Inhalation pharmacokinetics of technical grade 1,3-dichloropropene in rats

Kinetic data on the uptake of vapors of technical grade 1,3-dichloropropene (DCP) and resultant cis- and trans-DCP blood concentrations were obtained in rats exposed to 30, 90, 300, or 900 ppm DCP for 3 hr. The uptake of DCP did not increase proportionately with increasing exposure concentration due to an exposure level-related decrease in the respiratory ventilatory frequency of rats exposed to greater than or equal to 90 ppm DCP and the saturation of metabolism of DCP by rats exposed to greater than or equal to 300 ppm DCP. Absorption of inhaled DCP occurred primarily in the lower respiratory tract, although a small amount of the chemical was absorbed via the nasal mucosa, a known target tissue of inhaled DCP in rats. Following absorption, both isomers of DCP were, at less than or equal to 300 ppm exposure levels, rapidly eliminated from the bloodstream (3-6 min half-life). In addition, data obtained in rats exposed to 300 ppm DCP revealed that this rapid elimination phase was followed by a slower elimination phase having a 33-43 min half-life. Rats exposed to 900 ppm vapors also eliminated DCP in a biphasic manner; however, in this case the blood half-life of DCP during the initial phase of excretion was 14 to 27 min. Exposure to 90 ppm DCP also produced a significant decrease in renal (31%) and hepatic (41%), but not pulmonary, nonprotein sulfhydryl content. Overall, these data demonstrated that a combination of saturable metabolism and chemically induced changes in respiration control DCP uptake and body burden in rats.