Chlorpyrifos

Chlorpyrifos is the common name for the active ingredient in the pesticide Dursban®. The generic name is "O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl)phosphorothioate".¹ Chlorpyrifos is a white to tan crystalline solid with a mild mercaptan or solvent type odor. The melting point is low at 41.5° c-43.5° c. The crystal does not have a flash point.² Dursban is sold in several forms including a liquid emulsion, granules and powders. The liquid emulsion is the most common form. This emulsion form does have flammability rating of 1 and a flash point of 115° c.³ The fire hazard is caused largely by the xylene aromatic solvent. Chlorpyrifos will undergo an exothermic decomposition near 130° c which can generate higher temperatures if the heat is not disapated.⁴ Dursban® is classed as a broad-spectrum organophosphate insecticide. It was registered with the EPA in 1965.⁵ Dursban® was originally used against mosquitoes, but is no longer registered for that use. Chlorpyrifos is effective against many ground dwelling insects such as termites, ants, beetles and worms. It can be applied to the ground, crops, plants and animals directly.⁶

Chlorpyrifos consists of two ethyl groups bonded to Oxygen bonded to Phosphorus, a sulfur double bond to Phosphorus and a Nitrogen heterocyclic ring bonded to Oxygen bonded to Phosphorus. ⁷ One method of synthesis is a condensation with the temperature carefully controlled to avoid isomerization.⁸ A second method of synthesis is the reduction of pentachloropyridine with Zinc or electrochemically followed by partial hydrolysis and phosphorylation.⁹

The synthesis method utilized by DowElanco for the manufacture of Dursban® is covered by US and European patents.

Organophosphate esters are acetylcholinesterase inhibitors that prevent acetylcholine hydrolysis. Chlorpyrifos, other pesticides and nerve gases utilize an organophosphate ester as the active reaction site. When a nerve cell receives an impulse, acetylcholine is released to allow the electrical signal pass through the cell to the next nerve cell. The acetylcholine is then hydrolyzed and removed from the cell to allow the transmission of another impulse. Organophosphate esters can act as either of two mechanisms:

1. As classical competitive enzyme inhibitors, they have a high affinity for the active site, but are not substrates. The enzyme is occupied by the inhibitor for relatively long periods, and therefore cannot handle ACh efficiently, as a result of the saturation phenomenon.
2. The inhibitor acylates, the serine hydroxyl group of AChE, forming an ester more stable than acetate, such as a carbamate or phosphate. The hydrolysis of these stable esters takes a long time even if they are not reversible, as formerly thought. Acetylcholine cannot then be hydrolyzed, since the active site is covalently occupied.¹⁰

The following diagram shows the reaction of a phosphate ester with the S200 site on the acetylcholine enzyme.¹¹

The phosphate is first attacked by the Oxygen of the binding site. This deactivates the binding site. Once the X group, in the case of Chlorpyrifos, the X group is the ring, leaves the binding site is stable and unreactive. At this point, the reaction can be reversed by hydrolysis or nucleophilic addition of an oxime. The aging reaction removes one of the R groups from the organophosphate. Once the R group is removed through dealkylation, the reaction cannot be reversed. This unreactive enzyme is considered aged and will not function. When the enzyme is inhibited or aged, acetylcholine is not removed from the cell, and the cell continues to transmit the same nerve impulse repeatedly. The nerve impulses become continuous and cause neurological failure and death.

Organophosphates are detoxified differently in mammals and insects. "By taking advantage of differences in the processes of detoxication in the Insecta and Mammalia, compounds, eg, malathion and fenitrothion incorporate a high degree of insecticidal action and of safety to the human user and domestic animals."¹² Chlorpyrifos is metabolized in mammals and excreted quickly. Insects do not have the needed enzymes to metabolize Chlorpyrifos and cannot counter its effects. Chlorpyrifos is reactive by contact, ingestion and vapor action.¹³ "The half life of Chlorpyrifos in soil is usually between 60 and 120 days, but can range from 2 weeks to over 1 year, depending on the soil type, climate and other conditions."¹⁴

Chlorpyrifos is unlikely to cause injury of illness to humans, but can be dangerous even deadly in high concentrations. It does not accumulate in the body tissues. A 150 pound adult could consume 0.21 mg of Chlorpyrifos per day for a lifetime with no ill effects.¹⁵ Intentional exposure to pesticides is never recommended. Direct contact with the skin is the most probable cause of exposure. Treatments are available to counter act an overdose. Atropine can be utilized to counter act the muscarinic effects of the toxin. Oximes, such as 2-PAM/protopam, are recommended by Dursban®'s MSDS.¹⁶ Other treatments are Pralidoxime and Toxogonine (Obidoxime). Pralidoxime is a nucleophilic compound capable of regenerating acetylcholine esterase. The quaternary Nitrogen or Pralidoxime reacts with the active site of the enzyme allowing the oxime to form a bond to the Phosphorous of the Chlorpyrifos and remove the toxin. Toxogonine functions the same way, but is more toxic and less effective.¹⁷

Because of its broad-spectrum of activity and relative safety, Chlorpyrifos is widely used in agriculture and residentially. Many studies have sought to determine the health and environmental impacts of Chlorpyrifos. No evidence indicates that Chlorpyrifos adversely affects reproduction, causes mutations or cancer.¹⁸ Its effects have been shown to be solely neurological. Ongoing studies are working to learn more about Chlorpyrifos's effects. A study at Duke University is examining the functions and effects of neonatal and childhood exposure.¹⁹ The Dept. of Health Science at California State University has noted cases of individuals with abnormalities in immune system function after exposure to safe levels of Chlorpyrifos.²⁰ An UC Berkley study concludes that synthetic pesticide residues are insignificant when compared to the naturally occurring toxins in the American Diet.²¹ Chlorpyrifos is safer than many of the pesticides it has replaced such as Methyl Bromide. Its wide-spread use will continue until a safer pesticide is developed to replace it.

Next Page