PMID- 25697570
OWN - NLM
STAT- MEDLINE
DCOM- 20160129
LR  - 20181228
IS  - 1873-1708 (Electronic)
IS  - 0890-6238 (Linking)
VI  - 52
DP  - 2015 Apr
TI  - Absence of developmental toxicity in a canine model after infusion of a 
      hemoglobin-based oxygen carrier: Implications for risk assessment.
PG  - 101-7
LID - S0890-6238(15)00007-6 [pii]
LID - 10.1016/j.reprotox.2015.01.006 [doi]
AB  - Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated 
      for use in humans (HBOC-201) and approved for veterinary medicine (HBOC-301). We 
      infused pregnant beagles with HBOC-201 to test whether HBOC-induced developmental 
      toxicity previously observed in rats would occur in a species devoid of an 
      inverted visceral yolk sac (invVYS). Phase 1 assessed developmental toxicity of 
      6g/kg HBOC-201 on gestational day (GD) 21. Phase 2 investigated single infusions 
      of 6g/kg HBOC-201 on one of GDs 21, 25, 29 or 33. Phase 3 studied multiple 
      sequential infusions on GDs 21, 23,25,27,29, 31, and 33 at 0.52g/kg/day (3.6g/kg 
      total dose). Mild to moderate maternal toxicity occurred in all phases. There was 
      an unequivocal absence of developmental toxicity in all phases. Overall, our 
      hypothesis that HBOC, which interferes with the function of the invVYS, would not 
      affect the offspring in dogs was supported. The implications relative to human 
      risk are discussed.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Holson, J F
AU  - Holson JF
AD  - Ashland, OH, United States.
FAU - Stump, D G
AU  - Stump DG
AD  - WIL Research Laboratories, Ashland, OH, United States.
FAU - Pearce, L B
AU  - Pearce LB
AD  - Biologics Consulting Group, Alexandria, VA, United States.
FAU - Watson, R E
AU  - Watson RE
AD  - SNBL USA, Everett, WA, United States.
FAU - DeSesso, J M
AU  - DeSesso JM
AD  - Exponent, Inc., Alexandria, VA, United States; Georgetown University School of 
      Medicine, Washington, DC, United States. Electronic address: 
      jdesesso@exponent.com.
LA  - eng
PT  - Journal Article
DEP - 20150216
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Blood Substitutes)
RN  - 0 (Hemoglobins)
RN  - 0 (Oxyhemoglobins)
RN  - 1XQE66T19H (HBOC 201)
RN  - G02KA603BW (HBOC 301)
SB  - IM
MH  - Animals
MH  - *Blood Substitutes
MH  - Dogs
MH  - Embryonic Development/*drug effects
MH  - Female
MH  - Gestational Age
MH  - Hemoglobins/*toxicity
MH  - Models, Animal
MH  - Organogenesis/drug effects
MH  - Oxyhemoglobins/*toxicity
MH  - Pregnancy
OTO - NOTNLM
OT  - Dog
OT  - Hemoglobin-based oxygen carriers
OT  - Inverted yolk sac
EDAT- 2015/02/24 06:00
MHDA- 2016/01/30 06:00
CRDT- 2015/02/21 06:00
PHST- 2014/05/29 00:00 [received]
PHST- 2014/12/24 00:00 [revised]
PHST- 2015/01/20 00:00 [accepted]
PHST- 2015/02/21 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/01/30 06:00 [medline]
AID - S0890-6238(15)00007-6 [pii]
AID - 10.1016/j.reprotox.2015.01.006 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2015 Apr;52:101-7. doi: 10.1016/j.reprotox.2015.01.006. Epub 2015 
      Feb 16.