Acute intravenous toxicity of dimethyl sulfoxide, polyethylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains.
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.
Research Centre, Boehringer Mannheim Italia, Monza, Milan, Italy.
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P
Montaguti
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Melloni
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E
Cavalletti
D000818:Animals; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000633:toxicity; D004126:Dimethylformamide / Q000008:administration & dosage / Q000633:toxicity; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D001592:Benzyl Alcohols; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D004126:Dimethylformamide; D004121:Dimethyl Sulfoxide