Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 1). Effects of 2-weeks daily administration of estradiol benzoate.
As part of a collaborative project to assess whether a 2-weeks administration period is sufficient to detect testicular toxicity of various compounds, male rats were subcutaneously administered 0, 5, 20, 50 or 100 micrograms/kg of estradiol benzoate (E2B), a known testicular toxicant, daily for 2 or 4 weeks. After 4-weeks, suppression of body weight gain, increase in the weight of the adrenal gland, and gross changes such as decrease in size of the prostate and seminal vesicles, and increase in size of the adrenal gland were observed in the 5, 20, 50 and 100 micrograms/kg groups. On histopathological examination, degeneration/necrosis of Pachytene spermatocytes, atrophy of Leydig cells, mature spermatid retention (Lee, et al., 1993) at stages IX, X and XI, and atrophy of ducts of the epididymides were also observed in the 5, 20, 50 and 100 micrograms/kg groups. After 2-weeks, the same changes were also observed with 20, 50 and 100 micrograms/kg, but not 5 micrograms/kg. These results indicate that the toxic effects of E2B are detectable by administration for 2 weeks at an appropriate dose level.
Hata
J
J
Safety Research Department, Pharmaceuticals Development Research Laboratories, Teijin Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
Takahashi
H
H
Nakahara
C
C
Namiki
A
A
Uno
H
H
Asano
S
S
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D018675:Toxicity Tests
C074283:estradiol 3-benzoate; D004958:Estradiol