Toxicity of Polyoxyethylene Hydrogenated Castor Oil 60 (Hco-60) in Experimental Animals

Abstract

HCO-60, a polyoxyethylene castor oil derivative, is used as a solubilizer in the injectable formulations of lipophilic agents. This study was performed to examine the toxicity of HCO-60 in various experimental animals including dogs, monkeys, rabbits, guinea pigs and rats. With 1.25 or 2.5 mg/kg of HCO-60 injected i.v. to dogs, blood pressure decreased, flush, swelling and itching appeared after injection, and with 10 mg/kg of HCO-60 there was additionally a decrease of spontaneous motility. In the two higher dose groups, these symptoms paralleled an increase of histamine levels. Since degranulation was observed after injection in the mast cells of the skin, but not in the liver of dogs, the histamine in the plasma was considered to be released from the mast cells of the skin. Pretreatment with diphenhydramine, a H1-receptor antagonist, suppressed the decrease of blood pressure induced by HCO-60. These findings show that the toxicity of HCO-60 is associated with histamine release from the mast cells. No symptoms occurred in monkeys, rabbits, guinea pigs or rats with 50 or 100 mg/kg of i.v. of HCO-60, and there was no change in plasma histamine levels. This study demonstrated that the toxicity of HCO-60 is species specific to dogs among the animals tested.

Co-administration of Tacrolimus Suppresses Pharmacokinetic Modulation of Multiple Subcutaneously Administered Human Interferon-alpha in Beagle Dogs

“…It has been reported that intravenous administration of more than 1.25 mg/kg HCO-60 causes anaphylaxis-like symptoms such as flushes and decrease of blood pressure as a result of histamine release from mast cells in dogs, whereas these effects are not observed in monkeys, rabbits, guinea pigs or rats. 21) These findings are consistent with our current study and previous observations. 8) If caused by additives such as solubilizers, severe anaphylaxis-like symptoms may modulate the PK profile of the main drug and thereby the crossover study must be terminated.…”

Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use

“…Acute toxicity studies were conducted for PEG-60 hydrogenated castor oil in various animals including male and female Beagle dogs, male and female cynomolgus monkeys, male New Zealand white rabbits, male Hartley guinea pigs, and male S-D rats. Overall results showed systemic and irritant effects only in dogs, and not in the other animals tested, indicating species-specific effects (22) .…”

Acute tacrolimus toxicity in a non-transplant patient

“…Anaphylaxis has been reported with IV administration, although it is thought to be due to the castor oil derivative in the injectable formulation [13]. The description of tacrolimus toxicity is confounded by the concomitant use of other immunosuppressants or the co-existence of underlying pathology.…”