Time course of the tri-o-cresyl phosphate-induced testicular lesion in F-344 rats: enzymatic, hormonal, and sperm parameter studies.

Tri-o-cresyl phosphate (TOCP), a known neurotoxic compound, causes testicular toxicity in both leghorn roosters and Fischer 344 rats. The present study was initiated to follow the onset of the testicular lesion through possible changes in sperm numbers and production, serum hormones, and various enzyme activities. Rats were administered TOCP daily (150 mg/kg) for periods of 3, 7, 10, 14, or 21 days. Vehicle-treated animals served as controls. Sperm motility and sperm number per milligram cauda epididymis were both lower in treated animals by Day 10. Testicular weight to body weight ratio was significantly decreased only in the longest treatment duration animals (21 days). Testicular neurotoxic esterase and nonspecific esterase activities were also inhibited, while beta-glucuronidase activity was not affected. Luteinizing and follicle-stimulating hormone levels were normal, as were both serum and interstitial fluid testosterone concentrations. Sertoli cell fluid secretion, as measured by testis weight increase after efferent duct ligation, showed no significant changes. Other organs (spleen, liver, kidney, pancreas, small intestine, adrenal and pituitary glands) had no overt signs of pathology as observed by light microscopy in animals treated for 21 days. A separate group of animals was treated for 21 days and subsequently examined after 98 days of observation (two cycles of the rat seminiferous epithelium). No recovery of spermatogenesis was seen, indicating that the toxicity was irreversible at the dose used. The effects noted in these studies further define the testicular lesion produced by TOCP and show that 150 mg/kg/day for 21 days produced irreversible testicular toxicity.