The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.
The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.
Maruho Co., Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan. Electronic address: inoue_czo@mii.maruho.co.jp.
Kenji
K
Inoue
Maruho Co., Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan.
Akimu
A
Ochi
Maruho Co., Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan.
Akira
A
Koda
LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
Yumi
Y
Wako
LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
Kazufumi
K
Kawasako
Maruho Co., Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan.
Takaaki
T
Doi
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D003299:Cooperative Behavior; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008702:Methaqualone / Q000633:toxicity*; D015162:Micronucleus Tests; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects; D012957:Societies, Pharmaceutical
D002273:Carcinogens; D008702:Methaqualone
Hepatocarcinogen; Integration; Liver micronucleus assay; Methapyrilene hydrochloride; Rat; Repeated-dose toxicity study