Suicide and exposure to organophosphate insecticides: Cause or effect?

BACKGROUND: Suicide using pesticides as agent is recognized as a major cause of pesticide poisoning. METHODS: A literature review of mortality and morbidity studies related to suicide among pesticide-exposed populations, and of human and animal studies of central nervous system toxicity related to organophosphate (OP) pesticides was performed. RESULTS: Suicide rates are high in farming populations. Animal studies link OP exposure to serotonin disturbances in the central nervous system, which are implicated in depression and suicide in humans. Epidemiological studies conclude that acute and chronic OP exposure is associated with affective disorders. Case series and ecological studies also support a causal association between OP use and suicide. CONCLUSIONS: OPs are not only agents for suicide. They may be part of the causal pathway. Emphasizing OPs solely as agents for suicide shifts responsibility for prevention to the individual, reducing corporate responsibility and limiting policy options available for control.     

Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review

Background: Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial.

Objective: To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers.

Methods: Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers.

Results: Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual–spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance.

Conclusions: Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected.     

Use of biomarkers to indicate exposure of children to organophosphate pesticides: implications for a longitudinal study of children's environmental health

Because of their history of widespread use in the United States and unknown long-term health effects, organophosphate pesticides (OPs) are being considered as a chemical class of interest in planning for the National Children's Study, a longitudinal study of children's environmental health. The availability and appropriate use of biomarkers to determine absorbed doses of environmental chemicals such as OPs are critical issues. Biomarkers of OP exposure are typically measured in blood and urine; however, postpartum meconium has been shown to be a promising matrix for assessing cumulative in utero exposure to the fetus, and studies are currently in progress to determine the utility of using saliva and amniotic fluid as matrices. In this article, we discuss the advantages and disadvantages of the currently available OP exposure monitoring methods (cholinesterase inhibition in blood, pesticides in blood, metabolites in urine and alternative matrices); study design issues for a large, long-term study of children's environmental health; and current research and future research needs. Because OPs are rapidly metabolized and excreted, the utility of one-time spot measurements of OP biomarkers is questionable unless background exposure levels are relatively stable over time or a specific time frame of interest for the study is identified and samples are collected accordingly. Biomarkers of OP exposure can be a valuable tool in epidemiology of children's environmental health, as long as they are applied and interpreted appropriately.     

Environmental and biological monitoring of exposure to organophosphorus pesticides: application to occupationally and non-occupationally exposed adult populations

The purpose of the study was to assess non-dietary exposure of workers and the general population in the Paris area to some organophosphorus (OP) pesticides. In total, 21 workers from different occupational places (two greenhouses, three florist shops and three veterinary departments) and 20 subjects assumed to be non-occupationally exposed were recruited. Indoor air, hand wipes, and three first morning urine samples were collected. Seven OPs were measured by GC/ECD and GC/TSD, and six urinary dialkylphosphate metabolites by GC/PFPD. All indoor air samples from the workplaces and only one-third of the samples from the residences contained at least one of the seven OPs. However, almost all participants were dermally exposed to OPs. Total OP indoor air and cutaneous levels were significantly higher for workers than for the general population (air median = 185 pmol/m3 versus nondetectable, P < 0.0001; hands median = 1250 pmol/hands versus 475 pmol/hands, P = 0.03). From the air, gardeners and florists were mainly exposed to methyl-OPs and veterinary staff to ethyl-OPs (mainly diazinon). From their hands, all subjects were exposed to methyl-OPs, with gardeners and florists exposed to somewhat but not significantly higher levels. Ethyl-OPs were more found frequently and at higher levels on the hands of veterinary workers. Total OP levels in indoor air and from hand wipes were significantly correlated (Spearman R = 0.34, P = 0.03). DAP detection frequencies and levels were not different between workers and the general population (workers median=168 nmol/g creat and general population median = 241 nmol/g creat, P = 0.31), and did not correlate with air or hand levels. Subjects not occupationally exposed showed significant residential exposure to OPs, more frequently from their hands than from the air. Different occupations were associated with different exposure profiles and levels. The lack of differences in DAP levels between the different groups of exposure suggests that dietary exposure to OP residues and exposure to other OPs are involved.     

Developmental and polyamine metabolism alterations in Rhinella arenarum embryos exposed to the organophosphate chlorpyrifos

Organophosphorus pesticides (OPs) are widely applied in the Alto Valle of Río Negro and Neuquén, Argentina, due to intensive fruit growing. Amphibians are particularly sensitive to environmental pollution, and OPs may transiently accumulate in ponds and channels of the region during their reproductive season. Organophosphorus pesticide exposure may alter amphibian embryonic development and the reproductive success of autochthonous species. In the present study, embryos of the common toad Rhinella arenarum were employed to assess developmental alterations and to study polyamine metabolism, which is essential to normal growth, as a possible target underlying the effects of the OP chlorpyrifos. As the duration of chlorpyrifos exposure increased and embryonic development progressed, the median lethal concentration (LC50) values decreased, and the percentage of malformed embryos increased. Developmental arrest was also observed and several morphological alterations were recorded, such as incomplete and abnormal closure of the neural tube, dorsal curvature of the caudal fin, reduction of body size and caudal fin length, atrophy, and edema. An early decrease in ornithine decarboxylase (ODC) activity and polyamine levels was also observed in embryos exposed to chlorpyrifos. The decrease in polyamine contents in tail bud embryos might be a consequence of the reduction in ODC activity. The alteration of polyamine metabolism occurred before embryonic growth was interrupted and embryonic malformations were observed and may be useful as a biomarker in environmental studies. Environ. Toxicol. Chem. 2012; 31: 2052-2058. ? 2012 SETAC.     

Tactile vibration thresholds after acute poisonings with organophosphate insecticides

This study evaluated the association between acute poisoning with organophosphate pesticides (OPs) and quantitative tactile vibration thresholds. Thresholds of the dominant index fingers and big toes of 56 men hospitalized for acute poisoning with OPs were measured at hospital discharge (1-24 days after poisoning) and around seven weeks later (24-176 days after poisoning), and compared with those of controls. Thresholds of the big toes of men with severe intentional poisonings due to neuropathic OPs (metamidophos and chlorpyrifos) increased between the first and second examinations. Threshold impairment was not detected in the index finger regardless of poisoning agent or severity. The development of threshold impairment as a consequence of severe intentional poisonings with neuropathic OPs is consistent with other reports indicating that only severe OP poisonings produce sensory peripheral nerve effects.     

长期接触低剂量有机磷农药对人体健康影响的研究进展

有机磷农药（OPs）是我国使用量最大的一类农药之一，广泛使用于水果、蔬菜、烟草、棉花等作物。近年来，由OPs引起的急性中毒事件已逐步减少，而长期低剂量暴露OPs对人体健康的危害逐渐引起了人们的重视。越来越多的研究发现长期低剂量暴露OPs与人体肿瘤的发生，不良生殖结局，神经及神经行为功能的异常有密切关系。     

Tactile Vibration Thresholds after Acute Poisonings with Organophosphate Insecticides

Abstract

This study evaluated the association between acute poisoning with organophosphate pesticides (OPs) and quantitative tactile vibration thresholds. Thresholds of the dominant index fingers and big toes of 56 men hospitalized for acute poisoning with OPs were measured at hospital discharge (1–24 days after poisoning) and around seven weeks later (24–176 days after poisoning), and compared with those of controls. Thresholds of the big toes of men with severe intentional poisonings due to neuropathic OPs (metamidophos and chlorpyrifos) increased between the first and second examinations. Threshold impairment was not detected in the index finger regardless of poisoning agent or severity. The development of threshold impairment as a consequence of severe intentional poisonings with neuropathic OPs is consistent with other reports indicating that only severe OP poisonings produce sensory peripheral nerve effects.     

The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence

The epidemiological studies presented in this paper refer to the association between agricultural occupation of parents and the incidence of infertility, congenital malformations, miscarriage, low birthweight, small-for-gestational-age (SGA) birth, preterm delivery and stillbirth. The results of the analyses showed that employment in agriculture increases the risk of specific morphological abnormalities in sperm, including the decreased sperm count per ejaculate and declined percentage of viable sperm. In general, no effect of exposure to pesticides on sexual hormones was observed. The data on the effect of employment in agriculture on the time to pregnancy are unequivocal, but most of them suggest that there is a relationship between the decreased fecundability ratio and pesticide exposure. Nor does the research on the sex ratio of offspring provide explicit results. The analyses indicate that parental employment in agriculture could increase the risk of congenital malformations in the offsprings, particularly such as orofacial cleft, birthmarks in the form of hemangioma as well as musculoskeletal and nervous system defects. The data on the effect of occupational exposure to pesticides on birthweight are inconsistent. Although most of epidemiological studies do not reveal a significantly increased risk of SGA, a slower pace of fetal development corresponding to SGA in the population of women exposed to pyrethroids has been recently reported. There are also some indications that exposure to pesticides may contribute to stillbirth and female infertility. The literature review suggests a great need to increase awareness of workers who are occupationally exposed to pesticides about their potential negative influence on fertility and pregnancy outcome. In the light of existing although still limited evidence of adverse effects of pesticide exposure on fertility during the preconceptual period, it is necessary to reduce the exposure to pesticides.     

Exposure to organophosphate (OP) pesticides and health conditions in agricultural and non-agricultural workers from Maule,Chile

The objective was to evaluate the characteristics of exposure to OP pesticides and health status in Chilean farm workers from the Maule Region. An occupational health questionnaire was administered in 207 agricultural and non-agricultural workers. For the group of agricultural workers, we asked about specific occupational exposure history and symptoms of OP pesticide poisoning. The main health problem of the exposed group was previous OP pesticide poisoning (p < 0.001). Fifty-six percent of agricultural workers reported symptoms consistent with acute OP pesticide poisoning. The use of respiratory personal protective equipment and younger age were protective against these symptoms, and number of years of OP pesticide exposure was positively associated with reporting symptoms of poisoning. Of the pesticide applicators 47 % reported using chlorpyrifos. The regulations regarding use and application of pesticides should be strengthened, as should training and intervention with workers to improve the use of personal protective equipment.     

Using physiologically-based pharmacokinetic models to incorporate chemical and non-chemical stressors into cumulative risk assessment: a case study of pesticide exposures

Cumulative risk assessment has been proposed as an approach to evaluate the health risks associated with simultaneous exposure to multiple chemical and non-chemical stressors. Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models can allow for the inclusion and evaluation of multiple stressors, including non-chemical stressors, but studies have not leveraged PBPK/PD models to jointly consider these disparate exposures in a cumulative risk context. In this study, we focused on exposures to organophosphate (OP) pesticides for children in urban low-income environments, where these children would be simultaneously exposed to other pesticides (including pyrethroids) and non-chemical stressors that may modify the effects of these exposures (including diet). We developed a methodological framework to evaluate chemical and non-chemical stressor impacts on OPs, utilizing an existing PBPK/PD model for chlorpyrifos. We evaluated population-specific stressors that would influence OP doses or acetylcholinesterase (AChE) inhibition, the relevant PD outcome. We incorporated the impact of simultaneous exposure to pyrethroids and dietary factors on OP dose through the compartments of metabolism and PD outcome within the PBPK model, and simulated combinations of stressors across multiple exposure ranges and potential body weights. Our analyses demonstrated that both chemical and non-chemical stressors can influence the health implications of OP exposures, with up to 5-fold variability in AChE inhibition across combinations of stressor values for a given OP dose. We demonstrate an approach for modeling OP risks in the presence of other population-specific environmental stressors, providing insight about co-exposures and variability factors that most impact OP health risks and contribute to children's cumulative health risk from pesticides. More generally, this framework can be used to inform cumulative risk assessment for any compound impacted by chemical and non-chemical stressors through metabolism or PD outcomes.     

Pesticide exposure and women's health

BACKGROUND: Research on pesticide-related health effects has been mostly focused in industrialized countries and in men. This paper discusses critical issues related to women's pesticide exposure and its effects on women's health. METHODS: The literature on pesticides was reviewed with emphasis on data related to women. Attention was focused on research suggesting different conditions of exposure or different response to pesticides by sex. Studies on cancer and reproductive effects were used as illustrative examples. RESULTS: Women are increasingly exposed to pesticides in developing countries, where women's poisoning and other pesticide-related injuries seem to be greatly underestimated. Many of the effects of pesticides in human health will be the same for men and women, but not always. Some organochlorine pesticides have been related to breast cancer in post-menopausal women. However, knowledge about other pesticides is much more limited. Epidemiological studies assessing maternal exposure to individual pesticides and abortion, fetal death, or congenital defects are not conclusive, although some suggestive associations have been observed. CONCLUSIONS: Gender-sensitive research is needed to properly address the study of women's pesticide exposures and related adverse outcomes. A better understanding of potential gender-environment and sex-environment interactions related to pesticide exposure and health effects in women is needed.     

Organophosphate Pesticide Exposure in School-Aged Children Living in Rice and Aquacultural Farming Regions of Thailand

Organophosphate pesticides (OPs) are widely used in agricultural sectors in Thailand. Previous studies have documented that children residing in agricultural areas have higher exposure to OPs than children living in other residential areas. The objective of this study was to quantify urinary biomarkers of OP exposure and determine the environmental conditions and activities that predict their levels among children living in Central Thailand farming regions. In October 2011, 53 6–8-year-old participants were recruited from Pathum Thani Province, Thailand. Twenty-four lived in rice farming communities at Khlong Luang District where OPs are the pesticides used frequently. Twenty-nine participants, living in aquacultural farming communities at Lum Luk Ka District where OPs are not used, were recruited to serve as controls for pathways of exposure (e.g., residential, dietary) other than occupational/paraoccupational exposures encountered in rice farming. Household environments and participants’ activities were assessed using a parental structured interview. Urine samples (first morning voids) were collected from participants for OP urinary metabolite (i.e., dialkylphosphates [DAPs] and 3,5,6-trichloro-2-pyridinol [TCPy]) measurements. The levels of most urinary OP metabolites were significantly higher in participants who lived in a rice farming community than those who lived in an aquacultural farming community (P < .05). The results from linear regression analysis revealed that the frequency of OP application on rice farms (∑DAP: P = .001; TCPy: P = .001) and living in a rice farming community (∑DAP: P = .009; TCPy: P < .001) were significant predictors of urinary DAP metabolite levels in participants. Increasing TCPy levels were significantly related to proximity to rice farm (P = .03), being with parent while working on a farm (P = .02), playing on a farm (P = .03), and the presence of observable dirt accumulated on the child’s body (P = .02). In conclusion, OP metabolite levels among children who live in rice farming communities were strongly influenced by farming activity, household environments, and child behaviors, suggesting that these are the primary pathways in which children living in these agricultural communities in Thailand were exposed to OPs.     

Peripheral nervous system function and organophosphate pesticide use among licensed pesticide applicators in the Agricultural Health Study

Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function.Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS).Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates.Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold.Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators.     

Semen quality and reproductive sex hormone levels in Peruvian pesticide sprayers

To determine the association between occupational pesticide exposure and semen quality among sprayers using organophosphate (OPs) pesticides, 31 pesticide sprayers and 80 men who were not exposed were studied. Semen and blood samples were obtained one day after last pesticide application. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, and fructose and zinc concentrations. Blood samples were analyzed for sex hormones. Pesticide sprayers had significantly reduced age-adjusted seminal volume, percentage of motility, percentage of sperm with normal morphology, serum luteinizing hormone, serum testosterone levels, and seminal zinc concentration (a marker of prostate function), as well as significantly increased time of liquefaction, seminal pH, percentage of immature sperm morphology, and leukocyte concentration. These findings provide further evidence that occupational exposures to OP pesticides adversely affect semen quality and sex hormones.     

Influence of pesticide regulation on acute poisoning deaths in Sri Lanka

OBJECTIVES: To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s, aimed to reduce the number of deaths - the majority from self-poisoning - by limiting the availability and use of highly toxic pesticides. METHODS: Information on legislative changes was obtained from the Ministry of Agriculture, national and district hospital admission data were obtained from the Sri Lanka Health Statistics Unit, and individual details of deaths by pesticide poisoning were obtained from a manual review of patients' notes and intensive care unit records in Anuradhapura. FINDINGS: Between 1986 and 2000, the total national number of admissions due to poisoning doubled, and admissions due to pesticide poisoning increased by more than 50%. At the same time, the case fatality proportion (CFP) fell for total poisonings and for poisonings due to pesticides. In 1991_92, 72% of pesticide-induced deaths in Anuradhapura were caused by organophosphorus (OP) and carbamate pesticides - in particular, the WHO class I OPs monocrotophos and methamidophos. From 1991, the import of these pesticides was reduced gradually until they were banned for routine use in January 1995, with a corresponding fall in deaths. Unfortunately, their place in agricultural practice was taken by the WHO class II organochlorine endosulfan, which led to a rise in deaths from status epilepticus - from one in 1994 to 50 in 1998. Endosulfan was banned in 1998, and over the following three years the number of endosulfan deaths fell to three. However, at the end of the decade, the number of deaths from pesticides was at a similar level to that of 1991, with WHO class II OPs causing the most deaths. Although these drugs are less toxic than class I OPs, the management of class II OPs remains difficult because they are, nevertheless, still highly toxic, and their toxicity is exacerbated by the paucity of available facilities. CONCLUSION: The fall in CFP amidst a rising incidence of self-poisoning suggests that Sri Lanka's programmes of pesticide regulation were beneficial. However, a closer inspection of pesticide-induced deaths in one hospital revealed switching to other highly toxic pesticides, as one was banned and replaced in agricultural practice by another. Future regulation must predict this switching and bear in mind the ease of treatment of replacement pesticides. Furthermore, such regulations must be implemented alongside other strategies, such as integrated pest management, to reduce the overall pesticide availability for self-harm.     

Toxicity due to organophosphorus compounds: what about chronic exposure?

The inappropriate use of toxic chemicals is common in developing countries, where it leads to excessive exposure and high risks of unintentional poisoning. The risks are particularly high with the pesticides used in agriculture, where poor rural populations live and work in close proximity to these compounds, which are often stored in and around the home. It is estimated that 99% of all deaths from pesticide poisoning occur in developing countries. Whilst the acute toxicity of pesticides has been well documented, there is still relatively little known of the effects on health of chronic pesticide exposure. Organophosphate insecticides have been extensively used in agriculture in developing countries, with little protection for the communities and individuals thus exposed. Given the indisputable chronic exposure of vulnerable groups to organophosphate compounds, including pregnant women, the fetus and young children, the potential for widespread adverse effects is considerable. Thus, whilst there is some evidence that chronic exposure may have adverse effects on health, there is an urgent need for high-quality observational and interventional studies of both occupational and environmental exposure to these compounds.     

Occupational exposures to metals, solvents and pesticides: recent evidence on male reproductive effects and biological markers

This review is based primarily on the recent epidemiological studies conducted in occupational settings in order to explore the relationship between exposures to chemical agents and the possible effects on male reproductive function. The paper examines evidence of the effects of metals, solvents, pesticides and dioxin. The effects considered are primarily the possible alterations of sperm quality and reduction of fertility. Many studies have identified small groups of workers with exposures to these agents, presenting some alteration in the spermatological or fertility profile, but the results are difficult to replicate in other settings with different individuals and different levels of exposure. From examination of the concentrations of environmental and occupational pollutants in the blood and in the seminal fluid of exposed individuals, it appears that, in general, the concentrations are much lower in the seminal fluid and in sperm cells, making this a less useful marker of exposure.     

Dialkyl phosphate metabolites of organophosphorus in applicators of agricultural pesticides in Majes – Arequipa (Peru)

Background  

Organophosphorus (OPs) pesticides are the most commonly used pesticides in Peruvian agriculture. The population at risk for OPs exposure includes formulators, applicators and farmers. Majes Valley is the most important agricultural center of the Southern region of Peru. The present study was aimed to determine the knowledge about using OPs, safety practice and urinary dialkylphosphate metabolites on OP applicators in the Majes Valley, Peru.     

长期低剂量接触有机磷农药效应标志物研究进展

有机磷酸酯类农药（OP）是我国大陆目前生产和使用最多的一种农药,其长期低剂量接触多见于生产、仓储、销售、混配、施用等过程,在农药的职业危害控制中占有十分重要的地位。探讨长期低剂量接触OP的效应标志物,对于及时发现职业接触人群早期健康损害,预防和控制慢性农药中毒具有十分重要的意义。