Combined Toxicity Research Articles

Polystyrene microplastics exacerbated the toxicity of okadaic acid to the small intestine in mice

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 μg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1β and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.

Quantifying and normalizing the combined phytotoxicity of mixed-valence chromium in soil integrated by toxicity equivalence

When Cr(VI) and Cr(III) coexist, the reasonable assessment of the combined toxicity of chromium in soil and its ecological risk is still not well resolved. In the present study, exogenous mixed concentration combinations were set up to determine the interaction and combined toxicity of Cr(VI) and Cr(III), which were quantified as measured total and resin extractable forms for dose-response experiments with barley root elongation. The concept of toxicity equivalence "α" (the ratio of toxicity intensity coefficient between Cr(VI) and Cr(III), which can be expressed as the relative toxic strength of Cr(VI) to Cr(III)) was proposed for the toxicity assessment of mixed-valence chromium in soil. The results showed that the dose-response relationship was determined more precisely by the extended independent action model (e-IA) than traditional models (e.g., concentration addition model), and the mutual antagonism for resin extractable form (Resin-Cr) was stronger than the measured total form (T-Cr). The values of toxicity equivalence (α) between coexisting Cr(VI) and Cr(III) as Resin-Cr and T-Cr were 0.74 and 160, respectively, which indicated Resin-Cr(III) had relatively stronger toxicity than Resin-Cr(VI), while T-Cr(III) was much less than T-Cr(VI). The α values between Cr(VI) and Cr(III) decreased with their more active forms (decreased to about 0.5% of the original), even as total concentration and activity in solutions, making a dialectical view of the toxicity of both in different forms necessary. Finally, the log-logistic models were developed, enabling mixed-valence Cr toxicity to be assessed from a unilateral perspective using the Cr(III) equivalence concentration (Cr(III)-eq). This work provided innovative ideas for ecological threshold studies for mixed-valence metals in soils.

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20mg/kg of rabeprazole sodium only, and 800mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Macrophage polarization as a novel endpoint for assessing combined risk of phthalate esters

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

A platform technology for ultra-long acting intratumoral therapy

Intratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and “bathes” the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor. When MS ~ SN-38 was injected locally, tissues showed high levels of SN-38 with a long half-life of ~ 1 week. IT MS ~ SN-38 was ~ tenfold more efficacious as an anti-tumor agent than systemic SN-38. We also propose and provide an example that long-acting IT therapy might enable safe use of two drugs with overlapping toxicities. Here, long-acting IT MS ~ SN-38 is delivered with concurrent systemic PARP inhibitor. The tumor is exposed to both drugs whereas other tissues are exposed only to the systemic drug; synergistic anti-tumor activity supported the validity of this approach. We propose use of this approach to increase efficacy and reduce toxicities of combinations of immune checkpoint inhibitors such as αCTLA-4 and αPD-1.

Effect of Lead and Chromium on the Toxicity of Glyphosate Herbicides to African Catfish Clarias Gariepinus (Burchell 1822)

There is a growing increase in pollution of the aquatic ecosystems with a wide range of chemicals including herbicides and heavy metals input through anthropogenic activities, leading to disruption of ecological balance. This study used a static toxicity bioassay to examine the interaction between heavy metals (Pb and Cr) and organophosphorus herbicides (analytical grade glyphosate, commercially formulated - Roundup and Forceup) on African catfish (Clarias gariepinus BURCHELL 1822). Lethal concentrations (LC50) for roundup (RU), forceup (FU), analytical grade glyphosate (AGG), chromium (Cr), and lead (Pb) were 17.23 mg/l, 4877 mg/l, 131.12 mg/l, 21.16 mg/l, and 74.82 mg/l respectively. In addition, fish exposed to varying concentration of chromium (5.0 mg/l and 7.5 mg/l) and lead (20 mg/l and 25 mg/l) with glyphosate (RU: 10 mg/l; FU: 4300 mg/l; and AGG: 100 mg/l) for 96 hours were examined for biochemical parameters. Blood plasma examined for liver and kidney profile indices showed that kidney functions’ parameters (protein, albumin, AST-aspartate aminotransferase, ALT-alanine aminotransferase and Bilirubin) and liver functions parameters (urea and creatinine) increased significantly (p&lt;0.05) when glyphosates combined with lead and chromium treated groups compared with the control group. This study therefore, showed that low concentrations of combined toxicants of glyphosates and heavy metals (Cr and Pb) will synergistically induce deleterious effects on the liver and kidney of Clarias gariepinus.

Polystyrene microplastics enhanced the toxicity of cadmium to rice seedlings: Evidence from rice growth, physiology, and element metabolism

Microplastics (MPs) and cadmium (Cd) are toxic to rice; however, the effects and mechanisms of their combined exposure are unclear. The combined exposure effects of polystyrene microplastics (PS-MPs) with different particle sizes (1–10 μm, 50–150 μm) and concentrations (50, 500 mg·L−1) and Cd on rice were explored. PS-MPs combined with Cd amplifies the inhibition of each individual exposure on the height and biomass of rice seedlings, and they showed antagonistic effects. PS-MPs reduced the content of chlorophyll and increased the content of carotenoid rice seedlings significantly. High concentrations of PS-MPs enhanced the inhibition of Cd on chlorophyll content. Cd, PS-MPs single and combined exposures significantly altered the antioxidant enzyme (POD, CAT, SOD) activities in rice seedlings. Under PS-MPs exposure, overall, the MDA content in shoots and roots exhibited opposite trends, with a decrease in the former and an increase in the latter. In comparison with Cd treatment, the combined exposures' shoot and root MDA content was reduced. Cd and PS-MPs showed “low concentration antagonism, high concentration synergism” on the composite physiological indexes of rice seedlings. PS-MPs significantly increased the Cd accumulation in shoots. PS-MPs promoted the root absorption of Cd at 50 mg·L−1 while inhibited at 500 mg·L−1. Cd and PS-MPs treatments interfered with the balance of microelements (Mn, Zn, Fe, Cu, B, Mo) and macroelements (S, P, K, Mg, Ca) in rice seedlings; Mn was significantly inhibited. PS-MPs can enhance of Cd's toxicity to rice seedlings. The combined toxic effects of the two contaminants appear to be antagonistic or synergistic, relying on the particle size and concentration of the PS-MPs. Our findings offer information to help people understanding the combined toxicity of Cd and MPs on crops.

Insights into the synergistic toxicity mechanisms caused by nano- and microplastics with triclosan using a dose-dependent functional genomics approach in Saccharomyces cerevisiae

The emergence of polystyrene (PS) nano- and microplastics (NMPs) and triclosan (TCS) as environmental contaminants has raised concerns about their combined toxicities to organisms, but the complex toxicity arising from their interactions and the underlying molecular mechanisms remain obscure to us. In this study, we comprehensively detected the combined toxicity of PS-NMPs and TCS via the dose-dependent yeast functional genomics profiling. Firstly, our findings demonstrated that the combined exposure to PS-NMPs and TCS elicited a synergistic toxic effect in which the toxicity depended on the size of the PS-NMPs. Secondly, we found that TCS exposure, either alone or in combination with PS-NMPs, influenced lipid biosynthetic processes and ATP export pathways, while the unique responsive genes triggered by combined exposure to TCS and PS-NMPs are significantly enriched in mitochondrial translation, ribosomal small subunit assembly, and tRNA wobble uridine modification. Thirdly, our results demonstrated that point of departure (POD) at the pathway level was positively correlated with IC50, and POD was a more sensitive predictor of toxicity than the apical toxicity endpoints. More importantly, our findings suggested that the combined exposure of PS-NMPs in a size-dependent manner not only alleviated the harmful effects of TCS on glycerophospholipid metabolism, but also exacerbated its negative impact on oxidative phosphorylation. Collectively, our study not only provides new insights into the intricate molecular mechanisms that control the combined toxicity of PS-NMPs and TCS, but also confirms the effectiveness of the dose-dependent functional genomics approach in elucidating the molecular mechanisms of the combined toxicity of pollutants.

Environmentally relevant concentrations of nickel and imidacloprid induce reproductive toxicity in earthworm (Eisenia fetida fetida)

The current research investigates individual and combined toxicity effects of nickel (Ni) and imidacloprid (IMI) on earthworm species Eisenia fetida fetida. Employing standardized toxicity parameters, we assessed the impact of environmentally relevant concentrations (ERC) of Ni, IMI, and their mixtures on key biomarkers and reproductive fitness of earthworms. Our findings reveal concentration-dependent responses with discernible adverse effects on physiological parameters. The ERC obtained for Ni was 0.095 ppm, and for imidacloprid was 0.01 ppm. Two concentrations (ERC and 1/5th) of both toxicants (individually and in combinations) were further given for 14 days, and parameters like avoidance behaviour, antioxidants, histology, and metabolomic profile were observed. The behaviour of earthworms was noted, where at 24–48 h, it was found to be in control soil, while later, at 72–96 h, they migrated to toxicants-treated soil. Levels of antioxidants (superoxide dismutase, catalase, reduced glutathione, ascorbic acid), lipid peroxidation, and lactate dehydrogenase were elevated in the testis, spermatheca, ovary, and prostate gland in a high concentration of Ni + IMI. Histological studies showed more vacuolization and disruption of epithelium that was increased in the prostate gland of the Ni + IMI high group, decreased number of spermatids, and damaged cell architecture was noted in testis and spermatheca of the Ni + IMI high group. The highest number of metabolites was found in Ni exposed group (181), followed by IMI (131) and Control (125). Thus, this study sheds light on the ecotoxicological effects of combinational exposure of these contaminants on an essential soil-dwelling organism, where IMI was more toxic than Ni, and both toxicants decreased earthworm reproductive fecundity.

Evaluation of the combined toxicity of heavy metals and chlorpyrifos: A comparison of electrochemical and MTT methods

AbstractIn the human living environment, heavy metals and chlorpyrifos can have harmful consequences due to their complex combination. In this study, binary, ternary, and quaternary combinations of three heavy metals and chlorpyrifos in different concentrations were evaluated for their combined toxic effects using an electrochemical method, and the MTT method was used to contrast the outcomes. The combined toxic effectiveness assessed by the electrochemical CI method revealed that, except for the binary combination of cadmium chloride and chlorpyrifos, which exhibited an antagonistic effect when mixed at an equal molar ratio, lead nitrate and chlorpyrifos showed an additive effect when combined, the quaternary combination exhibited a complex transition from synergistic to additive to antagonistic effects, the other mixtures showed consistent synergistic effects. When the ratio of heavy metals in the mixture was reduced, all of them displayed synergistic effects, except for the binary mixture of cadmium chloride and chlorpyrifos, which consistently maintained an antagonistic effect, and the ternary mixture of cadmium chloride, lead nitrate, and chlorpyrifos displayed additive effects. The complex toxicity mechanisms of the mixtures do not impact the response of cellular electrochemical signals coming from the intracellular purine bases on cytotoxicity. The electrochemical approach successfully captured the various combined toxic effects of the mixture, and the outcomes were consistent with the MTT method. This method is expected to emerge as a novel approach for detecting combined toxicity.

Insights into the combined toxicity and mechanisms of BDE-47 and PFOA in marine blue mussel: An integrated study at the physiochemical and molecular levels

The coexistence of multiple emerging contaminants imposes a substantial burden on the ecophysiological functions in organisms. The combined toxicity and underlying mechanism requires in-depth understanding. Here, marine blue mussel (Mytilus galloprovincialis L.) was selected and exposed to 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and perfluorooctanoic acid (PFOA) individually and in combination at environmental related concentrations to elucidate differences in stress responses and potential toxicological mechanisms. Characterization and comparison of accumulation, biomarkers, histopathology, transcriptomics and metabolomics were performed. Co-exposure resulted in differential accumulation patterns, exacerbated histopathological alterations, and different responses in oxidative stress and biomarkers for xenobiotic transportation. Moreover, the identified differentially expressed genes (DEGs) and differential metabolites (DEMs) in mussels were found to be annotated to different metabolic pathways. Correlation analyses further indicated that DEGs and DEMs were significantly correlated with the above biomarkers. BDE-47 and PFOA altered the genes and metabolites related to amino acid metabolism, energy and purine metabolism, ABC transporters, and glutathione metabolism to varying degrees, subsequently inducing accumulation differences and combined toxicity. Furthermore, the present work highlighted the pivotal role of Nrf2-keap1 detoxification pathway in the acclimation of M. galloprovincialis to reactive oxygen species (ROS) stress induced by BDE-47 and PFOA. This study enabled more comprehensive understanding of combined toxic mechanism of multi emerging contaminants pollution.

Effects of combined exposure to two bisphenol plasticizers (BPA and BPB) on Xenopus laevis development

Due to its endocrine disruptive activity, the plastic additive Bisphenol A (BPA) is classified as substance of very high concern (EU ECHA 2017). A correlation between environmental exposure to BPA and congenital defects has been described in humans and in experimental species including the amphibian Xenopus laevis, where severe branchial defects were associated to lethality. The exposure of X. laevis embryos to the BPA analogue bisphenol B (BPB) was recently linked to similar teratogenic effects, with BPB having relative potency about 3 times higher than BPA. The combined BPA-BPB exposure is realistic as both BPA and BPB are detected in human samples and environment. Limited experimental data are available on the combined developmental toxicity of BPA and BPB. The aim of the present work is to evaluate the effects of BPA and BPB mixture in the X. laevis development model, using R-FETAX procedure. The exposure was limited to the first day of development (corresponding to the phylotypic developmental period, common to all vertebrates). Samples were monitored for lethal effects during the full six-day test period and the external morphology was evaluated at the end of the test. Mixture effects were described by modelling, using the PROAST software package. Overall data modelling showed that dose-addiction could not be rejected, suggesting a health concern for co-exposure.

Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10–250 ng L−1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L−1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L−1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

Combined toxicity of polyvinyl chloride microplastics and copper to marine jacopever (Sebastes schlegelii)

Marine organisms commonly encounter co-stress resulting from the coexistence of microplastics (MPs) and heavy metals pollution in marine environments. Nevertheless, the combined effects and toxicity mechanisms of MPs and heavy metals on marine organisms remain unclear. This study integrated growth, physiological, morphological, and biochemical markers to assess the individual and combined toxicity of polyvinyl chloride MPs (PVC MPs, 1 × 104 particles/L) and copper (Cu, 200 μg/L) on marine jacopever (Sebastes schlegelii). The results revealed that co-exposure to MPs and Cu had a more detrimental impact on jacopever compared to the single-exposure groups, as evidenced by the enhanced growth inhibition, respiratory stress, and hepatotoxicity. This phenomenon may be attributed to PVC MPs accelerating the accumulation of Cu in jacopever liver. Therefore, peroxidation damage occurred in the co-exposed liver and may result in liver dysfunction. These findings contribute valuable insights into the risks associated with the coexistence of MPs and heavy metal pollution in marine ecosystems.

Potential mechanisms of aortic medial degeneration promoted by co-exposure to microplastics and lead

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.

Comparison of the toxic effects of polystyrene and sulfonated polystyrene on wheat under cadmium stress

With advances in plastic resource utilization technologies, polystyrene (PS) and sulfonated polystyrene (SPS) microplastics continue to be produced and retained in environmental media, potentially posing greater environmental risks. These plastics, due to their different physicochemical properties, may have different environmental impacts when compounded with other pollutants. The objective of this study was to investigate the combined toxic effects of PS and SPS on wheat using cadmium (Cd) as a background contaminant. The results demonstrated that Cd significantly impeded the normal growth of wheat by disrupting root development. Both PS and SPS exhibited hormesis at low concentrations and promoted wheat growth. Under combined toxicity, PS reduced oxidative stress and promoted the uptake of essential metal elements in wheat. Additionally, KEGG pathway analysis revealed that PS facilitated the repair of Cd-induced blockage of the TCA cycle and glutathione metabolism. However, high concentrations of SPS in combined toxicity not only enhanced oxidative stress and interfered with the uptake of essential metal elements, but also exacerbated the blocked TCA cycle and interfered with pyrimidine metabolism. These differences are related to the different stability (Zeta potential, Hydrodynamic particle size) of the two microplastics in the aquatic environment and their ability to carry heavy metal ions, especially Cd. The results of this study provide important insights into understanding the effects of microplastics on crops in the context of Cd contamination and their environmental and food safety implications.

Involvement of propranolol in suicides: cross-sectional study using coroner-reported data.

Propranolol is a beta-blocker medication indicated mostly for heart rhythm conditions and for physical symptoms of anxiety. Prescriptions for propranolol in the UK have increased since 2008. Recently, there have been concerns about the involvement of propranolol in intentional poisonings, but such deaths are not routinely reported. Therefore, use of coroner-reported and toxicology data enables unique investigation into the scale of involvement of propranolol in suicide. To describe the extent to which propranolol is involved in suicides, including patterns over time and characteristics of people whose suicide involved propranolol compared with other suicides. Data were derived from the National Programme on Substance Use Mortality (NPSUM). All suicides and deaths of undetermined intent between 2010 and 2021 in England, Wales and Northern Ireland were extracted, and a subset was identified where propranolol was involved in death. There were 4473 suicides of which 297 (6.6%) involved propranolol, with the proportion involving propranolol nearly quadrupling during the study period (3.4% v. 12.3%). Compared with all other suicides, a greater proportion of propranolol suicides were in women (56.6% v. 37.1%) and in people with diagnoses of depression (39.1% v. 27.1%) and anxiety (22.2% v. 8.6%). When suicide involved propranolol, an antidepressant was detected at post-mortem in 81.8% of deaths, most commonly a selective serotonin reuptake inhibitor (SSRIs) (51.5%), and most often citalopram (24.6%). A small number, but increasing proportion, of suicides reported to the NPSUM involve propranolol. Vigilance to the combined toxicity profile of medicines used alongside propranolol may be pertinent.

Insight into the mechanisms of combined toxicity of cadmium and flotation agents in luminescent bacteria: Role of micro/nano particles

Currently, risk assessment and pollution management in mines primarily focus on toxic metals, with the flotation agents being overlooked. However, the combined effects of metals and flotation agents in mines remain largely unknown. Therefore, this study aimed to evaluate the combined effects of Cd and two organic flotation agents (ethyl xanthate (EX) and diethyldithiocarbamate (DDTC)), and the associated mechanisms. The results showed that Cd + EX and Cd + DDTC exhibited synergistic toxicity. The EC50 values for luminescent bacteria were 1.6 mg/L and 1.0 mg/L at toxicity unit ratios of 0.3 and 1, respectively. The synergistic effects were closely related with the formation of Cd(EX)2 and Cd(DDTC)2 micro/nano particles, with nano-particles exhibiting higher toxicity. We observed severe cell membrane damage and cell shrinkage of the luminescent bacteria, which were probably caused by secondary harm to cells through the released CS2 during their decomposition inside cells. In addition, these particles induced toxicity by altering cellular levels of biochemical markers and the transcriptional levels of transport proteins and lipoproteins, leading to cell membrane impairment and DNA damage. This study has demonstrated that particulates formed by Cd and flotation agents contribute to the majority of the toxicity of the binary mixture. This study helps to better understand the complex ecological risk of inorganic metals and organic flotation agents in realistic mining environments.

Increasing Risks to the Health of the Invertebrates-Balancing between Harm and Benefit.

The article discusses the issue of extensive use of detergents and sanitizers in the time of new challenges associated with the COVID-19 (SARS-CoV-2) pandemic. These agents could pose threats to the existence of free-living invertebrates as essential components of the ecosystem. The biological effects of the mentioned classes of substances, their metabolites, and combined effects in the mixture have not been studied enough. The main challenges in trying to balance the threats and benefits of using such substances are the lack of knowledge of the biological effects of these products, the gaps in testing invertebrates' responses, and changes in environment-related regulations to minimize risks to animals and humans. Numerous studies in this field still leave research gaps, particularly concerning the combined toxicity of well-known and widely used disinfectants, surfactants, and heavy metals, posing potential future challenges. Additionally, the review identified the need for additional testing of invertebrates for their sensitivity to disinfectants and surfactants of different compositions, including improved (non-invasive) methods, studies for early life stages, and comparative studies of species resilience.

Triclosan-loaded aged microplastics exacerbate oxidative stress and neurotoxicity in Xenopus tropicalis tadpoles via increased bioaccumulation

Microplastics and chlorine-containing triclosan (TCS) are widespread in aquatic environments and may pose health risks to organisms. However, studies on the combined toxicity of aged microplastics and TCS are limited. To investigate the toxic effects and potential mechanisms associated with co-exposure to TCS adsorbed on aged polyethylene microplastics (aPE-MPs) at environmentally relevant concentrations, a 7-day chronic exposure experiment was conducted using Xenopus tropicalis tadpoles. The results showed that the overall particle size of aPE-MPs decreased after 30 days of UV aging, whereas the increase in specific surface area improved the adsorption capacity of aPE-MPs for TCS, resulting in the bioaccumulation of TCS under dual-exposure conditions in the order of aPE-TCS > PE-TCS > TCS. Co-exposure to aPE-MPs and TCS exacerbated oxidative stress and neurotoxicity to a greater extent than a single exposure. Significant upregulation of pro-symptomatic factors (IL-β and IL-6) and antioxidant enzyme activities (SOD and CAT) indicated that the aPE-TCS combination caused more severe oxidative stress and inflammation. Molecular docking revealed the molecular mechanism of the direct interaction between TCS and SOD, CAT, and AChE proteins, which explains why aPE-MPs promote the bioaccumulation of TCS, causing increased toxicity upon combined exposure. These results emphasize the need to be aware of the combined toxicity caused by the increased ability of aged microplastics to carry contaminants.