Reproductive tract lesions resulting from subchronic administration (63 days) of tri-o-cresyl phosphate in male rats.
An initial dose-range pilot study where animals were gavaged with between 100 and 1600 mg tri-o-cresyl phosphate (TOCP)/kg/day for 14 days resulted in decreased epididymal sperm density and disruption of the seminiferous epithelium in 100% of treated animals. A subchronic 63-day study (reflecting the 49-day length of the rat seminiferous epithelium cycle plus the 14-day transit time of spermatids through the epididymis was initiated. Dose-dependent (10 to 100 mg TOCP/kg/day) decreases in cauda epididymal sperm motility and density, testicular enzyme activities, and alterations in sperm morphology were observed. Concurrent pair-fed controls (matched to the highest dose group, 100 mg TOCP/kg/day) indicated that weight loss resulting from TOCP administration had minimal contributory effects to the testicular toxicity seen. Plasma alpha-tocopherol acetate (vitamin E) and testosterone concentrations were unaffected. Tri-p-cresyl phosphate (TPCP), the nonneurotoxic structural analog of TOCP, produced no toxic effects, demonstrating the necessity of the ortho-cresol moiety for induction of damage. A minimum effective (threshold) dose for observable testicular toxicity was determined to be 10-25 mg TOCP/kg in this study. These data suggest that TOCP interferes with spermatogenic processes and sperm motility directly and not via an androgenic mechanism or decreased vitamin E availability.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003408:Cresols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000032:analysis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000032:analysis; D014317:Tritolyl Phosphates / Q000633:toxicity*; D014810:Vitamin E / Q000097:blood
D003408:Cresols; D014317:Tritolyl Phosphates; D014810:Vitamin E; D013739:Testosterone; D004950:Esterases; C025541:tri-o-cresyl phosphate