Neurobehavioral problems following low-level exposure to organophosphate pesticides: A systematic and meta-analytic review

ArticleinCritical Reviews in Toxicology 43(1) · November 2012with78 Reads
DOI: 10.3109/10408444.2012.738645 · Source: PubMed
Abstract
Meta-analysis was carried out to determine the neurotoxic effects of long-term exposure to low levels of organophosphates (OPs) in occupational settings. Concern about the effects of OPs on human health has been growing as they are increasingly used throughout the world for a variety of agricultural, industrial and domestic purposes. The neurotoxic effects of acute poisoning are well established but the possibility that low-level exposure causes ill health is controversial. It is important to get a clear answer to this question as more individuals are at risk of low-level exposure than acute poisoning. Although a number of reviews on this topic have been published in the past, authors have come to conflicting conclusions. To date, none of these reviews have attempted quantitative evaluation of study findings using meta-analysis. This paper reviews the available evidence concerning the neurotoxicity of low-level occupational exposure to OPs and goes on to report the results of a meta-analysis of 14 studies which fulfilled criteria for this type of statistical analysis (means and standard deviations of dependant variables reported). Data were assimilated from more than 1600 participants. The majority of well designed studies found a significant association between low-level exposure to OPs and impaired neurobehavioral function which is consistent, small to moderate in magnitude and concerned primarily with cognitive functions such as psychomotor speed, executive function, visuospatial ability, working and visual memory. Unresolved issues in the literature which should become the focus of further studies are highlighted and discussed.
    • "Emerging evidence is also linking industrial chemicals to a pandemic of neurodevelopmental disorders [79] the implications of which have devastating consequences on family's and the global economy [80,81]. Whilst the cause of these neurodevelopmental problems is not yet clear, genetic factors are acknowledged as only playing a minor role [82,83] and several hypotheses point to environmental influences involving aberrations in the gastrointestinal microbiota [83], industrial chemicals [81,84,85], malnutrition [86,87], viruses and drugs [88] as potential causal agents. Environmental factors are also believed to account for a significant portion of cancer mortality worldwide [89]. "
    [Show abstract] [Hide abstract] ABSTRACT: A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the "-omics" fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the "exposome" and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health.
    Full-text · Article · Feb 2016
    • "A variety of long-term neurological consequences of acute poisonings with OPs have also been documented and include electroencephalogram abnormalities, mood disorders (e.g., anxiety and depression), deficits in psychomotor speed and coordination, and a variety of cognitive deficits (Brown and Brix, 1998; Miyaki et al., 2005; Pereira et al., 2014). A number of epidemiologic studies also suggest that exposures to OPs at levels not associated with acute symptoms of toxicity can result in long term neurobehavioral abnormalities especially cognitive abnormalities (e.g., deficits in attention, working memory, executive function, visuospatial ability and visual memory (Pope et al., 2005; Ross et al., 2013)). This article has not been copyedited and formatted. "
    [Show abstract] [Hide abstract] ABSTRACT: The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurological abnormalities. While the mechanism of the acute toxicity of OPs is attributed to inhibition of acetylcholinesterase (AChE), there is growing evidence that this may not account for all of the long term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent, diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long term neurological deficits that have been observed in humans who have been exposed to organophosphates.
    Full-text · Article · Dec 2015
    • "As far as we are aware, we were the first research team to attempt quantitative evaluation of study findings using meta-analysis to evaluate the literature regarding the neurotoxicity of low level occupational exposure to OPs. In 2012 our findings were reported online by the journal Critical Reviews in Toxicology and published in January 2013 (Mackenzie Ross et al, 2013). In summary, we reviewed literature published between 1960 and 2012, and assimilated data from 14 studies incorporating more than 1600 participants, using meta-analysis. "
    [Show abstract] [Hide abstract] ABSTRACT: We undertook a systematic review (incorporating meta-analysis) of the literature concerning the neurotoxicity of cumulative low level occupational exposure to organophosphate pesticides, which was published online by the journal Critical Reviews in Toxicology in 2012. As far as we are aware, we were the first research team to attempt quantitative evaluation of study findings on this topic, using meta-analysis. We wish to encourage others to apply systematic review techniques in chemical risk assessment to reduce bias, increase transparency and better inform public policy. We thought it would be useful to share our experience of undertaking a systematic review in the hope of dispelling misconceptions about the complexity, time and resource issues involved along with the view that meta-analysis is meaningless when studies are not homogeneous. In this commentary paper we reflect on aspects of the process which were relatively straightforward; aspects which were more challenging; the advantages of using systematic review techniques; and the advantages and limitations of using statistical techniques such as meta-analysis in this context.
    Article · Nov 2015
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