Pesticide Excretion - Pesticide Biotransformation and Disposition - page 180

and salts, takes place in the proximal part of the tubule. This reabsorption may be
active, as in the case of glucose, amino acids, and peptides, whereas water, chloride, and
other ions are passively reabsorbed. Reabsorption of water and ions also occurs in the
distal tubule and in the collecting duct.
Reabsorption of xenobiotics is usually passive and controlled by the same prin-
ciples that regulate their passage across any membrane. That is, lipophilic compounds
cross cell membranes more rapidly than polar compounds; hence, lipophilic toxicants
will tend to be passively reabsorbed more than polar toxicants and, overall, elimination
of polar toxicants and their polar metabolites will be facilitated.
Tubular Secretion
Tubular secretion is another important mechanism for excretion of solutes by the kid-
ney. Secretion across the wall of the tubule is generally active, using two systems, one
for the secretion of organic acids, including conjugates, and the other for the secretion
of organic bases. Passive secretion may occur as a result of a process known as diffusion
trapping. Un-ionized weak acids and bases pass across the membrane into the lumen of
the tubule and, depending on the pH of the urine, one or the other may become ion-
ized and unable to diffuse back across the lumen wall. Diffusion trapping is, of course,
extremely sensitive to variations in urine pH, a factor that may be utilized to speed
elimination of toxicants. For example, alkalinization of the urine by ingestion of bicar-
bonate speeds up the elimination of salicylate.
Tubular secretion, and hence excretion, of organic anions has been known to be of
importance in the excretion of certain pesticides for some time ( Pritchard and James,
1982 ). 2,4-Dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid
are usually applied as salts or esters, the latter being readily hydrolyzed in the body, and
studies of their excretion have emphasized the parent acids, although various conju-
gates are also transported by the organic anion transport system ( Erne, 1966; Pritchard
and James, 1982 ). Active tubular secretion of 2,4-D has been demonstrated in a num-
ber of species, including the rabbit ( Dybing and Kolberg, 1967 ), rat ( Fang et al., 1973 ),
chicken ( Erne and Sperber, 1974 ), dog ( Hook et al., 1976 ), goat ( Orberg, 1980 ), and
flounder ( Pritchard and James, 1979 ).
1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its principal metabolite,
1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), are highly lipophilic and the lat-
ter is recalcitrant to further metabolism. Thus, DDT and, to a greater extent, DDE
are sequestered in body lipids and have an extremely long half-life in the body. Some
portion of DDT, however, is metabolized to an organic acid, 2,2-bis(p-chlorophenyl)
acetic acid (DDA), by dechlorination and oxidation at the one-position ( Pinto et al.,
1965 ). DDA is a substrate for the organic acid transport system ( Pritchard, 1976, 1978 )
and, as a consequence, is excreted considerably more rapidly than DDT or DDE.