Neurobehavioral problems following low-level exposure to organophosphate pesticides: a systematic and meta-analytic review.
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.
- SourceAvailable from: Phillip Williams[Show abstract] [Hide abstract]
ABSTRACT: The use of pesticides is ubiquitous worldwide, and these chemicals exert adverse effects on both target and nontarget species. Understanding the modes of action of pesticides, as well as quantifying exposure concentration and duration, is an important goal of clinicians and environmental health scientists. Some chemical exposures result in adverse effects on the nervous system. The nematode Caenorhabditis elegans (C. elegans) is a model lab organism well established for studying neurotoxicity, since the components of its nervous system are mapped and known, and most of its neurotransmitters correspond to human homologs. This review encompasses published studies in which C. elegans nematodes were exposed to pesticides with known neurotoxic actions. Endpoints measured include changes in locomotion, feeding behavior, brood size, growth, life span, and cell death. From data presented, evidence indicates that C. elegans can serve a role in assessing the effects of neurotoxic pesticides at the sublethal cellular level, thereby advancing our understanding of the mechanisms underlying toxicity induced by these chemicals. A proposed toxicity testing scheme for water-soluble chemicals is also included.Journal of Toxicology and Environmental Health Part B 09/2014; 17(5):284-306. · 5.15 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Differences among outcomes required separate analyses on adults and adolescents.•Scores in tests on memory and attention were consistently lower in exposed adults.•Poisonings, subject characteristics or within-study bias did not explain the differences among studies.•Neuropsychological performances of exposed workers were related to exposure duration.•Further investigations are needed to specify the risk of adolescents and women.Environmental Research 01/2015; 136. · 3.95 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Humans are exposed to distinct structural classes of insecticides with different neurotoxic modes of action. Since calcium homeostasis is essential for proper neuronal function and development, we investigated the effects of insecticides from different classes (pyrethroid: (α-)cypermethrin; organophosphate: chlorpyrifos; organochlorine: endosulfan; neonicotinoid: imidacloprid) and mixtures thereof on the intracellular calcium concentration ([Ca(2+)]i). Effects of acute (20 min) exposure to (mixtures of) insecticides on basal and depolarization-evoked [Ca(2+)]i were studied in vitro with Fura-2-loaded PC12 cells and high resolution single-cell fluorescence microscopy. The data demonstrate that cypermethrin, α-cypermethrin, endosulfan, and chlorpyrifos concentration-dependently decreased depolarization-evoked [Ca(2+)]i, with 50% (IC50) at 78 nM, 239 nM, 250 nM and 899 nM, respectively. Additionally, acute exposure to chlorpyrifos or endosulfan (10 μM) induced a modest increase in basal [Ca(2+)]i, amounting to 68±8 nM and 53±8 nM, respectively. Imidacloprid did not disturb basal or depolarization-evoked [Ca(2+)]i at 10 μM. Following exposure to binary mixtures, effects on depolarization-evoked [Ca(2+)]i were within the expected effect additivity range, while the effect of the tertiary mixture was less than this expected additivity effect range. These results demonstrate that different types of insecticides inhibit depolarization-evoked [Ca(2+)]i in PC12 cells by inhibiting VGCCs in vitro at concentrations comparable to human occupational exposure levels. Moreover, the effective concentrations in this study are below those for earlier described modes of action. Since inhibition of VGCCs appears to be a common and potentially additive mode of action of several classes of insecticides, this target should be considered in neurotoxicity risk assessment studies.Toxicological Sciences 06/2014; · 4.48 Impact Factor