A dermal penetration rate (flux), predicted from physical properties of 132 chemicals, is suggested as an index of the dermal absorption potential of industrial chemicals. The prediction is designed for organic nonelectrolytes. Two reference values are recommended as criteria for skin notation: 1) dermal absorption potential, which relates to dermal absorption raising the dose of nonvolatile chemicals or biological levels of volatile chemicals 30% above those observed during inhalation exposure to TLV-TWA only--dermal absorption of chemicals belonging to this category should be considered when data obtained by biological monitoring are interpreted; and 2) dermal toxicity potential, which relates to dermal absorption that triples biological levels as compared with levels observed during inhalation exposure to TLV-TWA only. Chemicals belonging in this category should carry a skin notation. The toxicity criteria may not be valid for chemicals whose TLVs are based on preventing irritation and discomfort.
The head space method for determination of tissue-gas partition coefficients was modified to make it suitable for determination of tissue-gas partition coefficients of water soluble solvents. The method was used to determine tissue-gas partition coefficients of acetone, 2-butanone, methanol, ethanol, 1-propanol, 2-propanol and isobutanol for six representative tissues (muscle, kidney, lung, white and gray matter of brain, and adipose tissue). Blood-gas partition coefficients and distribution between plasma and erythrocytes were also determined. Relation between tissue-blood and fat-blood partition coefficients of 35 hydrophilic and hydrophobic substances of different chemical structure is described by linear correlation equations which can be used for prediction of tissue-gas partition coefficients of any chemical for which blood-gas and fat-gas partition coefficients are known. The correlation equations are based on all currently available data.
No abstract
Since statistical analysis proved the intercorrelation of tissue-gas partition coefficients of chemicals with similar chemical structures, bioavailability is controlled by one parameter dependent on the physicochemical properties of the chemicals and two constants distinguishing the tissues. Oil-gas partition coefficients are suggested to describe the biosolubility of volatile halogenated aliphatic chemicals. Tissue-gas partition coefficients derived from oil-gas partition coefficients were substituted in a pharmacokinetic model in order to study the effect of biosolubility on uptake, distribution, and elimination of inhaled chemicals. The simulation was focused on occupational exposures (8 h/day, 5 days/wk). Desaturation curves for all tissues show three exponential decays. The analysis of the simulation data indicates three patterns in behavior of inhaled vapors and gases in the body. Tissue uptake of poorly soluble chemicals (oil-gas partition coefficient less than 10) is flow limited at the beginning of exposure, but the partial pressures of such chemicals in the body equilibrate very rapidly with ambient air. Increased pulmonary uptake compensates for metabolic clearance. The rapid response of tissue concentrations to changes in exposure concentrations indicates that the toxic effect can easily be induced by short-term increase of exposure concentration, and that emergence from the reversible effect is rapid when exposure ceases. Tissue uptake of chemicals with oil-gas partition coefficients between 10 and 10(4) is flow limited during the entire 8-h exposure. Tissue concentrations increase slowly. Pulmonary uptake, being restricted by alveolar ventilation, compensates at steady state only for the amount of chemical removed by metabolic clearance. Therefore, tissue concentrations at steady state are lower than biosolubility. Accumulation during occupational exposure is obvious. Dumping of inhaled chemicals in adipose tissue protects the target organ from the occasional short-term increases in the exposure concentration. Tissue uptake of highly soluble chemicals (oil-gas partition coefficients greater than 10(4)) is limited by alveolar ventilation and exposure concentration. The rising and declining of tissue concentrations is very slow, half-times being in the magnitude of months and years. Metabolism reduces the half-time significantly. A lagging acute toxic effect can develop as the chemical accumulates in the body; the effect is most likely to persist long after the termination of the exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
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