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. 2023 Jan 15:373:13-21.
doi: 10.1016/j.toxlet.2022.10.008. Epub 2022 Nov 1.

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

Barbara G Schmitt  1 , Joseph Tobin  2 , Debra A McNett  3 , Jaeshin Kim  3 , Jeremy Durham  3 , Kathleen P Plotzke  3
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Free article

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

Barbara G Schmitt et al. Toxicol Lett. .
Free article

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.

Keywords: D4; Fischer 344; Octamethylcyclotetrasiloxane; Pharmacokinetics; Sprague Dawley CD; Strain-specificity.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Barbara Schmitt reports financial support was provided by American Chemistry Council Silicones Environmental Health and Safety Center. Barbara Schmitt reports a relationship with American Chemistry Council Silicones Environmental Health and Safety Center that includes: board membership. Joe Tobin reports a relationship with American Chemistry Council Silicones Environmental Health and Safety Center that includes: board membership. Debra McNett reports a relationship with American Chemistry Council Silicones Environmental Health and Safety Center that includes: board membership. Jeremy Durham reports a relationship with American Chemistry Council Silicones Environmental Health and Safety Center that includes: board membership. Kathleen Plotzke reports a relationship with American Chemistry Council Silicones Environmental Health and Safety Center that includes: board membership.

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