Factors Determining the Toxicity of Organic Pollutants to Animals and Plants - Organic Pollutants: An Ecotoxicological Perspective - page 24

Considering again movement across phospholipid bilayers, where only passive
diffusion is involved, compounds below a certain molecular weight (about 800 kDa)
with very high K ow values tend to move into membranes but show little tendency to
move out again. In other words, they do not move across membranes to any impor-
tant extent, by passive diffusion alone. On the other hand, they may be cotransported
across membranes by endogenous hydrophobic molecules with which they are asso-
ciated (e.g., lipids or lipoproteins). There are transport mechanisms, for example,
phagocytosis (solids) and pinocytosis (liquids), which can move macromolecules
across membranes. The particle or droplet is engulfed by the cell membrane, and
then extruded to the opposite side, carrying associated xenobiotics with it. The lip-
ids associated with membranes are turned over, so lipophilic compounds taken into
membranes and associated with them may be cotransported with the lipids to other
cellular locations. Compounds of low K ow do not tend to diffuse into lipid bilayers at
all, and consequently, do not cross membranous barriers unless they are sufficiently
small and polar to diffuse through pores (see the preceding text). The blood-brain
barrier of vertebrates is an example of a nonpolar barrier between an organ and sur-
rounding plasma, which prevents the transit of ionized compounds in the absence of
any specific uptake mechanism. The relatively low permeability of the capillaries of
the central nervous system to ionized compounds is the consequence of two condi-
tions: (1) the coverage of the basement membranes of the capillary endothelium by
the processes of glial cells (astrocytes) and (2) the tight junctions that exist between
capillaries, leaving few pores. Lipophilic compounds (organochlorine insecticides,
organophosphorous insecticides, organomercury compounds, and organolead com-
pounds) readily move into the brain to produce toxic effects, whereas many ionized
compounds are excluded by this barrier.

2.3.2 m e T a b o l i s m

2.3.2.1 general considerations
After uptake, lipophilic pollutants tend to move into hydrophobic domains within
animals or plants (membranes, lipoproteins, depot fat, etc.), unless they are
biotransformed into more polar and water soluble with compounds having low K ow .
Metabolism of lipophilic compounds proceeds in two stages:

Phase 1 Phase 2

Pollutant Metabolite Conjugate

Endogenous
molecule

In phase 1, the pollutant is converted into a more water-soluble metabolites, by oxi-
dation, hydrolysis, hydration, or reduction. Usually, phase 1 metabolism introduces
one or more hydroxyl groups. In phase 2, a water-soluble endogenous species (usu-
ally an anion) is attached to the metabolite—very commonly through a hydroxyl
group introduced during phase 1. Although this scheme describes the course of
most biotransformations of lipophilic xenobiotics, there can be departures from it.