Decomposition of microplastics using copper oxide/bismuth vanadate-based photocatalysts: Insight mechanisms and environmental impacts.

To mitigate marine pollution, we improved the photo-Fenton reaction of modified nanoscale CuO/BiVO4 photocatalysts to resolve the challenge of efficient microplastic degradation in wastewater treatment. Material property analysis and computational results revealed that deposition of CuO onto BiVO4 nanocomposites improved photocatalytic activity by promoting an excess of electrons in CuO and surface charge transfer, resulting in an increased production of e--h+ for ROS generation via H2O2 activation. 1O2 was dominated and identified through quenching experiments, XPS analysis, and EPR. ROS generation increased via H2O2 activation, causing major surface abrasion and increased carbonyl and vinyl indices in microplastics. Treated water had minimal impact on Lycopersicon esculentum Mill. seedling growth but caused considerable mortality in cell lines and Moina macrocopa mortality at greater dosages due to their sensitivity to ions and H2O2 residuals. Overall, this treatment can effectively degrade microplastics, but the dilution of treated water is still needed before being discharged.

Bringing the emerging organophosphate flame retardants (eOPFRs) into view: A hidden ecological and human health threat.

The production and usage of organophosphate flame retardants (OPFRs) in textiles, plastics, and electronics have surged, with phosphorus-based flame retardants constituting over 30 % of the global consumption of flame retardants. Meanwhile, concerns regarding the potential hazards of OPFRs to ecosystems and human health including disruptions in the endocrine system, inhibition of reproduction, and manifestation of developmental defects have intensified. However, our comprehensive data analysis has unveiled a pronounced and critical knowledge gap, as at present, a majority of studies emphasize the attributes of traditional OPFRs, such as triphenyl phosphate (TPHP), while emerging OPFRs (eOPFRs) remain undeservedly overlooked. We elaborated on the current advancements and challenges regarding eOPFRs research and demonstrated that eOPFRs exhibit considerable diversity in terms of their chemical structures, substantial residue levels, broad sources of occurrence, and limited understanding of their potent (eco)toxicological implications. In light of these attributes, it becomes evident that the environmental and health risks of eOPFRs can be comparable to, if not surpass, those attributed to traditional OPFRs. This compelling observation underscores an imperative need for heightened research focus and extensive research efforts dedicated to the study of eOPFRs, rather than still focusing on the realm of their traditional counterparts. Despite the challenges ahead, the emphasized environmental surveillance and toxicological assessment are imperative to prevent the potential evolution of these compounds into a significant ecological and human health threat.

Challenges Associated with Biological Safety Assessments for Drug-Device Combination Products.

Biological safety assessments for drug-device combination products involve evaluation of the drug container closure and the device constituent part. When the device constituent part is the drug delivery system as well as the drug container closure system, both device and drug-based packaging standards have been deemed applicable. Approaches used for the biological safety assessment of medical devices differ from those used for pharmaceutical packaging/delivery systems. One area of difference is the extent to which chemical characterization with toxicological assessment is used either in addition to, or in place of, biological in vivo or in vitro tests. Differences also exist in the way nonclinical studies are used to evaluate the safety of medical devices or drug delivery systems. The lack of alignment in standards and guidance has resulted in confusion over what combination of tests and methods of evaluation constitute a biological safety assessment that will meet regulatory expectations for a drug-device combination product. The intent of this article is to discuss the challenges created when the packaging or delivery system is also a device constituent part of a drug-device combination product. Suggestions are offered regarding approaches that may be useful for conducting suitable biological safety assessments for drug-device combination products.

Zebrafish as model organisms for toxicological evaluations in the field of food science.

Food safety has long been an area of concern. The selection of stable and efficient model organisms is particularly important for food toxicology studies. Zebrafish (Danio rerio) are small model vertebrates, and 70% of human genes have at least one zebrafish ortholog. Zebrafish have advantages as model organisms due to their short life cycle, strong reproductive ability, easy rearing, and low cost. Zebrafish embryos have the advantage of being sensitive to the breeding environment and thus have been used as biosensors. Zebrafish and their embryos have been widely used for food toxicology assessments. This review provides a systematic and comprehensive summary of food toxicology studies using zebrafish as model organisms. First, we briefly introduce the multidimensional mechanisms and structure-activity relationship studies of food toxicological assessment. Second, we categorize these studies according to eight types of hazards in foods, including mycotoxins, pesticides, antibiotics, heavy metals, endocrine disruptors, food additives, nanoparticles, and other food-related ingredients. Finally, we list the applications of zebrafish in food toxicology studies in line with future research prospects, aiming to provide a valuable reference for researchers in the field of food science.

Oral nicotine pouches with an aftertaste? Part 1: screening and initial toxicological assessment of flavorings and other ingredients.

Nicotine pouches are oral products that deliver nicotine without containing tobacco. Previous studies mainly focused on the determination of known tobacco toxicants, while yet no untargeted analysis has been published on unknown constituents, possibly contributing to toxicity. Furthermore, additives might enhance product attractiveness. We therefore performed an aroma screening with 48 different nicotine-containing and two nicotine-free pouches using gas chromatography coupled to mass spectrometry, following acidic and basic liquid-liquid extraction. For toxicological assessment of identified substances, European and international classifications for chemical and food safety were consulted. Further, ingredients listed on product packages were counted and grouped by function. Most abundant ingredients comprised sweeteners, aroma substances, humectants, fillers, and acidity regulators. 186 substances were identified. For some substances, acceptable daily intake limits set by European Food Safety Agency (EFSA) and Joint FAO/WHO Expert Committee on Food Additives are likely exceeded by moderate pouch consumption. Eight hazardous substances are classified according to the European CLP regulation. Thirteen substances were not authorized as food flavorings by EFSA, among them impurities such as myosmine and ledol. Three substances were classified by International Agency for Research on Cancer as possibly carcinogenic to humans. The two nicotine-free pouches contain pharmacologically active ingredients such as ashwagandha extract and caffeine. The presence of potentially harmful substances may point to the need for regulation of additives in nicotine-containing and nicotine-free pouches that could be based on provisions for food additives. For sure, additives may not pretend positive health effects in case the product is used.

The impact of early-life exposure to three agrochemicals on survival, behavior, and gut microbiota of stingless bees (Partamona helleri).

Over the last few decades, agrochemicals have been partially associated with a global reduction in bees' population. Toxicological assessment is therefore crucial for understanding the overall agrochemical risks to stingless bees. Therefore, the lethal and sublethal effects of agrochemicals commonly used in crops (copper sulfate, glyphosate, and spinosad) on the behavior and gut microbiota of the stingless bee, Partamona helleri, were assessed using chronic exposure during the larval stage. When used at the field-recommended rates, both copper sulfate (200 µg of active ingredient/bee; a.i µg bee-1) and spinosad (8.16 a.i µg bee-1) caused a decrease in bee survival, while glyphosate (148 a.i µg bee-1) did not show any significant effects. No significant adverse effects on bee development were observed in any treatment with CuSO4 or glyphosate, but spinosad (0.08 or 0.03 a.i µg bee -1) increased the number of deformed bees and reduced their body mass. Agrochemicals changed the behavior of bees and composition of the gut microbiota of adult bees, and metals such as copper accumulated in the bees' bodies. The response of bees to agrochemicals depends on the class or dose of the ingested compound. In vitro rearing of stingless bees' larvae is a useful tool to elucidate the sublethal effects of agrochemicals.

Bioinsecticide spinosad poses multiple harmful effects on foragers of Apis mellifera.

There are multifactorial causes for the recent decline in bee populations, which has resulted in compromised pollination and reduced biodiversity. Bees are considered one of the most important non-target insects affected by insecticides used in crop production. In the present study, we investigated the effects of acute oral exposure to spinosad on the survival, food consumption, flight behavior, respiration rate, activity of detoxification enzymes, total antioxidant capacity (TAC), brain morphology, and hemocyte count of Apis mellifera foragers. We tested six different concentrations of spinosad for the first two analyses, followed by LC50 (7.7 mg L-1) for other assays. Spinosad ingestion decreased survival and food consumption. Exposure to spinosad LC50 reduced flight capacity, respiration rate, and superoxide dismutase activity. Furthermore, this concentration increased glutathione S-transferase activity and the TAC of the brain. Notably, exposure to LC50 damaged mushroom bodies, reduced the total hemocyte count and granulocyte number, and increased the number of prohemocytes. These findings imply that the neurotoxin spinosad affects various crucial functions and tissues important for bee performance and that the toxic effects are complex and detrimental to individual homeostasis.

Safety evaluation of Balanced Health Care Dan-A medicinal formulation containing traditional edible ingredients in lung tumor-loaded mice.

Chinese formulation-based medicinal food has been widely used in clinical trials, but its safety is not well studied. In this research, the edible safety assessment of Balanced Health Care Dan-a formulation containing traditional edible ingredients that were initially formulated to reduce side effects for lung cancer patients-was studied in mice based on biochemical and gut microbial analyses. The experimental mice were subcutaneously loaded with lung tumor A549 cells and then administrated with Balanced Health Care Dan (200 mg/kg or 400 mg/kg b.w. in gavage feeding) for 4 weeks. The body weight, blood parameters, and pathogenic phenotype in tissues were examined. No toxicological symptom was found in experimental mice compared with the normal control. Comprehensive analyses were also conducted to evaluate intestinal microbiota that are associated with many diseases. Balanced Health Care Dan modified the gut microbiota structure in a positive way. In conclusion, the Chinese formulation-based medicinal food has shown no toxicological effect in mice within 4 weeks of feeding experiment and has the potential to be used in clinical trials.

Preliminary toxicological assessment of heated tobacco products: A review of the literature and proposed strategy.

Heated tobacco products (HTP) have become increasingly common in many countries worldwide. The principle of heating tobacco, without combustion, to produce a nicotine-containing aerosol with remarkably reduced levels of other known toxins, compared to combusted tobacco cigarettes, is now well established. As these products are intended as alternatives to traditional combusted products, during the early stages of their development, it is important for manufacturers to ensure that the design of the product does not lead to any unintentionally increased or new risk for the consumer, compared to the traditional products that consumers seek to replace. There is limited guidance from tobacco product regulations concerning the requirements for performing such preliminary toxicological assessments. Here, we review the published literature on studies performed on HTPs in the pursuit of such data, outline a proposed approach that is consistent with regulatory requirements, and provide a logical approach to the preliminary toxicological assessment of HTPs.

Analysis of metals and metalloid in commercial fish species from the Galapagos Marine Reserve: Toxicological and nutritional assessment.

Aquatic pollution derived from metal presence in the Galapagos Islands could affect biodiversity and human health. This research provide a baseline on food safety in commercial fish species of the Galapagos Islands. We sampled muscle tissue of pelagic (Acanthocybium solandri) and demersal (Caulolatilus affinis, Pontinus clemensi, Hyporthodus mystacinus, and Paralabrax albomaculatus) species. Metal and metalloid concentrations per species were analyzed by Inductively Coupled Plasma Optical Spectrometry (ICP-OES). According to the Food and Agriculture Organization (FAO) regulation none of the studied species should be ingested; and according to the European Food Safety Authority (EFSA) regulation, all the studied species were above the Maximum Allowable Concentration (MAC) for Cd. According to EFSA, C. affinis should not be commercialized. Finally, A. solandri, P. clemensi and H. mystacinus do not represent a human health risk since its Margen of Safety (MoS) < 1 for people of up to 100 kg of body weight.

Ninety-day oral toxicological profiling of Kolaviron (an extract of Garcinia kola) in male and female rats.

There remains an insufficiency of data on the long-term toxicological profile of Garcinia kola Heckel and its extract, Kolaviron (KV), despite several studies on its pharmacological effects. This research was designed to investigate the long-term histopathological, hematological, biochemical, hormonal, reproductive, and oxidative effects of 90 days administration of KV to male and female rats, as well as additional 30 days reversibility study to assess the potential for reversal of induced effects. Fifty-six male and female Wistar rats divided into four groups were treated orally with distilled water/propylene glycol, 20 mg/kg KV, 100 mg/kg KV, and 500 mg/kg KV for 90 days. At the end of 90 days and 30 additional days of reversibility study, 5 ml blood was collected from animals for relevant analyses. Vital organs were harvested for histopathological assessments. In this study, KV did not elicit any adverse effect on histopathological presentations of vital organs which were generally non-abnormal. There was significant increase (p < 0.05) in LEU, MON, EOS%, BAS%, HCT (male animals) and LYM%, EOS%, BAS%, RBC, hemoglobin and MCH (female animals). There was significant diminution (p < 0.05) in cholesterol, triglycerides, LDL, and VLDL levels, with significant increase (p < 0.05) in HDL level in both male and female animals. KV elicited a non-significant increase in sperm count accompanied by a significant increase (p < 0.05) in levels of Follicle stimulating hormone (FSH) and testosterone in male rats. Furthermore, KV elicited significant (p < 0.001-0.05) elevation in the levels of GSH, SOD and CAT, and diminution in the level of MDA. The findings in this study suggest that long-term administration of KV is considerably safe with some variations in response between male and female animals. The possible sustenance of observed effects after cessation of KV administration, lipid lowering, erythropoiesis inducing, and immune system boosting activities of KV were confirmed in this study.

p-Nitrophenol contaminated soil remediation in a spray-type coaxial cylindrical dielectric barrier discharge plasma system.

In the present work, plasma remediation of p-nitrophenol (PNP) contaminated soil was performed in a novel spray-type coaxial cylindrical dielectric barrier discharge (DBD) system at ambient temperature. This system is capable of generating large-size nonthermal plasma (NTP) and improving the diffusion and transfer of chemical active species around the dispersed soil particles. Several key parameters including plasma treatment time, discharge voltage, soil granular size, the entry speed of soil, PNP initial concentration, gas variety, and gas flow rate were investigated in terms of PNP degradation and energy efficiencies. Under the optimized experimental conditions, 54.2% of PNP was degraded after only 50 s discharge treatment, indicating that the spray-type coaxial cylindrical DBD system can degrade organic pollutants in soil more quickly compared to other plasma systems due to its efficient transfer of reactive oxygen and nitrogen species (RONS) into the contaminated soil. The possible PNP degradation pathways were proposed based on intermediates identification results and the role of reactive species analysis. The toxicological assessment of the PNP decomposition products was conducted by quantitative structure-activity relationship (QASR) analysis. This work is expected to provide a potential plasma technology for rapid and efficient processing of industrial organic pollutants contamination soil.

Application of zebrafish in the study of the gut microbiome.

Zebrafish (Danio rerio) have attracted much attention over the past decade as a reliable model for gut microbiome research. Owing to their low cost, strong genetic and development coherence, efficient preparation of germ-free (GF) larvae, availability in high-throughput chemical screening, and fitness for intravital imaging in vivo, zebrafish have been extensively used to investigate microbiome-host interactions and evaluate the toxicity of environmental pollutants. In this review, the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm-blooded animal models are first summarized. Then, the roles of zebrafish gut microbiome on host development, metabolic pathways, gut-brain axis, and immune disorders and responses are addressed. Furthermore, their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed. We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification, resistance against bacterial infection, and disease prevention and cure. Overall, the zebrafish model promises a brighter future for gut microbiome research.

The Content and Toxicological Risk Assessment of Trace Elemental Impurities (Pb and Cr) in Snacks from Ogun State, Southwestern Nigeria.

The monitoring of food contamination by trace elemental impurities (TEIs) are major health challenges in developing countries. The present study evaluated the content and toxicological risk assessment of TEIs in commonly consumed snack/junk foods from Ogun State, Nigeria. TEIs (Pb and Cr) were determined in sixty snack food samples purchased from Ijebu Ode, Ogun State, southwestern Nigeria. The TEIs were analysed in quadruplicates using atomic absorption spectrometry with flame atomization. TEI data were subjected to simple descriptive and inferential statistics. The toxicological risk assessment of TEIs was evaluated for hazard quotient (HQ), hazard index (HI) and cancer risk (CR) using the United States Environmental Protection Agency-Integrated Risk Information System (USEPA-IRIS) model. Data showed the varying Pb levels of 8.22 ± 1.57 mg/kg in sausage to 12.25 ± 4.27 mg/kg in cocoyam chips higher than the permissible limit of the Codex Alimentarius of the Joint World Health Organization and Food and Agriculture Organization. The toxicological risk assessment revealed the HQs greater than 1.0 for Pb and Cr in most snack foods consumed by adults and children, indicating adverse health problems. The CRs of Pb (children) and Cr (adults and children) also breached the acceptable limit of 1.0 × 10-4, signifying possible lifetime development of cancer. It is therefore necessary to periodically monitor the TEIs in snacks to protect the public health.

Comparison of the Toxic Effects of Pristine and Photocatalytically Used TiO2 Nanoparticles in Mice.

TiO2 nanoparticles used in the photocatalytic degradation of pollutants in water treatment processes undergo physiochemical changes; therefore, their toxicological effects may be potentially different from those of the pristine nanoparticles. This study compared the toxic effects of exposure to pristine and photocatalytically used TiO2 nanoparticles in mice. To obtain used TiO2, the nanoparticles were used for photocatalytic degradation of a model pollutant under UV irradiation several times. Two groups of mice were exposed to pristine (PT group) and photocatalytically used TiO2 (UT group) at three different concentrations (5-20 mg/m3) using whole-body exposure chambers (2 h/day, 5 days/weeks, 4 weeks). Exposure to both pristine and used TiO2 increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphate (ALP), lactate dehydrogenase (LDH), C-reactive protein (CRP), and creatine kinase (CK-MB) significantly. Both exposed groups showed higher levels of WBC, lymphocytes, platelets, hematocrits, hemoglobin, and mean corpuscular volume (MCV) and lower levels of RBC and mean corpuscular hemoglobin concentration (MCHC) in a concentration-dependent manner. In all analyses, there were small non-significant differences between the PT and UT groups. More pathological changes were observed in the lung, kidney, and brain of the UT group, while the PT group showed more pathological effects in the liver and heart. The histological observations indicated that damage was mostly in the form of vascular endothelial injury. These two types of TiO2 may activate different pathways to promote adverse effects. Further studies are required to evaluate and distinguish the mechanisms through which pristine and used TiO2 induce toxicity.

Temporal-spatial survey of PAHs and PCBs in the Atlantic Iberian northwest coastline, and evaluation of their sources and risks for both humans and aquatic organisms.

Herein, sixteen priority sixteen priority polycyclic aromatic hydrocarbons (PAHs) and seven polychlorinated biphenyls (PCBs), considered seawater quality indicators, were quantified in four beaches of the Iberian (Portuguese) northwest coastline, including one ornithological reserve. These seashores are close to an important industrial region and a harbour. Water samples were extracted for PAHs and PCBs in their aqueous phase (DAP) and suspended particulate matter (SPM) and analysed by GC-MS/MS. Annual average concentrations reached ∼8 ng/L (DAP) and ∼100 ng/g dw (SPM) for PAHs and ∼3 ng/L (DAP) and ∼19 ng/g dw (SPM) for PCBs. PAHs and PCBs had fluctuations suggestive of seasonality. The possible origins of PAHs point to pyrogenic (forest fires) and petrogenic activities linked to maritime transports. The source(s) of PCBs appear to be related with leaks from waste sorting centres located in the vicinity of the sampling sites, together with the burning of contaminated materials. Toxic equivalents (TEQs) suggested a low carcinogenic potential for PAHs in seawater samples (∼0.3 ng/L and ∼4 ng/g dw, for DAP and SPM). Evaluation of risk coefficients for Σ16 PAHs revealed "Low-risk" of both matrices in all sampling areas. PCBs thyroid toxicity equivalents (TEQs-TH), suggested a low impact on biota (∼7.0E-05 ng/L and ∼5.2E-04 ng/g dw, for DAP and SPM). However, in vivo acute assays with Artemia salina exposed to environmental concentrations of PAHs, PCBs, and mixtures, confirmed the theoretical approach, showing that this coastline is not "Risk-free". This fact calls for further toxicological approaches to fully understand the risks posed by these compounds locally.

Material Risks of Homeopathic Medicinal Products: Regulatory Frameworks, Results of Preclinical Toxicology, and Clinical Meta-Analyses and Their Implications.

Homeopathy is widely used and broadly accepted by health care professionals and the general public but less in academic circles. To assess possible material health risks of homeopathic medicinal products, it is necessary to identify, select, and synthesize the findings of recent reviews of controlled homeopathic clinical trials. Matching these findings with experimental data from toxicological studies helps to clarify what is known and not known about the material risks of homeopathic medicines. Rules for toxicological risk assessment and management need to be applied independently of individual attitudes towards specific therapeutic options. European regulatory bodies have developed special protocols and decision trees to assure the safety of nonindividualized homeopathic remedies. This narrative review leads to suggestions that could ease and improve toxicological decision making. No homeopathy-specific type or pattern of side effects could be extracted from the meta-analysis data. No differences in the frequency of adverse reactions between homeopathic treatment and placebo treatment could be seen, no matter whether adverse events were reported in a quantitative or a qualitative manner. Some patterns of side effects show that adverse reactions do not necessarily correlate with treatment but with the condition of the patient. Overall, the controlled clinical data available for the material risk assessment of homeopathic remedies support the statement that, if a risk exists, it must be so small that it has not yet been established. To make our risk findings useful for personal decisions regarding homeopathy, we provide a thought experiment based on four different health situations and ask the question: is homeopathy as a monotherapy or as an add-on treatment an option or should it be rejected?

Cell Death Mediated by the Pyroptosis Pathway with the Aid of Nanotechnology: Prospects for Cancer Therapy.

Pyroptosis, a unique form of programmed cell death (PCD) that is characterized by DNA fragmentation, chromatin condensation, cellular swelling with big bubbles, and leakage of cell content, has been proven to have a close relationship with human diseases, such as inflammatory diseases and malignant tumors. Since a new gasdermin-D (GSDMD) protein was identified in 2015, various strategies have been developed to induce pyroptosis for cancer therapy, including ions, small-molecule drugs and nanomaterials. Although there are a number of reviews about the close relationship between the pyroptosis mechanism and the occurrence of various cancers, a summary covering recent progress in the field of nanomedicines in pyroptosis-based cancer therapy has not yet been presented. Therefore, it is urgent to fill this gap and light up future directions for the use of this powerful tool to combat cancer. In this Minireview, recent progress in cancer treatment based on pyroptosis induced by nanoparticles will be described in detail, the design highlights and the therapeutic advantages are emphasized, and future perspectives in this emerging area are proposed.

Acute, reproductive, and developmental toxicity of essential oils assessed with alternative in vitro and in vivo systems.

Essential oils (EOs) have attracted increased interest for different applications such as food preservatives, feed additives and ingredients in cosmetics. Due to their reported variable composition of components, they might be acutely toxic to humans and animals in small amounts. Despite the necessity, rigorous toxicity testing in terms of safety evaluation has not been reported so far, especially using alternatives to animal models. Here, we provide a strategy by use of alternative in vitro (cell cultures) and in vivo (Caenorhabditis elegans, hen's egg test) approaches for detailed investigation of the impact of commonly used rosemary, citrus and eucalyptus essential oil on acute, developmental and reproductive toxicity as well as on mucous membrane irritation. In general, all EOs under study exhibited a comparable impact on measured parameters, with a slightly increased toxic potential of rosemary oil. In vitro cell culture results indicated a concentration-dependent decrease of cell viability for all EOs, with mean IC50 values ranging from 0.08 to 0.17% [v/v]. Similar results were obtained for the C. elegans model when using a sensitized bus-5 mutant strain, with a mean LC50 value of 0.42% [v/v]. In wild-type nematodes, approximately tenfold higher LC50 values were detected. C. elegans development and reproduction was already significantly inhibited at concentrations of 0.5% (wild-type) and 0.1% (bus-5) [v/v] of EO, respectively. Gene expression analysis revealed a significant upregulation of xenobiotic and oxidative stress genes such as cyp-14a3, gst-4, gpx-6 and sod-3. Furthermore, all three EOs under study showed an increased short-time mucous membrane irritation potential, already at 0.5% [v/v] of EO. Finally, GC-MS analysis was performed to quantitate the relative concentration of the most prominent EO compounds. In conclusion, our results demonstrate that EOs can exhibit severe toxic properties, already at low concentrations. Therefore, a detailed toxicological assessment is highly recommended for each EO and single intended application.