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Due to past massive usage and persistent nature, pentachlorophenol (PCP) residues are prevalent in environments, posing a potential threat to various organisms such as sessile filter-feeding bivalves. Although humoral immunity and its crosstalk with cellular one are crucial for the maintaining of robust antimicrobic capability, little is known about the impacts of PCP on these critical processes in bivalve mollusks. In this study, pathogenic bacterial challenge and plasma antimicrobic capability assays were carried out to assess the toxic effects of PCP on the immunity of a common bivalve species, blood clam (Tegillarca granosa). Moreover, the impacts of PCP-exposure on the capabilities of pathogen recognition, hemocyte recruitment, and pathogen degradation were analyzed as well. Furthermore, the activation status of downstream immune-related signalling pathways upon PCP exposure was also assessed. Data obtained illustrated that 28-day treatment with environmentally realistic levels of PCP resulted in evident declines in the survival rates of blood clam upon Vibrio challenge along with markedly weakened plasma antimicrobic capability. Additionally, the levels of lectin and peptidoglycan-recognition proteins (PGRPs) in plasma as well as the expression of pattern recognition receptors (PRRs) in hemocytes were found to be significantly inhibited by PCP-exposure. Moreover, along with the downregulation of immune-related signalling pathway, markedly fewer chemokines (interleukin 8 (IL-8), IL-17, and tumor necrosis factor α (TNF-α)) in plasma and significantly suppressed chemotactic activity of hemocytes were also observed in PCP-exposed blood clams. Furthermore, compared to that of the control, blood clams treated with PCP had markedly lower levels of antimicrobic active substances, lysozyme (LZM) and antimicrobial peptides (AMP), in their plasma. In general, the results of this study suggest that PCP exposure could significantly impair the antimicrobic capability of blood clam via undermining humoral immunity and disrupting humoral-cellular crosstalk., 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 Elsevier Ltd. All rights reserved.)

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women's test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment., 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. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pentachlorophenol (PCP) is widely found in coastal environments and has various adverse effects, and its potential impact on coral reef ecosystems concerning. The scleractinian coral Montipora digitata was used for PCP stress experiments in this study. Phenotypes, physiological indicators, microbial diversity analysis and RNA sequencing were used to investigate the mechanisms underlying the responses of corals to acute and chronic PCP exposure. After 96 h of acute exposure, coral bleaching occurred at 1000 μg/LPCP and there was a significant decrease in Symbiodiniaceae density, Fv/Fm, and chlorophyll a content. Exposure to different concentrations of PCP significantly increased the content of malondialdehyde (MDA), leading to oxidative stress in corals. Chronic PCP exposure resulted in bleaching at 60 days, with the Fv/Fm significantly reduced to 0.461. Microbial diversity analysis revealed an increase in the abundance of potential pathogens, such as Vibrio, during acute PCP exposure and the emergence of the degrading bacterium Delftia during chronic PCP exposure. Transcriptional analysis showed that PCP exposure caused abnormal carbohydrate and amino acid metabolism in zooxanthella, which affected energy supply, induced immune responses, and disrupted symbiotic relationships. Corals respond to injury by boosting the expression of genes associated with signal transduction and immune response. Additionally, the expression of genes associated with environmental adaptation increased with chronic PCP exposure, which is consistent with the results of the microbial diversity analysis. These results indicate that PCP exposure might affect the balance of coral- zooxanthellae symbiosis in the stony coral M. digitata, impairing coral health and leading to bleaching., 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. Published by Elsevier B.V.)

Marine nano-titanium dioxide (nano-TiO 2 ) and pentachlorophenol (PCP) pollution are escalating concerns in coastal areas. This study investigated the combined effects of continuous exposure to nano-TiO 2 (25 nm, 100 nm) and PCP (0, 1, 10 μg/L) for 28 days on the antioxidant, digestive, and immune abilities of the swimming crab Portunus trituberculatus. Compared with the control group, the interaction between nano-TiO 2 and PCP was significantly higher than exposure to a single stressor, with a pronounced decrease in amylase activity observed due to the reducing nano-TiO 2 particle sizes. Resulting in increased MDA and SOD activity. The expression levels of Toll4, CSP3, and SER genes in crab hemolymph showed perturbations following exposure to nano-TiO 2 and PCP. In summary, according to the results of CAT, GPX, PES and AMS enzyme activities, it was concluded that compared to the larger particle size (100 nm), the single stress of nano-TiO 2 at a smaller particle size (25 nm) and co-stress with PCP have more significant impacts on P. trituberculatus. However, the potential physiological regulation mechanism of the interaction between these pollutants remains elusive and requires further study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Youji Wang reports financial support was provided by National Natural Science Foundation. Youji Wang reports financial support was provided by Shanghai Dawning Project. Youji Wang reports a relationship with National Natural Science Foundation of China that includes: funding grants. Youji Wang reports a relationship with Shanghai Dawning Project that includes: funding grants. If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Pentachlorophenol (PCP) is a widely used pesticide. However, whether PCP and its metabolite chloranil have endocrine-disrupting effects by inhibiting placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) remains unclear. The study used in vitro assays with human and rat placental microsomes to measure 3β-HSD activity as well as human JAr cells to evaluate progesterone production. The results showed that PCP exhibited moderate inhibition of human 3β-HSD1, with an IC 50 value of 29.83 μM and displayed mixed inhibition in terms of mode of action. Conversely, chloranil proved to be a potent inhibitor, demonstrating an IC 50 value of 147 nM, and displaying a mixed mode of action. PCP significantly decreased progesterone production by JAr cells at 50 μM, while chloranil markedly reduced progesterone production at ≥1 μM. Interestingly, PCP and chloranil moderately inhibited rat placental homolog 3β-HSD4, with IC 50 values of 27.94 and 23.42 μM, respectively. Dithiothreitol (DTT) alone significantly increased human 3β-HSD1 activity. Chloranil not PCP mediated inhibition of human 3β-HSD1 activity was completely reversed by DTT and that of rat 3β-HSD4 was partially reversed by DTT. Docking analysis revealed that both PCP and chloranil can bind to the catalytic domain of 3β-HSDs. The difference in the amino acid residue Cys83 in human 3β-HSD1 may explain why chloranil is a potent inhibitor through its interaction with the cysteine residue of human 3β-HSD1. In conclusion, PCP is metabolically activated to chloranil as a potent inhibitor of human 3β-HSD1., 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. Published by Elsevier B.V.)

Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosis-like cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress., 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. Published by Elsevier Ltd.)

Tetracycline antibiotics play a vital role in animal husbandry, primarily employed to uphold the health of livestock and poultry. Consequently, when manure is reintegrated into farmland, tetracycline antibiotics can persist in the soil. Simultaneously, to ensure optimal crop production, organochlorine pesticides (OCPs) are frequently applied to farmland. The coexistence of tetracycline antibiotics and OCPs in soil may lead to an increased risk of transmission of tetracycline resistance genes (TRGs). Nevertheless, the precise mechanism underlying the effects of OCPs on tetracycline antibiotics and TRGs remains elusive. In this study, we aimed to investigate the effects of OCPs on soil tetracycline antibiotics and TRGs using different concentrations of doxycycline (DOX) and pentachlorophenol (PCP). The findings indicate that PCP and DOX mutually impede their degradation in soil. Furthermore, our investigation identifies Sphingomonas and Bacillus as potential pivotal microorganisms influencing the reciprocal inhibition of PCP and DOX. Additionally, it is observed that the concurrent presence of PCP and DOX could impede each other's degradation by elevating soil conductivity. Furthermore, we observed that a high concentration of PCP (10.7 mg/kg) reduced the content of efflux pump tetA, ribosome protective protein tetM, tetQ, and passivating enzyme tetX. In contrast, a low PCP concentration (6.4 mg/kg) only reduced the content of ribosome protective protein tetQ. This suggests that PCP may reduce the relative abundance of TRGs by altering the soil microbial community structure and inhibiting the potential host bacteria of TRGs. These findings have significant implications in understanding the combined pollution of veterinary antibiotics and OCPs. By shedding light on the interactions between these compounds and their impact on microbial communities, this study provides a theoretical basis for developing strategies to manage and mitigate their environmental impact, and may give some information regarding the sustainable use of antibiotics and pesticides to ensure the long-term health and productivity of agricultural systems., 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.)

Stress from chemical pollutants is among the key issues that have adverse impacts on coral reefs. As a persistent organic pollutant, pentachlorophenol (PCP) has been detected in the seawater of Weizhou Island and was proved to have significant adverse effects on aquatic animals. However, little is known about its effects on scleractinian coral. Therefore, we investigated the response of the coral Porites lutea to PCP stress. Coral bleaching, photosynthesis parameters and antioxidant enzyme activities of P. lutea under PCP exposure were documented. After 96 h of exposure, significant tissue loss and bleaching occurred when the PCP concentration exceeded 100 μg/L. The density of symbiotic zooxanthellae decreased from 2.06 × 10 6 cells/cm 2 to 0.93 × 10 6 cells/cm 2 when the PCP concentration increased from 1 μg/L- 1000 μg/L. Long-term exposure of 120 days to PCP at 0.1 μg/L also led to coral bleaching, the maximum photochemical quantum yield of PSII in P. lutea nubbins significantly decreased to 0.482. The analysis of microbial community distribution indicated that the increase of the pathogenic bacterium Citrobacter may be one of the inducers of coral bleaching. Conjoint analysis of transcriptomics and proteomics showed that the metabolism of amino acids and carbohydrates in zooxanthellae was abnormal, leading to the destruction of its symbiotic relationship with the host. The immune system of the host was disrupted, which could be linked to the prevalence of coral pathema. The toxic responses of PCP on both zooxanthellae and its host were further confirmed by the upregulation of the differential metabolites including 1-naphthylamine and phosphatidylcholine, etc., 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.)

Sodium pentachlorophenol (PCP-Na) is widespread in the marine environment; however, its impact on marine organisms remains under-researched. Moerella iridescens and Exopalaemon carinicauda are marine species of economic importance in China and under threat from PCP-Na pollution. Thus, this study aimed to assess the toxicity and detoxification metabolism of PCP-Na on M. iridescens and E. carinicauda. The study revealed that the 96 h median lethal concentration (LC50) of PCP-Na for M. iridescens and E. carinicauda were 9.895 mg/L and 14.143 mg/L, respectively. A species sensitivity distribution (SSD) for PCP-Na was developed specifically for marine organisms, determining a hazardous concentration to 5% of the species (HC 5 ) of 0.047 mg/L. During the sub-chronic exposure period, PCP-Na accumulated significantly in M. iridescens and E. carinicauda, with highest concentrations of 41.22 mg/kg in the soft tissues of M. iridescens, 42.58 mg/kg in the hepatopancreas of E. carinicauda, and only 0.85 mg/kg in the muscle of E. carinicauda. Furthermore, the study demonstrated that detoxifying metabolic enzymes and antioxidant defense system enzymes of E. carinicauda responded stronger to PCP-Na compared to M. iridescens, suggesting that E. carinicauda may possess a stronger detoxification capacity. Notably, five biomarkers were identified and proposed for monitoring and evaluating PCP-Na contamination. Overall, the results indicated that M. iridescens and E. carinicauda exhibit greater tolerance to PCP-Na than other marine species, but they are susceptible to accumulating PCP-Na in their tissues, posing a significant health risk. Consequently, conducting aquatic health risk assessments in areas with potential PCP-Na contamination is strongly recommended., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pentachlorophenol (PCP) is a ubiquitous environmental toxicant with various adverse effects. Although its neurotoxicity has been reported, the underlying mechanism and subsequent detoxification remain unclear. In this study, embryos and adult zebrafish were exposed to PCP to determine its potential neurotoxic mechanism and protective indicators. The survival rate, heart rate, mobility time, active status and moving distance were significantly decreased in larvae after 30 μg/L PCP exposure. Likewise, the mobile time, latency to the first movement, velocity and moving distance of adult zebrafish were significantly reduced by PCP exposure. Untargeted metabolomics analysis of larvae revealed that arginine and proline metabolism was the primary pathway affected by PCP exposure, reflected by increased proline and decreased citrulline (CIT) contents, which were confirmed by quantitative data. PCP exposure suppressed the conversion from arginine to CIT in larvae by downregulating the expression of nos1 and nos2a. Ornithine content was increased in the brains and intestines of adult zebrafish after PCP exposure, which inhibited ornithine catabolism to CIT by downregulating otc, resulting in reduced CIT. Intriguingly, CIT supplementation significantly restored the neurobehavioral defects induced by PCP in larvae and adult zebrafish. CIT supplementation upregulated the expression of ef1α and tuba1 in larvae and inhibited the downregulation of ef1α in the brains of adult zebrafish. Taken together, these results indicated that CIT supplementation could protect against PCP-induced neurotoxicity by upregulating the expression of genes involved in neuronal development and function., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lei Li reports financial support was provided by National Natural Science Foundation of China. Zhan Zhang reports financial support was provided by Natural Science Foundation of Jiangsu Province., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nano-TiO 2 can act as a vector to organic compounds, such as pentachlorophenol (PCP) posing a potential threat to the marine ecosystems. Studies showed that nano pollutant toxicity can be modulated by abiotic factors, but little is known about the potential influence of biotic stressors (such as predators) on the physiological responses to pollutants in marine organisms. We explored the effects of n-TiO 2 and PCP on the mussel Mytilus coruscus in the presence of its natural predator, the swimming crab Portunus trituberculatus. Exposure to n-TiO 2 , PCP, and predation risk showed interactive effects on antioxidant and immune parameters of the mussels. Elevated activities of catalase (CAT), glutathione peroxidase (GPX), acid phosphatase (ACP) and alkaline phosphatase (AKP), suppressed activity of superoxide dismutase (SOD), lower levels of glutathione (GSH) and increased malondialdehyde (MDA) levels indicated dysregulation of the antioxidant system and immune stress induced by single PCP or n-TiO 2 exposure. Integrated biomarker (IBR) response values showed the effect of PCP was concentration dependent. Of the two used n-TiO 2 sizes (25 and 100 nm), larger particles induced higher antioxidant and immune disturbances indicating higher toxicity possibly due to higher bioavailability. Compared to single PCP exposure, the combination of n-TiO 2 and PCP enhanced the imbalance of SOD/CAT and GSH/GPX and led to elevated oxidative lesions and activation of immune-related enzymes. Overall, the combined impacts of pollutants and biotic stress exhibited a greater magnitude of adverse effects on antioxidant defense and immune parameters in mussels. The toxicological effects of PCP were exacerbated in the presence of n-TiO 2 , and the deleterious impact of these stressors was further amplified under predator-induced risk after prolonged (28 days) exposure. However, the underlying physiological regulatory mechanisms governing the interplay of these stressors and predatory cues on mussels remain elusive, warranting further investigation., 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.)

Pentachlorophenol (PCP) has been widely used as an insecticide for killing oncomelania (the intermediate host of schistosome) in China and leads to severe environmental contamination. Poyang Lake, as the largest freshwater lake and bird habitat in China, was once a schistosomiasis epidemic area. In this study, the concentrations of PCP in water and aquatic products from Poyang Lake were determined and analyzed, and then the human health ambient water quality criteria (AWQC) was derived based on native parameters of Poyang Lake basin. Finally, a comprehensive analysis of the health risks of drinking water and different types of aquatic products consumption was carried out. The results showed that PCP concentrations were ranged from 0.01 to 0.43 μg/L in surface water and 3.90 to 85.95 μg/kg in aquatic products. Due to the carcinogenicity of PCP, the human health AWQC for PCP are 0.02 μg/L for consumption of water and organisms and 0.03 μg/L for consumption of organisms only. Deterministic and probabilistic risk analysis indicated that the non-carcinogenic risk of PCP were acceptable in Poyang Lake, while the carcinogenic risk cannot be ignored. The health risks of PCP caused by aquatic products consumption were higher than that by drinking water. The percentages of acceptable risk for the population in Poyang Lake Basin were 99.95% at acceptable level of 10 -4 . Based on the sensitivity analysis, the impact of PCP concentrations on health risk values ranged from 53 to 82%. The study provided valuable information for regional water quality criteria development and water quality assessment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Pentachlorophenol (PCP) is used as pesticide and wood preservative. We have previously shown that PCP causes oxidative damage in rat intestine., Aim: This study aimed to delineate the possible therapeutic potential of curcumin (CUR) and gallic acid (GA) against PCP-induced damage in rat intestine., Methods: PCP alone group received 125 mg PCP/kg body weight/day orally for 4 days. Animals in combination groups received CUR or GA (100 mg/kg bw) for 18 days and PCP (125 mg/kg bw) for the last four days. Rats were sacrificed and intestinal preparations were analyzed for various parameters., Results: Administration of PCP alone altered the activities of metabolic, antioxidant and brush border membrane enzymes. It also increased DNA-protein crosslinking and DNA-strand scission. Animals in combinations groups showed significant amelioration against PCP-induced oxidative damage. Histological abrasions were seen in PCP alone group which were reduced in the intestines of combination groups. CUR was more effective protectant than GA., Conclusions: CUR and GA protected rat intestine from PCP-mediated changes in the activities of metabolic, antioxidant and brush border membrane enzymes. They also prevented DNA damage and histological abrasions. The antioxidant character of CUR and GA may be responsible for the diminution of PCP-mediated oxidative damage., 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 Ltd. All rights reserved.)

With the development of industry, agriculture and intensification of human activities, a large amount of nano-TiO 2 dioxide and pentachlorophenol have entered aquatic environment, causing potential impacts on the health of aquatic animals and ecosystems. We investigated the effects of predators, pentachlorophenol (PCP) and nano titanium dioxide (nano-TiO 2 ) on the gut health (microbiota and digestive enzymes) of the thick-shelled mussel Mytilus coruscus. Nano-TiO 2 , as the photocatalyst for PCP, enhanced to toxic effects of PCP on the intestinal health of mussels, and they made the mussels more vulnerable to the stress from predators. Nano-TiO 2 particles with smaller size exerted a larger negative effect on digestive enzymes, whereas the size effect on gut bacteria was insignificant. The presence of every two of the three factors significantly affected the population richness and diversity of gut microbiota. Our findings revealed that the presence of predators, PCP, and nano-TiO 2 promoted the proliferation of pathogenic bacteria and inhibited digestive enzyme activity. This research investigated the combined stress on marine mussels caused by nanoparticles and pesticides in the presence of predators and established a theoretical framework for explaining the adaptive mechanisms in gut microbes and the link between digestive enzymes and gut microbiota., 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.)

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pentachlorophenol (PCP) is ubiquitous and moderately persistent in the environment, and it is an identified human carcinogen. Previous animal experiments indicate that toxic mechanisms of PCP include oxidative stress. However, no epidemiological study has reported the association between PCP exposure and oxidative stress; such association in pregnant women, a vulnerable population, is of particular interest. This study aimed to characterize PCP concentrations in 2304 urine samples from 768 pregnant women, explore its determinants, and evaluate the associations between PCP exposure and three oxidative stress biomarkers across three trimesters. The median concentrations of PCP (100% detected) in the first, second, and third trimester were 0.61, 0.59, and 0.48 ng/mL, respectively, with a significant decrease trend. The intraclass correlation coefficient of specific gravity (SG)-adjusted PCP was 0.26, indicating high variability for PCP across the three trimesters. PCP concentrations were significantly higher in older, pre-pregnancy overweight, multiparous, high-income, and employed women during pregnancy. Urinary PCP was markedly lower in samples collected during spring compared to other seasons. Linear mixed effect models for repeated measures revealed that ln-transformed SG-adjusted PCP was significantly associated with increased 8-hydroxy-2'-deoxyguanosine (8-OHdG; percent change [%Δ] caused by each interquartile range increase of PCP: 46.2, 95% confidence interval [CI]: 40.2, 52.5) and 8-hydroxyguanosine (8-OHG;%Δ [95% CI]: 44.8 [40.1, 49.8]), but the positive association with 4-hydroxy2-nonenal-mercapturic acid (HNE-MA) was not significant. PCP was also positively associated with increased 8-OHdG and 8-OHG in each trimester using general linear models, and its associations with HNE-MA were only significant at T1 (%Δ [95% CI]: 19.1 [1.05, 40.3]) and T2 (%Δ [95% CI]: 12.6 [0.32, 26.3]). Our findings provide valuable information about PCP exposure characteristics during pregnancy and the potential effects of PCP exposure on oxidative stress in pregnant women., 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 B.V. All rights reserved.)

Currently, research on toxic effects of PCP Na is greatly insufficient. The aim of this study is to explore the toxic effects of PCP-Na for better conducting future work on PCP-Na toxicology. For this purpose, S. constricta adults were exposed to PCP-Na for toxicity testing. The results showed that PCP-Na could easily bioaccumulate in S. constricta and significantly affected both phrase I and II metabolism enzymes. Meanwhile, PCP-Na strongly activated antioxidant system and caused PC, LPO and DNA damage. In addition, neurotoxicity and immunotoxicity of PCP-Na was demonstrated in this study. Interestingly, we observed that PCP-Na significantly affected the expression of genes of electron transport chain and induced key enzymes of glycolysis, indicating that PCP-Na may act as an uncoupler of oxidative phosphorylation, interfering with energy supply and causing energy compensation. This study is the first to fully analyze and provide a new perspective on the toxicity of PCP-Na., 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.)

The ubiquitous presence of pentachlorophenol (PCP) in ocean environments threatens marine organisms. However, its effects on immunity of marine invertebrates at environmentally realistic levels are still largely unknown. In this study, the immunotoxicity of PCP to a representative bivalve species was evaluated. In addition, its impacts on metabolism, energy supply, detoxification, and oxidative stress status were also analysed by physiological examination as well as comparative transcriptomic and metabolomic analyses to reveal potential mechanisms underpinning. Results illustrated that the immunity of blood clams was evidently hampered upon PCP exposure. Additionally, significant alterations in energy metabolism were detected in PCP-exposed clams. Meanwhile, the expressions of key detoxification genes and the in vivo contents (or activity) of key detoxification enzymes were markedly altered. Exposure to PCP also triggered significant elevations in intracellular ROS and MDA whereas evident suppression of haemocyte viability. The abovementioned findings were further supported by transcriptomic and metabolomic analyses. Our results suggest that PCP may hamper the immunity of the blood clam by (i) constraining the cellular energy supply through disrupting metabolism; and (ii) damaging haemocytes through inducing oxidative stress. Considering the high similarity of immunity among species, many marine invertebrates may be threatened by PCP, which deserves more attention., 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 B.V. All rights reserved.)

Pentachlorophenol (PCP) was once a widely employed organochlorine pesticide and wood preservative in United States. Due to its toxicity, the U.S. Environmental Protection Agency has classified it as a restricted-use pesticide and established as a liver carcinogen. Earlier reports have indicated increased production of inflammatory mediators like IL-1β and TNF-α by immune cells, including NK cells, lymphocytes, or monocytes -on PCP exposure. Yet, there is only scant information available regarding the detailed molecular mechanisms affected by acute or chronic exposure of humans to PCP. Considering this, we examined PCP-induced inflammation and downstream signaling events in-(a) human lung adenocarcinoma cells (A549) with type II alveolar epithelial characteristics; and (b) human liver carcinoma cells (HepG2). Treatment of these cells with 1 μM and 10 μM concentration of PCP for 24 h duration resulted in a significant induction of cytokines/chemokines including IL-1β, IL-6, TNF-α, IL-8, CCL2, and CCL5. Assessment of mRNA expression showed upregulated levels of danger-associated molecular patterns (DAMPs)-high mobility group box-1 (HMGB1) and heat shock protein 70 (Hsp70) as well as TLR-4 receptor in PCP-challenged cells. Increased expression of transcription factors-NF-κB and STAT3 provide further insight into the molecular mechanisms underlying PCP-induced toxicity/pathology. Interestingly, antibody-mediated neutralization of DAMPs abrogates PCP-mediated transcriptional induction of cytokines, chemokines and transcription factors in HepG2 and A549 cells. Overall, our findings demonstrate the important role of DAMPs in PCP-induced inflammatory responses., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pentachlorophenol (PCP) is a chlorophenolic compound that is widely used as pesticide, biocide and as a wood preservative to treat utility poles and wharf pilings. PCP is rapidly absorbed through the gastrointestinal tract and enters the blood where it generates active oxygen species in target cells. We have, therefore, examined the protective effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) against PCP-induced cyto-and geno-toxicity in human red blood cells (RBC) and lymphocytes, respectively. Human RBC were incubated at 37°C with 0.75 mM PCP, either alone or in presence of different concentrations of DHB (0.05-2.0 mM). Several biochemical parameters were determined in whole cells and hemolysates. Incubation of RBC with PCP alone increased the formation of reactive oxygen and nitrogen species (ROS and RNS) that resulted in oxidation of proteins, lipids, cellular thiols and plasma membrane damage. The antioxidant defense system was impaired and glucose metabolism was inhibited. However, prior treatment of RBC with DHB lowered ROS and RNS generation and attenuated PCP-induced oxidative damage of cell components. DHB alone enhanced electron transport by the plasma membrane redox system and also prevented its inhibition by PCP. DHB significantly prevented PCP-induced transformation of RBC morphology from normal biconcave shape to spherocytes, spiculated acanthocytes and echinocytes. DHB protected human lymphocytes from PCP-induced DNA damage and strand breaks, lysosomal membrane damage and collapse of the mitochondrial membrane potential. These results show that DHB mitigates PCP-induced cytotoxicity and can potentially function as a chemoprotective agent against the harmful effects of PCP and possibly other chlorophenols.

In November 2018, the Camp Fire devastated the mountain community of Paradise, CA. The burning of plastic pipes, wiring, construction materials, paint, and car batteries released toxic chemicals into the environment, contaminating the air, soil, and local waterways. Examples of toxins that were identified in the creeks and waterways in and around Paradise included pentachlorophenol (PCP), chrysene, and polyaromatic hydrocarbons. The effects of some of these chemicals on embryonic development, hematopoiesis (blood formation), and the immune system have not been thoroughly studied. Defining safe levels and the long-term effects of exposure is imperative to understanding and mitigating potential negative future outcomes. To perform these studies, we utilized zebrafish (Danio rerio), a commonly used vertebrate model system to study development. We observed the adverse effects of PCP on the development of zebrafish by using fluorescence microscopy, and saw that increased concentrations of PCP decreased the numbers of normal red blood cells and myeloid cells. Additionally, we observed that animal survival decreased in response to increasing concentrations of PCP. Furthermore, the prevalence of characteristic physical deformities such as tail curvature were greater in the treatment groups. Lastly, runx1, cmyb, and cd41 expression was reduced in fish treated with PCP. These results suggest that PCP has a previously underappreciated effect on blood and immune cell development and future studies should be performed to determine the molecular mechanisms involved., Competing Interests: D.L.S. is a scientific consultant and has received compensation from Finless Foods, Inc. and Xytogen Biotech, Inc. This does not alter our adherence to PLoS policies on sharing data and materials. All other authors declare no competing interests.

Interactions between nanomaterials (NMs) and coexisting contaminants are important contributors to their joint biological effects, while the reverse actions of bioresponses in determining the toxic interaction between NMs and contaminants were rarely understood. Here, we investigated the toxic interaction and mechanism between TiO 2 NMs (nTiO 2 ) and pentachlorophenol (PCP) in soil using the model nematode (Caenorhabditis elegans). PCP (0.5-50 mg/kg) and nTiO 2 (50-5000 mg/kg) co-exposures induced antagonistic effects on the survival, growth, and locomotion of nematodes, and the levels of ultrastructural damage and oxidative stress exhibited consistent alterations. Soil PCP concentrations changed insignificantly after the single or combined exposures, indicating a negligible direct interaction between PCP and nTiO 2 under the soil condition. Transcriptomic analysis revealed that after 50 mg/kg PCP exposure, half of differentially expressed genes were involved in epidermal collagen synthesis, while the PCP-nTiO 2 co-exposure particularly activated genes related to antistress responses and the positive regulation of physiological functions. Further biochemical analysis demonstrated the antagonistic interactions were derived from two aspects: 1) PCP-induced epidermal collagen incrassation lowered the bioaccumulation and toxicity of nTiO 2 ; 2) nTiO 2 -activated glutathione detoxification pathway alleviated PCP-induced toxicity. These findings highlight the key role of bioresponses in determining toxic interactions between NMs and co-contaminants., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rapid progress in technologies opened the new era of computer-leaded analytics, leaving humans more space for experimental design and decision making. Here we demonstrate the machine learning analysis workflow represented by spectral clustering, elucidation of evolutionary conserved transcription regulation, and network analysis using reverse engineering. Analysis of genes induced by the Pentachlorophenol toxic chemical revealed two subnetworks, one orchestrated by Interferon and another by Nuclear receptor factor 2 (NRF2) gene. Furthermore, network-inference based analysis identified a gene network module composed of genes associated with interferon signaling and their regulatory interaction with downstream genes, especially TRIM family proteins involved in responses of innate immune systems., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Carboxylated multi-walled carbon nanotubes (MWCNT-COOH) exerts strong adsorption capacity for pentachlorophenol (PCP) and they inevitably co-occur in the environment, but few studies have characterized the effects of MWCNT-COOH on the bioavailability of PCP and its oxidative and tissue damages to fish. In this work, we assessed the PCP accumulation in different organs and the induced oxidative and tissue damages of goldfish following 50-d in vivo exposure to PCP alone or co-exposure with MWCNT-COOH. Our results indicated that PCP bioaccumulation in goldfish liver, gill, muscle, intestine and gut contents was inhibited after co-exposure with MWCNT-COOH in uptake phase. PCP exposure alone and co-exposure with MWCNT-COOH evoked severe oxidative and tissue damages in goldfish bodies, as indicated by significant inhibition of activities of antioxidant enzymes, remarkable decrease in glutathione level, simultaneous elevation of malondialdehyde content, and obvious histological damages to liver and gill. The decreased accumulation of PCP in the presence of MWCNT-COOH led to the reduction of PCP-induced toxicity to liver tissues, as confirmed by the alleviation of hepatic oxidative damages. However, co-exposure groups had higher concentrations of PCP in the tissues than PCP treatment alone (p < 0.05 each) in the depuration phase, revealing that MWCNT-COOH-bound pollutants might pose higher risk once desorbed from the nanoparticles. These results provided substantial information regarding the combined effects of PCP and MWCNT-COOH on aquatic species, which helps to deeply understand the potential ecological risks of the emerging pollutants., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Chlorophenols are not only noticed in an effluvium of industries but also can emerge from the water treatment plants for domestic supply which poses a high threat for crop production and human health. Therefore, research on their risks to ecosystem and human health via ecotoxicological tests to derivate permissible environmental contaminant concentrations is necessary. The chlorophenols produced in the course of chlorination of potable water is an outcome of natural carboxylic acids/organic material and those chlorophenols occurred as emerging disinfection byproducts (EDBPs). Among chlorophenols, pentachlorophenol (PCP) has been recently identified as one of the important EDBPs. The main objective was to evaluate the PCP-induced genotoxicity and the oxidative damage in two plant species, i.e., Allium cepa and Vigna radiata. Genotoxicity of PCP was examined at three selected concentrations based on EC 50 (half-maximal effective concentrations) values in both the plants along with the defense mechanism. EC 50 value for A. cepa and V. radiata was 0.7 mg/L and 35 mg/L. Root length inhibition, DNA laddering, lipid peroxidation, H 2 O 2 content, and antioxidant enzymatic assays evaluated revealed a dose-dependent response. PCP influenced defense enzyme glutathione peroxidase (GPX) and ascorbate peroxidase (APX) action in both plants and showed deprivement of catalase (CAT) with the increase of PCP concentrations. PCP-invaded toxicity management by these plants implied that A. cepa is more sensitive than V. radiata regarding PCP-induced toxicity.

Bacteria detection and toxicity measurement are essential in many aspects. Becoming increasingly popular in recent years, paper-based analytical devices (PADs) have proven to be cost-effective, portable and eco-friendly with quantitative diagnostic results. In this work, by a straightforward soaking-drying method, a resazurin-deposited PAD has been developed for rapid bacteria detection and biotoxicity measurement. The colorimetric response on the PAD was generated from metabolic reduction of resazurin by Enterococcus faecalis, a facultative anaerobic bacterial strain. After recording and quantifying the colorimetric response with Hue value by a smartphone, the bioassay on PAD enables the detection of resazurin reduction kinetics difference among bacteria at various densities in 10 min. Thereby, the bioassay on PAD was applied to study the toxicity of two chlorophenols, i.e. pentachlorophenol (PCP) and 4-chlorophenol (4-CP), to E. faecalis. Compared to growth-based inhibition test, which takes 5 h, this assay shows higher efficiency, i.e. in 30 min, the biotoxicity difference between PCP and 4-CP can be identified., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Discharged carbon nanotubes (CNTs) likely interact with co-existing organic contaminants (OCs) and pose joint toxicity to environmental microbes. Herein, hydrophobic pentachlorophenol (PCP) and hydrophilic ciprofloxacin (CIP) were used as representative OCs and their joint toxicities with CNTs to Bacillus subtilis were systematically investigated at cellular, biochemical, and omics levels. The 3-h bacterial growth half inhibitory concentrations of CNTs, PCP, and CIP were 12.5 ± 2.6, 3.5 ± 0.5, and 0.46 ± 0.03 mg/L, respectively, and they all could damage cell membrane, increase intracellular oxidative stress, and alter bacterial metabolomics and transcriptomics; while CNTs-PCP and CNTs-CIP binary exposures exhibited distinct additive and synergistic toxicities, respectively. CNTs increased bacterial bioaccumulation of PCP and CIP via destabilizing and damaging cell membrane. PCP reduced the bioaccumulation of CNTs, while CIP had no significant effect; this difference could be owing to the different effects of the two OCs on cell-surface hydrophobicity and CNTs electronegativity. The additive toxicity outcome upon CNTs-PCP co-exposure could be a result of the balance between the increased toxicity from increased PCP bioaccumulation and the decreased toxicity from decreased CNTs bioaccumulation. The increased bioaccumulation of CIP contributed to the synergistic toxicity upon CNTs-CIP co-exposure, as confirmed by the increased inhibition of topoisomerase Ⅳ activity and interference in gene expressions regulating ABC transporters and lysine biosynthesis. The findings provide novel insights into environmental risks of CNTs., 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.)

Understanding the degradation of pentachlorophenol (PCP) by indigenous microorganisms stimulated by an electron donor and shuttle in paddy soil, and the influences of PCP/electron donor/shuttle on the native microbial community are important for biodegradation and ecological and environmental safety. Previous studies focused on the kinetics and the microbial actions of PCP degradation, however, the effects of toxic and antimicrobial PCP and electron donor/shuttle on the microbial community diversity and composition in paddy soil are poorly understood. In this study, the effects of PCP, an electron donor (lactate), and the electron shuttle (anthraquinone-2, 6-disulfonate, AQDS) on the microbial community in paddy soil were investigated. The results showed that the presence of PCP reduced the microbial diversity compared to the control during PCP degradation, while increased the microbial diversity was observed in response to lactate and AQDS. The addition of PCP stimulated the microorganisms involved in PCP dechlorination, including Clostridium, Desulfitobacterium, Pandoraea, and unclassified Veillonellaceae, which were dormant in raw soil without PCP stress. In all of the treatments with PCP, the addition of lactate or AQDS enhanced PCP dechlorination by stimulating the growth of functional groups involved in PCP dechlorination and by changing the microbial community during dechlorination process. The microbial community tended to be uniform after complete PCP degradation (28 days). However, when lactate and AQDS were present simultaneously in PCP-contaminated soil, lactate acted as a carbon source or electron donor to promote the activities of microbial community, and AQDS changed the redox potential because of the production of reduced AQDS. These findings enhance our understanding of the effect of PCP and a biostimulation method for PCP biodegradation in soil ecosystems at the microbial community level, and suggest the appropriate selection of an electron donor/shuttle for accelerating the bioremediation of PCP-contaminated soils., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study investigated the influences of titanium dioxide nanoparticles (n-TiO 2 ) on the thyroid endocrine disruption and neurobehavioral defects induced by pentachlorophenol (PCP) in zebrafish (Danio rerio). Embryos (2 h post-fertilization) were exposed to PCP (0, 3, 10, and 30 μg/L) or in combination with n-TiO 2 (0.1 mg/L) until 6 days post-fertilization. The results showed that n-TiO 2 alone did not affect thyroid hormones levels or transcriptions of related genes. Exposure to PCP significantly decreased thyroid hormone thyroxine (T4) content, thyroid stimulating hormone (TSH) level and transcription of thyroglobulin (tg), but significantly increased 3,5,3'-triiodothyronine (T3) level and upregulation of deiodinase 2 (dio2). In comparison, the co-exposure with n-TiO 2 significantly reduced the content of T3 by depressing the potential targets, tg and dio2. For neurotoxicity, the single and co-exposure resulted in similar effects with significant downregulation of neurodevelopment-related genes (ELAV like RNA Binding Protein 3, elavl3; Growth associated protein-43, gap43; α-tubulin) and inhibited locomotor activity. The results indicated that the presence of n-TiO 2 significantly enhanced the PCP-induced thyroid endocrine disruption but not the neurobehavioral defects in zebrafish larvae., 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.)

Pentachlorophenol (PCP) is a widespread and persistent hydrophobic organic pollutant in the environment despite its restricted public use. Risk assessment of such hydrophobic organic compounds (HOCs) is challenging because sorption and volatilization issues during toxicity test often lead to inconsistent exposure concentration. Considering the hydrophobicity of the PCP, in this study, a passive dosing format was applied by adopting a silicone O-ring as a reservoir and evaluated its applicability on the determination of PCP on Daphnia magna. Results obtained with passive dosing method were compared with that of solvent spiking method. We hypothesized that the passive dosing method may provide more reliable and accurate toxicity results than conventional solvent spiking approach. As a result, the partition coefficient of PCP between methanol and a test medium (log K MeOH:ISO ) was 2.1, which enabled the maintenance of reliable exposure concentration throughout the experiment. In the acute toxicity tests, passive dosing and solvent spiking showed similar EC50 values of 576 and 485 µg/L for 24 h, and 362 and 374 µg/L for 48 h, respectively, which overlap with EC50 values of previous studies. Altogether, both methods were suitable for the acute toxicity assessment of hydrophobic PCP.

This paper presents the use of a commercial quartz crystal microbalance (QCM) to investigate live-cell activity in water-based toxic solutions. The QCM used in this research has a resonant frequency of 10 MHz and consists of an AT-cut quartz crystal with gold electrodes on both sides. This QCM was transformed into a functional biosensor by integrating with polydimethylsiloxane culturing chambers. Rainbow trout gill epithelial cells were cultured on the resonators as a sensorial layer. The fluctuation of the resonant frequency, due to the change of cell morphology and adhesion, is an indicator of water toxicity. The shift in the resonant frequency provides information about the viability of the cells after exposure to toxicants. The toxicity result shows distinct responses after exposing cells to 0.526 μM of pentachlorophenol (PCP) solution, which is the Military Exposure Guidelines concentration. This research demonstrated that the QCM is sensitive to a low concentration of PCP and no further modification of the QCM surface was required.

Purpose: Course evaluations by students are a standard tool that U.S. universities use to monitor the quality of their product. Here, the authors examine an alternative method of monitoring instructional quality that differs from traditional approaches in that it does not rely on students' ratings. The authors sought to glean relevant diagnostic information about course effectiveness from in-class exams used to assess students' learning progress (i.e., cognitively diagnostic assessments that explicitly target instructional content)., Method: The authors used data from an end-of-course, cumulative exam given in 2015 and in 2016 to 200 first-year medical students. They mapped the exam questions to 4 attributes and analyzed the students' overall mastery of the content tested and the percentage of students mastering each attribute., Results: Analyses of the cognitively diagnostic assessment data revealed the percentage of the cohort who achieved/failed to achieve mastery of each of the attributes, discreet mastery profiles that distinguish among students with similar scores, and the percentage of the cohort within each of the 16 attribute mastery profiles. Analysis allowed the authors to evaluate how well the course content was delivered., Conclusions: Cognitively diagnostic assessments enable in-class tests to appraise which skills specified in the curriculum have/have not been mastered by the students and how many students have mastered/failed to master which particular skills. Hence, if the learning goals have been well defined at the beginning of a course, then cognitively diagnostic assessments can show to what degree the instructional objectives have actually been accomplished.

The environmental contaminants pentachlorophenol (PCP) and 4, 4'-dichlorodiphenyltrichloroethane (DDT) are detected in some human blood samples at levels as high as 5 μM (PCP) and 260 nM (DDT). Several cancers are associated with exposures to these contaminants. IL-6 is a pro-inflammatory cytokine that when dysregulated stimulates inflammatory diseases and tumor progression. Immune cells exposed to PCP at 0.05-5 μM and DDT at 0.025-2.5 μM showed increased secretion of IL-6 when the cell preparations contained either T lymphocytes or monocytes. Increased IL-6 secretion was due to PCP and DDT induced cellular production of the cytokine and was dependent on MAP kinase signaling pathways (in the case of PCP). Compound-induced increases in IL-6 production were in part due to increases in either the transcription of and/or stability of its mRNA. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by immune cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present study, in vivo antioxidant properties of the n-butanol extract obtained from aerial parts of Perralderia coronopifolia were investigated in term of its hepatoprotective effect of female Wistar albino rats (n, 36; average age, 48 ± 5 days; weighing 150 ± 18 g) against PCP (pentachlorphenol)-induced toxicity. PCP (20 mg/kg b.w.) and plant extract (50 mg/kg b.w.) were administered daily by gavages for 2 weeks. Vitamin E (100 mg/kg b.w.) was given intraperitoneally as a positive control. Lipid peroxidation (LPO) levels, reduced glutathione (GSH) levels, and glutathione peroxidase (GPx) activities were evaluated in liver homogenates. While, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglyceride parameters were analyzed in serums. The liver fragments were observed using light microscopy. Experimental results exhibited that PCP-treated group has a significant increase in the liver lipid peroxidation (LPO) levels of animals while decreased in plant extract-treated group. In addition, PCP caused significant decreases in glutathione peroxidase (GPx) activities and reduced glutathione (GSH) levels. Moreover, PCP induced hepatotoxicity by increasing serum transaminase enzymes, cholesterol, and triglyceride levels. While, these levels were restored to control value in animals treated with plant extract. The regularized levels of LPO, GSH, cholesterol, triglyceride, transaminase enzymes, and GPx activities revealed the antioxidant properties of the extract plant as well as of the vitamin E. The histological study showed the hepatoprotective effect of our extracts against PCP-induced acute intoxication, protecting the hepatic architecture and decreasing the functional and structural alterations of the liver. The plant extract had high antioxidant potential and completely prevented the toxic effect of PCP on the above of liver and serum parameters.

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 μm for PCP and 260 nm for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin (IL)-1β is a proinflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL-1β are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL-1β. This study shows that the increased secretion of IL-1β seen with both contaminants is due to compound-induced increases in the production of this cytokine. Increased production began within 6 hours of exposure to PCP and continued to increase up to 24 hours. DDT-induced stimulation of IL-1β appeared to be maximal after 6 hours of exposure and then diminished by 24 hours. The increases seen in IL-1β production stimulated by PCP appear to be at least partially due to compound-induced increases in IL-1β mRNA. Although DDT caused increased production of IL-1β, it did not appear to cause consistent increases in its mRNA. PCP- and DDT-induced increases in IL-1β production were dependent primarily on the p38 mitogen-activated protein kinase pathway. These results indicate that both PCP and DDT are able to increase IL-1β production in a p38 mitogen-activated protein kinase-dependent manner, which may have the potential to influence chronic inflammation., (© 2019 John Wiley & Sons, Ltd.)

As knowledge regarding mechanisms of pentachlorophenol (PCP) toxicity in neuronal cell lines is limited, the aim of the study was to evaluate the effects of PCP and its active metabolites, tetrachloro-1,4-benzoquinone (TCBQ) and tetrachlorohydroquinone (TCHQ) in human neuroblastoma SH-SY5Y cells. All compounds induced cytotoxic effects in time- and dose-dependent manners, and resulted in differential modes of cell death. Reduced mitochondrial membrane potential (ΔᴪM) and oxidative damage lead to apoptosis and necrosis following TCBQ and PCP exposure, respectively. Time-dependent investigations revealed transient ΔᴪM recovery in TCHQ exposed cells, and redox stress. Sufficient ΔᴪM recovery allowed apoptosis completion in TCHQ exposed cells, whereas overwhelming metabolic and oxidative stress saw a conversion from apoptotic to necrotic-like cell death. The onset of mitochondrial dysfunction preceded that of redox damage for all compounds, indicating that oxidative damage is secondary to ΔᴪM insult. Cytotoxic events were further linked to cell cycle. S phase and G2/M blocks were observed after 12 h exposure to TCBQ and TCHQ, respectively, while a G1 block occurred after 24 h exposure to PCP. This study provides new insight regarding time-dependant toxic effects of PCP and its metabolites in human neuronal cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The expense and time required for in vivo reproductive and developmental toxicity studies have driven the development of in vitro alternatives. Here, we used a new in vitro split luciferase-based assay to screen a library of 177 toxicants for inhibitors of apoptosome formation. The apoptosome contains seven Apoptotic Protease-Activating Factor-1 (Apaf-1) molecules and induces cell death by activating caspase-9. Apaf-1-dependent caspase activation also plays an important role in CNS development and spermatogenesis. In the in vitro assay, Apaf-1 fused to an N-terminal fragment of luciferase binds to Apaf-1 fused to a C-terminal fragment of luciferase and reconstitutes luciferase activity. Our assay indicated that pentachlorophenol (PCP) inhibits apoptosome formation, and further investigation revealed that PCP binds to cytochrome c. PCP is a wood preservative that reduces male fertility by ill-defined mechanisms. Although the data show that PCP inhibited apoptosome formation, the concentration required suggests that other mechanisms may be more important for PCP's effects on spermatogenesis. Nonetheless, the data demonstrate the utility of the new assay in identifying apoptosome inhibitors, and we suggest that the assay may be useful in screening for reproductive and developmental toxicants., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Chemical pollutants often co-occur and can interact to cause unexpected combined toxic effects. Both pentachlorophenol (PCP) and copper-1,10-phenanthroline [Cu(OP)2], used as wood preservatives, coexist in fluids and tissues of ordinary population. Our previous studies demonstrate that a combination of subtoxic PCP and Cu(OP)2 causes synergistic toxicity on Escherichia coli and hepatocarcinoma cells. However, it is not clear whether this effect also occurs in normal hepatocytes; and if so, what are the differences as compared with the hepatocarcinoma cells. We demonstrate that the combination of low-toxic PCP and Cu(OP)2 (0-1.6 µM; PCP/Cu(OP)2 molar ratio: 2:1) induces a concentration-dependent intracellular copper accumulation, apoptosis, caspase-3/9 activation, depolarization of mitochondrial membrane potential, and oxidative stress (reactive oxygen species increasing and glutathione/oxidized glutathione ratio decreasing) in both normal hepatocytes HL-7702 and hepatocarcinoma HepG2 cells. However, HepG2 cells are more susceptible to the above molecular events as compared with HL-7702 cells. Further data reveal that PCP/Cu(OP)2 markedly decreases X chromosome-linked inhibitor of apoptosis (XIAP), p-ERK-1/2, and p-JNK protein expression in HepG2, but not HL-7702. Overexpression of XIAP gene in HepG2 significantly blocks PCP/Cu(OP)2-induced cytotoxicity, caspase activity, apoptosis, ROS accumulation, and antioxidant genes expression. These results suggest that the combination of low-toxic PCP and Cu(OP)2 preferentially induce synergistic cytotoxicity in human hepatocarcinoma cells by XIAP-ROS-apoptosis pathway, compared with the normal hepatocytes. The present data not only confirm the synergistic toxicity of PCP/Cu(OP)2 combination in normal liver cells, but also suggest a possible opportunity in developing new therapeutic approaches for liver cancer by sensitizing cancer cells to chemotherapy., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pentachlorophenol (PCP) and its byproduct hexachlorobenze (HCB) are two co-existing persistent environmental chemicals, but their combined toxicity remains unclear. In this study, adult zebrafish were exposed to 5 (low dose) and 25 μg·L -1 (high dose) of PCP, HCB or their combination for 21 days, and the impact on endocrine and reproduction was investigated. Results showed that combined exposure to 25 μg·L -1 PCP and 25 μg· L -1 HCB significantly increased the plasma estradiol (E2) and testosterone (T) levels, altered the expressions of genes along the hypothalamic-pituitary-gonadal-liver (HPGL) axis, inhibited gonadal development, and eventually lead to decreased egg production of F0 zebrafish as well as inhibited development of F1 eggs/larvae. Compared to the combined exposure of high doses, significantly lower levels of plasma E2 and T were observed for either the high PCP or high HCB alone exposure, indicating a synergistic effect of the two chemicals on endocrine disruption after combination. Furthermore, the high PCP alone exposure inhibited the gonadal development in both the males and females, while the HCB alone exposure did not. Comparison of exposure effects indicated a greater decrease of mature gametes levels and egg production in the high combined group when compared to the high HCB alone group, but no significant difference was observed between the high combined group and the high PCP alone group. Taken together, the results suggested that combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish, and result in reproduction impairments, with PCP being the primary contributor., (Copyright © 2018. Published by Elsevier Ltd.)

Pentachlorophenol (PCP) is often used as chlorinated hydrocarbon herbicides and insecticides, which has been suggested that toxicity of carcinogenic effect, teratogenic effect and reproductive system. However, there was still precious known about the underlying molecular mechanism of PCP on mammalian early development. To explore the developmental toxicity of PCP and its potential mechanism, pregnancy ICR mice except controls were exposed to PCP (0.02, 0.2 or 2 mg/kg) during gestation day (GD) 0.5 to GD8.5 in this study. We found that the fetal loss rate was increased and placental chorionic villi structure was disorder in hematoxylin-eosin staining (HE) on GD16.5. Meanwhile, autophagosomes were observed in chorionic villi through Transmission Electron Microscope (TEM). Moreover, the mRNA and/or protein expression of P62, LC3-ІІ/LC3-І and Beclin1 were increased in placenta, indicating the occurrence of autophagy. Then, to further explore the autophagy mechanism, microRNA (miR)-30a-5p, an expression inhibitor of Beclin1, was predicted through bioinformatics predictions and RT-PCR, and it was reduced in PCP-treated mice. Transfection and luciferase reporter gene test were used to verify the interaction between Beclin1 and miR-30a-5p. These results firstly indicate that, PCP exposure could downregulate the expression of miR-30a-5p, and then induced autophagy through upregulation of Beclin1 to result in fetal loss. Our study laid a foundation for understanding the PCP developmental toxicity through autophagy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Our previous study showed that tetrachlorobenzoquinone (TCBQ) mediated the activation of Nod-like receptor protein 3 (NLRP3) inflammasome, which involves K + efflux, reactive oxygen species (ROS) production, and mitochondrial DNA damage. In addition, TCBQ down-regulates NLRP3 ubiquitination and promotes the activation of NLRP3 inflammasome. However, the induction of NLRP3 inflammasome by atypical pathways has not yet been characterized. Using human umbilical vein endothelial cells (HUVEC), we discovered that TCBQ activates caspase 1/4/5 and cleaves gasdermin D (GSDMD) into N-terminal and C-terminal cleavage products. In parallel, TCBQ also activates receptor interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) signaling pathways. The N-terminal fragments of GSDMD and MLKL translocate from cytoplasm to cell membrane and form oligomers and membrane pores on the cell membrane. The formation of membrane pores not only promotes the extracellular secretion of interleukin 1 beta (IL-1β) but also affects cellular ion homeostasis, in particular promotes K + outflow, which further activates NLRP3 inflammasome and aggravates cellular inflammation. These results indicated that GSDMD and MLKL play important roles in TCBQ-induced endothelial pro-inflammatory responses, which may point to potential therapeutic approaches for TCBQ-mediated toxicity.

Background: The impacts of man-made chemicals, in particular of persistent organic pollutants, are multifactorial as they may affect the integrity of ecosystems, alter biodiversity and have undesirable effects on many organisms. We have previously demonstrated that the belowground mycobiota of forest soils acts as a buffer against the biocide pollutant pentachlorophenol. However, the trade-offs made by mycobiota to mitigate this pollutant remain cryptic., Results: Herein, we demonstrate using a culture-dependent approach that exposure to pentachlorophenol led to alterations in the composition and functioning of the metacommunity, many of which were not fully alleviated when most of the biocide was degraded. Proteomic and physiological analyses showed that the carbon and nitrogen metabolisms were particularly affected. This dysregulation is possibly linked to the higher pathogenic potential of the metacommunity following exposure to the biocide, supported by the secretion of proteins related to pathogenicity and reduced susceptibility to a fungicide. Our findings provide additional evidence for the silent risks of environmental pollution, particularly as it may favour the development of pathogenic trade-offs in fungi, which may impose serious threats to animals and plant hosts.

The standard Folsomia candida test (ISO 11267), in which only the survival and reproduction of the parental generation (F0) were determined, is insufficient to assess the toxicity of chemicals, like endocrine disrupting chemicals (EDCs), since the effects of EDCs could last for several generations and sometimes can be transgenerational. It's necessary to assess the effects on subsequent generations to address the long-term consequences of these chemicals exposure. In this study, the effects of pentachlorophenol (PCP) and 2,2',4,4'-tetrabromodiphenyl (BDE47) were assessed on F0 and the first filial generation (F1) of F. candida after 28-day or 10-day exposure of F0. In the 28-day exposure method, F0 was exposed to PCP or BD47 for 28 days and F1 was exposed for about 21 days. In the 10-day exposure method, F0 was exposed for 10 days and F1 was not exposed. The F. candida reproduction of F0 and F1 can be assessed in both methods, while transgenerational effects can further be evaluated in the 10-day exposure method. The numbers of F1 and F2 (second filial generation) juveniles in the 28-day exposure method and F1 juveniles in the 10-day exposure method decreased significantly for the PCP treatment. For BDE47, only the number of F1 juveniles in the 28-day exposure method significantly decreased. The EC50 values of F0 reproduction (the number of F1 juveniles) in the 28-day exposure method were 89 and 306 mg/kg dry soil for PCP and BDE47, respectively. Results suggested that PCP could affect F. candida egg hatching or juvenile survival and adult reproductive capacity, while BDE47 was more likely to affect egg hatchability or juvenile survival rather than adult reproductive capacity. It also indicated that F. candida exposed to PCP or BDE47 could recover in clean soil. Transgenerational effects were not observed for neither PCP nor BDE47 in this study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pentachlorophenol (PCP) is a organochlorine biocide that, unlike most other organochlorines, is still in use as timber preservative. Its water solubility, high toxicity, bioaccumulation potential, and the concentrations reported in estuarine waters (up to 0.1 µg L -1 ) indicate it may pose a risk in coastal environments. Aquatic environrmental regulations are commonly based on standard freshwater organisms that may not represent the sensitivity of marine species. The present study consists of a water quality criteira reevalutation of PCP in coastal waters based on toxicity tests conducted recording sensitive endpoints of marine species representative of coastal ecosystems, following QA/QC standard procedures. The toxicity thresholds (EC 10 ) found were 4.69 µg L -1 for Paracentrotus lividus sea-urchin embryos, 6.47 µg L -1 for Mytilus galloprovincialis mussel larvae, and 78.4 µg L -1 for Isochrysis galbana cells. Therefore, there is only one order of magnitude between the predicted no-effect concentration (PNEC) for early life stages of bivalves and echinoderms and the maximum concentrations actually recorded in coastal water, which yields a remarkable risk quotient for PCP in these highly productive marine habitats. In addition, we have reviewed the ecotoxicological data on PCP toxicity on marine species representative of the main systematic groups, from algae to chordates, and derived a probabilistic acute saltwater quality criterion of 2.66 µg L -1 , intended to protect 95% of the marine species. Lack of adequate protection for marine ecosystems in some current PCP national guidelines has been identified.

Resazurin is widely used as a metabolic indicator for living cells, however, there has been considerable debate in the literature with regards to the specific location in the cell where the non-fluorescent resazurin is reduced to the strongly fluorescent resorufin. This lack of clarity about the reduction site makes the use of resazurin reduction data in cytotoxicity studies difficult to interpret. In this study, E. faecalis, a Gram-positive and facultative anaerobic bacterial strain, and the most toxic chlorophenol, pentachlorophenol (PCP), were chosen as models for an anaerobe and toxicant, respectively. By studying the kinetics of resazurin reduction by E. faecalis after different treatments (cell disruption, bacterial filtration, and pre-exposure to toxicant), we confirmed that resazurin reduction to resorufin by live Gram-positive and facultative anaerobic bacterial cells can only happen intracellularly under anaerobic conditions, while resorufin reduction to dihydroresorufin can happen both intracellularly and extracellularly. Based on the understanding of these fundamental mechanisms, we suggest that resazurin reduction can be used as a quick bioassay for measuring cytotoxicity., (© 2017 Wiley Periodicals, Inc.)

Species sensitivity distribution (SSD) model is often used to extrapolate the chemicals' effects from the ecotoxicological data on individual species to ecosystems, and is widely applied to derive water quality criteria or to assess ecological risk. Because of the influence of various factors, the ecotoxicological data of a specific chemicals to an individual usually exist in a range. The feasibility of interval ecotoxicological data directly applied to build SSD model has not been clearly stated. In the present study, by means of Bayesian statistics, the half maximal effective concentration (EC 50 ) of pentachlorophenol (PCP) to 161 aquatic organisms, which were organized into 7 groups, i.e., single determined value, geometric mean estimation, median estimation, interval data, and combination of single determined data with other groups, were used to develop SSD models and to estimate the minimum sample sizes. The results showed that the interval data could be directly applied to build SSD model, and when combined with single point data could give the narrowest credible interval that indicates a stable and robust SSD model. Meanwhile, the results also implied that at least 6-14 ecotoxicological data were required to build a stable SSD model. It suggests that the utilization of interval data in building SSD model can effectively enhance the availability of ecotoxicological data, reduce the uncertainty brought by sample size or point estimation, and provide a reliable way to widen the application of SSD model., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Caspase proteases play an essential role in cell apoptosis and inflammation, thus matter greatly in animal development and other biological processes. As a ubiquitous environmental pollutant, pentachlorophenol (PCP) is considered to have adverse effects on animal apoptosis during embryonic development, yet the evidence that PCP interfere with caspase genes was seldom reported. To uncover the effects of PCP on caspases expression in early embryos of zebrafish, two concentrations of PCP (5 μg/L and 200 μg/L) were chosen and 14 types of caspase genes at two different developmental stages, 8 h post-fertilization (hpf) and 24 hpf were analyzed. Lower survival and hatching rates, distinct developmental delay and morphological deformities of head and tail were observed. PCP, especially in the high concentration, significantly altered the expressions of most caspase genes. At 8 hpf, PCP had the most significant inductive effects on gene casp8l2 with fold changes (FCs) of 6.87 at 5 μg/L and 4.48 at 200 μg/L, and casp6l1 (with FCs of 3.15/3.69), and inhibitory effects on caspa (with FCs of 0.93/0.53) and caspb (with FCs of 0.99/0.57). At 24 hpf, PCP had the most significant effects on casp6l2, casp9, and caspc. PCP exposure possibly disrupted intrinsic apoptosis pathway considering its effects on casp9 expression. In addition, most caspase genes exhibited higher levels at 24 hpf than 8 hpf except caspc. Our results suggested that PCP had different effects on varied caspase genes, which probably resulting in a profound impact on caspase proteins and apoptosis processes and, ultimately, developmental abnormality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pentachlorophenol (PCP) was used in large quantities, and mainly for killing the intermediate host snails of schistosome in China, thereby resulting in ubiquitous PCP residue in the environment. However, studies considering the carcinogenicity of PCP for humans mainly focused on occupational workers, and the actual carcinogenicity of PCP for general population is uncertain. To investigate the association between cancer risks and PCP exposure in a community population, an ecological study was conducted in three contaminated areas along the Yangtze River. Standardized rate ratio (SRR) was calculated to represent the risk of cancer incidence, by using incidence in the low PCP exposure category as the reference group. A total of 15,962 cancer records were collected, and 76 water samples and 213 urine samples in three areas were examined. Our findings suggested that compared with the low PCP group, the high PCP group had significantly excessive incidences of various cancers related to different organs including lymph (SRR = 19.44, 95% CI = 15.00-25.19), blood (SRR = 17.24, 95% CI = 12.92-23.01), nasopharynx (SRR = 3.97, 95% CI = 3.75-4.21), gallbladder (SRR = 3.46, 95% CI = 3.09-3.87), pancreas (SRR = 3.41, 95% CI = 3.07-3.79), respiratory system (SRR = 3.41, 95% CI = 3.27-3.57) and liver (SRR = 3.31, 95% CI = 3.09-3.56). Taken together, our present study provides evidence that general community population exposed to high level of PCP exhibits a broader spectrum of increased cancer risks as compared to occupational groups., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Glutathione S-transferases (GST) play a prominent role in protecting cells against oxidative stress. Our previous study showed that the reactive oxygen species (ROS) generated from pentachlorophenol (PCP) could cause an acute impact on freshwater bivalve Anodonta Woodiana, but its chronic toxicity remain unclear. In order to investigate the chronic effect of PCP, clams A. Woodiana were randomly grouped into PCP treated group in which animals were administrated with 13.9 μg/L concentrations of PCP, and control group those with similar volume dimethyl sulfoxide. In addition, two complete GST sequences were isolated from A. Woodianaa and respectively named AwGST1 and AwGST2. The full-length cDNA of AwGST1 was consisted of a 5' untranslated region (UTR) of 132 bp, a 3' UTR of 80 bp and an open reading frame (ORF) of 609 bp encoding a polypeptide of 203 amino acids. The full-length cDNA of AwGST2 contained a 5' UTR of 57 bp, a 3' UTR of 291 bp and an ORF of 678 bp encoding a polypeptide of 226 amino acids. The constitutive expression levels of AwGST1 and AwGST2 were examined in different tissues including foot, mantle, adductor muscle, heart, hepatopancreas, hemocytes and gill. Administration of PCP could result in a significant increase of AwGST1 and AwGST2 expression in the hepatopancreas, gill and hemocytes. In the hepatopancreas, AwGST1 mRNA levels of PCP treated group increased more than 28.73% at day 1, then 70.37% (P < 0.05) at day 3, reach to 6.64 times (P < 0.01) at day 15 in contrasted with that of control group. AwGST2 increased more 18.18%, 82.88% (P < 0.05) and 2.43 times (P < 0.01) at day 1, 3 and 15, respectively. In the gill, AwGST1 expression showed a significant up-regulation in the PCP treated group during experiment observed compared with that of control group, mRNA level of AwGST2 increased more than 1.44 times (P < 0.05). In addition, expressions of AwGST1 and AwGST2 were significantly induced after PCP treatment in the hemocytes. These results indicated that up-regulations of AwGST1 and AwGST2 expression in bivalve A. woodiana are contribute to against oxidative stress derived from PCP treatment during experiment observed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)