Fate of inhaled hexachlorocyclopentadiene in albino rats and comparison to the oral and IV routes of administration

Abstract

Hexachlorocyclopentadiene (C56) is extremely toxic when inhaled by rats, but only moderately toxic when administered orally. The difference in toxicity as a function of route of exposure was studied by determining the absorption, distribution, and ultimate fate of C56 following acute oral, inhalation, and iv exposure. For rats treated with a single oral dose (5 μg/kg) of 14C-C56, radiocarbon was primarily excreted in the 0–72 hr feces (68.2%). Animals treated with equivalent inhaled and iv doses eliminated 23.1 and 31.4% of the dose in the 0–72 hr feces, respectively. Urinary radiocarbon was equivalent to 24.4, 23.1, and 31.4% of the dose for oral, inhalation and iv treatments, respectively. Biliary excretion following all exposure routes was between 9 and 18% of the dose, indicating that the large amount of radiocarbon in the feces of orally treated rats was due to poor absorption of C56 from the gastrointestinal tract. For all exposure routes, the lungs appeared to be a major site of C56 toxicity upon post-mortem examination. This study suggests that the direct damage to lung tissue by inhaled C56 and low bioavailability of orally administered C56 contribute substantially to the difference in toxicity between oral and inhalation exposure to C56. A recently developed inhalation exposure system which allows quantitative administration of toxicant vapors to rats is also described in this report.