Nonclinical toxicological evaluation of occidiofungin, a unique glycolipopeptide antifungal.
Occidiofungin, a glycolipopeptide obtained from the liquid culture of Burkholderia contaminans MS14, has been identified as a novel fungicide. The present study was designed to initially assess the in vitro toxicity in a rat hepatoma (H4IIE) cell line and acute toxicological effects of occidiofungin using a mouse model. In vitro toxicity was observed in all variables at 5 μmol/L. B6C3F1 mice were given single and repeat doses of occidiofungin up to 20 mg/kg. Key effects were a reduction in body and organ weights. However, no significant decrease in body weight was noted at a dose of 1 mg/kg, which is comparable to the dose level of other cyclic glycopeptide antifungal agents currently approved for human use. Microscopic examination of treated mice did not identify any signs of organ-specific toxicity at the dose levels tested.
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Wei
W
Tan
Jim
J
Cooley
Frank
F
Austin
Shi-En
SE
Lu
Stephen B
SB
Pruett
Leif
L
Smith
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D019117:Burkholderia / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D023382:Toxicity Tests, Acute
D000935:Antifungal Agents; D001427:Bacterial Toxins; D006020:Glycopeptides; D010456:Peptides, Cyclic; C576718:occidiofungin