The metabolism and disposition of tris(1,3-dichloro-2-propyl) phosphate (fyrol FR-2) in the rat

Fyrol FR-2, a flame retardant, was readily absorbed from the skin and gastrointestinal tract and rapidly distributed throughout the body, with the highest concentration being observed in kidney, liver, and lung. The route of administration had little effect on Fyrol FR-2 distribution. Its absorption and distribution from the gastrointestinal tract was unaffected over a dose range of two orders of magnitude. Fyrol FR-2 was subject to rapid and extensive metabolic degradation. Within the first 24 hr, greater than 80% of the radio-activity was excreted in urine, feces, or expired as CO₂. The major metabolite eliminated in the urine was bis(1,3-dichloro-2-propyl) phosphate. Fyrol FR-2 was rapidly metabolized in vitro by a NADPH-dependent microsomal mixed-function oxidase system as well as a glutathione dependent transferase system present in the soluble fraction. The microsomal enzymes metabolized Fyrol Fr-2 to 1,3-dichloro-2-propanol, 3-chloro-1,2-propanediol, and bis(1,3-dichloro-2-propyl) phosphate as well as at least one unidentified metabolite. The soluble fraction metabolized Fyrol FR-2 to one metabolite which is probably a glutathione conjugate formed with the intact Fyrol FR-2 molecule.