Montaguti P, Melloni E, Cavalletti E
Research Centre, Boehringer Mannheim Italia, Monza, Milan, Italy.
Arzneimittelforschung. 1994 Apr;44(4):566-70.
Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology. Haemolytic and precipitation potential tests in vitro were performed to assess the blood compatibility of the investigated solvents and its relationship with the observed symptoms. The single tested solvents did not show any major differences in acute toxicity in the three tested strains with the exclusion of DMSO (less toxic in CD2F1) and BeOH and EtOH (less toxic in B6D2F1). The tested dose ranges in the three strains (in ml/kg) were 1.0-5.66 for DMSO, 2.0-8.0 for PEG 400, 1.0-4.0 for DMF, 0.75-4.24 for EtOH, 0.025-0.4 for BeOH. The lowest tested dose was a safe dose and the highest one was the dose causing mortality in no more than half the animals in each group. The in vitro results suggest avoiding the use of BeOH (which also is more toxic than the other solvents in the in vivo test) and DMSO and using PEG400, EtOH and DMF even though the latter induced a body weight decrease in the B6D2F1 mouse strain. As a general conclusion, dilution of these solvents in water is suggested to ameliorate their blood compatibility and the use of doses not higher than the lowest dose tested in this study is recommended.
在许多临床前试验(主要是肿瘤学和毒理学试验)中使用的三种近交系小鼠品系(CD2F1、B6D2F1和C57BL/6N)中,测定了一些溶剂,即二甲基亚砜(DMSO)、聚乙二醇400(PEG 400)、二甲基甲酰胺(DMF)、无水乙醇(EtOH)和苯甲醇(BeOH)的急性静脉毒性。进行了体外溶血和沉淀潜力试验,以评估所研究溶剂的血液相容性及其与观察到的症状的关系。除DMSO(在CD2F1中毒性较小)以及BeOH和EtOH(在B6D2F1中毒性较小)外,单一测试的溶剂在三种测试品系中的急性毒性没有显示出任何重大差异。三种品系的测试剂量范围(以ml/kg计)分别为:DMSO为1.0 - 5.66,PEG 400为2.0 - 8.0,DMF为1.0 - 4.0,EtOH为0.75 - 4.24,BeOH为0.025 - 0.4。最低测试剂量为安全剂量,最高测试剂量是每组中导致不超过半数动物死亡的剂量。体外试验结果表明应避免使用BeOH(其在体内试验中也比其他溶剂毒性更大)和DMSO,可使用PEG400、EtOH和DMF,尽管后者在B