Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.
The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.
Funabashi
H
H
Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd., 33-94 Enoki-cho, Suita-shi, Osaka 564-0053, Japan.
Fujioka
M
M
Kohchi
M
M
Tateishi
Y
Y
Matsuoka
N
N
D000284:Administration, Oral; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013805:Theobromine / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests
D013805:Theobromine