title: Antibiotics in the human food chain: establishing no effect levels of tetracycline, neomycin, and erythromycin using a chemostat model of the human colonic microflora.
abstract: A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150 mg/60 kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d.
authors.affiliation: TechLab, Inc., 2001 Kraft Drive, Blacksburg, VA 24060-6358, USA. rjcarman@techlab.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Carman
authors.forename: Mary Alice
authors.initials: MA
authors.lastname: Simon
authors.forename: H Earl
authors.initials: HE
authors.lastname: Petzold
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wimmer
authors.forename: Monica R
authors.initials: MR
authors.lastname: Batra
authors.forename: A Haydée
authors.initials: AH
authors.lastname: Fernández
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Miller
authors.forename: Mary
authors.initials: M
authors.lastname: Bartholomew
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects; D001647:Bile Acids and Salts / Q000032:analysis; D001681:Biological Assay; D003106:Colon / Q000382:microbiology*; D015169:Colony Count, Microbial; D004917:Erythromycin / Q000032:analysis / Q000633:toxicity; D005227:Fatty Acids / Q000032:analysis; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D020387:Food Chain; D005966:Glucuronidase / Q000032:analysis; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism; D009355:Neomycin / Q000032:analysis / Q000633:toxicity; D009601:Nitroreductases; D019055:No-Observed-Adverse-Effect Level; D010084:Oxidation-Reduction; D013431:Sulfates / Q000032:analysis; D013752:Tetracycline / Q000032:analysis / Q000633:toxicity; D001617:beta-Glucosidase / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D005227:Fatty Acids; D013431:Sulfates; D004917:Erythromycin; D009247:NADH, NADPH Oxidoreductases; D009601:Nitroreductases; C021106:azoreductase; D001617:beta-Glucosidase; D005966:Glucuronidase; D013752:Tetracycline; D009355:Neomycin