[Mutagenicity tests of suplatast tosilate (IPD-1151T)].
1. The reverse mutation test was carried out on suplatast tosilate (IPD-1151T) at dose range of 50-5000 micrograms/plate using Salmonella typhimurium strains TA100, TA1535, TA98 TA1538 and TA1537, and Escherichia coli strains WP2, WP2uvrA. In all tester strains no significant differences were observed in the number of revertant colonies as compared with solvent control in the absence or presence of mammalian metabolic activation system. 2. The chromosomal aberration test on IPD-1151T was carried out using cultured Chinese hamster lung cells (CHL). The cells were treated with IPD-1151T at the doses of 125, 250 and 500 micrograms/ml without S9 Mix and at the doses of 1250, 2500 and 5000 micrograms/ml with S9 Mix. The incidence of structural- and numeral-aberration was 0-4% in the absence or presence of mammalian metabolic activation system, no significant increases were observed in the incidence of chromosomal aberrations. 3. The micronucleus test using BDF1 male mice was conducted in order to evaluate the in vivo mutagenicity of IPD-1151T. IPD-1151T was orally administered at doses of 625, 1250, 2500 and 5000 mg/kg, with a sampling time of 24 hr. The frequency of polychromatic erythrocytes with micronuclei (MNPCE) was 0.23% in the lowest dose (625mg/kg) of IPD-1151T, but the frequency of MNPCE was 0.03-0.13% in the groups treated with 1250-5000 mg/kg of IPD-1151T and no significant increases were observed with dose dependence. The results indicated that IPD-1151T was negative, even in the assessment standard using our background data. 4. The present study indicates that IPD-1151T has no in vitro and in vivo mutagenic potential.
Ohuchida
A
A
Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Furukawa
A
A
Sato
S
S
Maeda
Y
Y
Kashihara
A
A
Mizumoto
T
T
Yoshida
R
R
D000284:Administration, Oral; D000818:Animals; D001190:Arylsulfonates / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004926:Escherichia coli; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium; D013452:Sulfonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D014158:Transcription, Genetic
D001190:Arylsulfonates; D006633:Histamine Antagonists; D009153:Mutagens; D013452:Sulfonium Compounds; C073028:suplatast tosilate