Dissociation-induced depletion of high-energy reactant molecules as a mechanism for pressure-dependent rate constants for bimolecular reactions.

In 1922, Lindemann proposed the now-well-known mechanism for pressure-dependent rate constants for unimolecular reactions: reactant molecules with sufficiently high energies dissociate more quickly than collisions can reestablish the Boltzmann distribution of the internal energies of the molecule during its dissociation at low pressures - yielding pressure-dependent rate constants for unimolecular reactions due to the preferential depletion of the high energy states capable of dissociation. In the last century, incredible progress has been made in achieving a far greater understanding of and quantitative predictions for unimolecular and association reactions. In the modern era, pressure-dependent phenomenological rate constants are now nearly universally used to describe the rates of unimolecular and associative reactions in phenomenological kinetic modeling.

Validation of intratracheal instillation as an alternative for aerosol inhalation toxicity testing.

In collecting inhalation toxicity data for the evaluation of the health hazard from occupational exposure to the aerosols of a drug or a chemical, the determination of the inhaled dose in relation to the animal response is most desirable. Intratracheal administration is most likely to deliver an exact dose of a compound to the lungs of an experimental animal. In a series of tests, microliter (microl) quantities of a solution or a suspension of a test material were nebulized into the trachea of an anesthetized rat using an intratracheal fast instillation (ITFI) method.

Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats.

The effectiveness of three techniques to deliver a diazo dye suspension into the lungs of rats was compared. The intratracheal nebulization (ITN) technique delivered 10 microl of the suspension per 5-ml puff of air in 10 puffs as an aerosol. The intratracheal fast instillation (ITFI) technique delivered 100 microl of the suspension in a single 2-ml puff of air as droplets.

Alterations in the cardiopulmonary effects and pharmacokinetics of a bisphosphonate drug by a cytochrome P-450 inhibitor in conscious rats.

U-91502, a bisphosphonate for arthritic inflammation treatment, was evaluated for its parental toxicity. The objective was to differentiate between the parent drug and a reactive metabolite(s) as the proximate cause of the toxic effects using two methods. The first method was to block the metabolism of U-91502 with a broad-spectrum cytochrome P-450 inhibitor, 1-aminobenzotriazole (ABT), to increase its toxicity.

Retinopathy from inhaling 4,4'-methylenedianiline aerosols.

4,4'-Methylenedianiline (MDA) is an important chemical intermediate in the production of isocyanates and polyurethane elastomers and polymers. The health hazards from acute inhalation exposure to the aerosols were evaluated. Guinea pigs of albino and pigmented strains were exposed nose-only to the aerosols of MDA in polyethylene glycol 200 (PEG) solution.