Light and electron microscopic evidence of tri-o-cresyl phosphate (TOCP)-mediated testicular toxicity in Fischer 344 rats.
Somkuti-SG; Lapadula-DM; Chapin-RE; Abou-Donia-MB
Toxicol Appl Pharmacol 1991 Jan; 107(1):35-46
A time course study was done in rats to examine testicular toxicity of tri-o-cresyl-phosphate (78308) (TOCP) by light and electron microscopy. Male Fischer-344-rats were given 150mg/kg TOCP in corn- oil by gavage for 1, 3, 5, 7, 10, 14 or 21 successive days. Sections of testis and epididymis were prepared and analyzed by light and transmission electron microscopy. TOCP did not significantly alter body weights of treated rats, and no clinical signs of organophosphate toxicity were observed. Lesions were first noted after 3 days of exposure and indicated inhibition of spermiation and of condensation of spermatid residual bodies. By 5 days, columnar and spherical shaped vacuoles were noted in stage-XII tubule germinal epithelium and were localized by electron microscopy to Sertoli cells. Widespread dilation of smooth and rough endoplasmic reticulum was noted, along with basally located spermatid heads in Sertoli cells. Severity of lesions increased with time. Primary changes included increased seminiferous epithelial vacuolation and numbers of abnormal residual bodies and giant cells, along with sperm karyorrhexis. Sperm density per tubule decreased with continued exposure such that 90% of seminiferous tubules were without sperm by 14 days. In later stages, spermatid or spermatocyte nuclei were observed within multinucleated giant cells. Spermatogonia did not appear to be affected, and Leydig cells demonstrated no consistent alterations. The authors conclude that TOCP has an initial toxic effect on Sertoli cells and subsequently causes severe disruption of spermatogenesis.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Laboratory-animals; In-vivo-studies; Toxic-effects; Organo-phosphorus-compounds; Reproductive-system; Microscopic-analysis; Histopathology
Pharmacology Duke University Medical Center Box 3813 Durham, NC 27710
Neurotoxic Disorders; Neurotoxic-effects
Toxicology and Applied Pharmacology
Duke University, Durham, North Carolina