Toxicity of novel anti-hepatitis drug bicyclol: a preclinical study.
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.
Liu
Geng-Tao
GT
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, 1 Xian Nong Tan St, Beijing 100050, China. liugt@imm.ac.cn
Li
Yan
Y
Wei
Huai-Ling
HL
Lu
Hong
H
Zhang
Hui
H
Gao
Yu-Gui
YG
Wang
Ling-Zhi
LZ
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
D001713:Biphenyl Compounds; D013723:Teratogens; C477843:bicyclol