Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues.

Partition coefficients are required for developing physiologically based pharmacokinetic models used to assess the uptake, distribution, tabolism, and elimination of volatile chemicals in mammals. A gas-phase vial equilibration technique is presented for determining the liquid:air and tissue:air partition coefficients for low-molecular-weight volatile chemicals. This technique was developed from two previously described medium:air methods, relied solely on measurement of chemical concentration in the gas phase, and, compared to earlier work, extends the range of chemicals and tissues examined. Partition coefficients were determined with 0.9% saline, olive oil, and blood, liver, muscle, and fat tissues from rats for 55 compounds. Human blood:air coefficients were determined for 36 compounds and several blood:air values were also determined in the mouse and for one compound in the hamster. An approach is described for predicting the tissue solubilities of untested compounds based on oil:air and saline:air coefficients using regression analyses. A similar approach is used to model fat:air coefficients in terms of oil:air values and to model human blood: air coefficients in terms of rat blood:air coefficients.

[1]  M E Andersen,et al.  A physiologically-based description of the inhalation pharmacokinetics of styrene in rats and humans. , 1983, Developments in toxicology and environmental science.

[2]  H J Clewell,et al.  Metabolism of inhaled dihalomethanes in vivo: differentiation of kinetic constants for two independent pathways. , 1986, Toxicology and applied pharmacology.

[3]  M E Andersen,et al.  Physiological model for tissue glutathione depletion and increased resynthesis after ethylene dichloride exposure. , 1988, The Journal of pharmacology and experimental therapeutics.

[4]  H J Clewell,et al.  A physiologically based simulation approach for determining metabolic constants from gas uptake data. , 1986, Toxicology and applied pharmacology.

[5]  H. Rees.  The partition coefficients of styrene between blood and air and between oil and blood , 1974 .

[6]  M E Andersen,et al.  A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. , 1984, Toxicology and applied pharmacology.

[7]  Vera Fiserova-Bergerova,et al.  Determination and prediction of tissue-gas partition coefficients , 1986, International archives of occupational and environmental health.

[8]  H J Clewell,et al.  Quantitative evaluation of the metabolic interactions between trichloroethylene and 1,1-dichloroethylene in vivo using gas uptake methods. , 1987, Toxicology and applied pharmacology.

[9]  Vera Thomas,et al.  Biological-Mathematical Modeling of Chronic Toxicity. , 1981 .

[10]  A Sato,et al.  A structure-activity relationship of some chlorinated hydrocarbons. , 1979, Archives of environmental health.

[11]  A Sato,et al.  A vial-equilibration method to evaluate the drug-metabolizing enzyme activity for volatile hydrocarbons. , 1979, Toxicology and applied pharmacology.

[12]  M. Andersen.  Recent advances in methodology and concepts for characterizing inhalation pharmacokinetic parameters in animals and man. , 1982, Drug metabolism reviews.

[13]  E. Scott,et al.  Variability of glutathione S-transferase of human erythrocytes. , 1980, American journal of human genetics.

[14]  V. Fiserova-Bergerova,et al.  Effects of biosolubility on pulmonary uptake and disposition of gases and vapors of lipophilic chemicals. , 1984, Drug metabolism reviews.

[15]  H. van Rees.  The partition coefficients of styrene between blood and air and between oil and blood. , 1974, Internationales Archiv fur Arbeitsmedizin.

[16]  O. Igwe,et al.  Interaction between 1,2-dichloroethane and tetraethylthiuram disulfide (disulfiram). II. Hepatotoxic manifestations with possible mechanism of action. , 1986, Toxicology and applied pharmacology.

[17]  F. A. Smith,et al.  Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. , 1987, Toxicology and applied pharmacology.

[18]  A Sato,et al.  Partition coefficients of some aromatic hydrocarbons and ketones in water, blood and oil. , 1979, British journal of industrial medicine.

[19]  M E Andersen,et al.  Modeling the tissue solubilities and metabolic rate constant (Vmax) of halogenated methanes, ethanes, and ethylenes. , 1988, Toxicology letters.

[20]  H J Clewell,et al.  A physiological pharmacokinetic model for dermal absorption of vapors in the rat. , 1986, Toxicology and applied pharmacology.

[21]  M. Andersen,et al.  The significance of multiple detoxification pathways for reactive metabolites in the toxicity of 1,1-dichloroethylene. , 1980, Toxicology and applied pharmacology.