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Environment International Jan 2020The present study reports one of the few cases in which organophosphate (OP) and pyrethroid (PYR) pesticide human exposure is evaluated in family contexts by the...
The present study reports one of the few cases in which organophosphate (OP) and pyrethroid (PYR) pesticide human exposure is evaluated in family contexts by the analysis of mother/child pair samples. Urinary concentrations of 6 organic metabolites of organophosphates and 2 pyrethroids were measured in mothers and their 7-to 8-year-old children (n = 168) in a general population from the central area of Slovenia. The results were adjusted for specific gravity and creatinine. The most abundant OP metabolite in children was 4-nitrophenol (PNP) (median 0.7 ng/ml) and in mothers (0.45 ng/ml), representing parathion exposure. 3-Phenoxibenzoic acid (3-PBA) (0.26 ng/ml), the general metabolite of pyrethroids, and 3,5,6-trichloro-2-pyridinol (TCPY) (0.16 ng/ml; chlorpyriphos) were the second most abundant compounds in children and mothers, respectively. The geometric mean specific gravity adjusted concentrations of OPs and PYRs were statistically significantly higher in children than in their mothers (between 3% and 24% higher), with the exception of TCPY (26% lower). All OP and PYR metabolites found in higher concentration in children showed significant positive correlations with the metabolite concentrations found in the mothers (p < 0.05 and 0.01), involving the fact that higher maternal concentrations were associated with higher children levels. These differential mother-children distributions and significant correlations were observed for the 2 types of pesticides studied, OPs and PYRs, which have different chemical properties. This agreement is consistent with the incorporation of the pesticides because of the general activities developed in the family context, instead of pesticide-dependent specific inputs. Comparison of the estimated daily intakes with the acceptable daily intakes of all detected metabolites revealed no significant risk of adverse health effects from exposure to these pesticides.
Topics: Attention; Child; Environmental Exposure; Female; Humans; Mothers; Organophosphates; Pesticides; Pyrethrins
PubMed: 31706197
DOI: 10.1016/j.envint.2019.105264 -
Annals of the New York Academy of... Aug 2016Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its... (Review)
Review
Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4-nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase. We have been investigating inhibitors of CYP-mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH-cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP-mediated biotransformation. Using menadione as the redox-cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion-induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the Food and Drug Administration for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion-induced neurotoxicity.
Topics: Animals; Cholinesterase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Delivery Systems; Humans; Insecticides; Organophosphate Poisoning; Parathion; Vitamin K 3
PubMed: 27441453
DOI: 10.1111/nyas.13156 -
Cancer Causes & Control : CCC Nov 2023Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined... (Meta-Analysis)
Meta-Analysis
PURPOSE
Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence.
METHODS
We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis.
RESULTS
Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07).
CONCLUSION
We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.
Topics: Young Adult; Adolescent; Humans; Male; Adult; Female; Pesticides; Hodgkin Disease; Prospective Studies; Occupational Exposure; Agriculture
PubMed: 37418114
DOI: 10.1007/s10552-023-01748-1 -
Journal of Toxicology 2020Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus... (Review)
Review
Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.
PubMed: 33029136
DOI: 10.1155/2020/3007984 -
Sensors (Basel, Switzerland) Dec 2022In this study, nanostructured gold was successfully prepared on a bare Au electrode using the electrochemical deposition method. Nanostructured gold provided more...
In this study, nanostructured gold was successfully prepared on a bare Au electrode using the electrochemical deposition method. Nanostructured gold provided more exposed active sites to facilitate the ion and electron transfer during the electrocatalytic reaction of organophosphorus pesticide (methyl parathion). The morphological and structural characterization of nanostructured gold was conducted using field-emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), which was further carried out to evaluate the electrocatalytic activity towards methyl parathion sensing. The electrochemical performance of nanostructured gold was investigated by electrochemical measurements (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)). The proposed nanostructured gold-modified electrode exhibited prominent electrochemical methyl parathion sensing performance (including two linear concentration ranges from 0.01 to 0.5 ppm (R = 0.993) and from 0.5 to 4 ppm (R = 0.996), limit of detection of 5.9 ppb, excellent selectivity and stability), and excellent capability in determination of pesticide residue in real fruit and vegetable samples (bok choy and strawberry). The study demonstrated that the presented approach to fabricate a nanostructured gold-modified electrode could be practically applied to detect pesticide residue in agricultural products via integrating the electrochemical and gas chromatography coupled with mass spectrometry (GC/MS-MS) analysis.
Topics: Methyl Parathion; Pesticides; Organophosphorus Compounds; Gold; Pesticide Residues; Nanocomposites; Electrodes; Electrochemical Techniques; Limit of Detection; Metal Nanoparticles
PubMed: 36560305
DOI: 10.3390/s22249938 -
Neurochemical Research Jan 2021Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of...
Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q (CoQ) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ supplementation (5 μM) was able to restore cellular CoQ status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.
Topics: Cell Line, Tumor; Cell Survival; Chlorpyrifos; Dichlorvos; Electron Transport Complex II; Electron Transport Complex III; Humans; Insecticides; Methyl Parathion; Mitochondria; Neurons; Ubiquinone
PubMed: 32306167
DOI: 10.1007/s11064-020-03033-y -
Journal of Medical Toxicology :... Dec 2018The gap between the number of patients on transplant waiting lists and patients receiving transplants is growing. Use of organs from donors who have died following... (Review)
Review
INTRODUCTION
The gap between the number of patients on transplant waiting lists and patients receiving transplants is growing. Use of organs from donors who have died following pesticide exposure remains controversial. This study reviews the literature related to transplantation from this group.
METHODS
A literature search was undertaken on PubMed using the following keywords: 'insecticide', 'pesticide', 'rodenticide', 'organophosphate', 'carbamate', 'paraquat', 'poisoning', 'toxicity', 'overdose', 'intoxication', 'ingestion', 'organ donation or procurement', 'transplant', 'allograft transplant', and 'expanded criteria organ donation'; 21 specific pesticides/insecticides were also added to the search; the indexes for EAPCCT/NACCT meeting abstracts 2008-2017 were also searched. Identified publications were reviewed and if described human donation/transplantation of ≥ 1 solid organ(s), the following was extracted: (i) compound(s) ingested; (ii) donor demographics; (iii) organ(s) transplanted; and (iv) graft function at follow-up.
RESULTS
Ten papers were identified describing 20 fatalities (1999-2017) related to the following pesticide exposures: organophosphate, 8 cases; aldicarb, 4; paraquat, 3; parathion, 1; malathion, 1; carbofuran/carbamate, 1; carbamate, 1; and brodifacoum, 1 and no further cases were identified from EAPCCT/NACCT abstracts. Donors were aged 12-50 (25.9 ± 11.9) years. Forty-four organs were transplanted: 28 kidneys, 7 livers, 6 corneas, and 3 hearts. Forty recipients had outcome reported: 3 (7.5%) patients died, 3 (7.5%) had graft failure/dysfunction and 34 (85.0%) had good graft function. Overall survival with good function was 96%, 71%, 83%, and 67% for kidneys, livers, corneas and hearts respectively.
CONCLUSION
Review of the published literature suggests that solid organ donation following exposure to a pesticide is associated with good short-to-medium-term graft organ function following transplantation, particularly for transplanted kidneys and corneas.
Topics: Humans; Organ Transplantation; Pesticides; Tissue Donors; Treatment Outcome
PubMed: 29987646
DOI: 10.1007/s13181-018-0673-5