Biology Reference
In-Depth Information
Extravascular Dose
Humans are not typically exposed to pesticides by the intravenous route, but by extra-
vascular routes (oral, dermal, inhalation), and the pesticide must be absorbed to enter
the blood. Absorption is assumed to occur by a first-order process with an absorption
rate constant
k
a
as shown in
Figure 6.5
. For extravascular exposure, then, the rate of
removal of the chemical from the body is the net difference in the rates of introduc-
tion (by absorption) and elimination (by metabolism and excretion):
dA
dt
(29)
=
k A
−
k A
.
a
a
e
In Eq. (29),
A
a
is the mass of chemical at the site of absorption and
A
is the mass of
chemical in the body. As was noted earlier, extravascular exposure to chemicals is dif-
ferent from intravenous exposure, in that it cannot be assumed that 100% of the dose is
absorbed. Some fraction
F
of the dose (
D
) is absorbed, or only the product
FD
is bio-
available. The rate of removal of the chemical from the site of absorption is:
dA
dt
= −
a
k A
a
.
(30)
Solving for
A
as a function of time in the preceding equations yields:
exp(
−
k t
)
−
exp(
−
k t
)
,
e
a
A
=
k FD
(31)
t
a
k
−
k
a
e
which can be rewritten in terms of concentration to yield:
k FD
V
exp(
−
k t
)
−
exp(
−
k t
)
.
a
e
a
C
=
(32)
t
k
−
k
d
a
e
A typical plasma concentration-time curve for a compound that is absorbed by a
first-order process, rapidly equilibrates between blood and tissues and is eliminated by
a first-order process is shown in
Figure 6.5
. After oral administration to rats, the plasma
concentration vs. time profiles for triclopyr (
Timchalk et al., 1996
), diazinon (
Wu et al.,
1996
), and paraquat (
Chui et al., 1988
) are all described by the model in
Figure 6.5
. Some
time after administration, absorption is essentially complete and Eq. (32) is reduced to:
k FD
V
exp(
−
−
k t
)
.
a
e
C
=
(33)
t
k
k
d
a
e
Taking the logarithm of both sides of Eq. (33) yields:
k FD
V k
k t
a
e
log
C
=
log
=
2 303
.
(34)
t
(
−
k
)
.
d
a
e
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