Page 136 - The Toxicology of Fishes
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116                                                        The Toxicology of Fishes


                                   A
                                          140
                                      TCDD CONCENTRATION (pg/g)  100
                                          120
                                     WHOLE-BODY  60
                                           80



                                           40
                                           20
                                            0
                                             0        50       100       150       200
                                   B
                                         1.00

                                         0.80
                                     NET ASSIMILATION  EFFICIENCY  0.60




                                         0.40

                                         0.20

                                         0.00
                                             0        50       100       150       200
                                                               DAYS
                       FIGURE 3.28 Accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in brook trout. Measured whole-body con-
                       centrations (A) and calculated assimilation efficiencies (B) are shown as individual points. Simulations were obtained using
                       a physiologically based toxicokinetic model for brook trout. Dashed lines were generated using a “fecal partitioning” gut
                       submodel. Solid lines were obtained by imposing a “diffusion limitation” on dietary uptake. Vertical lines delineate the
                       three phases of the study: loading (0 to 28 days), maintenance (29 to 105 days), and depuration (105 to 182 days). (Adapted
                       from Nichols, J.W. et al., Environ. Toxicol. Chem., 17, 2422–2434, 1998.)

                        The primary advantage of this simple gut description is that it is not necessary to fit the value of a first-
                       order absorption rate constant. In a very simplistic way, the model also accounts for changes in chemical
                       affinity that accompany digestion (through its impact on P ) and the concentrating effect of a reduction in
                                                                  fb
                       meal volume (by specifying both Q food  and Q ). Moreover, because chemical is allowed to accumulate in
                                                        fec
                       blood flowing to the gut tissue compartment, the model provides for the possibility of decreased absorption
                       efficiency due to a decline in the gradient for uptake. The disadvantage of this model is that it cannot account
                       for kinetic limitations that may prevent an equilibrium from being established between feces and blood.
                        In the brook trout study, measured whole-body TCDD residues were lower than those predicted by
                       the fecal partitioning model, suggesting the existence of a kinetic limitation on dietary uptake (Figure
                       3.28). A second model was therefore developed that incorporated a diffusion limitation on the chemical
                       flux between feces and tissues of the intestinal tract. For the feces:

                                               dt = (  C food) −( Q C fec) − ( C fec − C gt P fgt)
                                          dA fec   Q food      fec   k gt      P                (3.108)
                       where A   is the amount of  TCDD in feces, k   is a first-order rate constant, C   is the chemical
                                                             gt
                             fec
                                                                                        gt
                       concentration in gut tissues, and P  is the feces–gut tissue equilibrium partition coefficient. For tissues
                                                 fgt
                       of the intestinal tract:
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