Page 529 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

496 SECTION | VI Insecticides

VetBooks.ir R I. — X — R — O –— –— –—H VX (VR). These compounds are highly toxic and pose
II.
— O
continuous threats to the lives of humans as well as
—
C
animals since they can be used as chemical weapons of
–— N
1
–— 2
–— P –—R 1 — O CH 3 mass destruction (CWMD). Unlike so many incidents in
humans, animals have also been victims in some inci-
R 2 — dents of military operations. These compounds produce
R — O–— C–— CH 3
–— N–— toxicity by directly inhibiting AChE, and are much more
1
CH 3 potent than OP pesticides. Their chemical structures are
shown in Fig. 37.3. For details of toxicity of these
compounds, refer to Watson et al. (2006, 2015) and
FIGURE 37.1 General structure for organophosphorus (I) and carba- Rembovskiy et al. (2015).
mate (II) insecticides. Adapted from Timchalk, C., 2006. Physiologically
based pharmacokinetic modeling of organophosphorus and carbamate
pesticides. In R.C. Gupta (Ed.), Toxicology of Organophosphate CARBAMATES
and Carbamate Compounds. Academic Press/Elsevier, Amsterdam,
pp. 103 125 The carbamate (CM) compounds are esters of carbamic
acid. Unlike OPs, CM compounds are not structurally
complex. Chemical structures of some commonly used
Basic structures of OPs and CMs are shown in Fig. 37.1. CM insecticides are shown in Fig. 37.4, and brief toxi-
There are at least 13 types of OPs (Table 37.1). Despite dif- cological data of CMs is provided in Table 37.3.For
ferences in chemical structures, all OPs share one thing in the details of CMs, readers are referred to Gupta
common: they all have a pentavalent phosphorus atom and (2006) and Gupta and Milatovic (2012).Currently,the
a characteristic phosphoryl bond (PO) or thiophosphoryl volume of CMs used exceeds OPs because of their rel-
bond (PS). Essentially, OPs are esters of phosphoric acid ative safety.
with varying combinations of oxygen, carbon, sulfur and/or
nitrogen attached. Of course, the chemistry of these com- PHARMACOKINETICS OF OPs AND CMs
pounds is much more complex. The OPs that are derivatives
of phosphoric or phosphonic acid possess anticholinesterase Pharmacokinetics deals with the rate limiting processes
activity, unlike those that are derivatives of phosphinic acid. of absorption, distribution, metabolism and excretion
Usually, OP compounds have two alkyl substituents and an (ADME). The ADME of some OP and CM insecticides in
additional substituents group (the leaving group, which is animals have been described (Tomokuni et al., 1985;
more labile to hydrolysis than the alkyl group). Some OPs, Gupta, 1994; Wu et al., 1996; Timchalk, 2006, 2010;
such as dichlorvos, monocrotophos and trichlorfon, are Gupta and Milatovic, 2012; Gupta et al., 2017). These
direct AChE inhibitors, while those of the phosphorothio- insecticides gain entry into the body mainly through oral,
ates type, such as bromophos, diazinon, fenthion and para- dermal, or inhalation exposure. Ingestion of food contami-
thion, possess minimal anticholinesterase (anti-AChE) nated with pesticides residue is common, while dermal
activity and require desulfuration to analogous oxon before exposure is more relevant when these insecticides are
acquiring anti-AChE activity and hypercholinergic effects. used as ectoparasiticides in the form of dust, dip, or oily
Also, OPs that are used as defoliants (S,S,S-tributyl phos- solution. Inhalation of airborne insecticides occurs during
phorotrithioate and S,S,S-tributyl phosphorotrithioite), or soon after aerial spray, particularly due to chemical
herbicides (glyphosate and gluphosinate), flame retardants, drift. Once the insecticide reaches a portal of entry, it is
and plasticizers are of very low mammalian toxicity. available for absorption. It is established that following
absorption, these insecticides are well distributed in tis-
sues throughout the body. Being lipophilic, maximum
OP PESTICIDES
levels of these compounds are usually found in the adi-
The majority of OP compounds are used as pesticides. pose tissue and brain.
Chemical descriptions for commonly used compounds In terms of metabolism, OP insecticides may follow
and their toxicity are given in Table 37.2. Chemical struc- either activation and/or detoxification. Activation
tures of some of the commonly used OP pesticides are implies that the metabolite is more toxic than the parent
shown in Fig. 37.2. compound, e.g., the conversion of malathion to malaox-
on. This process is often called “lethal synthesis.” On
the other hand, detoxification implies that the metabolite
OP NERVE AGENTS/GASES
is less toxic than the parent compound, e.g., the conver-
OP nerve agents include tabun (GA), sarin (GB), soman sion of malathion to malathion monoacid and malathion
(GD), cyclosarin (GF), venom toxin (VX), and Russian diacid. Unlike OPs, CMs are metabolized to less toxic or