The “Tuebingen Desiccator” System, a Tool to Study Oxidative Stress In Vivo and Inhalation Toxicokinetics

Abstract

The “Tuebingen desiccator,” a gas‐tight all‐glass closed chamber system (CCS), has been established in Herbert Remmer's Institute of Toxicology, University of Tuebingen, to investigate the mechanisms underlying the exhalation of endogenous volatile hydrocarbons in rats under oxidative stress. Remmer and associates confirmed the former view that ethane and n‐pentane were derived from polyunsaturated fatty acids, and they demonstrated that propane, n‐butane and isobutane were released from amino acids. Hydrocarbons exhaled following acute ethanol treatment of rats resulted predominantly from ethanol‐dependent inhibition of their metabolism and partly from oxidation of proteins. Exhalation of alkanes in carbon tetrachloride exposed rats did not reflect liver damage, which was, however, directly linked to the amount of carbon tetrachloride metabolized. As has first been shown in Herbert Remmer's institute by investigating the fate of inhaled vinyl chloride in rats, the CSS proved to be also an excellent tool for studying toxicokinetics of inhaled gaseous xenobiotics by means of gas uptake experiments. Based on results gained by such studies, it was recently demonstrated that knowledge of compound‐specific physicochemical and species‐specific physiological parameters are often sufficient to predict important toxicokinetic properties of inhaled chemicals such as tissue burdens at steady state. By means of the CCS, not only kinetics of a parent gaseous substance but also of gaseous metabolites can be investigated in vivo, as exemplified for ethylene oxide and 1,2‐epoxy‐3‐butene, metabolites of ethylene and 1,3‐butadiene, respectively. Gas uptake studies in closed chamber systems are now worldwide used for determining toxicokinetic parameters relevant for physiological toxicokinetic modeling.

Key Words :

• Closed chamber system
• Oxidative stress
• Endogenous hydrocarbons
• Volatile organic compounds
• Inhalation toxicokinetics