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Lindane (LDN) is a well-known herbicidal drug that exerts deleterious impacts on vital body organs including the liver. Catechin (CTN) is a plant-based flavonoid that demonstrates various pharmacological abilities. This trial was executed to evaluate the ameliorative efficacy of CTN to combat LDN instigated hepatotoxicity in male albino rats (Rattus norvegicus). Thirty-two rats were categorized into four groups including control, LDN (30 mg/kg), LDN (30 mg/kg) + CTN (40 mg/kg) and CTN (40 mg/kg) alone treated group. It was observed that LDN dysregulated the expressions of PI3K/PIP3/Akt and Nrf-2/Keap-1 pathway. Moreover, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme‑oxygenase-1 (HO-1) and glutathione reductase (GSR) were subsided after LDN intoxication. Besides, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), ALT (Alanine aminotransferase), AST (Aspartate transaminase), Gamma-glutamyl transferase (GGT) and ALP (Alkaline phosphatase) were increased whereas reduced the levels of albumin and total proteins in response to LDN exposure. Additionally, LDN administration escalated the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, the gene expressions of Bcl-2-associated X protein (Bax) and Cysteinyl aspartate-acid proteases-3 (Caspase-3) were enhanced whereas the expression of B-cell lymphoma-2 (Bcl-2) was lowered following the LDN treatment. LDN instigated various histological impairments in hepatic tissues. Nonetheless, concurrent administration of CTN remarkably ameliorated liver impairments via regulating aforementioned disruptions owing to its antioxidant, anti-apoptotic and histo-protective potentials., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lindane is a broad-spectrum insecticide widely used on fruits, vegetables, crops, livestock and on animal premises to control the insects and pests. The extensive use of pesticides and their residues in the soil and water typically join the food chain and thus accumulate in the body tissues of human and animals causing severe health effects. The study was designed to determine the toxicity effects of sub-lethal concentrations of lindane on hemato-biochemical profile and histo-pathological changes in Rohu (Labeo rohita). A significant increase in the absolute (p<0.05) and relative (p<0.05) weights was observed along with severe histo-pathological alterations in liver, kidneys, gills, heart and brain at 30μg/L and 45μg/L concentration of lindane. A significant (p<0.05) decrease in RBCs count, PCV and Hb concentration while a significant (p<0.05) increased leukocytes were observed by 30μg/L and 45μg/L concentrations of lindane at 45 and 60 days of the experiment. Serum total protein and albumin were significantly (p<0.05) decreased while hepatic and renal enzymes were significantly (p<0.05) increased due to 30μg/L and 45μg/L concentrations of lindane at days-45 and 60 of experiment compared to control group. The observations of thin blood smear indicated significantly increased number of erythrocytes having nuclear abnormalities in the fish exposed at 30μg/L and 45μg/L concentrations of lindane. ROS and TBARS were found to be significantly increased while CAT, SOD, POD and GSH were significantly decreased with an increase in the concentration and exposure time of lindane. The results showed that lindane causes oxidative stress and severe hematological, serum biochemical and histo-pathological alterations in the fish even at sub-lethal concentrations., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Afzal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persistent organic pollutants (POPs), which encompass pesticides and industrial chemicals widely utilized across the globe, pose a covert threat to human health. β-hexachlorocyclohexane (β-HCH) is an organochlorine pesticide with striking stability, still illegally dumped in many countries, and recognized as responsible for several pathogenetic mechanisms. This study represents a pioneering exploration into the neurotoxic effects induced by the exposure to β-HCH specifically targeting neuronal cells (N2a), microglia (BV-2), and C57BL/6 mice. As shown by western blot and qPCR analyses, the administration of β-HCH triggered a modulation of NF-κB, a key factor influencing both inflammation and pro-inflammatory cytokines expression. We demonstrated by proteomic and western blot techniques epigenetic modifications in H3 histone induced by β-HCH. Histone acetylation of H3K9 and H3K27 increased in N2a, and in the prefrontal cortex of C57BL/6 mice administered with β-HCH, whereas it decreased in BV-2 cells and in the hippocampus. We also observed a severe detrimental effect on recognition memory and spatial navigation by the Novel Object Recognition Test (NORT) and the Object Place Recognition Task (OPRT) behavioural tests. Cognitive impairment was linked to decreased expression of the genes BDNF and SNAP-25, which are mediators involved in synaptic function and activity. The obtained results expand our understanding of the harmful impact produced by β-HCH exposure by highlighting its implication in the pathogenesis of neurological diseases. These findings will support intervention programs to limit the risk induced by exposure to POPs. Regulatory agencies should block further illicit use, causing environmental hazards and endangering human and animal health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Decades after most countries banned hexachlorocyclohexane, HCH isomers still pollute the environment. Many studies described HCH as a pro-diabetic factor; nevertheless, the effect of HCH isomers on pancreatic beta-cells remains unexplored. This study investigated the effects of a one-month exposure to α-HCH, β-HCH, and γ-HCH on protein expression in human (NES2Y) and rat (INS1E) pancreatic beta-cell lines. α-HCH and γ-HCH increased proinsulin and insulin levels in INS1E cells, while β-HCH showed the opposite trend. α-HCH altered the expression of PKA, ATF3, and PLIN2. β-HCH affected the expression of GLUT1, GLUT2, PKA, ATF3, p-eIF2α, ATP-CL, and PLIN2. γ-HCH altered the expression of PKA, ATF3, PLIN2, PLIN5, and IDH1. From the tested proteins, PKA, ATF3, and PLIN-2 were the most sensitive to HCH exposure and have the potential to be used as biomarkers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Stress responses of fish to disruption of oxygen homeostasis include adjusted oxygen consumption rate (MO 2 ) as well as the hyperventilation consisting of changes in breathing frequency (f v ) and amplitude (f ampl ). However, studying the HVR in very small organisms such as zebrafish (Danio rerio) embryos and larvae is challenging, and breathing movements (i.e., f v ) are usually manually counted, which is time- and human resource-intense, error-prone and does not provide information on the amplitude of breathing movements of the response, the breathing amplitude (f ampl ). Hence, in the present study, a new automated method was developed to simultaneously measure f v and f ampl in small zebrafish embryos and larvae with the computer software DanioScope™. To compare HVR strategies at different life-stages of zebrafish and the physiologically linked MO 2 , hatched 4 d old embryos and early gill-breathing 12 d old larvae were treated with the HVR-inducing neurotoxic compound lindane (γ-hexachlorocyclohexane; γ-HCH) as a model substance. Comparison of manually counted f v with f v data measured by DanioScope™ at both life-stages showed high to moderate agreement between the two methods with respect to f v in control fish and in fish treated with lower lindane concentrations (3 - 18% deviation at 25 µg/L γ-HCH). With increasing lindane concentrations (100 and 400 µg/L γ-HCH), however, manual counts showed an average underestimation of f v by up to 30%, mainly due to very fast, rapidly successive, and indistinct movements of the fish, which cannot be properly detected by manual counts. Automated measurement thus proved significantly more sensitive, although several pre- and post-processing steps are needed. The improved automated detection of f v and the first reliable estimation of f ampl in small fish embryos and larvae, as well as the inclusion of MO 2 , may provide new insights into different respiratory strategies and may, thus, represent a tool to lower the detection limit for reactions of different life-stages of fish to environmental stressors. In the present study, this became evident, as early gill-breathing 12 d old zebrafish larvae showed symptoms of respiratory failure (i.e., increase in f v , f ampl and MO 2 , followed by subsequent lethargy) after exposure to lindane, whereas skin-breathing in 4 d old embryos proved mainly insensitive to the paralytic effects of lindane., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of effective measures for the remediation of lindane contaminated sites is the need of the hour. In this study, a potent lindane degrading bacteria, identified as Rhodococcus rhodochrous NITDBS9 was isolated from an agricultural field of Odisha that could utilize up to 87% of 100 mg L -1 lindane when grown under liquid culture conditions in mineral salt media in 10 days. The bacteria could produce biofilm in lindane-containing media. Rhodococcus rhodochrous NITDBS9 was further characterized for its plant growth-promoting properties and it was found that the bacteria showed abilities for phytohormone, ammonia and biosurfactant production, etc. This could be beneficial for the bioremediation and improvement of crop production in contaminated sites. Ecotoxicity studies carried out for lindane, and its degradation products in mung bean and mustard seeds showed a reduction in toxicity of lindane after treatment with NITDBS9. NITDBS9 was used with a previously isolated potent lindane degrading strain Paracoccus sp. NITDBR1 in a dual mixed culture for the enhanced removal of lindane in the liquid system i.e. up to 93% in 10 days. Cytotoxicity studies were conducted with lindane before and after treatment with the single and dual mixed cultures on human skin fibroblast and HCT116 cell lines. They revealed a significant reduction in toxicity of lindane after it was bioremediated with the single and dual mixed cultures. Therefore, our proposed strategy could be efficiently used for the detoxification of the lindane-contaminated system, and further work should be done to study the use of these cultures in the contaminated soil system.

Objective: Aim: The aim of the research is to study the immunohistochemical markers of the endothelium of blood vessels and myocardial ventricles under chronic exposure to sodium bichromate and lindane, as well as in conjunction with damaging biochemical agents contained in the blood., Patients and Methods: Materials and Methods: The object of the experiment was outbred white mice (males). The study was carried out in 3 groups: 1st group - control, 2nd group - exposure to sodium bichromate 5 mg/kg, 3rd group - exposure to organochlorine pesticide lindane 100 mg/kg. In this experiment authors used the next methods: immunohistochemical method., biochemical research, statistical analysis., Results: Results: The data obtained from an experimental study show that the level of cardiomarkers in blood plasma is characterized by different changes when exposed to these two compounds. Basically, the predominance of the effect of sodium bichromate on the LDH level is noted as compared to the effect of lindane; on the CK-MB level, their effects were the same, i.e., there is an increase in their level in blood plasma., Conclusion: Conclusions: Thus, long-term exposure to sodium bichromate leads to the activation of angiogenesis, destruction of the integrity of the endothelium, and this, in turn, leads to reparative changes located around in the myocardial cells.

The discharge of lindane wastes in unlined landfills causes groundwater and soil pollution worldwide. The liquid waste generated (a mixture of 28 chlorinated organic compounds, COCs) constitutes a dense non-aqueous phase liquid (DNAPL) that is highly persistent. Although in situ chemical oxidation (ISCO) is effective for degrading organic pollutants, the low COCs solubility requires high reaction times. Simultaneous injection of surfactants and oxidants (S-ISCO) is a promising technology to solve the limitation of ISCO treatment. The current work studies the remediation of highly polluted soil (COCs = 3682 mg/kg) obtained at the Sardas landfill (Sabiñáñigo, Spain) by ISCO and S-ISCO treatments. Special attention is paid to acute soil toxicity before and after the soil treatment. Microtox®, modified Basic Solid-Phase Test (mBSPT) and adapted Organic Solvent Sample Solubilization Test (aOSSST) were used for this scope. Persulfate (PS, 210 mM) activated by alkali (NaOH, 210 mM) was used in both ISCO and S-ISCO runs. A non-ionic and biodegradable surfactant selected in previous work, Emulse®3 (E3, 5, and 10 g/L), was applied in S-ISCO experiments. Runs were performed in soil columns filled with 50 g of polluted soil, with eight pore volumes (Pvs) of the reagents injected and 96 h between successive Pv injections. The total treatment time was 32 days. The results were compared with those corresponding without surfactant (ISCO). After remediation treatments, soils were water-washed, simulating the conditions of groundwater flux in the subsoil. The treatments applied highly reduced soil toxicity (final soil toxicity equivalent to that obtained for non-contaminated soil, mBSPT) and organic extract toxicity (reduction > 95%, aOSSST). Surfactant application did not cause an increase in the toxicity of the treated soil, highlighting its suitability for full-scale applications.

A growing amount of evidence suggests that microbial diversity loss may have negative effects on soil ecosystem function. However, less attention has been paid to the determinants of the relationship between community diversity and soil functioning under pollution stress. Here we manipulated microbial diversity to observe how biotic and abiotic factors influenced soil multi-functions (e.g. lindane degradation, soil respiration and nutrient cycling). Results showed that protist community was more sensitive to dilution, pollution stress, and sodium acetate addition than bacterial and fungal community. Acetate addition accelerated the lindane removal. Any declines in microbial diversity reduced the specialized soil processes (NO 3 -N production, and N 2 O flux), but increased soil respiration rate. Dilution led to a significant increase in consumers-bacterial and fungi-bacterial interaction as evidenced by co-occurrence network, which possibly played roles in maintaining microbiome stability and resilience. Interestingly, pollution stress and resource availability weaken the relationship between microbial diversity and soil functions through the bottom-up trophic interaction and environmental preference of soil microbiome. Overall, this work provides experimental evidence that loss in microbial diversity, accompanied with changes in trophic interactions mediated biotic and abiotic factors, could have important consequences for specialized soil functioning in farmland ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to β-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lindane contamination in different environmental matrices has been a global concern for long. Bacterial consortia consisting of Paracoccus sp. NITDBR1, Rhodococcus rhodochrous NITDBS9, Ochrobactrum sp. NITDBR3, NITDBR4 and NITDBR5 were used for the bioremediation of soil artificially contaminated with lindane. The bacteria, Paracoccus sp. NITDBR1 and Rhodococcus rhodochrous NITDBS9, have been selected based on their lindane degrading capacity in liquid culture conditions (~80-90 %). The remaining three bacteria were chosen for their auxiliary properties for plant growth promotion, such as nitrogen fixation, phosphate solubilization, indole-3-acetic acid production and ammonia production under in vitro conditions. In this study, market wastes, mainly vegetable wastes, were added to the soil as a biostimulant to form a biomixture for assisting the degradation of lindane by bioaugmentation. Residual lindane was measured at regular intervals of 7 days to monitor the biodegradation process. It was observed that the consortium could degrade ~80% of 50 mg kg -1 lindane in soil which was further increased in the biomixture after six weeks of incubation. Bioassays performed on plant seeds and cytotoxicity studies performed on human skin fibroblast and HCT116 cell lines revealed that the groups contaminated with lindane and treated with the bacterial consortium showed lower toxicity than their respective controls without any bacteria. Hence, the use of both pesticide degrading and plant growth-promoting bacteria in a consortium can be a promising strategy for improved bioremediation against chemical pesticides, particularly in soil and agricultural fields, simultaneously enhancing crop productivity in those contaminated soil., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Organochlorine pesticide lindane in the environment and biota results in the potential risks on ecosystem and human health. Lindane can adversely affect the locomotion and nervous system, yet the potential neurotoxicity of lindane over generations remains uncertain. In this study, the neurotoxicity and underlying mechanisms in Caenorhabditis elegans (C. elegans) were investigated after parental (P0) exposure to lindane at environmentally relevant concentrations over generations. Exposure to lindane at concentrations of 10-100 ng/L significantly decreased body bends and head thrashes in P0 generation. Significant decrease of fluorescence labeled different neurotransmitters, and clear morphological changes by exposure to lindane at 10-100 ng/L suggested that lindane could induce the neuronal damage in C. elegans. During the transgenerational process, decreased locomotive behaviors were also observed in F1-F3 generations, and head thrashes returned to normal levels in F4 generation. Moreover, lindane exposure down-regulated the expression of dat-1, dop-1, glr-1 and mod-1genes, while up-regulated unc-30 gene in P0 generation, which recovered to normal levels in F4 generation. Interestingly, eat-4 continued to be regulated from inhibition to stimulation in P0-F4 generations, suggesting that glutamatergic transmission may more contribute to the neurotoxicity of lindane over generations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides., Methods: In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD., Results: Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein., Conclusions: This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The β-isomer of hexachlorocyclohexane (β-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of β-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating β-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting β-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from β-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

Widespread pollution of agricultural soil is posing great risks to food safety and human health. The absence of human health-based Generic Assessment Criteria (GAC) for agricultural land means Chinese farmers struggle to manage these risks efficiently and effectively. Cadmium (Cd) and hexachlorocyclohexane (HCH), two of the most concerned contaminants, demonstrate threshold toxicity meaning that background exposure (MDI oral ) is considered when deriving soil Generic Assessment Criteria (GAC). The CLEA (Contaminated Land Exposure Assessment) model was used to derive GAC for Cd and HCH that reflect differences in diet and soil characteristics across 19 provinces/cities. For both cadmium and alpha-HCH, Sichuan had the lowest GAC of 0.379 mg kg -1 and 0.0136 mg kg -1 , respectively, resulting from its significant high MDI oral values, which are approximately six to nine times larger than the average MDI oral for all the 19 provinces/cities. Jiangxi province had the highest GAC of 1.230 mg kg -1 and 0.0866 mg kg -1 , respectively, for cadmium and alpha-HCH, caused by its notable low MDI oral values and low vegetable consumption rate. Human health risk assessment based on regional GAC for Cd revealed that agricultural land with very high to high risks is located in southern China, while very low-risk land is located in northern China. For HCH, alpha- and gamma-HCH pose negligible health risks, but beta-HCH poses some health risk in some of the provinces/cities. When applying the regional GAC for beta-HCH, agricultural land in Beijing and Sichuan posed the highest risk, and those in Heilongjiang and Jiangxi had the lowest risk. This reflects the significant influence of background and vegetable consumption pathway on the GAC. Regional GACs could simplify and speed up risk assessment of agricultural land in different regions of China, by avoiding the need to calculate site-specific assessment criteria, thus saving time and money by avoiding over or under remediation., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Lindane, an organochlorine pesticide, causes detrimental impacts on the environment and human health owing to its high toxicity, low degradation, and bioaccumulation. Its toxic nature can be overcome by biological and eco-friendly approaches involving its degradation and detoxification. The biodegradation of lindane was assessed using actinobacterial species Thermobifida cellulosilytica TB100 (T. cellulosilytica), Thermobifida halotolerans DSM 44931 (T. halotolerans) and Streptomyces coelicolor A3 (S. coelicolor). The degradation conditions of Lindane such as pH, temperature, inoculum volume, glucose concentration and number of days were optimized under broth conditions. Lindane degradation at different concentrations was studied in soil using reverse phase-high performance liquid chromatography over a 30 day period. A bioassay test was performed on seeds of Lactuca sativa (Lettuce) to assess the success of bioremediated soil. Maximum lindane degradation in soil was observed using T. cellulosilytica sp. The degradation trend for different concentrations of lindane using T. halotolerans in sterilized soil was 55 mg kg -1 (82%) ˃ 155 mg kg -1 (75%) ˃ 255 mg kg -1 (70%) after an incubation period of 30 days. Lindane degradation in soil followed the first order reaction kinetics. Phytotoxicity test on seeds of Lactuca sativa showed considerably good vigor index values for the bioremediated sterilized and non-sterilized soil by T. cellulosilytica, T. halotolerans and S. coelicolor in comparison to the contaminated soil without bacteria. This confirms that these actinobacterial species can be implemented in bioaugmentation of contaminated sites to efficiently remediate high lindane concentrations., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The toxicity, volatility and persistence of the obsolete organochlorine pesticide hexachlorocyclohexane (HCH), makes reclamation of contaminated areas a priority for the health and welfare of neighboring human communities. Microbial diversity and functions and their relation to spontaneous vegetation in post-excavation situations, are essential indicators to consider in bioaugmentation or microbe-assisted phytoremediation strategies at field scale. Our study aimed to evaluate the effects of long-term HCH contamination on soil and plant-associated microbial communities, and whether contaminated soil has the potential to act as a bacterial inoculum in post-excavation bioremediation strategies. To scrutinize the role of vegetation, the potential nitrogen fixation of free-living and symbiotic diazotrophs of the legume Lotus tenuis was assessed as a measure of nutrient cycling functions in soil under HCH contamination. Potential nitrogen fixation was generally not affected by HCH, with the exception of lower nifH gene counts in excavated contaminated rhizospheres, most probably a short-term HCH effect on early bacterial succession in this compartment. HCH shaped microbial communities in long-term contaminated bulk soil, where we identified possible HCH tolerants such as Sphingomonas and Altererythrobacter. In L. tenuis rhizosphere, microbial community composition was additionally influenced by plant growth stage. Sphingobium and Massilia were the bacterial genera characteristic for HCH contaminated rhizospheres. Long-term HCH contamination negatively affected L. tenuis growth and development. However, root-associated bacterial community composition was driven solely by plant age, with negligible HCH effect. Results showed that L. tenuis acquired possible HCH tolerant bacteria such as the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade, Sphingomonas, Massilia or Pantoea which could simultaneously offer plant growth promoting (PGP) benefits for the host. Finally, we identified an inoculum with possibly HCH tolerant, PGP bacteria transferred from the contaminated bulk soil to L. tenuis roots through the rhizosphere compartment, consisting of Mesorhizobium loti, Neorhizobium galegae, Novosphingobium lindaniclasticum, Pantoea agglomerans and Lysobacter bugurensis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pakistan is an agro-economy country where hexachlorocyclohexane (HCH) pesticides are being used to improve crop productivity, as a result the risk of contamination of soil and sediment has been increased. HCH exhibits all the characteristics of persistent organic pollutants (POP), and was therefore added to the list of 'new POPs' in 2009. This review report revealed that the major rivers of Pakistan such as the Indus Basin, River Ravi, River Chenab and their tributaries all are contaminated with HCH and the highest residual concentration (4,090 ng/g) was detected in a pesticide burial ground in Hyderabad city. Major sources of HCH contamination were identified as agricultural runoff, discharge of untreated industrial effluents and surface runoff. In order to manage HCH pollution, various ex-situ and in-situ remediation techniques along with their merits and demerits are thoroughly reviewed. Among these, microbial bioremediation is a low cost, environment friendly, effective in-situ remediation technique for remediation of HCH. Overall, the information provided in this manuscript will provide a future reference to the scientific community and bridge the knowledge gap between HCH release in the environment and their mitigation through proper treatment methods.

Lindane persists in the environment and bioaccumulates as an organochlorine pesticide and can pose risks to ecological environments and human health. To explore the long-term toxicity and underlying mechanisms of lindane, Caenorhabditis elegans was chosen as an animal model for toxicological study. The indicators of physiological, oxidative stress and cell apoptosis were examined in nematodes chronically exposed to environmentally relevant concentrations of lindane (0.01-100 ng/L). The data suggested that exposure to lindane at doses above 0.01 ng/L induced adverse physiological effects in C. elegans. Significant increases of ROS production and lipofuscin accumulation were observed in 100 ng/L of lindane-exposed nematodes, suggesting that lindane exposure induced oxidative stress in nematodes. Exposure to 10-100 ng/L of lindane also significantly increased the average number of germ cell corpses, which indicated cell apoptosis induced by lindane in C. elegans. Moreover, chronic exposure to 100 ng/L lindane significantly influenced the expression of genes related to oxidative stress and cell apoptosis (e.g., isp-1, sod-3, ced-3, and cep-1 genes). These results indicated that oxidative stress and cell apoptosis could play an important role in toxicity induced by lindane in nematodes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A total of 90 wooden toys were collected, and six wood preservatives (chlorophenols and lindane) were analyzed by using gas chromatography-tandem mass spectrometry to assess the exposure risk of children to wood preservatives through oral contact with wooden toys. The detection rates of six preservatives ranged from 2.2% to 22.2%. The contents of the preservatives ranged from 0.6 µg/kg to 9.6 µg/kg. 2,4-Dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) had higher detection rates and contents than other preservatives. Thus, their migration behaviors from toys to saliva were further investigated. In 11 positive samples, the max migration ratios of 2,4-DCP and 2,4,6-TCP ranged from 7.1% to 20.3% and from 11.1% to 24.8%, respectively. For children aged 3-36 months, the daily average 2,4-DCP exposure level associated with wooden toys ranged from 2.7 pg/(kg day) to 46.9 pg/(kg day), and the daily average 2,4,6-TCP exposure ranged from 3.6 pg/(kg day) to 69.4 pg/(kg day). The contribution to exposure provided by the saliva mobilization pathway was more than that provided by the ingestion of scraped-off toys, and the exposure level of 2,4,6-TCP was greater than that of 2,4-DCP. The max hazard quotient for 2,4-DCP was 1.9 × 10 -4 , and the max cancer risk for 2,4,6-TCP was 1.2 × 10 -9 . The above results indicated that although wood preservatives were distributed in wooden toys, exposure arising from directly mouthing these materials currently does not pose unacceptable risks to children., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In the present study, chemical analysis of contaminants (three classes of organic pollutants and seven metals) and elutriate toxicity test were adopted to evaluate the potential environmental hazards of dredged sediment samples from five sites (SS1-5) along Huangpu River Channel (Shanghai Harbor, China). The metal Pb, Cu, Cr, Zn and the organic pollutants including total hexachlorocyclohexane (HCHs) and total dichlorodiphenyltrichloroethane (DDTs) in the five samples exceeded the threshold for effects level (TEL) to varying degrees. The probable effect concentration quotients (Q PECm ) of contaminants from the five dredged samples were all above 0.25, which means potential toxicity risks. Elutriate toxicity tests using medaka fish (Oryzias melastigma) and manila clam (Ruditapes philippinarum) showed that SS2 caused mortality to both species and SS1 caused mortality to fish. To explore the molecular biomarkers that may reflect the toxic effects, differential expressed genes were identified by RNA-Seq-based transcriptome profiling from the survived clams exposed to the two polluted elutriates (SS1, SS2). In clams exposed to SS1 and SS2 elutriate, 368 and 860 differential expressed genes (DEGs) were up-regulated, 199 and 1304 genes were down-regulated, respectively. Fourteen DEGs were selected from the enriched pathways that reflect cytotoxicity and responses to xenobiotics for the following quantitative real time PCR analysis. The transcriptomic profiling and the selected gene's expression patterns from clams exposed to SS1 and SS2 showed significant differences with the non-contaminated and control groups. Using the expression data of the selected gene battery in Factor Analysis allowed the discrimination between contaminated and non-contaminated sites and may reflect an influence gradient of sites. The development of the assay of these molecular biomarkers may provide a rapid and high-throughput tool for the quality assessment of the dredging sediments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although increased contact time (aging) of pesticides in the soil decreases their bioavailability, this does not mean that the bound residues formed during the aging process pose fewer risk to the soil environment. Here the earthworm Eisenia fetida was exposed to organochlorine pesticide lindane in soil under different durations of lindane aging and exposure. The results of de novo RNA sequencing followed by molecular and biochemical validations demonstrated the aged lindane showed a different tendency to disrupt acetylcholine (ACh) transmission with the effects of fresh lindane to gamma-aminobutyric acid. Using own-developed earthworm activity test, we confirmed aged lindane prompted earthworms to exclusively exhibit a significant hypoactivity in locomotion, which could be explained by the inhibition of Ach system. This study suggested that the toxicity of pesticides would not depend solely on their free state components, and the awareness of long-term environmental risks from the bound states needs to be raised., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lindane is a highly toxic organochlorine pesticide and widely exist in water with harmful effects on fish. Although some genes have been found to be regulated by lindane in fish, the transcriptional response of fish exposed to lindane is still unknown. In this research, the transcriptional changes of zebrafish larvae exposed to 0.2 mg/L lindane from 96 to 120 hpf were studied by RNA sequencing. Our transcriptome identified 554 up-regulated and 118 down-regulated genes and the differentially expressed genes were closely related to the neuromast development, RNA silencing genes, ion transport, and response to estrogen. In addition, we characterized two sensitive and novel lindane-induced ABCG (ATP binding cassette G subfamily) transporter genes- abcg5 and abcg8. Abcg5 and abcg8 genes are located on chromosome 13 of zebrafish and contain 1956/2024 bp open reading frame. The polypeptide deduced by CDS amplification contains 652/676 amino acids and has most of the functional domains and key residues defined in human and mouse ABCG5/Abcg5 or ABCG8/Abcg8. Only when the co-expression of Abcg5 and Abcg8 enable them to transport to the cell membrane surface in 293T cells. In addition, lindane can induce the transcriptional expression of abcg5 and abcg8 genes, and overexpression of Abcg5 and Abcg8 significantly reduced the toxicity of lindane to zebrafish larvae, which means that zebrafish Abcg5 and Abcg8 are potential efflux transporters of lindane. Therefore, these findings provide useful insights for further understanding the zebrafish larvae's transcriptional response and detoxification ability after acute exposure to lindane., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fetal and infant exposures to β-hexachlorocyclohexane (β-HCH) occur through placental and breastmilk transfers. No studies have examined the relationship between β-HCH and child intelligence quotient (IQ). This study examined associations between in utero β-HCH exposure and cognitive development in 7-year-old children. Data from women and children (n = 256) participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study were evaluated. We assessed exposure to β-HCH by measuring maternal serum concentration during pregnancy. We administered the Wechsler Intelligence Scale for Children (WISC), Fourth Edition, to children at age 7. Analyses were adjusted for maternal age, country of birth, work status, parity, and other pesticide exposures, language used for child cognitive assessment, and duration of breastfeeding. Higher serum β-HCH concentrations were associated with higher cognitive scores across all unadjusted models for the full-scale and sub-scale cognitive tests. In the adjusted models, a 10-fold increase in serum β-HCH concentration was associated with a 4.5-point increase in Working Memory IQ score (95% CI, 0.6 to 8.3; p = 0.02). We observed no significant interaction by length of breastfeeding or sex on associations. Our findings suggest that prenatal exposure to β-HCH is not adversely related to IQ at age 7 in a cohort of Mexican American children with fairly high exposure in utero as measured by maternal serum levels. Future research must replicate these findings in other study cohorts of women and children.

This paper focuses on the removal of lindane from soil washing effluents (SWEs) using combined electrochemical -biological processes. In particular, it has been evaluated the influence of the anodic material used in the electrolysis of the SWE on the biodegradability and toxicity of the effluents. Four anode materials were tested: Boron Doped Diamond (BDD), Carbon Felt (CF), and Mixed Metal Oxides Anodes with iridium and ruthenium (MMO-Ir and MMO-Ru). These materials were tested at different current densities and electric current charges applied. Lindane, TOC, sulphate, and chlorine species concentrations were monitored during electrochemical experiments, showing important differences in their evolution during the treatment. In spite of reaching a good removal of lindane with all the materials tested, results showed that Boron Doped Diamond working at 15 mA cm -2 achieved the best biodegradability results in the electrolyzed effluents, because the ratio BOD 5 /COD increased from 0.2 to 0.5, followed by Carbon Felt anode. Regarding toxicity, Carbon Felt decreased toxicity by 80%. Opposite to what it was expected, MMO anodes did not achieve biodegradability improvement and they only showed reduction in toxicity at high electrical charges., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Breast milk, especially colostrum, is not just a source of nutrients and immune factors for the newborn, but also accumulates environmental persistent pollutants and its diverse microbes affect the early colonization of the newborn's gut. Little is known about associations between environmental pollutants and the microbial composition of human colostrum. We assessed the influence of hexachlorocyclohexane (HCH), a persistent organic pollutant (POP), in colostrums on the microbial composition of human colostrum samples. HCH concentrations in 89 colostrum samples collected from a population living on the easternmost island of China were measured via gas chromatography equipped with mass spectrometer (GC-MS), HCH exposure risks for infants via dietary intake of breast milk were assessed, and for 29 colostrum samples the microbiota were profiled using 16S rRNA gene pyrosequencing to assess the association with HCH exposure levels. Our study confirmed high colostrum exposure levels of total HCHs (12.19 ± 13.68 μg L -1 ) in this Chinese population. We predominantly identified Proteobacteria (67.6%) and Firmicutes (25.1%) in colostrum and microbial diversity at the genus level differed between samples with different HCH levels; e.g., Pseudomonas which contains several HCH degrading strains was found in significantly higher abundance in γ-HCH rich samples. Also, microbes that were statistically significantly associated with HCH levels were also highly correlated with each other (false discovery rate (FDR)＜0.01) and clustered in network analysis. Microbial diversity is associated with HCH levels in human colostrum and these associations might be attributable to their HCH degrading ability. These finding provide first insights into the role that environmental persistent pollutants may play in the microbial composition of human colostrum and the colonization of the infant gut., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Bioremediation using actinobacterium consortia proved to be a promising alternative for the purification of co-contaminated environments. In this sense, the quadruple consortium composed of Streptomyces sp. M7, MC1, A5, and Amycolatopsis tucumanensis AB0 has been able to remove significant levels of Cr(VI) and lindane from anthropogenically contaminated soils. However, the effectiveness of the bioremediation process could not be evaluated only by analytical monitoring, which is complex mainly due to the characteristics of the matrix, producing non-quantitative analyte recoveries, or interferences in the detection stage and quantification. However, the effectiveness of the bioremediation process cannot be evaluated only through analytical monitoring, which is complex due mainly to the characteristics of the matrix, to the recoveries of non-quantitative analytes or to interferences in the detection and quantification stage. For this reason, it is essential to have tools of ecological relevance to assess the biological impact of pollutants on the environment. In this context, the objective of this work was to establish the appropriate bioassays to evaluate the effectiveness of a bioremediation process of co-contaminated soils. For this, five model species were studied: four plant species (Lactuca sativa, Raphanus sativus, Lycopersicon esculentum, and Zea mays) and one animal species (Eisenia fetida). On plant species, the biomarkers evaluated were inhibition of germination (IG) and the length of hypocotyls/steam and radicles/roots of the seedling. While on E. fetida, mortality (M), weight lost, coelomocyte concentration and cell viability were tested. These bioindicators and the battery of biomarkers quantified in them showed a different level of sensitivity, from maximum to minimum: E. fetida > L. esculentum > L. sativa > R. sativus ≫>Z. mays. Therefore, E. fetida and L. esculentum and their respective biomarkers were selected to evaluate the effectiveness of the bioremediation process due to the capability of assessing the effect on the flora and the fauna of the soil, respectively. The joint application of these bioindicators in a field scale bioremediation process is a feasible tool to demonstrate the recovery of the quality and health of the soil., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Proteomic analysis was carried out in substantia nigra (SNi) and hippocampus (Hi) isolated from rat offspring born to mothers exposed to lindane (orally; 0.25 mg/kg) from gestation day 5 (GD5) to GD 21 and subsequently rechallenged (orally; 2.5 mg/kg X 21 days) at adulthood (12 weeks). 2D gel electrophoresis revealed no significant differences in the expression of proteins in brain regions isolated from prenatally exposed offspring at adulthood. Significantly greater magnitude of alterations was observed in the expression of proteins related to mitochondrial and energy metabolism, ubiquitin-proteasome pathway, structural and axonal growth leading to increased oxidative stress in Hi and SNi isolated from rechallenged offspring when compared to control offspring treated postnatally with lindane. Western blotting and DNA laddering showed a greater magnitude of increase in apoptosis in the Hi and SNi of rechallenged offspring. Ultrastructural analysis demonstrated disrupted mitochondrial integrity, synaptic disruption and necrotic structures in the brain region of rechallenged offspring. Neurobehavioral studies also demonstrated a greater magnitude of alterations in cognitive and motor functions in rechallenged rats. The data suggest that prenatal exposure of lindane induces persistent molecular changes in the nervous system of offspring which are unmasked leading to neurodegeneration following rechallenge at adulthood., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lindane is an organochlorine pesticide that is highly persistent in the environment. The amassing of lindane has been identified worldwide and has been found to be very toxic to the environment, human, and animal health. Therefore, urgent consideration and management of the problem is necessary. The current study intends to isolate and identify lindane degrading rhizospheric bacteria from Phragmites karka and to study its degradation kinetics. Also, plant growth promoting potential of the bacterium was evaluated in the presence and absence of studied pesticide. Rhizospheric bacteria were isolated by standard enrichment technique in Mineral Salt Medium. Microbacterium sp. P27 showed the highest degradation percentage, 82.7 ± 1.79% for 50 mg l -1 lindane, after 15 days. Degradation was also studied at different concentrations of lindane. Maximum degradation was achieved at 10 mg l -1 followed by 50 mg l -1 and 100 mg l -1 lindane. Microbacterium sp. P27 showed positive result for Indole-3-acetic acid production, ammonia production, and 1-aminocyclopropane-1-carboxylate deaminase activity. Presence of lindane revealed a concentration-dependent decrease in plant growth promoting activity. Since the isolated bacterial strain possesses lindane degrading capacity and also other characters that help in plant growth promotion, the isolate can be an important candidate for the progress of bioremediation strategy.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1β and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1β and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1β level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1β and IL-6 in the cortex and thalamus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Prenatal exposure to low doses of lindane, an organochlorine insecticide used in public health and agriculture, induced a persistent increase in the expression of cerebral cytochrome P450s (CYPs) in rat offspring and modify the adult response to a later exposure of xenobiotics. To understand the mechanism involved in the modification of adult response, rat offspring exposed prenatally to lindane (p.o.; 0.25 mg/kg b.wt. from gestation day 5-21) were rechallenged with lindane (p.o.; 5 mg/kg X 5 days) postnatally at 9- or 18- or 27 weeks. The greater magnitude of increase in the expression of cerebral CYPs in rechallenged offspring and decline in the magnitude of increase in CYPs with increasing age correlated with the amount of lindane accumulating in the brain. Significant alterations in the circulatory levels of hormones in the rechallenged offspring suggest that these alterations may partly account for the persistence in the increase in the cerebral CYPs during development. Epigenetic data further revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of cerebral CYPs isolated from rechallenged offspring at 9- or 18- or 27 weeks. Bisulphite sequencing revealing critical CpG methylation changes in the promoter regions in rechallenged offspring at 9 weeks demonstrated imprinting of the cerebral CYPs. Further, a greater magnitude of increase in apoptosis in the brain of rechallenged offspring has suggested that enhanced responsiveness of cerebral CYPs, which may result due to alterations in circulatory hormones, increased accumulation of lindane in the brain and epigenetic regulation of CYPs, is of toxicological relevance., (Copyright © 2019. Published by Elsevier Inc.)

Background: One of the most worrying consequence of the production and use of persistent organohalogen pollutants (POPs) is the high accumulation in Arctic populations because of long-range transport. Study of the effects in these populations may illustrate human impacts that are difficult to assess in other locations with lower exposure to these compounds and more diverse pollutant influences., Objective: We aimed to identify the main maternal characteristics influencing on the accumulation of these compounds and the effects on the newborns in a highly exposed Arctic population (Chukotka, Russia)., Methods: Organochlorine and organobromine compounds were analysed in maternal venous serum (n = 250). The study included data on residence, educational level, age, parity and body mass index (BMI) from self-reported questionnaires and measured anthropometric characteristics of newborns., Results: Concentrations of β-hexachlorocyclohexanes, hexachlorobenzene, 4,4'-DDT and polychlorobiphenyls were high when compared with those generally found in adult populations later than year 2000. The polybromodiphenyl ethers were negligible. These POP concentrations were higher than in Alaska and Arctic Norway and similar to those in Canada. The Chukotka mothers living in inland areas showed significant lower concentrations than those living in the coast (p < 0.001) except for 4,4'-DDT. The population from the Chukotsky District, a specific coastal area, showed the highest concentrations. Residence was therefore a main concentration determinant (p < 0.001) followed by maternal age, and in some cases parity and BMI (p < 0.05). 4,4'-DDT showed an association with the anthropometric characteristics of the newborns (p < 0.05). Mothers with higher 4,4'-DDT concentrations had longer gestational ages and gave birth to infants with higher weight and length., Conclusions: The maternal accumulation patterns of POPs were mainly related with residence. Most of these compounds were found in higher concentration in women living at coastal areas except 4,4'-DDE and 4,4'-DDT which were of inland origin. This last pesticide was the pollutant showing positive associations with gestational age and newborn's weight and length. To the best of our knowledge, this is the first study reporting statistically significant associations between maternal 4,4'-DDT exposure and anthropometric characteristics of the newborns., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Extracellular DNA in the environment may play important roles in genetic diversity and biological evolution. However, the influence of environmental persistent organic contaminants such as organochlorinated pesticides (e.g., hexachlorocyclohexanes [HCHs]) on the enzymatic degradation of extracellular DNA has not been elucidated. In this study, we observed expedited enzymatic degradation of extracellular DNA in the presence of α-HCH, β-HCH and γ-HCH. The HCH-expedited DNA degradation was not due to increased deoxyribonuclease I (DNase I) activity. Our spectroscopic and computational results indicate that HCHs bound to DNA bases (most likely guanine) via Van der Waals forces and halogen bonds. This binding increased the helicity and accumulation of DNA base pairs, leading to a more compact DNA structure that exposed more sites susceptible to DNase I and thus expedited DNA degradation. This study provided insight into the genotoxicity and ecotoxicity of pesticides and improved our understanding of DNA persistence in contaminated environments., Competing Interests: The authors declare no competing interests.

Lindane exposure is claimed to be involved in pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance state by an as yet unknown mechanism. The redox sensitive kinases (RSKs) and heat shock proteins (HSPs) interfere with insulin signaling and induce insulin resistance. The present study was designed to explore the mechanism of insulin resistance induced by sub-toxic lindane exposure. In an in vitro study, exposure to 60 mg/L and 120 mg/L of lindane for 18 h on rat L6 myoblasts derived myotubes significantly increased malondialdehyde level & superoxide dismutase activity, decreased total antioxidant level and insulin-induced glucose uptake in a dose dependent manner. The extent of activation of RSKs and HSP25 as measured by western blot from the extent of phosphorylation of IκBα, p38 MAPK, JNK & HSP25 in lindane-exposed myotubes was higher. HSP70 was induced and insulin signaling as measured from tyrosine phosphorylation of insulin receptor (IR) & insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt was attenuated in comparison to those in untreated myotubes. We conclude that sub-toxic lindane exposure induces oxidative stress, activates RSKs & HSP25 and induces HSP25. These in turn, impair insulin signaling to impart insulin resistance in myotubes induced by sub-toxic lindane exposure., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The correlation between endocrine active contaminants in the environment and alterations in reproductive development of Sarotherodon melanotheron from Lagos lagoon has been investigated. Sediment and a total of 155 fish (74 males and 81 females) were collected between November 2014-March 2015 from selected contaminated sites (Ikorodu, Oworonshoki, Makoko and Idumota) and a putative control site (Igbore) along the lagoon. Sediment contaminant analysis revealed, significantly higher concentration of lindane, dieldrin, 4-iso-nonylphenol, 4-t-octylphenol and monobutyltin cation at the contaminated sites. Examination of gross morphological and histological changes of fish gonads showed a 27.4% prevalence of intersex in the sampled fish, of which 78% were males (testes-ova) and 22% were females (ovo-testis). Quantitative PCR (qPCR) of liver transcripts revealed the presence of vitellogenin (vtg) levels in male fish from contaminated sites. Zona radiata proteins (zrp) mRNA levels were significantly higher in females, compared to male fish. In general, significantly lower vtg and zrp transcripts levels were recorded at Igbore (control site), compared with contaminated sites. Principal component analysis (PCA) showed site and sex relationship in biological responses and contaminants, including trace metals, demonstrating that measured endocrine responses in fish were associated with contaminant burden in sediment. In addition, positive relationships were observed in male fish from Idumota, Oworonshoki and Ikorodu with vtg and dieldrin/4-iso-nonyphenol, with higher levels in male fish, compared to females. Further, contaminants from the Makoko, Oworonshoki and Ikorodu sites were positively associated with higher GSI and zrp in females. More importantly, the severity of intersex and changes in vtg transcripts imply a progressive feminization of male fish with concomitant alteration in the reproductive health of fish inhabiting the Lagos lagoon., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Environmental exposure to the highly persistent chlorinated pesticides including dieldrin and lindane is postulated to be a risk factor to the development of Parkinson's disease, a devastating movement disorder. We have previously reported that the combined treatment with dieldrin and lindane induces a cooperative toxicity in the rat N27 dopaminergic neuronal cells through increased oxidative stress and mitochondrial dysfunction. In this study, we investigated the involvement of NADPH oxidase (NOX) proteins in the combined treatment with dieldrin and lindane-induced dopaminergic neurotoxicity. Immunoblot analysis demonstrated the presence of NADPH Oxidase 1 (Nox1) isoform and p67 phox in N27 neurons. Furthermore, treatment with dieldrin and lindane upregulated the cellular expression of Nox1 but not p67 phox protein. Functionally, dieldrin and lindane-induced ROS production was attenuated, in a dose-dependent manner, by Nox inhibitors diphenylene iodonium and apocynin. Subcellular localization analysis of Nox1 and p67 phox proteins indicated colocalization of both subunits with mitochondria in untreated cells. Treatment with dieldrin and lindane further increased mitochondrial colocalization of Nox1 protein, suggesting a potentially prominent role for mitochondrial Nox1 protein in dieldrin and lindane-induced ROS generation in dopaminergic neurons and its contribution to the combined organochlorinated pesticide-induced neurotoxicity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The levels and spatial distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in freshwater products from Northeast China were investigated by gas chromatography coupled to isotope dilution high-resolution mass spectrometry. All samples were on-spot sampled from main production regions of freshwater products in Northeast China, and these samples were used to systematically assess the potential health risks of OCPs and PCBs associated with consumption of these fishery products. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexane (HCHs), hexachlorobenzene (HCB) and PCBs were the major pollutants with 100% detection rates, and their levels ranged from 0.086 to 58, 0.038-3.3, 0.093-4.5 and 0.032-1.4 ng g -1 wet weight, respectively. The estimated dietary intakes of these contaminants were all below their corresponding acceptable daily intakes. Significant regional differences in the levels of OCPs and PCBs (P ≦ 0.001) were found in samples from Liaoning and Inner Mongolia. The results showed that the concentrations of targeted contaminants in aquatic products had species-specific characteristics, and the levels of targeted pollutants in Oncorhynchus mykiss and Eriocheir sienesis were significantly higher than those in other aquatic product species. Advisories on ten species of aquatic products suggested that consumption of Eriocheir sinensis, Oncorhynchus mykiss and Cyprinus carpio at a rate exceeding 15 meals per month would pose a cancer risk. A health risk assessment indicated that exposure to these pollutants through freshwater products consumption would cause a non-ignorable potential carcinogenic risk to humans., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The reproductive and breeding success of wader species is negatively affected by various anthropogenic factors, including persistent organochlorine pollutants (POPs). We aimed to study the association of POPs in feathers with the reproductive success of the spur-winged lapwing (Vanellus spinosus). For this purpose, data on reproductive parameters and feather samples were collected from a breeding population consisting of 19 pairs near Boğazkent district in Antalya, Turkey. Mean concentrations of total polychlorinated biphenyls (ΣPCBs) and organochlorine pesticides (ΣOCPs) were found to be 54 ± 16 ng/g and 520 ng/g in all samples, respectively. In particular, PCB 151 and β-hexachlorocyclohexane had a negative association the various reproductive parameters in the species under consideration. Fledgling success (n = 25) was calculated to be 37.4%, which was negatively associated with the ΣOCP concentrations (r = - 0.99, p = 0.01). According to the results, POP residues are one of the associated factors on the reproductive success of spur-winged lapwing along, with agricultural activity and predation. It is indicated that the species needs a protection plan for prevention declining reproductive success and population size species in Turkey. Besides, our results suggest that bird feathers are a non-destructive bio-monitoring tools to estimate of contamination levels of organic pollutants in a population.

Exposure to environmental toxicants that target ovarian follicles can have long-lasting effects on women's reproductive health and health of the offspring. Experiments in rodents have contributed knowledge about the effects of individual toxicants on ovarian follicles. However, little is known about the effects of mixtures of toxicants on ovarian follicular health. We studied the combined effects of low, physiologically- and environmentally-relevant concentrations of toxicants on murine secondary ovarian follicles cultured in an encapsulated three-dimensional (3D) system. Exposure to lindane and 7,12-dimenthylbenz(a)anthracene (DMBA) led to decreased follicle survival, impaired development and compromised maturation in a concentration-dependent manner. DMBA showed a greater toxicity to cultured follicles compared to lindane. The mixtures of lindane and DMBA did not produce a synergistic toxic effect on follicles. Rather, ovarian follicles exposed to the mixtures showed survival and growth patterns similar to the follicles exposed to the same concentrations of individual toxicants. Our findings regarding follicle toxicity at such low concentrations help informing what might be overlooked when regulating environmental toxicants. The proposed 3D culture system allowed studying the effects of mixtures of environmental toxicants in a physiological setting, providing much needed information on how simultaneous exposure to multiple toxicants affects complex and sensitive biological structures, such as ovarian follicles., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Proteomic studies were carried out in immature (3 week), adult (18 week) and aged (48 week) rats to understand the age dependent vulnerability to lindane induced neurodegeneration. 2-D and western blot analysis of protein extracts of hippocampus and substantia-nigra isolated from lindane treated rats (2.5 mg/kg; p.o. X 21 days) revealed marked dysregulation in the expression of proteins related to ubiquitin proteasome pathway, antioxidant activity, chaperones, energy metabolism, calcium homeostasis and proteins involved in neurodegeneration. These alterations were associated with marked increase in reactive oxygen species formation, lipid peroxidation, reduced glutathione content and antioxidant enzyme activities in lindane treated rats. Aged rats, in particular showed higher magnitude of alteration in these proteins when compared to immature or adult rats. Proteins involved in apoptosis and autophagy also showed marked alterations in their expression, particularly in the aged rats. Ultrastructural analysis revealed greater number of autophagic vesicle in hippocampus and substantia-nigra in treated aged rats. The data suggest that proteomic approaches could be used to investigate the vulnerability to lindane induced neurodegeneration in rats., (Copyright © 2018. Published by Elsevier Ltd.)

Toxicity of mine dump effluent containing five hexachlorocyclohexane (α, β, γ, δ and ε-HCH, sum 159.4 μg/L) and two trichlorobenzene (TCB, sum 65.2 μg/L) isomers to two microalgae (Scenedesmus quadricauda and Coccomyxa subellipsoidea) was studied over 24 h exposure and also with 2- and 10-fold diluted stock solution (i.e. 1×, 0.5× and 0.1× strength). Individual isomers revealed rather dose-dependent accumulation typically higher in Scenedesmus than in Coccomyxa (max. sum of HCH 14.99 μg/g DW with bioaccumulation factor 94) and δ-HCH was dominant isomer. TCB isomers showed low accumulation in algae. 0.1× dose elevated chlorophylls and carotenoids in Coccomyxa while enzymatic activities (SOD, CAT, and APX), thiols (glutathione and phytochelatin 2) and ascorbic acid were rather elevated by 1× dose in both species. Malic acid, rather than citric acid, increased in response to 0.5× and 1× concentration. Sum of fatty acids was higher in Coccomyxa than in Scenedesmus with palmitic, oleic, linoleic and α-linolenic acids being dominant compounds in both species. Detailed profiling revealed that saturated and monounsaturated fatty acids increased in Coccomyxa while polyunsaturated fatty acids in Scenedesmus in response to increasing dose of organochlorines. Accumulation of organochlorines and metabolic responses in algae are reported here for the first time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Lindane, which is one of the most persistent organochlorine pesticide contaminating the Aral Sea region, is associated with numerous pathologies of the female reproductive system, including infertility, due to its gap junction blocker activity. By using an in vitro model of reproductive toxicity consisting of mouse parietal granulosa cells (GCs) exposed to increasing concentrations of Lindane ranging from 1 to 100μM (L1; L10; L100), we aimed to ascertain the Lindane toxicity by evaluating the ultrastructure and expression of the cell death protein p53. GCs exposed to L1 showed an early sign of degeneration as chromatin marginalization and initial reduction of cell-to-cell contacts. Such effects increased at L10 with nuclear membrane invagination, cytoplasmic blebbing, reduction of microvilli and intercellular connections. L100 induced evident cellular damages with an extensive presence of vacuoles, cytoplasmic fragments, nuclear membrane vesiculation and abundant cellular debris. A dose-dependent increase of p53 expression was evident in the L1 and L10 groups but not in L100. These data provide evidence for a dose-dependent reproductive toxicity of the gap junction blocker Lindane, as seen in mouse GCs cultured in vitro by ultrastructural damage compatible with apoptosis. Since gap junctions may play a critical role in FSH-stimulated progesterone production, the ultrastructural damage here evidenced could explain the increase in the prevalence of reproductive pathologies and infertility in exposed women. Finally, this study provided a useful and repeatable model of reproductive toxicity in vitro, which is applicable to evaluate the detrimental effects of toxicants or the reversing effect of protective substances., (Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl 3 )/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl 3 /ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl 3 /ADP gave rise to concentration-dependent reductions in rat (EC 50 11.8×10 -6 M and 0.9×10 -3 M) and human myometrial contractions (EC 50 16.3×10 -6 M and 1.1×10 -3 M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC 50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl 3 /ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl 3 /ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl 3 /ADP., (Copyright © 2017. Published by Elsevier Inc.)

An ecotoxicological survey of soils that were polluted with wastes from lindane (γ-HCH) production assessed the effects of organochlorine compounds on the metabolism of microbial communities and the toxicity of these compounds to a native earthworm (Allolobophora chlorotica). Furthermore, the bioremediation role of earthworms as facilitators of soil washing and the microbial degradation of these organic pollutants were also studied. Soil samples that presented the highest concentrations of ε-HCH, 2,4,6-trichlorophenol, pentachlorobenzene and γ-HCH were extremely toxic to earthworms in the short term, causing the death of almost half of the population. In addition, these soils inhibited the heterotrophic metabolic activity of the microbial community. These highly polluted samples also presented substances that were able to activate cellular detoxification mechanisms (measured as EROD and BFCOD activities), as well as compounds that were able to cause endocrine disruption. A few days of earthworm activity increased the extractability of HCH isomers (e.g., γ-HCH), facilitating the biodegradation of organochlorine compounds and reducing the intensity of endocrine disruption in soils that had low or medium contamination levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The persistent organochlorine pesticides (OCPs) in soils are suspected to disturb soil biogeochemical cycles. This study addressed the dynamic changes in soil functionality under lindane and chlordecone exposures with or without maize plant. Decreases in soil ammonium concentration, potential nitrogen mineralization and microbial biomass were only OCP-influenced in bulk soils. OCPs appeared to inhibit the ammonification step. With plants, soil functionality under OCP stress was similar to controls demonstrating the plant influence to ensure the efficiency of C- and N-turnover in soils. Moreover, OCPs did not impact the microbial community physiological profile in all tested conditions. However, microbial community structure was OCP-modified only in the presence of plants. Abundances of gram-negative and saprophytic fungi increased (up to +93% and +55%, respectively) suggesting a plant stimulation of nutrient turnover and rhizodegradation processes. Nevertheless, intimate microbial/plant interactions appeared to be OCP-impacted with depletions in mycorrhizae and micro/meso-fauna abundances (up to -53% and -56%, respectively) which might have adverse effects on more long-term plant growth (3-4 months). In short-term experiment (28days), maize growth was similar to the control ones, indicating an enhanced plasticity of the soil functioning in the presence of plants, which could efficiently participate to the remediation of OCP-contaminated soils., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.