Reproductive tract lesions resulting from subchronic administration (63 days) of tri-o-cresyl phosphate in male rats.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Somkuti, SG; Lapadula, DM; Chapin, RE; Lamb, JC; Abou-Donia, MB

Published Date

  • June 15, 1987

Published In

Volume / Issue

  • 89 / 1

Start / End Page

  • 49 - 63

PubMed ID

  • 3590188

Pubmed Central ID

  • 3590188

International Standard Serial Number (ISSN)

  • 0041-008X

Digital Object Identifier (DOI)

  • 10.1016/0041-008x(87)90175-x


  • eng

Conference Location

  • United States