Toxic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate in female F344 rats.
Triaryl phosphates, including tricresyl phosphate (TCP and butylated triphenyl phosphates (BTP), are used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Recent reports implicate these compounds as endocrine and reproductive toxicants that can cause cholesteryl lipidosis in adrenocortical (AC) and ovarian interstitial (OI) cells, suggesting altered metabolism of steroid hormones or cholesterol or of both. We investigated potential mechanisms of BTP and TCP toxicity to determine if there were functional abnormalities of the adrenal cortex or ovary. Groups of intact (nine or 12) and ovariectomized (six) female F344 rats, 10-12 weeks of age, received 0, 0.4 g/kg TCP, or 1.7 g/kg BTP in sesame oil vehicle or 1.7 g/kg neat BTP for 20, 40, or 60 days. All rats administered BTP and TCP developed cholesteryl lipidosis in AC and OI cells; the TCP-treated group was most severely affected. Serum concentrations of androstenedione and corticosterone were unchanged, but estradiol levels were significantly (P < or = 0.05) elevated in BTP- and TCP-treated groups (14.5 times and 37.5 times greater than controls, respectively). Vaginal cytology revealed that BTP- but not TCP-treated females had abnormal reproductive cycles that were significantly prolonged in diestrus (3 times greater than control). There were significant elevations in serum total cholesterol (TCP-treated group was 1.3 times greater than controls), low-density lipoprotein (TCP-treated group was 1.8 times greater than controls), alanine transaminase (BTP-treated group was 2 times greater than controls), and albumin (a major serum estradiol-binding protein; BTP-treated group was 4.6 g/dl vs. 3.6 g/dl for controls).(ABSTRACT TRUNCATED AT 250 WORDS)
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000097:blood / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D004971:Estrus / Q000187:drug effects / Q000502:physiology; D005260:Female; D008064:Lipidoses; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D010755:Organophosphates / Q000633:toxicity*; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D014317:Tritolyl Phosphates / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects / Q000502:physiology; D014621:Vagina / Q000187:drug effects / Q000502:physiology
D001798:Blood Proteins; D010755:Organophosphates; D014317:Tritolyl Phosphates; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D000410:Alanine Transaminase; D003345:Corticosterone; C025541:tri-o-cresyl phosphate; C005445:triphenyl phosphate