Urinary biomarkers of drinking-water disinfection byproducts in relation to diminished ovarian reserve risk: A case-control study from the TREE cohort.

BACKGROUND: Disinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR). OBJECTIVE: To assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk. METHODS: A total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR. RESULTS: Elevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m2), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004). CONCLUSIONS: Exposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology.

Sub-lethal toxicity of five disinfection by-products on microalgae determined by flow cytometry - Lines of evidence for adverse outcome pathways.

Standardised tests are often used to determine the ecotoxicity of chemicals and focus mainly on one or a few generic endpoints (e.g. mortality, growth), but information on the sub-cellular processes leading to these effects remain usually partial or missing. Flow cytometry (FCM) can be a practical tool to study the physiological responses of individual cells (such as microalgae) exposed to a stress via the use of fluorochromes and their morphology and natural autofluorescence. This work aimed to assess the effects of five chlorine-based disinfection by-products (DBPs) taken individually on growth and sub-cellular endpoints of the green microalgae Raphidocelis subcapitata. These five DBPs, characteristic of a chlorinated effluent, are the following monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), bromochloroacetic acid (BCAA) and 1,1-dichloropropan-2-one (1,1-DCP). Results showed that 1,1-DCP had the strongest effect on growth inhibition (EC50 = 1.8 mg.L-1), followed by MCAA, TCAA, BCAA and DCAA (EC50 of 10.1, 15.7, 27.3 and 64.5 mg.L-1 respectively). Neutral lipid content, reactive oxygen species (ROS) formation, red autofluorescence, green autofluorescence, size and intracellular complexity were significantly affected by the exposure to the five DBPs. Only mitochondrial membrane potential did not show any variation. Important cellular damages (>10%) were observed for only two of the chemicals (BCAA and 1,1-DCP) and were probably due to ROS formation. The most sensitive and informative sub-lethal parameter studied was metabolic activity (esterase activity), for which three types of response were observed. Combining all this information, an adverse outcome pathways framework was proposed to explain the effect of the targeted chemicals on R. subcapitata. Based on these results, both FCM sub-cellular analysis and conventional endpoint of algal toxicity were found to be complementary approaches.

High formation of trichloroacetic acid from high molecular weight and ultra-hydrophilic components in freshwater raphidophytes upon chlorination.

Raphidophytes are flagellate unicellular algae that causes algal blooms in drinking water sources. In Japan, it was recently reported that the concentration of trichloroacetic acid (TCAA), a major chlorinated disinfection byproduct (DBP), increased dramatically in drinking water when the source water contained raphidophytes. Additionally, raphidophytes produced haloacetic acid (HAA) precursors, especially TCAA precursors, in high concentrations. However, their properties are still unknown, and thus, well-designed countermeasures against DBP formation have not yet been established. Therefore, in this study, the HAA precursors originated from raphidophytes in natural water collected from the algal blooms in Muro Dam (Nara Prefecture, Japan) and Gonyostomum semen (G. semen), a raphidophyte species, cultivated in the laboratory, were characterized to provide the information for establishing suitable treatment strategies. Using several high-performance liquid chromatography columns, solid-phase extraction cartridges, and ultrafiltration devices, and the spectral profiles, we discovered that the HAA precursors are highly hydrophilic and high-molecular-weight compounds with acidic and phenolic functional groups. Further characterization of the high-molecular-weight fraction (> 3 kDa) from the G. semen culture showed that the HAA precursors had a molecular weight of ~10-60 kDa, and that they were not protein molecules despite containing a large amount of nitrogen atoms. Furthermore, the TCAAFP of the fraction (310 ± 25 µg/mg C) were as high as phenol, known as a reactive TCAA model precursor. The presence of unique and unreported DBP precursors was confirmed.

Innovative electrochemical biosensor with nitrifying biofilm and nitrite oxidation signal for comprehensive toxicity detection in Tuojiang River.

Water toxicity detection, as a valuable supplement to conventional water quality measurement, is an important method for evaluating water environmental quality standards. However, the toxicity of composite pollutants is more complicated due to their mixture effects. This study developed a novel, rapid and interference-resistant detection method for water toxicity based on an electrochemical biosensor using peak current from nitrite oxidation as a signal. Toxicants could weaken the characteristic peak current of nitrite to indicate the magnitude of toxicity. The proof-of-concept study was first conducted using a synthetic water sample containing trichloroacetic acid (TCAA), and then the results were compared with those of the traditional toxicity colorimetric method (CCK-8 kit) and laser confocal microscopy (CLSM). The accuracy of the biosensor was further verified with water samples containing individual pollutants such as Cd2+ (50-150 µg/L), Cr6+ (20-80 µg/L) mixture, triclosan (TCS; 0.1-1.0 µg/L) and TCAA (10-80 µg/L), or a mixture of the above. The viability of the sensor was further validated with the actual water sample from the Tuojiang River. The results demonstrated that although the concentration of a single conventional pollutant in water did not exceed the discharge standard for surface water, the comprehensive toxicity of natural water should not be ignored. This method could be a beneficial supplement to conventional water quality detection to understand the characteristics of the water, and thus contribute to the next stage of water treatment.

Simple and fast determination of tetrodotoxin in human plasma based on hydrophilic-interaction/ion-exchange mixed-mode solid phase extraction combined with liquid chromatography-tandem mass spectroscopy.

In this study, we developed and validated a simple, fast and sensitive LC-MS/MS method for the measurement of tetrodotoxin (TTX) in human plasma. Three HILIC-type solid phase extraction (SPE) carriers (PSA, silica, Siphila i HILIX) with different stationary phase functional groups were compared. The Siphila i HILIX SPE plate containing multi-carboxyl groups was finally selected due to obviously better extraction recovery of TTX (about 80% of recovery from plasma samples) than the other two and no significant matrix effects were observed, which was speculated to have mixed-mode synergistic effects of hydrophilic interaction and ion exchange. 100µL plasma sample was precipitated rapidly with acetonitrile containing 1% trichloroacetic acid, and filtrates were loaded onto Siphila i HILIX 96 well SPE plate. After washed with 95% acetonitrile, TTX was eluted with 200µL of 50% acetonitrile containing 1% trichloroacetic acid. 2µL of elution solution was directly injected into LC-MS/MS and the total run time on a BEH amide column was 4.5 min. The method avoids the evaporation and ultrafiltration processes which is simple and timesaving (<30 min). TTX and internal standard (arginine-15N4) were monitored in positive mode using m/z 320.3→162.2 (quantification transition for TTX), 320.3→284.1 (confirmation transition for TTX) and 179.2→63.0 (transition for IS), respectively. The method was linear in the range of 0.1-20 ng/mL for TTX with the low limit of quantification (S/N > 10) of 0.1 ng/mL; the intra- and inter-assay accuracies were in the range of 98.5%-99.8% (relative standard deviations, RSDs ≤ 5.92%) and 98.8-99.5% (RSDs ≤ 6.23%), respectively. Biases of spiking analysis were ranged from -7.00% to 7.43% for healthy human plasma samples (RSDs ≤ 8.83%) and from -5.00% to 3.93% for hemolytic, high triglyceride, high cholesterol and high bilirubin plasma samples (RSDs ≤ 6.40%), which proved the good anti-interference property of the method. The results showed that the method is sensitive, accurate, specific, reliable, and can be used to monitor the concentration of TTX in plasma to meet the needs of clinical research and poisoning screening.

High-Performance Trichloroacetic Acid Sensor Based on the Intramolecular Hydrogen Bond Formation and Disruption of a Specially Designed Fluorescent o-Carborane Derivative in the Film State.

Discriminative and sensitive detection of environmentally important and health-related trichloroacetic acid (TCA) suffers from various problems such as bulky instruments and time-consuming operation as well as complex sample processing. Herein, we present a rapid, sensitive, and specific method for the detection of gaseous TCA using a fluorescent single-molecule array. An o-carborane-based benzothiazole derivative (CB-BT-OCH3) with specific fluorescence properties was specifically designed and utilized to fabricate a film-based single-molecule array. It was revealed that the fluorescent film is photochemically stable and extremely sensitive to TCA vapor, depicting an observable fluorescence color change from green to blue. The experimental detection limit is 0.2 ppm, which is lower than the safety limit (1 ppm) required by the threshold limit values and biological exposure indices. In addition, the film could show detectable intensity change within 0.2 s. On the basis of multiple signal responses, a conceptual two-channel-based fluorescent TCA sensor was developed. Importantly, the proposed conceptual sensor paves a new route to the development of specific fluorescent film-based sensor arrays with a single fluorophore as sensing units.

Formation and interdependence of disinfection byproducts during chlorination of natural organic matter in a conventional drinking water treatment plant.

It is crucial to explore the source, formation process and interdependence of disinfection byproducts (DBPs) to reduce their risk on public health. In this investigation, a source water was chlorinated to evaluate the initial formation rates and the maximum yields of trichloromethane (TCM), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA) based on a hyperbola model. The results showed that TCM achieved the highest initial formation rate and maximum theoretical concentration compared with DCAA and TCAA. The TCM yield can be used to forecast the yields of DCAA and TCAA throughout the whole reaction process, and the yields of chloral hydrate (CH), dichloroacetonitrile (DCAN) and 1,1,1-trichloropropanone (1,1,1-TCP) within the initial reaction stage. Besides, the raw water, settled water and filtered water collected from a drinking water treatment plant were divided into five fractions, respectively, by ultrafiltration membranes to evaluate their DBP formation after chlorination. Compared with the medium molecular weight species, high and low molecular weight organic matters exhibited relatively high specific regulated and unregulated DBP yields (expressed as µg/mg C), respectively. Humic acid-like compositions predominantly contributed to regulated DBP yields, while soluble microbial by-product-like compounds preferentially generated DCAN. The correlation study revealed that the TCM could also serve as an indicator for the measured DBPs from chlorination of sample fractions with different molecular weight. Finally, it was found that the theoretical cytotoxicity was enhanced during chlorination of filtered water compared with chlorination of settled water.

Synthesis and utilization of Co3O4 doped carbon nanofiber for fabrication of hemoglobin-based electrochemical sensor.

In this paper cobalt oxide (Co3O4) nanoparticles were mixed with polyacrylonitrile to prepare Co3O4 doped carbon nanofiber (CNF) composite by electrospinning and carbonization, which was further used to modify on carbon ionic liquid electrode (CILE). Hemoglobin (Hb) was immobilized on Co3O4-CNF/CILE surface with Nafion acted as the protective film to fabricate an electrochemical biosensor (Nafion/Hb/Co3O4-CNF/CILE). Electrochemical behavior of Hb on the electrode was investigated with a pair of quasi-reversible redox peak appeared on cyclic voltammogram and electrochemical parameters were calculated. Moreover, this biosensor had good analytical capabilities for electrocatalytic reduction of different substrates including trichloroacetic acid, potassium bromate and sodium nitrite with wider detection range from 40.0 to 260.0 mmol L-1, 0.1 to 48.0 mmol L-1 and 1.0 to 12.0 mmol L-1 by cyclic voltammetry, respectively. The proposed method showed excellent anti-interferences ability with good selectivity and was successful used for quantitative detection of real samples, which displayed the potential applications to develop into a new analytical device.

Electrochemically Sensing of Trichloroacetic Acid with Iron(II) Phthalocyanine and Zn-Based Metal Organic Framework Nanocomposites.

Rapid and accurate determination of disinfection byproducts (DBPs) has become an emerging need for environmental monitoring and has yet to be realized in electrochemical sensors with metal organic framework (MOF)-based materials. In this study, a highly sensitive electrochemical sensor for trichloroacetic acid (TCAA) detection based on iron(II) phthalocyanine (PcFe) and a Zn-based metal organic framework (ZIF-8) composite is fabricated. As an electrode material, ZIF-8 possesses a large surface area and porous structure, which exhibits high absorbability; meanwhile, PcFe (II), as the sensing element, undergoes a reduction process from PcFe (II) to PcFe (I) during the sensing process. In the presence of TCAA, PcFe (I) is reoxidized by TCAA, which shifts the reaction equilibrium and accelerates the electron transfer on the electrode interface. By analyzing the reduction current of PcFe (II), the quantitative detection of TCAA is realized. The sensor shows a limit of detection (LOD) of 1.89 nM, which is superior to other reported TCAA sensors, as well as a high sensitivity (826 µΑ/µM). Moreover, the good selectivity and stability of this sensing platform demonstrate its capability and promise in determination of trace DBPs. The reported sensor provides a new strategy for electrochemical detection of DBPs and could expand the applications of MOFs in emerging technologies for monitoring contaminants.

Chlorination by-product levels in hot tap water: Significance and variability.

People are exposed to chlorinated by-products (CBPs) through the consumption of cold tap water (CTW) (ingestion, inhalation, dermal contact) but also through the use of hot tap water (HTW) in such activities as showering and bathing (inhalation, dermal contact). This study focuses on the impact of residential water heating on CBP levels in tap water. Trihalomethane (THM) and haloacetic acid (HAA) levels were measured in the CTW and HTW of 50 residences located in two distribution systems supplied by chlorinated surface water during summer and winter. Results show important differences between CBP levels measured in cold and hot tap water. However, the magnitude of changes differs according to the specific species of THMs and HAAs, the season, the distribution system and the location within the same distribution system. Residential water heating led to an increase in average THM levels for the two distribution systems studied, which tended to be greater in winter. Residential water heating affected the two main HAA species found in the area studied (dichloroacetic (DCAA) and trichloroacetic (TCAA) acids) differently. In fact, the average DCAA levels increased due to water residential heating while a small change in average levels was observed for TCAA. However, the water heating impact on HAAs (in terms of importance and sometimes of tendency (increase vs. decrease)) may also differed between residences. The influence of seasons on the change in the average DCAA and TCAA levels (in µg/L) from residential water heating was not statistically significant except for TCAA levels in one distribution system. Results show the importance of considering site-specific characteristics of CTW (CBP level, temperature, residual chlorine, etc.) to estimate the levels of CBPs in HTW in CBP exposure assessment studies (and not to generalize for an entire population). The reported data can thus be useful in assessing for exposure to DBPs in epidemiological studies.

Electrochemical biointerfaces based on carbon nanotubes-mesoporous silica hybrid material: Bioelectrocatalysis of hemoglobin and biosensing applications.

We are reporting a novel biosensing platform based on a hybrid nanomaterial that combines the advantages of Nafion-coated multiwalled carbon nanotubes (MWCNTs) and mesoporous silica MCM41 nanoparticles functionalized with hemoglobin (Hb). MWCNTs-MCM41-Hb hybrid bioconjugate was characterized by scanning electron microscopy (SEM), UV-vis spectroscopy and electrochemical techniques after deposition at glassy carbon electrodes (GCE). The combination of the high surface area, biocompatibility and protein loading capacity of MCM41 nanoparticles and the high surface area and catalytic properties of MWCNTs allowed the direct electron transfer (DET) between Hb and the electrode surface. The electron transfer rate constant (k) and the surface coverage of electroactive Hb (ΓHb) were 5.2 s-1 and 4.7 × 10-10 mol cm-2, respectively. The GCE modified with the nanostructured architecture (GCE/MWCNTs-MCM41-Hb) was successfully used as a third-generation biosensor for the highly sensitive and selective quantification of nitrite (NO2-) and trichloroacetic acid (TCA) by taking advantage of the excellent biocatalytic activity of Hb and the efficient direct charge transfer of the heme group.

Associations Between Disinfection By-Product Exposures and Craniofacial Birth Defects.

OBJECTIVE: The aim of this study was to examine associations between craniofacial birth defects (CFDs) and disinfection by-product (DBP) exposures, including the sum of four trihalomethanes (THM4) and five haloacetic acids (HAA5) (ie, DBP9). METHODS: We calculated first trimester adjusted odds ratios (aORs) for different DBPs in a matched case-control study of 366 CFD cases in Massachusetts towns with complete 1999 to 2004 THM and HAA data. RESULTS: We detected elevated aORs for cleft palate with DBP9 (highest quintile aOR = 3.52; 95% CI: 1.07, 11.60), HAA5, trichloroacetic acid (TCAA), and dichloroacetic acid. We detected elevated aORs for eye defects with TCAA and chloroform. CONCLUSION: This is the first epidemiological study of DBPs to examine eye and ear defects, as well as HAAs and CFDs. The associations for cleft palate and eye defects highlight the importance of examining specific defects and DBPs beyond THM4.

Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population.

BACKGROUND: Evaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics. OBJECTIVE: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure. METHODS: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC (1,000 mg/kg) or vehicle (Alkamuls-EL620) and euthanized at various time points (n = 1/strain/time). Concentration­time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed. RESULTS: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude (~8-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPARα)-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung. CONCLUSIONS: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788.

In vitro bioacessibility and transport across Caco-2 monolayers of haloacetic acids in drinking water.

Water disinfection plays a crucial role in water safety but it is also a matter of concern as the use of disinfectants promotes the formation of disinfection by-products (DBPs). Haloacetic acids (HAAs) are one of the major classes of DBPs since they are frequently found in treated water, are ubiquitous, pervasive and have high water solubility, so a great concern emerged about their formation, occurrence and toxicity. Exposure to HAAs is influenced by consumption patterns and diet of individuals thus their bioavailability is an important parameter to the overall toxicity. In the current study the bioacessibility of the most representative HAAs (chloroacetic acid - MCAA, bromoacetic acid - MBAA, dichloroacetic acid - DCAA, dibromoacetic acid - DBAA, and trichloroacetic acid - TCAA) after simulated in vitro digestion (SIVD) in tap water and transport across Caco-2 monolayers was evaluated. Compounds were monitored in 8 points throughout the digestion phases by an optimized LC-MS/MS methodology. MCAA and MBAA were not bioaccessible after SIVD whereas DCAA, DBAA and TCAA are highly bioaccessible (85 ± 4%, 97 ± 4% and 106 ± 7% respectively). Concerning transport assays, DCAA and DBAA were highly permeable throughout the Caco-2 monolayer (apparent permeability and calculated fraction absorbed of 13.62 × 10(-6) cm/s and 90% for DCAA; and 8.82 × 10(-6) cm/s and 84% for DBAA), whereas TCAA showed no relevant permeability. The present results may contribute to efficient risk analysis studies concerning HAAs oral exposure from tap water taking into account the different biological behaviour of these chemically similar substances.

Validation of an HPLC-UV method for the identification and quantification of bioactive amines in chicken meat / Validação de metodologia por HPLC/UV para identificação e quantificação de aminas bioativas em carne de frango de corte

A high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was validated for the study of bioactive amines in chicken meat. A gradient elution system with an ultraviolet detector was used after extraction with trichloroacetic acid and pre-column derivatization with dansyl chloride. Putrescine, cadaverine, histamine, tyramine, spermidine, and spermine standards were used for the evaluation of the following performance parameters: selectivity, linearity, precision, recovery, limits of detection, limits of quantification and ruggedness. The results indicated excellent selectivity, separation of all amines, a coefficient of determination greater than 0.99 and recovery from 92.25 to 102.25% at the concentration of 47.2mg.kg-1, with a limit of detection at 0.3mg.kg-1 and a limit of quantification at 0.9mg.kg-1 for all amines, with the exception of histamine, which exhibited the limit of quantification, of 1mg.kg-1. In conclusion, the performance parameters demonstrated adequacy of the method for the detection and quantification of bioactive amines in chicken meat.(AU)

Um método de cromatografia líquida de alta eficiência (CLAE) para pesquisa de aminas bioativas em carne de frango foi validado. Foi utilizado um sistema de gradiente de eluição com detector ultravioleta, após extração com ácido tricloroacético e derivação pré-coluna com cloreto de dansila. Os padrões de putrescina, cadaverina, histamina, tiramina, espermidina e espermina foram utilizados para avaliação dos seguintes parâmetros de desempenho: seletividade, linearidade, precisão, recuperação, limites de detecção, limites de quantificação e robustez. Os resultados mostraram excelente seletividade e separação de todas as aminas, coeficiente de determinação superior a 0,99, recuperação entre 92,25 e 105,25% na concentração 47,2mg.kg-1, limites de detecção de 0,3mg.kg-1 e limite de quantificação de 0,9mg.kg-1 para todas as aminas, com exceção da histamina, que apresentou o limite de quantificação mais alto, de 1mg.kg-1. Foi concluído que os parâmetros de desempenho demonstraram adequação do método para detecção e quantificação de aminas bioativas em carne de frango.(AU)

Application of three-dimensional reduced graphene oxide-gold composite modified electrode for direct electrochemistry and electrocatalysis of myoglobin.

In this paper a three-dimensional (3D) reduced graphene oxide (RGO) and gold (Au) composite was synthesized by electrodeposition and used for the electrode modification with carbon ionic liquid electrode (CILE) as the substrate electrode. Myoglobin (Mb) was further immobilized on the surface of 3D RGO-Au/CILE to obtain an electrochemical sensing platform. Direct electrochemistry of Mb on the modified electrode was investigated with a pair of well-defined redox waves appeared on cyclic voltammogram, indicating the realization of direct electron transfer of Mb with the modified electrode. The results can be ascribed to the presence of highly conductive 3D RGO-Au composite on the electrode surface that accelerate the electron transfer rate between the electroactive center of Mb and the electrode. The Mb modified electrode showed excellent electrocatalytic activity to the reduction of trichloroacetic acid in the concentration range from 0.2 to 36.0 mmol/L with the detection limit of 0.06 mmol/L (3σ).

Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid.

By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L(-1) accompanied by a detection limit of 0.30 mmol·L(-1) (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors.

The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene.

Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparα-null, and humanized PPARα (hPPARα) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparα-null and hPPARα mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARα-responsive genes was observed in liver and kidney of hPPARα and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain-dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARα status affects the levels of the putative PPARα agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparα-null and hPPARα mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor-mediated toxicodynamic effects.

Development and validation of an universal interface for compound-specific stable isotope analysis of chlorine (37Cl/35Cl) by GC-high-temperature conversion (HTC)-MS/IRMS.

A universal application of compound-specific isotope analysis of chlorine was thus far limited by the availability of suitable analysis techniques. In this study, gas chromatography in combination with a high-temperature conversion interface (GC-HTC), converting organic chlorine in the presence of H2 to gaseous HCl, was coupled to a dual-detection system, combining an ion trap mass spectrometer (MS) and isotope-ratio mass spectrometer (IRMS). The combination of the MS/IRMS detection enabled a detailed characterization, optimization, and online monitoring of the high-temperature conversion process via ion trap MS as well as a simultaneous chlorine isotope analysis by the IRMS. Using GC-HTC-MS/IRMS, chlorine isotope analysis at optimized conversion conditions resulted in very accurate isotope values (δ(37)Cl(SMOC)) for measured reference material with known isotope composition, including chlorinated ethylene, chloromethane, hexachlorocyclohexane, and trichloroacetic acids methyl ester. Respective detection limits were determined to be <15 nmol Cl on column with achieved precision of <0.3‰.

Epistemology of contaminants of emerging concern and literature meta-analysis.

A meta-analysis was conducted to inform the epistemology, or theory of knowledge, of contaminants of emerging concern (CECs). The CEC terminology acknowledges the existence of harmful environmental agents whose identities, occurrences, hazards, and effects are not sufficiently understood. Here, data on publishing activity were analyzed for 12 CECs, revealing a common pattern of emergence, suitable for identifying past years of peak concern and forecasting future ones: dichlorodiphenyltrichloroethane (DDT; 1972, 2008), trichloroacetic acid (TCAA; 1972, 2009), nitrosodimethylamine (1984), methyl tert-butyl ether (2001), trichloroethylene (2005), perchlorate (2006), 1,4-dioxane (2009), prions (2009), triclocarban (2010), triclosan (2012), nanomaterials (by 2016), and microplastics (2022 ± 4). CECs were found to emerge from obscurity to the height of concern in 14.1 ± 3.6 years, and subside to a new baseline level of concern in 14.5 ± 4.5 years. CECs can emerge more than once (e.g., TCAA, DDT) and the multifactorial process of emergence may be driven by inception of novel scientific methods (e.g., ion chromatography, mass spectrometry and nanometrology), scientific paradigm shifts (discovery of infectious proteins), and the development, marketing and mass consumption of novel products (antimicrobial personal care products, microplastics and nanomaterials). Publishing activity and U.S. regulatory actions were correlated for several CECs investigated.