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

Vet Hum Toxicol. 2000 Aug;42(4):234-5.

Abstract

A 1-mo toxicity study followed by a 1-mo recovery period of recombinant human 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 were neither dead animals nor significant changes of body weight during the experimental period. In addition, no significant bFGF-related changes were found in ophthalmologic and histopathological examination, urinalysis and hematological, biochemical and organ weight parameters. At necropsy, red-brownish spots and/or nodule formations were recognized in a dose-dependent manner. 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 disappeared or were ameliorated during the recovery period. The above data suggests the NOAEL of bFGF in Beagle dogs is >480 mg/kg/d.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Dogs / blood
  • Dogs / metabolism*
  • Dogs / urine
  • Dose-Response Relationship, Drug
  • Drug Approval
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage
  • Fibroblast Growth Factor 2 / toxicity*
  • Guidelines as Topic
  • Humans
  • Injections, Subcutaneous / veterinary
  • Male
  • No-Observed-Adverse-Effect Level
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / toxicity*
  • Splenomegaly / chemically induced

Substances

  • Carcinogens
  • KCB-1 protein, recombinant
  • Recombinant Proteins
  • Fibroblast Growth Factor 2