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Toxicokinetics of perfluorooctane sulfonate in rainbow trout (Oncorhynchus mykiss)
Consoer, D., A. Hoffman, P. Fitzsimmons, Pat Kosian, AND J. Nichols. Toxicokinetics of perfluorooctane sulfonate in rainbow trout (Oncorhynchus mykiss). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 35(3):717-727, (2016).
The perfluoroalkyl acids (PFAAs) are widely used as surfactants, stain resistant coatings, and fire-fighting foams. Numerous studies have shown that PFAAs can accumulate in fish; however, the extent of accumulation varies widely depending on alkyl chain length and the identity of the acid terminal group. Thus, sulfonates such are perfluorooctane sulfonate (PFOS) tend to accumulate to a much greater extent than carboxylates such as perflurooctanoate (PFOA). To date, Agency efforts to regulate these compounds have been hampered by a lack of understanding of processes responsible for these differences in behavior. Thus, the goal of this study was to determine the mechanistic basis for observed differences in PFAA accumulation by fish. The results demonstrate that differences in accumulation of PFOS and PFOA by trout are largely due to differences in renal elimination. Importantly, renal clearance of PFOA appears to be mediated by specific membrane transporters, while elimination of PFOS may be limited by glomerular filtration. These findings provide critical information required to develop predictive models for accumulation of this important class of environmental contaminants.
Rainbow trout (Oncorhynchus mykiss) confined to respirometer-metabolism chambers were dosed with perfluorooctane sulfonate (PFOS) by intra-arterial injection and sampled to obtain concentration time-course data for plasma, and either urine or expired water. The data were then analyzed using a two-compartment clearance-volume model. Renal and branchial clearance rates (CLR and CLB; mL/d/kg) determined for all experiments averaged 19% and 81% of total clearance (CLT), respectively. Expressed as mean values for all studies, the steady-state volume of distribution (VSS) was 277 mL/kg and the terminal half-life (T1/2) was 86.8 d. Additional animals were exposed to PFOS in water, resulting in an average calculated branchial uptake efficiency of 0.36%. The CLR determined in the present study is approximately 75 times lower than that determined in earlier studies with PFOA. Previously, it was suggested that PFOA is a substrate for membrane transporters in the trout kidney. The present study suggests that glomerular filtration may be sufficient to explain the observed CLR for PFOS, although a role for membrane transporters cannot be ruled out. These findings demonstrate that models developed to predict the bioaccumulation of PFAAs by fish must account for differences in renal clearance of individual compounds.