Daphnia magna reveals contrasting effects of copper hydroxide nanopesticides and copper chloride in mixtures with commercial pesticide formulations.

This study investigated the occurrence, dissipation, and dietary risks of four pesticides (difenoconazole (DIF), prochloraz (PRO), spinosad (SPI), dinotefuran (DIN)) and their metabolites in pomegranates through nationwide field trials across six Chinese production regions. Results indicated that SPI and DIN dissipated within 7–14 days, while DIF and PRO had longer half-lives (4.91–12.90 days). All pesticide residues remained confined to peels without penetrating arils. Terminal residues were below China’s MRLs. While deterministic and probabilistic risk assessments confirmed acceptable acute and chronic risks from pomegranate consumption alone (%ARfD: 0.09–17.66%; %ADI: 0.21–17.65%), comprehensive multi-crop dietary assessment revealed unacceptable chronic exposure risks for children aged under 11 years (%ADI: 56.1–155%). The non-carcinogenic risk (%HQ) for PRO from pomegranate consumption was 2.1–21.0%, indicating acceptable safety. The study provides data for safe pesticide use while highlighting the urgent need to protect vulnerable pediatric populations from cumulative pesticide exposure across multiple food sources.

Rice sheath blight, caused by Rhizoctonia solani (R. solani) poses a significant threat to global rice production. Although prochloraz (PRO) is an effective fungicide, its poor photostability and low water solubility severely limit its field performance. We developed a sustainable, stimuli-responsive delivery system to enhance PRO efficacy and minimize environmental risks. Multilayered mesoporous nanoparticles (MSN@PMO) were synthesized via a hard-template route and converted into hollow periodic mesoporous organosilicas (H-PMO) by sodium carbonate etching. PRO was encapsulated in H-PMO and sealed with pectin, yielding a dual pH/pectinase responsive formulation (Pec@PRO-H-PMO, PPHP). PPHP exhibited sustained release for 144 h under acidic and enzymatic conditions, and showed markedly improved photostability, foliar adhesion and rainfastness compared with PRO technical concentrate (PRO TC) and PRO water emulsion (PRO EW). Bioassays demonstrated that PPHP exhibited 1.8 times greater antifungal activity against R. solani compared to PRO TC. Ecotoxicological analysis revealed 11.9 times higher zebrafish median lethal concentration (LC₅₀) values than PRO TC over 80% viability of human bronchial epithelial (BEAS-2B) cells at 18.4 mg/L, suggesting improved biosafety. The dual pH/pectinase triggered release of PPHP enhanced pesticide utilization and improved safety. This strategy presents a novel approach for developing stimuli-responsive pesticide delivery systems, aiming to strengthen crop disease control efficiency and mitigate environmental risks. © 2025 Society of Chemical Industry.

The pathogen Alternaria alternata infects a variety of plants and crops, notably poplars, and results in large financial losses. Using twelve chemical fungicides for fungicide sensitivity tests (FSTs) on A. alternata, the result showed that prochloraz (PCZ), mancozeb (MZ), and fludioxonil (FLU) have potent inhibitory effects against the pathogen through different mechanisms. To investigate how the pathogen responded to fungicide-induced stress, transcriptome and physiological investigations were carried out after treatments with three fungicides at their corresponding 50% effective concentration (EC50) doses. The MZ treatment produced a distinct genetic response; FLU treatment produced the greatest number of differentially expressed genes (DEGs), followed by PCZ. DEGs from FLU treatment were mostly engaged in ribosome biosynthesis, those from MZ treatment in lipid and carbohydrate metabolism, and those from PCZ treatment in carbohydrate metabolism, according to Gene Ontology (GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that FLU and PCZ treatments were associated with ribosome biogenesis, whereas MZ treatment was linked to the pyruvate metabolic pathway. Collinear trend analysis indicates that MZ exhibits a unique pattern, with FLU treatment causing the most significant overexpression of genes, followed by PCZ. The six categories of 88 elevated DEGs associated with fungal resistance include tyrosinase, ATP-binding cassette (ABC) transporters, major facilitator superfamily (MFS) transporters, antioxidant and cellular resilience genes, as well as genes involved in cell wall and membrane biosynthesis. Notably, the pathways involved in the synthesis of melanin and ergosterol exhibited the strongest response to FLU. The results of a correlation analysis between physiological indices and resistance-related genes indicated that melanin content, malondialdehyde (MDA) content, and tyrosinase activity were positively correlated with the majority of resistance-related DEGs, whereas soluble protein content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were negatively correlated, which is consistent with the observed trends in the measured physiological indicators. Taken together, this study provides a theoretical basis for developing more effective fungicides and chemical control strategies against A. alternata.

Degradable mesoporous organosilicon nanoparticles coated with chitosan-Cu2+ complexes with dual stimulus-response for efficient prochloraz delivery.

Mixture toxic mechanism of phoxim and prochloraz in the hook snout carp Opsariichthysbidens

Azole fungicides are highly suspected endocrine disruptors (EDs) and are frequently detected in surface water. Among them, there are prochloraz (PCZ), a commonly used moleculefor ED studies, and imazalil (IMZ), a highly suspected ED. Little is known about their toxicokinetic (TK) behavior in fish. Hence, research suggested that an improved risk assessment could be achieved by gaining insight into their TK behavior. The aim of this study is to understand and model the TK of both substances in different fish species, irrespective of the scheme of exposure. TK data from the literature were retrieved including different modes of exposure (per os and waterborne). In addition, two experiments on zebrafish exposed to either IMZ or PCZ were performed to address the lack of in vivo TK data. A physiologically based kinetic (PBK) model applied to IMZ and PCZ was developed, capable of modeling different exposure scenarios. The parameters of the PBK model were simultaneously calibrated on datasets reporting internal concentration in several organs in three fish species (original and literature datasets) by Bayesian methods (Monte Carlo Markov Chain). Model predictions were then compared to other experimental data (i.e., excluded from the calibration step) to assess the predictive performance of the model. The results strongly suggest that PCZ and IMZ are actively transported across the gills, resulting in a small fraction being effectively absorbed by the fish. The model's results also confirm that both molecules are extensively metabolized by the liver into mainly glucuronate conjugates. Overall, the model performances were satisfying, predicting internal concentrations in several key organs. On average, 90% of experimental data were predicted within a two-fold range. The PBK model allows the understanding of IMZ and PCZ kinetics profiles by accurately predicting internal concentrations in three different fish species regardless of the exposure scenario. This enables a proper understanding of the mechanism of action of EDs at the molecular initiating event (MIE) by predicting bioaccumulation in target organs, thus linking this MIE to a possible adverse outcome.

Carrier-free self-assembled nanoparticles based on prochloraz and fenhexamid for reducing toxicity to aquatic organism

Joint toxic mechanism of clothianidin and prochloraz in the earthworm (Eisenia fetida)

Precious metal-based Catalytic Membrane Reactors for continuous flow catalytic hydrodechlorination

Toxic interactions at the physiological and biochemical levels of green algae under stress of mixtures of three azole fungicides

Optimization of assay conditions to quantify ECOD activity in vivo in individual Daphnia magna. Assay performance evaluation with model CYP 450 inducers/inhibitors

Carbendazim (CBZ) and prochloraz (PCZ) are broad-spectrum fungicides used in agricultural peat control. Both fungicides leave large amounts of residues in fruits and are toxic to non-target organisms. However, the combined toxicity of the fungicides to non-target organisms is still unknown. Therefore, we characterized the toxic effects of dietary supplementation with CBZ, PCZ, and their combination for 90days in 6-week-old male Institute of Cancer Research (ICR) mice. CBZ-H (100mg/kg day), PCZ-H (10mg/kg day), and their combination treatments increased the relative liver weights and caused liver injury. The serum total cholesterol (TC), triglyceride (TG), glucose (Glu), pyruvate (PYR), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were reduced, and synergistic toxicity was observed. Hepatic transcriptome revealed that 326 differentially expressed genes (DEGs) of liver were observed in the CBZ treatment group, 149 DEGs in the PCZ treatment group, and 272 DEGs in the combination treatment group. According to KEGG enrichment analysis, the fungicides and their combination affected lipid metabolism, amino acid metabolism, and ferroptosis. In addition, the relative mRNA levels of key genes involved in lipid metabolism were also examined. Compared with individual exposure, combined exposure to CBZ and PCZ caused a more obvious decrease in the expression of some genes related to glycolipid metabolism. Furthermore, the relative mRNA levels of some key genes in the combination treatment group were lower than those in the CBZ and PCZ treated groups. In summary, CBZ, PCZ, and their combination generally caused hepatotoxicity and glycolipid metabolism disorders, which could provide new insights for investigating the combined toxicity of multiple fungicides to animals.

Interactive transgenerational effects of parental co-exposure to prochloraz and chlorpyrifos: Disruption in multiple biological processes and induction of genotoxicity

Application of catalytic hydrodechlorination for the fast removal of chlorinated azole pesticides in drinking water

The development of stimuli-responsive controlled release formulations is a potential method of improving pesticide utilization efficiency and alleviating current pesticide-related environmental pollution. In this study, a self-destruction redox-responsive pesticide delivery system using biodegradable disulfide-bond-bridged mesoporous organosilica (DMON) nanoparticles as the porous carriers and coordination complexes of gallic acid (GA) and Fe(III) ions as the capping agents were established for controlling prochloraz (PRO) release. The GA-Fe(III) complexes deposited onto the surface of DMON nanoparticles could effectively improve the light stability of prochloraz. Due to the decomposition of GA-Fe(III) complexes, the nano-vehicles had excellent redox-responsive performance under the reducing environments generated by the fungus. The spreadability of PRO@DMON-GA-Fe(III) nanoparticles on the rice leaves was increased due to the hydrogen bonds between GA and rice leaves. Compared with prochloraz emulsifiable concentrate, PRO@DMON-GA-Fe(III) nanoparticles showed better fungicidal activity against Magnaporthe oryzae with a longer duration under the same concentration of prochloraz. More importantly, DMON-GA-Fe(III) nanocarriers did not observe obvious toxicity to the growth of rice seedlings. Considering non-toxic organic solvents and excellent antifungal activity, redox-responsive pesticide controlled release systems with self-destruction properties have great application prospects in the field of plant disease management.

Triazole and imidazole fungicides represent an emerging class of pollutants with endocrine-disrupting properties. Concerning mammalian reproduction, a possible causative role of antifungal compounds in inducing toxicity has been reported, although currently, there is little evidence about potential cooperative toxic effects. Toxicant-induced oxidative stress (OS) may be an important mechanism potentially involved in male reproductive dysfunction. Thus, to clarify the molecular mechanism underlying the effects of azoles on male reproduction, the individual and combined potential of fluconazole (FCZ), prochloraz (PCZ), miconazole (MCZ), and ketoconazole (KCZ) in triggering in vitro toxicity, redox status alterations, and OS in mouse TM4 Sertoli cells (SCs) was investigated. In the present study, we demonstrate that KCZ and MCZ, alone or in synergistic combination with PCZ, strongly impair SC functions, and this event is, at least in part, ascribed to OS. In particular, azoles-induced cytotoxicity is associated with growth inhibitory effects, G0/G1 cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) generation, imbalance of the superoxide dismutase (SOD) specific activity, glutathione (GSH) depletion, and apoptosis. N-acetylcysteine (NAC) inhibits ROS accumulation and rescues SCs from azole-induced apoptosis. PCZ alone exhibits only cytostatic and pro-oxidant properties, while FCZ, either individually or in combination, shows no cytotoxic effects up to 320 µM.

Transcriptomic and targeted metabolomic analysis revealed the toxic effects of prochloraz on larval zebrafish

Human cytochrome P450 3A-mediated two-step oxidation metabolism of dimethomorph: Implications in the mechanism-based enzyme inactivation

Background and Aims: Prochloraz (PCZ) is an imidazole fungicide which is used in agriculture and gardening. PCZ, with endocrine disrupting effect, disrupts reproductive and developmental functions. Previously, the effects of PCZ on the estrogen and androgen receptors have been shown in vitro and in vivo. Because of endocrine disrupting effects, PCZ could influence nuclear receptors which acted as ER and AR antagonists. Besides, PCZ has been thought to have no genotoxic effects. Therefore, we aimed to investigate possible effects of PCZ on nuclear receptor genes and epigenetic mechanisms in human prostate carcinoma (PC-3) cells. Methods: In the present study, MTT and LDH tests were applied to evaluate the cell viability. Expression levels of nuclear receptor genes such as AhR, PXR, PPARα, PPARγ were studied on real-time quantitative PCR. For global DNA methylation analysis, the levels of 5-methylcytosine (5-mC%) were measured by elisa kit. Results: According to MTT and LDH test results, IC50 value of PCZ has been determined as 144.19 and 116.65 μM, respectively. There were significant changes for the expression levels of AhR, PPARα and PPARγ genes after 5-50 μM of PCZ treatments. 5 and 50 μM of PCZ decreased the levels of 5-mC% in the rates of 22.6% and 26.9%, respectively. Conclusion: It has been suggested that PCZ may cause alterations on the expressions of nuclear receptor genes which could be related to endocrine disrupting effects and may have implications on global DNA methylation.