Chlorpyrifos (CPS), also known as chlorpyrifos ethyl, is an organophosphate pesticide that has been used on crops, animals, in buildings, and in other settings, to kill several pests, including insects and worms. It acts on the nervous systems of insects by inhibiting the acetylcholinesterase enzyme. Chlorpyrifos was patented in 1966 by Dow Chemical Company.
Chlorpyrifos is considered moderately hazardous to humans (Class II) by the World Health Organization based on acute toxicity information dating to 1999. Exposure surpassing recommended levels has been linked to neurological effects, persistent developmental disorders, and autoimmune disorders. Exposure during pregnancy may harm the mental development of children.
In the United Kingdom, the use of chlorpyrifos was banned as of 1 April 2016 (with one minor exception). As of 2020, chlorpyrifos and chlorpyrifos-methyl were banned throughout the European Union, where they may no longer be used. In May 2025, the EU listed chlorpyrifos as a persistent organic pollutant (POP) under the Stockholm Convention on Persistent Organic Pollutants.
As of August 18, 2021, the U.S. Environmental Protection Agency (EPA) announced a ban on the use of chlorpyrifos on food crops in the United States. Most home uses of chlorpyrifos had already been banned in the U.S. and Canada since 2001. It is banned in several other countries and jurisdictions as well. The chlorpyrifos ban on food crops is the result of a 1999 lawsuit filed by Natural Resources Defense Council (NRDC) to force the EPA to take action on the riskiest pesticides, as well as five additional successful court orders obtained by Earthjustice to force the EPA to take action on a 2007 petition to ban chlorpyrifos filed by NRDC and the Pesticide Action Network of North America (PANNA).
Uses
Chlorpyrifos was used in about 100 countries around the world to control insects in agricultural, residential, and commercial settings. Its use in residential applications is restricted in multiple countries. According to Dow, in 2014 chlorpyrifos was registered for use in nearly 100 countries and is annually applied to approximately 8.5 million crop acres. The crops for which it was most useful include cotton, corn, almonds, and fruit trees, including oranges, bananas, and apples.
Chlorpyrifos was first registered for use in the United States in 1965 for the control of foliage and soil-born insects. The chemical became widely used in residential settings, on golf course turf, as a structural termite control agent, and in agriculture. Most residential use of chlorpyrifos has been phased out in the United States after many uses were banned. Agricultural use remains common though it is being banned in California and the EU. The US EPA banned the use of chlorpyrifos on food crops in 2021, though courts overturned this decision in 2023.
EPA estimated that, between 1987 and 1998, about 21 million pounds of chlorpyrifos were used annually in the US. In 2001, chlorpyrifos ranked 15th among pesticides used in the United States, with an estimated 8 to 11 million pounds applied. In 2007, it ranked 14th among pesticide ingredients used in agriculture in the United States.
Application Chlorpyrifos is normally supplied as a 23.5% or 50% liquid (emulsifiable concentrate). The recommended concentration for direct-spray pin point application is 0.5% and for wide area application a 0.03–0.12% mix is recommended (US). In Australia, large scale applications are between 35-130 g/Ha of active ingredient.
Kinetics Chlorpyrifos enters insects through several routes. Simon et al. 1998 report that insects are exposed to chlorpyrifos through ingesting treated food plants. They also found it to enter through skin and membranes of the respiratory system.
Mechanism of action Like other organophosphate pesticides chlorpyrifos acts by acetylcholinesterase inhibition.
Human toxicity Chlorpyrifos exposure may lead to acute toxicity at higher doses. Persistent health effects follow acute poisoning or from long-term exposure to low doses, and developmental effects appear in fetuses and children even at very small doses.
Acute health effects For acute effects, the World Health Organization classifies chlorpyrifos as Class II: moderately hazardous. The oral LD50 in experimental animals is 32 to 1000 mg/kg. The dermal LD50 in rats is greater than 2000 mg/kg and 1000 to 2000 mg/kg in rabbits. The 4-hour inhalation of LC50 for chlorpyrifos in rats is greater than 200 mg/m3.
Symptoms of acute exposure Acute poisoning results mainly from interference with the acetylcholine neurotransmission pathway, leading to a range of neuromuscular symptoms. Relatively mild poisoning can result in eye-watering, increased saliva and sweating, nausea, and headache. Intermediate exposure may lead to muscle spasms or weakness, vomiting, or diarrhea, and impaired vision. Symptoms of severe poisoning include seizures, unconsciousness, paralysis, and suffocation from lung failure.
Children are more likely to experience muscle weakness rather than twitching; excessive saliva rather than sweat or tears; seizures; and sleepiness or coma.
Frequency of acute exposure Acute poisoning is probably most common in agricultural areas in Asia, where many small farmers are affected. Poisoning may be due to occupational or accidental exposure or intentional self-harm. Precise numbers of chlorpyrifos poisonings globally are not available. Pesticides are used in an estimated 200,000+ suicides annually with tens of thousands due to chlorpyrifos. Organophosphates are thought to constitute two-thirds of ingested pesticides in rural Asia. Chlorpyrifos is among the commonly used pesticides used for self-harm.
In the US, the number of incidents of chlorpyrifos exposure reported to the US National Pesticide Information Center shrank sharply from over 200 in the year 2000 to less than 50 in 2003, following the residential ban.
Treatment Poisoning is treated with atropine and simultaneously with oximes such as pralidoxime. Atropine blocks acetylcholine from binding with muscarinic receptors, which reduces the pesticide's impact. However, atropine does not affect acetylcholine at nicotinic receptors and thus is a partial treatment. Pralidoxime is intended to reactivate acetylcholinesterase, but the benefit of oxime treatment is questioned. A randomized controlled trial (RCT) supported the use of higher doses of pralidoxime rather than lower doses. A subsequent double-blind RCT, that treated patients who self-poisoned, found no benefit of pralidoxime, including specifically in chlorpyrifos patients.
Tourist deaths Chlorpyrifos poisoning was described by New Zealand scientists as the likely cause of death of several tourists in Chiang Mai, Thailand who developed myocarditis in 2011. Thai investigators came to no conclusion on the subject, but maintain that chlorpyrifos was not responsible and that the deaths were not linked.
Long term
Development Epidemiological and experimental animal studies suggest that infants and children are more susceptible than adults to the effects of low-dose exposure. Chlorpyrifos has been suggested to have negative impacts on cognitive functions in the developing brain. The young have a decreased capacity to detoxify chlorpyrifos and its metabolites. It is suggested that adolescents differ from adults in the metabolism of these compounds due to the maturation of organs in adolescents. This results in disruption in nervous system developmental processes, as observed in animal experiments. There are several studies observed in animals that show that chlorpyrifos alters the expression of essential genes that assist in the development of the brain.
Human studies: In multiple epidemiological studies, chlorpyrifos exposure during gestation or childhood has been linked with lower birth weight and neurological changes such as slower motor development and attention problems. Children with prenatal exposure to chlorpyrifos have been shown to have lower IQs. They have also been shown to have a higher chance of developing autism, attention deficit problems, and developmental disorders. A cohort of 7-year-old children was studied for neurological damage from prenatal exposure to chlorpyrifos. The study determined that the exposed children had deficits in working memory and full scale intelligence quotient (IQ). In a study on groups of Chinese infants, those exposed to chlorpyrifos showed significant decreases in motor functions such as reflexes, locomotion, and grasping at 9 months compared to those not exposed. Exposure to organophosphate pesticides in general has been increasingly associated with changes in children's cognitive, behavioral and motor performance. Infant girls were shown to be more susceptible to harmful effects from organophosphate insecticides than infant boys.
Animal experiments: In experiments with rats, early, short-term low-dose exposure to chlorpyrifos resulted in lasting neurological changes, with larger effects on emotional processing and cognition than on motor skills. Such rats exhibited behaviors consistent with depression and reduced anxiety. In rats, low-level exposure during development has its greatest neurotoxic effects during the period in which sex differences in the brain develop. Exposure leads to reductions or reversals of normal gender differences. Exposure to low levels of chlorpyrifos early in rat life or as adults also affects metabolism and body weight. These rats show increased body weight as well as changes in liver function and chemical indicators similar to prediabetes, likely associated with changes to the cyclic AMP system. Moreover, experiments with zebrafish showed significant detriments to survivability, reproductive processes, and motor function. Varying doses created a 30%–100% mortality rate of embryos after 90 days. Embryos were shown to have decreased mitosis, resulting in mortality or developmental dysfunctions. In the experiments where embryos did survive, spinal lordosis and lower motor functions were observed. The same study showed that chlorpyrifos had more severe morphological deformities and mortality in embryos than diazinon, another commonly used organophosphate insecticide.
Adulthood Adults may develop lingering health effects following acute exposure or repeated low-dose exposure. Among agricultural workers, chlorpyrifos has been associated with slightly increased risk of wheeze, a whistling sound while breathing due to obstruction of the airways.
Among 50 farm pesticides studied, chlorpyrifos was associated with higher risks of lung cancer among frequent pesticide applicators than among infrequent or non-users. Pesticide applicators as a whole were found to have a 50% lower cancer risk than the general public, likely due to their nearly 50% lower smoking rate. However, chlorpyrifos applicators had a 15% lower cancer risk than the general public, which the study suggests indicates a link between chlorpyrifos application and lung cancer.
Twelve people who had been exposed to chlorpyrifos were studied over periods of 1 to 4.5 years. They were found to have a heightened immune responses to common allergens and increased antibiotic sensitivities, elevated CD26 cells, and a higher rate of autoimmunity, compared with control groups. Autoantibodies were directed toward smooth muscle, parietal cell, brush border, thyroid gland, myelin, and the subjects also had more anti-nuclear antibodies.
Chlorpyrifos methyl The Dow Chemical Company also developed chlorpyrifos methyl in 1966, which had a lower acute toxicity (WHO class III), but this appears to be no longer in commercial use. The molecule is similar to chlorpyrifos ethyl, but with a O,O dimethyl chain. Proposed applications included vector control.Tomlin CDS (2000) The Pesticide Manual 12th Ed. British Crop Protection Council (BCPC)