Geoscience Reference
In-Depth Information
4.1.2 Organophosphates
The general chemical structure of organophosphate pesticides is shown in Fig.
4.3
.
The functional group R usually is either ethyl or methyl. Pesticides with double-
bonded sulfur moieties are organothiophosphates but are converted to organophos-
phates in the liver. Phosphonate contains an alkyl (R-) in place of one alkoxy group
(RO). The ''leaving group'' is the principal metabolite for a specific identification.
Acute pesticide poisonings frequently involve organophosphate pesticides; these
pesticides were originally derived from chemical warfare agents developed during
World War II. Some common organophosphates in use today include chlorpyrifos,
diazinon, azinphos-methyl, malathion, and methyl-parathion, all of which appar-
ently share a common mechanism of cholinesterase inhibition and cause similar
health effects. Organophosphates poison insects and mammals primarily by phos-
phorylation of the acetylcholinesterase enzyme (AChE) at nerve endings. The result
is a loss of available AChE so that the affected organ becomes overstimulated by
the excess acetylcholine (ACh, the impulse-transmitting substance) in the nerve
ending. The enzyme is critical to normal control of nerve impulse transmission from
nerve fibers to smooth and skeletal muscle cells, glandular cells, and autonomic
ganglia, as well as within the central nervous system.
4.1.3 N-methyl Carbamate
The general chemical structure of N-methyl carbamate is shown in Fig.
4.4
.
Common N-methyl carbamates in use today include aldicarb, carbofuran, me-
thiocarb, oxamyl, and carbaryl. N-methyl carbamates share with organophosphates
the
capacity
to
inhibit
cholinesterase
enzymes
and,
therefore,
share
similar
symptomatology during acute and chronic exposure.
The N-methyl carbamate esters cause reversible carbamylation of the acetyl-
cholinesterase enzyme, allowing accumulation of acetylcholine, the neuromediator
substance, at parasympathetic neuroeffector junctions (muscarinic effects), at
skeletal muscle myoneural junctions and autonomic ganglia (nicotinic effects), and
in the brain (CNS effects). The carbamyl-acetylcholinesterase combination disso-
ciates more readily than the phosphoryl-acetylcholinesterase complex produced by
organophosphate compounds. This property has several important consequences:
1. It tends to limit the duration of N-methyl carbamate poisoning.
2. It accounts for the greater span between symptom-producing and lethal doses
than most organophosphate compounds.
3. It frequently invalidates the measurement of blood cholinesterase activity as a
diagnostic index of poisoning.
N-methyl carbamates are absorbed by inhalation and ingestion, and somewhat
by skin penetration, although the last tends to be a less toxic route.
