Environmental fate and risk evolution of calcium channel blockers from chlorine-based disinfection to sunlit surface waters.

Organic micropollutants present in disinfected wastewater and discharged to sunlit surface waters may be transformed by multiple processes, such as chlorination due to the presence of chlorine residuals, solar irradiation as well as solar-irradiated chlorine residues. This study reports, for the first time, the multi-scenario degradation kinetics, transformation products, and risk evolution of calcium channel blockers (CCBs), a class of emerging pharmaceutical contaminants with worldwide prevalence in natural waters and wastewater. It was found that the chlorination of the studied CCBs (amlodipine (AML) and verapamil (VER)) was dominated by the reaction of HOCl with their neutral species, with second-order rate constants of 6.15×104 M-1 s-1 (AML) and 7.93×103 M-1 s-1 (VER) at pH 5.0-11.0. Bromination is much faster than chlorination, with the measured kapp,HOBr values of 2.94×105 M-1 s-1 and 6.58×103 M-1 s-1 for AML and VER, respectively, at pH 7.0. Furthermore, both CCBs would undergo photolytic attenuations with hydroxyl and carbonate radicals as the dominant reactive species in water. Notably, free chlorine mainly contributed to their abatement during the solar/chlorine treatment. Additionally, the halogen addition on the aromatic ring was observed during chlorination and bromination of the two CCBs. Cyclization was observed under solar irradiation only, while the aromatic ring was opened in the solar/chlorine system. Some products generated by the three transformation processes exhibited non-negligible risks of high biodegradation recalcitrance and toxicity, potentially threatening the aquatic environment and public health. Overall, this study elucidated the environmental fate of typical CCBs under different transformation processes to better understand the resulting ecological risks in these environmental scenarios.

Degradation of methotrexate by unactivated and solar-activated peroxymonosulfate in water: Moiety-specific reaction kinetics and transformation product-associated risks.

Anticancer drugs have raised worldwide concern owing to their ubiquitous occurrence and ecological risks, necessitating the development of efficient removal strategies in water and wastewater treatment. Although peroxymonosulfate (PMS) is known to be a promising chemical in water decontamination, limited information is available regarding the removal efficiency of anticancer drugs by PMS and solar/PMS systems. This study first reports the moiety-specific reaction kinetics and mechanisms of methotrexate (MTX), an anticancer drug with widespread attention, by PMS (unactivated) and solar-activated PMS in water. It was found that MTX abatement by the direct PMS oxidation followed second-order kinetics, and the pH-dependent rate constants increased from 0.4 M-1 s-1 (pH 5.0) to 1.3 M-1 s-1 (pH 8.0), with a slight decrease to 1.1 M-1 s-1 at pH 9.0. The presence of chloride and bromide exerted no obvious influence on the removal of MTX by PMS. Furthermore, the chemical reactivity of MTX and its seven substructures with different reactive species was evaluated, and the degradation contributions of the reactive species involved were quantitatively analyzed in the solar/PMS system. The product analysis suggested similar reaction pathways of MTX by PMS and solar/PMS systems. The persistence, bioaccumulation, and toxicity of the transformation products were investigated, indicating treatment-driven risks. Notably, MTX can be removed efficiently from both municipal and hospital wastewater effluents by the solar/PMS system, suggesting its great potential in wastewater treatment applications. Overall, this study systematically evaluated the elimination of MTX by the unactivated PMS and solar/PMS treatment processes in water. The obtained findings may have implications for the mechanistic understanding and development of PMS-based processes for the degradation of such micropollutants in wastewater.

Unveiling the treatment-driven secondary risks of pharmaceuticals: New lessons from calcium channel blocker transformation by multiple oxidants.

The worldwide detection of numerous pharmaceuticals and their transformation products (TPs) in different environmental matrices has gained considerable concern about their potential ecological hazards. Increasing evidence suggested that calcium channel blockers (CCBs) are ubiquitous pharmaceutical pollutants in natural waters. However, their TPs, reaction pathways, and secondary risks have been limitedly known during oxidative water treatment. This study systematically assessed the TP formation and transformation mechanisms of two typical CCBs (i.e., amlodipine, AML; verapamil, VER) oxidized by ferrate(VI), permanganate, and ozone, as well as the in silico prediction on the TPs' properties. The high-resolution mass spectrometer analysis suggested a total of 16 TPs of AML and 8 TPs of VER identified for these reaction systems. Transformation of AML mainly proceeded through hydroxylation of the aromatic ring, ether bond cleavage, NH2 substitution by a hydroxyl group, and H-abstraction, while VER was oxidized via hydroxylation/opening of the aromatic ring and cleavage of the CN bond. Notably, certain TPs of both CCBs were estimated with low biodegradation, multi-endpoint toxicity, and high persistence and bioaccumulation, suggesting their severe risks to aquatic ecosystems. This study has implications for understanding the environmental behaviors, fate, and secondary risks of the globally prevalent and concerned CCBs under oxidative water treatment scenarios.

Chlorination of methotrexate in water revisited: Deciphering the kinetics, novel reaction mechanisms, and unexpected microbial risks.

Chlorination of a typical anticancer drug with annually ascending use and global prevalence (methotrexate, MTX) in water has been studied. In addition to the analysis of kinetics in different water/wastewater matrices, high-resolution product identification and in-depth secondary risk evaluation, which were eagerly urged in the literature, were performed. It was found that the oxidation of MTX by free available chlorine (FAC) followed first-order kinetics with respect to FAC and first-order kinetics with respect to MTX. The pH-dependent rate constants (kapp) ranged from 170.00 M-1 s-1 (pH 5.0) to 2.68 M-1 s-1 (pH 9.0). The moiety-specific kinetic analysis suggested that 6 model substructures of MTX exhibited similar reactivity to the parent compound at pH 7.0. The presence of Br- greatly promoted MTX chlorination at pH 5.0-9.0, which may be ascribed to the formation of bromine with higher reactivity than FAC. Comparatively, coexisting I- or humic acid inhibited the degradation of MTX by FAC. Notably, chlorination effectively abated MTX in different real water matrices. The liquid chromatography-high resolution mass spectrometry analysis of multiple matrix-mediated chlorinated samples indicated the generation of nine transformation products (TPs) of MTX, among which seven were identified during FAC oxidation for the first time. In addition to the reported electrophilic chlorination of MTX (the major and dominant reaction pathway), the initial attacks on the amide and tertiary amine moieties with C-N bond cleavage constitute novel reaction mechanisms. No genotoxicity was observed for MTX or chlorinated solutions thereof, whereas some TPs were estimated to show multi-endpoint aquatic toxicity and higher biodegradation recalcitrance than MTX. The chlorinated mixtures of MTX with or without Br- showed a significant ability to increase the conjugative transfer frequency of plasmid-carried antibiotic resistance genes within bacteria. Overall, this work thoroughly examines the reaction kinetics together with the matrix effects, transformation mechanisms, and secondary environmental risks of MTX chlorination.

Reactive High-Valent Iron Intermediates in Enhancing Treatment of Water by Ferrate.

Efforts are being made to tune the reactivity of the tetraoxy anion of iron in the +6 oxidation state (FeVIO42-), commonly called ferrate, to further enhance its applications in various environmental fields. This review critically examines the strategies to generate highly reactive high-valent iron intermediates, FeVO43- (FeV) and FeIVO44- or FeIVO32- (FeIV) species, from FeVIO42-, for the treatment of polluted water with greater efficiency. Approaches to produce FeV and FeIV species from FeVIO42- include additions of acid (e.g., HCl), metal ions (e.g., Fe(III)), and reductants (R). Details on applying various inorganic reductants (R) to generate FeV and FeIV from FeVIO42- via initial single electron-transfer (SET) and oxygen-atom transfer (OAT) to oxidize recalcitrant pollutants are presented. The common constituents of urine (e.g., carbonate, ammonia, and creatinine) and different solids (e.g., silica and hydrochar) were found to accelerate the oxidation of pharmaceuticals by FeVIO42-, with potential mechanisms provided. The challenges of providing direct evidence of the formation of FeV/FeIV species are discussed. Kinetic modeling and density functional theory (DFT) calculations provide opportunities to distinguish between the two intermediates (i.e., FeIV and FeV) in order to enhance oxidation reactions utilizing FeVIO42-. Further mechanistic elucidation of activated ferrate systems is vital to achieve high efficiency in oxidizing emerging pollutants in various aqueous streams.

Treatment-driven removal efficiency, product formation, and toxicity evolution of antineoplastic agents: Current status and implications for water safety assessment.

Antineoplastic compounds, designed for chemotherapeutic anticancer therapy, have become emerging contaminants of global concern over the past decade due to their ubiquitous occurrence, environmental persistence, and multiple adverse effects on aquatic ecosystems. Increasing efforts have been devoted to developing efficient strategies for remediating water containing these micropollutants. In this study, the physicochemical properties, natural attenuation, and chemical reactivity with aqueous oxidizing species of five antineoplastic drugs with the highest environmental prevalence (i.e., tamoxifen, cyclophosphamide, ifosfamide, 5-fluorouracil, and methotrexate) were summarized. The removal performance, transformation products (TPs) of varying structures, overall reaction pathways, and toxicity evolution during different treatments were evaluated and discussed. Additionally, the biodegradability and multi-endpoint toxicity of each TP were predicted using in silico QSAR software. Depending on their distinct inherent structures, the reactivity of the antineoplastics with oxidizing species varied, with hydroxyl radicals exhibiting unparalleled merits in rapid oxidation. Complete elimination of these contaminants was observed during oxidative treatments, but with inadequate mineralization. Notably, the increase in toxicity within multiple processes was determined based on both experimental bioassays and theoretical predictions. This may be attributed to the adverse effects induced by the large number of identified and unknown TPs individually and in combination. Together with the environmental persistence and low biodegradability of most TPs, these results necessitate the application of efficient post-treatments in conjunction with a more thorough water safety evaluation (e.g., using high-throughput screening) of the mixtures of treated water and wastewater.

Toxicity and bioaccumulation of copper in Limnodrilus hoffmeisteri under different pH values: Impacts of perfluorooctane sulfonate.

Aquatic oligochaete Limnodrilus hoffmeisteri (L. hoffmeisteri) has been commonly used as a lethal and/or sub-lethal toxicological model organism in ecological risk assessments in contaminated water environments. In this study, experiments were conducted to investigate the potential toxic effects of copper (Cu(II)) with or without perfluorooctane sulfonate (PFOS) under different pH values (6.0, 7.0 and 8.0) on LC50, bioaccumulation, and oxidative stress biomarkers in L. hoffmeisteri after 3 and 7 days. The LC50 values of Cu(II) decreased with the increasing pH and the addition of PFOS. After each exposure, increasing bioaccumulation of Cu(II) in L. hoffmeisteri was observed in the combined exposure treatments, whereas the bioaccumulation of PFOS decreased. Moreover, the activity of superoxide dismutase, the level of glutathione, and the content of malondialdehyde were significantly altered after these exposures, possibly indicating that the bioaccumulation of Cu(II) and PFOS caused adverse effects on antioxidant defenses of L. hoffmeisteri. The integrated biomarker response index, indicates that the combined effect was proposed as synergism, which is coincided with the results of toxic unit. Moreover, this work showed that aquatic environment may become more livable when water conditions changed from acidic to near-neutral or alkaline.

Effect of decabromodiphenyl ether (BDE-209) on a soil-biota system: Role of earthworms and ryegrass.

In the present study, the toxic effect of decabromodiphenyl ether (BDE-209), an important brominated fire retardant, on soil was evaluated by amending with different concentrations (0 mg/kg, 1 mg/kg, 10 mg/kg, and 500 mg/kg dry wt) for 40 d. The activities of 3 soil enzymes (urease, catalase, and alkaline phosphatase) were measured as the principal assessment endpoints. Meanwhile, the effects of natural environmental factors, such as light conditions and soil biota, on BDE-209 intoxication were studied. For the latter, 30 earthworms (Metaphire guillelmi) with fully matured clitella or ryegrass (Lolium perenne) with fully matured leaves were exposed in soil amended with BDE-209. The activities of the soil enzymes were adversely affected by BDE-209, especially for the high-concentration treatments, with greater adverse effects in the dark than in the light. The presence of earthworms reduced toxicity to BDE-209, whereas ryegrass did not. The calculated integrated biomarker response index, which provides a general indicator of the health status of test species by combining different biomarker signals, further validated these findings. Moreover, the antioxidant status (oxidant-antioxidant balance) of these 2 biota was assessed. Results indicated that BDE-209 significantly affected the activities of antioxidant enzymes (superoxide dismutase and catalase) and enhanced the levels of malondialdehyde in both species. The present study may facilitate a better understanding of the toxicity of BDE-209 toward the soil environment. Environ Toxicol Chem 2016;35:1349-1357. © 2015 SETAC.

Antagonistic joint toxicity assessment of two current-use phthalates with waterborne copper in liver of Carassius auratus using biochemical biomarkers.

Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are two kinds of widely-used phthalates, whereas Cu (II) is a common valence state of copper. They have been ubiquitously detected in the aquatic environment, but information on their joint toxicity on aquatic organisms is scarce. In this study, we evaluated the combined effects of copper and these two phthalates to the goldfish (Carassius auratus) by detecting the antioxidant responses in liver after exposure for 7 and 21 days. The exposure concentrations were in a range relevant to their levels in the natural aquatic environment. The results indicated that DBP, DEHP and Cu (II) can affect the antioxidant status in fish liver, evidenced by the significant alterations of antioxidant defenses (superoxide dismutase, catalase, glutathione) and malondialdehyde. Antagonistic effects were found in the joint toxicity of Cu (II) and DBP or DEHP using the integrated biomarker response (IBR) index. These findings have important implications in the risk assessments of phthalates mixed with some heavy metals in the aquatic environment.

Oxidative degradation of decabromodiphenyl ether (BDE 209) by potassium permanganate: reaction pathways, kinetics, and mechanisms assisted by density functional theory calculations.

This study found that decabromodiphenyl ether (BDE 209) could be oxidized effectively by potassium permanganate (KMnO4) in sulfuric acid medium. A total of 15 intermediate oxidative products were detected. The reaction pathways were proposed, which primarily included cleavage of the ether bond to form pentabromophenol. Direct oxidation on the benzene ring also played an important role because hydroxylated polybrominated diphenyl ethers (PBDEs) were produced during the oxidation process. The degradation occurred dramatically in the first few minutes and fitted pseudo-first-order kinetics. Increasing the water content decelerated the reaction rate, whereas increasing the temperature facilitated the reaction. In addition, density functional theory (DFT) was employed to determine the frontier molecular orbital (FMO) and frontier electron density (FED) of BDE 209 and the oxidative products. The theoretical calculation results confirmed the proposed reaction pathways.

Evaluation of single and joint toxicity of perfluorooctane sulfonate, perfluorooctanoic acid, and copper to Carassius auratus using oxidative stress biomarkers.

Perfluorooctane sulfonate, perfluorooctanoic acid, and copper have been recently regarded as ubiquitous environmental contaminants in aquatic ecosystems worldwide. However, data on their possible combined toxic effects on aquatic organisms are still lacking. In this study, a systematic experimental approach was used to assess the impacts of these chemicals and their mixtures on hepatic antioxidant status of Carassius auratus after 4 days. Oxidative stress was apparently observed for joint exposure by determining biochemical parameters (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and malondialdehyde). The integrated biomarker response index was calculated to rank the toxicity order, from which the synergistic effect was tentatively proposed for joint-toxicity action. In addition, these treatments significantly altered trace element homeostasis in different fish tissues, and the concentration distribution of these test chemicals was also measured. Taken together, these results provided some valuable toxicological data on the joint effects of perfluorinated compounds and heavy metals on aquatic species, which can facilitate further understanding on the potential risks of other coexisting pollutants in the natural aquatic environment.

Antioxidant status and Na(+), K (+)-ATPase activity in freshwater fish Carassius auratus exposed to different combustion products of Nafion 117 membrane: an integrated biomarker approach.

Nafion 117 membrane (N117), an important polymer electrolyte membrane (PEM), has been widely applied in numerous chemical technologies. Its increasing production and utilization will inevitably lead to the problem of waste disposal, with incineration as an important method. However, toxicity data of its combustion products on aquatic organisms have been seldom reported. The present study was therefore conducted to investigate the antioxidant response and Na(+), K(+)-ATPase activity in liver of Carassius auratus exposed to different combustion products of N117 for 5, 15, and 30 days. The concentrations of fluorine ion (F(-)) in the aquaria among the exposure durations were analyzed using the ion chromatography system. The results showed that these treatments have the capability to induce oxidative stress and suppress Na(+), K(+)-ATPase activity, as indicated by some significant alterations on these measured toxicity end-points in fish liver. According to the integrated biomarker response (IBR) index, the toxicity intensity of these experimental treatments was tentatively ranked. Taken together, these observations provided some preliminary data on the potential toxicity of the combustion products of N117 on aquatic organisms and could fill the information gaps in the toxicity database of the current-use PEM.

The effects of hydroxylated multiwalled carbon nanotubes on the toxicity of nickel to Daphnia magna under different pH levels.

Hydroxylated multiwalled carbon nanotubes (OH-MWCNTs), with large amounts of hydrophilic groups attached on the nanoparticle surface, have caused considerable concern because of their inevitable release into aquatic environments. They may interact with other contaminants such as heavy metals and even influence their toxicity, fate, and transport. In the present study, the stability of OH-MWCNTs suspended in aerated Nanjing tap water (moderately hard) was evaluated using the spectrophotometric method. The toxicity of OH-MWCNTs to Daphnia magna was determined, and nontoxic concentrations were used in acute toxicity, accumulation, and sorption tests. It was found that OH-MWCNTs increased the Ni toxicity in a concentration-dependent manner under different pH levels. Nickel adsorption onto the OH-MWCNTs and the uptake of OH-MWCNTs increased the exposure of D. magna to Ni, which was verified by sorption and accumulation tests conducted under different pH levels. The lower pH level contributed to a higher overall toxicity, which could be interpreted by the increasing amount of Ni adsorption onto OH-MWCNTs with the decreasing pH levels.

Comparative antioxidant status in freshwater fish Carassius auratus exposed to eight imidazolium bromide ionic liquids: a combined experimental and theoretical study.

Imidazolium bromide ionic liquids such as 1-alkyl-3-methylimidazolium bromides ([AMIm]Br) and 1-alkyl-2,3-dimethylimidazolium bromides ([AMMIm]Br) are common-use organic salts. However, data on comparative toxicological effects of these ILs are lacking for fish. In this study, a combined experimental and theoretical approach was applied to compare and analyze the effects of these ILs on biochemical biomarkers in liver of Carassius auratus treated with different concentrations (2 and 20mg/L) for 3 and 16d. Changes in the activities of superoxide dismutase, catalase, glutathione peroxidase, and in the levels of reduced glutathione and malondialdehyde were detected, indicating that these ILs exhibit potential biotoxicity. The integrated biomarker response (IBR) index suggested that 1-hexyl-3-methylimidazolium bromide ([HMIm]Br), 1-octyl-3-methylimidazolium bromide ([OMIm]Br), 1-hexyl-2,3-dimethylimidazolium bromide ([HMMIm]Br), and 1-octyl-2,3-dimethylimidazolium bromide ([OMMIm]Br) showed the highest biotoxicity under different concentrations or exposure time, while 1-ethyl-3-methylimidazolium bromide ([EMIm]Br) always showed the least stressful power towards the test organism. Quantum chemical calculations (electronic parameters, frontier molecular orbitals, and Wiberg bond order) were also conducted to interpret the experimental results. Notably, some descriptors were correlated with the toxicity order. In addition, theoretical calculations provided some valuable information on metabolic pathways of these ILs, which may help to get better understanding on their environmental behavior and fate. In general, the toxicological determination and analysis of these ILs were performed with a combined experimental and theoretical method, which may contribute to the future ecotoxicological studies.

Antioxidant responses in Carassius auratus and Lolium perenne exposed to the laboratory pollution.

Experiments conducted in the laboratories can produce numerous wastes, which could potentially affect the health of the researchers. In this study, the antioxidant responses in liver of Carassiua auratus and leaf of Lolium perenne were investigated after chronic exposure to the air pollution in four different laboratories. The obtained data showed that oxidative stress was induced in some laboratories, as indicated by some significantly altered biochemical parameters. Additionally, the toxicity order was tentatively proposed based on these responses. The results indicated that these biochemical indices can be used as the oxidative stress biomarkers to assess the effect of environmental pollution on the living organisms, and this study can facilitate the understanding of the risk assessment of laboratory pollution.

Biochemical biomarkers in liver and gill tissues of freshwater fish Carassius auratus following in vivo exposure to hexabromobenzene.

Hexabromobenzene (HBB) is a novel brominated flame retardant (BFR) with ample evidence of its ubiquitous existence in the aquatic ecosystems. However, to date, the toxicological effects of this BFR on fish have been inadequately researched. The present study was conducted, based on an in vivo model, to investigate HBB-induced biochemical changes in liver and gill tissues of Carassius auratus after medium-term exposure to different concentrations (10, 150, and 300 mg/kg) for 7, 14, and 25 days. Oxidative stress was evoked evidently for the prolonged exposure, demonstrated by significant inhibition in antioxidant enzymes activities including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, and a decrease in reduced glutathione level, as well as simultaneous elevation in malondialdehyde content. Moreover, Na(+) , K(+) -ATPase activity, and protein level were remarkably reduced in fish tissues. Based on the integrated biomarker response, the toxic potency in each treatment was distinguished, and the more severe stress was mainly noted with the increasing concentrations and the extending durations. It was also observed that liver exhibited more pronounced alterations in biochemical parameters than gill, probably indicating the vulnerability of liver to HBB-triggered oxidative stress. Taken together, the results of this study clearly showed that HBB was capable of inducing oxidative stress and inhibiting Na(+) , K(+) -ATPase activity in different tissues of C. auratus after medium-term exposure.

Subacute oral toxicity of BDE-15, CDE-15, and HODE-15 in ICR male mice: assessing effects on hepatic oxidative stress and metals status and ascertaining the protective role of vitamin E.

The present study examined the effects of oral exposure of 4,4'-dibromodiphenyl ether (BDE-15), 4,4'-dichlorodiphenyl ether (CDE-15), and 4,4'-dihydroxydiphenyl ether (HODE-15) on hepatic oxidative stress (OS) and metal status in Institute of Cancer Research (ICR) male mice. Furthermore, the role of vitamin E in ameliorating potential OS caused by BDE-15, CDE-15, and HODE-15 was investigated. Three groups of mice were exposed to 1.20 mg/kg(body weight)/day of each of the three toxicants for 28 days. Results showed that none of the three toxicants altered growth rates of mice, but significantly increased (P<0.05) relative liver weights and decreased relative kidney weights. Pathological changes including cell swelling, inflammation and vacuolization, and hepatocellular hypertrophy in livers were observed. Significant decreases (P<0.05 and P<0.01) in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and glutathione (GSH) levels, together with increases in malondialdehyde (MDA) content were recorded in all toxicant-treated groups. Hepatic copper levels increased in all toxicant-treated groups. Hepatic zinc levels decreased in the liver of BDE-15-treated mice, whereas they increased in the livers of CDE-15-treated and HODE-15-treated mice. In conclusion, daily exposure to the three toxicants perturbed metal homeostasis and increased OS in mouse liver. Experimental data indicated the hepatic oxidative toxicity of the three toxicants followed the order BDE-15

Oxidative stress biomarkers in freshwater fish Carassius auratus exposed to decabromodiphenyl ether and ethane, or their mixture.

Decabromodiphenyl ether (BDE-209) and its commercial alternative decabromodiphenyl ethane (DBDPE) are two structurally similar brominated flame retardants, with evidence of their ubiquitous existence in aquatic ecosystems. The present study was conducted to investigate the hepatic oxidative stress inducing potential of BDE-209, DBDPE, and their mixture in Carassius auratus after exposure to different doses (10, 50 and 100 mg/kg) for 7, 14 and 30 days. Results showed that oxidative stress was evoked evidently for the experimental groups with longer exposure duration, as indicated by significant inhibition in the antioxidant enzymes activities and decrease in the reduced glutathione level, as well as simultaneous elevation of lipid peroxidation level measured by malondialdehyde content. In addition, it was found that BDE-209 possessed a higher oxidative stress inducing ability than DBDPE. Considering the more pronounced antioxidant responses in combined exposure, the interaction of BDE-209 and DBDPE was presumed to be additive action.

Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene, phenol, and diphenyl ether in mice: a comparative and mechanism exploration.

The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated benzene, phenol, and diphenyl ether in mice were ascertained respectively under the consistent condition. The acute toxicity of four benzenes orders in fluorobenzene (FB) < iodobenzene < chlorobenzene≈bromobenzene, that of four phenols orders in 4-iodophenol≈4-bromophenol < 4-chlorophenol (4-MCP) < 4-fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'-iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl ether≈4,4'-dibromodiphenyl ether. General behavior adverse effects were observed, and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4-MFP produced toxic faster than other halogenated benzenes and phenols, as they had lower octanol-water partition coefficients. Pathological changes in liver and liver/kidney weight changes were also observed. Hepatic superoxide dismutase, catalase activities, and malondialdehyde level were tested after a 28-day exposure, which reflects a toxicity order basically consistent with that reflected by the LD50s. By theoretical calculation and building models, the toxicity of benzene, phenol, and diphenyl ether were influenced by different structural properties.