Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos (original) (raw)
Related papers
Correlating neurobehavioral performance with biomarkers of organophosphorous pesticide exposure
NeuroToxicology, 2011
There is compelling evidence that adverse neurobehavioral effects are associated with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral studies of pesticide applicators, greenhouse workers, agricultural workers and farm residents exposed repeatedly over months or years to low levels of OPs reveal a relatively consistent pattern of neurobehavioral deficits. However, only two studies have demonstrated a link between neurobehavioral performance and current biomarkers of OP exposure including blood cholinesterase (ChE) activity and urinary levels of OP metabolites. A variety of reasons may explain why so few studies have reported such correlations, including differing individual and group exposure histories, differing methodologies for assessing behavior and exposure, and lack of a reliable index of exposure. Alternatively, these data may suggest that current biomarkers (ChE, urine metabolites) are neither predictive nor diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This review focuses on the evidence that neurobehavioral performance deficits are associated with occupational OP pesticide exposure and concludes that research needs to return to the basics and rigorously test the relationships between neurobehavioral performance and both current (ChE and urine metabolites) and novel (eg, inflammation and oxidative stress) biomarkers using human and animal models. The results of such studies are critically important because OP pesticides are widely and extensively used throughout the world, including situations where exposure controls and personal protective equipment are not routinely used.
African Health Sciences
Background: Organophosphate (OP) pesticides are one of the most extensively used chemical compounds all over the world. Objective: The aim of this study is to determine whether occupational exposure of the formulators to the OP pesticides, under normal working conditions, is associated with any hematotoxic, hepatotoxic, nephrotoxic, neurotoxic, and respirotoxic responses among them. Methods: 28 OP formulation plant workers and 17 office workers participated in this cross-sectional study as the exposed and control groups, respectively. Blood and urine samples were collected to measure hematological, biochemical, and urinalysis parameters. American thoracic society questionnaire and spirometry tests were employed to assess the function of their respiratory system. Q16 questionnaire was also used to investigate the prevalence of neurobehavioral symptoms. The data were analyzed by SPSS v.22 software using Kolmogorov–Smirnov, T-test, Mann–Whitney U, Chi-square, Fisher, Pearson, and Spear...
Neuropsychiatric Evaluation in Subjects Chronically Exposed to Organophosphate Pesticides
Toxicological Sciences, 2003
Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on-and off-exposure periods (4.7 ؎ 0.9 and 4.5 ؎ 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.
Neurobehavioural effects among workers occupationally exposed to organophosphorous pesticides
Occupational and Environmental Medicine, 2003
Aims: To identify neurobehavioural deficits among workers exposed to organophosphorous (OP) pesticides in their occupation. Methods: This study was conducted during the period when pesticides were applied to cotton crops in the fields in Menoufiya Governorate, Egypt. Fifty two occupationally exposed male workers were compared to 50 unexposed male controls who were similar in age, socioeconomic class, and years of education (>12 years). All participants completed a questionnaire (assessing personal, occupational, and medical histories), general and neurological clinical examination, neurobehavioural test battery (including tests for verbal abstraction, problem solving, attention, memory, and visuomotor speed), personality assessment, and serological analysis for serum acetylcholinesterase. Results: After correcting for confounders of age and education, the exposed participants exhibited significantly lower performance than controls on six neurobehavioural tests (Similarities, Digit Symbol, Trailmaking part A and B, Letter Cancellation, Digit Span, and Benton Visual Retention). A longer duration of work with pesticides was associated with lower performance on most neurobehavioural tests after adjusting for multiple comparisons. Although serum acetylcholinesterase was significantly lower in the exposed than the control participants, it was not significantly correlated with either neurobehavioural performance or neurological abnormalities. Conclusions: Occupational exposure to OP pesticides was associated with deficits in a wider array of neurobehavioural functions than previously reported, perhaps because of higher exposure in this population. Moderate chronic OP exposure may not only affect visuomotor speed as reported previously, but also verbal abstraction, attention, and memory.
BMC Public Health, 2015
Health effects of pesticides are easily diagnosed when acute poisonings occurs, nevertheless, consequences from chronic exposure can only be observed when neuropsychiatric, neurodegenerative or oncologic pathologies appear. Therefore, early monitoring of this type of exposure is especially relevant to avoid the consequences of pathologies previously described; especially concerning workers exposed to pesticides on the job. For acute organophosphate pesticides (OPP) exposure, two biomarkers have been validated: plasma cholinesterase (ChE) and acetylcholinesterase (AChE) from erythrocytes. These enzymes become inhibited when people are exposed to high doses of organophosphate pesticides, along with clear signs and symptoms of acute poisoning; therefore, they do not serve to identify risk from chronic exposure. This study aims to assess a novel biomarker that could reflect neuropsychological deterioration associated with long-term exposure to organophosphate pesticides via the enzyme acylpeptide-hydrolase (ACPH), which has been recently identified as a direct target of action for some organophosphate compounds.
Cortex, 2016
Chlorpyrifos is an organophosphorus (OP) pesticide widely used around the world for agricultural operations. Although studies have examined exposure in children, there is limited information on adolescents who are occupationally exposed. Furthermore, there is limited research addressing the change in exposure patterns and outcomes across the application season. The goal of the current study was to examine the impact of chlorpyrifos exposure on neurobehavioral performance in adolescents before, during and after the application season. The longitudinal study was conducted in Egypt from April 2010 to January 2011, quantifying exposure and neurobehavioral performance with repeated measures prior to, during, and following the application period. At each test session, participants completed a neurobehavioral test battery and urine was collected for analysis of the chlorpyrifos metabolite 3,5,6-trichloro-2 pyridinol (TCPy) (biomarker of exposure). Cumulative
Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds
Frontiers in Neuroscience, 2017
Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.
Indian journal of biochemistry & biophysics
Organophosphate (OP) pesticides commonly used in agriculture in India are reported to cause poisoning. The effects of acute poisoning by pesticides are well-established; however, low and long-term exposure causing ill health is controversial. Further, the existing database regarding the toxicity effects of OP pesticides (triazophos and acephate) is much limited in India. In this study, we investigated the neurobehavioral, biochemical and immunological manifestation and their possible correlation with triazophos and acephate exposure in humans. A total number of 161 employees comprising control group (n=40), maintenance group (n=50) and exposed group (n=71) working in a unit manufacturing triazophos and acephate were enrolled in the study. Control group comprised of executives, clerks, security and peon, etc. Exposed and maintenance groups included workers engaged in production, formulation, transportation and maintenance of triazophos and acephate. Demographic profile and occupational history were recorded. A battery of neurobehavioral tests was employed as per ILO (1971) recommendations to evaluate neurobehavioral performance. In a subset study of population, serum samples were analyzed for immunological (IgG, IgM and IgA) and thyroid function tests (T3, T4 and TSH). Neurobehavioral findings indicated that exposed group of workers had performance deficiency in digit symbol test in percentage of accuracy, compared to the other groups. A significant (P <0.05) decrease in neurobehavioral performance like finger dexterity test (accuracy %), memory test (forward and backward) and digit symbol test (total) was observed in maintenance group, as compared to control and exposed groups. Workers of exposed group showed poor performance in only tweezer dexterity test (accuracy %). Serum IgM levels showed a significant increase in exposed subjects, indicating the impairment of immune system, while thyroid function was normal in study population. The study showed a possible correlation with exposure to OP pesticides in relation to impairment in some of the neurobehavioral and immunological parameters that might be useful in assessing OP poisoning.
A handbook of environmental toxicology: human disorders and ecotoxicology, 2020
Organophosphate (OP) pesticides are one of the most widely used insecticides in the world and concern about the effects of OPs on human health has been growing as they are increasingly used throughout the world. The neurotoxic effects of high-level acute poisoning are well established, but the possibility that long-term low-level exposure to OPs in doses below that causing acute toxicity causes ill health is controversial. In 2013 we published a systematic review of the literature regarding the neurotoxicity of long-term low-level exposure to organophosphate pesticides in adult populations. In this chapter we summarize and update our previous review, discuss possible reasons for divergent evaluations of the same literature and highlight unanswered questions and methodological considerations that future researchers need to address before firm conclusions can be drawn.