AN IN-VITRO METHOD FOR DETERMINATION OF TISSUE PARTITION-COEFFICIENTS OF NONVOLATILE CHEMICALS SUCH AS 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AND ESTRADIOL

The development of an in vitro vial equilibration technique for determining tissue and liquid partition coefficients for non-volatile chemicals is described. Radiolabeled chemical dissolved in propylene carbonate is equilibrated with tissues or liquid at 37 degrees C in a vial system. The solvent must be essentially immiscible with the test material. The amount of chemical movement to the tissue or liquid is compared to an appropriate reference vial, and tissue or liquid:solvent partition coefficients are calculated. Tissue:solvent values divided by blood:solvent values provide tissue:blood partition coefficients required for developing physiologically based pharmacokinetic models for chemicals. These models are useful for estimating internal tissue doses to assess human risk from exposure to chemicals. Partition coefficients for various rat tissues, 0.9% saline solution and olive oil were determined in this study for radiolabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and for the less fat-soluble compound, estradiol. The TCDD tissue:propylene carbonate partition coefficients were found to be: blood, 0.091; fat, 17.02; liver, 0.419; brain, 0.632; kidney, 0.305; muscle, 0.408. For estradiol, the tissue:propylene carbonate partition coefficients were: blood, 0.286; fat, 0.169; liver, 1.032; brain, 0.554. The TCDD results compared well with values reported and estimated from a more protracted in vivo approach. Thus, this current technique offers a simpler and time-saving alternative to in vivo approaches for determining the partition coefficients of non-volatile compounds.