Organophosphate Insecticides Research Articles

Characterization of multiple pesticide exposure in pregnant women in Brittany, France.

France is one of the biggest users of pesticides in Europe and exposure to pesticides is a current concern, especially when it occurs early in life. The aim of this study was to assess the exposure of pregnant women in Brittany (western France) with high pesticide use. The pesticides were selected according to agricultural practices. Forty pesticides or metabolites were measured in urine samples collected in 2004 from 296 pregnant women in Brittany. The samples were analyzed by ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) after a solid phase extraction (SPE) step. Twenty seven pesticides were detected: the most frequently detected were the metabolites of organophosphate and pyrethroid insecticides (>89%) and several herbicides (phenoxypropionic acid derivatives and fluazifop >60%). Organophosphate and pyrethroid metabolites were also quantified in highest levels with maximum values of 590 μg/l for dimethylphosphate and 5.4 μg/l for 3- phenoxybenzoic acid. For the other parent compounds, such as prochloraz, bromoxynil and procymidone, they were also detected in 10-29% of the samples. Our results are consistent with pesticide use at the time of collection. The median concentrations of organophosphorus and pyrethroids were of the same order of magnitude as those reported in other countries. Herbicides and fungicides (fluazifop-p-butyl, bromoxynil, and prochloraz) were measured for the first time in this biomonitoring study, showing the usefulness of measuring widely used pesticides locally to improve knowledge of exposure. The objective of this study is to assess the exposure of pregnant women in a region of Europe with high pesticide use.

Insecticide Resistance Profile and Mechanisms in An. gambiae s.l. from Ebolowa, South Cameroon.

Monitoring the trend of insecticide resistance and understanding associated genetic mechanisms is important for designing efficient malaria vector control strategies. This study was conducted to provide temporal data on insecticide resistance status and mechanisms in the major malaria vector Anopheles gambiae s.l. from Ebolowa, Southern Cameroon. Methods: Larvae of An. gambiae s.l. were collected from typical breeding sites throughout the city and reared to adulthood. Emerging adults were morphologically identified and WHO tube assays were performed to determine their susceptibility to carbamate, organophosphate and pyrethroid insecticides at diagnostic doses. When resistance was observed, its intensity was determined by performing WHO tube tests using 5 and 10 times the concentration of the diagnostic dose. Metabolic resistance mechanisms were investigated using insecticide-synergist assays. Sibling species of the An. gambiae complex were identified using SINE-PCR protocol. TaqMan assay was used to genotype the L1014F and L1014S kdr mutations, and the N1575Y mutation, an amplifier of the resistance conferred by the L1014F mutation. Results: Anopheles coluzzii was by far the dominant (99%) member of the An. gambiae s.l. complex in Ebolowa. The species was fully susceptible to carbamates and organophosphates, but resistant to all pyrethroid insecticides tested. Resistance was of moderate intensity for deltamethrin (mortality: 37%, 70% and 99% for 1×, 5× and 10× insecticide concentration, respectively) but rather of high intensity for permethrin (5% for 1×; 62% for 5× and 75% for 10×) and for alphacypermethrin (4.4% for 1×; 57% for 5× and 80% for 10×). Pre-exposure to the synergist PBO resulted in a full recovery of the susceptibility to delthametrin, but this was not observed for the other two pyrethroids tested. L1014S (kdr-East) and the N1575Y mutations were absent, whereas the L1014F (kdr-West) mutation was present at a high frequency (75%), showing a significant association with resistance to permethrin (OR = 3.8; 95%; CI [1.9−7.4]; p < 0.0001) and alphacypermethrin (OR = 3; 95%; CI [1.6−5.4]; p = 0.0002). Conclusion: The increased resistance of An. gambiae s.l. to pyrethroid insecticides as observed in Ebolowa poses a threat to the efficacy of LLINs used to protect populations from the bites of Anopheles mosquitoes that transmit malaria parasites. The present study further highlights the urgent need to implement resistance management strategies in order to maintain the effectiveness of insecticide-based vector control interventions and prevent a rebound in malaria-related mortality.

Insight into weevil biology from a reference quality genome of the boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae).

The boll weevil, Anthonomus grandis grandis Boheman, is one of the most historically impactful insects due to its near destruction of the US cotton industry in the early 20th century. Contemporary efforts to manage this insect primarily use pheromone baited traps for detection and organophosphate insecticides for control, but this strategy is not sustainable due to financial and environmental costs. We present a high-quality boll weevil genome assembly, consisting of 306 scaffolds with approximately 24,000 annotated genes, as a first step in the identification of gene targets for novel pest control. Gene content and transposable element distribution are similar to those found in other Curculionidae genomes; however, this is the most contiguous and only assembly reported to date for a member in the species-rich genus Anthonomus. Transcriptome profiles across larval, pupal, and adult life stages led to identification of several genes and gene families that could present targets for novel control strategies.

Coenzyme Q10 nanoparticles prevents monocrotophos exposure mediated neurotoxicity by attenuating the histological alterations in rats

Organophosphate (OP) insecticide monocrotophos (MCP) is extremely hazardous to all living beings. This study shows that coenzyme Q10 nanoparticles (CoQ10NPs) can protect rats from the neurotoxicity caused by MCP-induced oxidative stress. In this study, male albino rats were divided into six groups i.e. control, CoQ10NPs low dose (50mg/kg b. wt) treated group, CoQ10NPs high dose (100mg/kg b. wt) treated group, MCP (4.5mg/kg b. wt) exposed group, CoQ10NPs low dose + MCP (50mg and 4.5mg/kg b. wt) treated group and CoQ10NPs high dose + MCP (100mg and 4.5mg/kg b. wt) treated group. The observation showed the depletion in the level of AChE activity and elevation in the levels of protein oxidation and lipid peroxidation which indicated the emerging of oxidative stress resulting in the induction of neurotoxicity. A significant decrease in the level of various enzymatic and non-enzymatic antioxidants like glutathione (GSH), catalase and superoxide dismutase (SOD) was observed in rat brain. The histopathological study indicated the major structural alterations in neuronal tissues of rats. These additionally backed up the induction of toxic effects caused by MCP exposure in rats. The prior co-treatment of CoQ10NPs along with MCP exposure depicted the significant protection from the oxidative stress generation and improved the structural and histological alteration in the rat brain. Hence, it can be concluded that CoQ10NPs have the strong therapeutic potential to reduce the MCP-induced oxidative stress, indicating their protective effects against MCP-induced neuronal cell damage in rats.

The association between organophosphate insecticides, blood pressure dysregulation, and metabolic syndrome among U.S. Adults: NHANES 2015-2016

Organophosphate (OP) insecticides represent some of the most common environmental contaminants in the United States. Organophosphate insecticide use has been associated with numerous adverse health outcomes, including hypertension (HTN) and metabolic syndrome (MetS), but results from current studies are conflicting and inconclusive. In a study of 916 U.S. adults from the 2015–2016 NHANES cycle, we investigated the association between five dialkyl phosphate (DAP) metabolites of OP insecticides and blood pressure parameters (systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, HTN), as well the association between total body burden of DAPs with HTN and MetS. Weighted, multivariable linear regression revealed significant, inverse associations between diethylphosphate and systolic blood pressure (β= -0.16 p = 0.02), diethylthiophosphate and systolic blood pressure (β= -0.91 p = 0.01), total DAP exposure and systolic blood pressure (β= -0.13, p = 0.04), and between dimethylphosphate and diastolic blood pressure (β= -0.15, p = 0.0075). No significant associations were observed between total DAP exposure and odds of HTN. We additionally modeled the odds of abnormally high pulse pressure given specific quartile of total DAP exposure. Results showed a significant association between diethylphosphate and odds of abnormal pulse pressure (OR=1.29, 95% CI[1.01,1.65]), and between total DAP exposure and odds of abnormal pulse pressure (OR=1.05, 95% CI[1.03,1.10]). Lastly, we found that adults in the 3rd quartile of OP metabolite exposure had a 3.61 increased odds of having MetS when compared to individuals in the 1st quartile (OR=3.61, 95% CI[1.32,9.85]).Our preliminary findings support data from previous studies suggesting a role for OP insecticides in the pathogenesis of blood pressure dysregulation and MetS. Future studies are warranted to corroborate these findings, determine population-level clinical significance, and to elucidate potential mechanisms explaining these associations.

Advancing Fifth Percentile Hazard Concentration Estimation Using Toxicity-Normalized Species Sensitivity Distributions.

The species sensitivity distribution (SSD) is an internationally accepted approach to hazard estimation using the probability distribution of toxicity values that is representative of the sensitivity of a group of species to a chemical. Application of SSDs in ecological risk assessment has been limited by insufficient taxonomic diversity of species to estimate a statistically robust fifth percentile hazard concentration (HC5). We used the toxicity-normalized SSD (SSDn) approach, (Lambert, F. N.; Raimondo, S.; Barron, M. G. Environ. Sci. Technol.2022,56, 8278-8289), modified to include all possible normalizing species, to estimate HC5 values for acute toxicity data for groups of carbamate and organophosphorous insecticides. We computed mean and variance of single chemical HC5 values for each chemical using leave-one-out (LOO) variance estimation and compared them to SSDn and conventionally estimated HC5 values. SSDn-estimated HC5 values showed low uncertainty and high accuracy compared to single-chemical SSDs when including all possible combinations of normalizing species within the chemical-taxa grouping (carbamate-all species, carbamate-fish, organophosphate-fish, and organophosphate-invertebrate). The SSDn approach is recommended for estimating HC5 values for compounds with insufficient species diversity for HC5 computation or high uncertainty in estimated single-chemical HC5 values. Furthermore, the LOO variance approach provides SSD practitioners with a simple computational method to estimate confidence intervals around an HC5 estimate that is nearly identical to the conventionally estimated HC5.

Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish.

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate that only 0.1% of organophosphates reach their desired target. Moreover, multiple studies have shown that OP exposure in both humans and animals can lead to aberrations in embryonic development, defects in childhood neurocognition, and substantial contribution to neurodegenerative diseases such as Alzheimer's and Motor Neurone Disease. Here, we review the current state of knowledge pertaining to organophosphate exposure on both embryonic development and/or subsequent neurological consequences on behaviour, paying particular attention to data gleaned using an excellent animal model, the zebrafish (Danio rerio).

Occupational health surveillance and detection of emerging occupational diseases among Taiwan farmers, through analysis of national-based farmers' and medico-administrative databases.

The purpose of this study was to identify occupational injuries and diseases associated with agriculture in Asia, to provide a reference for prevention and hypotheses for future research. We matched data on agricultural workers (n = 963,124) enrolled in Taiwan's national Farmers Health Insurance since its inception in 1989, to general population controls of the same age, gender, and township. The study population was linked to the National Health Insurance Research Database from 2001 to 2016 for inpatient cases. Logistic regression was used to assess odds ratios for outcomes. Farmers had 2.76 times the risk of mycotic corneal ulcer (95% CI: 1.96-3.87) and 1.65 times the risk of typhus fever infections (95% CI: 1.47-1.85) compared to the general population. The odds ratio for poisonous animal bites was 2.22 (95% CI: 2.07-2.38), for falling into a storm drain or manhole was 2.04 (95% CI: 1.30-3.20), and for toxic effects from pesticides was 2.01 (95% CI: 1.92-2.11). The toxic effects of organophosphate and carbamate insecticides were correlated with the cultivation of rice, fruit trees, and flowers. Q fever and motorcycle accidents were associated with fruit tree cultivation. The study identifies agricultural occupational injuries and diseases that may inform occupational health policy and the development of prevention priorities to prevent occupational hazards for farmers.

Accelerated degradation of groundwater-containing malathion using persulfate activated magnetic Fe3O4/graphene oxide nanocomposite for advanced water treatment

Malathion (MT) is a widely used organophosphate insecticide with a broad spectrum. MT residues in the environment even at low concentrations can have adverse effects on humans, plants, animals, and ecosystems. In this study aimed to investigate the MT degradation yield from groundwater using persulfate activated magnetic Fe3O4/graphene oxide nanocomposite (PS/Fe3O4-GO MNCs). Thus, the effects of MT concentration, the dosage of PS and Fe3O4-GO MNCs, pH value along with reaction time were investigated and further optimized applying Response Surface Method (RSM). This model equation showed a sufficient match with the measured results from the experimental data with the correlation coefficient (R2) of 0.9819 according to the analysis of variance. For the optimal yield, MT concentration of 3.7 mg/L, PS of 2.25 mM, Fe3O4-GO MNCs dosage of 225 mg/L, reaction time of 22 min and pH of 4 were obtained. Moreover, for MT degradation, the estimated optimal degradation efficiency was 96.5 %. Furthermore, a distinct synergistic effect was observed upon the usage of Fe3O4-GO MNCs for PS activation. The MT degradation rate is generally characterized by a pseudo-first-order kinetic model. Besides, experiments with radical scavengers revealed that both OH∙ and SO4-∙radicals had significant functions in MT degradation yields, with sulphate radicals being the dominant species. Conclusively, results revealed that the PS/Fe3O4-GO MNCs degradation process is an effective method for remediating waters that have been polluted with MT and related pesticides.

Preconception exposure to malathion and glucose homeostasis in rats: Effects on dams during pregnancy and post-term periods, and on their progeny.

Understanding the individual and global impact of pesticides on human physiology and the different stages of life is still a challenge in environmental health. We analyzed here whether administration of the organophosphate insecticide malathion before pregnancy could affect glucose homeostasis during pregnancy and, in addition, generate possible later consequences in mothers and offspring. For this, adult Wistar rats were allocated into two groups and were treated daily (intragastric) with malathion (14 or 140 mg/kg, body mass (bm)) for 21–25 days. Corn oil was used as vehicle in the Control group. Subgroups were defined based on the absence (nulliparous) or presence (pregnant) of a copulatory plug. Pregnant rats were followed by an additional period of 2 months after the term (post-term), without continuing malathion treatment. Fetuses and adult offspring of males and females were also evaluated. We ran an additional experimental design with rats exposed to malathion before pregnancy at a dose of 0.1 mg/kg bm. Malathion exposure resulted in glucose intolerance in the mothers during pregnancy and post-term period, regardless of the exposure dose. This was accompanied by increased visceral adipose tissue mass, dyslipidemia, unchanged pancreatic β-cell mass, and varying insulin responses to glucose in vivo. The number of total newborns and birthweight was not affected by malathion exposure. Adult offspring from both sexes also became glucose-intolerant, regardless of the pesticide dose their dams were exposed to. This alteration could be associated with changes at the epigenomic level, as reduced hepatic mRNA content of DNA methylases and demethylases was found. We demonstrated that periconceptional exposure to malathion with doses aiming to mimic from work environment to indirect contamination predisposes progenitors and offspring rats to glucose intolerance. Thus, we conclude that subchronic exposure to malathion is a risk factor for gestational diabetes and prediabetes later in life.

Organophosphate insecticides disturb neuronal network development and function via non-AChE mediated mechanisms

Exposure to organophosphate (OP) insecticides has been related to several adverse health effects, including neurotoxicity. The primary insecticidal mode of action of OP insecticides relies on (irreversible) binding to acetylcholine esterase (AChE), with –oxon metabolites having a much higher potency for AChE inhibition than the parent compounds. However, OP insecticides can also have non-AChE-mediated effects, including changes in gene expression, neuroendocrine effects, disruption of neurite outgrowth and disturbance of the intracellular calcium (Ca2+) homeostasis. Since Ca2+ is involved in neurotransmission and neuronal development, our research aimed to assess the effects of two widely used OP insecticides, chlorpyrifos (CPF) and diazinon (DZ) and their respective -oxon metabolites, on intracellular Ca2+ homeostasis in human SH-SY5Y cells and rat primary cortical cultures. Furthermore, we assessed the acute and chronic effects of exposure to these compounds on neuronal network maturation and function in rat primary cortical cultures using microelectrode array (MEA) recordings. While inhibition of AChE appears to be the primary mode of action of oxon-metabolites, our data indicate that both parent OP insecticides (CPF and DZ) inhibit depolarization-evoked Ca2+ influx and neuronal activity at concentrations far below their sensitivity for AChE inhibition, indicating that inhibition of voltage-gated calcium channels is a common mode of action of OP insecticides. Notably, parent compounds were more potent than their oxon metabolites, with exposure to diazinon-oxon (DZO) having no effect on both neuronal activity and Ca2+ influx. Human SH-SY5Y cells were more sensitive to OP-induced inhibition of depolarization-evoked Ca2+ influx than rat cortical cells. Acute exposure to OP insecticides had more potent effects on neuronal activity than on Ca2+ influx, suggesting that neuronal activity parameters are especially sensitive to OP exposure. Interestingly, the effects of DZ and chlorpyrifos-oxon (CPO) on neuronal activity lessened after 48 h of exposure, while the potency of CPF did not differ over time. This suggests that neurotoxicity after exposure to different OPs has different effects over time and occurs at levels that are close to human exposure levels. In line with these results, chronic exposure to CPF during 10 days impaired neuronal network development, illustrating the need to investigate possible links between early-life OP exposure and neurodevelopmental disorders in children and highlighting the importance of non-AChE mediated mechanisms of neurotoxicity after OP exposure.

Participatory development of practical, affordable, insecticide-treated mosquito proofing for a range of housing designs in rural southern Tanzania

BackgroundInsecticidal mosquito-proof netting screens could combine the best features of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), the two most important front line vector control interventions in Africa today, and also overcome the most important limitations of these methods. This study engaged members of a rural Tanzanian community in developing and evaluating simple, affordable and scalable procedures for installing readily available screening materials on eave gaps and windows of their own houses, and then treating those screens with a widely used IRS formulation of the organophosphate insecticide pirimiphos-methyl (PM).MethodsA cohort of 54 households recruited upon consent, following which the structural features and occupant demographics of their houses were surveyed. Indoor mosquito densities were surveyed longitudinally, for approximately 3 months before and over 5 months after participatory house modification and screening using locally available materials. Each house was randomly assigned to one of three study arms: (1) No screens installed until the end of the study (negative control), (2) untreated screens installed, and (3) screened installed and then treated with PM, the insecticidal activity of which was subsequently assessed using standard cone assays.ResultsAlmost all (52) recruited households participated until the end, at which point all houses had been successfully screened. In most cases, screening was only installed after making enabling structural modifications that were accepted by the enrolled households. Compared to unscreened houses, houses with either treated or untreated screens both almost entirely excluded Anopheles arabiensis (Relative reduction (RR) ≥ 98%, P < < 0.0001), the most abundant local malaria vector. However, screens were far less effective against Culex quinquefasciatus (RR ≤ 46%, P < < 0.0001), a non-malaria vector causing considerable biting nuisance, regardless of their treatment status. While PM did not augment household level protection by screens against either mosquito species (P = 0.676 and 0.831, respectively), 8 months after treatment it still caused 73% and 89% mortality among susceptible insectary-reared Anopheles gambiae following exposures of 3 and 30 min, respectively.ConclusionsParticipatory approaches to mosquito proofing houses may be acceptable and effective, and installed screens may be suitable targets for residual insecticide treatments.

Carlina acaulis essential oil: a candidate product for agrochemical industry due to its pesticidal capacity

Carlina acaulis L. is a herb mainly used in central Europe as traditional medicine or food. Recently, C. acaulis essential oil (EO) and its nanoemulsion showed elevated efficacy against several insects of medical and agricultural importance. In the current study, efficacy of C. acaulis EO was estimated against several stored product pests. The EO was sprayed on wheat to control Acarus siro L. (adults, nymphs), Alphitobius diaperinus (Panzer) (adults, larvae), Oryzaephilus surinamensis (L.) (adults, larvae), Rhyzopertha dominica (F.) (adults), Sitophilus oryzae (L.) (adults), Tenebrio molitor L. (adults, larvae), Tribolium castaneum (Herbst) (adults, larvae), and Tribolium confusum Jacquelin du Val (adults, larvae). Carlina acaulis EO was mainly composed by carlina oxide (98.8%), with benzaldehyde (1.2%) and ar-curcumene (traces) as minor components. Both adults and nymphs of A. siro showed high mortality, i.e., 91.1 and 95.6%, after 7 days of initial exposure to 1000 ppm (1000 μL C. acaulis EO/kg wheat), respectively. This concentration provided the death of 25.6% of the exposed A. diaperinus adults at the termination of trials. Total mortality (100.0%) of A. diaperinus larvae was reached 2 and 4 days after initial exposure on wheat sprayed with 1000 and 500 ppm of C. acaulis EO, respectively. One thousand (1000) ppm of EO killed 96.7% of O. surinamensis adults and all larvae 7 and 2 days after initial exposure, respectively. Concerning adults of R. dominica and S. oryzae, 1000 ppm achieved complete mortality after 4 and 6 days of initial exposure, respectively. Tenebrio molitor adults reached 81.1% mortality after their 7-days exposure to 1000 ppm C. acaulis EO. All T. molitor larvae were dead after 7 or 4 days of initial exposure to 500 and 1000 ppm, respectively. Carlina acaulis EO caused 97.8 and 100.0% mortality to adults of T. castaneum after 7 and 5 days of initial exposure to 1000 and 500 ppm, respectively. Complete mortality was observed after 16 h (1000 ppm) and 2 days (500 ppm) of initial exposure for T. castaneum larvae. Similarly, both examined stages of T. confusum achieved 100.0% mortality at the concentrations of 500 and 1000 ppm, after 7 and 4 days (adults), and 1 day and 16 h (larvae) of exposure, respectively. Overall, C. acaulis EO demonstrated pesticidal efficacy higher to pirimiphos-methyl, a conventional organophosphate insecticide, against a wide range of stored-product pests. Therefore this EO represents a reliable option for further developing eco-friendly and non-hazardous pest management strategies.

تأثيرات الكادميوم في السمّية الحادة لمبيدات حشرية مثبطة لنشاط إنزيم الكولين إستيريز في الفئران

الملخص تهدف هذه الدراسة إلى إجراء فحص السمّية الحادة في ذكور الفئران لكل من الكادميوم ونماذج من المبيدات الحشرية الفسفورية العضوية والكارباميتية المثبطة لإنزيم الكولين إستيريز، وتداخلها مع الكادميوم في مستويات الجُرع المميتة الوسطية خلال 24 ساعة (الجم-50 LD50)، وتحليل الآيزوبولوغرام (Isobologram Analysis)، ومؤشر التداخل السمّي (Toxicity Index). بلغت الجم-50 للكادميوم في الفئران 8.6 ملغم/كغم (mg/kg) من وزن الجسم بالحقن في الخلب، وأظهرت الفئران المعاملة بالكادميوم علامات التمطّي مع صعوبة الحركة والمشي. وبلغت الجم-50 لكل من المبيدات الحشرية الفسفورية العضوية دايكلورفوس وديازينون وكوموفوس وكلوربايريفوس عن طريق التجريع الفموي "التزقيم" (Gavage) 81.6 و157.6 و192.4 و437.1 ملغم/كغم من وزن الجسم، على التوالي، في حين بلغت الجم-50 لمبيدَي الكارباميت كارباريل وميثوميل عن طريق الفم 940.2 و177.5 ملغم/كغم من وزن الجسم، على التوالي. وأظهرت الفئران المتسممة بهذه المبيدات علامات الإلعاب والتدمع وانتصاب الشعر والذيل والتمدد على أرضية القفص والتحزم العضلي (Muscle Fasciculation) والرجفة والاختلاج العصبي وصعوبة التنفس، ومن ثم الموت خلال 24 ساعة من التجريع. وعند حقن الكادميوم في الخلب قبل المبيدات الحشرية بنصف ساعة، انخفضت قيم الجم-50 (زيادة السمّية) لكل من الكادميوم (51.4 - 74%) والمبيدات الحشرية (48.3 - 86.8%) مقارنة بقيمها بعد إعطائها لوحدها في الفئران. وقد بيّن تحليل الآيزوبولوغرام للتداخل السمّي بين الكادميوم والمبيدات الحشرية أن نوع التداخل كان تآزريًا (Synergistic)، ودلّ مؤشر التداخل بين الكادميوم والمبيدات الحشرية جميعها على أن التداخل كان تآزريًا أيضًا لكون قيمه أقل من واحد. وتشير هذه النتائج إلى احتمالية حصول تداخل سمّي بين الكادميوم مع المبيدات الحشرية الفسفورية العضوية والكارباميتية، إذْ سبّب إعطاء هذه المركبات في الفئران بجرع سامة وحادة تداخلًا سمّيًا حادًا من النوع التآزري الذي تم الكشف عنه وفق تجارب الجرع المميتة الوسطية وتحليل الآيزوبولوغرام ومؤشر التداخل السمّي.

Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward.

Knowledge of the role in cancer etiology of environmental exposures as pesticides is a prerequisite for primary prevention. We review 63epidemiological studies on exposure to pesticides and cancer risk in humans published from 2017 to 2021, with emphasis on new findings, methodological approaches, and gaps in the existing literature. While much of the recent evidence suggests causal relationships between pesticide exposure and cancer, the strongest evidence exists for acute myeloid leukemia (AML) and colorectal cancer (CRC), diseases in which the observed associations were consistent across several studies, including high-quality prospective studies and those using biomarkers for exposure assessment, with some observing dose-response relationships. Though high-quality studies have been published since the IARC monograph on organophosphate insecticides in 2017, there are still gaps in the literature on carcinogenic evidence in humans for a large number of pesticides. To further knowledge, we suggest leveraging new techniques and methods to increase sensitivity and precision of exposure assessment, incorporate multi-omics data, and investigate more thoroughly exposure to chemical mixtures. There is also a strong need for better and larger population-based cohort studies that include younger and nonoccupationally exposed individuals, particularly during developmental periods of susceptibility. Though the existing evidence has limitations, as always in science, there is sufficient evidence to implement policies and regulatory action that limit pesticide exposure in humans and, hence, further prevent a significant burden of cancers.

Discovery of malathion resistance QTL in Drosophila melanogaster using a bulked phenotyping approach.

Drosophila melanogaster has proved an effective system with which to understand the evolutionary genetics and molecular mechanisms of insecticide resistance. Insecticide use has left signatures of selection in the fly genome, and both functional and quantitative genetic studies in the system have identified genes and variants associated with resistance. Here, we use D. melanogaster and leverage a bulk phenotyping and pooled sequencing "extreme quantitative trait loci" approach to genetically dissect variation in resistance to malathion, an organophosphate insecticide. We resolve 2 quantitative trait loci, one of which implicates allelic variation at the cytochrome P450 gene Cyp6g1, a strong candidate based on previous work. The second shows no overlap with hits from a previous genome-wide association study for malathion resistance, recapitulating other studies showing that different strategies for complex trait dissection in flies can yield apparently different architectures. Notably, we see no genetic signal at the Ace gene. Ace encodes the target of organophosphate insecticide inhibition, and genome-wide association studies have identified strong Ace-linked associations with resistance in flies. The absence of quantitative trait locus implicating Ace here is most likely because our mapping population does not segregate for several of the known functional polymorphisms impacting resistance at Ace, perhaps because our population is derived from flies collected prior to the widespread use of organophosphate insecticides. Our fundamental approach can be an efficient, powerful strategy to dissect genetic variation in resistance traits. Nonetheless, studies seeking to interrogate contemporary insecticide resistance variation may benefit from deriving mapping populations from more recently collected strains.

Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.

Predicting the insecticide-driven mutations in a crop pest insect: Evidence for multiple polymorphisms of acetylcholinesterase gene with potential relevance for resistance to chemicals.

The silverleaf whitefly Bemisia tabaci (Gennadius, 1889) (Homoptera: Aleyrodidae) is a serious invasive herbivorous insect pest worldwide. The excessive use of pesticides has progressively selected B. tabaci specimens, reducing the effectiveness of the treatments, and ultimately ending in the selection of pesticide-resistant strains. The management of this crop pest has thus become challenging owing to the level of resistance to all major classes of recommended insecticides. Here, we used in silico techniques for detecting sequence polymorphisms in ace1 gene from naturally occurring B. tabaci variants, and monitor the presence and frequency of the detected putative mutations from 30 populations of the silverleaf whitefly from Egypt and Pakistan. We found several point mutations in ace1-type acetylcholinesterase (ace1) in the studied B. tabaci variants naturally occurring in the field. By comparing ace1 sequence data from an organophosphate-susceptible and an organophosphate-resistant strains of B. tabaci to ace1 sequence data retrieved from GenBank for that species and to nucleotide polymorphisms from other arthropods, we identified novel mutations that could potentially influence insecticide resistance. Homology modeling and molecular docking analyses were performed to determine if the mutation-induced changes in form 1 acetylcholinesterase (AChE1) structure could confer resistance to carbamate and organophosphate insecticides. Mutations had small effects on binding energy (ΔGb) interactions between mutant AChE1 and insecticides; they altered the conformation of the peripheral anionic site of AChE1, and modified the enzyme surface, and these changes have potential effects on the target-site sensitivity. Altogether, the results from this study provide information on genic variants of B. tabaci ace1 for future monitoring insecticide resistance development and report a potential case of environmentally driven gene variations.

Pesticide exposure and cortical brain activation among farmworkers in Costa Rica

BackgroundPrevious epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. MethodsWe conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3–5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. ResultsWe found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (β = −2.3; 95% CI: −3.9, −0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (β = −3.1; 95% CI: −5.0, −1.2 and −2.3; 95% CI: −4.5, −0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. ConclusionOur findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex – neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

Association of environmental chemical exposure during pregnancy with subsequent breast cancer risk

Background and Aim: Breast cancer became the most common cancer globally as of 2021, accounting for 12% of all new annual cancer cases worldwide, according to the World Health Organization. Despite epidemiologic studies establishing a number of risk factors for breast cancer, additional research is needed to elucidate environmental exposures that increase breast cancer risk. In this study, we used highly informative, existing pregnancy cohort biospecimens with an untargeted high-resolution mass spectrometry (HRMS) approach to discover possible environmental chemical exposures associated with subsequent breast cancer occurrence. Methods: Archived pregnancy samples, collected between 1959-1967, from the Child Health and Development Studies in California, one of the largest prospective pregnancy cohorts, were analyzed and searched against the Toxic Exposome Database (T3DB). The samples included 2nd (T2) and 3rd (T3) trimester archival samples of 182 women who subsequently developed breast cancer, compared to T2 and T3 samples from 384 women who did not develop breast cancer. Metabolites and environmental chemicals extracted from 50 &amp;#x3bc;L aliquots of thawed pregnancy serum (n=1,148) were analyzed by HRMS with liquid chromatography followed by advanced data extraction, annotation and pathway enrichment analysis. Results: A large number of mass spectral features differed between cases and controls at p&amp;#x3c;0.05. Annotation of the discriminatory metabolites with T3DB showed increased abundance of accurate mass matches (within 5 ppm) to methylmercury and the organophosphate insecticide, tebupirimfos, in both T2 and T3 breast cancer cases compared to controls (P&amp;#x3c;0.05). Additional verification of chemical identities is ongoing. Available literature is mixed for mercury association with breast cancer; however, methylmercury has been found to stimulate proliferation of breast cancer cells in culture. Conclusions: In addition to a significant metabolic disruption, exposure to methylmercury or/and organophosphate insecticide during pregnancy is associated with subsequent breast cancer risk. Keyword: Breast cancer, environmental chemical exposure, metabolic disruption, high-resolution metabolomics, pregnancy.