Cremaphor® ELP (CrELP) has been used to emulsify and solubilize water-insoluble substances in the pharmaceutical industry for oral, topical and parenteral preparations, but its safety profile via the intravenous route is yet to be established. In the current report, a wide range of CrELP concentrations associated with different viscosities were formulated and administered intravenously to rats in order to evaluate the acute safety and tolerability. Doses of CrELP were administered once in a fixed volume (5 ml/kg) and
concentrations tested in mg/kg included 7.5, 75, 150, 375, 750, 1000, 1250, and 1500, with corresponding viscosites of 1,1, 1.08, 1.6, 3.6, 6, 18, 65 centiPoise (mPa.s), respectively. Mortality was observed within minutes of intravenous dosing with 1250 and 1500 mg/kg. Clinical signs of dyspnea, decreased activity, flat body posture, and rough hair coat were observed in rats given 750 or 1000 mg/kg. Plasma potassium (K+) levels were increased at 24 hours post dose compared to pre-dose values at all doses tested. Histopathologic
evaluations of the heart, kidney and lungs revealed myocardial necrosis and inflammation, renal tubular necrosis and pulmonary histiocytosis with hemorrhage. Collectively, the clinical signs, serum potassium levels and histopathogical findings in rats given 750 and 1000 mg/kg were consistent with compromised tissue perfusion. No adverse findings were observed in rats given 7.5, 75, 150 or 375 mg/kg CrELP and 375 mg/kg was considered the no adverse effect level (NOAEL) in this study
