Acute oral toxicity of colchicine in rats: effects of gender, vehicle matrix and pre-exposure to lipopolysaccharide.
The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg(-1) body weight) of colchicine (COL) was determined in young, mature male and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 microg kg(-1) body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females.
Wiesenfeld
Paddy L
PL
U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Division of Toxicology, Neurotoxicity and In Vitro Toxicology Branch, Laurel, MD, USA. paddy.wiesenfeld@fda.hhs.gov
Garthoff
Larry H
LH
Sobotka
Thomas J
TJ
Suagee
Jessica K
JK
Barton
Curtis N
CN
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003078:Colchicine / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D008070:Lipopolysaccharides; D014677:Pharmaceutical Vehicles; D003078:Colchicine