Abatement of pesticides residues in commercial farm soils by combined ozonation-solarization treatment.

The widespread use of pesticides against agricultural pest and diseases introduces these pollutants and their transformation products into soils. The toxicity and permanence of these substances make it necessary for the development of remediation strategies in order to mitigate contamination and to further protect consumers. This work was aimed to evaluate the applicability of ozonation-solarization technology in the degradation of pesticide residues in commercial farm soils. The trial was conducted in two exploitations devoted during decades to tomato cultivation under greenhouse and net systems. Treatments were carried out using a pipping network (both superficial and sub-superficial) that delivered ozone in gaseous state after covering the soil with gas-tight plastic film to avoid ozone leaks to atmosphere. Control soil treatments, without ozone exposure, were also conducted. After 40 days of treatment, mean degradation percentages of about 55-61% for both cultivation systems were obtained, when the reduction of these pollutants in the control soils was about 8-15%. Ozonation-solarization impact was also assessed by changes on soil physical-chemical properties. Results suggest that ozonation in combination with solarization technique could be considered as a feasible approach for the remediation of pesticide-polluted farm soils.

AChE-based electrochemical biosensor for pesticide detection in vegetable oils: matrix effects and synergistic inhibition of the immobilized enzyme.

Enzyme-based electrochemical biosensors have been widely deployed for the detection of a range of contaminants in different food products due to their significant advantages over other (bio)sensing techniques. Nevertheless, their performance is greatly affected by the sample matrix itself or by the matrix they are presented with in pretreated samples, both of which can impact the accuracy as well as the sensitivity of the measurements. Therefore, and in order to acquire reliable and accurate measurements, matrix effects and their influence on sensor performance should be taken into consideration. Herein, acetylcholinesterase (AChE)-modified electrochemical sensors were employed for the detection of pesticides in vegetable oils. Sensor interrogation with pretreated oil samples, spiked with carbofuran, revealed the inhibitory potential of the extracted matrix varies between different types of vegetable oil and their fatty acid content. In addition, synergies between the extracted matrix from different types of vegetable oils and the carbamate pesticide, carbofuran, were observed, which led to significant deviations of the sensor's performance from its anticipated behavior in buffered solution. Taking the aforementioned into consideration, appropriate calibration curves for each type of vegetable oil were drafted, which allowed for the highly reproducible determination of different pesticide concentrations in pretreated real samples. Collectively, a better understanding of AChE inhibition by single or multiple contaminants present in vegetable oils was gained, which can find many applications in numerous fields, ranging from sensor development to the design of new pesticides and medicinal products.

Considering degradation kinetics of pesticides in plant uptake models: proof of concept for potato.

BACKGROUND: Degradation kinetics of pesticides in plants are crucial for modeling mechanism-based pesticide residual concentrations. However, due to complex open-field conditions that involve multiple pesticide plant uptake and elimination processes, it is difficult to directly measure degradation kinetics of pesticides in plants. To address this limitation, we proposed a modeling approach for estimating degradation rate constants of pesticides in plants, using potato as a model crop. An operational tool was developed to backward-estimate degradation rate constants, and three pesticides were selected to perform example simulations. RESULTS: The simulation results of thiamethoxam indicated that the growth dynamics of the potato had a significant impact on the degradation kinetic estimates when the pesticide was applied during the early growth stage, as the size of the potato determined the uptake and elimination kinetics via diffusion. Using mepiquat, we demonstrated that geographical variations in weather conditions and soil properties led to significant differences in the dissipation kinetics in both potato plants and soil, which propagated the variability of the degradation rate constant. Simulation results of chlorpyrifos differed between two reported field studies, which is due to the effect of the vertical distribution of the residue concentration in the soil, which is not considered in the majority of recent studies. CONCLUSIONS: Our proposed approach is adaptable to plant growth dynamics, preharvest intervals, and multiple pesticide application events. In future research, it is expected that the proposed method will enable region-specific inputs to improve the estimation of the degradation kinetics of pesticides in plants. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Pectin functionalized metal-organic frameworks as dual-stimuli-responsive carriers to improve the pesticide targeting and reduce environmental risks.

Encapsulation of active ingredients into intelligent response controlled release carriers has been recognized as a promising approach to enhance the utilization efficiency and reduce the environmental risks of pesticides. In this work, an intelligent redox and pectinase dual stimuli-responsive pesticide delivery system was constructed by bonding pectin with metal-organic frameworks (FeMOF nanoparticles) which were loaded with pyraclostrobin (PYR@FeMOF-pectin nanoparticles). The successful fabrication of PYR@FeMOF-pectin nanoparticles was proved by a series of physicochemical characterizations. The results indicated that the loading capacity of PYR@FeMOF-pectin nanoparticles for pyraclostrobin was approximately 20.6%. The pectin covered on the surface of PYR@FeMOF nanoparticles could protect pyraclostrobin from photolysis and improve their spreadability on rice blades effectively. Different biological stimuli associated with Magnaporthe oryzae could trigger the release of pyraclostrobin from the pesticide-loaded core-shell nanoparticles, resulting in the death of pathogens. The bioactivity survey determined that PYR@FeMOF-pectin nanoparticles had a superior fungicidal activity and a longer duration against Magnaporthe oryzae than pyraclostrobin suspension concentrate. In addition, the FeMOF-pectin nanocarriers showed no obvious phytotoxicity and could enhance the shoot length and root length of rice plants. More importantly, PYR@FeMOF-pectin nanoparticles had an 8-fold reduction in acute toxicity to zebrafish than that of pyraclostrobin suspension concentrate. Therefore, the dual-responsive FeMOF-pectin nanocarriers have great potential for realizing site-specific pesticide delivery and promoting plant growth.

Occurrence and human health risk assessment of mineral elements and pesticides residues in bee pollen.

Bee pollen contains a diversity of bioactive components. Nevertheless, since pollen is retrieved from a variety of plants, including the cultivated ones which are subjected to agrochemical treatments, its contamination is unavoidable. In this context, 45 samples of pollen were analysed with optimized analytical methods for trace and macro elements (ICP-MS), pesticides and metabolites residues (LC & GC-MS/MS) content. According to the results, potassium and iron were the most abundant in terms of concentration and frequency of detection, while the contribution of the most hazardous elements, such as lead, arsenic, cadmium and mercury, to the total concentration of trace elements was lower than 1%. For pesticides, coumaphos was the most frequently detected in the examined samples (22%), followed by propargite, azoxystrobin, dimethoate and cypermethrin. Non-carcinogenic health risk assessment demonstrated in the majority of cases negligible risk for adults and children. On the contrary, carcinogenic risk assessment considering a worst case scenario disclosed nickel and in less extent chromium and arsenic, as risk drivers, exhibiting in several samples carcinogenic risk values for adults above the safety threshold. Yet, regarding that both adults and children unlikely will daily consume such pollen quantities, especially on a long-term basis, an overestimation of risk should be appraised.

Monitoring of polar pesticides and contaminants in edible oils and nuts by liquid chromatography-tandem mass spectrometry.

A single method was developed for the determination of polar pesticides (fosetyl-Al and its metabolite, phosphonic acid, and ethephon) and environmental contaminants (chlorate and perchlorate) in edible oils and nuts. Two extraction methods based on QuPPe-PO approach (Quick Polar Pesticides Method for products of Plant Origin) were optimized. In oils, a single extraction using water acidified with formic acid (1%) was performed, while in nuts, the clean-up step was modified. C18 was used as sorbent and an extra cleaning step with n-hexane was added. The extracts were analysed by liquid chromatography coupled to a triple quadrupole mass analyser (LC-QqQ-MS/MS). The method was validated and the limit of quantification was 0.01 mg kg-1 for all analyte-matrix combination. Recoveries from 70 to 120%, and intra and inter-day precision values ≤20% were obtained. Forty samples of edible oils and nuts were analysed, detecting phosphonic acid in nuts at concentrations up to 4.6 mg kg-1.

Bagging and non-bagging treatment on the dissipation and residue of four mixed application pesticides on banana fruit.

BACKGROUND: Bananas are vulnerable to disease and insect pests after producing fruit. In order to increase the yield and produce high-quality fruit, the insecticides and fungicides are mixed and applied 2-3 times on banana, then the fruit is bagged. Buprofezin, imidacloprid, difenoconazole, and pyraclostrobin are widely used on banana. However, there is a lack of research on the effect of fruit bagging on pesticide dissipation and residues on bananas. RESULTS: A versatile liquid chromatography-tandem mass spectrometry method with modified QuEChERS sample preparation has been developed for the determination of buprofezin, imidacloprid, difenoconazole, and pyraclostrobin in bananas. The recovery of four pesticides was satisfactory (74.96-98.63%) with reasonable relative standard deviation (≤ 8.78%). In Hainan and Guangzhou, the half-lives of the four pesticides were 4.68-13.9 and 5.63-20.4 days in non-bagged and bagged bananas, respectively. The significance analysis of the half-lives in the two sites showed that the dissipation rates of the three pesticides (imidacloprid, difenoconazole, pyraclostrobin) on whole bananas were significantly decreased by the effect of bagging (P < 0.05). However, there was no significant difference in the degradation of half-life of buprofezin under bagging and without bagging (P > 0.05). CONCLUSION: The high vapor pressure and the non-systemic property cause buprofezin to evaporate and dissipate the fastest among the four studied pesticides. The ultimate residues of four pesticides in bananas are lower than the maximum residue limits in China after three times of mixed applications under bagging or non-bagging. The results provide scientific data for evaluating the safety of four pesticides in banana bagging. © 2020 Society of Chemical Industry.

Cytotoxic Plant Extracts towards Insect Cells: Bioactivity and Nanoencapsulation Studies for Application as Biopesticides.

The potential of plant extracts as bioinsecticides has been described as a promising field of agricultural development. In this work, the extracts of Punica granatum (pomegranate), Phytolacca americana (American pokeweed), Glandora prostrata (shrubby gromwell), Ulex europaeus (gorce), Tagetes patula (French marigold), Camellia japonica red (camellia), Ruta graveolens (rue or herb-of-grace) were obtained, purified, and their activity against Spodoptera frugiperda (Sf9) insect cells was investigated. From the pool of over twenty extracts obtained, comprising different polarities and vegetable materials, less polar samples were shown to be more toxic towards the insect cell line Sf9. Among these, a dichloromethane extract of R. graveolens was capable of causing a loss of viability of over 50%, exceeding the effect of the commercial insecticide chlorpyrifos. This extract elicited chromatin condensation and the fragmentation in treated cells. Nanoencapsulation assays of the cytotoxic plant extracts in soybean liposomes and chitosan nanostructures were carried out. The nanosystems exhibited sizes lower or around 200 nm, low polydispersity, and generally high encapsulation efficiencies. Release assays showed that chitosan nanoemulsions provide a fast and total extract release, while liposome-based systems are suitable for a more delayed release. These results represent a proof-of-concept for the future development of bioinsecticide nanoformulations based on the cytotoxic plant extracts.

Miniaturized Salting-Out Assisted Liquid-Liquid Extraction Combined with Disposable Pipette Extraction for Fast Sample Preparation of Neonicotinoid Pesticides in Bee Pollen.

As the main source of nutrients for the important pollinator honeybee, bee pollen is crucial for the health of the honeybee and the agro-ecosystem. In the present study, a new sample preparation procedure has been developed for the determination of neonicotinoid pesticides in bee pollen. The neonicotinoid pesticides were extracted using miniaturized salting-out assisted liquid-liquid extraction (mini-SALLE), followed by disposable pipette extraction (DPX) for the clean-up of analytes. Effects of DPX parameters on the clean-up performance were systematically investigated, including sorbent types (PSA, C18, and silica gel), mass of sorbent, loading modes, and elution conditions. In addition, the clean-up effect of classical dispersive solid-phase extraction (d-SPE) was compared with that of the DPX method. Results indicated that PSA-based DPX showed excellent clean-up ability for the high performance liquid chromatography (HPLC) analysis of neonicotinoid pesticides in bee pollen. The proposed DPX method was fully validated and demonstrated to provide the advantage of simple and rapid clean-up with low consumption of solvent. This is the first report of DPX method applied in bee pollen matrix, and would be valuable for the development of a fast sample preparation method for this challenging and important matrix.

Residual analysis of chitosan-based agronanofungicides as a sustainable alternative in oil palm disease management.

The nanoformulations of pesticides have shown great interest from many parties due to their slow release capability and site-specific delivery. Hence, in this work, a new nanoformulation of a fungicide, namely chitosan-hexaconazole nanoparticles with a mean diameter size of 18 nm was subjected to the residual analysis on oil palm tissue, leaf and palm oil (crude palm oil and crude palm kernel oil) using a quick, easy, cheap, effective, rugged and safe (QuEChERS) method coupled with the gas chromatography-micro electron capture detector (GC-µECD). The chitosan-hexaconazole nanoparticles were applied using the trunk injection method at 4.5 g a.i./palm (standard single dose) and 9.0 g a.i./palm (double dose). The fungicide residue was analyzed at 0 (6 h after application), 1, 3, 7, 14, 30, 60, 90, and 120 days after treatment. The palm oil matrices; the crude palm oil (CPO) and crude palm kernel oil (CPKO) were found to be residue-free. However, it was observed that high accumulation of the fungicide in the stem tissue and leaf after the treatment using the chitosan-hexaconazole nanoparticles, which is good for better bioavailability for the treatment of the fungi, Ganoderma boninense. The dissipation kinetic at double dose treatment in the tissue and leaf was found to govern by the second-order kinetic with half-lives (t1/2) of 383 and 515 days, respectively.

Magnetically controlled colorimetric aptasensor for chlorpyrifos based on copper-based metal-organic framework nanoparticles with peroxidase mimetic property.

The fabrication of a magnetically controlled colorimetric aptasensor for chlorpyrifos is reported. The aptasensor was fabricated by the attachment of the colorimetric labels onto the magnetic carrier due to the hybridization reaction between the complementary DNA and aptamer. Chlorpyrifos detection was realized by monitoring the color changes of the TMB/H2O2 solution before and after incubation of the aptasensor with chlorpyrifos via exposure to external magnetic force. The color change was monitored at 650 nm by UV-Vis spectrophotometer. Under the optimal conditions, this magnetically controlled Cu-MOF-based aptasensor showed a detection limit of 4.4 ng/mL with a linear range of 0-1250 ng/mL. The colorimetric aptasensor displayed high selectivity for chlorpyrifos toward other interfering pesticides. The aptasensor was successfully applied for the spiked test of chlorpyrifos in fruits and vegetable samples with good recovery, which were in agreement with data obtained by GC-MS analysis. This magnetically controlled Cu-MOF-based sensing strategy not only leads to development of efficient and facile phase separation, but also expands the MOF's target scope from H2O2 or glucose to pesticides. Graphical abstract.

Eco-Friendly Castor Oil-Based Delivery System with Sustained Pesticide Release and Enhanced Retention.

The deposition of pesticides and their retention on plant surfaces are critical challenges for modern precision agriculture, which directly affect phytosanitary treatment, bioavailability, efficacy, and the loss of pesticides. Herein, a novel and eco-friendly waterborne polyurethane delivery system was developed to enhance the spray deposition and pesticide retention on plant surfaces. More specifically, biobased cationic and anionic waterborne polyurethane dispersions were synthesized from castor oil. Both cationic and anionic polyurethane dispersions exhibited remarkable microstructural, amphiphilic, and nanoparticle morphologies with a core-shell structure that served to encapsulate a biopesticide (azadirachtin) in their hydrophobic cores (WPU-ACT). The results indicated that the cationic WPU-ACT carriers exhibited a better sustained release behavior and a better protective effect from light and heat for azadirachtin. In addition, the simultaneous spray of anionic and cationic WPU-ACT significantly enhanced the spray deposition and prolonged the retention of pesticides due to the reduced surface tension and surface precipitation induced by the electrostatic interaction when two droplets with opposite charges come into contact with each other. A field efficacy assessment also indicated that the simultaneous spray of anionic and cationic WPU-ACT could control the infestation of brown planthopper in rice crops. Castor oil-based waterborne polyurethanes in this study work as an efficient pesticide delivery system by exhibiting enhanced deposition, rainfastness, retention ability, protection, and sustained release behavior, holding great promise for spraying pesticide formulations in modern and environmentally friendly agricultural applications.

Semisynthesis and Pesticidal Activities of Derivatives of the Diterpenoid Andrographolide and Investigation on the Stress Response of Aphis citricola Van der Goot (Homoptera: Aphididae).

To discover natural-product-based pesticides, 7ß-oxycarbonylandrographolide derivatives were stereoselectively constructed from a labdane diterpenoid andrographolide. Among them, 2'-(n)Pr-1',3'-dioxin-7ß-oxy(m-Cl)benzoylandrographolide (IIc), 2'-(n)Pr-1',3'-dioxin-7ß-oxyacetylandrographolide (IIf), 2'-(p-Me)Ph-1',3'-dioxin-7ß-oxy(o-Cl)benzoylandrographolide (Vb), and 2'-(p-Me)Ph-1',3'-dioxin-7ß-oxy(m-Cl)benzoylandrographolide (Vc) against Mythimna separata displayed the most promising growth inhibitory activity; 2'-(n)Pr-1',3'-dioxin-7ß-oxy(o-Cl)benzoylandrographolide (IIb: LC50 = 0.406 mg/mL) and IIc (LC50 = 0.415 mg/mL) exhibited the most pronounced acaricidal activity (andrographolide; LC50: 5.106 mg/mL) and good control effects against Tetranychus cinnabarinus; compounds Ic, IIe, and Va-c (LD50 = 0.035-0.039 µg/nymph) showed potent aphicidal activity (andrographolide: LD50 = 0.178 µg/nymph), and compounds IIe and Vb showed good control effects against Aphis citricola. Moreover, it was found that Hsp70 of A. citricola was an important gene involved in stress response to andrographolide and its derivatives.

Magnetic amino-functionalized hollow silica-titania microsphere as an efficient sorbent for extraction of pesticides in green and roasted coffee beans.

This study describes the synthesis and application of a magnetic amino-functionalized hollow silica-titania microsphere as a new sorbent for magnetic dispersive micro-solid phase extraction of selected pesticides in coffee bean samples. The sorbent was fully characterized by Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, transition electron microscopy, energy-dispersive X-ray spectroscopy, and vibrating sample magnetometry techniques. Significant extraction parameters affecting the proposed method, such as extraction time, sorbent amount, sample solution pH, salt amount, and desorption conditions (desorption solvent and time) were investigated and optimized. All the figures of merits were validated in coffee bean samples under the matrix-matched calibration method. Linear dynamic ranges were 5-250 µg/kg with the determination coefficients (R2 ) > 0.9980. The limits of detection for the pesticides of chlorpyrifos, malathion, hexaconazole, and atrazine were 1.42, 1.43, 1.35, and 1.33 µg/kg, respectively. Finally, the method was successfully applied for the determination of the pesticides in green and roasted coffee bean samples, and the obtained recoveries were in the range of 74-113% for spiked samples. The prepared sorbent could be used for the magnetic dispersive micro-solid phase extraction of pesticides in the plant-derived food matrix.

The True Value of Spirulina.

Algae products are attracting growing interest due to their pleasant taste and their high contents in protein, essential amino acids, vitamins, and minerals. Specifically, spirulina products are widely promoted for their high vitamin B12 content. So far, knowledge regarding the contamination with cyanotoxins, heavy metals, pesticides, or polycyclic aromatic hydrocarbons (PAHs) is scarce, although some studies reported high contaminant levels in spirulina products. The regular intake of spirulina, and very likely other algae products as well, as a dietary supplement in the gram range demands a closer monitoring of potentially harmful constituents.

Monoterpenes: Essential Oil Components with Valuable Features.

Medicinal plants have a wide range of secondary metabolites including monoterpene. These volatile compounds are the main components of essential oils, belonging to the isoprenoid group and possessing valuable features for plants and humans. This review provides comprehensive information on chemical structures and classification of monoterpenes. It describes their biosynthesis pathways and introduces plant families and species rich in noteworthy monoterpenes. Bio-activities, pharmacological and pesticide effects as well as their mechanism of action are reported. Applications of these compounds in various industries are also included.

Fluorescence assay for three organophosphorus pesticides in agricultural products based on Magnetic-Assisted fluorescence labeling aptamer probe.

There has been increasing recent concern about the agricultural use of organophosphorus pesticides. A rapid and sensitive fluorescence assay for the detection of three organophosphorus pesticides has therefore been developed using 6-carboxy-fluorescein labeling aptamer as the probe and functionalized magnetic nanoparticles as the separation carrier. The aptamer hybridized with complementary DNA conjugated on the surface of the magnetic nanoparticles to form a magnetic aptamer-complementary DNA complex. Upon introducing the target organophosphorus pesticide, the aptamer departed from the complementary DNA, resulting in the fluorescence signal. Under optimized conditions, the limits of detection (LODs, S/N = 3) for trichlorfon, glyphosate, and malathion were 72.20 ng L-1, 88.80 ng L-1, and 195.37 ng L-1, respectively. The method was applied for the detection of trichlorfon, glyphosate, and malathion in spiked lettuce and carrot samples. The recoveries were in the range of 79.4%-118.7%, which were in good agreement with those obtained by gas chromatography, and the relative standard deviations were also acceptable. The method therefore has high sensitivity, so provides a means for the detection of multiple organophosphorus pesticides.

Evaluation of biological activities, and exploration on mechanism of action of matrine-cholesterol derivatives.

To develop new potential pesticides, a series of matrine-cholesterol derivatives were prepared by modifications of two non-food bioactive products matrine and cholesterol. Two N-phenylsulfonylmatrinic esters (5i and 5j) showed the most potent insecticidal activity against Mythimna separata Walker. Two N-benzylmatrinic esters (5e and 5g) exhibited the most promising aphicidal activity against Aphis citricola Van der Goot. Especially compound 5e showed good control effects in the greenhouse against A. citricola. Some interesting results of their structure-activity relationships were also observed. By reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis of HMG-CoA reductase in apterous adults of A. citricola, it demonstrated that matrine and cholesterol may be the HMG-CoA reductase inhibitors, and the hydroxyl of cholesterol or the lactam ring of matrine may be important for acting with HMG-CoA reductase in A. citricola.

Potential Risk to Pollinators from Nanotechnology-Based Pesticides.

The decline in populations of insect pollinators is a global concern. While multiple factors are implicated, there is uncertainty surrounding the contribution of certain groups of pesticides to losses in wild and managed bees. Nanotechnology-based pesticides (NBPs) are formulations based on multiple particle sizes and types. By packaging active ingredients in engineered particles, NBPs offer many benefits and novel functions, but may also exhibit different properties in the environment when compared with older pesticide formulations. These new properties raise questions about the environmental disposition and fate of NBPs and their exposure to pollinators. Pollinators such as honey bees have evolved structural adaptations to collect pollen, but also inadvertently gather other types of environmental particles which may accumulate in hive materials. Knowledge of the interaction between pollinators, NBPs, and other types of particles is needed to better understand their exposure to pesticides, and essential for characterizing risk from diverse environmental contaminants. The present review discusses the properties, benefits and types of nanotechnology-based pesticides, the propensity of bees to collect such particles and potential impacts on bee pollinators.

Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes.

Herbal-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum), is often used for the treatment of liver diseases. However, serious concerns exist regarding the efficacy, composition, as well as the safety of these over-the-counter preparations. Therefore, the aim of the present study was to investigate the composition as well as chemical and biological safety of 26 milk thistle-based dietary supplements purchased from both the U.S. and Czech markets between 2016 and 2017. The study was focused on a determination of the composition of active ingredients, as well as analyses of possible contaminants including: mycotoxins, plant alkaloids, and pesticide residues, as well as the microbial purity. High-throughput analyses were performed using advanced U-HPLC-HRMS techniques. Large differences in the silymarin content were observed among individual milk thistle preparations, often in contrast with the information provided by the manufacturers. In addition, substantial inter-batch differences in silymarin content were also demonstrated. In all milk thistle preparations tested, large numbers and high concentrations of mycotoxins and several pesticides, as well as the substantial presence of microbiological contamination were detected, pointing to serious safety issues. In conclusion, our results strongly indicate the need for strict controls of the composition, chemical contaminants, as well as the microbiological purity of commercial milk thistle extracts used for the treatment of liver diseases. Poor definition of these preparations together with contamination by biologically active substances may not only account for the inconsistency of clinical observations, but also be responsible for possible herbal-based dietary supplements-induced liver injury.