Absorption - Pesticide Biotransformation and Disposition - page 28

et al., 1984 ). Other studies have determined that the in vitro permeability constants for
paraquat in various animal species (rat, hairless rat, nude rat, mouse, hairless mouse, rab-
bit, guinea pig) are 40-1600 times greater than for humans ( Walker et al., 1983 ). One
radiolabeled in vivo rat study reported a dermal bioavailability of 3.8% ( Chui et al.,
1988 ), which supports the claim that rodent studies can overestimate human absorp-
tion. Like paraquat, very little diquat is absorbed (0.3%) in the human forearm in vivo
( Maibach and Feldmann, 1974 ). Diquat absorption increased to 1.4% with occlusion
and to 3.8% with damaged skin. Data from these in vivo and in vitro studies suggest
that paraquat- or diquat-induced dermatotoxicity is a highly probable mechanism, a
priori, for dermal absorption of these hydrophilic and charged pesticides.
Specialized Transport
Active transport systems are characterized by (1) movement of solutes against a con-
centration or electrochemical gradient, (2) saturation at high solute concentration, (3)
specificity for structural and/or chemical features of the solute, (4) competitive inhibi-
tion by molecules transported by the same transporter, and (5) inhibition of transport
by compounds and/or processes that interfere with cellular metabolism. Facilitated dif-
fusion is similar to active transport, except that the solute moves only in the direction
of a concentration or electrochemical gradient and the expenditure of energy is not
required ( Figure 3.2 ). Additional types of specialized transport are exocytosis and endo-
cytosis, processes by which cells secrete and ingest large molecules, respectively. There
are two types of endocytosis: pinocytosis (cell drinking), which is the ingestion of flu-
ids and solutes, and phagocytosis (cell eating), which is the ingestion of large particles.
Phagocytosis is especially important in the removal of particulate matter in the respira-
tory tract. Recent studies have also suggested an even finer gradation in specific trans-
port processes (e.g., caveolae) that facilitate entry of different-sized material into the cell.
Many of the available commercial pesticides are transported across the skin and
GI tract by passive diffusion. However, there is some evidence that membrane trans-
port proteins play a significant role in the absorption mechanism in the GI tract
and account for pesticide influx and/or efflux of several pesticides. The hydrophilic
herbicide paraquat is thought to be absorbed by a mechanism that consists of facili-
tated, saturable, and diffusional components ( Heylings, 1991; Nagao et al., 1993 ). The
P-glycoprotein (P-gp/MDR1) is a transmembrane transporter in humans and animals
that is encoded by the ABCB1/MDR1 gene. This transporter is in various human tis-
sues such as the apical surface of intestinal epithelial cells. The interactions between
P-glycoproteins and the avermectin class pesticides and other classes of insecticides
such as methylparathion, endosulfan, cypermethrin, and fenvalerate have been well
documented ( Sreeramulu et al., 2007; Zhou, 2008 ). A similar or related mechanism has
been reported for the influx and efflux of neonicotinoids ( Brunet et al., 2008 ). These
interactions are important as they dictate the rate and extent of pesticide absorption