局

中国药业

CSTPCD
影响因子:1.369
ISSN:1006-4931
年,卷(期):2024.33(19)