Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 27). Repeated toxicity study on ethylene glycol monomethyl ether for 2 and 4 weeks to detect effects on male reproductive organs in rats.
As part of a collaborative project to determine the minimum administration period to detect compound effects on male reproductive organs in Sprague-Dawley (Crj:CD(SD)) male rats, 6- and 8-week-old rats were administered ethylene glycol monomethyl ether (EGME) daily at 100 and 200 mg/kg/day for 2 weeks or 100 mg/kg/day for 4 weeks, and histopathological changes in the testes and epididymides were examined. Testis and epididymis weights in the 2-week 200 mg/kg and 4-week 100 mg/kg groups were obviously decreased. On histopathological examination, severe degenerative changes in the testis such as atrophy of the seminiferous tubules and multinucleated giant cell formation were observed in all 2-week 200 mg/kg group rats. Degeneration of pachytene spermatocytes in Stages X IV-II, III and a decrease in the number of germ cells was observed with both 2 and 4 weeks treatments at 100 mg/kg/day. In the epididymides, the number of sperm in the caput decreased with 100 mg/kg/day groups after both 2 and 4 weeks. In addition, degeneration of pachytene spermatocytes induced by EGME was found to be exclusively due to apoptotic death. Similar testicular and epididymal changes were observed with 2 and 4 weeks treatments at 100 mg/kg/day of EGME. Therefore, we conclude that a 2 weeks administration period is sufficient for detection of EGME effects on male reproductive organs.
Watanabe
A
A
Laboratory for Toxicological Research, Institute for Life Science Research, Asahi Chemical Industry Co., Ltd., 632-1 Mifuku, Ohito-cho, Tagata-gun, Shizuoka 410-2321, Japan.
Nakano
Y
Y
Endo
T
T
Sato
N
N
Kai
K
K
Shiraiwa
K
K
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests
D005026:Ethylene Glycols; C005219:methyl cellosolve