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Archives of Toxicology May 2023The current approach for the risk assessment of chemicals does not account for the complex human real-life exposure scenarios. Exposure to chemical mixtures in everyday...
The current approach for the risk assessment of chemicals does not account for the complex human real-life exposure scenarios. Exposure to chemical mixtures in everyday life has raised scientific, regulatory, and societal concerns in recent years. Several studies aiming to identify the safety limits of chemical mixtures determined hazardous levels lower than those of separate chemicals. Following these observations, this study built on the standards set by the real-life risk simulation (RLRS) scenario and investigated the effect of long-term exposure (18 months) to a mixture of 13 chemicals (methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, butylparaben, bisphenol A and acacia gum) in adult rats. Animals were divided into four dosing groups [0xNOAEL (control), 0.0025xNOAEL (low dose-LD), 0.01xNOAEL (medium dose-MD) and 0.05xNOAEL (high dose-HD) (mg/kg BW/day)]. After 18 months of exposure, all animals were sacrificed, and their organs were harvested, weighed, and pathologically examined. While organ weight tended to be higher in males than in females, when sex and dose were taken into account, lungs and hearts from female rats had significantly greater weight than that of males. This discrepancy was more obvious in the LD group. Histopathology showed that long-term exposure to the chemical mixture selected for this study caused dose-dependent changes in all examined organs. The main organs that contribute to chemical biotransformation and clearance (liver, kidneys, and lungs) consistently presented histopathological changes following exposure to the chemical mixture. In conclusion, exposure to very low doses (below the NOAEL) of the tested mixture for 18 months induced histopathological lesions and cytotoxic effects in a dose and tissue-dependent manner.
Topics: Male; Humans; Rats; Female; Animals; No-Observed-Adverse-Effect Level; Rats, Sprague-Dawley; Pesticides; Food Additives; Organ Size
PubMed: 36892595
DOI: 10.1007/s00204-023-03455-x -
Veterinary World Jan 2023Diphenhydramine is an H1-antihistamine that counteracts the toxic effects of organophosphate and carbamate insecticides that inhibit cholinesterase (ChE) activity. This...
BACKGROUND AND AIM
Diphenhydramine is an H1-antihistamine that counteracts the toxic effects of organophosphate and carbamate insecticides that inhibit cholinesterase (ChE) activity. This meta-analysis aimed to investigate the effects of diphenhydramine on ChE inhibition induced by these insecticides in the plasma, erythrocytes, or whole brain of experimental animals.
MATERIALS AND METHODS
A data search was performed on erythrocyte, plasma, and brain ChE inhibition caused by organophosphate and carbamate insecticides in experimental animals (mice, rats, and chicks) treated with the antihistamine diphenhydramine in accordance with preferred reporting items for systematic reviews and meta-analysis, which was done by the two-group random-effects model meta-analysis. The meta-analysis included 18 records extracted from six studies that, appeared from 1996 to 2022.
RESULTS
Using the random-effects model, a two-group meta-analysis revealed that the combined effect size (ChE inhibition) was significantly more favorable in the control group than in the diphenhydramine intervention, as shown by a forest plot. The combined effect size (standardized mean difference) was 0.67, with a standard error of 0.3, a lower limit of 0.04, and an upper limit of 1.29 (p = 0.025). The heterogeneity was moderate, as I of the combined effect size was 74%, with a significant Cochrane Q-test result (Q = 65, p < 0.0001). Subgroup analysis indicated that, with brain ChE inhibition, the heterogeneity (I) became 5%, which was lower than ChE inhibition in plasma (84%) and erythrocytes (78%). No publication bias was identified using the funnel plot and Egger's test.
CONCLUSION
This meta-analysis suggests that, in addition to its documented antidotal action against ChE-inhibiting insecticides, diphenhydramine can also reduce the extent of ChE inhibition, especially in the brain, which is the main site of toxicity of these insecticides. There is a need for additional studies to assess such enzyme inhibition in different parts of the brain.
PubMed: 36855355
DOI: 10.14202/vetworld.2023.118-125 -
Scientific Reports Feb 2023Even though honey bees in the field are routinely exposed to a complex mixture of many different agrochemicals, few studies have surveyed toxic effects of pesticide...
Even though honey bees in the field are routinely exposed to a complex mixture of many different agrochemicals, few studies have surveyed toxic effects of pesticide mixtures on bees. To elucidate the interactive actions of pesticides on crop pollinators, we determined the individual and joint toxicities of thiamethoxam (THI) and other seven pesticides [dimethoate (DIM), methomyl (MET), zeta-cypermethrin (ZCY), cyfluthrin (CYF), permethrin (PER), esfenvalerate (ESF) and tetraconazole (TET)] to honey bees (Aplis mellifera) with feeding toxicity test. Results from the 7-days toxicity test implied that THI elicited the highest toxicity with a LC data of 0.25 (0.20-0.29) μg mL, followed by MET and DIM with LC data of 4.19 (3.58-4.88) and 5.30 (4.65-6.03) μg mL, respectively. By comparison, pyrethroids and TET possessed relatively low toxicities with their LC data from the range of 33.78 (29.12-38.39) to 1125 (922.4-1,442) μg mL. Among 98 evaluated THI-containing binary to octonary mixtures, 29.59% of combinations exhibited synergistic effects. In contrast, 18.37% of combinations exhibited antagonistic effects on A. mellifera. Moreover, 54.8% pesticide combinations incorporating THI and TET displayed synergistic toxicities to the insects. Our findings emphasized that the coexistence of several pesticides might induce enhanced toxicity to honey bees. Overall, our results afforded worthful toxicological information on the combined actions of neonicotinoids and current-use pesticides on honey bees, which could accelerate farther comprehend on the possible detriments of other pesticide mixtures in agro-environment.
Topics: Bees; Animals; Pesticides; Thiamethoxam; Insecticides; Neonicotinoids; Toxicity Tests; Dimethoate; Methomyl
PubMed: 36792894
DOI: 10.1038/s41598-023-29837-w -
International Journal of Food Science 2023To assess the contamination of processed chilli pepper and tomatoes, a report over the past four decades since the establishment of the Rapid Alert System for Food and...
To assess the contamination of processed chilli pepper and tomatoes, a report over the past four decades since the establishment of the Rapid Alert System for Food and Feed (RASFF) was retrieved and analysed. Out of the 887 notification reports assessed for eligibility, 446 were found regarding chilli pepper and tomato contamination. This study identified India as the country of origin with the highest number of reported cases relating to chilli pepper contamination. Italy and Türkiye were the countries with the highest number of reported cases regarding the exportation of adulterated tomatoes to other countries according to the RASFF report. Unauthorized dyes such as Sudan I, III, IV, orange II, rhodamine B, and para red were reported to have been detected in either chilli pepper or tomato in the supply chain. Almost all unauthorized dyes in this study were found to be more than the range (0.5 to 1 mg/kg) of the detection limit of Sudan dye and other related dyes using analytical methods set by the European Union. Unapproved pesticides by the European Union (EU) found in this study were acetamiprid, chlorothalonil, chlorpyrifos, dimethoate, methomyl, monocrotophos, omethoate, oxamyl, and thiophanate methyl. The present study indicates the persistence of chilli pepper and tomato contamination with harmful dyes and pesticide residues despite the ban on the use of certain chemicals in the food chain.
PubMed: 36684413
DOI: 10.1155/2023/5337150 -
Chemosphere Mar 2023Due to their extensive use and high biological activity, insecticides largely contribute to loss of biodiversity and environmental pollution. The regulation of...
Due to their extensive use and high biological activity, insecticides largely contribute to loss of biodiversity and environmental pollution. The regulation of insecticides by authorities is mainly focused on lethal concentrations. However, sub-lethal effects such as alterations in behavior and neurodevelopment can significantly affect the fitness of individual fish and their population dynamics and therefore deserve consideration. Moreover, it is important to understand the impact of exposure timing during development, about which there is currently a lack of relevant knowledge. Here, we investigated whether there are periods during neurodevelopment of fish, which are particularly vulnerable to insecticide exposure. Therefore, we exposed zebrafish embryos to six different insecticides with cholinergic mode of action for 24 h during different periods of neurodevelopment and measured locomotor output using an age-matched behavior assay. We used the organophosphates diazinon and dimethoate, the carbamates pirimicarb and methomyl as well as the neonicotinoids thiacloprid and imidacloprid because they are abundant in the environment and cholinergic signaling plays a major role during key processes of neurodevelopment. We found that early embryonic motor behaviors, as measured by spontaneous tail coiling, increased upon exposure to most insecticides, while later movements, measured through touch-evoked response and a light-dark transition assay, rather decreased for the same insecticides and exposure duration. Moreover, the observed effects were more pronounced when exposure windows were temporally closer to the performing of the respective behavioral assay. However, the measured behavioral effects recovered after a short period, indicating that none of the exposure windows chosen here are particularly critical, but rather that insecticides acutely interfere with neuronal function at all stages as long as they are present. Overall, our results contribute to a better understanding of risks posed by cholinergic insecticides to fish and provide an important basis for the development of safe regulations to improve environmental health.
Topics: Animals; Insecticides; Zebrafish; Diazinon; Cholinergic Agents; Phenotype
PubMed: 36646183
DOI: 10.1016/j.chemosphere.2023.137874 -
International Journal of Molecular... Dec 2022Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically...
Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: (Ⅰ) serine-initiated nucleophilic attack and (Ⅱ) C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps Ⅰ and Ⅱ, respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
Topics: Humans; Hydrolysis; Esterases; Molecular Dynamics Simulation; Methomyl; Carbamates; Quantum Theory
PubMed: 36613879
DOI: 10.3390/ijms24010433 -
Toxicology Reports 2022Regulations often are imposing long postmortem times before autopsy leading to certain toxicity-unrelated changes in biomarkers, which in turn may affect the reliability...
Regulations often are imposing long postmortem times before autopsy leading to certain toxicity-unrelated changes in biomarkers, which in turn may affect the reliability of toxicity evaluation during forensic investigations. Since methomyl pesticide shows significant toxicity and is frequently encountered in poisoning cases, the current study evaluated different parameters in methomyl intoxicated rats at three different postmortem intervals (Hour 0, Hour 3 and Hour 6). Eighteen adult Sprague Dawley rats were poisoned with methomyl to simulate actual methomyl poisoning cases. The time of death was assigned as Hour 0. The animals were divided into 3 groups ( = 6) to collect blood and tissue samples at the selected time points. Body weight, relative organ weight, protein concentration, methomyl concentration and acetylcholinesterase activity (AChE) were assessed in blood and different tissues (liver, spleen, kidney, brain, eye, and bone marrow) to evaluate the effect of postmortem sampling time. Outcomes revealed significant decreases in methomyl concentration in blood and bone marrow with advanced sampling time (P < 0.001). Similarly, there were significant reductions in AChE activity in the kidney (P < 0.01), while the enzyme activity significantly increased in brain samples (P < 0.05). Findings illustrated the importance of sampling time in toxicity studies because it could alter experimental results and impact consequent interpretations, as well as it may alter postmortem biomarkers in related forensic cases.
PubMed: 36518403
DOI: 10.1016/j.toxrep.2022.08.010 -
Insects Nov 2022A resistant strain (MRS) of was cultured by continuous selection with malathion for over 40 generations. The MRS exhibited 32.7-fold resistance to malathion compared to...
A resistant strain (MRS) of was cultured by continuous selection with malathion for over 40 generations. The MRS exhibited 32.7-fold resistance to malathion compared to the susceptible strain (MSS) and 13.5-fold, 2.9-fold and 4.8-fold cross-resistance for omethoate, methomyl and beta-cypermethrin, respectively. However, no cross-resistance was found to imidacloprid in this resistant strain. The realized heritability for malathion resistance was 0.02. Inhibitors of esterase activity, both triphenyl phosphate (TPP) and S,S,S,-tributyl phosphorotrithioate (DEF) as synergists, exhibited significant synergism to malathion in the MRS strain, with 11.77-fold and 5.12-fold synergistic ratios, respectively, while piperonyl butoxide (PBO) and diethyl maleate (DEM) showed no significant synergism in the MRS strain. The biochemical assay indicated that carboxylesterase activity was higher in MRS than in MSS. These results suggest that the increase in esterase activity might play an important role in resistance to malathion. Imidacloprid could be used as an alternative for malathion in the management of wheat aphid resistance.
PubMed: 36421946
DOI: 10.3390/insects13111043 -
Biology Oct 2022Pesticides are commonly used in modern agricultural systems to protect the plants from pests. Even though they potentially increase the crop yield, they have undesirable...
Pesticides are commonly used in modern agricultural systems to protect the plants from pests. Even though they potentially increase the crop yield, they have undesirable toxic effects on the consumers of plant products and nontarget host plants. However, there are limited studies to demonstrate the cytological changes induced by pesticides on plant cells. In the present study, we assess the cytological changes induced by two most commonly used insecticides, methomyl (ME) and imidacloprid (IM), using L. as model plant system. . seeds were exposed to various concentrations of ME and IM (0.1, 0.2, 0.3, 0.4 and 0.5%) for 1, 3, and 6 h, and their effects on seed germination (SG), radicle length (RL), mitotic index (MI), chromosomal aberrations frequency (CAF), and micronucleus frequency (MNF) were studied. The results indicate that these insecticides decrease MI in root-tip cells, and increase in the MNF in pollen-mother cells in a dose-dependent manner. Additionally, insecticide-treated groups showed a dose- and time-dependent increase in the percentage of aberrant meiotic cells. Clumped nuclei (CNU), stickiness (STC), bridges (BRs), laggards (LGs), secondary association (SA), and precocious separation (PS) were among the frequently observed anomalies. The findings of this study indicate that commonly used insecticides ME and IM have substantial genotoxic effects on the root-tip and pollen-mother cells of L.
PubMed: 36358252
DOI: 10.3390/biology11111549 -
Se Pu = Chinese Journal of... Sep 2022Chromatography combined with mass spectrometry is the most commonly used detection technology, and it offers the advantages of high sensitivity and high selectivity. The...
[Simultaneous determination of 40 plant growth regulators, fungicides, insecticides, and antibiotics in bean sprouts by QuEChERS-high performance liquid chromatography-tandem mass spectrometry].
Chromatography combined with mass spectrometry is the most commonly used detection technology, and it offers the advantages of high sensitivity and high selectivity. The quick, easy, inexpensive, effective, rugged, and safe (QuEChERS) method is low-cost, effective, and time efficient. The application of the QuEChERS has now been extended to the analysis of contaminants in food samples. The aim of the study was to identify different concentration levels of multiple harmful drug residues in bean sprouts. In this study, QuEChERS coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the simultaneous determination of 40 plant growth regulators, fungicides, insecticides, and antibiotics in bean sprouts. In the HPLC-MS/MS experiment, gibberellic acid, 4-fluorophenoxyacetic acid, chloramphenicol, 6-(2-isopentenyl)-adenine, 6-benzylaminopurine, 4-chlorophenoxyacetic acid, and 2,4-dichlorophenoxyacetic acid (2,4-D) were analyzed by MS/MS with negative electrospray ionization (ESI). The other 33 target analytes (chlormequat, ronidazole, metronidazole, pymetrozine, dimetridazole, methomyl, carbendazim, enoxacin, levofloxacin, pefloxacin mesylate, norfloxacin, ciprofloxacin, enrofloxacin, thiabendazole, lomefloxacin, chlorpyrifos, sarafloxacin, imidacloprid, etc.) were analyzed by MS/MS with positive electrospray ionization (ESI). Sensitive MS conditions were realized by optimizing the instrumental parameters such as the desolvent temperature, collision energy, spraying needle position, precursor ions, and product ions. Then, the optimal pretreatment method was determined by comparing the recovery rates of the 40 drugs obtained with different extraction solvents (methanol, acetonitrile, acetonitrile containing 0.1% ammonia, acetonitrile with 1% acetic acid), different extraction methods (ultrasonic extraction, shaking extraction), and purification with primary secondary amine (PSA) and C. In this study, the bean sprouts samples were extracted twice by 10 mL acetonitrile with 1% acetic acid, and extracted under ultrasonic conditions. Then, the extracting solution was only cleaned with 100 mg C. The chromatographic separation of the 40 compounds was accomplished on a Waters ACQUITY UPLC BEH C column (100 mm×2.1 mm, 1.7 μm) with gradient elution. Methanol and 0.01% formic acid aqueous solution were used as the mobile phases. The 40 compounds were analyzed in the multiple reaction monitoring (MRM) mode. The matrix matching external standard method was used for quantitative determination. The results showed that the 40 compounds could be analyzed within 15 min. Under the optimized conditions, the calibration curves showed good linearities for the 40 compounds, and the coefficients of determination () were greater than 0.99 in the range of 2-200 μg/L. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.1-3 μg/kg and 0.3-9 μg/kg, respectively. Using negative bean sprouts as the substrates, the recovery tests were carried out at three spiked levels of 5, 10, and 50 μg/kg. The average recoveries of the 40 drugs were 78.5% to 115.3%, and the corresponding relative standard deviations (RSDs) were 1.3% to 9.7% (=6). This method was successfully applied to the analysis of the 40 drug residues in 21 batches of local bean sprouts in Handan city. The results revealed the presence of extensive drug residues in the bean sprouts. The 26 batches were detected to varying degrees, among which 4-chlorophenoxyacetic acid, carbendazim, 6-benzyladenine, 2,4-D, enrofloxacin, and metronidazole were detected at high rates. The detection rates of 4-chlorophenoxyacetic acid, 6-benzyladenine, carbendazim, 2,4-D, gibberellic acid, and enrofloxacin were 28.6%, 19.0%, 9.5%, 9.5%, 4.8%, and 4.8%, respectively. The contents ranged from 37.5-352.4, 32.4-273.1, 28.8-38.7, 316.1-20.2, 19.9 and 13.6 μg/kg, respectively. Given its advantages of simplicity, rapidness, and high sensitivity, the developed method can be used for the rapid and accurate determination of trace levels of the 40 drug residues in large quantities of bean sprouts.
Topics: 2,4-Dichlorophenoxyacetic Acid; Acetonitriles; Adenine; Ammonia; Anti-Bacterial Agents; Benzimidazoles; Benzyl Compounds; Carbamates; Chloramphenicol; Chlormequat; Chlorpyrifos; Chromatography, High Pressure Liquid; Ciprofloxacin; Dimetridazole; Enoxacin; Enrofloxacin; Fungicides, Industrial; Gibberellins; Insecticides; Levofloxacin; Methanol; Methomyl; Metronidazole; Norfloxacin; Pefloxacin; Plant Growth Regulators; Purines; Ronidazole; Solvents; Tandem Mass Spectrometry; Thiabendazole
PubMed: 36156631
DOI: 10.3724/SP.J.1123.2021.12028