Chronic Toxicity Of Pesticides Research Articles

High-Resolution Metabolomic Assessment of Pesticide Exposure in Central Valley, California

Pesticides are widely used in the agricultural Central Valley region of California. Historically, this has included organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs). This study aimed to identify perturbations of the serum metabolome in response to each class of pesticide and mutual associations between groups of metabolites and multiple pesticides. We conducted high-resolution metabolomic profiling of serum samples from 176 older adults living in the California Central Valley using liquid chromatography with high-resolution mass spectrometry. We estimated chronic pesticide exposure (from 1974 to year of blood draw) to OPs, OCs, and PYRs from ambient sources at homes and workplaces with a geographic information system (GIS)-based model. Based on partial least-squares regression and pathway enrichment analysis, we identified metabolites and metabolic pathways associated with one or multiple pesticide classes, including mitochondrial energy metabolism, fatty acid and lipid metabolism, and amino acid metabolism. Utilizing an integrative network approach, we found that the fatty acid β-oxidation pathway is a common pathway shared across all three pesticide classes. The disruptions of the serum metabolome suggested that chronic pesticide exposure might result in oxidative stress, inflammatory reactions, and mitochondrial dysfunction, all of which have been previously implicated in a wide variety of diseases. Overall, our findings provided a comprehensive view of the molecular mechanisms of chronic pesticide toxicity, and, for the first time, our approach informs exposome research by moving from macrolevel population exposures to microlevel biologic responses.

Assessment of organochlorine and organophosphorus pesticides in various meats samples of maharashtra-india using gas chromatography

Chronic pesticide toxicity, recognized as a major health hazard in human food chain, comprises of foods from animal source. Devising analytical methods for estimating pesticide residues will help to monitor the status of these contaminants in animal source foods. In this study, two pesticide groups viz., organochlorine (OC) and organophosphorus (OP) compounds were selected to detect pollutants in various meat samples. To detect these pesticides gas chromatography (GC) method was used, standardized and validated. Validation studies on meat samples included accuracy, precision, linearity, limit of detection and quantification. A total of 240 numbers of meat samples of chicken, buffalo, sheep/goat and pig were collected from three different regions of Maharashtra and used in validation studies. The mean concentration of DDT residues in the chicken, buffalo, sheep/goat and pig meat was found to be 27.34, 10.67, 76.33 and 44.12 pg/kg, respectively. Mean concentration of HCH residues in chicken and pig meat was found to be 7.50 and 112.20 pg/kg, and was not detected in buffalo and sheep/goat meat. Mean concentration of Endosulfan and Aldrin residues in chicken, buffalo and sheep/goat meat were found to be 51.09, 23.18, 211.37 pg/kg and 111.48, 81.85, 54.79 pg/kg, respectively. Chlorpyrifos was not detected in any of the meat samples collected. However, the values of pesticide residue concentration in all the 240 nos. of meat samples were found to be below the MRLs values set by Codex Alimentarius Commission and European Commission Regulation (EC) No. 149/2008. Therefore, it is concluded that the standardized GC method can be used for the detection of pesticides in different matrices.

Morphogen signaling by Wnt/β-catenin pathway and microenvironmental alteration in the bone marrow of agricultural pesticide exposure-induced experimental aplastic anemia.

The etiologic link between pesticide toxicity and aplastic anemia in agricultural and agro-industrial setting has been frequently reported in epidemiological studies conducted worldwide. Chronic pesticide toxicity causes long-term bone marrow injury and perturbs the normal hematopoietic physiology, including survival of hematopoietic progenitor cells and bone marrow's blood cell forming ability. The purpose of this study is to understand the mechanism of pesticide toxicity-mediated bone marrow aplasia by studying Wnt/β-catenin signaling pathway and microenvironmental stromal components. An agricultural pesticide formulation comprising of cypermethrin, chlorpyriphos, and hexaconazole was used to induce bone marrow aplasia in inbred Swiss albino mice. Marrow failure followed by the onset of aplastic condition was confirmed by pancytopenic peripheral blood and hypocellular bone marrow filled with adipocytes. Significant downregulation of canonical Wnt/β-catenin signaling was identified by expression analysis of Wnt3a, β-catenin, and telomerase reverse transcriptase in the aplastic bone marrow hematopoietic stem/progenitor compartment. Along with signaling deregulation, disruption in both the osteoblastic and vascular stromal components was observed in the pesticide-exposed bone marrow microenvironment when compared to control. In this study, we tried to establish the correlation among disease pathophysiology, signaling deregulation in the hematopoietic cells, and bone marrow microenvironmental alteration during environmental exposure-mediated aplastic hematopoietic catastrophe, which may shed light on the unexplored mechanistic perspective of this fatal blood disease.

The new aspects of using some safe feed additives on alleviated imidacloprid toxicity in farmed fish: a review

AbstractIntensive fish culturing systems depend on provides optimal water quality conditions. Hence, the most important aquaculture practices are the removal of contamination elements related not only to the water quality parameters unacceptable for aquatic species but also to the undesirable effect on the health of fish and consumers. During the last three decades, common applications and production of pesticides have amplified progressively. Due to the excessive use of imidacloprid as a highly effective insecticide, elevated accumulation is expected in an aquatic environment. A large part of applied pesticides emitted into the environment and only a small portion of them reach the final biological target, where it caused several hazards, such as accumulation and toxicity to non‐target creatures. Plant‐derived secondary metabolites are getting great attention due to their safety and therapeutic functions. Also, several feed additives in animal diets can act as chemopreventive agents, which have the potential to decrease the toxicity risk of many pollutants and detoxification of activated metabolites. Understanding the internal action mechanisms of various safe feed additives could lead to the novel therapeutic approaches for acute and chronic pesticide toxicity. This review intends to summarize how safe feed additives alter or mitigate the toxic effects of imidacloprid in farmed fish.

Investigation of Acute and Chronic Toxicity Trends of Pesticides Using High-Throughput Bioluminescence Assay Based on the Test Organism Vibrio fischeri.

High-throughput acute and chronic toxicity tests using Vibrio fischeri were used to assess the toxicity of a variety of fungicides, herbicides, and neonicotinoids. The use of time points beyond the traditional 30min of an acute test highlighted the sensitivity and applicability of the chronic toxicity test and indicated that for some compounds toxicity is underestimated using only the acute test. The comparison of EC50 values obtained from acute and chronic tests provided insight regarding the toxicity mode of action, either being direct or indirect. Using a structure-activity relationship approach similar to the one used in hazard assessments, the relationship between toxicity and key physicochemical properties of pesticides was investigated and trends were identified. This study not only provides new information regarding acute toxicity of some pesticides but also is one of the first studies to investigate the chronic toxicity of pesticides using the test organism V. fischeri. The findings demonstrated that the initial bioluminescence has a large effect on the calculated effective concentrations for target compounds in both acute and chronic tests, providing a way to improve and standardize the test protocol. In addition, the findings emphasize the need for additional investigation regarding the relationship between a toxicant's physicochemical properties and mode of action in nontarget organisms.

Chronic toxicity of pesticides to the mRNA expression levels of metallothioneins and cytochrome P450 1A genes in rainbow trout

The hazardous effects of pesticides on various metabolic pathways are a great problem for environmental health and should be well determined. In the present study, the authors treated rainbow trout with 0.6 μg/L deltamethrin for 28 days and 1.6 mg/L 2,2-dichlorovinyl dimethyl phosphate for 21 days. After this time period, the authors observed alterations in mRNA expression levels of MT-A, MT-B and CYP-1A. Chronic exposure to low levels of pesticides may have a more significant effect on fish populations than acute poisoning. While both pesticides caused a significant increase on mRNA levels of MT-A and CYP-1A, MT-B mRNA levels were increased significantly only upon deltamethin administration. The significant increase in mRNA levels of the corresponding genes may be considered as a defence mechanism in addition to the antioxidants against oxidative stress, as well as a detoxification mechanism against adverse effects of pesticides.

Risk assessment induced by knapsack or conventional motor sprayer on pesticides applicators and farm workers in cotton season

Fakous Province in the Sharkia Governorate constitutes one of the largest agricultural areas in Egypt. The majority of people in this province rely on subsistence agriculture. In the cotton cultivation season the continuous application of pesticides is commonly used to increase agricultural productivity, using different types of spraying equipment. In this study a cohort of 210 intensive agricultural pesticide applicators and farm workers from Sawada and Akyad Elkepplia villages in Fakous Province were assessed according to the type of spraying equipment they used. Conventional motor (300 l/feddan or 0.42 ha) and knapsack motor sprayer (20 l/feddan) were commonly used by farmers. Contamination on applicators was detected on head, body (thorax/abdomen) and legs at different percentages according to the spraying tools. The recorded results revealed that contamination with pesticides due to knapsack motor sprayers 0.76% on head, 4.8% on body and 5.8% on legs; however, conventional motor sprayers induce contamination of 3.6% on head, 23.7% on body and 29.1% on legs. Several criteria for estimating pesticide contamination by previous delivery systems were used. The most important reference biomarker was serum acetyl cholinesterase (AchE) depression. Sprayers showed changes in serum glucose levels as well as reduced erythrocytic glutathione levels (GSH). However, an increase in both total serum protein and albumin was recorded also, alongside elevation in lipid peroxidation biomarker malondialdehyde (MDA). Changes in serum biochemistry regarding enzymes reflecting cytotoxicity were also recorded, such as inhibition of alanine aminotransferase (ALT) and glutathione-S-transferase (GST). An increase in aspartate aminotransferase (AST) and glutathione reductase (GR) was observed particularly in conventional motor sprayers. Changes in enzymes activities found in this study are linked to the adverse health effects related to chronic pesticide toxicity that may lead to pathophysiological diseases, cancer or neurodegenerative disorders, which warrants further investigation.

Biomarkers of cellular reaction to pesticide exposure in a rural population

In the present study we report data obtained from the evaluation of subjects occupationally exposed to pesticide mixtures from Santa Fe province, Argentina, using biomarkers for butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities, catalase (CAT), lipid peroxidation (by TBARS assay) and the Damage Index Comet Assay (DICA). Our results showed an AChE inhibition (25% and 15% in directly and indirectly groups, respectively) in relation to controls with no significant modifications in BChE. TBARS levels were higher (51%) in pesticide sprayers while CAT activity was reduced in both, applicators (61%) and non-applicators (43%). DICA was significantly increased in direct (83%) and indirect (98%) exposed groups, compared with controls. These results showed modifications in lipid peroxidation, antioxidant defence system, and DNA damage in lymphocytes of exposed workers. Further investigations are suggested in order to link our findings with adverse health effects observed in chronic pesticide toxicity, where oxidative damage plays a pathophysiological role.

Changes in antioxidant enzymes in humans with long-term exposure to pesticides

Different pesticides, including organophosphates (OPs), have been reported to induce oxidative stress due to generation of free radicals and alteration in antioxidant defence mechanisms. In this study, a cohort of 81 intensive agriculture workers (pesticide sprayers) was assessed twice during the course of a spraying season for changes in erythrocyte antioxidant enzymes. Acetylcholinesterase (AChE) was used as a reference biomarker. Sprayers presented lower levels of superoxide dismutase (SOD) and glutathione reductase (GR) as compared to controls independently of age, BMI, smoking habit or alcohol consumption. A positive correlation between SOD and AChE was observed at the high exposure period. Those individuals with a decrease in AChE greater than 15% exhibited lower SOD and catalase (CAT) activities at the same period. Glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) remained unaffected in the exposed population. Paraoxonase (PON1) polymorphism influenced erythrocyte CAT and GR, as subjects with the R allele presented lower CAT and higher GR levels. Whether or not the decreased enzyme activities found in this study are linked to the adverse health effects related to chronic pesticide toxicity (in which oxidative damage plays a pathophysiological role, such as cancer or neurodegenerative disorders) is an attractive hypothesis that warrants further investigation.

Effect of Long-Term Exposure to Pesticides on Plasma Esterases from Plastic Greenhouse Workers

Previous reports in animals consideredβ-glucuronidase activity as a novel biomarker of anticholinesterase (organophosphates and carbamates) pesticides exposure. Acid phosphatase activity was also shown to increase after organophosphates exposure. In addition, there is evidence that the paraoxonase status influences sensitivity to specific pesticides. In this study, activities ofβ-glucuronidase, acid phosphatase, cholinesterase, and paraoxonase were measured in plasma from plastic greenhouse workers exposed over the long term to different pesticides, including organophosphates and carbamates, in order to evaluate the potential chronic toxicity of pesticides at occupational level. Our results show that activities of paraoxonase and cholinesterase were decreased in applicators of pesticides compared to non-applicators. Likewise, it was found that activities ofβ-glucuronidase and acid phosphatase were associated with pesticide exposure in humans, and that both biochemical parameters were related to each other. Interestingly, the paraoxonase B allele (phenotyped in plasma) was associated with a higher risk of inhibition of cholinesterase activity above a 25% level, which supports the hypothesis that paraoxonase phenotypes are associated with susceptibility of humans to anticholinesterase pesticides toxicity.

Statistical analysis of honeybee survival after chronic exposure to insecticides.

Studies concerning long-term survival of honeybees raise the problem of the statistical analysis of mortality data. In the present study, we used a modeling approach of survival data of caged bees under chronic exposure to two pesticides (imidacloprid and deltamethrin). Our model, based on a Cox proportional hazard model, is not restricted to a specific hazard functional form, such as in parametric approaches, but takes into account multiple covariates. We consider not only the pesticide treatment but also a nuisance variable (variability between replicates). Moreover, considering the occurrence of social interactions, the model integrates the fact that bees do not die independently of each other. We demonstrate the chronic toxicity induced by imidacloprid and deltamethrin. Our results also underline the role of the replicate effect, the density-dependent effect, and their interactions with the treatment effect. None of these parameters can be neglected in the assessment of chronic toxicity of pesticides to the honeybee.

Association between human paraoxonase gene polymorphism and chronic symptoms in pesticide-exposed workers.

Pesticides, such as parathion, are metabolized by cytochrome p-450 system to paraoxon, which is a potent cholinesterase inhibitor. Paraoxonase (PON) catalyzes the hydrolysis of these toxic metabolites and protects against pesticide toxicity. A glutamine/arginine (Gln/Arg) polymorphism at amino acid position 192 of PON has been described. The Arg/Arg genotype is associated with higher serum paraoxonase activity compared to Gln/Gln. The Arg/Gln genotype is associated with intermediate serum PON activity. The potential association between PON genotype and symptoms of chronic pesticide toxicity was examined among 100 farm workers. As part of a cross-sectional study of pesticide toxicity among mixed-race farm workers in the Western Cape. South Africa, 100 farm workers were genotyped for polymorphism of the paraoxonase gene at amino acid position 192. Subjects with two or more of the following symptoms were considered to have evidence of chronic toxicity: abdominal pain, nausea, rhinorrhea, dizziness, headache, somnolence, fatigue, gait disturbance, limb numbness, paresthesias, limb pain, or limb weakness. In multivariable logistic regression analysis, the independent predictors of chronic toxicity were previous history of head trauma resulting in loss of consciousness (OR 2.8, 95% CI = 1.7-6.7), having worked as a pesticide applicator (OR 5.4, 95% CI = 3.2-8.9), and having one of the two "slow metabolism" (Gln/Gln or Gln/Arg) genotypes (OR 2.9, 95% CI = 1.7-6.9). Furthermore, the prevalence of chronic toxicity increased in a stepwise fashion from 15% among pesticide nonapplicators with a "fast metabolism" (Arg/Arg) genotype, to 42.9% among pesticide nonapplicators with "slow metabolism" (Gln/Gln or Gln/Arg) genotypes, to 58.8% among pesticide applicators with "fast metabolism" genotype, and 75.0% among pesticide applicators with "slow metabolism" genotypes (P = 0.001). Age, number of years on the job, smoking history, alcohol history, education level, plasma or red blood cell cholinesterase level, or previous history of acute organophosphate poisoning were not statistically significant predictors of chronic toxicity. The PON genotype is an important determinant of a farmworker's susceptibility to chronic pesticide poisoning.

An Evaluation of a Six Day Cyprinid EmbryoLarval Test for Estimating Maximum Allowable Toxicant Concentration of Pesticide Under Tropical Conditions

This study was designed to evaluate a six day embryo-larval test to arrive at a sensitive chronic effect threshold, (maximum allowable toxicant concentration or MATC) for pesticides. The embryo larval period of the Indian major carp Labeo rohita (Ham.) were exposed to sublethal levels of monocrotophos (an insecticide) during a 136 h exposure period. Among the end points observed, ‘hatching’ is found to be much less sensitive than ‘survival.’ Among the embryo life history phases exposed, the ‘free embryonic’ phase (22 to 96 h) is found to be as sensitive as the early apterolarval phase (96 to 136 h). A 96 h cyprinid embryo-free embryo toxicity test with “survival” as the end point is found to be a cost effective and rapid method for monitoring the chronic toxicity of pesticides to fishes under tropical conditions.

Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells: binding capability to the Ah receptor

Insecticides deserve particular attention since the general population is potentially exposed to such chemicals through many routes. We therefore tested the comparative acute and chronic toxicity of chemicals belonging to the major insecticides families (DDT, malathion and tetrachlorvinphos, carbaryl, cypermethrin, diflubenzuron), in hepatocytes, HepG2 and HaCaT cell lines. Two kinds of end-points were used: cytotoxicity parameters and CYP1A1 induction. Except for cypermethrin and diflubenzuron, all these chemicals exerted a cytotoxic effect in hepatocytes and HaCaT, but not in HepG2 cells. However, the induction of the EROD activity appeared more sensitive since a response was detected at lower concentrations. Significant differences were observed between the cell types and the insecticides. Furthermore, these chemicals were unable to displace [ 3H]TCDD from its binding sites, suggesting that they would not be a ligand of the Ah receptor. The experimental approach used herein may be a good means for predicting the acute and chronic toxicity of pesticides.