Relationship: 2016



AchE Inhibition leads to Decrease, Population trajectory

Upstream event


AchE Inhibition

Downstream event


Decrease, Population trajectory

Key Event Relationship Overview


AOPs Referencing Relationship


AOP Name Adjacency Weight of Evidence Quantitative Understanding
Acetylcholinesterase inhibition leading to acute mortality non-adjacent Low Low

Taxonomic Applicability


Sex Applicability


Life Stage Applicability


Key Event Relationship Description


  • AChE inhibition at the individual level may lead to a declining population trajectory.

Evidence Supporting this KER


Biological Plausibility


  • Wildlife studies including fish and birds have shown that exposure to AchE inhibitors can lead to physiological changes and behavioral alterations, which can make individuals more vulnerable to prey. It is biologically plausible that decreased survival and reproduction could decrease the population trajectory, if the scale of the changes were significant.

Empirical Evidence


  • Study of fourth instar Ailanthus silkworm exposed to malathion for 5 days found increased mortality, decreased AChE, and increases in Acetylcholine as compared to controls. Most moths did not emerge and those that emerged did not oviposit (Pant, 1983). 

  • Studies using earthworms (Lumbricus terrestris) found a significant increase in AChE inhibition and concurrent mortality after exposure methiocarb, and a significant reduction in the reproduction rate of adults after 4 weeks of exposure to concentrations recommended for use by the OECD in agricultural pest control (Calisi 2011).

  • In a pond study of bluegill and largemouth bass, chlorpyrifos treatment resulted in cumulative mortalities ranging from 46-55%. The authors presented data where the fish, especially the bluegill, fed heavily on the invertebrates in the first 7 days of the study thereby compounding the exposure that in the laboratory would be only via water (Macek 1972). 

  • Brain AChE activity was significantly (10-89%) inhibited in fathead minnows exposed to varying concentrations of Dursban. Increased sensitivity was observed in second generation fish (Pimephales promelas) exposed after hatch to chlorpyrifos (Jarvinen et al., 1983). Biomass of the second generation fish recruitable to the population was estimated using a model that assumed a normal distribution for the population and used total egg production, hatchability, survival, and fish weight as input variables. The model estimated a significant reduction in the recruitment population (Jarvinen et al., 1983).

  • In a study of Japanese medaka exposed to acute and subacute levels of chlorpyrifos,  brain reduced swimming speed and reduced AChE activity were correlated. The fish exhibited behavioral alterations, including decreased swimming speed and hypoactivity in the acute test, and social group hyperactivity and long time schooling in the subacute test.  These findings may indicate a subacute effect of chlorpyrifos on social behavior, which can pose a risk at the population level (Khalil 2013).

  • Rainbow trout exposed to diazinon at sub-lethal (0.1 and 0.2 mg/L) concentrations showed significantly reduced plasma AChE activity.  Effects of AchE inhibition included the following behavioral alterations, which could lead to decreased population trajectory over time: vertical and downward swimming patterns, swimming near the water surface, lethargic and erratic swimming, loss of schooling behavior, hyperactivity, seizures and convulsion (fish suffering from severe muscular contraction and tremor) and loss of buoyancy (Banaee 2011).

  • Larval zebrafish were exposed to chlorpyrifos, diazinon and parathion over the first five days of development to examine survival, AChE activity, and behavior. At non-lethal concentrations, chlorpyrifos was more effective than diazinon and parathion in producing 

  • AChE inhibition. At higher concentrations of diazinon and parathion, lethality occurs before they can produce the degree of AChE inhibition observed with chlorpyrifos at 300 nM. Motility at 6 dpf was examined using 300 nM, a concentration that does not cause mortality,  as a standard dose and tracking behavior for 2 minutes. At 300 nM, a concentration that does not affect survival, only chlorpyrifos significantly affected motility, reducing locomotor activity by 35% (Yen 2011).

  • White-crowned sparrows exposed to imidacloprid and chlorpyrifos during spring migration and exposed to low and high doses exhibited declines in fat stores and body mass for those exposed to imidacloprid, and failed orientation for both those exposed to imidacloprid and those exposed to chlorpyrifos. This that wild birds who consume insecticide treated seeds could be in impaired condition to migrate, have delayed migration, or improper direction, resulting in increased mortality or loss of breeding opportunities (Eng 2017).

  • A review of studies from captive and wild birds and mammals exposed to acute doses of OP and carbamate pesticides found acute effects thermoregulation (hypothermia), food consumption (anorexia, altered forging behavior), and reproduction (altered hormone levels, reduction in clutch and litter size, and alterations in behavior) (Grue 1997).

Uncertainties and Inconsistencies


  • In bluegill and largemouth bass, the principal mode of exposure was unclear. The relative uptake from pesticide-treated insects versus direct uptake from water was not quantifiable, although the data suggest that fish more readily metabolize insecticides introduced via diet than via oral exposure (Macek 1972).

  • Fish appeared to be more sensitive to exposure at a higher water temperature (Macek 1972).

Quantitative Understanding of the Linkage


  • Theoretical lethal concentration (ppb) was calculated dependent on average pond depth (m) and application rate (lb/A) of active ingredient (Macek 1972).

  • The use of exposure units (exposure concentration X exposure duration) is discussed as a tool for determining the effects of organophosphate pesticides on the environment (Jarvinen et al., 1983).

  • Magnitude and disruption of the changes in orientation may be due to differences in detoxification rate, strength of nAChr binding, reversibility of inhibition, and other compound-specific mechanisms of action (Eng 2017).

Response-response Relationship




Known modulating factors


Known Feedforward/Feedback loops influencing this KER


Domain of Applicability


  • Fish and aquatic invertebrates exposed to OP insecticides showing high AChE inhibition as compared to fish from untreated ponds, did not recover normal AChE activity for 28 days following exposure (Macek 1972).

  • Birds exposed to OP pesticides display behavioral changes (Eng 2017).

  • OP toxicity in birds and mammals is determined by multiple factors. Varying sensitivity within taxa is related to chemical affinity for binding with brain AChE, ability of hepatic and brain tissue to metabolize these compounds and activate latent inhibitors, and the affinity of parent compounds and their metabolites for nontarget esterases (Grue 1997).



  • Banaee,M., Sureda, A. Mirvaghefi, A.R. and K. Ahmadi. 2011. Effects of Diazinon on Biochemical Parameters of Blood in Rainbow Trout  (Oncorhynchus mykiss). Pestic. Biochem. Physiol. 99(1): 1-6.

  • Calisi, A., Lionetto, M.G., Schettino, T. 2011. Biomarker response in the earthworm Lumbricus terrestris exposed to chemical pollutants. Science of the Total Environment. 409, 4456-4464.

  • Eng, M.L., Stutchbury, B.J.M. & Morrissey, C.A. 2017. Imidacloprid and chlorpyrifos insecticides impair migratory ability in a seed-eating songbird. Sci Rep 7, 15176.

  • Grue, C.E., Gibert, P.L., Seeley, M.E. 1997. Neurophysiological and Behavioral Changes in Non-Target Wildlife Exposed to Organophosphate and Carbamate Pesticides: Thermoregulation, Food Consumption, and Reproduction. Amer. Zool., 37:369-388.

  • Jarvinen AW, Nordling BR, Henry ME. 1983. Chronic toxicity of dursban (chlorpyrifos) to the fathead minnow (Pimephales promelas) and the resultant acetylcholinesterase inhibition. Ecotoxicol Environ Saf 7:423–434.

  • Khalil,F., I.J. Kang, S. Undap, R. Tasmin, X. Qiu, Y. Shimasaki, and Y. Oshima. 2013. Alterations in Social Behavior of Japanese Medaka (Oryzias latipes) in Response to Sublethal Chlorpyrifos Exposure. Chemosphere. 92(1): 125-130.

  • Macek, K.J., Walsh, D.F., Hogan, J.W., Holz, D.D. 1972. Toxicity of the Insecticide Dursban to Fish and Aquatic Invertebrates in Ponds. Trans. Am. Fish. Soc., 101(3): 420-427.

  • Pant, R., Katiyar, S.K. 1983. Effect of malathion and acetylcholine on the developing larvae of Philosamia ricini (Lepidoptera: Saturniidae). J. Biosci. 5(1), 89-95.

  • Yen,J., S. Donerly, E.D. Levin, and E.A. Linney. 2011. Differential Acetylcholinesterase Inhibition of Chlorpyrifos, Diazinon and Parathion in Larval Zebrafish. Neurotoxicol. Teratol. 33(6): 735-741.