Developmental toxicity study of CBLB502 in Wistar rats

CBLB502 is a derivative of a microbial protein that binds to Toll-like receptor 5. It is demonstrated to reduce inflammatory response from acute stresses, such as radiation in animal models. We determined the potential developmental toxicity of CBLB502 in rats. Four groups of 25 time-mated female Wistar rats/group received subcutaneously 0, 30, 100, or 300 mu g/kg/day of CBLB502 from Gestation Days (GD) 6 to 17 at a dose volume of 1.0 mL/kg. Toxicokinetic evaluation was performed on GD 6 and 17. On GD 20 C-section was performed for uterine evaluation and blood samples collected from each dam for immunogenicity assay. Significant decrease in gestation body weight, weight changes and food consumption indicative of maternal toxicity were observed in all dose groups. Also adjusted body weight and weight changes were seen at 300 mu g/kg/day. No external, visceral and skeletal abnormalities were observed. The NOAEL for developmental toxicity was estimated to be >= 300 mu g/kg/day. (C) 2014 Published by Elsevier Inc.