PM2.5 exposure contributes to anxiety and depression-like behaviors via phenyl-containing compounds interfering with dopamine receptor.

As a global problem, fine particulate matter (PM2.5) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, the most important question is to clarify whether and how PM2.5 causally contributes to these mental disorders and which components are the most dangerous for crucial mitigation in a particular place. In the present study, we chronically subjected male mice to a real-world PM2.5 exposure system throughout the winter heating period in a coal combustion area and revealed that PM2.5 caused anxiety and depression-like behaviors in adults such as restricted activity, diminished exploratory interest, enhanced repetitive stereotypy, and elevated acquired immobility, through behavioral tests including open field, elevated plus maze, marble-burying, and forced swimming tests. Importantly, we found that dopamine signaling was perturbed using mRNA transcriptional profile and bioinformatics analysis, with Drd1 as a potential target. Subsequently, we developed the Drd1 expression-directed multifraction isolating and nontarget identifying framework and identified a total of 209 compounds in PM2.5 organic extracts capable of reducing Drd1 expression. Furthermore, by applying hierarchical characteristic fragment analysis and molecular docking and dynamics simulation, we clarified that phenyl-containing compounds competitively bound to DRD1 and interfered with dopamine signaling, thereby contributing to mental disorders. Taken together, this work provides experimental evidence for researchers and clinicians to identify hazardous factors in PM2.5 and prevent adverse health outcomes and for local governments and municipalities to control source emissions for diminishing specific disease burdens.

Sulfonamide disinfection byproducts exhibited severe toxicity to human commensal bacteria.

Many antibiotic disinfection byproducts have been detected but their toxicity has not been evaluated adequately. In this report, the chlorination reaction kinetics of five common sulfamides (SAs), reaction intermediates and their toxicity were investigated. Chlorination of sulfapyridine (SPD), sulfamethazine (SMT), sulfathiazole (STZ), and sulfisoxazole (SIZ) followed the second-order kinetics, and were degraded completely within 10 min. A large number of reaction intermediates were deteced by LC-MS, among which a total of 16 intermediates were detected for the first time. Toxicity of the five SAs chlorination solutions was evaluated separately by examining their effects on the growth rate of S. salivarius K12, a commensal bacterium in the human digestive system. After 30 min chlorination, solutions of SMT, STZ and sulfadiazine (SDZ) each exhibited severe toxicity by inhibiting the bacteria growth completely, whereas the inhibition was only 50 % and 20  % by SIZ and SPD respectively. Based on the comparison between toxicity test results and mass spectra, three SA chlorination intermediates, m/z 187.2 (C10H10N4), m/z 287.2 (C9H7N3O4S2) and m/z 215 (C7H10N4O2S/C12H14N4) were proposed to be the primary toxicants in the chlorination products. Our study demonstrated the power of combined approach of chemical analysis and toxicity testing in identifying toxic disinfection byproducts, and highlighted the ne ed for more research on the toxicity evaluation and risk assessment of antibiotic disinfection byproducts.

Nontargeted Identification of Organic Components in Fine Particulate Matter Related to Lung Tumor Metastasis Based on an Adverse Outcome Pathway Strategy.

Emerging studies implicate fine particulate matter (PM2.5) and its organic components (OCs) as urgent hazard factors for lung cancer progression in nonsmokers. Establishing the adverse outcome pathway (AOP)-directed nontargeted identification method, this study aimed to explore whether PM2.5 exposure in coal-burning areas promoted lung tumor metastasis and how we identify its effective OCs to support traceability and control of regional PM2.5 pollution. First, we used a nude mouse model of lung cancer for PM2.5 exposure and found that the exposure significantly promoted the hematogenous metastases of A549-Luc cells in lung tissues and the adverse outcomes (AOs), with key events (KEs) including the changed expression of epithelial-mesenchymal transition (EMT) markers, such as suppression of E-cad and increased expression of Fib. Subsequently, using AOs and KEs as adverse outcome directors, we identified a total of 35 candidate chemicals based on the in vitro model and nontargeted analysis. Among them, tributyl phosphate (C12H27O4P), 2-bromotetradecane (C14H29Br), and methyl decanoate (C11H22O2) made greater contributions to the AOs. Finally, we clarified the interactions between these OCs and EMT-activating transcription factors (EMT-ATFs) as the molecular initiation event (MIE) to support the feasibility of the above identification strategy. The present study updates a new framework for identifying tumor metastasis-promoting OCs in PM2.5 and provides solid data for screening out chemicals that need priority control in polluted areas posing higher lung cancer risk.

Emerging and traditional organophosphate esters in office air from Hangzhou, East China: Seasonal variations, influencing factors and human exposure assessment.

Eight emerging and six traditional organophosphate esters (OPEs) were investigated in office air from Hangzhou China with all the traditional OPEs and 5 out of 8 emerging OPEs detected. The median concentrations of ∑traditional OPEs and ∑emerging OPEs were 61,200 and 5.81 pg/m3, respectively. Butylphenyl diphenyl phosphate (BPDPP) and trisisopropyltrisphenyl phosphate (TIPPP) were observed for the first time in indoor air and Chinese office, respectively. The levels of ∑traditional OPEs decreased in the following order: summer > autumn > spring > winter. Conversely, no obvious trends were observed for emerging OPEs. ∑traditional OPEs (p < 0.001) and tri(chloroisopropyl) phosphate (TCIPP) (p < 0.01) concentrations were positively correlated with temperature. Interestingly, ∑emerging OPEs and the individual emerging OPEs analytes had no significant correlations with temperature (p > 0.05). ∑traditional OPEs, tris(2-chloroethyl) phosphate (TCEP) and TCIPP levels were significantly positively correlated with relative humidity (p < 0.05), while ∑emerging OPEs levels were negatively correlated with relative humidity (p < 0.05). Median intakes of traditional OPEs were estimated to be several orders of magnitude lower than the corresponding Reference Dose (RfD) values. The distinct environmental behaviors of emerging OPEs compared to traditional OPEs, coupled with the lack of established RfD values for them, underscore the need for their risk evaluations in future.

Enantiomer-specific burden of metalaxyl and myclobutanil in non-occupationally exposed population with evidence from dietary intake and urinary excretion.

Metalaxyl (MET) and myclobutanil (MYC) are two widely used chiral fungicides that may pose health risks to non-occupationally exposed populations. Here, the two fungicides were enantiomer-specific quantified in the dietary food and urine of residents in an Eastern China city, to determine the exposure and excretion of these contaminants in different populations. Results indicate that residues of MET and MYC varied with different food items at 0.42-0.86 ng/g fresh weight (FW) and 0.18-0.33 ng/g FW, respectively. In urine samples, the residual levels after creatinine adjusting (CR) ranged from 10.2 to 1715.4 ng/g CR for MET and were below the detection limit up to 320.7 ng/g CR for MYC. Significant age- and gender-related differences were separately found in urinary MET and MYC of different populations. Monte-Carlo simulations suggested that children had higher daily dietary intake (DDI) but lower urinary excretion (DUE) rates than youths, and thus may suffer higher body burdens. The residues of antifungally ineffective enantiomers (S-MET and R-MYC) were slightly higher than their antipodes in foods. Moreover, the enantiomer-selective urinary excretion resulted in higher retention of S-MET and R-MYC in the human body. Our results suggest that both dietary intake and urinary excretion should be enantiomer-specifically considered when assessing the exposure risk and body burden of chiral fungicides in the non-occupationally exposed population. Furthermore, substitutive application of enantiomer-enriched fungicide formulations can not only benefit the antifungal efficacy but also be safer for human health.

Contaminant occurrence, water quality criteria and tiered ecological risk assessment in water: A case study of antifouling biocides in the Qiantang River and its estuary, Eastern China.

Antifouling biocides may cause adverse effects on non-target species. This study aims to determine the distribution, sources, and ecological risks of antifouling biocides in the surface waters of the Qiantang River and its estuary in eastern China. The concentrations of total antifouling biocides were ranged from 12.9 to 215 ng/L for all water samples. Atrazine, diuron and tributyltin were the major compounds in the water bodies of the study area. The acute and chronic toxicity criteria for tributyltin, diuron and atrazine were derived for freshwater and saltwater, respectively, based on the species sensitivity distribution approach. The freshwater and saltwater criteria were slightly different, and the toxicity to aquatic organisms could be summarized as tributyltin > diuron > atrazine. The graded ecological risk rating showed that the long-term risk of TBT was significant in coastal waters. The pollution of TBT in the Qiantang River deserves further attention.

A cathodic photoelectrochemical immunoassay with dual signal amplification for the ultrasensitive detection of DNA damage biomarkers.

Toxicity screening and risk assessment of an overwhelmingly large and ever-increasing number of chemicals are vitally essential for ecological safety and human health. Genotoxicity is particularly important because of its association with mutagenicity, carcinogenicity and cancer. Phosphorylated histone H2AX (γH2AX) is an early sensitive genotoxic biomarker. It is therefore highly desirable to develop analytical methods for the detection of trace γH2AX to enable screening and assessment of genotoxicity. Here, we developed a novel cathodic photoelectrochemical (PEC) immunoassay with dual signal amplification for the rapid and ultrasensitive detection of γH2AX in cell lysates. A sandwich immuno-reaction targeting γH2AX was first carried out on a 96-well plate, using a secondary antibody/gold nanoparticle/glucose oxidase conjugate as the labeled detection antibody. The conjugate increased the production of H2O2 and thus provided the first mechanism of signal amplification. The immuno-reaction product containing H2O2 was then detected on a photocathode prepared from Bi2+xWO6 rich in oxygen vacancies, with H2O2 acting as electron acceptor. The oxygen vacancies acted as both adsorption and activation sites of H2O2 and thus enhanced the photocurrent, which provided another mechanism of signal amplification. As a result, an ultrasensitive immunoassay for γH2AX determination was established with a limit of detection of 6.87 pg/mL (S/N = 3) and a wide linear range from 0.01 to 500 ng/mL. The practicability of this assay was verified by detecting γH2AX in cell lysates exposed to known genotoxic chemicals. Our work offers a promising tool for the screening of genotoxic chemicals and opening a new avenue toward environmental risk assessment.

Water quality criteria derivation and tiered ecological risk evaluation of antifouling biocides in marine environment.

This study provides a comprehensive compilation of published toxicological and environmental data further used to assess the ecological risks of six antifouling biocides, including tributyltin (TBT), Irgarol 1051, Diuron, Chlorothalonil, 4,5-Dichloro-N-octyl-3(2H)-isothiazolone (DCOIT), and Dichlofluanid. The standard maximum concentration and standard continuous concentration of antifouling biocides were derived by the species susceptibility distribution method. Following that, the ecological risk assessment of antifouling biocides in the aquatic environment was conducted using the hazard quotient, margin of safety, joint probability curve, and Monte Carlo random sampling method. The following is a concise list of the antifouling biocide dangers associated with acute and chronic risks: Irgarol 1051 > TBT > Diuron > DCOIT > Chlorothalonil > Dichlofluanid. It is strongly advised that systematic and ongoing monitoring of these biocides in coastal areas take place, as well as the creation of acceptable and efficient environmental protection measures, to safeguard the coastal environment's services and functions.

Urinary metabolites of organophosphate esters and implications for exposure pathways in adolescents from Eastern China.

Ten urinary biomarkers of organophosphate esters (OPEs) from six parent OPEs were analyzed in urine from adolescents students in Eastern China. Bis (1,3-dichloro-2-propyl) phosphate, urinary biomarker of tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), was detected in all urine samples with the highest residual concentration of 6.2 ng/mL (median). Bis (1-chloro-propyl) hydroxyl-2-propyl phosphate, dibutyl phosphate, biomarkers of tris (1-chloro-2-propyl) phosphate (TCIPP), tri-n-butyl phosphate (TNBP), respectively, and tris (2-chloroethyl) phosphate (TCEP), were also frequently detected with median concentrations of 1.5, 2.6 and 0.3 ng/mL, respectively. Results indicate that exposure to OPEs, in particular to TDCIPP, TNBP, TCIPP and TCEP, was highly prevalent for adolescent students. The exposure pathways of OPEs were then evaluated according to the OPE internal body burdens (IBBs). Three pathways were identified as the main pathways for adolescents exposed to OPEs including dermal absorption, oral intake of food and dust and inhalation.

Residuals of organophosphate esters in foodstuffs and implication for human exposure.

Foodstuffs may be contaminated by organophosphate esters (OPEs) and become an important source of human exposure since OPEs are ubiquitous in the environment. In the present study, 10 OPEs were analyzed in various food matrices collected from a city in Eastern China including chicken, pork, fishes, vegetables, tofu, eggs, milk and cereals. The concentrations of Σ10OPEs ranged from 1.1 to 9.6 ng g-1 fresh weight (fw) in the foodstuffs. Cereals had the highest residual level of total OPEs with a mean value of 5.7 ng g-1 fw. Tris(2-ethylhexyl) phosphate was detected in all foodstuff samples and showed the highest median residual concentration of 1.3 ng g-1 fw among the OPE analogs. The daily dietary intake of OPEs was calculated as 3.6 and 2.4 µg d-1 for adults and children. Cereals were identified as the major contributor to the total OPEs among different types of foodstuffs. Preliminary exposure assessment revealed that the current non-cancer health risks of OPEs via dietary intake were in the range of 10-5-10-3, indicating low risk levels. Moreover, the hazard index of OPEs indicated that the risk for children (3 × 10-3) was higher than adults (2 × 10-3).

Organophosphate ester flame retardants and plasticizers in human placenta in Eastern China.

Organophosphate esters (OPEs) have been widely used in various products as alternatives to brominated flame retardants. Although widespread OPE exposure is expected in humans, the accumulation of OPEs has seldom been studied in the human body. In this study, 12 OPE analogs were analyzed in 50 human placentas collected in Eastern China. The concentrations of the 9 most frequently detected OPEs (Σ9OPEs) ranged from 34.4 to 862ng/g lipid weight (lw), with a median of 301ng/g lw. Tri(2-chloroethyl) phosphate (TCEP) was identified as the most abundant analog, with a median concentration of 142ng/g lw, followed by tributoxyethyl phosphate (TBEP) and triphenyl phosphate (TPhP). Statistical analysis showed no analog of OPEs or Σ9OPEs was positively correlated with the lipid content of the placentas. There were no correlations observed between the OPE concentrations and maternal characteristics. Food consumption habits exhibited weak effects on OPE levels in the placentas. Further investigation is required to determine the effects of OPEs on fetuses due to the expected increase in maternal exposure to these esters.

Occurrence and risk assessment of organophosphate esters in drinking water from Eastern China.

Organophosphate esters (OPEs) are ubiquitous in the environment and may pose potential health risks to humans. Drinking water is suspected as one possible exposure pathway of OPEs to humans. In this study, we investigated the residues of 9 OPEs in five types of drinking water in Eastern China. The median concentrations of Σ9OPEs were determined to be 3.99, 4.50, 27.6, 59.2 and 192ng/L in the bottled, well, barreled, direct drinking and tap waters, respectively. Triethyl phosphate (TEP) was the most abundant OPE in the tap water and filtered drinking water with median concentrations of 50.2 and 30.2ng/L, respectively. The mixture of tri(chloropropyl) phosphate (TCPP) and tri(chloroisopropyl) phosphate (TCIPP), named here as TCPP, dominated in the barreled and well water with median concentrations of 8.04 and 2.49ng/L, respectively. The calculated average daily doses of OPEs ranged from 0.14 to 7.07ng/kgbw/day for people consuming the five different types of drinking water. Among the drinking water, the tap water exhibited the highest exposure doses of OPEs. The calculated non-cancer hazard quotients (10(-4)-10(-7)) from OPEs were much lower than the theoretical threshold of risk. The carcinogenic risks posed by TCEP were very low (<10(-7)) for all types of drinking water. The results revealed that there was currently low risk to human health from exposure to OPEs through drinking water in Eastern China.

Particle size-specific distributions and preliminary exposure assessments of organophosphate flame retardants in office air particulate matter.

In this study, the concentrations, size-specific distributions, and preliminary exposure assessments of 10 organophosphate flame retardants (OPFRs) were investigated in suspended particulate matter collected from offices. OPFRs were detected in a range of 5.00-147.77 ng/m(3). Tri(chloropropyl) phosphate (TCPP) was the most abundant analog followed by tri(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPhP). Chlorinated OPFRs (TCPP, TCEP, and tris(1,3-dichloroisopropyl) phosphate (TDCPP)) contributed to about 77% of the total OPFRs. Size-specific distributions revealed that TCEP, tri-n-propyl phosphate (TnPP), TCPP, and tri-n-butyl phosphate (TnBP) shared a similar distribution pattern with a peak in the fraction 4.7-5.8 µm. A peak was also found in the distributions of tricresyl phosphate (TCrP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tri(2-ethylhexyl) phosphate (TEHP) but in different fractions. A bimodal distribution was observed for TDCPP, TPhP, and tributoxyethyl phosphate (TBEP). The results of mass median aerodynamic diameter (MMAD) indicated that TDCPP, TCrP, and TEHP were mainly located on ultrafine particles (≤1 µm), while TnPP, TBEP, and EHDPP mainly on fine particles (≤2.5 µm). Furthermore, MMADs of OPFRs were found to be positively correlated with their vapor pressures (Vp) (p < 0.01), indicating that OPFR analogs with low Vp were inclined to adsorb on small size particles. Preliminary exposure assessments suggested a low risk of exposure to OPFRs for people working in such offices, and inhaled OPFRs would mainly deposit in the head region of the respiratory tract.