Toxics, Volume 9, Issue 4 (April 2021) – 20 articles

Pharmaceuticals and hormones (PhACs) enter the aquatic environment in multiple ways, posing potential adverse effects on non-target organisms. They have been widely detected in drinking water sources, challenging water companies to reassure good quality drinking water. The aim of this study was to evaluate the concentration of sixteen PhACs in both raw and treated drinking water sources in the Metropolitan Area of Turin—where Società Metropolitana Acque Torino (SMAT) is the company in charge of the water cycle management—and evaluate the potential human health risks associated to these compounds. Multivariate spatial statistical analysis techniques were used in order to characterize the areas at higher risk of pollution, taking into account the already existing SMAT sampling points’ network. Health risks were assessed considering average detected concentrations and provisional guideline values for individual compounds as well as their combined mixture. As reported in the just-issued Drinking Water Directive 2020/2184/UE, in order to establish priority substances, a risk assessment of contaminants present in raw drinking water sources is required for monitoring, identifying potential health risks and, if necessary, managing their removal. The results showed negligibly low human health risks in both raw water sources and treated water. Full article

Flavoring agents are added to cigarettes to improve taste. There are mostly permitted food additives, but some of them are restricted for use in food, cosmetics, and toys, since they can cause allergic reactions. Previous studies have investigated the levels of flavoring agents in tobacco but none has focused on their content in filter tips and capsules. Moreover, no studies have assessed the risk of adding allergenic flavoring agents in cigarettes. Here, we developed and validated a simultaneous analysis method for 25 allergenic flavoring agents and menthol with gas chromatography–tandem mass spectrometry to determine levels of flavoring agents in the tobacco, filter tips, and capsules of 54 commercial cigarettes in Korea. All cigarettes contained at least one allergenic flavoring agent regardless of the inclusion of flavoring capsules. Importantly, the filter tips and the capsules contained higher levels of flavoring agents than tobacco, highlighting the importance of the quantification of flavoring agents in these parts of cigarettes. Nevertheless, the risk assessment based on their levels in cigarettes suggested that their exposure was maintained at a safe level. However, the risk assessed from maximum menthol, linalool, and cinnamaldehyde exceeded one-tenth of derived no-effect levels, suggesting the need for further studies on their risk to human health. Full article

The quantification and identification of saccharides in pristine marine aerosols can provide useful information for determining the contributions of anthropogenic and natural sources of the aerosol. However, individual saccharide compounds in pristine marine aerosols that exist in trace amounts are difficult to analyze due to their low concentrations. Thus, in this study, we applied gas chromatography–tandem mass spectrometry (GC-MS/MS) in multiple reaction monitoring (MRM) mode to analyze the particulate matter with an aerodynamic diameter equal or less than 2.5 μm (PM_2.5) samples, and the results were compared with those of conventional GC-MS. To investigate the chemical properties of pristine marine aerosols, 12 PM_2.5 samples were collected while aboard Araon, an ice-breaking research vessel (IBRV), as it sailed from Incheon, South Korea to Antarctica. The method detection limits of GC-MS/MS for 10 saccharides were 2–22-fold lower than those of GC-MS. Consequently, the advantages of GC-MS/MS include (1) more distinct peak separations, enabling the accurate identification of the target saccharides and (2) the quantification of all individual saccharide compounds with concentrations outside the quantifiable range of GC-MS. Accordingly, the time resolution for sampling saccharides in pristine marine aerosols can be improved with GC-MS/MS. Full article

Background: About half of the population in developing countries are exposed to indoor pollution such as combustion fuels at present. Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality globally and the primary cause of COPD in women is indoor air pollution exposure, while tobacco smoking is the leading cause in men. The aim of this systematic review and meta-analysis is to evaluate the correlation between the indoor air pollution and deaths related to COPD and COPD prevalence in South Asia. Methods: A systematic search on studies with sufficient statistical power has been conducted from 1985 until 30 June 2020, in English electronic databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in MEDLINE and PubMed databases with the terms Chronic Obstructive Pulmonary disease COPD or Chronic Bronchitis or Emphysema or COPD Deaths or Chronic Obstructive Lung Disease or Airflow Obstruction or Chronic Airflow Obstruction or Airflow Obstruction, Chronic or Bronchitis, Chronic and Mortality or Death or Deceased was conducted. Studies were eligible if they were Prospective controlled or non-controlled trials conducted in Southern Asia/ Asia and Retrospective studies conducted in Southern Asia/ Asia. Results: The results have concluded that long term exposure to indoor pollution had a significant effect on COPD deaths as well as its symptoms. Odd’s ratio was in a range of 1.05 (Randomized controlled trials) to 7.87 (Cross sectional studies) for all the studies mentioned. Meta-analysis observed a significantly higher Odds Ratio of 2.13 for COPD mortality and 2.08 for COPD prevalence on exposure to indoor air pollution. Conclusion: Exposure to solid fuel smoke is consistently and significantly correlated with COPD mortality and COPD prevalence in South Asian countries, in spite of heterogeneity observed in the studies included. For performing domestic tasks, initiatives are to be taken to reduce dependency on solid fuel by using cleaner alternatives or comparatively cleaner technology. Full article

Overuse of antibiotics has resulted in widespread contamination of the environment and triggered antibiotic resistance in pathogenic bacteria. Conventional wastewater treatment plants (WWTPs) are not equipped to remove antibiotics. Effluents from WWTPs are usually the primary source of antibiotics in aquatic environments. There is an urgent need for cost-effective, environment-friendly technologies to address this issue. Along with antibiotics, nutrients (nitrogen and phosphorus) are also present in conventional WWTP effluents at high concentrations, causing environmental problems like eutrophication. In this study, we tested vetiver grass in a plug flow reactor-based constructed wetland model in a greenhouse setup for removing antibiotics ciprofloxacin (CIP) and tetracycline (TTC), and nutrients, N and P, from secondary wastewater effluent. The constructed wetland was designed based on a previous batch reaction kinetics study and reached a steady-state in 7 days. The measured concentrations of antibiotics were generally consistent with the modeling predictions using first-order reaction kinetics. Vetiver grass significantly (p < 0.05) removed 93% and 97% of CIP and TTC (initial concentrations of 10 mg/L), simultaneously with 93% and 84% nitrogen and phosphorus, respectively. Results show that using vetiver grass in constructed wetlands could be a viable green technology for the removal of antibiotics and nutrients from wastewater. Full article

A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction was validated for the extraction of seven coumarin anticoagulant rodenticides (ARs) and 36 pharmaceutical active compounds (PhACs) residues in soil samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). The aim of this work was to develop a method for the monitoring of these compounds in agricultural lands as well as in forensic applications for the determination of ARs poisoning. As far as is known, this is the first time that a QuEChERS-based method is used for the extraction of ARs in soil, as well as on such a quantity of PhACs. A matrix effect study was carried out on samples of soil devoted to agriculture in the midland area of the Canary Islands (clay loam type). It was in house validated (accuracy, precision, and linearity) at seven spiked levels between 0.5 and 50 ng g⁻¹. The limits of quantification (LOQ) ranged between 0.5 and 50.0 ng g⁻¹ and the limits of detection (LOD) ranged from 0.024 to 6.25 ng g⁻¹. The method was then successfully used for both the determination of the target analytes in the soils from the agricultural plots that had been irrigated with regenerated water, and in the soil collected from underneath wild bird carcasses (which had been the subject of forensic investigation). Full article

Prenatal exposure to methylmercury (MeHg) affects child development after birth. However, many epidemiological studies have evaluated total mercury levels without analyzing speciation. Biomonitoring of MeHg and inorganic mercury (IHg) is essential to reveal each exposure level. In this study, we compared a high-throughput analysis for mercury speciation in blood using liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) and liquid chromatography-cold vapor atomic fluorescence spectrometry (LC-CVAFS). The validated LC-ICP-MS method was applied to 101 maternal blood and 366 cord blood samples in the pilot study of the Japan Environment and Children’s Study (JECS). The accuracy of the LC-CVAFS method ranged 90–115% determined by reference material analysis. To evaluate the reliability of 366 cord blood samples, fifty cord blood samples were randomly selected and analyzed using LC-CVAFS. The median (5th–95th percentile) concentrations of MeHg and IHg were 5.4 (1.9–15) and 0.33 (0.12–0.86) ng/mL, respectively, in maternal blood, and 6.3 (2.5–15) and 0.21 (0.08–0.49) ng/mL, respectively, in cord blood. Inter-laboratory comparison showed a relatively good agreement between LC-ICP-MS and LC-CVAFS. The median cord blood:maternal blood ratios of MeHg and IHg were 1.3 and 0.5, respectively. By analyzing speciation, we could focus on the health effects of each chemical form. Full article

Metabolites of polychlorinated biphenyls (PCBs)—hydroxylated PCBs (OH-PCBs), chlorobenzyl alcohols (CB-OHs), and chlorobenzaldehydes (CB-CHOs)—were incubated in vitro with the extracellular liquid of Pleurotus ostreatus, which contains mainly laccase and low manganese-dependent peroxidase (MnP) activity. The enzymes were able to decrease the amount of most of the tested OH-PCBs by > 80% within 1 h; the removal of more recalcitrant OH-PCBs was greatly enhanced by the addition of the laccase mediator syringaldehyde. Conversely, glutathione substantially hindered the reaction, suggesting that it acted as a laccase inhibitor. Hydroxylated dibenzofuran and chlorobenzoic acid were identified as transformation products of OH-PCBs. The extracellular enzymes also oxidized the CB-OHs to the corresponding CB-CHOs on the order of hours to days; however, the mediated and nonmediated setups exhibited only slight differences, and the participating enzymes could not be determined. When CB-CHOs were used as the substrates, only partial transformation was observed. In an additional experiment, the extracellular liquid of Irpex lacteus, which contains predominantly MnP, was able to efficiently transform CB-CHOs with the aid of glutathione; mono- and di-chloroacetophenones were detected as transformation products. These results demonstrate that extracellular enzymes of ligninolytic fungi can act on a wide range of PCB metabolites, emphasizing their potential for bioremediation. Full article

We studied the effects of a hydrophobized reversed-phase feed adsorbent in the form of a polyoctylated polysilicate hydrogel (POPSH) on productivity indicators, metabolic adaptation, and on the level of polychlorinated biphenyls (PCBs) in the blood of growing Holsteinized black-and-white heifers during the transition period. Two groups of two-month-old heifers of 20 head each were used. The experimental group received POPSH in addition to the main diet. The use of the adsorbent led to an increase in daily weight gain by 19.9% and to a decrease in the total concentration of PCB congeners found in whole blood by 40%. The greatest decrease in concentration (35–52%) was observed for tetra-, penta- and hexachlorobiphenyls. These results demonstrate the possibilities of effective protection of calves from lipophilic toxins of feed and their active decontamination. Full article

This study assessed the acute and chronic risk of pesticides, singly and as mixtures, for fish using comprehensive chemical data of four monitoring studies conducted in small- and medium-sized streams of Switzerland between 2012 and 2018. Pesticides were ranked based on single substance risk quotients and relative contribution to mixture risk. Concentrations of the pyrethroid insecticides, λ-cyhalothrin, cypermethrin and deltamethrin, and the fungicides, carbendazim and fenpropimorph, posed acute or chronic single substance risks. Risk quotients of eighteen additional pesticides were equal or greater than 0.1, and thirteen of those contributed ≥30% to mixture risk. Relatively few substances dominated the mixture risk in most water samples, with chronic and acute maximum cumulative ratios never exceeding 5 and 7, respectively. A literature review of toxicity data showed that concentrations of several pesticides detected in Swiss streams were sufficient to cause direct sublethal effects on fish in laboratory studies. Based on the results of our study, we conclude that pesticides detected in Swiss streams, especially pyrethroid insecticides, fungicides and pesticide mixtures, pose a risk to fish health and can cause direct sublethal effects at environmental concentrations. Sensitive life stages of species with highly specialized life history traits may be particularly vulnerable; however, the lack of toxicity data for non-model species currently prevents a conclusive assessment across species. Full article

DNA adductomics is a relatively new omics approach aiming to measure known and unknown DNA modifications, called DNA adducts. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. Recent advances in the field of mass spectrometry have allowed the possibility to perform a comprehensive analysis of adducts, for instance, by using a nontargeted data-independent acquisition method, with multiple precursor m/z windows as an inclusion list. However, the generated data are large and complex, and there is a need to develop algorithms to simplify and automate the time-consuming manual analysis that has hitherto been used. Here, a graphical user interface (GUI) program was developed, with the purpose of tracking a characteristic neutral loss reaction from tandem mass spectrometry of the nucleoside adducts. This program, called nLossFinder, was developed in the MATLAB platform, available as open-source code. Calf thymus DNA was used as a model for method optimization, and the overall adductomics approach was applied to DNA from amphipods (Monoporeia affinis) collected within the Swedish National Marine Monitoring Program. In the amphipod DNA, over 150 putative adducts were found in comparison to 18 using a manual approach in a previous study. The developed program can improve the processing time for large MS data, as it processes each sample in a few seconds, and hence can be applicable for high-throughput screening of adducts. Full article

Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that communicate across the body to stimulate specific receptors that bind DNA and regulate the expression of a suite of genes. These mechanisms, including gene regulation, DNA binding, and protein binding, can be tied to differences in individual susceptibility across a genetically diverse population. In this review, we posit that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure. We begin by summarizing how the biology of EDCs has implications for genetically diverse populations. We then describe how gene-environment interactions (GxE) across the complex pathways of endocrine signaling could lead to differences in susceptibility. We survey examples in the literature of individual susceptibility differences to EDCs, pointing to a need for research in this area, especially regarding the exceedingly complex thyroid pathway. Following a discussion of experimental designs to better identify and study GxE across EDCs, we present a case study of a high-throughput screening signal of putative GxE within known endocrine disruptors. We conclude with a call for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility. Full article

Polycyclic aromatic hydrocarbons (PAHs), 33 methylated PAHs (Me-PAHs), and 14 nitrated PAHs (NPAHs) were measured in wastewater treatment plants (WWTPs) to study the removal efficiency of these compounds through the WWTPs, as well as their source appointment and potential risk in the effluent. The concentrations of ∑PAHs, ∑Me-PAHs, and ∑NPAHs were 2.01–8.91, 23.0–102, and 6.21–171 µg/L in the influent, and 0.17–1.37, 0.06–0.41 and 0.01–2.41 µg/L in the effluent, respectively. Simple Treat 4.0 and meta-regression methods were applied to calculate the removal efficiencies (REs) for the 63 PAHs and their derivatives in 10 WWTPs and the results were compared with the monitoring data. Overall, the ranges of REs were 55.3–95.4% predicated by the Simple Treat and 47.5–97.7% by the meta-regression. The results by diagnostic ratios and principal component analysis PCA showed that “mixed source” biomass, coal composition, and petroleum could be recognized to either petrogenic or pyrogenic sources. The risk assessment of the effluent was also evaluated, indicating that seven carcinogenic PAHs, Benzo[a]pyrene, Dibenz[a,h]anthracene, and Benzo(a)anthracene were major contributors to the toxics equivalency concentrations (TEQs) in the effluent of WWTPs, to which attention should be paid. Full article

(1) Background: The incidence of hypertension in very low birthweight (VLBW) infants in a single neonatal intensive care unit (NICU) dropped markedly during a 2-year period when the IV fluid (IVF) in both the antenatal unit and the NICU temporarily changed to a di-2-ethylhexyl phthalate (DEHP)-free formulation. The objective of the current report is to document this observation and demonstrate the changes in incidence of hypertension were not associated with the variation in risk factors for hypertension; (2) Methods: The charts of all VLBW infants born in a single NICU during a 7-year span were reviewed. This time includes 32 months of baseline, 20 months of DEHP-free IVF, 20 months of IVF DEHP re-exposure, and two 4-month washout intervals. The group of interest was limited to VLBW infants with bronchopulmonary dysplasia (BPD). Chi-square analysis was used to compare incidence of hypertension among periods. Vermont Oxford NICU Registry data were examined for variation in maternal and neonatal risk factors for hypertension; Results: Incidence of hypertension in VLBW infants with BPD decreased from 7.7% (baseline) to 1.4% when IVF was DEHP-free, rising back to 10.1% when DEHP-containing IVF returned to use. Risk factors for neonatal hypertension were stable across the 3 study periods in the NICU’s group of VLBW infants; (3) Conclusions: Serendipitous removal of IVF containing DEHP resulted in near elimination of hypertension in one NICU—an effect entirely reversed after the same brand of DEHP-containing IVF returned to clinical use. These results suggest that DEHP exposure from IVF plays a major role in neonatal hypertension. Full article

Water is regarded as an important natural resource to sustain life, and its purification is an important criterion that determines its quality and usefulness. In this study, the incorporation of Fe³⁺ oxide onto a phenylenediamine (pPD) polymer matrix through chemical co-polymerization was prepared, and its arsenite and fluoride removal potentials at optimal conditions from aqueous solution were evaluated. The morphology and structural analysis of the synthesized Fe-doped pPD (Fe-pPD) were comparatively evaluated using the FT-IR, SEM, EDS, and XRD techniques. Fe was successfully incorporated onto pPD matrix as confirmed by different morphological characterizations. The rate of adsorption of F⁻ and As³⁺ onto the Fe-pPD composite best followed the pseudo-second-order kinetic model. The experimental data for both As³⁺ and F⁻ onto the Fe-pPD composite better fit the Freundlich isotherm model at different operating temperatures. Overall, the synthesized composite exhibited a strong affinity towards fluoride uptake (96.6%) than arsenite uptake (71.14%) with a maximum capacity of 6.79 (F⁻) and 1.86 (As³⁺) mg/g. Additionally, the synthesized adsorbent showed some level of antimicrobial activity against common water-borne bacterial. Therefore, the Fe-doped pPD composite has the potential ability for inorganic metal species pollutants remediation and bacterial disinfection in community-level water purification processes. Full article

Sulfoxaflor is the first member of the neonicotinoid-sulfoximine insecticides that acts as an agonist of nicotinic acetylcholine receptors (nAChRs). This study investigated the acute effects of sulfoxaflor on acetylcholinesterase (AChE; EC 3.1.1.7) enzyme activity in the brain and muscle tissues of zebrafish (Danio rerio) as a model organism. The zebrafish were exposed to 0.87 mg/L (2.5% of 96 h 50% lethal concentration (LC₅₀), 1.75 mg/L (5% of 96 h LC₅₀) and 3.51 mg/L (10% of 96 h LC₅₀) of sulfoxaflor for 24 h–48 h and 96 h periods. AChE enzyme activities were analysed by a spectrophotometric method in the brain and muscle tissues. The results of this study showed that in vivo acute sulfoxaflor exposure significantly increased AChE enzyme activity in the brain and muscle tissues of zebrafish. The induction percentages of AChE were between 10 and 83%, and 19 and 79% for brain and muscle tissues, respectively. As a result, it was found that sulfoxaflor had an effect on AChE enzyme activity in the two main tissues containing this enzyme, and it can be considered as a potential neuroactive compound for zebrafish. Full article

Chronic obstructive pulmonary disease (COPD), the leading cause of mortality and morbidity worldwide, is characterized by abnormal activation of inflammatory cells. The increased pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), further amplify the inflammation. We evaluated the dose response relationship of IL-1β and TNF-α levels and severity of airflow limitation, and differential responses in IL-1β and TNF-α between biomass COPD (BMS-COPD) and tobacco smoke COPD (TS-COPD) using a case control design in 160 subjects. Patients with COPD had higher serum levels of both IL-1β and TNF-α compared to healthy controls. A large difference in TNF-α was observed between TS-COPD and BMS-COPD, where TS-COPD patients had much higher levels. Serum IL-1β levels were higher in BMS-COPD. Levels of IL-1β correlated better with severity of airflow limitation than TNF-α levels. Both TNF-α and IL-1β levels had a negative linear relationship with Forced Expiratory Volume in 1st second (FEV1) and six-minute walk distance. The correlations were stronger with FEV1 than six-minute walk distance. The correlations of TNF-α and IL-1β with St George Respiratory Questionnaire (SGRQ) scores and body mass index (BMI) were not significant. In conclusion, the levels of pro-inflammatory cytokines TNF-α and IL-1β are differently elevated in TS-COPD and BMS-COPD, respectively. Full article

This paper elaborates on the potential toxicants detected in inland water, freshwater crustaceans, and tilapia in an island that experienced mining disasters in 1993 and 1996. Specimen samples were collected in six municipalities of the island province in 2019 and presence of metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) were analyzed using Inductively Coupled Plasma-Optical Emission Spectrometer (ICP-OES). Potential ecological risks analysis followed the Hakanson approach. Canonical correspondence analysis PAST Version 3.22, IBM SPSS 25.0, and Pearson correlation were employed for statistical analysis, and GIS Pro 2.5 for mapping of sampling locations and spatial distribution. Results showed that Mn and Zn concentration was highest in surface water (SW) and groundwater (GW), respectively. All metal concentration values exceeded the maximum permissible limit by regulatory international organizations. Elevated concentration of Cr, Cu, Fe, Mn, and Zn was detected in both crustaceans and tilapia. The calculated health hazard indices were greater than one, which means potential high adverse effects on public health when ingested. The municipality of Sta. Cruz and Torrijos recorded higher potential ecological risk among the six municipalities. Results of the correlation analysis suggested that metals in SW and GW have a similar origin, mutual dependence, and identical behavior during transport. Full article

To understand changes in enzyme activity and gene expression as biomarkers of exposure to methylmercury, we exposed loggerhead turtle erythrocytes (RBCs) to concentrations of 0, 1, and 5 mg L⁻¹ of MeHg and de novo transcriptome were assembled using RNA-seq. The analysis of differentially expressed genes (DEGs) indicated that 79 unique genes were dysregulated (39 upregulated and 44 downregulated genes). The results showed that MeHg altered gene expression patterns as a response to the cellular stress produced, reflected in cell cycle regulation, lysosomal activity, autophagy, calcium regulation, mitochondrial regulation, apoptosis, and regulation of transcription and translation. The analysis of DEGs showed a low response of the antioxidant machinery to MeHg, evidenced by the fact that genes of early response to oxidative stress were not dysregulated. The RBCs maintained a constitutive expression of proteins that represented a good part of the defense against reactive oxygen species (ROS) induced by MeHg. Full article

Communicating individual human biomonitoring results to study participants has been the subject of debate for some time. This debate is dominated by ethical considerations from a researchers’ perspective on whether or not to communicate, thereby overlooking more practice-based questions from a participants’ perspective on what and how to communicate. We conducted a small scale follow-up study based on eleven face-to-face interviews with mothers participating in the third cycle of the Flemish Environment and Health Study (FLEHS III 2012–2015) to investigate how they experienced and interpreted individual biomonitoring results. Key findings indicate that respondents were generally satisfied with participating in the biomonitoring study, but the report-back process especially lacked contextualized information and interactive communication options to better comprehend and cope with personal results. These findings also argue in favor of a more tailored approach in which report-back methods, formats and content are diversified according to the type of results and the preferences of participants. A reflexive research practice with active engagement in follow-up research is crucial to improve participants’ understanding and use of personal biomonitoring results. Full article