Frederick J. Di Carlo

Effects of Biosolubility on Pulmonary Uptake and Disposition of Gases and Vapors of Lipophilic Chemicals

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)

Structure-Activity Relationships (Sar) and Structure-Metabolism Relationships (Smr) Affecting the Teratogenicity of Carboxylic Acids

(1990). Structure-Activity Relationships (Sar) and Structure-Metabolism Relationships (Smr) Affecting the Teratogenicity of Carboxylic Acids. Drug Metabolism Reviews: Vol. 22, No. 5, pp. 411-449.

Summary of Carcinogenicity Data Generated by the National Cancer Institute/National Toxicology Program

(1984). Summary of Carcinogenicity Data Generated by the National Cancer Institute/National Toxicology Program. Drug Metabolism Reviews: Vol. 15, No. 5-6, pp. 1251-1273.

Bunolol Metabolism by Dogs: Urinary Excretion of 5-Hydroxytetralone

1. Anion exchange and t.l.c. were used to collect the polar drug metabolites present in urine of dogs treated orally with [14C]bunolol. 2. A new metabolite, 5-hydroxytetralone, was isolated, purified, and identified by u.v.,i.r. and mass spectroscopy. 3. 5-Hydroxytetralone represented 1.7% dose excreted in urine collected for 24 h after bunolol administration. 4. Properties of the metabolite are discussed in relation to the question of whether 5-hydroxytetralone was excreted as a conjugate.

Preface to Volume 3

Information Management, Innovation Management and Industrial Engineering are becoming increasingly interesting to both the academic researchers and management practitioners. It is essential to explore enterprise management system from the theoretical viewpoint; it is also absolutely essential to the survival, growth and prosperity of any company to have some means to manage innovation in the process of Economic Globalization and under the Knowledge Economy environment. As Chinas domestic economy is fast expanding, more and more enterprises and scholars in and outside China are paying high attentions to management innovation.