2. Organophosphates
• Organophosphorus (OP) compounds are usually esters, amides or thiol derivatives of
phosphoric acid .
• They decompose within days to weeks after application.
• They break down to phosphoric acid, alcohols, and thiols.
• Organophosphorus compounds are metabolized quickly by animals – no
bioaccumulation.
• They tend to be more acutely toxic than organochlorines.
• They form a large family (> 50 000 compounds) of chemical agents with biological
properties that have important, and sometimes unique, applications for the benefit of
mankind.
• A large group of chemicals used for protecting crops, livestock, human health and as
warfare agents.
• They are also been used as plasticizers, stabilizers in lubricating and hydraulic oils, flame
retardants, and gasoline additives.
3. • some pesticides in this group are extremely toxic e.g. disulfoton and
parathion, while others are relatively safe e.g. malathion.
• Some are rapidly degrading e.g. dichlorvos and mevinphos, while
others are extremely persistent e.g. parathion, azinphos methyl.
• Some are systemic e.g. dimethoate, disulfoton, demeton-S-methyl,
monocrotophos, and methamidophos while others are contact e.g.
dichlorvos, and mevinphos.
• Some have a fumigant action e.g. dichlorvos.
• Can be foliar or soil- applied, or can be used as a seed dressing e.g.
chlorpyriphos and disulfoton.
5. Organophosphates
• On the basis of structural characteristics they are divided into at least 13 types :
phosphates, phosphonates, phosphinates, phosphorothioates (S=),
phosphonothioates (S=), phosphorothioates (S substituted), phosphonothioates (S
substituted), phosphorodithioates, phosphorotrithioates, phosphoramidothioates .
• The first OPs were synthesised in the 19th century and used widely in the 1930s.
• The German chemist Gerhard Schrader synthesised many commercial OPs of
which parathion is still used as a common pesticide.
• At the beginning of the Second World War the development of OP substances
switched to highly toxic compounds employed as nerve warfare agents, e.g. sarin,
soman and tabun .
6. Organophosphates
• X is the “leaving group,” that is displaced when the OP
phosphorylates acetylcholinesterase (AChE), and is the most
sensitive to hydrolysis.
• R1 and R2 are most commonly alkoxy groups (i.e., OCH3 or
OC2H5).
• other chemical substitutes are also possible; either an
oxygen or a sulfur are also attached to the phosphorus with
a double bond.
7. • There are commonly three types of organophosphates :
A)
B)
C)
•tend to be the most volatile
•break down the fastest
•more stable than type A
•break down into type A
•some insects absorb type B and C better
than type A
•generally, but not always less toxic than
type A
8. Organophosphates
•type A
•highly toxic – LD50 = 25mg/kg
•used in fly strips and flea collars due to its
volatility
•type B
•extremely toxic – LD50 = 3mg/kg
•non-specific – can easily kill birds and fish and bees
•may be responsible for more human deaths than any other
pesticide
•still used in developing countries
•type C
•slightly toxic – LD50 = 985mg/kg
•widely used agriculturally and domestically
•used to spray communities to reduce mosquitoes and other
pestsmalathion
9. OPs as Pesticides
• Most widely used pesticides for insects control.
• First organophosphate insecticide was Tetraethylpyrophosphate (TEPP), and it
was approved in Germany in 1994.
• It was marketed as substitute for Nicotine to control Aphids.
• Because of its high mammalian toxicity and rapid hydrolysis in water, TEPP was
replaced by other OP insecticides.
• Parathion was another widely used insecticide due to its stability in aqueous
solutions and its broad range of insecticidal activity.
• However, its high mammalian toxicity through all routes of exposure led to the
development of less hazardous compounds.
• Malathion in particular, has low mammalian toxicity because mammals possess
certain enzymes, the carboxylesterases, that readily hydrolyze the carboxyester
link, detoxifying the compound.
10. Organophosphates
• Two examples of OP pesticides are methyl-parathion with a bonded S
atom and methyl-paraoxon with a bonded O atom.
• . The structure of toxic OP warfare agents: (a) tabun, (b) soman, (c)
sarin.
11. Organophosphates
• A single droplet of Sarin , if inhaled or in contact with the skin, can be absorbed
into the bloodstream and paralyze the nervous system, leading to respiratory
failure and immediate death.
12. MECHANISM OF TOXICITY
• The toxicity of OPs depends on their chemical structure, metabolism in
target organism, concentration (i.e. dose), mode of application, degree of
decomposition, mode of entering organisms, etc.
• The best described OPs toxic effects are the neurological symptoms
following acute poisoning as a consequence of the primary target (AcHE).
• Acute organophosphorus poisoning occurs after dermal, respiratory, or oral
exposure to either low volatility pesticides or high volatility nerve agents
(e.g., sarin, tabun).
• Acetylcholinesterase inhibition by organophosphorus pesticides or
organophosphate nerve agents can cause acute parasympathetic system
dysfunction, muscle weakness, seizures, coma, and respiratory failure.
13. Organophosphates
• Residues linger on fruits and vegetables.
• The degree of absorption depends on the contact time with the skin,
the lipophilicity of the agent involved and the presence of solvents.
• The rate of absorption also varies with the skin region affected. For
example, parathion is absorbed more readily through scrotal skin,
axillae and skin of the head and neck than it is through the skin of the
hands and arms.
• Following absorption, OP compounds accumulate rapidly in fat, liver,
kidneys and salivary glands.
14. Organophosphates
• Organophosphates interfere with cholinesterase activity.
• Cholinesterase is an enzyme that breaks down acetylcholine.
• Acetylcholine is an important neurotransmitter.
• High levels of acetylcholine cause convulsions, irregular heartbeat,
and death.
• Organophosphates thus act as irreversible cholinesterase inhibitors
because the organophosphate-cholinesterase bond is not
spontaneously reversible without pharmacological intervention.
• Most poisoning occurs through acute exposure of people applying the
insecticides.
16. Organophosphates
• The inhibition of cholinesterase activity leads to the accumulation of
acetylcholine at synapses, causing overstimulation and subsequent
disruption of transmission in both the central and peripheral nervous
systems.
• Chronic occupational exposure to OPs has been linked to increased
risk for cancer development such as non-Hodgkin lymphoma and
some types of leukaemia.
17. Organophosphates
• Direct immunotoxic effects of OPs can be due to:
1. inhibition of serine hydrolases (complement system) or esterases
(lymphocyte and monocyte membranes) in the immune system;
2. oxidative damage of immune system organs;
3. changes in signal transduction pathways that control proliferation
and immune cell differentiation.
18. Adverse and Environmental Effects
• These pesticides result in acute toxic reactions. If the victim is removed from
exposure, recovery is very rapid.
• There are usually no after effects provided renewed exposure is avoided.
• Very mild exposure to organophosphates causes headache, and common cold.
• When acute poisoning is severe, the following symptoms occur: cold sweating,
salivation, nausea, bronchoconstriction, tightness of chest, decreased blood
pressure and eye pupil constriction.
• Chronic effects of poisoning include: impaired reasoning capacity, embryo-
deforming effects (teratogenic), chromosome abnormalities (mutagenic) and
carcinogenic effects.
• Organophosphates in birds cause behavioral changes: decreased nest
attentiveness and death of chicks.
• They are also harmful to fish.
19. Adverse and Environmental Effects
• OP are polar, so are not stored body fat. They are readily excreted in
urine.
• They are fast-acting, and are effective against both larva and adults.
• they are non-selective.
• avoid applying sub lethal doses as this encourages the development
of resistance.
•
20. Organophosphates
• Organophosphates are found in pesticides and nerve gas. Due to their
particularly sinister properties, many countries have banned the use
of organophosphates in agriculture.
• Organophosphates poisonings are becoming less common for
paramedics, but hold a very high level of mortality and are dangerous
for all persons involved.
