title: Toxicity of novel anti-hepatitis drug bicyclol: a preclinical study.
abstract: OBJECTIVE
  To study the toxicity of bicyclol to animals.
  
  
  METHODS
  Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d. Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol (150, 300, 600 mg/kg, 100-400 folds corresponding to the proposed therapeutic dose (1.5 mg/(kg.d)) of bicyclol for patients) once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2% sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6, 50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.
  
  
  RESULTS
  The oral LD(50) of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.
  
  
  CONCLUSIONS
  Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, 1 Xian Nong Tan St, Beijing 100050, China. liugt@imm.ac.cn
authors.forename: Geng-Tao
authors.initials: GT
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Huai-Ling
authors.initials: HL
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Gao
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006505:Hepatitis / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens
chemical_list: D001713:Biphenyl Compounds; D013723:Teratogens; C477843:bicyclol