Page 48 - The Toxicology of Fishes

28 The Toxicology of Fishes

bioavailability relationships similar to that discussed above for ammonia, with the lower part of this
sigmoidal curve reflecting the contribution of phenolate ions. This mechanism would explain reduced slopes
of uptake vs. pH when uptake becomes low at high pH, such as can be observed for three of the chemicals
in Figure 2.6; however, it could not explain high rates of uptake in the presence of substantial ionization.
Figure 2.8 explores the relative importance of these mechanisms by applying a mathematical model for
predicting gill uptake of ionizable organic chemicals (Erickson et al., 2006a,b). In the absence of the above
mechanisms by which phenolate ion can contribute to uptake, the model-predicted uptake (dotted line) is
extremely low because PCP is so highly ionized, and is two to four orders of magnitude below the observed
uptake rate constants. This rate would be expected if the epithelium contained barriers completely imper-
meable to the phenolate ion and if the kinetics of interconversion between the un-ionized and ionized
species were slow compared to transport processes in the gill. Adding the first mechanism discussed above
(rapid interconversion of phenolate ion and un-ionized phenol) to the model (dashed line) accounts for
most of the difference between the dotted line and the data. Also, adding pH changes in gill water to the
model (dash-dotted line) provides additional improvement to model predictions at high pH, bringing the
predictions very close to the observed data. Adding the final mechanism (some permeability of cellular
membranes to the phenolate ion) to the model has only a small effect on the full model predictions (solid
line), because the rate constants in this dataset are relatively high.
The example in Figure 2.8 should not be treated as being generally reflective of the relative importance
of these different mechanisms to phenol bioavailability. As already noted, membrane permeability for
the phenolate ion will become more important when uptake rates drop to levels lower than addressed
in this example, such as in Figure 2.6. The rapid interconversion of phenolate ion and un-ionized phenol
has a particularly large effect in the example in Figure 2.8 but appears to be less important for the
conditions of PCP uptake in Figure 2.6 and even less important for the other chemicals in Figure 2.6.
The relative importance of these mechanisms will vary substantially depending on properties of the
chemical, fish, and exposure of interest.
This section considered a more complicated bioavailability situation than for ammonia, addressing a
variety of the physical, chemical, and biological processes introduced earlier in Figure 2.3. Of particular
note is that a chemical species in exposure water can contribute to bioavailability even if it is not directly
absorbed by the organism, because of changes in chemical speciation that occur within the gill. Phenol
bioavailability might be even more complicated due to processes and factors not discussed here (e.g.,
the influence of other chemical constituents, such as organic matter, on phenol speciation), so the material
here should be treated as an example of how to approach certain aspects of bioavailability assessments,
not as a comprehensive discussion of all aspects of phenol bioavailability.
The mechanisms discussed above for the contribution of phenolate ion to phenol uptake can also affect
phenol elimination (Erickson et al., 2006b), and this can have consequences for bioavailability assess-
ments. Because any such effects on elimination are more important for steady-state accumulation than
during the initial stages of accumulation, the pH dependence of phenol accumulation would be expected
to vary with time. Available data do not allow confirmation of such an effect of time on bioavailability,
but this possibility illustrates how the meaning of bioavailability might be conditional on the specific
exposure situation and must be carefully defined.

Cationic Metals: Copper
The assessment of the risks of metals to fish is often difficult because of large and complex effects of
exposure water characteristics on metal toxicity. The nature and magnitude of these effects can differ
among metals, toxicity endpoints, fish species, and routes of exposure. This section focuses on the acute
lethality of copper to freshwater fish which has been reported by various authors to vary with pH,
hardness, alkalinity, suspended solids, dissolved organic compounds, and various other inorganic cations
and anions. Most, although not all, of this variation in toxicity can be attributed to effects of these
physicochemical factors on copper bioavailability.
Some understanding of toxicity mechanisms can help in understanding the effects of environmental
factors on toxicity and bioavailability. Acute copper lethality in freshwater fish has been related to
disruption of osmoregulation at fish gills. In particular, copper has been demonstrated to reduce sodium