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in the world. The chemical name of DDT is 1,1
-(2,2,2-trichloroethylididene)-bis(4-
chlorobenzene) (CAS No. 50-29-3). It is known almost universally as DDT or
p,p
-DDT.
DDT and its metabolite DDE are highly persistent, and environmental and human tissue
residues are still detectable, even in areas in which DDT has not been used for decades.
Metabolism of DDT in the rat is shown in
Figure 9.2
and is reviewed by
Smith
(2010)
.
Organophosphorus Insecticides
There are numerous chemical types of organophosphorus insecticides, including phos-
phates, phosphorothioates, phosphorphorodithioates, phosphonates, etc. These and
others are classified by
Chambers et al. (2010)
in a scheme based on the central phos-
phorus atom and the four atoms immediately surrounding it.
Chlorpyrifos
Chlorpyrifos is an organophosphorothionate insecticide with the chemical name
O,O
-
diethyl-
O
-(3,5,6-trichloro-2-pyridinyl) phosphorothionate (CAS No. 2921-89-2). It is
widely used in agriculture. In the United States and elsewhere it was also used in pub-
lic health and residential pest control, but recently the U.S. Environmental Protection
Agency has banned residential use in the United States.
The oxon derivative is formed metabolically by CYP isoforms and is an irreversible
inhibitor of acetylcholinesterase. Chlorpyrifos is also known to have other, noncholin-
ergic effects. These include inhibition, in humans, of the oxidative metabolism of both
testosterone and estradiol.
Metabolism of chlorpyrifos in human hepatocytes is shown in
Figure 9.3
a and that
of chlorpyrifos oxon in
Figure 9.3
b. A review of chlorpyrifos toxicology is provided by
Testai et al. (2010)
.
Phorate
Phorate is a phosphorodithioate insecticide (chemical name
O,O
-diethyl-
S
-
ethylthiomethylphosphorodithioate, CAS No. 298-02-2). Phorate is used in agriculture
as a soil and systemic insecticide and sold under a number of names, the most com-
mon of which is Thimet. The mode of action of phorate is, first, activation to an oxon
by CYP, followed by inhibition of acetylcholinesterase by the oxon. While both the
P
S sulfur and the thioether sulfur are metabolized by cytochrome P450, the thio-
ether sulfur is also attacked by the flavin-containing monooxygenase (
Figure 9.4
) (
Levi
and Hodgson, 1988
).
Neonicotinoid Insecticides—Imidacloprid
Imidacloprid (chemical name
N
-[1-((6-chloro-3-pyridyl)methyl)-4,5-dihydroimidazol-
2-yl], CAS No. 138261-41-3) is an important representative of a relatively new class of
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