Page 120 - The Toxicology of Fishes

100 The Toxicology of Fishes

Waterborne Exposure
Kinetic studies with fish may be conducted by exposing small fish or juveniles of larger species to a
chemical in water. Typically, the exposure is initiated with a fixed number of fish and at each sampling
time a subset of animals is collected to determine whole-body chemical concentrations. The exposure
may be conducted using a flow-through system that maintains a constant concentration of toxicant in
the exposure water. Alternatively, fish may be exposed in a static system, which may or may not be
renewed during the progress of a test. The aqueous concentration of toxicant in a static exposure system
may decline over time due to absorption by the test organisms. Additional losses may occur due to
adsorption to the test container, volatilization, photodegradation, and microbial metabolism.

Flow-Through Exposure—The rate of toxicant accumulation in fish dosed in a flow-through exposure
(dX/dt; usually normalized to body weight) is proportional to the difference between the concentration
of toxicant in the exposure water (C ) and the concentration unbound in the plasma water (C ):
w
p,u
dX dt = ( ρ C w − C p u, ) (3.37)
/
The C is constant during the exposure, and the C can be replaced with X/V, where V is the apparent
w
p,u
volume of distribution of the toxicant referenced to the exposure water. The units of V and ρ are usually
normalized to body weight; for example, if X had units of ng/g, and C and C had units of ng/mL,
w
p,u
then V would have units of mL/g and ρ would have units of mL/hr/g. ρ is often the same as CL , as
b
discussed on pages 95 to 96. Integration of Equation 3.37 gives an equation for X as a function of time:
ρ
X = VC w(1 − e −(/ Vt ) ) (3.38)
This equation can be fit to experimentally determined values of X at various times to determine values
for ρ and V, and the elimination half-life can be calculated as:
t = 0.693V/ρ (3.39)
1/2
Equation 3.38 predicts that X will exponentially approach a limiting value equal to VC . The value of
w
V is equivalent to the bioconcentration factor (BCF), as described later in this chapter.
When a metabolite of the toxicant is formed during the exposure, this model may be extended to
permit simultaneous characterization of its toxicokinetics. One approach is to determine the total amount
of metabolite formed, including that in the fish and in the exposure water. Quantification of the amount
eliminated to the exposure water is complicated by the need to measure metabolite in water flowing
from the exposure vessel. The appropriate rate equations for this situation are:

dX dt = ( ρ C w − C p u, ) − CL C p u, (3.40)
/
m
dM dt = CL C p u, (3.41)
/
m
where CL is the metabolism clearance for metabolite formation. The integrated form of Equation 3.40
m
is (Benet, 1972):
−
X = X ss(1 − e ) (3.42)
kt
el
where
X ss = ρ VC w (ρ + CL m) (3.43)
k el = (ρ + CL m V) (3.44)

The integrated form of Equation 3.41 is: