A dynamic closed-loop recirculating inhalation chamber for conducting pharmacokinetic and short-term toxicity studies

Abstract

Tests for evaluating the hazard of inhalation exposure generally require large quantities of the chemical of interest. This paper describes an inhalation technique that involves a dynamic closed-loop recirculating system which uses only small amounts of toxicant since the test atmosphere to which the animals are exposed is recycled. Carbon dioxide and water are continually removed while the oxygen and test substance absorbed by the animals are replenished. The approach described is different from other closed-loop chambers since the test substance is continuously added to the chamber and the air concentration is continuously measured. The technique was successfully used to expose 20 adult rats for up to 12 consecutive hours to 100 ppm of 14C-carbon tetrachloride yet only 2–3 mL of test material were consumed. The inhalation chambers were fabricated from standard 40-liter cylindrical glass bell jars. A high number of air changes (35–40 equivalent chamber volumes per hour) permitted exposure of as many as five adult rats per 10 liters of chamber volume. This closed-loop approach should prove to be especially useful for evaluating the risk of exposure to very expensive materials or when only limited quantities of a test material are available. These systems may also be used to expose rats and other small animals to radioisotopes in studies which evaluate the uptake, distribution, metabolism, and excretion of volatile xenobiotics.