Page 528 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 37

Organophosphates and Carbamates

Ramesh C. Gupta, Magdalini Sachana, Ida M. Mukherjee, Robin B. Doss,
Jitendra K. Malik and Dejan Milatovic

INTRODUCTION compounds, Gerhard Schrader (a chemist at the I.G.
Farbenindustrie) led the exploration of the OP class of
Organophosphates (OPs) and carbamates (CMs) are com-
compounds that could be used as insecticides. One of the
monly used in agriculture, industry and around homes/
earliest OP insecticides synthesized by Schrader was para-
gardens throughout the world. In addition, these chemicals
thion, which is still used worldwide. Prior to World War II,
are used in veterinary and human medicine. Both types of
the German Ministry of Defense developed highly toxic
chemicals produce their toxicity by virtue of inhibition of the OPs of the G series (tabun, sarin and soman) and diisopro-
acetylcholinesterase (AChE) enzyme, which terminates the
pyl phosphorofluoridate. In the 1950s, OP compounds with
action of the neurotransmitter acetylcholine (ACh) at the syn-
super toxicity of the V series, such as VX and VR, were
apses in nervous tissue and at the neuromuscular junctions
synthesized in the United Kingdom and the Soviet Union.
(NMJs). These chemicals are referred to as “anticholinester-
Since World War II, thousands of OPs have been synthe-
ase agents”. OPs, with strong AChE inhibiting potential, are
sized in the search for compounds with species selectivity,
also used as nerve agents or nerve gases in chemical warfare.
i.e., more toxicity to insects and less toxicity to mammals.
Many compounds of both classes are extremely toxic
Malathion is an example, as it has been used for more than
and lack species selectivity. Their inadvertent/accidental
half a century as the most popular insecticide. Today, more
use continues to pose a threat to human and animal health,
than 200 OPs are in use for a variety of purposes, such as
wildlife and aquatic systems, and the environment. Small
protection of crops, grains, gardens, homes and public
animals often encounter poisoning with these insecticides
health.
via malicious activity or accidental exposure, while live-
The first carbamate compound, physostigmine (eserine
stock may ingest freshly sprayed crop or contaminated
alkaloid), was isolated from calabar beans (ordeal poison)
feed. Although these compounds are neurotoxicants, they
of a perennial plant Physostigma venenosum in the mid-
produce a variety of cholinergic and noncholinergic effects.
1860s. The compound was used to treat glaucoma. About
The latest evidence suggests that while cholinergic mechan-
50 years later, an aromatic ester of carbamic acid, neo-
isms play a critical role in the initial stage of toxicity,
stigmine, was synthesized and used in the treatment of
neuronal damage/death appears to occur through noncholi-
myasthenia gravis. Most of the carbamates (esters of car-
nergic mechanisms. OPs and CMs are discussed together
bamic acid) that are used as pesticides were synthesized
here because they produce similar toxic effects in poisoned
in the 1960s and 1970s. Carbaryl was the first CM com-
animals. This chapter describes various aspects of toxicity
pound used as an insecticide. The most toxic compound
of OP and CM compounds and therapeutic interventions in
of this class, aldicarb, was synthesized by mimicking the
animals. For more details, readers are referred to publica-
structure of ACh. Like OPs, thousands of CMs have been
tions elsewhere (Gupta, 2006; Satoh and Gupta, 2010;
synthesized, but fewer than two dozen compounds have
Gupta and Milatovic, 2012; Gupta et al., 2017).
been used practically. Today, CMs are preferred for pesti-
cide use over OPs because some OPs have been found to
be extremely neurotoxic, while others cause delayed neu-
BACKGROUND
ropathy in animals as well as in humans. In essence, both
Tetraethyl pyrophosphate was the first OP compound syn- OPs and CMs have broad applications in agriculture and
thesized in 1854 by Philipe de Clermont. In 1932, Lange veterinary medicine and as a result of their indiscriminate
and Kruger described the synthesis of dimethyl and diethyl use acute poisonings often result in animals, birds, fish,
phosphorofluoridate. Based on the chemistry of these and wildlife.
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00037-4
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