Pesticide Excretion - Pesticide Biotransformation and Disposition - page 178

Pesticide absorption and distribution

Hydrophilic pesticides Lipophilic pesticides

Major routes
of excretion

Phase I
Metabolism

Phase I
Metabolism

Renal

Phase II
Metabolism

Phase II
Metabolism

Hepatic

Minor routes
of excretion
Gender-linked
(milk, eggs, fetus)
Alimentary(GI tract, saliva),
Sweat, Hair

Figure 8.1 Routes of excretion in vertebrates.

first be metabolized into a form simulating that used by the body for the elimina-
tion of endogenous compounds. In general, they are metabolized by phase I and phase
II xenobiotic-metabolizing enzymes to conjugation products that are more polar and
hence more hydrophilic than the parent compound, and then excreted primarily by
either the renal or the hepatic route. Although similar anion and cation transport
systems are found in both the kidney and liver, they differ in the type of excretory
products that are eliminated. The renal system eliminates molecules of molecular mass
smaller than 400-500 Daltons, whereas the liver handles larger molecules. The molecu-
lar mass threshold between renal and biliary excretion varies with species ( Hirom et al.,
1972 ), although in most species there are excretory products that are excreted by both
systems. In addition to excretion via the bile, highly lipophilic chemicals that are recal-
citrant to metabolism may be excreted as the parent chemical by a number of alterna-
tive routes, although in terms of the overall excretion of pesticides these are generally
of minor importance compared to urine and bile. General aspects of the excretion of
toxicants and their metabolites may be found in Matthews (1994) , Pritchard and James
(1982) , Tarloff and Wallace (2008, 2010) and LeBlanc (2010) and a summary of the
overall process is shown in Figure 8.1 .
The excretion of pesticides and their metabolites has not been extensively investi-
gated, perhaps because the rate of excretion seldom appears to be a rate-limiting step
in the ultimate expression of toxicity. However, urinary metabolites continue to be uti-
lized as biomarkers of exposure.