Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 25). Effects of 2- and 4- week repeated-dosing of dibromoacetic acid.
To assess the sensitivity of rats to a testicular toxicant, 2- and 4-week repeated-dose studies using dibromoacetic acid (DBAA) were performed. Four groups of 6- or 8-week old male SD rats were given DBAA at a daily dosage of 0, 5, 50 or 250 mg/kg. The highest dose was given for 2 weeks, and the others for 2 and 4 weeks. There were no effects on body or testicular weights in any of the DBAA-treated groups. However, the mean absolute epididymal weight in the 250 mg/kg group was significantly lower than that of the control group. Histopathologically, atypical residual bodies (ARBs) and retention of Step 19 spermatids were evident with this high dose. In the same group, ARBs in the epididymal ducts and narrowing of these lumina were also observed. Retention of Step 19 spermatids was similarly apparent in the testes of animals given 50 mg/kg for 2 or 4 weeks, and in one animal given 5 mg/kg for 4 weeks. Based on these data, DBAA testicular toxicity is histopathologically detectable within 2-weeks of repeated dosing at an appropriate dose.
Tsuchiya
T
T
Toxicology Laboratory, Kazusa Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5 Yana, Kisarazu, Chiba 292-0812, Japan.
Ooyama
N
N
Murakami
T
T
Sano
F
F
Sugimoto
J
J
Mutai
M
M
D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; 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; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests
D000085:Acetates; C088674:dibromoacetic acid