Temperature dependence of di-2-ethylhexyl phthalate (DEHP) pharmacokinetics in rainbow trout

Rainbow trout (Salmo gairdneri) acclimated at 6, 12, or 18 degrees C received 400 micrograms [14C]DEHP/kg as an intraaortic bolus. DEHP disappeared rapidly from plasma, with an estimated 50% of the dose eliminated after 5 hr. Plasma concentration-time data were analyzed using a three-compartment model and by the statistical moment method; both analyses yielded similar parameter estimates. The apparent steady-state volume of distribution (Vss) and the apparent volume of the deep peripheral compartment (V3) increased exponentially with increasing temperature (log V proportional to temperature) while the volumes of the central (V1) and shallow peripheral (V2) compartments were not systematically affected. The total body clearance of DEHP increased linearly with increasing temperature, while the capacity to hold DEHP increased more rapidly, resulting in the biological persistence and potential for bioaccumulation of DEHP to increase with increased temperature. Both the terminal elimination half-life and the mean residence time increased exponentially with increasing temperature; the half-life increased from 79.5 to 130 hr between 6 and 18 degrees C. Simulations with the model indicated that the distribution of DEHP was temperature sensitive; this finding may have important implications for the temperature sensitivity of DEHP toxicity or carcinogenicity.