A study of vehicles for dosing rodent whole embryo culture with non aqueous soluble compounds.
In rodent whole embryo culture (WEC), finding vehicles for non-aqueous-soluble compounds has been problematic due to developmental toxicity associated with many solvents. The purpose of this study was to identify alternative vehicles for insoluble compounds. In WEC, we evaluated carrier solutions containing bovine serum albumin (BSA) and glycerol as well as the solvents, formamide, dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and ethanol, for relative teratogenicity and delivery of the insoluble teratogen, all-trans retinoic acid (RA). At a concentration of <or=0.04%, formamide and DMF exhibited no significant toxicity to cultured rat embryos and were effective at delivering RA to the embryo. The BSA and glycerol carrier solutions were not teratogenic, although both inhibited robust formation of yolk sac vasculature. Both solutions delivered RA to the cultured rat embryos at higher doses. In summary, all four solvents/solutions may have utility as vehicles dependent upon the chemical properties of the compound to be solubilized.
Augustine-Rauch
Karen A
KA
Department of Reproductive Toxicology, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA. karen.augustine@bms.com
Zhang
Qin
Q
Kleinman
Mark
M
Lawton
Richard
R
Welsh
Michael J
MJ
D000818:Animals; D003314:Corn Oil; D004121:Dimethyl Sulfoxide; D004126:Dimethylformamide / Q000737:chemistry; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol; D005260:Female; D005990:Glycerol / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine; D012997:Solvents; D013723:Teratogens / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*; D014212:Tretinoin / Q000008:administration & dosage / Q000633:toxicity
D014677:Pharmaceutical Vehicles; D012997:Solvents; D013723:Teratogens; D012710:Serum Albumin, Bovine; D000431:Ethanol; D014212:Tretinoin; D003314:Corn Oil; D004126:Dimethylformamide; D005990:Glycerol; D004121:Dimethyl Sulfoxide