title: Gavage administration of the fungal toxin fumonisin B1 to female Sprague-Dawley rats.
abstract: The fungal toxin fumonisin B1 (FB1) is a contaminant of corn-based foods and feeds produced by members of the genus Fusarium. Fumonisin B1 toxicity was examined using gavage administration of purified toxin to female Sprague-Dawley rats. For 11 consecutive days each rat received a single dose of FB1 at the following concentrations: control (saline), 1, 5, 15, 35, or 75 mg FB1/kg body weight/d. Significantly depressed body weight and food consumption occurred at 35 and 75 mg FB1/kg/d. By the end of the dosing period there were no significant changes in food consumption. Kidneys and bone marrow were most sensitive to FB1 exposure. Changes in renal morphology were observed from 5 to 75 mg FB1/kg/d, accompanied by transient changes in urine osmolality and urine enzyme levels. Increased cellular vacuolation was the primary change associated with bone-marrow toxicity, starting at doses of 5 mg FB1/kg/d. Hepatotoxicity was indicated by reduced liver weight, elevated serum alanine amonitransferase (ALT), and mild histopathological changes occurring at doses of 15 mg FB1/kg/d and higher. Increased cytoplasmic vacuolation of adrenal cortex cells occurred in rats treated with 15 mg FB1/kg/d and higher, indicating that the adrenals are also potential targets of FB1. Elevated serum cholesterol, which is a consistent response to FB1 was observed at 5 mg FB1/kg/d and higher. Based on responses in this study, gavage is an appropriate substitute for longer feeding studies. Compared to previous work with male rats, gender-related difference in FB1 responses lacked consistency but indicated that males may be marginally more sensitive than female Sprague-Dawley rats.
authors.affiliation: Toxicology Research Division, Food Directorate, Health Canada, Ottawa, Canada. Genevieve_Bondy@inet.hwc.ca
authors.forename: G S
authors.initials: GS
authors.lastname: Bondy
authors.forename: C A
authors.initials: CA
authors.lastname: Suzuki
authors.forename: R W
authors.initials: RW
authors.lastname: Mueller
authors.forename: S M
authors.initials: SM
authors.lastname: Fernie
authors.forename: C L
authors.initials: CL
authors.lastname: Armstrong
authors.forename: S L
authors.initials: SL
authors.lastname: Hierlihy
authors.forename: M E
authors.initials: ME
authors.lastname: Savard
authors.forename: M G
authors.initials: MG
authors.lastname: Barker
mesh_terms: D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002264:Carboxylic Acids / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D005260:Female; D037341:Fumonisins; D007441:Intubation, Gastrointestinal; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013950:Thymus Gland / Q000187:drug effects; D016482:Urinalysis
chemical_list: D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; C056933:fumonisin B1