US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA.
Aquat Toxicol. 2014 Nov;156:65-73. doi: 10.1016/j.aquatox.2014.07.022. Epub 2014 Aug 8.
Rainbow trout (Oncorhynchus mykiss) confined to respirometer-metabolism chambers were dosed with perfluorooctanoate (PFOA) by intra-arterial (i.a.) injection and sampled to obtain concentration time-course data for plasma, urine, and expired water. The data were then analyzed by compartmental modeling to estimate rates of renal and branchial clearance. Averaged across all animals, the renal clearance rate (1.35mL/h/kg) was more than ten times greater than the branchial clearance rate (0.12mL/h/kg). The average whole-body elimination half-life was 12.6d, which is somewhat longer than values obtained in previous studies with smaller trout. The tissue distribution of PFOA was assessed by collecting tissues at the end of chambered exposures and in a separate tissue time-course experiment. From the time-course study it appeared that an internal steady-state was established within 24h of i.a. injection. Consistent with previous studies, the rank order of PFOA concentration in tissues at steady state was: plasma>liver>kidney>muscle. In a second set of chambered experiments, fish were exposed to PFOA in water to determine the rate of branchial uptake. Branchial uptake rates were too low to assess directly by measuring PFOA concentrations in inspired and expired water. Uptake rate constants (mean 0.19L/d/kg; 0.1% uptake efficiency) were therefore estimated by compartmental modeling using plasma concentration time-course data and model parameters derived from the elimination experiments. It is clear from this effort that elimination of PFOA by trout occurs primarily via the renal route. This finding is consistent with numerous studies of mammals and suggests that trout possess membrane transporters that facilitate the movement of PFOA from plasma to urine.
虹鳟鱼(Oncorhynchus mykiss)被限制在呼吸代谢室中,通过动脉内(i.a.)注射给药,并取样以获得血浆、尿液和呼出水中的浓度时间过程数据。然后通过房室模型分析来估计肾脏和鳃清除率。在所有动物中,平均肾脏清除率(1.35mL/h/kg)是鳃清除率(0.12mL/h/kg)的十倍以上。平均全身消除半衰期为 12.6d,略长于以前用较小的鳟鱼进行的研究中获得的值。通过在室暴露结束时收集组织和在单独的组织时间过程实验中收集组织来评估 PFOA 的组织分布。从时间过程研究中可以看出,在动脉内注射后 24h 内建立了内部稳态。与以前的研究一致,在稳态时组织中 PFOA 的浓度顺序为:血浆>肝脏>肾脏>肌肉。在第二组室实验中,鱼在水中暴露于 PFOA 以确定鳃吸收的速率。由于无法直接通过测量吸入和呼出水中的 PFOA 浓度来评估鳃吸收速率,因此使用房室模型根据血浆浓度时间过程数据和消除实验得出的模型参数来估算吸收速率常数(平均值 0.19L/d/kg;0.1%吸收效率)。从这项工作中可以清楚地看出,PFOA 被鳟鱼消除主要通过肾脏途径。这一发现与许多哺乳动物的研究一致,表明鳟鱼具有膜转运蛋白,可促进 PFOA 从血浆向尿液的移动。