title: Evaluation of subchronic toxicity of dietary administered Cry1Ab protein from Bacillus thuringiensis var. Kurustaki HD-1 in F344 male rats with chemically induced gastrointestinal impairment.
abstract: Bacillus thuringiensis (Bt) proteins are developed for genetically modified crops and the Bt proteins demonstrate no evidence of toxicity by the oral route in traditional animal models. However, the possible toxicity of Bt proteins under conditions of reduced gastric acid secretion and/or small intestinal damage has not been investigated. In the present study, we therefore evaluated following four F344 rat groups with a purified Bt protein Cry1Ab from B. thuringiensis var. Kurustaki HD-1. Gastrointestinal impairment (GI) alone and GI+Bt protein fed (GI+Bt) groups were given i.p. injections of famotidine to reduce gastric acid secretion twice a day at 30mg/kg body weight in weeks 2 and 4. GI and GI+Bt groups were additionally fed diets containing 80ppm indomethacin for induction of intestinal damage during weeks 1 and 3. Bt alone and GI+Bt groups were also fed diet containing Bt protein Cry1Ab at a concentration of 10ppm in weeks 2 and 4. A no treatment control group was also included. At the end of week 4, all animals were euthanized under ether anesthesia, blood samples were collected for hematology and serum biochemistry and a complete necropsy was performed. No significant changes indicative of toxicity of the Bt protein Cry1Ab used here were noted with any of the parameters investigated. In conclusion, no significant toxicological effects were detected in this subchronic gastrointestinal impairment rat model.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Onose
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Mai
authors.initials: M
authors.lastname: Hasumura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ueda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001413:Bacillus thuringiensis / Q000737:chemistry*; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000633:toxicity*; D004032:Diet; D004435:Eating / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D015738:Famotidine; D005744:Gastric Acid / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000150:complications*; D006460:Hemolysin Proteins / Q000633:toxicity*; D007213:Indomethacin; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D004731:Endotoxins; D006460:Hemolysin Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; D015738:Famotidine; D007213:Indomethacin