Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment.

摘要: Abstract Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated for use in humans (HBOC-201) and approved veterinary medicine (HBOC-301). We infused pregnant beagles with HBOC-201 to test whether HBOC-induced developmental toxicity previously observed rats would occur a species devoid of an inverted visceral yolk sac (invVYS). Phase 1 assessed 6 g/kg on gestational day (GD) 21. 2 single infusions one GDs 21, 25, 29 or 33. 3 studied multiple sequential 23,25,27,29, 31, 33 at 0.52 g/kg/day (3.6 g/kg total dose). Mild moderate maternal occurred all phases. There was unequivocal absence Overall, our hypothesis that HBOC, which interferes the function invVYS, not affect offspring dogs supported. The implications relative human risk are discussed.