title: Toxicity of culture material of Fusarium verticillioides strain MRC 826 to nonhuman primates.
abstract: We conducted a chronic feeding study in vervet monkeys (Cercopithecus aethiops) over 13.5 years. The experimental design consisted of two dietary treatment groups, each including males and females, fed varying levels of culture material of Fusarium verticillioides (Sacc.) Nirenberg (= F. moniliforme Sheldon) strain MRC 826 mixed into their daily food ration. Two females were included as treatment controls. We conducted blood chemical analyses bimonthly and recorded all clinical signs during the course of the experiment. We took liver biopsies at various stages during the initial phase of the experiment. Several monkeys were terminated in extremis during the experiment. Detailed feed intake profiles were determined 5 years after the experiment began, and the fumonisin B (FB) mycotoxin content of the feed was determined during the final stages of the experiment. The apparent FB consumption patterns were related to changes observed in the biochemical parameters in the blood and urine, including the liver function enzymes and creatinine clearance as well as differential blood counts and sphingolipid levels in the serum and urine. An apparent no-effect threshold for kidney and liver damage is estimated to be between 0.11 and 0.18 mg FB/kg body weight (bw)/day, which corresponds to a feed contamination level of between 8.21 and 13.25 mg FB/kg bw diet. Apart from the effects on the liver and kidney, a wide variety of parameters, including cholesterol and creatine kinase, were also adversely affected. Several blood parameters, including white and red blood cells, also significantly decreased in the treated animals. The serum sphinganine level and the sphingosine/sphinganine ratio, monitored toward the end of the experiment, significantly increased in both the low-dose and high-dose animals. The present study provides important information about the diversity of lesions induced by culture material of F. verticillioides in vervet monkeys and the dosage levels of fumonisins to be used in long-term studies in nonhuman primates.
authors.affiliation: Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg, South Africa. wentzel.gelderblom@mrc.ac.za
authors.forename: W C
authors.initials: WC
authors.lastname: Gelderblom
authors.forename: J V
authors.initials: JV
authors.lastname: Seier
authors.forename: P W
authors.initials: PW
authors.lastname: Snijman
authors.forename: D J
authors.initials: DJ
authors.lastname: Van Schalkwyk
authors.forename: G S
authors.initials: GS
authors.lastname: Shephard
authors.forename: W F
authors.initials: WF
authors.lastname: Marasas
mesh_terms: D000821:Animal Feed; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000633:toxicity*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D037341:Fumonisins; D005670:Fusarium / Q000145:classification / Q000472:pathogenicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D012044:Regression Analysis; D012737:Sex Factors; D013107:Sphingolipids / Q000097:blood / Q000378:metabolism / Q000652:urine
chemical_list: D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; D013107:Sphingolipids; C056933:fumonisin B1; D003404:Creatinine