Elsevier

Neurotoxicology and Teratology

Volume 28, Issue 6, November–December 2006, Pages 694-703
Neurotoxicology and Teratology

Neuropsychological sequelae from acute poisoning and long-term exposure to carbamate and organophosphate pesticides

https://doi.org/10.1016/j.ntt.2006.07.004Get rights and content

Abstract

This research examines the effects of different degrees of pesticide exposure on neuropsychological performance. Exposures varied from acute poisoning coupled with chronic exposure to low or high levels of chronic exposure (defined by years of exposure). A cross-sectional neuropsychological and biochemical study was conducted in greenhouse farmers from southern Spain: data from 24 acutely poisoned workers and 40 non-poisoned but chronically (low or high) exposed sprayers were compared to 26 controls. We examined performance on 21 neuropsychological tests that assessed attention, memory, praxis, gnosis, motor coordination, naming and reasoning and also examined values of plasmatic cholinesterase. Results indicated statistically significant neuropsychological deficits in the acute poisoning and high chronic exposure groups after controlling for confounds, whereas similar performance was seen in the low chronic exposed subjects and controls. Subjects who were acutely poisoned performed worse than the other groups on perceptual, visuomotor, visual memory and mood state domains. Both the acutely poisoned and the chronically high exposed subjects obtained significantly lower scores in the perceptual, verbal memory and visuomotor domains. Levels of butyrylcholinesterase were related to the seasonal sprayer activity except in the case of acutely poisoned subjects. Conclusions: Both acutely poisoned long-term workers and chronically high (> 10 years) exposed workers exhibited similar disturbances in perception and visuo-motor processing, in the absence of any related acute effect of butyrylcholinesterase inhibition. In the case of acutely poisoned subjects, verbal and perceptive learning and recall and constructive abilities were also impaired. These results point to the need for follow-up studies to assess the possible sequelae of chronic and acute exposure to pesticides and their interactions.

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.

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