Effect of vapor concentration on the disposition of inhaled 2,3-dichloropropene in Fischer-344 rats

Abstract

2,3-Dichloropropene (DCP) is an intermediate used in the manufacture of carbamate herbicides and there is potential for human exposure during the manufacturing process. DCP is a known mutagen in bacteria systems and some structural analogs of DCP are carcinogenic. Since little is known about the disposition of DCP in animals after inhalation, studies were conducted in male Fischer-344 rats to determine the effect of vapor concentration on absorption and excretion. Uptake and elimination of 14C was studied in rats after nose-only inhalation of 17, 240, or 1650 nmol of [14C]DCP vapor/liter of air (0.4, 6, or 40 ppm, respectively, at 760 mm and 25 degrees C) for 6 hr. The percentage of inhaled DCP absorbed averaged 38% and was not statistically different at any vapor concentration, although minute volume was lower during exposure to 1650 nmol/liter. Urine, feces, and expired air were collected from rats for 65 hr after exposure. Rats were sacrificed and tissues, carcass, excreta, and expired air were analyzed for 14C. Routes of 14C excretion were independent of vapor concentration, with 50% of the 14C excreted in urine, 13% in feces, approximately 7% as CO2, and less than 1% as DCP in expired air. Rates of 14C excretion were also independent of vapor concentration, with the half-times averaging 9.9 hr (urine), 13.6 hr (feces), and 0.9 hr (14CO2). Sixty hours after inhalation, 29% of the initial body burden of 14C remained in the carcass. Most was associated with the pelt, but some 14C was found in all tissues. Respiratory tract, GI tract, liver, and kidney were tissues with the highest 14C contents. The results indicate that DCP metabolism and excretion rates are relatively constant throughout the vapor concentration range studied. This suggests that results from more detailed pharmacokinetic studies (and possibly toxicity studies) at one DCP concentration may be extrapolated to other concentrations within this range.