Bioplatform for Detecting Organophosphorus Compound Exposure.

Environmental contamination by fluorinated chemicals, in particular chemicals from the per- and polyfluoroalkyl substances (PFAS) class, has raised concerns around the globe because of documented adverse impacts on human health, wildlife, and ecosystem quality. Recent studies have indicated that pesticide products may contain a variety of chemicals that meet the PFAS definition, including the active pesticide ingredients themselves. Given that pesticides are some of the most widely distributed pollutants across the world, the legacy impacts of PFAS addition into pesticide products could be widespread and have wide-ranging implications on agriculture and food and water contamination, as well as the presence of PFAS in rural environments. The purpose of this commentary is to explore different ways that PFAS can be introduced into pesticide products, the extent of PFAS contamination of pesticide products, and the implications this could have for human and environmental health. We submitted multiple public records requests to state and federal agencies in the United States and Canada and extracted relevant data from those records. We also compiled data from publicly accessible databases for our analyses. We found that the biggest contributor to PFAS in pesticide products was active ingredients and their degradates. Nearly a quarter of all US conventional pesticide active ingredients were organofluorines and 14% were PFAS, and for active ingredients approved in the last 10 y, this had increased to 61% organofluorines and 30% PFAS. Another major contributing source was through PFAS leaching from fluorinated containers into pesticide products. Fluorination of adjuvant products and "inert" ingredients appeared to be limited, although this represents a major knowledge gap. We explored aspects of immunotoxicity, persistence, water contamination, and total fluorine load in the environment and conclude that the recent trend of using fluorinated active ingredients in pesticides may be having effects on chemical toxicity and persistence that are not given adequate oversight in the United States. We recommend a more stringent risk assessment approach for fluorinated pesticides, transparent disclosure of "inert" ingredients on pesticide labels, a complete phase-out of post-mold fluorination of plastic containers, and greater monitoring in the United States. https://doi.org/10.1289/EHP13954.

The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n= 85), rural inhabitants (environmental exposure, EE, n= 60), and an unexposed group conformed by people living far from agricultural areas (U, n= 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p< .001). OP exposure was the main predictor of genotoxicity (β=16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β=-12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.

Objective: To investigate if case fatality and other indicators of the severity of human pesticide poisonings can be used to prioritize pesticides of public health concern. To study the heterogeneity of data across countries, cause of poisonings, and treatment facilities. Methods: We searched literature databases as well as the internet for studies on case-fatality and severity scores of pesticide poisoning. Studies published between 1990 and 2014 providing information on active ingredients in pesticides or chemical groups of active ingredients were included. The variability of case-fatality-ratios was analyzed by computing the coefficient of variation as the ratio of the standard deviation to the mean. Findings: A total of 149 papers were identified of which 67 could be included after assessment. Case-fatality-ratio (CFR) on 66 active ingredients and additionally on 13 groups of active ingredients were reported from 20 countries. The overall median CFR for group of pesticides was 9%, for single pesticides 8%. Of those 12 active ingredients with a CFR above 20% more than half are WHO-classified as “moderately hazardous” or “unlikely to present acute hazard”. Two of seven pesticides considered “unlikely to present hazard in normal use” showed a CFR above 20%. The cross-study variability of reported case fatality was rather low. Studies most often utilized the Glasgow Coma Score for grading the severity of poisoning. Conclusion: Although human pesticide poisoning is a serious public health problem, an unexpectedly small number of publications report on the clinical outcomes within our study period. However, CFRs of acute human pesticide poisoning are available for several groups of pesticides as well as for active ingredients showing moderate cross-study variability. Our results underline that CFR is an indicator of the human toxicity of pesticides and can be utilized to prioritize highly hazardous pesticides especially since there is limited correspondence between the animal-test-based hazard classification and the human CFR of the respective pesticide. The reporting of available poisoning data should be improved, human case-fatality data are a reasonable tool to be included systematically in the periodic statutory review of pesticides and their regulation.

BackgroundPesticide exposure during susceptible windows and at certain doses are linked to numerous birth defects. Early experimental evidence suggests an association between active ingredients in pesticides and holoprosencephaly (HPE), the most common malformation of the forebrain in humans (1 in 250 embryos). No human studies to date have examined the association. This study investigated pesticides during multiple windows of exposure and fetal risk for HPE. It is hypothesized that pre-conception and early pregnancy, the time of brain development in utero, are the most critical windows of exposure.MethodsA questionnaire was developed for this retrospective case-control study to estimate household, occupational, and environmental pesticide exposures. Four windows of exposure were considered: preconception, early, mid and late pregnancy. Cases were identified through the National Human Genome Research Institute’s ongoing clinical studies of HPE. Similarly, controls were identified as children with Williams-Beuren syndrome, a genetic syndrome also characterized by congenital malformations, but etiologically unrelated to HPE. We assessed for differences in odds of exposures to pesticides between cases and controls.ResultsFindings from 91 cases and 56 controls showed an increased risk for HPE with reports of maternal exposure during pregnancy to select pesticides including personal insect repellants (adjusted odds ratio (aOR) 2.89, confidence interval (CI): 0.96–9.50) and insecticides and acaricides for pets (aOR 3.84, CI:1.04–16.32). Exposure to household pest control products during the preconception period or during pregnancy was associated with increased risk for HPE (aOR 2.60, OR: 0.84–8.68). No associations were found for occupational exposures to pesticides during pregnancy (aOR: 1.15, CI: 0.11–11.42), although exposure rates were low. Higher likelihood for HPE was also observed with residency next to an agricultural field (aOR 3.24, CI: 0.94–12.31).ConclusionsObservational findings are consistent with experimental evidence and suggest that exposure to personal, household, and agricultural pesticides during pregnancy may increase risk for HPE. Further investigations of gene by environment interactions are warranted.

Isonicotinic acid derivatives are used in the development of new antibacterial agents, active ingredients in pesticides and herbicides. In addition, isonicotinic acid is a precursor for the synthesis of isoniazid, one of the most effective anti-TB drugs. Considering the importance of isoniazid in the treatment of tuberculosis, improving methods of synthesizing isonicotinic acid has a direct impact on the availability and cost of this life-saving drug. The goal of this work was to investigate the efficiency of V-Cr-O catalyst in the oxidation of 4-methylpyridine to produce isonicotinic acid, to study its composition and properties. Research methods. Methods of chemical analysis, scanning electron microscope (SEM), Raman spectroscopy were applied. Results and Discussion. In this work, the processes of isonicotinic acid synthesis by oxidation of 4-methylpyridine on the V-Cr-O catalyst were studied. Analysis of the obtained results showed that with an increase in the water feed, there is a general tendency towards a decrease in the conversion of 4-methylpyridine at all temperatures. For example, at a temperature 300oC, the degree of conversion drops from 91.72% at 1.79 g/h to 84.20% at 6.6 g/h. The yield of isonicotinic acid increases as the amount of water rises, reaching its peak at 47.46% with a temperature of 360°C and a water supply of 6.6 g/h. In contrast, the minimum yield is only 15.27% at 280°C with a water supply of 1.79 g/h. This highlights the positive correlation between water supply and yield, especially at higher temperatures.

As of November 1977, the American Chemical Society's Chemical Abstracts Service computer registry of chemicals contained 4039907 distinct entities, and has been growing at an average rate of about 6000 per week. How many of these chemicals are in everyday use? Current estimates from the Environmental Protection Agency indicate that there may be as many as 50000 commonly used chemicals, not including pesticides, pharmaceuticals, and food additives. The EPA estimates that there may be as many as 1500 different active ingredients in pesticides. The Food and Drug Administration estimates that there are about 4000 active ingredients in drugs and about 2000 other ancillary compounds used in the drug industry. The FDA also estimates that there are about 2500 additives used for nutritional value and flavouring and 3000 chemicals used to preserve processed food. Thus there seem to be about 63000 chemicals in common use.

Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides

BackgroundMultiple epidemiological studies have shown that exposure to single pesticide active ingredients or chemical groups is associated with adverse neurobehavioral outcomes in farmers. In agriculture, exposure to multiple pesticide active ingredients is the rule, rather than exception. Therefore, occupational studies on neurobehavioral effects of pesticides should account for potential co-exposure confounding. MethodsWe conducted a cross-sectional study of 288 Ugandan smallholder farmers between September and December 2017. We collected data on self-reported use of pesticide products during the 12 months prior to survey and estimated yearly exposure-intensity scores for 14 pesticide active ingredients using a semi-quantitative exposure algorithm. We administered 11 neurobehavioral tests to assess five neurobehavioral domains. We implemented a Bayesian Model-Averaging (BMA) approach to examine the association between exposure to multiple pesticides and neurobehavioral outcomes, while accounting for multiple testing. We applied two levels of inference to determine (1) which neurobehavioral outcomes were associated with overall pesticide exposure (marginal inclusion probability (MIP) for covariate-only models <0.5) and (2) which specific pesticide active ingredients were associated with these outcomes (MIP for models where active ingredient was included >0.5). ResultsSeventy-two percent of farmers reported use of pesticide products that contained at least one of 14 active ingredients, while the applicators used in median three different active ingredients (interquartile range (IQR) 4) in the 12 months prior to the study. The most widely used active ingredients were glyphosate (79%), cypermethrin (60%), and mancozeb (55%). We found that overall pesticide exposure was associated with impaired visual memory (Benton Visual Retention Test (BVRT)), language (semantic verbal fluency test), perceptual-motor function (Finger tapping test), and complex attention problems (Trail making A test and digit symbol test). However, when we looked at the associations for individual active ingredients, we only observed a positive association between glyphosate exposure and impaired visual memory (-0.103 [95% Bayesian Credible Interval (BCI)] [-0.24, 0] units in BVRT scores per interquartile range (IQR) increase in annual exposure to glyphosate, relative to a median [IQR] of 6 [3] units in BVRT across the entire study population). ConclusionsWe found that overall pesticide exposure was associated with several neurobehavioral outcome variables. However, when we examined individual pesticide active ingredients, we observed predominantly null associations, except for a positive association between glyphosate exposure and impaired visual memory. Additional epidemiologic studies are needed to evaluate glyphosate’s neurotoxicity, while accounting for co-pollutant confounding.

Pesticides applied to agricultural land have been shown to decrease the quality of water entering the Great Barrier Reef lagoon. This issue is addressed by the Reef 2050 Water Quality Improvement Plan which includes a pesticide reduction target. As part of a wider educational strategy, one method that could help meet the target is to provide stakeholders with information that assists in the selection and use of pesticide active ingredients (PAIs) that pose a lower risk to aquatic environments compared to those currently used. This study developed a Pesticide Decision Support Tool (PDST) in collaboration with stakeholders for the sugar cane industry. The PDST covers all PAIs registered and applied to sugar cane in Australia and four additional PAIs registered for use on crops grown in rotation with sugar cane. The PDST incorporates both the measure of mobility and persistence of a PAI and the measure of effect, which is based on the PAI application rate and ecotoxicity threshold value. The aquatic risk, which is the product of the measure of effect and the measure of mobility and persistence, is a measure of the likelihood that a PAI will reach the aquatic environment and cause harmful effects. Insecticide active ingredients (e.g., cadusafos, chlorpyrifos) posed the greatest aquatic risk, followed by herbicide active ingredients (e.g., MSMA, metolachlor), while fungicide AIs typically had a lower aquatic risk. An interactive spreadsheet allows characteristics, including application rate and tank mixes, to be considered when assessing the potential risk. While focusing on sugar cane, the results are equally appropriate to other crops that use the same PAIs provided the application rates are corrected to the new crop. In addition, the approach used in the PDST can be applied internationally and to any PAIs with sufficient toxicity, mobility, and persistence data.

Decreasing efficacy of fungicides and the withdrawal of further hazardous active ingredients in pesticides from use have prompted the search for alternative methods of crop protection. Essential oils (EOs) are secondary metabolites of plants and have been proven to show antibacterial, antifungal, and pest-repellent properties. This study was undertaken to determine the activity of grapefruit, rosemary, pine, sage, and thyme EOs against the fungus Cercospora beticola, which is the most dangerous pathogen of sugar beet and the causal agent of Cercospora leaf spot. According to the determined Minimum Inhibitory Concentration (MIC), thyme EO was found the most effective against C. beticola. For most of the fungal isolates tested, the MIC of this EO was 0.313 mL/L. Thyme EO also inhibited the growth of multi-resistant isolates. Based on the results obtained, thyme EO was subjected to further testing in field conditions, where its efficiency in controlling C. beticola was also proven. The results indicate that the use of thyme EO may be a promising method for the protection of sugar beets, although it requires further optimization in the context of its inclusion in sustainable protection programs assuming a reduced number of synthetic fungicide treatments.

The research on acute dermal toxicity has consistently been a crucial component in assessing the potential risks of human exposure to active ingredients in pesticides and related plant protection products. However, it is difficult to directly identify the acute dermal toxicity of potential compounds through animal experiments alone. In our study, we separately integrated 1735 experimental data based on rabbits and 1679 experimental data based on rats to construct acute dermal toxicity prediction models using machine learning and deep learning algorithms. The best models for the two animal species achieved AUC values of 78.0 and 82.0%, respectively, on 10-fold cross-validation. Additionally, we employed SARpy to extract structural alerts, and in conjunction with Shapley additive explanation and attentive FP heatmap, we identified important features and structural fragments associated with acute dermal toxicity. This approach offers valuable insights for the detection of positive compounds. Moreover, a standalone software tool was developed to make acute dermal toxicity prediction easier. In summary, our research would provide an effective tool for acute dermal toxicity evaluation of pesticides, cosmetics, and drug safety assessment.

Many agricultural pesticides include substances that are known to be harmful to human health and while some have been banned from developed countries, they are still being used in developing countries such as Brazil. Recent studies have shown that low-level chronic dietary exposure to pesticides can affect the human gut microbiota. This possible hazardous effect of pesticides on human health has not been specifically recognized by government regulatory agencies. In Brazil, for instance, of the 10 best-selling active ingredients in pesticides in 2019, two are considered extremely toxic, Paraquat and Chlorpyrifos. Even though Paraquat has been banned in Brazil since 2020, the values of maximum residue limits (MRLs) of toxic pesticides allowed in the country are still higher than in other countries. Unfortunately, many developing countries still lack the resources and expertise needed to monitor adequately and systematically the presence of pesticide residues on food. In this work, we raise awareness to the danger the chronic exposure to high dietary levels of pesticides can pose to the public, especially considering their prolonged effects on the gut microbiome.

In Denmark, a political decision was taken to achieve, before 1997, a 50% reduction in the bulk of active ingredients in pesticides consumed, compared with average consumption in the period 1981/1985. To meet this requirement, a computer‐based decision support system has been developed. In order to minimize doses, the system combines the concept of factor adjusted doses and expert knowledge. Herbicide doses are adjusted on the basis of the sensitivity of different weed species and their growth stages. Based on actual field observations, the system suggests suitable herbicides, the normal dose, the actual dose, prices per ha, etc. In future, doses will probably also be factor‐adjusted according to climatic conditions, competitive ability of cereal cultivars and soil type. The need for control of individual weed species (thresholds) is based on expert knowledge. Ongoing long‐term studies on seed production by weeds, competition studies etc. will hopefully help to establish more exact models for economic thresholds. After satisfactory validation through field trials, the system will be continuously updated with new findings in weed research. The system has been on the market in Denmark since spring 1991.

Forty years ago, in the enormously praised and fiercely criticized book, "Silent Spring", Rachel Carson demonstrated the dangers of pesticides to humans and ecosystems and called for precaution in their use. Yet, the majority of environmental regulations passed since 1962 have primarily addressed pollutant discharge rather than cleaner products and technologies. The number of active ingredients in pesticides used in the United States has risen from 32 in 1939 to 860 in recent times, while the overall volume of agrochemicals applied has nearly doubled since the publication of Silent Spring. The last 40 years have brought significant changes with respect to environmental policies, agricultural technologies, urbanization, civil rights, women's rights, the roles of non-profit organizations and community development, and increased poverty, hunger, and economic inequality. In recent years, new voices, new analyses, and new movements have emerged offering fresh perspectives on how we can answer Carson's clarion call to protect our planet and ourselves.

This study compares three pesticide-risk indicators: 1) the environmental impact quotient (EIQ), 2) the toxicity, human health, and persistency hazard rating system (THP), and 3) the pesticide environmental risk indicator (PERI) to evaluate the environmental impacts of active ingredients in pesticides. Environmental risk scores were obtained and evaluated for commonly used pesticides in Kumluca region of Turkey. The risk scores of EIQ and THP were in good agreement. This study provides an example applicable in other areas where environmental measurements of pesticides are either unaffordable or not physically feasible. The selected pesticide risk indicators are easily applied and helpful tools for pest management practitioners. However, site specific components (surface runoff, particle transport processes, and spatial variability of pesticide transport in soil) and exposure of consumers to pesticide residues are missing in the selected indicators. Forensic methods and approaches could be applied in conjunction with existing indicator models to better understand pesticide fate and transport and improve their selection and application pattern.