One-month parenteral toxicity study of recombinant human basic fibroblast growth factor in dogs

A 1-mo toxicity study followed by a 1-mo recovery period of recombinant hum an basic fibroblast growth factor (bFGF) was performed using Beagle dogs at doses of 30, 120 or 480 mg/kg/d to estimate the no observed adverse effect level (NOAEL). Subcutaneous thickening was seen and its incidence, as well as that of stiffness of the injection sites, increased with dose. There we re neither dead animals nor significant changes of body weight during the e xperimental period. In addition, no significant bFGF-related changes were f ound in ophthalmologic and histopathological examination, urinalysis and he matological, biochemical and organ weight parameters. At necropsy, red-brow nish spots and/or nodule formations were recognized in a dose-dependent man ner. Splenomegaly was noted in the 480 mg/kg group, but these findings had a low incidence in all dose groups. The findings in the dosing period disap peared or were ameliorated during the recovery period. The above data sugge sts the NOAEL of bFGF in Beagle dogs is >480 mg/kg/d.