Genotoxic mode of action and threshold exploration of 2-methyl furan under 120-day sub-chronic exposure in male Sprague-Dawley rats.

2-Methylfuran (2-MF) is an important member of the furan family generated during food thermal processing. An in-vivo multiple endpoint genotoxicity assessment system was applied to explore the genotoxic mode of action and threshold of 2-MF. Male Sprague-Dawley rats received 2-MF by oral gavage at doses of 0.16, 0.625, 2.5, and 10 mg/kg.bw/day for 120 days. An additional 15 days were granted for recovery. The Pig-a gene mutation frequency of RET and RBC showed significant increases among the 2-MF groups on day 120. After a 15-day recovery period, the Pig-a gene mutation frequency returned to levels similar to those in the vehicle control. The tail intensity (TI) values of peripheral blood cells at a dose of 10 mg/kg.bw/day significantly increased from day 4 and remained at a high level after the recovery period. No statistical difference was found in the micronucleus frequency of peripheral blood between any 2-MF dose group and the corn oil group at any timepoint. 2-MF may not induce the production of micronuclei, but it could cause DNA breakage. It could not be ruled out that 2-MF may accumulate in vivo and cause gene mutations. Hence, DNA, other than the spindle, may be directly targeted. The mode of action of 2-MF may be that it was metabolized by EPHX1 to more DNA-active metabolites, thus leading to oxidative and direct DNA damage. The point of departure (PoD) of 2-MF-induced genotoxicity was derived as 0.506 mg/kg bw/day.

Human biomonitoring of dioxins, furans, and non-ortho dioxin-like polychlorinated biphenyls (PCBs) in blood plasma from Old Crow, Yukon, Canada (2019).

Dioxins, furans, and dioxin-like polychlorinated biphenyls (PCBs) are a group of persistent and toxic chemicals that are known to have human health effects at low levels. These chemicals have been produced for commercial use (PCBs) or unintentionally as by-products of industry or natural processes (PCBs, dioxins, and furans). Additionally, dioxin-like PCBs were formerly used in electrical applications before being banned internationally (2004). These chemicals are widely dispersed in the environment as they can contaminate air and travel hundreds to thousands of kilometers before depositing on land or water, thereafter, potentially entering food chains. Community concerns surrounding the safety of traditional foods prompted a human biomonitoring project in Old Crow, Yukon Territory (YT), Canada (2019). Through collaborative community engagement, dioxins and like compounds were identified as a priority for exposure assessment from biobanked samples. In 2022, biobanked plasma samples (n = 54) collected in Old Crow were used to measure exposures to seven dioxins, ten furans, and four dioxin-like PCBs. 1,2,3,6,7,8-HxCDD, 1,2,3,7,8,9-HxCDD, 1,2,3,4,6,7,8-HpCDD, OCDD, 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF, PCB 126, and PCB 169 were detected in at least 50 % of samples. Among these analytes, the only congener at elevated levels was PCB 169, which was approximately ∼2-fold higher than the general population of Canada. No significant sex-based or body mass index (BMI) differences in biomarker concentrations were observed. Generally, the concentrations of the detected congeners increased with age, except for 1,2,3,4,6,7,8-HpCDD. For the first time, this research measures dioxin and like-compound exposures in Old Crow, advancing the information available on chemical exposures in the Arctic. Further research could be directed towards the investigation of PCB 169 exposure sources and temporal monitoring of exposures and determinants.

Mechanism-based cytotoxicity trend prediction of furan-containing pollutants present in a mixture.

Human exposure to furan-containing pollutants (FCPs) has raised concerns due to their high risk of toxicity. A substantial number of approximately 8500 recorded compounds containing a furan ring exist which have been analytically or in biologically studied. A significant portion of these compounds is found in the everyday environments of individuals, particularly when ingested through food. Consequently, there is a need for a universal approach to rapidly predict the potential toxicity trends of FCPs. In this study, we developed a bromine labeling-based platform that combines LC-ICP-MS and LC-ESI-MS techniques to absolutely quantify FCP-induced protein adduction. The LC-ESI-MS approach facilitated the identification of FCP-derived protein adducts and optimized liquid chromatographic conditions for analyte separation. By employing a well-designed bromine-containing compound as a general internal standard, LC-ICP-MS-based technique enabled to absolutely assess bromine-labeled protein adduction. The protein adduction efficiencies of furan, 2-methylfuran, and 2,5-dimethylfuran were found to be 2.68, 2.90, and 0.37 molecules per 10,000 FCP molecules that primary hepatocytes received, respectively. Furthermore, we observed that 2-methylfuran exhibited the highest cytotoxicity, followed by furan and 2,5-dimethylfuran, which aligned with the order of their protein adduction. Thus, the protein adduction efficiency of FCPs could serve as a potential index for predicting their toxicity trends.

Ecotoxicological assessment of biomass-derived furan platform chemicals using aquatic and terrestrial bioassays.

An environmental toxicological assessment of fourteen furanic compounds serving as valuable building blocks produced from biomass was performed. The molecules selected included well studied compounds serving as control examples to compare the toxicity exerted against a variety of highly novel furans which have been additionally targeted as potential or current alternatives to biofuels, building blocks and polymer monomers. The impact of the furan platform chemicals targeted on widely applied ecotoxicity model organisms was determined employing the marine bioluminescent bacterium Aliivibrio fischeri and the freshwater green microalgae Raphidocelis subcapitata, while their ecotoxicity effects on plants were assessed using dicotyledonous plants Sinapis alba and Lepidium sativum. Regarding the specific endpoints evaluated, the furans tested were slightly toxic or practically nontoxic for A. fischeri following 5 and 15 min of exposure. Moreover, most of the building blocks did not affect the growth of L. sativum and S. alba at 150 mg L-1 for 72 h of exposure. Specifically, 9 and 11 out of the 14 furan platform chemicals tested were non-effective or stimulant for L. sativum and S. alba respectively. Given that furans comprise common inhibitors in biorefinery fermentations, the growth inhibition of the specific building blocks was studied using the industrial workhorse yeast Saccharomyces cerevisiae, demonstrating insignificant inhibition on eukaryotic cell growth following 6, 12 and 16 h of exposure at a concentration of 500 mg L-1. The study provides baseline information to unravel the ecotoxic effects and to confirm the green aspects of a range of versatile biobased platform molecules.

Role of covalent modification by hepatic aldehydes in dictamnine-induced liver injury.

Dictamnine is a representative furan-containing hepatotoxic compound. Administration of dictamnine caused acute liver injury in mice and the metabolic activation of furan to reactive epoxy intermediate was responsible for the hepatotoxicity. This study aimed to characterize the protein adduction by endogenous hepatic aldehydes and investigate its role in dictamnine-induced hepatotoxicity. In the liver sample of dictamnine-treated mice, the protein adduction by five aldehydes was characterized as lysine residue-aldehyde adducts using high-resolution UPLC-Q/Orbitrap MS after exhaustive proteolytic digestion. The levels of protein adduct were increased at 2-3 h after the treatment with dictamnine. The formation of protein adduction increased with increasing doses of dictamnine. Inhibition of the bioactivation by CYP3A inhibitor ketoconazole prevented the protein adduction. Treatment with 2,3-dihydro-dictamnine, an analog of dictamnine that was unable to form the epoxy intermediate, did not lead to an increase in protein adduction. Application of aldehyde dehydrogenase-2 activator ALDA-1 or nucleophilic trapping reagent N-acetyl-L-lysine significantly reduced the protein adduction and attenuated dictamnine-induced liver injury without affecting the bioactivation. In conclusion, the metabolic activation of the furan ring of dictamnine resulted in the protein adduction by multiple hepatic aldehydes and the protein modification played a crucial role in dictamnine-induced liver injury.

Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

To reduce reliance on long-term in vivo studies, short-term data linking early molecular-based measurements to later adverse health effects is needed. Although transcriptional-based benchmark dose (BMDT) modeling has been used to estimate potencies and stratify chemicals based on potential to induce later-life effects, dose-responsive epigenetic alterations have not been routinely considered. Here, we evaluated the utility of microRNA (miRNA) profiling in mouse liver and blood, as well as in mouse primary hepatocytes in vitro, to indicate mechanisms of liver perturbation due to short-term exposure of the known rodent liver hepatotoxicant and carcinogen, furan. Benchmark dose modeling of miRNA measurements (BMDmiR) were compared to the referent transcriptional (BMDT) and apical (BMDA) estimates. These analyses indicate a robust dose response for 34 miRNAs to furan and involvement of p53-linked pathways in furan-mediated hepatotoxicity, supporting mRNA and apical measurements. Liver-sourced miRNAs were also altered in the blood and primary hepatocytes. Overall, these results indicate mechanistic involvement of miRNA in furan carcinogenicity and provide evidence of their potential utility as accessible biomarkers of exposure and disease.

Neurotoxicity of furan in juvenile Wistar rats involves behavioral defects, microgliosis, astrogliosis and oxidative stress.

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells.

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 µM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity.

The role of microRNAs in the toxic mechanisms of furan and 3-MCPD and links to cancer risk - a review.

Contaminants formed during food processing are of increasing concern to public and food safety experts, as well as international risk assessment organizations. The emergence of 'omic' technologies (e.g. genomics and transcriptomics) have greatly increased the mechanistic knowledge of the toxicity associated with these compounds, and consequently have provided a better understanding of their potential adverse effects. Of note, microRNAs (miRNAs) have emerged as being of key importance during the development of cancer as well as being associated with food-processing contaminants. MiRNAs have been demonstrated to trigger toxic processes in hepatic and renal tissues due to exposure to toxic compounds such as furan and 3-monochloropropane-1,2-diol (3-MCPD), respectively. In this review, we consider the roles of miRNAs in the toxicity process and the challenges that lay ahead in order to translate this knowledge to the benefit of industrial food processing.

Theoretical study on the degradation mechanism, kinetics and toxicity for aqueous ozonation reaction of furan derivatives.

The compounds including furan-2,5-dicarboxylic acid (FDCA), 2-methyl-3-furoic acid (MFA), and 2-furoic acid (FA), containing Furan ring are considered to be possessing high ozone reactivity, although in depth studies of their ozonation processes have not been carried out yet. Hence, mechanism, kinetics and toxicity by quantum chemical, and their structure activity relationship are being investigated in this study. Studies of reaction mechanisms revealed that during the ozonolysis of three furan derivatives containing C=C double bond, furan ring opening occurs. At temperature (298 K) and pressure of 1 atm, the degradations rates of 2.22 × 103 M-1 s-1 (FDCA), 5.81 × 106 M-1 s-1 (MFA) and 1.22 × 105 M-1 s-1 (FA) suggested that the reactivity order is: MFA > FA > FDCA. In the presence of water, oxygen and ozone, the Criegee intermediates (CIs) as the primary products of ozonation would produce lower molecule weight of aldehydes and carboxylic acids by undergoing degradation pathways. The aquatic toxicity reveals that three furan derivatives play green chemicals roles. Significantly, most of the degradation products are least harmful to organisms residing in the hydrosphere. The mutagenicity and developmental toxicity of FDCA is minimum as compared to FA and MFA, which shows the applicability of FDCA in a wider and broader field. Results of this study reveal its importance in the industrial sector and degradation experiments.

Eriodictyol attenuates Furan induced testicular toxicity in Rats: Role of oxidative stress, steroidogenic enzymes and apoptosis.

Furan (C4H4O) is a naturally occurring organic compound. It develops as a result of the thermal processing of food and stimulates critical impairments in male reproductive tract. Eriodictyol (Etyol) is a natural dietary flavonoid possessing diverse pharmacological potentials. The recent investigation was proposed to ascertain the ameliorative potential of eriodictyol against furan-instigated reproductive dysfunctions. Male rats (n = 48) were classified into 4 groups: untreated/control, furan (10 mg/kg), furan+ eriodictyol (10 mg/kg + 20 mg/kg) and eriodictyol (20 mg/kg). At the 56th day of the trial, the protective effects of eriodictyol were evaluated by assessing various parameters. Results of the study revealed that eriodictyol attenuated furan-induced testicular toxicity in the biochemical profile by increasing catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) along with glutathione reductase (GSR) activities, whereas reduced the reactive oxygen species (ROS) along with malondialdehyde (MDA) levels. It also restored the normal state of sperm motility, viability, the count of hypo-osmotic tail swelled sperm as well as epididymal sperm number along with reduced sperm anomalies (morphological) tail, mid-piece and head. Furthermore, it elevated the decreased levels of luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) as well steroidogenic enzymes (17ß-HSD, StAR protein & 3ß-HSD) and testicular anti-apoptotic marker (Bcl-2) expression, whereas, down-regulating apoptotic markers (Bax & Caspase-3) expression. Eriodictyol treatment also effectively mitigated the histopathological damages. The outcomes of the current study provide fundamental insights into the ameliorative potential of eriodictyol against furan-instigated testicular toxicity.

A biochemical and histology experimental approach to investigate the adverse effect of chronic lead acetate and dietary furan on rat lungs.

Despite lead widespread environmental pollution, its effect on humans and livestock's respiratory systems remains inadequately investigated. Similarly, furan is industrially relevant with enormous environmental presence. Lead and furan can be ingested -via lead pipes contaminated water and heat-treated food respectively. Thus, humans are inadvertently exposed continuously. Lead toxicity is well studied, and furan have earned a position on the IARC's list of carcinogens. Here, we evaluate the effect of co-exposure to lead and furan on rat lungs. Thirty Wistar rats were grouped randomly into six cohorts (n = 6) consisting of a control group, furan alone group, lead acetate (PbAc) alone group and three other groups co-exposure to graded PbAc (1, 10 & 100 µg/L) alongside a constant furan (8 mg/kg) dose. After twenty-eight days, enzymatic and non-enzymatic antioxidant, oxidative stress and inflammatory biomarkers were biochemically evaluated. The ELISA-based technique was used to measure oxidative-DNA damage (8-OHG), tumour protein 53 (TP53) expressed and tumour necrotic factor-alpha (TNF-α) level. Dose-dependent increases (p < 0.05) in reactive oxygen and nitrogen species, malondialdehyde, nitric oxide, myeloperoxidase, TNF-α and TP53 level, with an associated decrease (p < 0.05) in enzymatic and non-enzymatic antioxidants were observed in the furan, PbAc and the co-treated rats relative to the control. In addition, PbAc and furan treatment impaired the histoarchitectural structures of rat lungs, exemplified by pro-inflammatory cell infiltration and trafficking into the bronchioles and alveolar spaces. Co-exposure to furan and PbAc may contribute to lung dysfunction via loss of redox balance, genomic damage/instability, inflammation and disrupted histoarchitectural features.

Influence of furan and lead co-exposure at environmentally relevant concentrations on neurobehavioral performance, redox-regulatory system and apoptotic responses in rats.

Furan and lead are contaminants of global concern due to the potential public health threat associated with their exposure. Herein, the neurobehavioral performance, biochemical effects and histological alterations associated with co-exposure to furan (8 mg/kg) and lead acetate at low, environmentally realistic concentrations (1, 10 and 100 µg PbAc/L) for 28 uninterrupted days were investigated in rats. The results demonstrated that locomotor, motor and exploratory deficits associated with separate exposure to furan and lead was exacerbated in the co-exposed rats. Furan and lead co-exposure aggravated the marked decrease in acetylcholinesterase activity and antioxidant status, elevation in oxido-inflammatory stress indices and caspases activation in the cerebrum and cerebellum of exposed rats compared with control. Furan and lead co-exposure worsened neuronal degeneration as verified by histomorphometry and histochemical staining. Collectively, furan and lead acts together to exacerbate neurotoxicity via inhibition of cholinergic system, induction of oxido-inflammatory stress and caspases activation in rats.

Accidental lead in contaminated pipe-borne water and dietary furan intake perturbs rats' hepatorenal function altering oxidative, inflammatory, and apoptotic balance.

Inadvertent exposure to furan and Pb is associated with hepatorenal abnormalities in humans and animals. It is perceived that these two chemical species may work in synergy to orchestrate liver and kidney damage. Against this background, we investigated the combined effect of furan and incremental lead (Pb) exposure on hepatorenal dysfunction. Wistar rats (n = 30; 150 g) were treated for 28 days accordingly: Control; FUR (8 mg/kg), PbAc (100 µg/L), FUR + PbAc1 (8 mg/kg FUR + 1 µg/L PbAc); FUR + PbAc1 (8 mg/kg FUR + 10 µg/L PbAc), and FUR + PbAc1 (8 mg/kg FUR + 100 µg/L PbAc). Biomarkers of hepatorenal function, oxidative stress, inflammation, DNA damage, and apoptosis were examined. Furan and incrementally Pb exposure increased the levels of hepatorenal biomarkers and oxidative and pro-inflammatory mediators, including lipid peroxidation, reactive oxygen and nitrogen species, and interleukin-1 beta. Increased DNA damage, caspases- 9 and -3, and atypical histoarchitecture of the hepatorenal tissues exemplified furan and Pb treatment-related perturbations. Furthermore, the levels of antioxidants and IL-10 were also suppressed. Furan and Pb dose-dependently exacerbated hepatorenal derangements by altering the redox and inflammatory rheostats, worsened DNA damage, and related apoptotic onset that may potentiate hepatorenal disorders in humans and animals. The findings validate the synergistic effect of furan and Pb in the pathophysiology of kidney and liver disorders.

Toxicity, genotoxicity, and carcinogenicity of 2-methylfuran in a 90-day comprehensive toxicity study in gpt delta rats.

2-Methylfuran (2-MF) exists naturally in foods and is used as a flavoring agent. Furan, the core structure of 2-MF, possesses hepatocarcinogenicity in rodents. Accumulation of toxicological information on furan derivatives is needed to elucidate their carcinogenic mode of action. In the current study, we examined the comprehensive toxicological studies of 2-MF using gpt delta rats. 2-MF was intragastrically administered to groups of 10 male and 10 female Sprague-Dawley gpt delta rats at a dose of 0, 1.2, 6, or 30 mg/kg/day for 13 weeks. Effects of 2-MF on the hepatobiliary system including an increase in serum alkaline phosphatase were observed in the 6 and 30 mg/kg groups, and cholangiofibrosis was found in the 30 mg/kg group. The no observed adverse effect level was set at 1.2 mg/kg/day for both sexes and 1.14 mg/kg/day was determined as the benchmark dose low. The acceptable daily intake was calculated to be 11.4 µg/kg/day. Increases in the number and areas of glutathione S-transferase placental form-positive foci in the 30 mg/kg group were apparent, suggesting the hepatocarcinogenicity of 2-MF in rats. By contrast, the lack of increase in in vivo mutagenicity in the liver implied that 2-MF hepatocarcinogenesis may not involve genotoxic mechanisms.

Glycidamide and cis-2-butene-1,4-dial (BDA) as potential carcinogens and promoters of liver cancer - An in vitro study.

Acrylamide and furan are environmental and food contaminants that are metabolized by cytochrome P450 2E1 (CYP2E1), giving rise to glycidamide and cis-2-butene-1,4-dial (BDA) metabolites, respectively. Both glycidamide and BDA are electrophilic species that react with nucleophilic groups, being able to introduce mutations in DNA and perform epigenetic remodeling. However, whereas these carcinogens are primarily metabolized in the liver, the carcinogenic potential of acrylamide and furan in this organ is still controversial, based on findings from experimental animal studies. With the ultimate goal of providing further insights into this issue, we explored in vitro, using a hepatocyte cell line and a hepatocellular carcinoma cell line, the putative effect of these metabolites as carcinogens and cancer promoters. Molecular alterations were investigated in cells that survive glycidamide and BDA toxicity. We observed that those cells express CD133 stemness marker, present a high proliferative capacity and display an adjusted expression profile of genes encoding enzymes involved in oxidative stress control, such as GCL-C, GSTP1, GSTA3 and CAT. These molecular changes seem to be underlined, at least in part, by epigenetic remodeling involving histone deacetylases (HDACs). Although more studies are needed, here we present more insights towards the carcinogenic capacity of glycidamide and BDA and also point out their effect in favoring hepatocellular carcinoma progression.

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds.

Furan-containing compounds are abundant in nature, and many, but not all, have been found to be hepatotoxic and carcinogenic. The furan ring present in the chemical structures may be one of the domineering factors to bring about the toxic response resulting from the generation of reactive epoxide or cis-enedial intermediates, which have the potential to react with biomacromolecules. This review sets out to explore the relationship between the metabolic activation and hepatotoxicity of furan-containing compounds on the strength of scientific reports on several typical alkylated furans, synthetic pharmaceuticals, and components extracted from herbal medicines. The pharmacological activities as well as concrete evidence of their liver injuries are described, and the potential toxic mechanisms were discussed partly based on our previous work. Efforts were made to understand the development of liver injury and seek solutions to prevent adverse effects. SIGNIFICANCE STATEMENT: This review mainly elucidates the vital role of metabolic activation in the hepatotoxicity of furan-containing compounds through several typical chemicals studied. The possible mechanisms involved in the toxicities are discussed based on collective literatures as well as our work. Additionally, the structural features responsible for toxicities are elaborated to predict toxicity potentials of furan-containing compounds. This article may assist to seek solutions for the occurring problems and prevent the toxic effects of compounds with furan(s) in clinical practice.

Bromuconazole caused genotoxicity and hepatic and renal damage via oxidative stress process in Wistar rats.

Bromuconazole is a triazole pesticide used to protect vegetables and fruits against diverse fungi pathologies. However, its utilization may be accompanied by diverse tissue injuries. In this study, we evaluated the biochemical and histopathological modifications, and we analyzed genotoxic and oxidative stress, in the aim to examine bromuconazole effects in the liver and kidney. We subdivided animals into four groups, each one contains six adult male Wistar rats. Untreated rats received daily a corn oil (vehicle) orally. Three oral bromuconazole doses were tested (1, 5, and 10 % of LD50) daily for 28 days. Bromuconazole increased the plasma activities of alkaline phosphatase, lactate dehydrogenase, and transaminases. It also increased the plasma levels of creatinine and uric acid. Histopathological check showed that bromuconazole caused organ damage. This study makes known that bromuconazole caused conspicuous DNA damage either in hepatic or kidney tissues, with a significant increase in the levels of malondialdehyde and protein carbonyl followed by an enhancement in catalase and superoxide dismutase enzymatic activities, and these increases are in a dose-dependent manner. In other side, we found that Glutathione-S-transferase and peroxidase activities raised. Our outcomes highlight that bromuconazole exposure induced genotoxic damage and organ damage which may be caused by the disturbances of oxidative stress statue in the liver and kidney.