Comparative pharmacokinetic studies of 14C-octamethylcyclotetrasiloxane (14C-D4) in Fischer 344 and Sprague Dawley CD rats after single and repeated inhalation exposure

Abstract

Octamethylcyclotetrasiloxane (D4) is a high production volume chemical that has been subject to thorough toxicological investigations. Animal studies with the substance were conducted with either Fischer 344 or Sprague Dawley CD rats. While the pharmacokinetic fate of D4 in Fischer rats is well understood, little information exists on Sprague Dawley CD rats, where reproductive effects have been demonstrated. The objective of this study was to explore the pharmacokinetic behavior in both rats, and to identify potential strain-specific differences. Fischer and Sprague Dawley CD rats were exposed for six hours to 700 ppm of 14C-D4 vapor either with or without preceding 14-day exposure to non-radiolabeled D4. Time-course data in blood, tissues and excreta were obtained through 168 h post-exposure and analyzed for both total radioactivity and parent D4. The data confirm that repeated exposure results in increased metabolism in both rat strains, confirming the findings of earlier studies of auto-induction of CYP2B1/2 by D4. The results also indicate that D4 is subject to strain-specific pharmacokinetic behavior, and that Fischer rats appear to metabolize D4 to a greater extent than Sprague Dawley CD rats.