Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 15). Two-week and 4-week administration study of methyl methanesulfonate (MMS).
This study was conducted to assess whether a 2-week treatment period is as effective as 4-week treatment for detection of drug-induced toxicity on the male rat reproductive organs using methyl methanesulfonate (MMS). A two-week study at dose levels of 20 or 40 mg/kg and a 4-week study with 20 mg/kg were conducted. The results can be summarized as follows. No deaths and no apparent clinical signs were observed. Body weights and food consumption were decreased at 40 mg/kg in the 2-week study along with testis and epididymis weights. In the 4-week study, epididymis weights were decreased at 20 mg/kg. The rats treated with 20 mg/kg in the 4-week study and those treated with 40 mg/kg in the 2-week study showed decrease of germ cells, exfoliation of germ cells, vacuolar degeneration of Sertoli cell and cell debris in epididymal ducts on histopathological observation. MMS impairment of spermatogenesis was confirmed by stage analysis. It was concluded that a treatment period of 2 weeks is sufficient to allow evaluation of toxic effects of MMS on the male reproductive organs.
Ozawa
S
S
Toxicology Research Laboratories, Kissei Pharmaceutical Co., Ltd., 2320-1 Maki, Minamiazumi, Nagano 399-8305, Japan.
Yokoi
R
R
Kitamura
T
T
Kuriyama
K
K
Kobayashi
K
K
Shibata
N
N
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D008297:Male; D008741:Methyl Methanesulfonate / Q000008:administration & dosage / Q000633:toxicity*; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests
D009153:Mutagens; D008741:Methyl Methanesulfonate