Assessing pesticides in the atmosphere: A global study on pollution, human health effects, monitoring network and regulatory performance.

Pesticides are widely used in agriculture, but their impact on the environment and human health is a major concern. While much attention has been given to their presence in soil, water, and food, there have been few studies on airborne pesticide pollution on a global scale. This study aimed to assess the extent of atmospheric pesticide pollution in countries worldwide and identify regional differences using a scoring approach. In addition to analyzing the health risks associated with pesticide pollution, we also examined agricultural practices and current air quality standards for pesticides in these countries. The pollution scores varied significantly among the countries, particularly in Europe. Asian and Oceanic countries generally had higher scores compared to those in the Americas, suggesting a relatively higher level of air pollution caused by pesticides in these regions. It is worth noting that the current pollution levels, as assessed theoretically, pose minimal health risks to humans. However, studies in the literature have shown that excessive exposure to pesticides present in the atmosphere has been associated with various health problems, such as cancer, neuropsychiatric disorders, and other chronic diseases. Interestingly, European countries had the highest overall pesticide application intensities, but this did not necessarily correspond to higher atmospheric pesticide pollution scores. Only a few countries have established air quality standards specifically for pesticides. Furthermore, pollution scores across states in the USA were investigated and the global sampling sites were mapped. The findings revealed that the scores varied widely in the USA and the current sampling sites were limited or unevenly distributed in some countries, particularly the Nordic countries. These findings can help global relevant environmental agencies to set up comprehensive monitoring networks. Overall, the present research highlights the need to create a pesticide monitoring system and increase efforts to enhance pesticide regulation, ensure consistency in standards, and promote international cooperation.

Quantifying pesticide emissions for drift deposition in comparative risk and impact assessment.

Estimating emissions of chemical pesticides used in agriculture is an essential component in evaluating the potential toxicity-related impacts on humans and ecosystems in various comparative risk and impact assessment frameworks, such as life cycle assessment, environmental footprinting, absolute environmental sustainability assessment, chemical substitution, and risk prioritization. Emissions related to drift deposition-usually derived from drift experiments-can reach non-target areas, and vary as a function of crop characteristics and application technique. We derive cumulative drift deposition fractions for a wide range of experimental drift functions for use in comparative and mass-balanced approaches. We clarify that cumulative drift deposition fractions require to integrate the underlying drift functions over the relevant deposition area and to correct for the ratio of deposition area to treated field area to arrive at overall mass deposited per unit mass of applied pesticide. Our results show that for most crops, drift deposition fractions from pesticide application are below 0.03 (i.e. 3% of applied mass), except for grapes and fruit trees, where drift fractions can reach 5% when using canon or air blast sprayers. Notably, aerial applications on soybeans can result in significantly higher drift deposition fractions, ranging from 20% to 60%. Additionally, varying the nozzle position can lead to a factor of five differences in pesticide deposition, and establishing buffer zones can effectively reduce drift deposition. To address remaining limitations in deriving cumulative drift deposition fractions, we discuss possible alternative modelling approaches. Our proposed approach can be implemented in different quantitative and comparative assessment frameworks that require emission estimates of agricultural pesticides, in support of reducing chemical pollution and related impacts on human health and the environment.

Global assessment of honeybee exposure to pesticides through guttation consumption: An indicator approach.

Guttation consumption is a potential pathway of pesticide residue exposure in honeybees. However, modeling tools for assessing honeybee exposure to pesticide residues in guttation drops are lacking. In this study, we propose an indicator-based approach for qualitatively or quantitatively analyzing the guttation-based exposure pathway, allowing us to conduct region-specific pesticide residue exposure assessments for honeybees. Exposure scores (the product of guttation production and residue level scores) were established to compare or rank honeybee exposure to pesticide residues via guttation intake across locations using three specified indicators (i.e., air temperature, relative humidity, and precipitation intensity). Warm, dry regions had high residue level scores (indicating high residue levels in guttation), whereas cold, wet regions had high guttation production scores (indicating high possibilities of guttation formation on leaf surfaces); their exposure scores were a combination of these two values. We evaluated and ranked honeybee exposure to imidacloprid residue across regions in Brazil, China, the United States, and selected European Union member states, revealing that pesticide application in many Brazilian federative units may raise honeybee risks due to high exposure scores. We also compared the guttation pathway to other common exposure pathways (nectar and pollen), suggesting that for some moderately lipophilic compounds, the guttation exposure pathway may not be ignored and should be further evaluated.

Assessment of Alzheimer's disease-related biomarkers in patients with obstructive sleep apnea: A systematic review and meta-analysis.

Increasing evidence links Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). The core AD cerebrospinal fluid (CSF) biomarkers, including amyloid-ß 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau), can reflect key elements of AD pathophysiology before the emergence of symptoms. Besides, the amyloid-ß (Aß) and tau burden can also be tested by positron emission tomography (PET) scans. Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were searched until August 2022 to assess the AD-related biomarkers measured by PET scans and CSF in OSA patients. The overall analysis showed significant differences in Aß42 levels (SMD = -0.93, 95% CI:-1.57 to -0.29, P < 0.001) and total tau (t-tau) levels (SMD = 0.24, 95% CI: 0.01-0.48, P = 0.308) of CSF, and Aß burden (SMD = 0.37, 95% CI = 0.13-0.61, P = 0.69) tested by PET scans between the OSA and controls. Furthermore, CSF Aß42 levels showed significant differences in patients with moderate/severe OSA compared with healthy control, and levels of CSF Aß42 showed differences in OSA patients with normal cognition as well. Besides, age and BMI have influences on heterogeneity. Our meta-analysis indicated abnormal AD-related biomarkers (CSF and PET scans) in patients with OSA, supporting the current hypothesis that OSA, especially moderate/severe OSA, may start the AD neuropathological process. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021289559].

Modeling pesticide residues in nectar and pollen in support of pesticide exposure assessment for honeybees: A generic modeling approach.

Pesticide residues in nectar and pollen of plants can damage honeybees; however, few modeling approaches have simulated residue levels in nectar and pollen in support of exposure assessment for honeybees. This study introduced a generic modeling approach based on plant uptake models and simple partitioning rules that specifies soil incorporation and foliar spray application scenarios of pesticides and is flexible for conducting variability analysis for various environmental conditions, pesticide application patterns, chemical individuals, and plant varieties. The results indicated that, in general, systemic or moderate lipophilicity (log KOW of ~2.5) pesticides have relatively high simulated residue levels in nectar and pollen because of the enhanced residue uptake process from soil. For non-systemic or highly lipophilic pesticides, the residue uptake via leaf surface deposition pathway can be enhanced, and more residues will be bioaccumulated in pollen than nectar due to a relatively high lipid content of pollen (as compared to nectar), but the overall residue levels in nectar and pollen are lower than systemic or moderately lipophilic pesticides. The variability analysis showed that environmental conditions, pesticide application patterns, chemical properties, and plant varieties cause considerable variations in simulated residue levels in nectar and pollen, indicating that spatiotemporal, chemical, and plant-related factors must be considered in pesticide exposure assessment for honeybees. Moreover, the comparison between the simulated and measured data showed a high degree of consistency, indicating that the proposed model could be used to conduct a screening-level pesticide exposure assessment for honeybees.

Nerve regeneration in rat peripheral nerve allografts: An assessment of the role of endogenous neurotrophic factors in nerve cryopreservation and regeneration.

Peripheral nerve injury is a common clinical problem that often leads to significant functional impairment or even complete paralysis. Allograft has been proposed as a potential repair strategy for peripheral nerve injuries. Furthermore, peripheral nerve cryopreservation may result in nearly unlimited supply of grafts. However, the concentration of neurotrophic factors secreted by Schwann cells (SCs) in the local micro-environment after transplantation may not be sufficient for the survival of neuronal soma and axonal regeneration. Here, we investigated the effect of endogenous neurotrophic factors (ENTFs) on nerve regeneration in rats after the allograft of a cryopreserved sciatic nerve. ENTFs were highly expressed in the sciatic nerves pretreated for 14 days. Although the number of surviving cells in the sciatic nerves and their immunogenicity were low in the 14-day group after 4 weeks of cryopreservation, they continued to express high levels of ENTFs in vitro. At 1 week postoperation, the 14-day Allo group showed low plasma levels of interleukin-2, interferon-γ and tumour necrosis factor-alpha and low cellular immune response. At 20 weeks postoperation, nerve regeneration and functional recovery in the 14-day Allo group was similar to that in the fresh isograft group but better than that in the cryopreserved-fresh allograft and fresh allograft groups. Thus, ENTFs were induced in vitro after pretreatment of the sciatic nerve. Following cryopreservation, the sciatic nerves with high levels of ENTFs continued to express high levels of ENTFs in vitro. The immune response after allograft was weak, which promoted recipient nerve regeneration.

Quantifying exposure source allocation factors of pesticides in support of regulatory human health risk assessment.

One of the challenges while assessing the aggregate exposure risk of pesticides is quantifying exposure doses from various exposure pathways. To address this issue, a regulatory screening approach is proposed for evaluating pesticide allocation factors (AFs) for major exposure pathways for rural and urban residents. This was achieved by integrating dynamiCrop and other screening models to estimate the potential human intake of residues from major crops at harvest, livestock products, and main environmental media (air, water, and soil). The AFs were calculated from the average daily dose factors (ADDFs) of pesticides via major exposure pathways, where a large AF of an exposure pathway indicates that a greater margin of exposure should be given to that exposure pathway. The simulated results for many current-use pesticides showed that the ingestion of crops had pesticide AFs close to 1.0, which indicated that the crop exposure pathway contributed to a significant portion of the total exposure to pesticides. In contrast, for legacy pesticides with high lipophilicity and low degradability in the environment, the simulated AFs for major environmental compartments (air, freshwater, and soil) accounted for relatively large exposures. As legacy pesticides have been banned globally, exposure pathways via the food web and environmental media cannot be neglected because of their high lipophilicity and environmental persistence. Although other factors such as geographical conditions and living habits should be considered to improve the spatial resolution of the model, the method proposed in this study can serve as a preliminary tool to conduct screening-level risk assessments for populations by considering the allocated exposure to pesticides via major exposure pathways.

Improving screening model of pesticide risk assessment in surface soils: Addressing regional specific human exposure risks and regulatory management.

In this study, a simple screening approach was proposed to evaluate region-specific population health risks of soil pesticides, which was achieved by introducing region-specific factors of pesticides, including fate factors (FFs), environmental distribution factors (DFs), and intake factors (IFs). These region-specific factors were characterized using simple weather variables and calculated the characterization factors (CFs) to link pesticide emissions to population exposure risks. The CF at the reference state indicates the potential of a pesticide entering the human body. Simulations for over 700 pesticides showed that pesticides that are thermodynamically stable in soil organics have large CFs. In addition, we conducted a case study on the region-specific risk assessment of malathion in the United States. The results indicated that colder regions have larger CFs of malathion than those of the warmer regions due to the large FF values for the same emission rates. However, from a regulatory perspective, colder regions should have less strict malathion soil standards than those of warmer regions as children in colder regions spend limited time outdoors. Although other region-specific factors such as soil type and population density need to be considered to improve the model, the approach proposed in this study can be used as a simple screening tool to evaluate region-specific population health risks and manage soil residues for different regions.

Improving screening model of pesticide risk assessment in surface soils: Considering degradation metabolites.

As pesticides can be degraded to toxic metabolites in the soil, metabolite toxicity should be considered in human health risk assessments. In this study, a screening-level modeling framework was developed to manage pesticides in surface soil, which was discussed under discrete and continuous emission scenarios. In addition, we selected glyphosate and its major metabolite (aminomethylphosphonic acid or AMPA) as examples to conduct screening-level risk management at regional, national, and global scales. The results indicated that if soil AMPA were not considered, human health risks could be significantly underestimated because of the large half-life of AMPA in the soil. For example, the added concentration factors of AMPA were simulated as 0.19 and 6.72 considering all major elimination pathways and considering the degradation pathway alone, respectively, indicating that AMPA formation could lead to severe extra health burdens. Furthermore, the evaluation of current glyphosate soil standards suggested that toxic metabolites should be considered in the regulatory process; otherwise, many standards could theoretically trigger high levels of soil AMPA, which could result in serious human health damage. Our proposed screening-level model can help to improve risk assessment and regulatory management of pesticides in surface soils.

An equivalency iterative algorithm for cancer risk assessment of chemical mixtures with additive effects.

To better estimate cumulative cancer risks and avoid the overestimated risk from the linear extrapolation, an equivalency iterative algorithm associated with a carcinogenesis hypothesis was introduced for a mixture of chemicals with the same mode of action (MOA). A lognormal dose-response function was applied for carcinogenic chemicals. Under some circumstances, the repetitive random iterative algorithm could be transformed into the nonrepetitive one. It was also demonstrated that the equivalent value for a lognormal-based equivalency iterative algorithm with the same shape parameter was independent of the operation order. Based on the theorems of the algorithm and Plackett and Hewlett's minimum effective dose assumption, the sum of toxicity-weighted dose for a mixture of chemicals was mathematically derived. Compared to the estimation of risk by the linear extrapolation method (e.g., cancer slope factors), the equivalency iterative algorithm for lognormal functions can avoid overestimated risk significantly, which can help better estimate the cumulative cancer risk for a mixture of chemicals with the same MOA.

Introducing relative potency quotient approach associated with probabilistic cumulative risk assessment to derive soil standards for pesticide mixtures.

Children can be exposed to organophosphate and carbamate mixtures, which pose additive health effects via soil exposure. However, only 23 countries have soil standard values for organophosphate and carbamate pesticides, and most regulatory jurisdictions do not consider the cumulative exposure. This study derived proposed soil standards for organophosphates and carbamates by introducing the relative potency quotient approach (RPQ). The probabilistic cumulative risk assessment was also applied to evaluate current soil standards of pesticide mixtures. The U.S. Environmental Protection Agency (EPA) have soil standards of 19 organophosphates and five carbamates. However, these standards cannot protect population health via chronic exposure in conservative and semi-conservative scenarios based on the probabilistic risk assessment because the U.S.EPA simplified the regulatory process for the cumulative exposure to pesticide mixtures and omitted the soil allocation factor, which should be set for aggregate exposure. The analysis of proposed soil standards developed by the RPQ approach indicates that some human behavior variables, such as soil intake rate and exposure duration, have stronger impacts on the proposed soil standards than human biometric variables like body weight. This study may be helpful to develop regulatory standards and a framework for pesticide mixtures having additive health effects.

Global variations in pesticide regulations and health risk assessment of maximum concentration levels in drinking water.

Pesticides are used worldwide in agricultural, residential garden, and commercial applications. The control of pesticide exposure is a worldwide problem since pesticide can enter human body via ingestion, inhalation, and dermal contact. For drinking water, many regulatory jurisdictions respond by specifying the maximum concentration level (MCL) of a pesticide that may occur. At least 145 regulatory jurisdictions in 103 nations have specified at least 5474 pesticide MCLs in drinking water. Unfortunately, regulatory agencies often disagree on the magnitude of MCLs. For individual pesticides, MCLs often vary five, six, or even seven orders of magnitude. An analysis of the drinking water MCL distributions of the 25 most commonly regulated pesticides (N > 100 MCLs each) is presented in this study. Health risk uncertainty models are applied to compute uncertainty bounds around realistic MCL values for each pesticide and to help examine whether these MCLs can protect human health or not. Results indicated that at least 162 MCLs for 23 of the 25 pesticides considered were found to exceed upper human health risk uncertainty bounds indicating that these MCLs may not be adequate to protect human health. Also, health risk characterization factors were computed based on the estimation of maximum legal exposures to quantify human health damage caused by drinking water pesticide MCLs, and results indicated that some pesticide MCLs could cause over 19,000 Disability-Adjusted Life Years (DALYs) per million population. These MCLs distributions are highly influenced by several value clusters dominated by U.S., World Health Organization, and European Union (EU) indicating that consensus MCLs may be emerging for these most commonly regulated pesticides.