A method for direct measurement of systemic uptake and elimination of volatile organics in small animals.

ABSTRACT

A method was developed which was suitable for toxicokinetic studies requiring direct, repetitive sampling of blood and breath during exposures of small animals to volatile chemicals. Anesthetized male Sprague-Dawley rats were tracheostomized, and a specially fabricated one-way breathing valve was inserted directly into the trachea, in order that the inhaled and exhaled breath streams could be separated and independently sampled. The desired concentration of 1,1,1-trichloroethane was generated in a gas sampling bag, which was connected to the inlet side of the valve for inhalation exposures. Rats dosed with 1,1,1-trichloroethane by gavage inhaled ambient air through the valve. A pneumotachograph was positioned in the influent air stream to measure respiration. Respiratory rate, minute volume, and core temperature were continuously recorded on a physiograph. Samples of inspired and expired air were periodically collected from sampling ports immediately adjacent to the breathing valve and were analyzed for their 1,1,1-trichloroethane content by gas chromatography. Using this system, it was possible to determine percentage systemic uptake at any given time and to monitor cumulative uptake (i.e., total dose received) over the course of inhalation exposures. Alveolar concentrations were calculated by taking into account the respiratory indexes and dead space volume. A femoral vein was cannulated, so that concentrations of the chemical in the blood and breath could be measured concurrently. Data from rats dosed orally and by inhalation with 1,1,1-trichloroethane are presented to illustrate the applicability of the method in kinetics studies of volatile chemicals.