Organophosphate Insecticides: Neurodevelopmental Effects

Abstract

Organophosphate (OP) insecticides are used to control pests in agricultural food and ornamental plant production, and in building and home settings. One major adverse effect in mammals from OP exposure is neurotoxicity, including developmental neurotoxicity (DNT), which is toxicity to the developing nervous system of the fetus or child as a consequence of exposure while in the womb or at a young age. The DNT effects have been investigated in laboratory studies using experimental animals, in vitro cell cultures, and nonmammalian systems, as well as in epidemiological studies of human exposure. Chlorpyrifos is an example of an OP with an extensive database of such studies. Screening for potential DNT effects is conducted per governmental guidelines with the results intended for regulatory purposes such as registration of the pesticide for use or continued use. Academic research studies generally focus on characterization of DNT effects, including mode of action (MOA) and comparative toxicity between chemicals. DNT effects are determined by clinical observations; a battery of tests for behavior (functional observational battery, FOB); tests for motor and sensory function, cognition involved in learning and memory, anxiety, depression, and social behavior; and pathological and morphological examination of the brain. While the MOA for acute neurotoxicity of OPs is from the inhibition of acetylcholinesterase (AChE) activity, there is evidence that some of the DNT effects may be independent of AChE inhibition. This is demonstrated by the finding from laboratory studies of DNT at exposure doses lower than those causing AChE inhibition in the brain. Epidemiological studies have revealed associations between prenatal and postnatal exposures to some OP insecticides and alterations of neurological functions and development later in life.