Absorption - Pesticide Biotransformation and Disposition - page 26

Extracellular
space

Phospholipid
bilayer

Intracellular
space

Energy

Diffusion
via
pores

Simple
diffusion

Active
transport

Facilitated
diffusion

Figure 3.2 Schematic of the plasma membrane and mechanisms of transport across the membrane.

cross membranes by passive transport, which requires the expenditure of no energy, or
by specialized transport systems. The ability of a chemical to cross various membrane
barriers is determined by its physicochemical properties, which include lipophilicity,
molecular size, and ionization.

Transport Mechanisms
Passive Transport
Passive transport occurs by simple diffusion or via pores in the plasma membrane
( Figure 3.2 ). Most lipophilic molecules cross membranes by simple diffusion in accord
with Fick's first law of diffusion (see equation below), which states that the flux or rate
at which a molecule diffuses across the plasma membrane is proportional to the con-
centration gradient, the membrane surface area, and the permeability coefficient of the
molecule. The permeability coefficient is the product of the partition coefficient and
the diffusion coefficient.

diffusion coefficient × surface area × partition coeffici ent × conc. gradient

flux =

skin or membrane thickness

Theoretically, the determinants of flux or diffusion rates across the skin or gastro-
intestinal (GI) tract may be altered clinically or experimentally through manipulation
of pesticide formulations. If lipid solubility increases, the penetrant may remain in the
stratum corneum of the skin and form a reservoir. Some compounds can also form
a reservoir in the dermis. These scenarios can prolong absorption half-life across the
skin, which can also prolong the body burden of the penetrant. Ingestion of very lipid