Reproductive tract lesions resulting from subchronic administration (63 days) of tri-o-cresyl phosphate in male rats.
Somkuti-SG; Lapadula-DM; Chapin-RE; Lamb-JC IV; Abou-Donia-MB
Toxicol Appl Pharmacol 1987 Jun; 89(1):49-63
The biochemical and morphological effects of tri-o-cresyl-phosphate (78308) (TOCP) on the male reproductive system were studied in rats. In a preliminary study, male Fischer-344-rats were given 0 or 100 to 1600mg/kg TOCP orally for 14 days. The animals were observed for signs of intoxication. Selected rats were killed and the testes were removed for histopathological examination. Sperm density per milligram cauda was determined. TOCP at doses above 400mg/kg caused nearly 100 percent mortality within 48 hours. Groups given 200 and 400mg/kg had 60 and 70 percent mortality, respectively. All animals given 100mg/kg TOCP survived. Symptoms of acute cholinergic toxicity were seen in all animals except the 100mg/kg group. Decreased epididymal sperm density and disruption of the seminiferous epithelium were observed. Rats were given 0, 10, 25, 50, 75, or 100mg/kg TOCP daily for 63 days. An additional group was administered 100mg/kg tri-p-cresyl-phosphate (78320) (TPCP) for comparison purposes. At the end of the experiment, the rats were killed and the testes were removed and examined for histopathological changes. Sperm morphology and motility were examined. Plasma vitamin-E and testosterone concentrations were determined. Testicular neurotoxic-esterase (NTE), nonspecific esterase (NSE), and acetylcholinesterase (AChE) activities were measured. TOCP caused dose dependent decreases in sperm motility, sperm density, and testicular NSE and AChE. Rats given 10mg/kg TOCP showed normal sperm morphology. Pathological lesions such as disrupted sperm cell architecture were seen consistently in all animals given 50mg/kg or higher doses. Dose dependent increases in numbers of abnormal spermatozoa were seen. Plasma testosterone and vitamin-E concentrations were not significantly affected by TOCP. TPCP produced no signs of testicular toxicity. The authors conclude that 25mg/kg TOCP is the lowest dose for testicular toxicity. The no observable effect dose is 10mg/kg.
NIOSH-Publication; NIOSH-Grant; Phosphorus-compounds; Cholinesterase-inhibitors; In-vivo-studies; Laboratory-animals; Reproductive-system; Reproductive-effects; Enzymatic-effects; Dose-response
Toxicology and Applied Pharmacology
Pharmacology Duke University Department of Pharmacology Durham, NC 27710