Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 14). Comparison of the effects of 2- and 4-weeks intravenous administration of etoposide.
In order to examine whether effects on male reproductive organs following 2-weeks administration of Etoposide (ET) are detectable, ET was administered intravenously once a week to rats for 2 and 4 weeks at 5 and 10 mg/kg/week. No deaths and no drug-related changes in body weight or in gross pathology were observed. However, decreased testis and/or thymus weights were noted. And histopathological examination revealed decrease and/or loss of spermatogonia and spermatocytes in the testes. It was evident that the target cells of the test article in the male reproductive organs are spermatogonia. Atrophy of the medulla and increase of immature lymphocytes in the cortex of the thymus and increase of fatty cells and increase of immature hematopoietic cells in the bone marrow were also apparent. The histological changes in the testis, thymus and bone marrow suggest that ET inhibits cellular mitosis which reflects its mechanism of action as an anticancer agent. It is concluded that effects of ET on male reproductive organs can be detected by histopathological examination of the testes after 2-weeks repeated administration.
Kawaguchi
M
M
Toxicology Group, Omiya Research Laboratory, Nikken Chemicals Co., Ltd., 1-346 Kitabukuro-cho, Omiya-shi, Saitama 330-0835, Japan.
Nagaoka
Y
Y
Kagawa
M
M
Kasai
Y
Y
Wachi
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity*; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity*; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D018675:Toxicity Tests
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide