ABSTRACT
In this study, the rGO-PEI-AgNPs sensor was designed as a new effective platform to sensitive monitoring of deltamethrin in human plasma samples. For this purpose, reduced graphene oxide (rGO)-supported polyethylenimine (PEI) was used as a suitable substrate for dispersion of silver nanoparticles (AgNPs) as amplification and catalytic element. Therefore, a novel interface (rGO-PEI-AgNPs) was prepared by the fully electrochemical method on the surface of glassy carbon electrodes. The engineered nano-sensor showed a wide dynamic range of 10 nM to 1 mM and low limit of quantification (LLOQ) as 10 nM in human plasma sample, which revealed excellent analytical performance for the recognition of deltamethrin with high sensitivity and reproducibility through differential pulse voltammetry and square wave voltammetry techniques. The results confirm that rGO-PEI-AgNPs as a novel biocompatible interface can provide appropriate, reliable, affordable, rapid, and user-friendly diagnostic tools in the detection of deltamethrin in human real samples.
Subject(s)
Electrochemical Techniques/methods , Metal Nanoparticles/chemistry , Nitriles/analysis , Pesticides/analysis , Pyrethrins/analysis , Body Fluids/chemistry , Electrochemical Techniques/instrumentation , Electrodes , Equipment Design , Graphite/chemistry , Humans , Kinetics , Limit of Detection , Microscopy, Electron, Scanning , Nitriles/blood , Pesticides/blood , Polyethyleneimine/chemistry , Pyrethrins/blood , Sensitivity and Specificity , Silver/chemistryABSTRACT
The synthesized sheet-like polypyrrole (ppy) nanowires were used as solid phase extraction materials, followed by gas chromatography-mass spectrometry (GC-MS) for the detection of traces residues of pyrethroid pesticides in human plasma. A multiresidue method was developed and verified for the determination of trace pyrethroid residues (transfluthrin, allethrin, resmethrin, fenpropathrin, etofenprox, fenvalerate) in human plasma. In this study, using the cationic surfactant cetyltrimethylammonium bromide (CTAB) as a soft template, ppy nanowires with regular morphology were prepared by oxidative polymerization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and other techniques were employed for characterization. Molecular dynamics analyses were used to simulate the adsorption mechanism of each pyrethroid and ppy nanowires. Based on density analysis, molecular recognition analysis, and binding energy, the van der Waals force was considered as an important driving force for the adsorption of pyrethroids and ppy nanowires. The limits of detection (LOD) of six pyrethroids were 0.008-0051 ng mL-1, and the limits of quantification (LOQ) were 0.028-0.162 ng mL-1. The relative standard deviations of ppy nanowires were 2.12-5.09%, and the recoveries of six pyrethroids ranged from 76.9 to 110.4%. The enrichment factors were within the range of 47.09-51.30. The experimental results showed that the method could be an efficient detection method for trace residue analysis of pyrethroid pesticides in complex biological samples. It would be advantageous for clinical monitoring and toxicological studies of pyrethroids.
Subject(s)
Molecular Dynamics Simulation , Nanowires/chemistry , Pesticides/blood , Polymers/chemistry , Pyrethrins/blood , Pyrroles/chemistry , Solid Phase Microextraction/methods , Adsorption , Gas Chromatography-Mass Spectrometry , Humans , Hydrogen Bonding , Ions , Reproducibility of Results , Spectroscopy, Fourier Transform Infrared , Thermodynamics , Thermogravimetry , Time Factors , X-Ray DiffractionABSTRACT
The objective of this study was to obtain data on pathways of absorption of the synthetic pyrethroids deltamethrin (DLM) and cis-permethrin (CPM) following oral administration to rats. Adult male Sprague-Dawley rats with cannulated mesenteric lymph ducts and hepatic portal veins were given single doses of either 5 mg/kg DLM or 60 mg/kg CPM via the duodenum and lymph and portal blood samples collected for up to 300 min. The pyrethroid dosing vehicles (5 mL/kg body weight) were either corn oil or glycerol formal. Levels of DLM and CPM in lymph and portal blood samples were determined by high-performance liquid chromatography-mass spectrometry-mass spectrometry. Over the time period studied, levels of both DLM and CPM following administration in either corn oil or glycerol formal were greater in lymph than in portal blood. Lymphatic uptake of both DLM and CPM was enhanced following dosing in glycerol formal than in corn oil. The results of this study suggest that after oral administration to rats, these two pyrethroids are predominantly absorbed via the lymphatic system rather than via portal blood. The data obtained in this study thus support a recently developed physiologically-based pharmacokinetic (PBPK) model to evaluate age-related differences in pyrethroid pharmacokinetics in the rat, where it was assumed that absorption of pyrethroids was predominantly via lymphatic uptake.
Subject(s)
Insecticides/pharmacokinetics , Lymph/metabolism , Nitriles/pharmacokinetics , Permethrin/pharmacokinetics , Portal Vein/metabolism , Pyrethrins/pharmacokinetics , Administration, Oral , Animals , Biological Transport , Insecticides/blood , Male , Nitriles/blood , Permethrin/blood , Pyrethrins/blood , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Pyrethroid pesticide use is increasing worldwide, although the full extent of associated health effects is unknown. An epigenome-wide association study (EWAS) with exploratory pathway analysis may help identify potential pyrethroid-related health effects. METHODS: We performed an exploratory EWAS of chronic ambient pyrethroid exposure using control participants' blood in the Parkinson's Environment and Genes Study in the Central Valley of California (N = 237). We estimated associations of living and working near agricultural pyrethroid pesticide applications in the past 5 years (binary) with site-specific differential methylation, and used a false discovery rate (FDR) cut off of 0.05 for significance. We controlled for age, sex, education, cell count, and an ancestral marker for Hispanic ethnicity. We normalized methylation values for Type I/II probe bias using Beta-Mixture Quantile (BMIQ) normalization, filtered out cross-reactive probes, and evaluated for remaining bias with Surrogate Variable Analysis (SVA). We also evaluated the effects of controlling for cell count and normalizing for Type I/II probe bias by comparing changes in effect estimates and p-values for the top hits across BMIQ and GenomeStudio normalization methods, and controlling for cell count. To facilitate broader interpretation, we annotated genes to the CpG sites and performed gene set overrepresentation analysis, using genes annotated to CpG sites that were associated with pyrethroids at a raw p < 0.05, and controlling for background representation of CpG sites on the chip. We did this for both a biological process context (Gene Ontology terms) using missMethyl, and a disease set context using WebGestalt. For these gene set overrepresentation analyses we also used an FDR cut off of 0.05 for significance of gene sets. RESULTS: After controlling for cell count and applying BMIQ normalization, 4 CpG sites were differentially methylated in relation to pyrethroid exposures. When using GenomeStudio's Illumina normalization, 415 CpG sites were differentially methylated, including all four identified with the BMIQ method. In the gene set overrepresentation analyses, we identified 6 GO terms using BMIQ normalization, and 76 using Illumina normalization, including the 6 identified by BMIQ. For disease sets, we identified signals for Alzheimer's disease, leukemia and several other cancers, diabetes, birth defects, and other diseases, for both normalization methods. We identified minimal changes in effect estimates after controlling for cell count, and controlling for cell count generally weakened p-values. BMIQ normalization, however, resulted in different beta coefficients and weakened p-values. CONCLUSIONS: Chronic ambient pyrethroid exposure is associated with differential methylation at CpG sites that annotate to a wide variety of disease states and biological mechanisms that align with prior research. However, this EWAS also implicates several novel diseases for future investigation, and highlights the relative importance of different background normalization methods in identifying associations.
Subject(s)
Pesticides/blood , Pyrethrins/blood , Aged , Aged, 80 and over , Biological Monitoring , California , CpG Islands , DNA Methylation , Epigenome , Female , Genome-Wide Association Study , Humans , Male , Middle AgedABSTRACT
Although ethanol withdrawal depression is one of the prominent reasons for ethanol consumption reinstatement and ethanol dependence, its neurochemical basis is not clearly understood. The present study investigated the role of the agmatinergic system in ethanol withdrawal-induced depression using the forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression-like behavior, as evidenced by increased immobility time in the FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 µg/rat, i.c.v. [intracerebroventricularly]), moxonidine (50 µg/rat, i.c.v.), 2-BFI (20 µg/rat, i.c.v.), L-arginine (80 µg/rat, i.c.v.), amino-guanidine (25 µg/rat, i.c.v.), and arcaine (50 µg/rat, i.c.v.) by their once-daily administration during the withdrawal phase (Days 21, 22, and 23). The antidepressant effect of agmatine in ethanol-withdrawn rats was potentiated by the imidazoline receptor I1 agonist moxonidine (25 µg/rat, i.c.v.) and the imidazoline receptor I2 agonist, 2-BFI (10 µg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by the imidazoline receptor I1 antagonist, efaroxan (10 µg/rat, i.c.v.) and the imidazoline receptor I2 antagonist, idazoxan (4 µg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol-withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of the endogenous agmatinergic system and the imidazoline receptors system in ethanol withdrawal-induced depression. The data project agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression.
Subject(s)
Agmatine/therapeutic use , Alcoholism/therapy , Depression/prevention & control , Substance Withdrawal Syndrome/drug therapy , Agmatine/analysis , Animals , Brain Chemistry , Depression/etiology , Imidazoline Receptors/drug effects , Imidazoline Receptors/physiology , Male , Pyrethrins/administration & dosage , Pyrethrins/blood , Rats , Rats, Sprague-Dawley , Substance Withdrawal Syndrome/complicationsABSTRACT
Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1-9 mg/kg) and bifenthrin (BIF; 0.5-12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1-6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6-7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans.
Subject(s)
Aging/metabolism , Cerebellum/drug effects , Cyclopropanes/toxicity , Hydrocarbons, Fluorinated/toxicity , Liver/drug effects , Pyrethrins/toxicity , Administration, Oral , Aging/blood , Animals , Body Temperature/drug effects , Cerebellum/metabolism , Cyclopropanes/administration & dosage , Cyclopropanes/blood , Dose-Response Relationship, Drug , Hydrocarbons, Fluorinated/administration & dosage , Hydrocarbons, Fluorinated/blood , Liver/metabolism , Male , Pyrethrins/administration & dosage , Pyrethrins/blood , Rats , Rats, Wistar , Tissue Distribution , ToxicokineticsABSTRACT
Lambda-cyhalothrin (LCT) is a broad-spectrum pesticide widely used in agriculture throughout the world. This pesticide is considered a potential contaminant of surface and underground water as well as food, posing a risk to ecosystems and humans. In this sense, we decided to evaluate the activity of enzymes belonging to the purinergic system, which is linked with regulation of extracellular nucleotides and nucleosides, such as adenosine triphosphate (ATP) and adenosine (Ado) molecules involved in the regulation of inflammatory response. However, there are no data concerning the effects of LCT exposure on the purinergic system, where extracellular nucleotides act as signaling molecules. The aim of this study was to evaluate nucleotide hydrolysis by E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase), Ecto-NPP (ecto-nucleotide pyrophosphatase/phosphodiesterase), ecto-5'-nucleotidase and ecto-adenosine deaminase (E-ADA) in platelets and liver of adult rats on days 7, 30, 45 and 60 after daily gavage with 6.2 and 31.1â¯mg/kg bw of LCT. Gene expression patterns of NTPDases1-3 and 5'-nucleotidase were also determined in those tissues. In parallel, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3- trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] were measured in plasma. Results showed that exposure rats to LCT caused a significant increase in the assessed enzymes activities. Gene expression pattern of ectonucleotidases further revealed a significant increase in E-NTPDase1, E-NTPDase2, and E-NTPDase3 mRNA levels after LCT administration at all times. A dose-dependent increase in LCT metabolite levels was also observed but there no significant variations in levels from weeks to week, suggesting steady-steady equilibrium. Correlation analyses revealed that LCT metabolites in the liver and plasma were positively correlated with the adenine nucleotides hydrolyzing enzyme, E-ADA and E-NPP activities in platelets and liver of rats exposed to lambda-cyhalothin. Our results show that LCT and its metabolites may affect purinergic enzymatic cascade and cause alterations in energy metabolism.
Subject(s)
Blood Platelets/drug effects , Gene Expression Regulation/drug effects , Liver/drug effects , Nitriles/pharmacology , Nucleotidases/genetics , Purine Nucleosides/metabolism , Pyrethrins/pharmacology , Adenosine Deaminase/genetics , Adenosine Deaminase/metabolism , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Animals , Blood Platelets/enzymology , Blood Platelets/metabolism , Chromatography, High Pressure Liquid , Hydrolysis , Liver/enzymology , Liver/metabolism , Male , Mass Spectrometry , Nitriles/blood , Nitriles/metabolism , Nucleotidases/metabolism , Pyrethrins/blood , Pyrethrins/metabolism , Pyrophosphatases/genetics , Pyrophosphatases/metabolism , Rats , Rats, WistarABSTRACT
Developmental neurotoxicity (DNT) studies via dietary method of administration have been conducted for zeta-cypermethrin, a pyrethroid insecticide. The objectives of the current study were to determine the toxicokinetics (TK) of zeta-cypermethrin in postnatal day (PND) 11, 21 and 90 rats after gavage doses and use the internal exposure data from the DNT and TK studies to calculate an offspring NOAEL in mg/kg/day during lactation. The DNT studies showed that zeta-cypermethrin is not a developmental neurotoxicant. The NOAEL for maternal and offspring was determined to be 125â¯ppm (9.0 and 21.4â¯mg/kg/day for dams during gestation and lactation, respectively), based on systemic toxicity of reductions in maternal body weight, body weight gains and food consumption and offspring body weight at 300â¯ppm (LOAEL). The TK data from the gavage study showed that dose normalized Cmax and AUC is approximately 3-fold and 2-fold higher in PND 11 and 21 than those in PND 90 rats. By using the mean maternal/offspring plasma concentrations (535/245â¯ng/mL) during lactation day LD/PND 5-21 from the range-finding DNT studies, a conservative 3.1X relative TK factor (exposure ratio from the gavage study) and equation 3.1â¯×â¯535/21.4â¯=â¯245/x, the offspring NOAEL of 125â¯ppm was calculated to be 3.2â¯mg/kg/day during lactation. The offspring NOAEL based on internal exposure data from DNT studies and TK data after gavage doses is considered conservative for risk assessment for all human populations including infants and children for zeta-cypermethrin.
Subject(s)
Insecticides/toxicity , Neurotoxicity Syndromes , Pyrethrins/toxicity , Animals , Female , Insecticides/blood , Insecticides/pharmacokinetics , Male , Maternal-Fetal Exchange , No-Observed-Adverse-Effect Level , Pregnancy , Pyrethrins/blood , Pyrethrins/pharmacokinetics , Rats, Sprague-DawleyABSTRACT
Pyrethroids, organic compounds similar to natural pyrethrums, constitute the majority of insecticides. Pyrethroids are widely used around the world owing to their excellent selective toxicity to certain insects. In addition, they are easily found in daily life, accounting for most household pesticides. Owing to the easy access to pyrethroid insecticides, pyrethroid-related accidents and suicides have occurred yearly. For the first time, nine pyrethroids commonly used in South Korea and their seven major metabolites were simultaneously analyzed and validated in human plasma using liquid chromatography triple quadrupole mass spectrometry. Plasmas spiked with these pyrethroids and their metabolites were prepared and deproteinized via the addition of acetonitrile. This deproteinized supernatant was filtered and directly injected to ascertain the liquid chromatography-tandem mass spectrometry. For a sensitive and reproducible analysis, all the pyrethroid and metabolite analysis conditions for the multiple reaction monitoring mode were optimized in advance and employed. The validation parameters of the method, including the specificity, linearity, limit of detection, limit of quantification, accuracy, precision, recovery, matrix effect, and stability were also evaluated. The R2 value of linearity was greater than 0.997 for all the analytes, the accuracy ranged from 81.8% to 112.3%, the precision from 0% to 10.1%, and the recovery from 90.9% to 112.4%, depending on the analyte. The stability was 97.0% to 107.0% in fresh plasma and 97.6% to 107.7% in corrupt plasma. The results were satisfactory for all the validation parameters. Furthermore, authentic pyrethroid-poisoned samples were analyzed using this validation method, to determine the suitability; deltamethrin and its metabolites, cis-DBCA and 3-PBA, were successfully analyzed.
Subject(s)
Forensic Toxicology/methods , Insecticides/blood , Pyrethrins/blood , Chromatography, Liquid , Drug Stability , Humans , Limit of Detection , Specimen Handling , Tandem Mass SpectrometryABSTRACT
Deltamethrin (DLM) is a commonly used pesticide that helps to control crop destruction, disease, and nuisance insects. In rodents DLM can produce choreoathetosis, salivation, and decreased acoustic startle responses (ASR). Herein, adult Sprague Dawley rats were assessed for ASR 2 h after DLM delivered in 5 ml/kg corn oil, however no decrease was observed. Therefore, a test-retest protocol was used to reduce variability, and the effects on ASR on postnatal day 15 (P15) and adult rats were assessed 2, 4, 6, and 8 h after DLM administration (0, 1, 2, or 4 mg/kg for P15 rats and 0, 2, 8, or 25 mg/kg for adults). In a separate set of rats identically treated, DLM levels were determined in blood and brain. DLM (8 or 25 mg/kg) in adult rats decreased ASR up to 4 h, whereas in P15 rats decreases were observed between 2 and 8 h. The adult 25 mg/kg group showed consistent signs of salivation and tremor, whereas in P15 rats salivation was observed in the 2 and 4 mg/kg groups and tremor was observed at all doses over the 8-h period. Mortality was observed in all P15 dose groups but not in adults. Dose-dependent increases of DLM in blood and brain regardless of age were observed. At approximately equivalent whole brain concentrations, effects were more pronounced in P15 rats than in adult rats. Comparable brain levels of DLM do not explain differences in ASR and tremor between the P15 and adult rats. These data indicate age-dependent differences in sensitivity to DLM.
Subject(s)
Insecticides/toxicity , Nitriles/pharmacology , Nitriles/toxicity , Pyrethrins/pharmacology , Pyrethrins/toxicity , Reflex, Startle/drug effects , Acoustic Stimulation , Animals , Brain/drug effects , Brain/metabolism , Female , Insecticides/blood , Insecticides/pharmacokinetics , Male , Nitriles/blood , Pyrethrins/blood , Random Allocation , Rats , Rats, Sprague-Dawley , Salivation/drug effects , Tremor/chemically induced , Tremor/metabolismABSTRACT
A controlled kinetic study was conducted in volunteers dermally exposed to the widely used lambda-cyhalothrin pyrethroid pesticide to document the time courses of relevant biomarkers of exposure, in order to better assess biomonitoring data in workers. Matador® EC120 formulation (120 g/l) was applied on 40 cm2 of the forearm at a 0.25 mg/kg dose of lambda-cyhalothrin and left without occlusion or washing for 6 h. The application site was then washed thoroughly with soap and water. The kinetic time courses of cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were determined in plasma and urine up to 84 h post-application. Results show that the fraction of lambda-cyhalothrin absorbed in the body was rapidly cleared following dermal contact. According to CFMP and 3-PBA plasma profiles, calculated mean apparent absorption half-lives (t1/2) were 3 and 7.3 h, respectively, and corresponding mean apparent elimination t1/2 were 11.2 and 7.6 h. These differences suggest some metabolism at the site-of-entry and storage of metabolites by the dermal route. Toxicokinetic parameters calculated from urinary profiles confirm the values of absorption and elimination rates. Metabolites were almost completely excreted over the 84-h period post-application and, on average, 0.12 and 0.08% of the applied lambda-cyhalothrin dose was recovered in the urine as CFMP and 3-PBA, respectively, indicating a low dermal absorption fraction of this pyrethroid. This study showed the potential use of CFMP and 3-PBA biomarkers for the assessment of dermal exposure to lambda-cyhalothrin pyrethroid.
Subject(s)
Insecticides/pharmacokinetics , Nitriles/pharmacokinetics , Pyrethrins/pharmacokinetics , Administration, Cutaneous , Adult , Area Under Curve , Benzoates/blood , Benzoates/urine , Biotransformation , Environmental Monitoring , Female , Half-Life , Humans , Insecticides/blood , Insecticides/toxicity , Male , Nitriles/blood , Nitriles/toxicity , Pyrethrins/blood , Pyrethrins/toxicity , Skin Absorption , Young AdultABSTRACT
Toxicokinetics of cyfluthrin after single oral [20â¯mg/kg body weight (bw)] and intravenous (IV) (3â¯mg/kg bw) doses were studied in rats. Serial blood samples were obtained after oral and IV administration. Brain tissue samples were also collected after oral administration. Cyfluthrin concentrations in plasma and brain tissues (hypothalamus, striatum, hippocampus and frontal cortex) were quantified using liquid chromatography tandem mass spectrometry (LC/MS). Cyfluthrin disposition was best described by the use of a two-compartment open model. When given orally, plasma kinetics showed an extensive oral absorption of cyfluthrin and a slow elimination. The area under the concentration-time curve [AUC (0-24h)] and maximal plasma concentration (Cmax) were 6.11⯱â¯1.06â¯mgâ¯h/L and 0.385⯱â¯0.051⯵g/mL, respectively; ß phase elimination half-life (T1/2ß) was (17.15⯱â¯1.67â¯h). Oral bioavailability was found to be 71.60⯱â¯12.36%. After oral administration, cyfluthrin was widely distributed to brain tissues. AUC (0-24h) was significant higher in all tested brain tissues than in plasma. The largest discrepancy was found for hypothalamus. AUC (0-24h), Cmax and T1/2ß in hypothalamus were 19.36⯱â¯2.56â¯mgâ¯h/L, 1.21⯱â¯0.11⯵g/g and 22.73⯱â¯1.60â¯h, respectively. Assuming the identified toxicokinetics parameters, this study serves to better understand mammalian toxicity of pyrethroid cyfluthrin and to design further studies to characterize its neurotoxicity.
Subject(s)
Insecticides/pharmacokinetics , Nervous System/metabolism , Nitriles/pharmacokinetics , Pyrethrins/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Biological Availability , Infusions, Intravenous , Insecticides/blood , Insecticides/toxicity , Male , Nitriles/blood , Nitriles/toxicity , Pyrethrins/blood , Pyrethrins/toxicity , Rats, Wistar , Tissue Distribution , ToxicokineticsABSTRACT
To control agricultural pests and meet the increasing food demands, pesticides use has been increased substantially over time. Although pesticides are relatively specific to their targets, they can affect non-target organisms and are hazardous for the population around the application areas particularly to the individuals engaged in different types of agricultural activities. This situation is worse in developing and under-developed countries where personal protective equipment is merely used and regulatory guidelines are hardly practiced. In the present study, DNA damage in women exposed to pesticides while picking cotton with bare hands was assessed using single cell gel electrophoresis assay or comet assay. The presence of pesticides in blood serum of exposed individuals was also analyzed using high-performance liquid chromatography. Blood samples were collected from 138 (69 exposed and 69 control) randomly selected females from a major cotton growing area (Bahawalpur District) of the Punjab province of Pakistan. DNA damage, as determined by the mean comet tail length, was significantly higher (p < 0.001) in the exposed group compared to the unexposed. A positive correlation of DNA damage with age and exposure time was also observed. Residues of three pesticides, cyhalothrin, endosulfan, and deltamethrin found significantly higher (p < 0.001) in the serum samples of the exposed group compared to the unexposed. It was observed that the groups with higher mean comet tail length also had a higher concentration of pesticides in their serum samples indicating a positive association of DNA damage and pesticide exposure. The present study suggests that exposure to pesticides leads to DNA damage.
Subject(s)
Crops, Agricultural , DNA Damage , Farmers , Gossypium , Mutagens/adverse effects , Occupational Exposure/adverse effects , Pesticide Residues/adverse effects , Seeds , Adult , Aged , Case-Control Studies , Comet Assay , Endosulfan/adverse effects , Endosulfan/blood , Environmental Monitoring/methods , Female , Humans , Middle Aged , Nitriles/adverse effects , Nitriles/blood , Pakistan , Pesticide Residues/blood , Pyrethrins/adverse effects , Pyrethrins/blood , Risk Assessment , Sex Factors , Young AdultABSTRACT
There is increasing concern that infants and children may be at increased risk of neurological effects of pyrethroids, the most widely used class of insecticide. The objectives of this investigation were to (1) characterize the dose-dependent toxicokinetics (TK) of deltamethrin (DLM) for exposures ranging from environmentally relevant to acutely toxic; (2) determine the influence of an aqueous versus oil vehicle on oral absorption and bioavailability; and (3) determine whether DLM exhibits low-dose, age-equivalent internal dosimetry. Serial arterial plasma samples were obtained for 72 h from adult, male Sprague Dawley rats given 0.05-5.0 mg DLM/kg as an oral bolus in corn oil (CO). DLM exhibited linear, absorption rate-limited TK. Increases in maximum plasma concentration (Cmax) and AUC∘∞ were directly proportional to the dose. Oral bioavailability was quite limited. The vehicle and its volume had modest effect on the rate and extent of systemic absorption in adult rats. Postnatal day (PND) 15, 21, and 90 (adult) rats received 0.10, 0.25, or 0.50 mg DLM/kg orally in CO and were sacrificed periodically for plasma, brain, and liver collection. Age-dependent differences between PND 15 and 90 plasma Cmax and AUC∘24 values progressively diminished as the dose decreased, but there was a lack of low dose age equivalence in these brain and liver dosimeters. Other maturational factors may account for the lack of the low-dose age equivalence in brain and liver. This investigation provides support for the premise that the relatively low metabolic capacity of immature subjects may be adequate to effectively eliminate trace amounts of DLM and other pyrethroids from the plasma.
Subject(s)
Aging/blood , Drug Carriers/chemistry , Nitriles , Oral Mucosal Absorption , Pyrethrins , Administration, Oral , Animals , Biological Availability , Dose-Response Relationship, Drug , Male , Nitriles/administration & dosage , Nitriles/blood , Nitriles/toxicity , Pyrethrins/administration & dosage , Pyrethrins/blood , Pyrethrins/toxicity , Rats, Sprague-Dawley , Tissue Distribution , ToxicokineticsABSTRACT
A toxicokinetic model has been optimized to describe the time profiles of common biomarkers of exposure to permethrin and cypermethrin: trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans-DCCA) and 3-phenoxybenzoic acid (3-PBA). The model then served to reproduce urinary time courses in exposed agricultural workers and predict corresponding absorbed doses. It allowed for the prediction of the main routes of exposure in workers during the study period. Modeling showed that simulating exposure mostly by the oral route, during the 3-day biomonitoring period, provided best-fits to the urinary time courses of most workers. This is compatible with an inadvertent oral exposure during work. According to best-fit scenarios, absorbed doses in workers reconstructed with the model reached a maximum of 2.4 µg/kg bw/day and were below the absorbed dose limits associated with an exposure to the reference dose values established by the U.S. Environmental Protection Agency (0.06 and 0.25 mg/kg bw/day for cypermethrin and permethrin, respectively) and the Acceptable Operator Exposure Level set by the European Commission (0.06 mg/kg bw/day for cypermethrin). Modeling was further used to derive biological reference values for cypermethrin and permethrin exposure. Respective values of 7 and 29 nmol/kg bw/day of trans-DCCA, and 3 and 13 nmol/kg bw/day of 3-PBA were obtained. None of the workers presented values above these biological reference values.
Subject(s)
Insecticides/pharmacokinetics , Occupational Exposure/analysis , Permethrin/pharmacokinetics , Pyrethrins/pharmacokinetics , Administration, Oral , Benzoates/pharmacokinetics , Farmers , Humans , Insecticides/blood , Insecticides/urine , Permethrin/blood , Permethrin/urine , Pesticides , Pyrethrins/blood , Pyrethrins/urine , Quebec , Reference Values , Skin Absorption , ToxicokineticsABSTRACT
Bullfrog, as a kind of amphibians, can be easily exposed to varied pollutants in the environment for the reason of its habitats and highly permeable skin. We investigated the degradation kinetics and residues of α-cypermethrin in bullfrog by two different methods of administration for the environmental monitoring the behavior of one of the most used pesticides in the amphibians. The oral administration and water exposure of α-cypermethrin on bullfrog was studied in this work. α-Cypermethrin and its main metabolites of cis-3-(2',2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) and 3-phenoxybenzoic acid (3-PBA), which have been determined that having correlation with a number of epidemic diseases, were detected simultaneously. The method for residue analysis in the bullfrog's organs was validated. The average recoveries for α-cypermethrin were ranged from 71.7% to 100.3% and the limit of quantification was 0.005mg/kg. The average recoveries of its metabolites at levels between 0.002 and 0.5mg/kg ranged between 77.9% and 102.4% with a limit of quantification of 0.002mg/kg. Furthermore, the enantiomers of α-cypermethrin were separated on gas chromatograph (GC) equipped with a chiral column of BGB-172 and the metabolites were detected by gas chromatography (GC) after derivatization. After exposure of α-cypermethrin on bullfrog, the enantioselective degradation behavior was observed and its metabolites were detected in bullfrog tissues. The dynamic trends of α-cypermethrin and its metabolites were fitted to a two-compartment model except 3-PBA fitting to one-compartment model in skin. Concentration of α-cypermethrin and its metabolites in bullfrog's organs increased and reached an equilibrium state during water exposure of α-cypermethrin. Liver and kidney were the major organs for α-cypermethrin and its metabolites retention in both experiments.
Subject(s)
Environmental Monitoring/methods , Insecticides/metabolism , Pyrethrins/metabolism , Water Pollutants, Chemical/metabolism , Administration, Oral , Animals , Benzoates/analysis , Benzoates/blood , Benzoates/metabolism , Chromatography, Gas , Insecticides/analysis , Insecticides/blood , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Organ Specificity , Pyrethrins/analysis , Pyrethrins/blood , Rana catesbeiana , Stereoisomerism , Tissue Distribution , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/bloodABSTRACT
Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of ß-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis- and trans-permethrin in corn oil at seven dose levels. The pyrethroid with the highest percentage in the dosing solution was trans-permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1h. At 3.5h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis-permethrin were the predominate pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total pyrethroid concentration between blood and brain was linear (r=0.93). The pyrethroids with the lowest fraction in blood were trans-permethrin and ß-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed pyrethroid blood and brain concentration was described using a sigmoidal Emax model with the Effective Concentration50 being more sensitive for brain than blood. The data suggests summed pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of pyrethroids administered as a mixture under the conditions used in this study.
Subject(s)
Brain/metabolism , Insecticides , Motor Activity/drug effects , Pyrethrins , Animals , Drug Interactions , Insecticides/blood , Insecticides/pharmacokinetics , Insecticides/toxicity , Male , Pyrethrins/blood , Pyrethrins/pharmacokinetics , Pyrethrins/toxicity , Rats , Rats, Long-EvansABSTRACT
This study analyzed the associations of farmers' exposure to organophosphates (OPs), organosulfurs (OSs), organonitrogens (ONs) and pyrethroids (PYRs) with parameters of the blood complete counts (CBC), a blood chemistry panel (BCP) and the conventional nerve conduction studies among 224 farmers in China in 2012. Two health examinations and a series of follow-up field surveys were conducted. Multiple linear regression analyses were used to evaluate the associations. The results show considerable associations between multiple groups of pesticides and several CBC parameters, but it was not enough to provide evidence of hematological disorders. The short- and medium-term OPs exposures were mainly associated with liver damage and peripheral nerve impairment, respectively, while OSs exposure might induce liver damage and renal dysfunction. The neurotoxicity of ONs was second only to OPs in addition to its potential liver damage and the induced alterations in glucose. In comparison, the estimated results show that PYRs would be the least toxic in terms of the low-dose application. In conclusion, occupational exposures to pesticides with heterogeneous chemical structures are associated with farmer health in different patterns, and the association between a specific group of pesticides and farmer health also differs between the short- and medium-term exposures.
Subject(s)
Chemical and Drug Induced Liver Injury/blood , Neural Conduction/drug effects , Occupational Exposure/adverse effects , Pesticides/adverse effects , Adult , Blood Cell Count , China , Farmers , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Occupational Exposure/analysis , Organophosphates/adverse effects , Organophosphates/blood , Pesticides/blood , Pyrethrins/adverse effects , Pyrethrins/bloodABSTRACT
United States Environmental Protection Agency has recommended estimating pyrethroids' risk using cumulative exposure. For cumulative risk assessment, it would be useful to have a bioanalytical method for quantification of one or several pyrethroids simultaneously in a small sample volume to support toxicokinetic studies. Therefore, in the present study, a simple, sensitive and high-throughput ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous analysis of seven pyrethroids (fenvalerate, fenpropathrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, cypermethrin and deltamethrin) in 100 µL of rat plasma. A simple single-step protein precipitation method was used for the extraction of target compounds. The total chromatographic run time of the method was 5 min. The chromatographic system used a Supelco C18 column and isocratic elution with a mobile phase consisting of methanol and 5 mM ammonium formate in the ratio of 90 : 10 (v/v). Mass spectrometer (API 4000) was operated in multiple reaction monitoring positive-ion mode using the electrospray ionization technique. The calibration curves were linear in the range of 7.8-2,000 ng/mL with correlation coefficients of ≥ 0.99. All validation parameters such as precision, accuracy, recovery, matrix effect and stability met the acceptance criteria according to the regulatory guidelines. The method was successfully applied to the toxicokinetic study of cypermethrin in rats. To the best of our knowledge, this is the first LC-MS-MS method for the simultaneous analysis of pyrethroids in rat plasma. This validated method with minimal modification can also be utilized for forensic and clinical toxicological applications due to its simplicity, sensitivity and rapidity.
Subject(s)
Chromatography, High Pressure Liquid/methods , Pyrethrins/blood , Tandem Mass Spectrometry/methods , Ammonium Compounds/chemistry , Animals , Calibration , Chemical Precipitation , Drug Stability , Limit of Detection , Male , Pyrethrins/chemistry , Rats , Rats, WistarABSTRACT
Pesticide mixtures are common in the streams of agricultural or urban catchments. Individual and cartel toxicity of four different pesticides, namely Endosulfan, Carbofuran, Methyl parathion and Cypermethrin were studied. Sub acute exposure (1/10th of LC50) for 1, 7, 15, 30 and 60 days in Clarias batrachus active tissues such as brain, gills, blood and liver were evaluated. Growth, hepatosomatic index and survival performance were decreased, inhibition of brain acetylcholinesterase, gills Na(+)/K(+) ATPase activities, and abnormal behavior are noticed. The characteristics of the blood respiratory burst activity, erythrocyte count, contents of hematocrit and hemoglobin are dwindled. Plasma total proteins and liver glycogen decreased whereas blood glucose and serum creatinine, triglycerides are elevated. The immunological attributes such as white blood cell count was elevated, whereas albumin, globulins and lysozyme activity significantly decreased. Hepatic superoxide dismutase, catalase and glutathione S-transferase activities and lipid peroxidation levels are elevated, whereas glutathione peroxidase and glutathione are reduced. Toxicity effect of pesticides reached to a crest on 30th day and showed a descent thereafter except in endosulfan which mounted its detrimental effect throughout the experimental period. Toxicity trends of the present study are determined to be highest in Mix group followed by cypermethrin, methyl parathion and carbofuran. Indiscriminate application of these chemicals pose a toxic threat to non-target organisms, damage the ecosystems and jeopardizes human health.