TESTICULAR EFFECTS OF 1,3,5-TRINITROBENZENE (TNB) .1. DOSE-RESPONSE AND REVERSIBILITY STUDIES

Testicular effects of TNB were characterized after single and multiple oral doses of TNB at 0, 35.5, and 71 mg/kg. Male Fischer 344 (F344) r ats were killed after a single dose or after 4 and 10 daily doses of T NB. Testicular effects were not evident at the light microscope level in rats killed after a single dose of TNB or after 4 daily doses at 35 .5 mg/kg of TNB. Rats receiving 4 daily doses of TNB at 71 mg/kg had t he earliest evidence of testicular damage, with necrosis and degenerat ion of pachytene spermatocytes including a significant decrease in tes ticular weight. Rats dosed at 35.5 mg/kg for 10 d had severe testicula r lesions, in addition to the decrease in testicular weight. There was degeneration of round and elongate spermatids, and formation of multi nucleate syncytial cells. The epididymis was devoid of sperm, instead containing exfoliated syncytial spermatids. Rats dosed at 71 mg/kg of TNB for 10 d had testicular atrophy and cessation of spermatogenesis. These rats also had apoptic cells in the ventral prostate. To assess t he extent of reversibility in these atrophied testis, rats were allowe d to recover for 10 or 30 d after 10 doses of TNB (71 mg/kg). A signif icant regenerative attempt with proliferating spermatocytes were prese nt at 10 d and elongate spermatids were evident at 30 d. These reversi bility studies indicate testicular effects of TNB are at least partial ly reversible.