Page 133 - The Toxicology of Fishes
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Toxicokinetics in Fishes                                                    113


                              0.8    6.0    1.0


                                                                                       TCE
                           HCE CONCENTRATION (mg/kg)   0.4  0.2  PCE CONCENTRATION (mg/kg)   3.0  1.5  TCE CONCENTRATION (mg/kg)  0.5  0.25  PCE
                                            0.75
                                     4.5
                              0.6


                                                                                       HCE







                              0.0    0.0    0.0
                                              0   4   8   12  16   20  24  28   32  36  40  44   48
                                                                     HOURS
                       FIGURE 3.26 Concentration time course of tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane
                       (HCE) in arterial blood of adult channel catfish. Catfish were simultaneously exposed to all three chloroethanes in water.
                       Solid lines represent simulations generated using a PBTK model incorporating the branchial uptake description given by
                       Erickson and McKim (1990b). Measured values are shown as individual points. (Adapted from Nichols, J.W. et al., Aquat.
                       Toxicol., 27, 83–112, 1993.)

                       of capillaries with chemical diffusion from water to blood perpendicular to the capillary axis. Given
                       these assumptions Equation 3.97 simplifies to:

                                                       k x =  k b(1 −  e − kd kb )              (3.102)
                                                                   /
                       This description suggests that dermal flux may be limited by the capacity of the skin surfaces to support
                       chemical diffusion (k ) and the capacity of blood flowing to the skin (k ) to remove chemical once it
                                       d                                       b
                       has been absorbed. The terms k  and k  are analogous to those given in Equations 3.99 and 3.100, except
                                              b
                                                    d
                       that in this case diffusivity, area, and thickness refer to the skin diffusion barrier, and the relevant blood
                       flow rate is that to skin. As in the gill model given by Erickson and McKim (1990b), diffusive flux was
                       assumed to be limited by chemical diffusion in the aqueous phase of the diffusion barrier. Using this
                       model, dermal flux (F ) may be calculated as the product of k  and the concentration gradient for uptake:
                                                                     x
                                       s
                                                      F s = (   C P bw)                         (3.103)
                                                          k C w −
                                                           x
                                                                  a
                       The chemical concentration in venous blood draining the skin is then calculated by adding this flux to
                       the amount of chemical already present in arterial blood perfusing the skin.
                        This model was used to compare the capacities of gill and skin surfaces to support chemical uptake in
                       small fish. Lien and McKim (1993) exposed fathead minnows and Japanese medaka to 2,2′,5,5′-tetra-
                       chlorobiphenyl (TCB), and Lien et al. (1994) exposed fathead minnows to a homologous series of three
                       chlorinated ethanes. Model predictions (gill only and gill plus skin) were evaluated by comparison with
                       measured whole-body chemical residues. Based on this analysis, approximately 50% of the total uptake
                       of TCB was attributed to dermal absorption. The contribution of dermal absorption to the uptake of the
                       three chloroethanes ranged from 20 to 30% and tended to increase with the degree of chlorine substitution.
                        A more complex description of dermal uptake is required if chemical accumulation by skin tissue
                       impacts chemical flux between water and blood. Following the approach used by McDougal et al. (1990)
                       to describe dermal flux of chemical vapors by rats, Nichols et al. (1996) developed a dermal uptake model
                       for fish that incorporates a discrete skin compartment. The model structure was also changed somewhat
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