Low Dietary Uptake Efficiencies and Biotransformation Prevent Biomagnification of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5) in Rainbow Trout.

With octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) being considered for evaluation under the UN Stockholm Convention on Persistent Organic Pollutants, which specifically acknowledges risks of biomagnification of persistent organic pollutants in traditional foods, a study into the mechanism of the biomagnification process of D4 and D5 in Rainbow trout was conducted by combining the absorption-distribution-metabolism-excretion for bioaccumulation (ADME-B) approach to determine intestinal and somatic biotransformation rates and radiochemical analyses to identify metabolite formation. High rates of intestinal biotransformation of D4 and D5 (i.e., 2.1 (0.70 SE) and 0.88 (0.67 SE) day-1, respectively) and metabolite formation [i.e., 52.0 (17 SD)% of D4 and 56.5% (8.2 SD)% of D5 were metabolized] were observed that caused low dietary uptake efficiencies of D4 and D5 in fish of 15.5 (2.9 SE)% and 21.0 (6.5 SE)% and biomagnification factors of 0.44 (0.08 SE) for D4 and 0.78 (0.24 SE) kg-lipid·kg-lipid-1 for D5. Bioaccumulation profiles indicated little effect of growth dilution on the bioaccumulation of D4 and D5 in fish and were substantially different from those of PCB153. The study highlights the importance of intestinal biotransformation in negating biomagnification of substances in organisms and explains differences between laboratory tests and field observations of bioaccumulation of D4 and D5.

Pharmacokinetics of aminomethylpropanol in rats following oral and a novel dermal study design.

This study determined the oral and dermal ADME of 2-amino-2-methyl-1-propanol (AMP), a substituted aliphatic alcohol used in a number of industrial and consumer products. Groups of 4 male Fischer 344 rats received either a single bolus oral or dermal dose of 18 mg/kg (14)C-AMP in water. The dermal dose was applied to an area of 12 cm(2) on the back of the rats for 6h under semi-occluded conditions and fitted with rodent jackets to prevent grooming. Time-course blood and excreta were collected, radioactivity determined and blood and urine analyzed for AMP and metabolites. The orally administered (14)C-AMP was rapidly absorbed and eliminated in urine. Elimination of radioactivity from blood was biphasic with a rapid alpha phase (t(1/2 alpha) approximately 1h) followed by a slower beta phase (t(1/2 beta)=41+/-4h plasma and 69+/-34 h RBC). Total urinary elimination accounted for 87-93% of the dose, most (72-77%) within the first 48 h. Fecal elimination accounted for only 3-10%. Only 3-4% of the dose was found in tissues 168h post-dosing. The total dermal absorption of (14)C-AMP was 42% that included approximately 8% of the dose remaining at the application site 162 h after washing. Less than 1% of the applied dose remained in the stratum corneum and approximately 6% of the dose was found in tissues. Urinary elimination was 43% of the administered dose, most ( approximately 17%) within 48 h, and approximately 2% was eliminated in feces. It took much longer to reach plasma C(max) after dermal application (8.5+/-4.7 h in plasma and 4.0+/-2.8h in RBC) than the oral dose (0.3h) and the AUC(0-->alpha) for dermal dose was approximately 8-fold lower than with the oral dose. Again, elimination of the radioactivity from blood was biphasic with apparent t(1/2 alpha) of 9+/-6 and 2+/-1h for plasma and RBC, respectively. However, the alpha phase was "flipped-flopped" due to relatively slow dermal penetration and rapid elimination of the systemically absorbed dose, which was corrected to approximately 0.3 h after separating alpha elimination phase from the absorption. The slope of the beta phase became parallel to the oral route upon cessation of the absorption from the dose site skin, between 18 and 42 h post-washing. No metabolite of AMP was detected either in blood or excreta of any rat. Results of this study suggests that toxicologically significant concentrations of AMP are unlikely to be achieved in the systemic circulation and/or target tissues in humans as a result of dermal application of products containing AMP. Additionally, systemically absorbed dose will be rapidly eliminated from the body with little remaining at the application site.

Determination of the dietary absorption efficiency of hexachlorobenzene with the channel catfish (Ictalurus punctatus).

This study was designed to experimentally measure the assimilation efficiency of hexachlorobenzene (HCB) in a warm-water, benthic-feeding fish species, the channel catfish (Ictalurus punctatus). Catfish were exposed to (14)C-radiolabeled HCB in catfish food over a 28-day exposure period, followed by a 14-day clearance period. Over the experimental period, the total (14)C residues were measured in fish tissue and a simple two-box kinetic model was applied to the data to simulate uptake and clearance dynamics. No detectable metabolism of HCB by catfish was found. A two-box kinetic model effectively modeled the uptake and clearance of (14)C-HCB in catfish, with a calculated assimilation efficiency of the chemical into the whole catfish of 67% (growth corrected). The growth-corrected pseudo first-order elimination half-life of (14)C-HCB from whole catfish was determined to be 29 days (k(2)=0.024 day(-1)).

Quantitation of 17alpha-ethinylestradiol in aquatic samples using liquid-liquid phase extraction, dansyl derivatization, and liquid chromatography/positive electrospray tandem mass spectrometry.

A rapid and sensitive method for the analysis of 17alpha-ethinylestradiol (EE2) in environmental aqueous samples has been developed. Aquatic samples were extracted using liquid-liquid extraction, and organic phase extracts were concentrated and derivatized with dansyl chloride. Analysis was performed using high-performance liquid chromatography with positive electrospray ionization and tandem mass spectrometry (HPLC/ESI-MS/MS). Deuterated 17alpha-ethinylestradiol was used as internal standard and was added to samples before extraction. A limit of quantitation of 1 ng/L was obtained using a 25 mL aqueous sample. The average recovery of EE2 spiked into a 25 mL tapwater sample was 100%. This highly sensitive quantitation method is useful for measuring low levels of EE2 in aqueous environmental samples.