Chlorpyrifos is an organophosphate insecticide. Like other organophosphates, its insecticidal action is due to the inhibition of the enzyme cholinesterase , which regulates the neurotransmitter acetylcholine in the nervous system. Acetylcholine accumulates in the insect’s nerve endings, which results in excessive transmission of nerve impulses, and the target pest dies.

Cholinesterases become inhibited (or inactivated) when they are exposed to a variety of naturally-occurring and manmade substances, including some types of pesticides. When they are inhibited, these enzymes no longer properly regulate nerve function. Because the body is continually making cholinesterases, inhibition occurs without signs or symptoms of toxicity unless exposures to the inhibiting substances become too great.

In humans, cholinesterase enzymes are naturally produced by the body. In the brain, cholinesterase is essential for proper nerve function. Researchers generally agree that the inhibition of brain cholinesterase is the primary means by which chlorpyrifos exposure results in adverse effects.

Some Causes of Cholinesterase Inhibition

  • Certain medications
  • Some components of food (e.g. glycoalkaloids, which are found in small amounts in potatoes)
  • Certain health conditions (liver disease, malnutrition, anemia, hepatitis, etc.)

Cholinesterase also occurs in red blood cells and in blood plasma, where it performs no known bodily function. Plasma cholinesterase is most sensitive to inhibition by chlorpyrifos and brain cholinesterase is least sensitive. As such, inhibition of blood cholinesterase is an early and sensitive indicator of chlorpyrifos exposure.

Chlorpyrifos inhibits essentially all plasma cholinesterase and more than 30% of red blood cell cholinesterase before affecting brain cholinesterase and causing any overt signs or symptoms of toxicity as a result of brain cholinesterase inhibition.

Based on these findings, advisory bodies and regulators (e.g., World Health Organization , U.S. EPA , California Department of Pesticide Regulation ) have thus far concurred that restricting authorized uses to keep chlorpyrifos exposures too low to inhibit even blood cholinesterases provides an effective safeguard against the potential for toxic effects.

Further Resources

“Cholinesterase Inhibition”, Extension Toxicology Network, Toxicology Information Brief, 1993

“Acetylcholinesterase and Insecticide Inhibition” (educational animation) Department of Entomology, Texas A&M University, 2004

Clegg, D.J. and van Gemert, M. “Determination of the reference dose for chlorpyrifos: proceedings of an expert panel.”, Journal of Toxicology and Environmental Health, Part B Critical Reviews, 1999, Volume 2(3), 211-255.