Residue analysis, dissipation patterns of chlorfenapyr, diafenthiuron and their corresponding metabolites in tea trees, and dietary intake risk assessment.

BACKGROUND: Recently, chlorfenapyr and diafenthiuron have been widely used to prevent and control diseases and pests in tea production. However, rare studies have investigated the dissipation patterns of chlorfenapyr, diafenthiuron and their metabolites simultaneously in tea matrices. Here, we established an analytical method to investigate the degradation patterns of five target compounds in tea shoots and made tea samples. Moreover, the dietary intake risk assessment of chlorfenapyr-diafenthiuron mixture among Chinese populations was evaluated based on the supervised field experiment. RESULTS: The mean recoveries of the primary analytes at five spiking levels were between 95.6% and 112.6% in tea shoots and made tea, respectively, and the values of RSD (relative standard deviation) were lower than 9.7% for all the target analytes. The field trial results showed that the half-lives of chlorfenapyr and diafenthiuron based on the residue definition were 10.0-12.4 days and 4.3-5.9 days, respectively, in tea shoots. For the dietary intake risk assessment, the risk quotient (RQ) values in made tea ranged from 30.4% to 73.9% at the pre-harvest interval of 14 days, which were significantly less than 100%. CONCLUSION: The accuracy and precision of the developed method were satisfied by the measurement requirements according to the validation results. The dynamic dissipation experiments suggested that diafenthiuron was much easier to dissipate than chlorfenapyr. Moreover, the existence of tralopyril made the half-life of chlorfenapyr significantly increase, indicating that practical application of chlorfenapyr should take careful consideration of its metabolite. Finally, the potential chronic dietary risks of the chlorfenapyr-diafenthiuron mixture to human communities were within the acceptable range. © 2022 Society of Chemical Industry.

A Fatal Case of Chlorfenapyr Poisoning and the Therapeutic Implications of Serum Chlorfenapyr and Tralopyril Levels.

Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient's signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

Environmentally relevant concentrations of tralopyril affect carbohydrate metabolism and lipid metabolism of zebrafish (Danio rerio) by disrupting mitochondrial function.

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. However, there is little information available on the toxicity of tralopyril to aquatic organisms. In this study, the effect of TP on carbohydrate and lipid metabolism, and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. Adverse modifications in carbohydrate metabolism were observed in larvae: hexokinase (HK) activity, succinate dehydrogenase (SDH) activity, and adenosine triphosphate (ATP) content were significantly decreased; and transcript expression of genes (GK, HK1, and PCK1) was also significantly changed. Changes of TG content, FAS activity and transcript expression of genes (ACO, ehhadh, and fas) indicate that TP disrupt lipid metabolism in zebrafish larvae. The change in expression of genes (ndufs4, Sdhα, and uqcrc2) involved in the mitochondrial respiratory complexes, and genes (polg1 and tk2) involved in the mitochondrial DNA replication and transcription indicates that these adverse effects on carbohydrate and lipid metabolism are caused by mitochondrial dysfunction.

Vectorizing Pro-Insecticide: Influence of Linker Length on Insecticidal Activity and Phloem Mobility of New Tralopyril Derivatives.

To improve the proinsecticidal activity and phloem mobility of amino acid-tralopyril conjugates further, nine conjugates were designed and synthesized by introducing glutamic acid to tralopyril, and the length of the linker between glutamic acid and tralopyril ranged from 2 atoms to 10 atoms. The results of insecticidal activity against the third-instar larvae of P. xylostella showed that conjugates 42, 43, 44,and 45 (straight-chain containing 2-5 atoms) exhibited good insecticidal activity, and their LC50 values were 0.2397 ± 0.0366, 0.4413 ± 0.0647, 0.4400 ± 0.0624, and 0.4602 ± 0.0655 mM, respectively. The concentrations of conjugates 43-45 were higher than that of conjugate 42 in the phloem sap at 2 h, and conjugate 43 showed the highest concentration. The introduction of glutamic acid can improve phloem mobility. The in vivo metabolism of conjugates 42 and 43 was investigated in P. xylostella, and the parent compound tralopyril was detected at concentrations of 0.5950 and 0.3172 nmol/kg, respectively. According to the above results, conjugates 42 and 43 were potential phloem mobile pro-insecticide candidates.

Effects of introducing theanine or glutamic acid core to tralopyril on systemicity and insecticidal activity.

Tralopyril was the active agent of a pro-insecticide chlorfenapyr. To simultaneously solve the problems of the phytotoxicity and non-systemic insecticidal activity of tralopyril, four new tralopyril conjugates containing theanine or glutamic acid moieties were designed and synthesized. Their phytotoxicity to tea shoot, phloem systemicity, and insecticidal activity were evaluated. Phytotoxic symptoms were not observed after the tea shoots were exposed to the four conjugates at concentrations of 2mM. The phloem mobility test on Ricinus communis L. seedlings confirmed that all four conjugates were mobile in the sieve tubes. Results of insecticidal activity against the third-instar larvae of Plutella xylostella showed that only conjugate 20 exhibited activity with an LC50 value of 0.5882±0.0504mM. After root application to tea seedlings, conjugate 20 showed obviously systemic insecticidal activity against Dendrothrips minowai Priesner, while chlorfenapyr showed no attribute of that. A new conjugate as potential phloem mobile pro-insecticide candidate was provided and so a novel strategy of pro-insecticide for improved phloem systemicity was proposed.

Influence of Pyranose and Spacer Arm Structures on Phloem Mobility and Insecticidal Activity of New Tralopyril Derivatives.

Six new conjugates were designed and synthesized by introducing glucose, methyl glucuronate or glucuronic acid moieties on tralopyril. Phytotoxicity and phloem mobility results demonstrated that the introduction of glucose, methyl glucuronate or glucuronic acid moieties can simultaneously solve the tough phytotoxicity problem and phloem mobility transformation of tralopyril. Conjugates 12 and 18 containing the glucuronic acid moiety exhibited higher phloem mobility than conjugates 9, 11, 15 and 17. Conjugates 15, 17 and 18 with methoxymethyl groups on the tralopyril pyrrole nitrogen atom showed activity against Plutella xylostella, while conjugates 9, 11 and 12 with a methene group on the pyrrole N showed no activity. Cabbage roots were incubated in a buffered solution containing conjugates 15, 17 and 18 at 4 mM for 72 h. Only 18 showed systemic insecticidal activity with 100% mortalityagainst P. xylostella, while 15 and 17 showed lower activity andchlorfenapyr showed no activity. The glucuronic acid promoiety imparted more phloem mobility to tralopyril than glucose and methyl glucuronate. The methoxymethyl group bond on the tralopyril skeleton was the key factor in determining the insecticidal activity of the conjugates. A promising systemic proinsecticide containing glucuronic acid and tralopyril moieties was proposed.

Chlorfenapyr poisoning: a systematic review.

INTRODUCTION: Chlorfenapyr, a N-substituted halogenated pyrrole, is a broad-spectrum insecticide. The insecticidal activity of chlorfenapyr depends on its biotransformation by hepatic cytochrome P450 monooxygenases to tralopyril, which uncouples mitochondrial oxidative phosphorylation and disrupts adenosine triphosphate production. Neither the metabolism of chlorfenapyr nor the mechanism of tralopyril is completely elucidated. Acute human chlorfenapyr poisoning is not well characterized, and best practice in management following acute exposure is unclear. The purpose of this review is to characterize acute human chlorfenapyr poisoning by its clinical course, laboratory investigations, and imaging findings and propose a management plan for acute human chlorfenapyr exposure. METHODS: We systematically searched PubMed, Web of Science, Google Scholar, and EMBASE from inception to April 2024 across all languages for human chlorfenapyr and tralopyril cases, with descriptions of exposure, clinical manifestations, and clinical course included. Only manuscripts and abstracts from scientific conferences with sufficient clinical data following acute human exposures were included. In vitro studies, animal studies, agricultural studies, environmental impact studies, and non-clinical human studies were excluded. We then reviewed citations of included studies for additional eligible publications. Non-English publications were translated using Google Translate or primarily translated by our authors. The study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. RESULTS: We identified 3,376 publications of which 48 met study inclusion criteria, describing 75 unique cases of human poisoning from ingestion, inhalation, dermal exposure, and intra-abdominal injection of chlorfenapyr. No cases of tralopyril exposure were identified. The median time from exposure to symptom onset was six hours (interquartile range 1-48 hours). The most frequent initial or presenting signs/symptoms included diaphoresis, nausea and/or vomiting, and altered mental status. While hyperthermia (≥38 degrees centigrade) was less common at presentation, hyperthermia developed in 61 percent of all patients and was temporally associated with clinical deterioration and death. Most common laboratory abnormalities included elevated blood creatine kinase activity, hepatic aminotransferase activities, and lactate concentration. Imaging studies of the central nervous system often showed extensive symmetrical white matter abnormalities with swelling. Case fatality was 76 percent, and survivors commonly experienced sustained neurological sequelae. Management strategies were highly varied, and the effectiveness of specific medical interventions was unclear. DISCUSSION: Acute human chlorfenapyr poisoning is characterized by a latent period as long as 14 days, deterioration over hours to days, and can result in serious morbidity and mortality. Development of hyperthermia, likely driven by oxidative phosphorylation uncoupling by tralopyril, is an ominous clinical sign and is temporally associated with clinical decompensation and death. Laboratory abnormalities, particularly elevated creatine kinase activity, hepatic aminotransferase activities, and lactate concentration, were common, but only creatine kinase activity differed amongst survivors and fatalities. Best clinical practice in the management of patients exposed to chlorfenapyr is unclear, and we opine that a conservative approach with close clinical monitoring and supportive care is prudent. LIMITATIONS: The limitations of all reviews include their inherent retrospective and observational nature as well as publication bias that emphasizes severe outcomes, thus impacting the spectrum of illness and skewing mortality percentage. In addition, we interrogated a finite number of databases for publications on human chlorfenapyr exposure and there were limited cases with laboratory testing to confirm chlorfenapyr poisoning. Analysis of our systematic review was not powered to detect differences between groups, comparative statistics were not performed, and significance is not reported. CONCLUSIONS: Acute human chlorfenapyr toxicity is characterized by a latent period following exposure, development of new or progression of established signs/symptoms, potential for critical illness, rapid deterioration, serious morbidity, and mortality. A conservative approach to patient management is prudent.

Tralopyril poisoning due to respiratory exposure.

INTRODUCTION: Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via inhalation. CASE PRESENTATIONS: Two workers developed heat intolerance, diaphoresis, and weight loss after occupational inhalational exposure to tralopyril. Patient 1: The exposure was due to the absence of respiratory protection. Magnetic resonance imaging showed abnormal signals in the bilateral periventricular white matter, corpus callosum, basal ganglia, brainstem, and spinal cord. The patient's blood tralopyril concentrations on days 1, 3, 5, 8, and 11 post-admission were 1.09 mg/L, 1.04 mg/L, 1.01 mg/L, 0.71 mg/L, and 0.313 mg/L, respectively. Haemoperfusion (HA330), haemoperfusion (HA380), and haemodiafiltration were performed on days 1-3, 5-8, and 9-10, respectively. Patient 2: The patient's symptoms followed inappropriate use of respiratory protection. His blood tralopyril concentrations on days 1, 4, 5, and 6 were 0.592 mg/L, 0.482 mg/L, 0.370 mg/L, and 0.228 mg/L, respectively. DISCUSSION: The patients presented with features typical of chlorfenapyr poisoning, which suggests that tralopyril is the main toxic metabolite of chlorfenapyr. CONCLUSION: Tralopyril can be absorbed by inhalation, leading to delayed clinical symptoms and organ damage, including toxic encephalopathy and spinal cord damage.

Residue and dietary intake risk assessment of lufenuron and chlorfenapyr and its corresponding metabolite in cabbage under field conditions.

A simple, low-cost, and highly sensitive method using a modified QuECHERS procedure based on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) was established to simultaneously quantify lufenuron and chlorfenapyr and the corresponding metabolite tralopyril in cabbage for the first time. On the basis of this method, terminal residue and dietary risk of lufenuron and chlorfenapyr in cabbage were investigated. The recoveries of lufenuron, chlorfenapyr, and tralopyril ranged from 88 to 110%, with relative standard deviation of less than 12.4%. The field trial results showed that at the pre-harvest interval (PHI) of 21 days, the terminal residues of lufenuron, chlorfenapyr, and tralopyril in the supervised trials were not higher than 0.02 mg/kg, and the highest detected residue levels of lufenuron, chlorfenapyr, and tralopyril were 0.047, 0.055, and <0.02 mg·kg-1 at 14-day pre-harvest respectively, which were lower than the maximum residue limits (MRLs) for cabbage established in China. For the dietary risk assessment, the national estimated daily intakes (NEDIs) as proportion of acceptable daily intakes (ADIs) were 80.4% and 29.9% for chlorfenapyr and lufenuron respectively indicating an acceptable dietary risk to Chinese population.

The fate and potential hazards of chlorfenapyr and one metabolite tralopyril in cabbages: A comprehensive investigation.

The potential hazards of chlorfenapyr warrant attention owing to its widespread application on vegetables. A comprehensive investigation of the fate of chlorfenapyr in the ecosystem is imperative. This paper presents a method for detecting chlorfenapyr and tralopyril in cabbages, which exhibits good linearity (determination coefficients > 0.99) and satisfactory recoveries (82.50 %-108.03 %). Chlorfenapyr residues in cabbages demonstrate a positive correlation with its application dose and time. Tralopyril can inhibit the dissipation of chlorfenapyr, as evidenced by the half-lives of 5.67-11.14 d (chlorfenapyr) and 6.91-14.77 d (total chlorfenapyr). The results of terminal residues (<2.0 mg/kg) and dietary risk assessment (<100 %) suggest preharvest intervals of 14 d (greenhouse) and 10 d (open-field). Additionally, the uptake of chlorfenapyr in cabbages is limited (translocation factor < 1), while the downward translocation predominantly occurs through phloem transport. The findings provide valuable insights for understanding the fate and potential risks of chlorfenapyr in cabbages.

Long-term tralopyril exposure results in endocrinological and transgenerational toxicity: A two-generation study of marine medaka (Oryzias melastigma).

This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 µg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.

Design, synthesis, insecticidal activities and translocation of amino acid-tralopyril conjugates as vectorizing agrochemicals.

BACKGROUND: Conjugating amino acid moieties to active ingredients has been recognized as an effective method for improving the precise targeting of the active form to the specific site. Based on the vectorization strategy, a series of amino acid-tralopyril conjugates were designed and synthesized as novel proinsecticide candidates, with the potential capability of root uptake and translocation to the foliage of crops. RESULTS: Bioassay results showed excellent insecticidal activities of some conjugates, in particular, the conjugates 6b, 6e, and 7e, against the diamondback moth (Plutella xylostella), with equivalent insecticidal activity to chlorfenapyr (CFP). Importantly, conjugate 6e exhibited significantly higher in vivo insecticidal activity against P. xylostella than CFP. Furthermore, the systemic test experiments with Brassica chinensis demonstrated that conjugates 6e and 7e could be transported to the leaves, in contrast to CFP, which remained in the root. CONCLUSION: This study demonstrated the feasibility of amino acid fragment conjugation as a vectorization strategy for transporting non-systemic insecticides into the leaves of B. chinensis while maintaining in vivo insecticidal activity. The findings also provide insights for subsequent mechanism studies on the uptake and transport of amino acid-insecticide conjugates in plants. © 2023 Society of Chemical Industry.

Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism.

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.

Chronic exposure to tralopyril induced abnormal growth and calcium regulation of turbot (Scophthalmus maximus).

Tralopyril is an emerging marine antifouling agent with limited data on its effects on fish growth and calcium regulation. To determine the changes induced by long-term exposure to tralopyril, multi-levels (such as molecular, biochemical, and individual levels) responses were measured in turbot at different concentrations (1 µg/L, 20 µg/L). The results showed that 1 µg/L mainly affected the immune response, while 20 µg/L affected the synthesis and metabolism of steroids and fat. However, different concentrations of tralopyril affected the synthesis, secretion and action of parathyroid hormone and growth hormone. The expression of GH/IGF axis gene and the level of growth hormone increased significantly, leading to abnormal growth. The energy tradeoff between immunity and growth at 1 µg/L tralopyril pressure may inhibit growth. The change of Ca2+ level was accompanied by the disturbance of PTH-related gene expression. The results of molecular docking showed that the disturbance of Ca2+ regulation might be attributed to the inhibition of vitamin D receptor by tralopyril, which affected the vitamin D signaling pathway. This study provides scientific data for the in-depth understanding and risk assessment of the toxicological effects of tralopyril and reveals the potential threat of tralopyril to environmental health.

Effects of tralopyril on histological, biochemical and molecular impacts in Pacific oyster, Crassostrea gigas.

Recently, the toxic effects of tralopyril, as a new antifouling biocide, on aquatic organisms have aroused widespread attention about the potential toxicity. However, the mechanism of tralopyril on marine mollusks has not been elaborated clearly. In this study, the histological, biochemical and molecular impacts of tralopyril on adult Crassostrea gigas were investigated. The results indicated that the 96 h LC50 of tralopyril to adult Crassostrea gigas was 911 µg/L. After exposure to tralopyril (0, 40, 80 and 160 µg/L) for 6 days, the mantle mucus secretion coverage ratio of Crassostrea gigas was increased with a dose-dependent pattern. Catalase (CAT) activity was significantly increased, amylase (AMS) activity, acid phosphatase (ACP) activity and calcium ion (Ca2+) concentration significantly decreased. Meanwhile, integrated biomarker responses (IBR) index suggested that higher concentrations of tralopyril caused severer damage to Crassostrea gigas. In addition, the mRNA expression levels of biomineralization related genes in the mantle were significantly upregulated. Collectively, this study firstly revealed the histological, biochemical and molecular impacts of tralopyril exposure on adult Crassostrea gigas, which provided new insights for understanding the toxicity of tralopyril in marine mollusks.

Effects of ocean acidification and tralopyril on bivalve biomineralization and carbon cycling: A study of the Pacific Oyster (Crassostrea gigas).

The combined effects of emerging pollutants and ocean acidification (OA) on marine organisms and marine ecosystems have attracted increasing attention. However, the combined effects of tralopyril and OA on marine organisms and marine ecosystems remain unclear. In this study, Crassostrea gigas (C. gigas) were exposed to tralopyril (1 µg/L) and/or OA (PH = 7.7) for 21 days and a 14-day recovery acclimation. To investigate the stress response and potential molecular mechanisms of C. gigas to OA and tralopyril exposure alone or in combination, as well as the effects of OA and/or tralopyril on bivalve biomineralization and marine carbon cycling. The results showed that the combined toxicity was between that of acidification and tralopyril alone. Single or combined exposure activated the general stress defense responses of C. gigas mantle, affected energy metabolism and biomineralization of the organism and the carbon cycle of the marine ecosystem. Moreover, acidification-induced and tralopyril-induced toxicity showed potential recoverability at molecular and biochemical levels. This study provides a new perspective on the molecular mechanisms of tralopyril toxicity to bivalve shellfish and reveals the potential role of tralopyril and OA on marine carbon cycling.

Effects of short-term exposure to tralopyril on physiological indexes and endocrine function in turbot (Scophthalmus maximus).

Tralopyril is an emerging marine antifouling agent with potential toxic effects on non-target aquatic organisms. To evaluate the toxicity of tralopyril, to turbot (Scophthalmus maximus), we assessed biomarkers, including oxidative stress, neurotoxicity, and osmotic homeostasis regulation enzymes, after a 7-day exposure to tralopyril (5 µg/L, 15 µg/L, 30 µg/L). Superoxide dismutase activity was significantly decreased at 30 µg/L, and Ca2+-Mg2+-ATPase activity in the gills was significantly increased at 15 µg/L and 30 µg/L. No statistically significant differences in the responses of acetylcholinesterase and nitric oxide were detected. In addition, 15 µg/L and 30 µg/L tralopyril induced hyperthyroidism, reflected by significantly increased of T3 levels. The expression levels of hypothalamus-pituitary-thyroid axis-related genes were also upregulated. The molecular docking results showed that the thyroid system disruption was not caused by competitive binding to the receptor. In addition, the integrated biomarker response index showed that 15 µg/L tralopyril had the greatest effect on turbot. In general, tralopyril caused oxidative damage, affected energy metabolism, and interfered with the endocrine system. These findings could provide reference data for assessing the ecological risk of tralopyril in marine environments.

Determination of Market, Field Samples, and Dietary Risk Assessment of Chlorfenapyr and Tralopyril in 16 Crops.

The frequent and massive use of chlorfenapyr has led to pesticide residues in crops, threatening food safety and human health. However, there is limited research on the detection of tralopyril, which is the major metabolite of chlorfenapyr with high toxicity. This study aimed to develop a novel, sensitive, and highly efficient method for the determination of chlorfenapyr and tralopyril residues in 16 crops. The optimized purification procedure provided satisfactory recovery of 76.6-110%, with relative standard deviations of 1.3-11.1%. The quantification values of pesticides in crop matrixes were all 0.01 µg kg-1. The optimal method was adopted to determine the chlorfenapyr and tralopyril residues in field trials in 12 regions in China and monitor their residues in 16 agricultural products. The results of the dissipation and terminal residue experiments show that the final residue of chlorfenapyr was less than MRL (maximum residue limit) and no tralopyril was detected in the field samples. Moreover, the qualification proportion of these residues in market samples were up to 99.5%. The RQ (risk quotient) values of chlorfenapyr and chlorfenapyr with consideration of tralopyril were both apparently lower than an RQ of 100%, indicating an acceptable level. This research provides a thorough long-term dietary risk evaluation on chlorfenapyr and tralopyril and would provide reference for their scientific and safe utilization.

Bioaccumulation, Metabolism and the Toxic Effects of Chlorfenapyr in Zebrafish (Danio rerio).

Chlorfenapyr is widely used as an insecticide/miticide. Tralopyril, the active metabolite of chlorfenapyr, is used as an antifouling biocide in antifouling systems, and negatively affects aquatic environments. However, it is unclear whether tralopyril is a metabolite of chlorfenapyr in aquatic vertebrates, and there is little data on the bioaccumulation and toxicity of chlorfenapyr to aquatic vertebrates. In this study, the bioaccumulation and elimination of chlorfenapyr in zebrafish were assessed, and tralopyril, the active metabolite of chlorfenapyr, was determined. The effects of chronic exposure to chlorfenapyr on zebrafish liver and brain oxidative damage, apoptosis, immune response, and metabolome were investigated. These results showed that chlorfenapyr has a high bioaccumulation in zebrafish, with bioaccumulation factors of 864.6 and 1321.9 after exposure to 1.0 and 10 µg/L chlorfenapyr for 21 days, respectively. Chlorfenapyr at these concentrations also rapidly accumulated in zebrafish, reaching 615.5 and 10336 µg/kg on the second and third days of exposure, respectively. Chlorfenapyr was degraded to tralopyril in zebrafish; therefore, both chlorfenapyr and tralopyril should be considered when evaluating the risk of chlorfenapyr to aquatic organisms. In addition, chronic exposure caused oxidative damage, apoptosis, and immune disorders in zebrafish liver. Chronic exposure also altered the levels of endogenous metabolites in liver and brain. After 9 days of depuration, some indicators of oxidative damage, apoptosis, and immunity returned to normal levels, but the concentration of endogenous metabolites in zebrafish liver was still altered. Overall, these results provide useful information for evaluating the toxicity and environmental fate of chlorfenapyr in aquatic vertebrates.

Tralopyril induces developmental toxicity in zebrafish embryo (Danio rerio) by disrupting the thyroid system and metabolism.

Tralopyril, an antifouling biocide, widely used in antifouling systems to prevent underwater equipment from biological contamination, which can pose a potential risk to aquatic organisms and human health. However, there is little information available on the toxicity of tralopyril to aquatic organisms. Herein, zebrafish (Danio rerio) were used to investigate the toxicity mechanisms of tralopyril and a series of developmental indicators, thyroid hormones, gene expression and metabolomics were measured. Results showed that tralopyril significantly decreased the heart-beat and body length of zebrafish embryos-larvae exposed to 4.20 µg/L or higher concentrations of tralopyril and also induced developmental defects including pericardial hemorrhage, spine deformation, pericardial edema, tail malformation and uninflated gas bladder. Tralopyril decreased the thyroid hormone concentrations in embryos and changed the transcriptions of the related genes (TRHR, TSHß, TSHR, Nkx2.1, Dio1, TRα, TRß, TTR and UGT1ab). Additionally, metabolomics analysis showed that tralopyril affected the metabolism of amino acids, energy and lipids, which was associated with regulation of thyroid system. Furthermore, this study demonstrated that alterations of endogenous metabolites induced the thyroid endocrine disruption in zebrafish following the tralopyril treatment. Therefore, the results showed that tralopyril can induce adverse developmental effects on zebrafish embryos by disrupting the thyroid system and metabolism.