Biology Reference
In-Depth Information
soluble pesticides, which are not miscible in the aqueous intestinal fluid, can be pre-
sented as emulsions and brought into solution through the action of detergent-like bile
acids. The products of this mixing are large-surface-area micelles (hydrophobic inte-
rior) that deliver the lipids to the brush border of the intestine for diffusion across the
membrane.
Water readily traverses the plasma membrane through pores and may carry with it
small hydrophilic solutes. The pores in most cells are approximately 4 Å in diameter. In
the kidney glomeruli, however, the pores may be as large as 70-80 Å in diameter, which
permits more efficient renal elimination of potentially toxic compounds. Weak organic
acids and bases may cross plasma membranes by simple diffusion when they are non-
ionized. Ionized weak organic acids and bases, however, slowly permeate the plasma
membrane through pores.
According to the Brønsted-Lowry theory, an acid is a proton donor and a base is
a proton acceptor. The ratio of non-ionized to ionized molecules of a weak organic
acid or base depends on the dissociation constant (
K
a
) and the pH of the medium
(
Table 3.1
). The dissociation constant is usually expressed in terms of its negative log-
arithm, and the relationship between p
K
a
and pH is derived from the Henderson-
Hasselbalch equation as shown in
Table 3.1
. The p
K
a
is the pH at which 50% of the
acid or base is ionized. The concept of p
K
a
is particularly important for oral absorption
(see Absorption from the Gastrointestinal Tract) and often overlooked when assessing
dermal absorption (see Percutaneous Absorption).
The penetration of acidic and basic pesticides through skin can be influenced by
the skin surface pH, which is weakly acidic (pH 4.2-5.6). Paraquat and diquat are
hydrophilic pesticides that exist as fixed charged cations and remain dissociated at all
pH values. Very little paraquat or diquat is, therefore, expected to be absorbed by skin,
although percutaneous absorption of paraquat has resulted in systemic effects and deaths
in humans (
Smith, 1988
). Dermal absorption studies in human volunteers demonstrated
0.29, 0.23, and 0.29% absorption in the leg, forearm, and forearm, respectively (
Wester
Table 3.1
Acids and Bases According to the Brønsted-Lowry Theory
Acid
Base
AH ↔ A
H
B
H
↔ BH
Representation
Definition
Proton donor (AH)
Proton acceptor (B)
[
A H
AH
][
]
[
B H
BH
][
]
Dissociation constant (
K
a
)
K
a
K
a
[
]
[
]
p
K
a
log
1
K
a
p
K
a
pH
log
[
AH
A
]
p
K
a
pH
log
[
BH
B
]
log
K
a
[
]
[
]
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