National Toxicology Program technical report series
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Natl Toxicol Program Tech Rep Ser · Sep 1994
NTP Toxicology and Carcinogenesis Studies of Tricresyl Phosphate (CAS No. 1330-78-5) in F344/N Rats and B6C3F1 Mice (Gavage and Feed Studies).
Tricresyl phosphate is an organophosphate plasticizer widely used in vinyl plastics and as a fire retardant additive for hydraulic fluids. Toxicology and carcinogenesis studies were conducted by administering a mixed isomer preparation of 79% tricresyl phosphate esters (consisting of 21% tri- m-cresyl phosphate, 4% tri- p-cresyl phosphate, less than 1% tri- o-cresyl phosphate, and other unidentified tricresyl phosphate esters) by gavage to groups of F344/N rats and B6C3F1 mice for 16 days and 13 weeks, and in feed to groups of F344/N rats and B6C3F1 mice for 13 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 16-DAY GAVAGE STUDY IN RATS: Groups of 10 male and 10 female rats received tricresyl phosphate in corn oil by gavage at doses of 0, 360, 730, 1,450, 2,900, or 5,800 mg/kg body weight, 5 days per week, for a total of 13 or 14 doses in a 16-day period. ⋯ Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of tricresyl phosphate in male or female F344/N rats that received 75, 150, or 300 ppm. There was no evidence of carcinogenic activity of tricresyl phosphate in male or female B6C3F1 mice that received 60, 125, or 250 ppm. Nonneoplastic lesions associated with exposure to tricresyl phosphate included cytoplasmic vacuolization of the adrenal cortex and ovarian interstitial cell hyperplasia in female rats, increased incidences of clear cell focus, fatty change, and ceroid pigmentation of the liver in male mice, and increased severity of ceroid pigmentation of the adrenal cortex in female mice.