Neuropsychological sequelae from acute poisoning and long-term exposure to carbamate and organophosphate pesticides
Introduction
Organophosphates (OP) and carbamates are widely used as pesticides in industry, farming and chemical warfare. These toxic compounds can be absorbed through the skin, mucous membranes, gastrointestinal and the respiratory tracts, and produce their toxic effects by the inhibition of acetylcholinesterase (AChE) and the subsequent accumulation of synaptic acetylcholine (ACh) in peripheral and central nervous systems [8], [20], [40]. Acute effects from pesticide poisoning include nicotinic and muscarinic symptoms [24]. Furthermore, exposure to high concentrations of these cholinesterase inhibitors (CIs) may have chronic or long-term effects that have been linked to delayed-onset peripheral neuropathies and neuropsychological changes [17]. In the latter case, the delayed effect may result from the permanent inhibition of different serine hydrolases such as the neuropathy target esterase (NTE), which yields a covalent modification of an active serine residue site, producing a permanent inhibition of the enzyme. Nevertheless, this irreversible inhibition may not be the direct cause of the neuropathy, but the results of a new function of the modified enzyme, which would be toxic [18].
A number of studies have reported psychological and neuropsychological effects, together with motor impairments after acute poisoning episodes [9], [17], [33], [35], [38], [43], [45]. Although the dysfunctions vary according to the task, the type of pesticide and the severity of poisoning, the above studies all describe a common profile of impaired cognitive functions and altered mood states: decreased academic abilities, motor skills, increased psychological distress, post-traumatic stress disorder, as well as self-reported symptoms of depression, irritability and confusion.
Nevertheless, in most of these studies there has not been adequate control of the time elapsed between the poisoning event and the subsequent evaluation, making it difficult to distinguish between acute alterations after poisoning and long-term sequelae. A number of epidemiological studies suggest neurobehavioural and/or neurocognitive effects after long-term exposure to pesticides [3], [10], [11]. Especially remarkable in this context are the studies which reveal a linear relationship between degree of exposure, in terms of years working with pesticides, and neuropsychological impairment [19].
The purpose of our work was to evaluate the possible long-term neurocognitive sequelae produced by acute intoxication with OP and carbamates (acute poisoning group) in comparison with non-acutely poisoned, but nevertheless chronically exposed individuals with exposures for a number of years to these same compounds (chronic exposure groups). With the exception of only one case, all the subjects diagnosed with acute hypercholinergic syndrome due to pesticide exposure were greenhouse workers who had been exposed to pesticides for a variable number of years, who all returned to the same job immediately after recovery. We decided to compare their neuropsychological performance with that of subjects from a previous study in which we evaluated the effects of chronic subacute exposure. In this previous study [32], we demonstrated a significant relationship between long-term exposure (more than 10 years working with pesticides) and impaired neuropsychological performance (perceptual functioning, visuomotor praxis and integrative task performance time).
Section snippets
Participants
In southeastern Spain, a large part of employment and income is concentrated in intensive agriculture in greenhouses. These are crops grown under plastic of 70 × 15 km, corresponding to almost 30,000 ha of greenhouses.
We recruited by phone 24 poisoned farmers (acutely poisoned group) who received treatment in the Internal Medicine Department of the Hospital de Poniente (Almeria, Spain) and who had suffered accidental poisoning with OP and/or carbamates within the past 3 months (between September
Characteristics of the study group and exposure variables
The acutely poisoned and non-poisoned but chronically exposed workers and control subjects had comparable educational levels. The average age was different as shown by F values and the associated probability, with the low exposed group being younger than the others (see Table 1). Symptoms recorded in the acutely poisoned and chronically exposed groups mainly included muscarinic and nicotinic symptoms (see Table 2), with a larger number and proportion of symptoms in the acutely poisoned group.
Discussion
In the present study we have tried to find a possible association between acute intoxication by CIs and functional alterations of the CNS, by using an extensive neuropsychological evaluation at two time points after the acute poisoning event. The outcomes of the acutely poisoned group were compared with those of workers also chronically exposed to pesticides and to controls. The chronic exposure groups included a high chronic group (more than 10 years of exposure) and workers with constant
Conclusions
Neuropsychological performance deficits have been clearly demonstrated, suggesting a likely dysfunction of the Central Nervous System. These are derived from chronic exposure and from acute episodes of poisoning in workers in intensive agriculture environments (greenhouses with high humidity and temperature). The disturbances observed mainly affect speed of processing, visuo-motor performance, visuo-perceptual abilities and anxiety. Our data confirm the utility of plasma BuChE activity for
Acknowledgment
This research was supported by research grants PM 96-0102 (MEC, Spain) and PM 99-0146 (MCYT, Spain). We are grateful to Caroline Coope for revising the English language text.
References (45)
- et al.
Spatial working and reference memory in rats bred for autonomic sensitivity to cholinergic stimulation: acquisition, accuracy, speed and effects of cholinergic drugs
Neurobiol. Learn. Mem.
(1995) Anticholinesterases: dramatic aspects of their use and misuse
Neurochem. Int.
(1998)- et al.
Pharmacology and toxicology of cholinesterase inhibitors: uses and misuses of a common mechanism of action
Environ. Toxicol. Pharmacol.
(2005) - et al.
Neuropsychological effects of long-term exposure to organophosphate pesticides
Neurotoxicol. Teratol.
(2005) - et al.
Chronic central nervous system effects of acute organophosphate pesticide intoxication
Lancet
(1991) - et al.
Selective effects of carbamates pesticides on rat neuronal nicotinic acetylcholine receptors on rat brain acetylcholinesterase
Toxicol. Appl. Pharmacol.
(2003) - et al.
Organophosphate poisoning
Ann. Emerg. Med.
(1987) - et al.
Clinico-neuropsychological assessment methods in behavioral neurotoxicology
Organophosphorus Ester-induced chronic neurotoxicity
Arch. Environ. Health
(2003)- et al.
Exposición a plaguicidas organofosforados en trabajadores de invernaderos del Pais Vasco
Med. Clin.
(1993)
Neuropsychological effects of long-term exposure to pesticides: results from the French phytoner study
Environ. Health Perspect.
An inventory for measurement of depression
Arch. Cen. Psychiat. A
Contribution to Neuropsychological Assessment
Manual de uso del programa estadístico SPSS/PC+
Central nervous system effects of acute organophosphate poisoning in a two-year follow-up
Scand. J. Work, Environ. & Health
Neurobehavioural effects among workers occupationally exposed to organophosphorous pesticides
Occup. Environ. Med.
Long-term use of organophosphates and neuropsychological performance
Am. J. Ind. Med.
Butyrilcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocite acetylcholinesterase inhibition in farmers exposed to pesticides
Hum. Hered.
Test de Colores y palabras (Stroop)
Evaluación de la afasia y trastornos relacionados
Structural roles of acetylcholinesterase variants in biology and pathology
Eur. J. Biochem.
Cited by (84)
Identifying and preventing the neurotoxic effects of pesticides
2022, Advances in NeurotoxicologyPesticides and Parkinson's disease: Current and future perspective
2021, Journal of Chemical NeuroanatomyThe effectiveness of chemical solutions on the removal of carbaryl residues from cucumber and chili presoaked in carbaryl using the HPLC technique
2020, Food ChemistryCitation Excerpt :There are around 49,000 to 61,000 cases of pesticide intoxication reported each year in Thailand with a mortality rate of between 76 and 97 per 100,000 population (Panuwet et al., 2012; Tawatsin et al., 2015). Carbamate pesticides are acetylcholinesterase inhibitors, which cause the accumulation of acetylcholine in synapses and neuromuscular junctions, resulting in symptoms associated with interruption of normal muscarinic and nicotinic acetylcholine receptor functions (Lerman, Hirshberg, & Shteger, 1984; Roldan-Tapia et al., 2006). Also, research has indicated that acetylcholinesterase inhibitors, and oxidative stress of carbamate, might have a role in the induction of mutations in gene coding, resulting in carcinogenesis (Dhouib et al., 2014; Jorsaraei, Maliji, Azadmehr, Moghadamnia, & Faraji, 2014; Mahajan et al., 2007).