[9] Chlorpyrifos is considered moderately hazardous to humans (Class II) by the World Health Organization based on acute toxicity information dating to 1999.

[34][35][36] 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.

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.

[62] 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.

[citation needed] Chlorpyrifos may affect other neurotransmitters, enzymes and cell signaling pathways, potentially at doses below those that substantially inhibit acetylcholinesterase.

[64][65] Laboratory experiments in rats and cell cultures suggest that exposure to low doses of chlorpyrifos may alter serotonin signaling and increase rat symptoms of depression; change the expression or activity of several serine hydrolase enzymes, including neuropathy target esterase and several endocannabinoid enzymes; affect components of the cyclic AMP system; and influence other chemical pathways.

Further, infants produce low levels of PON1 until six months to several years after birth, likely increasing the risk from chlorpyrifos exposure early in life.

[72] In 2011, EPA estimated that, in the general US population, people consume 0.009 micrograms of chlorpyrifos per kilogram of their body weight per day directly from food residue.

"[77] Humans can be exposed to chlorpyrifos by way of ingestion (e.g., residue on treated produce, drinking water), inhalation (especially of indoor air), or absorption (i.e., through the skin).

A study done in an agricultural community in Washington State showed that children who lived in closer proximity to farmlands had higher levels of chlorpyrifos residues from house dust.

[90][91] Grower and pesticide industry groups argued that the air levels documented in these studies are not high enough to cause significant exposure or adverse effects.

In Britain, the rivers Roding (1985), Ouse (2001), Wey (2002 & 2003), and Kennet (2013) all experienced insect, shrimp, or fish kills as a result of small releases of concentrated chlorpyrifos.

[33] Guidelines for Washington state recommend that chlorpyrifos products should not be applied to flowering plants such as fruit trees within 4–6 days of blossoming to prevent bees from directly contacting the residue.

[100] Adult bees exposed to sub-lethal effects of chlorpyrifos (0.46 ng/bee) exhibited altered behaviors: less walking; more grooming, particularly of the head; more difficulty righting themselves; and unusual abdominal spasms.

[110] Chlorpyrifos is sold in restricted-use products for certified pesticide applicators to use in agriculture and other settings, such as golf courses or for mosquito control.

[112] In 2000, manufacturers reached an agreement with the EPA to voluntarily restrict the use of chlorpyrifos in places where children may be exposed, including homes, schools and day care centers.

[113][114] In 2007 Pesticide Action Network North America and Natural Resources Defense Council (collectively, PANNA) submitted an administrative petition requesting a chlorpyrifos ban, citing harm to the brains of developing children.

"[117] In an 30 October 2015 statement Dow AgroSciences disagreed with the EPA's proposed revocation and "remain[ed] confident that authorized uses of chlorpyrifos products, as directed, offer wide margins of protection for human health and safety."

In a November 2016 press release, DOW argued that chlorpyrifos was "a critical tool for growers of more than 50 different types of crops in the United States" with limited or no viable alternatives.

It is authorized for use in about 100 nations, including the U.S., Canada, the United Kingdom, Spain, France, Italy, Japan, Australia and New Zealand, where it is registered for protection of essentially every crop now under cultivation.

The EPA concluded that, while "uncertainties" remain, a number of studies provide "sufficient evidence" that children experience neurodevelopment effects even at low levels of chlorpyrifos exposure.

[126] In August, it was revealed that in fact Pruitt and other EPA officials had met with industry representatives on dozens of occasions in the weeks immediately prior to the March decision, promising them that it was "a new day" and assuring them that their wish to continue using chlorpyrifos had been heard.

[130] On 14 December, 2022 the EPA filed a Notice of Intent to Cancel (NOIC) for three chlorpyrifos pesticide products because they bear labeling for use on food, despite the ban.

[131][needs update] However, on November 2, 2023 the United States Court of Appeals for the Eighth Circuit nixed a 2021 rule issued by the Environmental Protection Agency banning all neurotoxic insecticide on all food crops.

In the event of an environmental release above its reportable quantity of 1 lb or 0.454 kg, facilities are required to immediately notify the National Response Center (NRC).

For example, in 2005, the EPA filed an administrative complaint against JSH Farms, Inc. (Wapato, Washington) with proposed penalties of $1,680 for using chlorpyrifos in 2004 without proper equipment.

[161] The Australian Pesticides and Veterinary Medicine Authority's Chlorpyrifos Chemical Review, began July 2015,[162] made the final decision in September 2024.

[166] The European Food Safety Authority released a statement in July 2019 which concluded that the approval criteria for chlorpyrifos which apply to human health are not met.

The report stated that chlorpyrifos is clearly a potent acetylcholinesterase inhibitor, that it can be absorbed by ingestion, inhalation, and through the skin, and that epidemiological evidence supports the hypothesis that it is a human developmental neurotoxin that can cause early cognitive and behavioral deficits through prenatal exposure.