Historical Background
A pesticide is any substance intended for preventing, destroying, repelling or mitigating any pest. They are usually define according to the pest they are intended for: insecticides, fungicides, nematocides, herbicides and rodenticides. Fumigants are less specific agents used to kill insects, nematodes, weed seeds and fungi in soil or stored grains, fruits and vegetables.
Pesticides can be classified into four generations. The first generation pesticides includes mostly natural products like sulfur, arsenic and nicotine. The Chinese used sulfur as a fumigant around 1000 BC. Arsenic was used as a pesticide in Europe sice the 16th century. An extract of the tobbaco plant has also been use as early as th 1700's.
Moden synthetic chemicals were used as pesticides starting with the second generation pesticides. These included the organochloride pesticides DDT, dieldrin, aldrin, lindane and many herbicides. DDT was first synthesized by Ziedler in 1874, then rediscovered by Paul Muller in 1939 (1948 Nobel Price).
Third generation pesticides include the organophosphates, carbamates and 2,4-D. The organochloride and carbamate compounds use started in the 1930's and are currently the prominent insecticides in use. There has been an increase in use since the organochloride compounds were banned in some countries in the 1970's. Some organophosphates are used as warfare agents: tabun, sarin, soman, VX and CMPF.
Fourth generation pesticides are developed by genetic engineering. Plants are developed that secrete their own toxins or that are resistant to herbicide. Although generaly believe to be safer than previous generations, this is still not compleately known.
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Organochloride Pesticides
The organochloride pesticides are excellent insecticides, in part because they linger in the environment, requiring less frequent application, but alsobecause of their low toxicity to humans. They were used extensively in the 1940's, 1950's and 1960's, and are still used in areas where mosquito-trasmitted diseases are a mayor health problem.
Although
the organochlorides are carcinogenic in rodents, there is no such evidence in
humans. Doses as high as 285 mg/kg of DDT have been accidentally ingested by
humans with no fatal results.
Only one case of fatal poisoning after oral exposure has been documented. One once of 5% DDT was ingested by a 1-year old child. Clinical signs included cough and vomiting followed by tremors and convulsions. The child then became comatose and died.
DDT acts on the central
nervous system by interfering with the movement of ions through neuronal membranes.
There appear to be at least four mechanisms by which DDT affects ion movement,
all possibly functioning simultaneouslly. DDT both delays closing of the sodium
channel and prevents the full opening of potassium channels. It also targets
a specific neuronal ATPases that controls the rate of Na
,
K
and Ca
fluxes, and plays a vital role in neuronal repolarization. DDT may also inhibit
Ca
transport by binding to calmodulin. These actions combine to effectively maintain
the depolarization of the nerve membrane, potentiating the release of transmitters,
leading to CNS excitation manifested by hyperexitability, tremors and convulsions.
The organochlorides are very persistent chemicals, not readily broken down in the environment. Rachel Carson, in her book Silent Spring, drew attention to their persistance in the environment and possible effects on avian wildlife. They seem to interfere with the ability of birds to movilize enough calcium for stable egg shell formation. For this reason, their use has been banned in the US and other countries were populations of many important avian speciaes had been on the decline.
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Organophosphates and Carbamates
The organophosphates and carbamates degrade rapidly in the environment, therefore are not bioaccumulated as are the organochlorides and cause less chronic effects. Unfortunatelly, they have a reater potential for the developments of insect resistance and for human toxicity. They are readily absorbed by inhalation, skin contact and ingestion, resulting in acute systemic poisoning. Dermal exposure can lead to toxicity, even death.
These agents act by binding to and inhibiting acethylcholinesterase (AChE), resulting in the accumulation of acethylcholine and overstimulation of the cholinergic system. Initially, a weak, reversiblwe bond is formed between the pesticide and AChE. A more permanent bon forms over time, a process is known as aging. Before aging of the bond, the bindiong is reversible. After aging has occurred, recovery depends mostly on de novo enzyme synthesis, which takes about 2 weeks.
Several organophosphates can cause delayed peripheral neuropathy due to distal axonal degeneration, known as organophosphate-induced distal neurophaty or OPIDN. OPIDN begins 7-14 days after treatment for acute poisoning. It is an overall motor disorder including flacidity or paralysis of the extremities and hyperactive reflexes, may involve hands or forearms paralysis, and often mimics Guillain Barre syndrome.
The toxic effects are directly related to the amount of AChE inhibited. A critical mass of AChE must be inactivated before signs of poisoning manifest.
There are two main types od AChE: plasma AChE and red blood cell (RBC) AChE. Organophosphates inhibit both enzymes, while carbamates only inhibit RBC AChE except at very high doses. Plasma AChE (also known as pseudocholinesterase) is produced in the liver, while RBC AChE is regenerated only with the RBC (about 1% per day). Plasma AChE is more liabile than RBC AChE and more rapidly inactivated by organophosphates. Plasma AChE is also more rapidly regenerated than RBC AChE.
Red blood cell AChE is the same enzyme as that found in the nervous system. Levels of RBC AChE best reflect the degree of actual enzyme inactivation at the neuroeffector sites. However, basal levels of RBC AChE vary widely from person to person (4x variation), making it difficult to interpret test results without baseline value for the patient. Usually, inhibition of 20% to 50% is regarded as evidence of toxicity.
Accumulation of acetylcholine in the brain causes sensory and behavioural disturbances, incoordination and respiratory failure (possible cause of death). Other effects depend on enzyme inhibition at the cholinergic neuromuscular junction. Organophosphates cause both muscarinic and nicotinic effects. Carbamates cause mostly muscarinic effects.
Cholinesterase activity, both plasma and RBC, serve as indirect biological indicators. Both enzymes should be tested to obtain a full interpretation. Direct biological indicators are useful but require blood or urine sampling soon after exposure and a qualified reference laboratory to perfome the analysis. Metabolites are detectable in urine up to 48 hours after exposure, while in blood they are detyectable only for a few hours.
Since the organophosphates and carbamates are often used in crop application, there is a risk of toxicity from occupational exposure. They are also used for home application, and must be applied frequently. Farm workers, pesticide formulators and home exterminators are at greatest risk. Children are more succeptible than adults, as are people with a genetic predisposition to low cholinesterase levels.
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Ohter Pesticides
incomplete
Natural compounds: pyrethrins (pyrethroids aret eh synthetic form) and nicotine.
Pyrethrins:
Nicotine:
Herbicides: chlorophenoxy compounds and diquat/paraquat
Chlorophenoxy herbicides
Diquat/paraquat
Rodenticides
incomplete
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