Page 543 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

510 SECTION | IV Insecticides

VetBooks.ir 8 10 tons of the inactive alpha and beta isomers are CI CI CI CI CI
formed. Because of the widespread use of t-HCH, the
environment has become contaminated with the inactive
alpha and beta-HCH isomers.
CH
Overcoming the problem of insect resistance to the 3 * CI CI CI
OCs has also been associated with toxicity. A major CI
CH 3
mechanism of insect resistance to DDT was found to be
enzymatic dechlorination of DDT to dichlorodiphenyldi- CH 2 O CI CI
chloroethylene (Bonner and Yarbrough, 1988). While
Toxaphene Kepone
working to overcome resistance to DDT, it was discov-
ered that certain nontoxic DDT analogs and other com- CI
CI CI CI
pounds suppressed resistance when coapplied with DDT.
Toxicity to parent compounds as well as congeners has CI CI
been associated with use of the OCs. CI
O CI
The beginning of the science of toxicology can be CI
traced to the problems associated with use of DDT and
CI CI CI
the subsequent impact on man and the environment. CI CI
Rachel Carson’s book Silent Spring brought the problems Chlordane Dieldrin
associated with the use of DDT to national attention in
1962. OCs continue to be an environmental contaminant CI CI
as evident in this 2010 study (Ding et al., 2010).
The structures of various OC insecticides are shown in
Fig. 38.1.
CI CI
PHARMACOKINETICS/TOXICOKINETICS DDE

OC insecticides can be absorbed orally and topically, with
absorption being rapid due to the lipid solubility of these CI CH CI
compounds (Buck et al., 1976; Marth et al., 1989). In the
presence of animal or vegetable fat the gastrointestinal CI C CI
absorption is increased. OC insecticides are not highly
volatile, so inhalation is not a normal route of exposure CI
(Jaeger et al., 1973). Absorption of the OCs after inhala- DDT
tion exposure occurs primarily by mucocillary trapping
FIGURE 38.1 Structures of common organochlorines.
followed by gastrointestinal absorption. Distribution is to
the liver, kidney, brain, and adipose tissue (Buck and
Van Note, 1968; Buck, 1970; Booth and McDowell,
1975; Mrema et al., 2013). The acute toxicity caused is of
TABLE 38.1 Tissue Distribution of Endosulfan
concern, but bioaccumulation from chronic exposures is
equally important (Starr and Clifford, 1972). Chlorinated Tissue Endosulfan (ppb)
hydrocarbons are highly lipid soluble and persist in the Adipose tissue 4105
environment; as a result, bioaccumulation occurs in the
Liver ,50
food chain from the environment to animals and humans
(Mount et al., 1980; Oehme, 1991; Safe and Krishnan, Brain 80
1995; Watanabe et al., 1999; Backer et al., 2001; Smith Kidney 59
and Gangolli, 2002; Harris et al., 2005).
Stomach content 3541
As with all xenobiotics, the toxicity of the OCs is
related to absorption, distribution, metabolism and elimi-
nation (Jaeger et al., 1975; Beasley et al., 1994).
Tissue distribution of endosulfan in a human consum-
ing 100 mL of endosulfan is presented in Table 38.1 hydrocarbons, like paradichlorobenzene, undergo glucuro-
(Quick, 1992). nidation and sulfation. The cyclodiene insecticides, such
The diphenyl aliphatics, such as DDT, are dechlori- as endrin, are rapidly converted to epoxides by MFOs.
nated by mixed function oxidases (MFOs). Aryl Methoxychlor is rapidly eliminated compared to DDT by