Disposition of Decamethylcyclopentasiloxane in Fischer 344 Rats Following Single or Repeated Inhalation Exposure to 14C-Decamethylcyclopentasiloxane (14C-D5)

The disposition of decamethylcyclopentasiloxane (D5) in male and female Fischer 344 rats following single or repeated inhalation exposures was evaluated. Animals were administered a single 6-h nose-only exposure to 7 or 160 ppm 14C-D5 or fourteen 6-h nose-only exposures to unlabeled D5 followed on day 15 by a 6-h exposure to 14C-D5. Subgroups of exposed animals were used to evaluate body burden, distribution, elimination, and deposition on the fur. Retention of radioactivity following single and repeated exposures was relatively low (approximately 1–2% of inhaled D5). Radioactivity and parent D5 were widely distributed to tissues of both male and female rats, with the maximum concentration of radioactivity observed in most tissues by 3 h postexposure. Fat was a depot for D5, with elimination occurring much slower than observed for plasma and other tissues. In all groups, the primary route for elimination of radioactivity was through expired air. Analyses for parent D5 indicated that essentially all the radioactivity in the expired volatiles was unchanged D5. Repeated exposure gave rise to higher levels of parent D5 in the lung and fat of both sexes and in female liver relative to the single exposure. In fat, immediately after sacrifice approximately 50% of the radioactivity was attributed to parent. Five polar metabolites of D5 were identified in urine, with no parent D5 detected. Radiochromatograms demonstrated two peaks in feces. One corresponded to the retention time for D5. The second has been putatively identified as hydroxylated D5.

[1]  A. C. Guyton,et al.  Measurement of the respiratory volumes of laboratory animals. , 1947, The American journal of physiology.

[2]  J. Mauderly Respiration of F344 rats in nose‐only inhalation exposure tubes , 1986, Journal of applied toxicology : JAT.

[3]  J. A. Mccay,et al.  Toxicology and humoral immunity assessment of decamethylcyclopentasiloxane (D5) following a 1-month whole body inhalation exposure in Fischer 344 rats. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[4]  P. Thévenaz,et al.  Inhalation toxicology of decamethylcyclopentasiloxane (D5) following a 3-month nose-only exposure in Fischer 344 rats. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  K. Plotzke,et al.  Extraction of octamethylcyclotetrasiloxane and its metabolites from biological matrices. , 1998, Analytical biochemistry.

[6]  S. Choudhuri,et al.  Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5). , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  Ekaterina Gibiansky,et al.  Applying Bailer's Method for AUC Confidence Intervals to Sparse Sampling , 2004, Pharmaceutical Research.

[8]  J. Tobin,et al.  In vitro and in vivo percutaneous absorption of 14C-octamethylcyclotetrasiloxane (14C-D4) and 14C-decamethylcyclopentasiloxane (14C-D5). , 2008, Regulatory toxicology and pharmacology : RTP.