Metabolism of 14 C-octamethylcyclotetrasiloxane ([ 14 C]D 4 ) or 14 C-decamethylcyclopentasiloxane ([ 14 C]D 5 ) orally gavaged in rainbow trout (Oncorhynchus mykiss)

• Published in: Toxicology letters 2017-10, Vol.279 Suppl 1, p.115-124
• Main Authors: Domoradzki, Jeanne Y, Sushynski, Jacob M, Thackery, Lisa M, Springer, Timothy A, Ross, Timothy L, Woodburn, Kent B, Durham, Jeremy A, McNett, Debra A
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Carbon Isotopes; Environmental Pollutants - blood; Environmental Pollutants - metabolism; Environmental Pollutants - pharmacokinetics; Environmental Pollutants - urine; Oncorhynchus mykiss; Prednisolone - analogs & derivatives; Siloxanes - metabolism; Siloxanes - pharmacokinetics
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2017.03.025

Critical factors (uptake, distribution, metabolism and elimination) for understanding the bioaccumulation/biomagnification potential of Octamethylcyclotetrasiloxane (D ) and Decamethylcyclopentasiloxane (D ) siloxanes in fish were investigated to address whether these chemicals meet the "B" criteria of the Persistent, Bioaccumulative, and Toxic (PBT) classification. A metabolism study was conducted in rainbow trout whereby a 15mg [ C]D /kg bw or [ C]D /kg bw as a single bolus oral dose was administered via gavage. Of the administered dose, 79% (D ) and 78% (D ) was recovered by the end of the study (96-h). Eighty-two percent and 25% of the recovered dose was absorbed based on the percentage of recovered dose in carcass (69% and 17%), tissues, bile and blood (12% and 8%) and urine (1%) for D and D , respectively. A significant portion of the recovered dose (i.e. 18% for D and 75% for D ) was eliminated in feces. Maximum blood concentrations were 1.6 and 1.4μg D or D /g blood at 24h post-dosing, with elimination half-lives of 39h (D ) and 70h (D ). Modeling of parent and metabolite blood concentrations resulted in estimated metabolism rate constants (k ) of 0.15 (D ) and 0.17day (D ). Metabolites in tissues, bile, blood, and urine totaled a minimum of 2% (D ) and 14% (D ) of the absorbed dose. The highest concentration of C-activity in the fish following D administration was in mesenteric fat followed by bile, but the opposite was true for D . Metabolites were not detected in fat, only parent chemical. In bile, 94% (D ) and 99% (D ) of the C-activity was due to metabolites. Metabolites were also detected in the digestive tract, liver and gonads. Approximately 40% of the C-activity detected in the liver was due to the presence of metabolites. Urinary elimination represented a minor pathway, but all the C-activity in the urine was associated with metabolites. Clearance may occur via enterohepatic circulation of metabolic products in bile with excretion via the digestive tract and urinary clearance of polar metabolites.