Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos

Muller, Mariel; Hess, Leonardo; Tardivo, Agustina; Attademo, Andrés M.; Poletta, Gisela Laura; Simoniello, María Fernanda; Yodice, Agustina; Lavarello, Simona; Chialvo, Dante R.; Scremin, Oscar U.

doi:10.1016/j.neuro.2014.08.012

Cited by 24 publications

(15 citation statements)

References 73 publications

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“…In addition, somatosensory evoked potentials (SEPs), which assess the relay of sensory signals from the periphery to the brain, were altered following this same exposure paradigm. All doses of CPF decreased the negative wave amplitudes, while only the highest CPF dose (10 mg/kg/d) decreased the positive wave amplitude (Muller et al, 2014). …”

Section: Mechanisms Of Chronic Op Neurotoxicitymentioning

confidence: 99%

“…Muller et al (2014) observed that repeated CPF exposure alters rat brain electroencephalograph (EEG), a measurement that represents the summation of synchronized electrical currents in the brain. Following 7 days of 0.1, 1, and 10 mg/kg/d CPF exposure, which inhibits plasma ChE activity by 0, 50, and 80%, dose-dependent disturbances in EEG rhythms were detected, first decreasing the power spectra at low frequencies and then increasing the power spectra at frequencies higher than 4 Hz.…”

Section: Mechanisms Of Chronic Op Neurotoxicitymentioning

confidence: 99%

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Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

et al. 2017

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Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

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Section: Mechanisms Of Chronic Op Neurotoxicitymentioning

confidence: 99%

Section: Mechanisms Of Chronic Op Neurotoxicitymentioning

confidence: 99%

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

et al. 2017

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“…It has become one of the most widely studied pesticides from both human health and environmental perspectives since the prohibiting of high toxicity pesticides. The primary target organ for chlorpyrifos toxicity is the central and peripheral nervous system [7], due to the ability of the chlorpyrifos to inhibit the enzyme activity of acetylcholinesterase [8]. In 2007, the Unite States Environmental Protection Agency (US EPA) released a draft initial list of 73 chemicals for Endocrine Disruptor screening which included the classic OP insecticide CPF [9].…”

Section: Introductionmentioning

confidence: 99%

Chlorpyrifos is estrogenic and alters embryonic hatching, cell proliferation and apoptosis in zebrafish

Feng

et al. 2015

Chemico-Biological Interactions

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“…Table includes a study performed on adult male Sprague–Dawley and Wistar rats treated with CPF for 7 days (Muller et al, ). Sprague–Dawley rats showed a significantly delayed ASR at 10 mg kg −1 day −1 .…”

Section: Neurodevelopmental and Neurobehavioral Effects Of Cpf In Rodmentioning

confidence: 99%

“…Sensory evoked potential waves (P1‐N1‐P2) were assessed in Wistar rats and an increase in the N1 amplitude at 0.1 mg kg −1 day −1 CPF was observed. The increase in the N1 amplitude without a concomitant significant increase in the preceding P1 wave indicated the spreading of neuronal activation toward the upper layers of the cerebral cortex, which potentiates pro‐convulsant activity (Muller et al, ). A previous study reported that acute sc treatment with CPF at 1.0 mg kg −1 day −1 was a pro‐convulsant in 16–17 day old rats by inducing a lowered threshold for kindling in the amygdala (NOEL = 0.3 mg kg −1 day −1 ) (Wurpel, Hirt, & Bidanset, ).…”

Section: Neurodevelopmental and Neurobehavioral Effects Of Cpf In Rodmentioning

confidence: 99%

Effects of low‐dose chlorpyrifos on neurobehavior and potential mechanisms: A review of studies in rodents, zebrafish, and Caenorhabditis elegans

Silva

2020

Birth Defects Research

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Objectives Exposure to chlorpyrifos (CPF), a neurotoxic insecticide, is implicated with adverse neurodevelopmental effects in children through noncholinergic mechanisms. Methods This review presents qualitative and quantitative evidence in three animal models (rodent, zebrafish, and Caenorhabditis elegans), for neurodevelopmental and behavioral effects occurring at CPF doses lower than those inhibiting acetylcholinesterase (AChE). Results CPF treatment in rodents at low noncholinergic doses during neurodevelopment showed behavioral effects, including locomotor activity, neuromotor function (NMF), cognition, anxiety, social behavior, and maternal care. Zebrafish and C. elegans, which are transparent during development, allow for detailed analysis of specific systems; further, they exhibit neurotoxic effects closely emulating those observed in mammalian pathways. Qualitative results showed concordance among rodents, zebrafish and C. elegans for adverse effects on locomotor activity, NMF, and AChE inhibition. Male rodents had greater sensitivity for effects on locomotor activity than females and exposure during the gestation day 10–14 window showed consistent increases in locomotor activity at low CPF doses (≤1.0 mg kg−1 day−1). Zebrafish had cognitive and anxiety deficits after CPF treatment at low doses and young adult C. elegans had reproductive dysfunction associated NMF and disruption of the serotonergic pathway. Quantitative data for all three species showed neurobehavioral effects after exposure to CPF doses approximately 2–10‐fold below the threshold for AChE inhibition. Conclusions Taken together, these findings provided a weight‐of‐evidence for low‐dose CPF neurotoxicity and noncholinergic mechanisms. Variability in laboratories, exposure methods, tests, sex, and animal species/strain might have contributed to the inconsistent results. The detrimental CPF effects during early development are relevant to human populations.

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Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos

Cited by 24 publications

References 73 publications

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

Chlorpyrifos is estrogenic and alters embryonic hatching, cell proliferation and apoptosis in zebrafish

Effects of low‐dose chlorpyrifos on neurobehavior and potential mechanisms: A review of studies in rodents, zebrafish, and Caenorhabditis elegans

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