Page 146 - The Toxicology of Fishes

126 The Toxicology of Fishes

As a practical matter, it is important that the extrapolated portion of the AUC be relatively small
(ideally, less than 10% of the total AUC). Due to the fact that the extrapolated part is just that, there is
some uncertainty in its true value, as the log-linear phase may not continue on the extrapolated line.
Calculating the AUMC also involves determination of that part of the total area that lies beyond the
last measured plasma concentration. If a log-linear phase is present:

AUMC tlast−∞ = tC p last + C plast (3.122)
last
,
,
,
z λ z λ 2
and AUMC is then AUMC 0–t,last + AUMC t,last–∞ . The problem of extrapolation is larger for AUMC than
for AUC because much more of the C ,t profile has been defined by the measured concentrations than
p
has been defined by the C ,t profile.
pt
Bioconcentration, Bioaccumulation, and Biomagnification
In this section, chemical bioconcentration, bioaccumulation, and biomagnification in fish are treated as
special topics because of their importance in the context of current regulatory approaches. By convention,
the term bioconcentration refers to the accumulation of waterborne chemicals by aquatic animals through
nondietary routes (Veith et al., 1979). The importance of bioconcentration as a measure of chemical
accumulation by fish has been recognized since the 1960s (Hamelink et al., 1971). By the, 1970s,
however, it had become apparent that uptake of very hydrophobic organic compounds by fish within an
environmental setting was dominated by the dietary route of exposure (Bruggeman et al., 1981, 1984).
The term bioaccumulation refers to the accumulation of chemicals by all possible routes of exposure.
As described below, bioconcentration and bioaccumulation are expressed by referencing the chemical
concentration in a fish to that in water or sediment. The term biomagnification refers to a stepwise
increase in chemical concentration in organisms representing successively higher trophic levels, resulting
from the ingestion of contaminated organisms at lower trophic levels. Biomagnification is expressed,
therefore, by referencing the extent of chemical bioaccumulation in a predator to that of its prey.
Processes that control the rate and extent of chemical accumulation in fish were described in earlier
sections of this chapter. Thus, uptake directly from water is dependent on factors that control chemical
flux across the gills and skin, including the bioavailability of waterborne compounds, limitations on
uptake imposed by water and blood flows, and the relative affinity of chemicals for blood, skin, and
water. Similarly, the rate of uptake from dietary sources is dependent on the oral bioavailability of
ingested compounds and the extent to which these compounds become concentrated in prey items.
Elimination of parent compounds may occur at the gills, skin, and gut or by secretion into bile or urine.
Chemical accumulation may be substantially reduced by biotransformation. In controlled exposures
with rainbow trout, Barron et al. (1989) found that measured concentrations of the phthalic acid ester
di-2-ethylhexylphthalate were 100 to 1000 times lower than those predicted from chemical hydropho-
bicity. Similar findings have been reported for several azaarenes (Southworth et al., 1980) and polycyclic
aromatic hydrocarbons (PAHs) (Jonsson et al., 2004). Experimental inhibition of metabolism resulted
in an increase in bioconcentration of pentachlorophenol (Stehly and Hayton, 1989a).
In field sampling efforts, low levels of bioaccumulation in fish have been found for hydrophobic but
easily metabolized PAHs (Varanasi et al., 1989). Lower than expected levels of bioaccumulation for
some lower chlorinated dibenzo-p-dioxins and dibenzo-p-furans in field-caught fish were also attributed
to metabolism (Opperhuizen and Sijm, 1990). Care is required, however, when interpreting field sampling
data because metabolism may occur at multiple sites within a food web, altering the concentration of
chemical to which a fish is exposed.
In Chapter 14, Mackay and Milford describe a chemical fate and transport model and show how this
model can be used to predict chemical concentrations in a water–sediment system. Outputs from such
models are often used as inputs to models of chemical bioconcentration and bioaccumulation in fish.
Models of bioconcentration and bioaccumulation take different forms, depending on simplifying assump-
tions and the need to mechanistically describe controlling processes. In regulatory applications, it is