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Saudi Journal of Biological Sciences Nov 2019Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3 h has induced significant increase in the lymphocytic DNA...
Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3 h has induced significant increase in the lymphocytic DNA damage. Compared to control, comet data from highest concentration of phorate (1000 µM) showed 8.03-fold increase in the Olive tail moment (OTM). Cytokinesis blocked micronucleus (CBMN) assay revealed 6.4-fold increase in binucleated micronucleated (BNMN) cells following the exposure with phorate (200 µM) for 24 h. The nuclear division index (NDI) in phorate (200 µM) treated cells reduced to 1.8 vis-à-vis control cells showed NDI of 1.94. Comparative to untreated control, 60.43% greater DCF fluorescence was quantitated in lymphocytes treated with phorate (500 µM), affirming reactive oxygen species (ROS) generation and oxidative stress. Flow cytometric data of phorate (200 µM) treated lymphocytes showed 81.77% decline in the fluorescence of rhodamine 123 (Rh123) dye, confirming the perturbation of mitochondrial membrane potential (Δ). Calf thymus DNA (ct-DNA) treated with phorate (1000 µM) exhibited 2.3-fold higher 8-Hydroxy-2'-deoxyguanosine (8-oxodG) DNA adduct formation, signified the oxidative DNA damage. The alkaline unwinding assay revealed 4.0 and 6.5 ct-DNA strand breaks when treated to phorate and phorate-Cu (II) complex. Overall, the data unequivocally suggests the cyto- and genotoxic potential of phorate in human lymphocytes, which may induce comparable toxicological consequences in persons occupationally or non-occupationally exposed to insecticide phorate.
PubMed: 31762602
DOI: 10.1016/j.sjbs.2019.04.008 -
Antibiotics (Basel, Switzerland) Nov 2022Phorate is a systemic, broad-spectrum organophosphorus insecticide. Although it is commonly used worldwide, phorate, like other pesticides, not only causes environmental...
Phorate is a systemic, broad-spectrum organophosphorus insecticide. Although it is commonly used worldwide, phorate, like other pesticides, not only causes environmental pollution but also poses serious threats to human and animal health. Herein, we measured the blood glucose concentrations of high-fat-diet-fed mice exposed to various concentrations of phorate (0, 0.005, 0.05, or 0.5 mg/kg); we also assessed the blood glucose concentrations of high-fat-diet-fed mice exposed to phorate; we also assessed the distribution characteristics of the resistance genes in the intestinal microbiota of these mice. We found that 0.005 and 0.5 mg/kg of phorate induced obvious hyperglycaemia in the high-fat-diet-fed mice. Exposure to phorate markedly reduced the abundance of in the mouse intestine. The resistance genes , and were significantly upregulated in the test group compared with the control group. Efflux pumping was the primary mechanism of drug resistance in the , and found in the mouse intestine. Our findings indicate that changes in the abundance of the intestinal microbiota are closely related to the presence of antibiotic-resistant bacteria in the intestinal tract and the metabolic health of the host.
PubMed: 36358236
DOI: 10.3390/antibiotics11111584 -
Toxics Apr 2022It has been estimated that approximately one in seven of all global suicides is due to pesticide self-poisoning, mostly in rural areas of developing countries....
It has been estimated that approximately one in seven of all global suicides is due to pesticide self-poisoning, mostly in rural areas of developing countries. Organophosphorus (OP) compounds are a group of pesticides exerting their toxicological effects through non-reversible inhibition of the enzyme acetylcholinesterase (AChE). Among these compounds, phorate (thimet) is one of the most dangerous compounds, the use of which is restricted in many countries. A case of intentional suicide after phorate ingestion in a 24-year-old Bengali male is described. This is the second case of suicidal ingestion of phorate reported in the forensic literature, and the first presenting complete toxicological findings.
PubMed: 35622619
DOI: 10.3390/toxics10050205 -
Neurotoxicology Sep 2018Organophosphorus (OP) compounds, including pesticides and chemical warfare nerve agents (CWNA), are threats to the general population as possible weapons of terrorism or...
Evaluating the broad-spectrum efficacy of the acetylcholinesterase oximes reactivators MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against phorate oxon, sarin, and VX in the Hartley guinea pig.
Organophosphorus (OP) compounds, including pesticides and chemical warfare nerve agents (CWNA), are threats to the general population as possible weapons of terrorism or by accidental exposure whether through inadvertent release from manufacturing facilities or during transport. To mitigate the toxicities posed by these threats, a therapeutic regimen that is quick-acting and efficacious against a broad spectrum of OPs is highly desired. The work described herein sought to assess the protective ratio (PR), median effective doses (ED), and therapeutic index (TI = oxime 24-h LD/oxime ED) of MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against the OPs sarin (GB), VX, and phorate-oxon (PHO). All OPs are representative of the broader classes of G and V chemical warfare nerve agents and persistent pesticides. MMB4 DMS and HLö-7 DMS were previously identified as comparative efficacy leads warranting further evaluations. 2-PAM Cl is the U.S. FDA-approved standard-of-care oxime therapy for OP intoxication. Briefly, PRs were determined in male guinea pigs by varying the subcutaneously (SC) delivered OP dose followed then by therapy with fixed levels of the oxime and atropine (0.4 mg/kg; administered intramuscularly [IM]). EDs were determined using a similar approach except the OP dose was held constant at twice the median lethal dose (2 × LD) while the oxime treatment levels were varied. The ED information was then used to calculate the TI for each OP/oxime combination. Both MMB4 DMS and HLö-7 DMS provided significant protection, i.e., higher PR against GB, VX, and PHO when compared to atropine controls, but significance was not readily demonstrated across the board when compared against 2-PAM Cl. The ED values of MMB4 DMS was consistently lower than that of the other oximes against all three OPs. Furthermore, based on those EDs, the TI trend of the various oximes against both GB and VX was MMB4 DMS > HLö-7 DMS > 2-PAM Cl, while against PHO, MMB4 DMS > 2-PAM Cl > HLö-7 DMS.
Topics: Animals; Chemical Warfare Agents; Cholinesterase Inhibitors; Cholinesterase Reactivators; Guinea Pigs; Insecticides; Male; Organophosphates; Organothiophosphorus Compounds; Oximes; Phorate; Pralidoxime Compounds; Pyridinium Compounds; Sarin
PubMed: 30056178
DOI: 10.1016/j.neuro.2018.07.014 -
International Journal of Hygiene and... Apr 2018Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and...
BACKGROUND
Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and auditory function are unknown. Here we examined associations between prenatal OP exposure and grating visual acuity (VA) and auditory brainstem response (ABR) during infancy.
METHODS
30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Grating visual acuity (VA) (n = 179-200) and auditory brainstem response (ABR) (n = 139-183) were assessed at 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and central conduction time, and head circumference (HC). Associations between sensory outcomes during infancy and cord OPs were examined using linear mixed models.
RESULTS
Prenatal chlorpyrifos exposure was associated with lower 9-month grating VA scores; scores were 0.64 (95% CI: -1.22, -0.06) points lower for exposed versus unexposed infants (p = 0.03). The OPs examined were not associated with infant ABR latencies, but chlorpyrifos and phorate were both significantly inversely associated with HC at 9 months; HCs were 0.41 (95% CI: 0.75, 0.6) cm and 0.44 (95% CI: 0.88, 0.1) cm smaller for chlorpyrifos (p = 0.02) and phorate (p = 0.04), respectively.
CONCLUSIONS
We found deficits in grating VA and HC in 9-month-old infants with prenatal exposure to chlorpyrifos. The clinical significance of these small but statistically significant deficits is unclear. However, the disruption of visual or auditory pathway maturation in infancy could potentially negatively affect downstream cognitive development.
Topics: Adult; Chlorpyrifos; Cohort Studies; Developmental Disabilities; Environmental Pollutants; Evoked Potentials, Auditory, Brain Stem; Female; Fetal Blood; Hearing; Hearing Disorders; Humans; Infant; Insecticides; Male; Maternal Exposure; Mothers; Organophosphorus Compounds; Phorate; Pregnancy; Prenatal Exposure Delayed Effects; Sensation; Vision Disorders; Vision, Ocular; Visual Acuity
PubMed: 29402694
DOI: 10.1016/j.ijheh.2018.01.010 -
Movement Disorders : Official Journal... May 2022Dream-enacting behavior is a characteristic feature of rapid eye movement sleep behavior disorder, the most specific prodromal marker of synucleinopathies. Pesticide...
BACKGROUND
Dream-enacting behavior is a characteristic feature of rapid eye movement sleep behavior disorder, the most specific prodromal marker of synucleinopathies. Pesticide exposure may be associated with dream-enacting behaviors, but epidemiological evidence is limited.
OBJECTIVES
To examine high pesticide exposure events in relation to dream-enacting behaviors among farmers in the Agricultural Health Study.
METHODS
We conducted multivariable logistic regression analyses to examine high pesticide exposure events reported from 1993 to 1997 in relation to dream-enacting behaviors assessed from 2013 to 2015 among 11,248 farmers (age 47 ± 11 years).
RESULTS
A history of dream-enacting behaviors was reported by 939 (8.3%) farmers. Compared with farmers who did not report any high pesticide exposure event, those who reported were more likely to endorse dream-enacting behaviors 2 decades later (odds ratio = 1.75; 95% confidence interval [CI], 1.49-2.05). The association appeared stronger when there was a long delay in washing with soap and water after the event (2.63 [95% CI, 1.62-4.27] for waiting >6 hours vs. 1.71 [95% CI, 1.36-2.15] for washing within 30 minutes) and when the exposure involved the respiratory or digestive tract (2.04 [95% CI, 1.62-2.57] vs. 1.58 [95% CI, 1.29-1.93] for dermal contact only). In the analyses of specific pesticides involved, we found positive associations with two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), four organophosphate insecticides (phorate, ethoprop, terbufos, and parathion), two herbicides (alachlor and paraquat), and fungicides as a group.
CONCLUSIONS
This study provides the first epidemiological evidence that high pesticide exposures may be associated with a higher risk of dream-enacting behaviors. © 2022 International Parkinson and Movement Disorder Society.
Topics: Adult; Agriculture; Farmers; Humans; Insecticides; Middle Aged; Occupational Exposure; Pesticides
PubMed: 35152487
DOI: 10.1002/mds.28960 -
Environmental Health Perspectives Aug 2006We recently reported a link between use of the organophosphate pesticide phorate and risk of prostate cancer among applicators with a family history of prostate cancer...
BACKGROUND
We recently reported a link between use of the organophosphate pesticide phorate and risk of prostate cancer among applicators with a family history of prostate cancer in the Agricultural Health Study (AHS).
OBJECTIVE
This finding, together with findings of associations between other organophosphate pesticides and cancer more broadly, prompted us to examine phorate exposure and overall cancer incidence in the AHS. Adding 3 years of follow-up and using more detailed exposure information allowed us to see whether the prostate cancer finding held.
METHODS
The AHS is a prospective study of licensed restricted-use pesticide applicators from North Carolina and Iowa. To our knowledge, this is the largest examination of workers occupationally exposed to phorate. Pesticide exposure and other information was collected using two self-administered questionnaires completed from 1993 to 1997. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CI), adjusting for potential confounders.
RESULTS
Phorate use was not related to the incidence of all cancers combined or to any individual cancer, although we had insufficient numbers to study non-Hodgkin lymphoma or leukemia, which have been linked to organophosphates in other studies. Although prostate cancer risk was not significantly related to phorate use overall or among those without a family history, the risk tended to increase among applicators with a family history of prostate cancer. The interaction RR was 1.53 (95% CI, 0.99-2.37).
CONCLUSION
The observed statistical interaction suggests a gene-environment interaction between family history and phorate exposure in the incidence of prostate cancer, but other explanations are also possible.
Topics: Adult; Aged; Agricultural Workers' Diseases; Alcohol Drinking; Cohort Studies; Follow-Up Studies; Humans; Insecticides; Iowa; Male; Middle Aged; North Carolina; Occupational Exposure; Phorate; Prostatic Neoplasms; Socioeconomic Factors; Surveys and Questionnaires; Zea mays
PubMed: 16882526
DOI: 10.1289/ehp.8911 -
Sensors (Basel, Switzerland) Jul 2022In this work, we reported a rapid and sensitive fluorescence assay in homogenous solution for detecting organophosphorus pesticides by using tetramethylrhodamine...
In this work, we reported a rapid and sensitive fluorescence assay in homogenous solution for detecting organophosphorus pesticides by using tetramethylrhodamine (TAMRA)-labeled aptamer and its complementary DNA (cDNA) with extended guanine (G) bases. The hybridization of cDNA and aptamer drew TAMRA close to repeated G bases, then the fluorescence of TAMRA was quenched by G bases due to the photoinduced electron transfer (PET). Upon introducing the pesticide target, the aptamer bound to pesticide instead of cDNA because of the competition between pesticide and cDNA. Thus, the TAMRA departed from G bases, resulting in fluorescence recovery of TAMRA. Under optimal conditions, the limits of detection for phorate, profenofos, isocarbophos, and omethoate were 0.333, 0.167, 0.267, and 0.333 µg/L, respectively. The method was also used in the analysis of profenofos in vegetables. Our fluorescence design was simple, rapid, and highly sensitive, which provided a means for monitoring the safety of agricultural products.
Topics: Aptamers, Nucleotide; DNA, Complementary; Fluorescence; Organophosphorus Compounds; Pesticides
PubMed: 35957269
DOI: 10.3390/s22155712 -
Environment International Sep 2018Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
BACKGROUND
Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
OBJECTIVE
We assessed associations between pesticide use and other farm exposures and incident hypothyroidism and hyperthyroidism in female spouses of farmers in the Agricultural Health Study (AHS).
METHODS
We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals for risk of thyroid disease in 24,092 spouses who completed at least one follow-up questionnaire.
RESULTS
We identified 1627 hypothyroid and 531 hyperthyroid cases over 20 years of follow-up. The fungicides benomyl, maneb/mancozeb, and metalaxyl, the herbicide pendimethalin, and among those over 60 years of age the insecticides parathion and permethrin (applied to crops) were associated with elevated hypothyroidism risk, with HR ranging from 1.56-2.44. Conversely, the insecticide phorate, and the herbicides imazethapyr and metolachlor were associated with decreased risk (HR ranging 0.63-0.73), as were long-term farm residence and other farm-related activities (HR ranging 0.69-0.84). For hyperthyroidism, the insecticide diazinon, the fungicides maneb/mancozeb, and the herbicide metolachlor were associated with increased risk (HR ranging 1.35-2.01) and the herbicide trifluralin with decreased risk (HR: 0.57).
CONCLUSIONS
Several individual pesticides were associated with increased risk of hypothyroidism and hyperthyroidism, although some pesticides were associated with decreased risk. Some of the findings, specifically associations with fungicides, are consistent with results from an earlier analysis of prevalent diseases in AHS spouses.
Topics: Female; Follow-Up Studies; Humans; Male; Occupational Exposure; Pesticides; Spouses; Surveys and Questionnaires; Thyroid Diseases
PubMed: 29908479
DOI: 10.1016/j.envint.2018.05.041 -
Toxics Apr 2022Transmission Electron Microscopic (TEM) assessments were performed on the renal cells of common carp to observe the deleterious effects of two organophosphate...
Transmission Electron Microscopic (TEM) assessments were performed on the renal cells of common carp to observe the deleterious effects of two organophosphate insecticides, Phorate and Dimethoate. Pesticides such as Phorate and Dimethoate often pollute aquatic systems where they may negatively impact fish, but so far, the ultrastructural toxicity of these pesticides remains poorly understood. Here, we use Transmission Electron Microscopy (TEM) to determine how acute exposure to sublethal concentrations of these two pesticides may affect the renal cells of common carp . For each insecticide, the fish were divided in four experimental conditions: a control and three different exposure concentrations of the pesticide. The Phorate treated fish were exposed to three sublethal concentrations of 0.2 mg/L, 0.4 mg/L, 0.6 mg/L for a duration of 24, 48 & 72 h. The dimethoate treated fish were exposed to three sublethal concentrations of 0.005 mL/L, 0.01 mL/L, 0.015 mL/L for a duration of 24, 48 and 72 h. The two-dimensional transmission electron microscopy revealed ultrastructural abnormalities in the treated fish renal cells when exposed to two toxicants including deformation in the glomerulus, vacuolization of cytoplasm, degenerative nucleus and damaged mitochondria. Furthermore, the ultrastructural abnormalities were more prominent with the increase in the concentrations of both the insecticides and also with their exposure period. Overall, these results provide important baseline data on the ultrastructural toxicity of Phorate and Dimethoate and will allow important follow-up studies to further elucidate the underlying cellular mechanisms of pesticide toxicity in wildlife.
PubMed: 35448438
DOI: 10.3390/toxics10040177