Toxicological Interactions Research Articles

Toxic effects of microplastic (polyethylene) exposure: Bioaccumulation, hematological parameters and antioxidant responses in crucian carp, Carassius carassius

The purpose of this study was to evaluate the toxic effects of polyethylene microplastics (PE-MPs) by measuring the bioaccumulation, hematological parameters, and antioxidant responses in crucian carp (Carassius Carassius) exposed to waterborne 22–71 μm PE-MPs. C. carassius (mean weight, 24.0 ± 2.1 g; mean length, 13.1 ± 1.2 cm) were exposed to PE-MPs at concentration of 0, 4, 8, 16, 32, and 64 mg/L for 2 weeks. The accumulation of PE-MPs in each tissue of C. carassius was significantly increased in proportion to the PE-MPs concentration; the highest accumulation was observed in the intestine, followed by the gills and liver. Hematological parameters, plasma components and antioxidants responses were significantly affected by PE-MPs in a concentration-dependent manner. Exposure to ≥32 mg/L PE-MPs induced a significant decrease in red blood cells (RBCs), hemoglobin (Hb) content, and hematocrit values. However, exposure to ≥32 mg/L PE-MPs induced oxidative stress in the liver, gill, and intestine of C. carassius, thereby resulting in a significant increase in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) and a decrease in glutathione (GSH) levels. The effects of interaction between the PE-MPs and exposure periods showed no significant changes in bioaccumulation, hematological parameters, plasma components and antioxidant responses. These finding indicate that the exposure to ≥32 mg/L PE-MPs could cause a significant accumulation in specific tissues of C. carassius, resulting in changes in hematological parameters, plasma components, and antioxidant responses. However, the interaction between PE-MPs and exposure periods had no significant effects, thereby suggesting the lack of toxicological interactions between PE-MPs and exposure periods in C. carassius.

Toxicological interactions between Spinosad and Essential Oils in the Mediterranean Fruit Fly, Ceratitis capitata

Toxicological interactions between Spinosad and Essential Oils in the Mediterranean Fruit Fly, Ceratitis capitata

Leaching of herbicides mixtures from pre-exposed agricultural plastics severely impact microalgae

Farmlands represent a source of aged plastics and pesticides to the surrounding environments. It has been shown that chemicals can be sorbed and desorbed from plastics, but the interaction between plastic and mixtures of pesticides and their effects on freshwater biota has not been assessed yet. The aim of the work was to assess the potential role of agricultural plastics as vectors for a mixture of two herbicides and the impact of the herbicide mixture lixiviated from them towards the freshwater microalga Chlamydomonas reinhardtii. Pristine and aged polyethylene plastics collected from agricultural areas were exposed to the herbicides, bifenox, oxyfluorfen and their mixtures. The microalgae were exposed for 72 h to the leachates desorbed from plastics and the effect was quantified in terms of total chlorophyll content and several physiological parameters assessed by flow cytometry. Our results showed that changes in physicochemical properties (hydroxyl and carbonyl index, hydrophobicity, texture) in aged plastics increased their capacity to retain and to desorb the herbicides. Microalgae exposed to leachates containing bifenox, oxyfluorfen, or their mixture showed reactive oxygen species overproduction, lipid peroxidation, membrane potential hyperpolarization, intracellular pH acidification, and a loss of metabolic activity. The toxicological interactions of the leachate mixture were assessed using the Combination Index (CI)-isobologram method showing antagonism at low effect levels turning to synergism when the effect increased. In this work, we proved the hypothesis that ageing increases the capacity of agricultural plastics to behave as vector for toxic chemicals to the biota.

Eugenol and menthol synergize the toxicity of permethrin in the blood-sucking bug, Triatoma infestans

The blood-sucking bug, Triatoma infestans, is one of the main vectors of Chagas disease in America. It is usually controlled with pyrethroids, but the emergence of resistance to these insecticides creates the need to look for alternative products. Eugenol, menthol and menthyl acetate are botanical monoterpenes, which produce lethal and sublethal effects on insects. The purpose of this work was to determine what type of toxicological interactions occur when binary mixtures, formed by the pyrethroid permethrin and sublehtal doses of eugenol, menthol or menthyl acetate, are applied to T. infestans. First instar nymphs were exposed to filter papers impregnated with the insecticides. The number of knocked down insects was registered at different times and Knock Down Time 50% (KT50) values were calculated. The following KT50 values with their corresponding 95% Confidence Intervals were obtained: permethrin, 47.29 (39.92 - 56.32) min; permethrin + eugenol, 34.08 (29.60 - 39.01) min; permethrin + menthol, 27.54 (23.28 - 32.55) min; permethrin + menthyl acetate, 43.62 (39.99 - 47.59) min. Eugenol and menthol increased the speed of action of permethrin (synergism), but menthyl acetate had no effect on it (additivity). These results provide the basis to further explore interactions between conventional insecticides and plant monoterpenes as potential tools for controlling T. infestans.

Combined effects of fluoroquinolone antibiotics and organophosphate flame retardants on Microcystis aeruginosa.

As freshwater harmful algal blooms continue to rise in frequency and severity, increasing focus is made on the effects of mixed pollutants and the dominant cyanobacterial species Microcystis aeruginosa (M. aeruginosa). However, few studies have investigated whether M. aeruginosa has a synergistic relationship with two common pollutants, namely, organophosphate flame retardants (OPFRs) and fluoroquinolone antibiotics (FQs). In this paper, three FQs and three OPFRs commonly detected in freshwaters were selected to construct a ternary mixture of FQs, a ternary mixture of OPFRs, and a six-component mixture of OPFRs and FQs. The effects of single substance and mixture on the growth of M. aeruginosa were determined at 24, 48, 72, and 96h, and the toxicities of the mixture were evaluated by concentration addition model and independent action model. The results showed that the mixture of FQs and the mixture of OPFRs do not show toxicological interaction. However, partial mixtures of OPFRs and FQs showed antagonism or synergism at different concentrations and times. This indicated that combined toxicities of OPFRs and FQs on M. aeruginosa were mixture ratio dependent, concentration dependent and time dependent. This study improves our understanding of the role of OPFRs and FQs in cyanobacterial outbreaks of Microcystis.

OOCDB: A Comprehensive, Systematic, and Real-time Organs-on-a-chip Database

Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro. Organs-on-a-chip technology, as opposed to traditional two-dimensional cell culture and animal models, can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs. Despite the fact that many organs-on-a-chip-related data have been published, none of the current databases have all of the following functions: searching, downloading, as well as analyzing data and results from the literature on organs-on-a-chip. Therefore, we created an organs-on-a-chip database (OOCDB) as a platform to integrate information about organs-on-a-chip from various sources, including literature, patents, raw data from microarray and transcriptome sequencing, several open-access datasets of organs-on-a-chip and organoids, and data generated in our laboratory. OOCDB contains dozens of sub-databases and analysis tools, and each sub-database contains various data associated with organs-on-a-chip, with the goal of providing researchers with a comprehensive, systematic, and convenient search engine. Furthermore, it offers a variety of other functions, such as mathematical modeling, three-dimensional modeling, and citation mapping, to meet the needs of researchers and promote the development of organs-on-a-chip. The OOCDB is available at http://www.organchip.cn.

Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2-New Data for a Possible Role in the Long COVID Pattern.

It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson's disease (PD) or Alzheimer's Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.

Metabolomic analysis of combined exposure to microplastics and methylmercury in the brackish water flea Diaphanosoma celebensis.

Owing to their widespread distribution and high bioaccumulation, microplastics (MPs) and mercury (Hg) are considered major threats to the ocean. MP interacts with Hg because of its high adsorption properties. However, their toxicological interactions with marine organisms, especially combined effects at the molecular level, are poorly understood. This study investigated the single and combined effects of MP and Hg on the metabolic profile of the brackish water flea Diaphanosoma celebensis. A total of 238 metabolites were significantly affected by MP, Hg, or MP + Hg. Metabolite perturbation patterns showed that toxicity of Hg and MP + Hg was similar and that of MP was not significant. Among the 223 metabolites affected by Hg, profiles of 32 unannotated metabolites were significantly different from those of MP + Hg, and combined effects of MP + Hg decreased the effect of Hg on 25 of these metabolites. Only 11 annotated metabolites were significantly affected by Hg or MP + Hg and were related to carbohydrate, lipid, vitamin, and ecdysteroid metabolism. Ten metabolites were decreased by Hg and MP + Hg and were not significantly different between the exposure groups. Enrichment analysis showed that galactose, starch, and sucrose metabolism were the most affected pathways. These findings suggest that MP has negligible toxic effect, and Hg can induce energy depletion, membrane damage, and disruption of growth, development, and reproduction. Although the impact of MP was negligible, the combined effects of MP + Hg could be metabolite specific. This study provides better understanding of the combined effects of MP and Hg on marine organisms.

Evaluation of joint toxicity of BTEX mixtures using sulfur-oxidizing bacteria

Benzene (B), toluene (T), ethylbenzene (E), and xylenes (X) are petrochemicals vital in various industrial and commercial processing but identified as priority pollutants due to their high toxicity. The objective of this study was to investigate the toxicological nature of BTEX mixtures under controlled laboratory aquatic conditions using sulfur-oxidizing bacteria (SOB). Results from individual BTEX tests demonstrated that the order of toxicity among BTEX was X ≥ E > T > B. Comparisons of dose-effect curves for BTEX suggest that the biochemical mode of action of B in SOB was different from those of T, E, and X. Toxicological interactions of BTEX in mixtures were studied using concentration addition (CA), independent action (IA), and combination index (CI)-isobologram models. The CI model approximated the actual toxicity of BTEX mixtures better than the CA and IA models. In most cases, BTEX induced synergistic interactions in mixtures. However, in some B-containing mixtures, antagonism was observed at low effective levels. The effective level (fa)-CI plots and polygonograms illustrate that synergistic interactions of BTEX became stronger with an increase in effective levels. In addition, ternary and quaternary mixtures were found to provoke stronger synergism than binary mixtures. The present study suggests that the CI-isobologram model is a suitable means to evaluate diverse toxicological interactions of contaminants in mixtures.

The single and combined effects of mercury and polystyrene plastic beads on antioxidant-related systems in the brackish water flea: toxicological interaction depending on mercury species and plastic bead size

Plastics are considered as a major threat to marine environments owing their high usage, persistence, and negative effects on aquatic organisms. Although they often exist as mixtures in combination with other pollutants (e.g., mercury (Hg)) in aquatic ecosystems, the combined effects of plastics and ambient pollutants remain unclear. Therefore, in the present study, we investigated the toxicological interactions between Hg and plastics using two Hg species (HgCl2 and MeHgCl) and different-sized polystyrene (PS) beads (diameter: 0.05, 0.5, and 6-μm) in the brackish water flea Diaphanosoma celebensis. The single and combined effects of Hg and PS beads on mortality were investigated, and changes in the antioxidant system and lipid peroxidation were further analyzed. After 48-h exposure to single Hg, HgCl2 induced a higher mortality rate than MeHgCl. The combined exposure test showed that 0.05-μm PS beads can enhance the toxicity of both the Hg species. The expression of GST-mu, glutathione S-transferease (GST) activity and malondialdehyde (MDA) content increased significantly after exposure to Hg alone (HgCl2 or MeHgCl) exposure. Combined exposure with PS beads modulated the effects of Hg on the antioxidant system depending on bead size and the Hg species. In particular, the 0.05-μm beads significantly increased the expression level of GST-mu, GST activity and MDA content, regardless of Hg species. These findings suggest that toxicological interactions between Hg and PS beads depend on the type of Hg species and the size of PS beads; nano-sized 0.05-μm PS beads can induce synergistic toxicity with Hg.

Mycotoxin contamination in feeds and feed materials in China in year 2020.

A survey of mycotoxin contamination in feed commodities in China was performed and the regional differences of mycotoxin contamination in new season corn was assessed during January 2020–November 2020 in this research. 1,610 samples were analyzed for the major mycotoxins, namely aflatoxins, zearalenone (ZEN), trichothecenes type B, fumonisins (FUM), fusariotoxin T-2 (T-2) and ochratoxin A (OTA) using methods of liquid chromatography—tandem mass spectrometry and enzyme linked immunosorbent assay. Generally, aflatoxins occurred in 16% of all samples, and ZEN, trichothecenes type B and FUM were more prevalent with positive rates of 47, 72, and 63%, respectively. T2 and OTA were rarely detected. In new season corn, samples were also seriously contaminated with ZEN, trichothecenes type B, and FUM at positive rates of 47, 76, and 79%, respectively, and their averages of positives were 112, 735, and 3,811 μg/kg, respectively. The patterns of mycotoxin occurrence showed distinct regional trends in new season corn samples. Samples from Shandong province were highly contaminated with FUM, while special attention should be paid to aflatoxins in Anhui and Jiangsu provinces of East China. The contents of trichothecenes type B and ZEN from northern to southern provinces showed downward trends. In new season corm, co-occurrence of mycotoxins was widespread, and combinations of ZEN, trichothecenes type B, and FUM were frequently observed in this study. Trichothecenes type B and ZEN concentrations showed a positive correlation coefficient of 0.294, suggesting that toxicological interactions of these toxins deserve attention.

SAHmap: Synergistic-antagonistic heatmap to evaluate the combined synergistic effect of mixtures of three pesticides on multiple endpoints of Caenorhabditis elegans

The environmental pollution caused by toxic chemicals such as pesticides has become a global problem. The mixture of dichlorvos (DIC), dimethoate (DIM), aldicarb (ALD) poses potential risks to the environment and human health. To fully explore the interaction of complex mixtures on Caenorhabditis elegans behavioral toxicity endpoint. This study created a synergistic-antagonistic heatmap (SAHmap) based on the combination index to systematically describe the toxicological interaction prospect of the mixture system. It was shown that the three pesticides and their binary as well as ternary mixture rays have significant concentration-response relationship on three behavioral endpoints of nematodes, From the perspective of synergistic-antagonistic heatmaps, all the mixture rays in the DIC-DIM mixture system showed strong synergism on the three behavioral and lethal endpoints. In the ternary mixture system, the five mixture rays showed different interaction between the behavioral endpoint and the lethal endpoint, and showed slight synergism to two behavioral endpoints as a whole. The emergence of synergism should arouse our attention to these hazardous chemicals. In addition, the use of SAHmap and the significant linear correlation among three behavioral endpoints further improved the efficiency of the study on the behavioral toxicity of pesticide mixtures to Caenorhabditis elegans.

Acute and chronic ecotoxicological effects of pharmaceuticals and their mixtures in Daphnia similis

Pharmaceuticals have increasingly received attention from the scientific community due to their growing intake, improved detection and potential ecological risks. Several pharmaceuticals, including antidepressants, anti-inflammatory and antidiabetic compounds and antibiotics, have been described as contaminants in different water matrices. In this context, the aim of the present study was to assess the acute and chronic effects of four classes of pharmaceuticals (acetylsalicylic acid, fluoxetine, metformin and ciprofloxacin) individually and in binary and quartenary mixture. Furthermore, the toxicity of binary mixtures containing the antidepressant fluoxetine was also evaluated. The results of the single acute and chronic toxicity assays indicate lower acetylsalicylic acid and higher fluoxetine toxicity towards Daphnia similis. Regarding the evaluated mixture toxicity, the nature of potential toxicological interactions was predicted by applying mathematical concentration addition and independent action models. The findings revealed both antagonistic and synergistic features, depending on the applied amounts and doses. Finally, the chronic assays performed with the quaternary mixture indicated the presence of a hormetic effect at low concentrations. In sum, the present study demonstrated that the effects of individual pharmaceuticals can underestimate the risk level of these contaminants in the environment.

P463 Toxicological evaluation of Aureobasidum pullulans var. pullulans induced mycotoxicosis in amurine model

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesThe genus Aureobasidium includes 14 species, amongst which Aureobasidium pullulans is the most well-known species. Aureobasidium pullulans, includes two well-documented varieties found in indoor environments and associated with health issues: A. pullulans var. pullulans and A. pullulans var. melanogenum. Aureobasidium pullulans is a mold belonging to the family Dothioraceae. It colonizes nails, hair, and skin in humans. Deleterious immune reactions may occur in humans, like hypersensitivity pneumonitis and allergies. Respiratory allergies may result due to high levels of Aureobasidium in the air. The metabolites of the mold, like mycotoxin, are known to cause toxic-irritant effects. In view of this, the present work evaluates the effects of the toxic secondary metabolites of A. pullulans var. pullulans (CBS 577.93) in a murine model.In order to maximize the toxicological potential of A. pullulans pullulans (CBS 577.93) for the production of mycotoxins, an understanding of its mode of action in an animal model is necessary. In the present study, we report the mycotoxicological activity of A. pullulans pullulans (CBS 577.93) in experimental mice.Material and MethodsMycotoxins isolated from A. pullulans pullulans (CBS 577.93) were used for the experimental induction of mycotoxicosis in Swiss mice (C3HHC strain). The mycotoxin was administered intraperitoneally (IP) and intranasally (IN). To assess the toxic effects of the A. pullulans mycotoxins, eight organs, namely liver, lungs, kidney, spleen, stomach, heart, brain, and testis, were taken into consideration. The hematological, histopathological, and biochemical aspects of A. pullulans-induced mycotoxicosis were investigated.ResultsBehavioral observations—A significant decrease in the consumption of feed in both IN and IP groups was noted. The weights of the mice increased in both the IP and IN groups.Anatomical observations—Gross lesions on the liver and lungs and the presence of cysts or polyps were noted on autopsy in both groups. Likewise, relative organ body weight percentage also increased in all the organs except the testis.Hematological analysis—Lymphocytosis and neutropenia were observed in IP as well as IN groups.Biochemical analyses—Elevated malondialdehyde (MDA), reduced catalase (CAT) and superoxide dismutase (SOD) production; abnormal levels of aspartate transaminase (AST) and alanine transaminase (ALT) were observed, which signifies A. pullulans mycotoxin induced oxidative stress.Histological observations—Histopathological changes characterized by inflammation and amyloid in the liver, edema in the lungs, tubule hypertrophy in renal tissues, angiectasis in the spleen, hyperplasia in gastric tissues, neurodevelopmental anomaly in the brain, and degeneration in the testis were observed.Cell apoptosis factor—The reduced activity of caspase-3 enzyme was noted in both the mycotoxicosis-induced groups.ConclusionThus, from the present study, we concluded that mycotoxins isolated from A. pullulans (CBS 577.93) documented toxicity in all eight organs, with the testis and lungs being the worst affected organs. Even at a very small concentration and short exposure, the mycotoxin caused severe damage to the vital organs. New risk assessment approaches should be considered to investigate the toxicological interactions of A. pullulans mycotoxins in the indoor environment and in animal models.

Introduction of Flavor Chemical Eugenol Attenuating the Synergistic Toxicological Interactions of Flavor Mixtures.

The flavor chemicals benzyl alcohol (BEA), phenylethanol (PHA), and cinnamaldehyde (CID) and their binary mixtures have high toxicity sensitivity to the lethal endpoint of Caenorhabditis elegans. Some binary flavor mixtures even have synergistic toxicological interactions. Eugenol (EUG) is closely related to human life and has many special nonlethal effects on organisms. The effect of its introduction on the combined toxicities of flavor mixtures is worth studying. We introduced EUG into three binary (BEA-PHA, BEA-CID, and PHA-CID) and one ternary (BEA-PHA-CID) flavor mixture systems. Five representative mixture rays were selected from each of the four mixture systems using the uniform design ray (UD-Ray) method. The lethal toxicity of each mixture ray to C. elegans was measured at three different exposure volumes (100, 200, and 400 μL), and a dose–effect model was established. The new parameter iSPAN was used to quantitatively characterize the toxicity sensitivity of each chemical and mixture ray. The toxicological interaction of each mixture was evaluated by the toxicological interaction heatmap based on the combination index (CI). It can be seen that all flavor chemicals and their ternary and quaternary mixture rays have high iSPANs, and the highest value is 16.160 (BEA-PHA-CID-EUG-R1 at 400 μL). According to the heatmap and CI, the introduction of EUG attenuates the synergistic toxicological interactions of flavor mixtures, leading to the transformation ofsynergistic interactions in flavor mixtures into additive action and even antagonistic interaction, and the CI value of the antagonistic interaction is up to 1.8494 (BEA-CID-EUG-R4 at 400 μL).

Long-term effects of lithium and lithium-microplastic mixtures on the model species Daphnia magna: Toxicological interactions and implications to 'One Health'.

Environmental contamination with lithium (Li) and microplastics (MP) has been steadily increasing and this trend is expected to continue in the future. Many freshwater ecosystems, which are crucial to reach the United Nations Sustainable Development Goals, are particularly vulnerable to Li and MP contamination, and other pressures. The long-term effects of Li, either alone or combined with MP (Li-MP mixtures), were investigated using the freshwater zooplankton micro-crustacean Daphnia magna as model species. In the laboratory, D. magna females were exposed for 21 days to water concentrations of Li (0.02, 0.04, 0.08 mg/L) or Li-MP mixtures (0.02 Li + 0.04 MP, 0.04 Li + 0.09 MP mg/L, 0.08 Li + 0.19 MP mg/L). In the range of concentrations tested, Li and Li-MP mixtures caused parental mortality, and decreased the somatic growth (up to 20% and 40% reduction, respectively) and the reproductive success (up to 93% and 90% reduction, respectively). The 21-day EC50s of Li and Li-MP mixtures on D. magna reproduction were 0.039 mg/L and 0.039 Li + 0.086 MP mg/L, respectively. Under exposure to the highest concentration of Li (0.08 mg/L) and Li-MP mixtures (0.08 Li + 0.19 MP mg/L), the mean of D. magna population growth rate was reduced by 67% and 58%, respectively. Based on the population growth rate and using data from a bioassay testing the same concentrations of MP alone and carried simultaneously, the toxicological interaction between Li and MP was antagonism under exposure to the lowest and the highest concentrations of Li-MP mixtures, and synergism under exposure to the medium concentration of Li-MP mixtures. These findings highlight the need of further investigating the combined effects of contaminants, and the threat of long-term environmental contamination with Li and MP to freshwater zooplankton, biodiversity, ecosystem services and 'One Health'.

Assessing the toxicological interaction effects of imidacloprid, thiamethoxam, and chlorpyrifos on Bombus terrestris based on the combination index

In modern agricultural production, a variety of pesticides are widely used to protect crops against pests. However, extensive residues of these pesticides in the soil, water, and pollen have negatively affected the health of nontarget organisms, especially among pollinators such as bumblebees. As an important pollinator, the bumblebee plays a vital role in agricultural production and the maintenance of ecosystem diversity. Previous research has focused on the effects of a single pesticide on pollinating insects; however, the synergistic effects of multiple agents on bumblebees have been not studied in detail. Imidacloprid, thiamethoxam, and chlorpyrifos are three of common pesticides known for severe effects on bumblebee health. It is still unknown what synergistic effects of these pesticides on pollinators. In our test, the individual and combined toxicities of chlorpyrifos, thiamethoxam, and imidacloprid to bumblebees after 48 h of oral administration were documented by the equivalent linear equation method. Our results showed that the toxicity of each single pesticide exposure, from high to low, was imidacloprid, thiamethoxam, and chlorpyrifos. All binary and ternary combinations showed synergistic or additive effects. Therefore, our research not only shows that the mixed toxicity of insecticides has a significant effect on bumblebees, but also provides scientific guidelines for assessing the safety risks to bumblebees of these three insecticide compounds. In assessing the risk to pollinating insects, the toxicity levels of laboratory experiments are much lower than the actual toxicity in the field.

Toxicological Interactions of Disinfection Byproducts Mixtures of Halogenated Acetamides and Haloacetic Acids on Freshwater Bacteria

Toxicological Interactions of Disinfection Byproducts Mixtures of Halogenated Acetamides and Haloacetic Acids on Freshwater Bacteria

Combined effects of polystyrene microplastics and cadmium on oxidative stress, apoptosis, and GH/IGF axis in zebrafish early life stages

The toxicological interactions of microplastics (MPs) and heavy metals have been paid much attention in aquatic organism. The mechanisms are not fully clear, particularly in fish early life stages. To the end, zebrafish embryos were exposed to 500 μg/L MPs, 5 μg/L cadmium (Cd), and their combination for 30 days. Body weight, adsorption characteristics of Cd onto MPs, Cd accumulation, oxidative stress, apoptosis, and growth hormone/insulin-like growth factor-I (GH/IGF) axis were examined. Exposure to MPs and Cd alone reduced body weight, which was aggravated by co-exposure. An increase in reactive oxygen species (ROS) levels was observed in larvae exposed to Cd or MPs + Cd, suggesting an induction of oxidative stress. Lipid peroxidation levels were not affected by exposure to MPs and Cd alone but dramatically enhanced by co-exposure, which may be explained by the reduction of total antioxidant capacity (TAOC) and activity levels of Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) after co-exposure. Increased apoptotic cells were observed in the vertebral body of larvae exposed to Cd, the esophagus of larvae exposed to MPs, and both organs of larvae exposed to MPs + Cd, which was further confirmed by changes in the activities of Caspase-3, Caspase-8 and Caspase-9. PCR array on the transcription of genes related to growth, oxidative stress and apoptosis was examined, showing that the combined exposure resulted in greater magnitude of changes than MPs and Cd alone. The results indicate that MPs can enhance the negative effects of Cd on growth, oxidative damage and apoptosis in early life stages of zebrafish. However, the adsorption of Cd onto MPs was not observed and the combined exposure did not increase the Cd content in larvae compared to the single Cd exposure, implying that vector role of MPs in Cd uptake is negligible.

Study on the Combined Toxicities and Quantitative Characterization of Toxicity Sensitivities of Three Flavor Chemicals and Their Mixtures to Caenorhabditis elegans.

It was shown that flavor chemicals with high toxicity sensitivities mean that small changes in their effective concentrations can lead to significant changes in toxicity. Flavors are widely used in personal care products. However, our study demonstrated that some flavor chemicals and their mixture rays have high toxicity sensitivities to Caenorhabditis elegans (C. elegans), which may have an impact on human health. In this paper, three flavor chemicals (benzyl alcohol, phenethyl alcohol, and cinnamaldehyde) were used as components of the mixture, and three binary mixture systems were constructed, respectively. Five mixture rays were designed for each mixture system by a direct equipartition ray design method. The lethal toxicities of the three flavor chemicals and mixture rays to C. elegans at three exposure volumes were determined. A new concept (inverse of the negative logarithmic concentration span (iSPAN)) was introduced to quantitatively evaluate the toxicity sensitivity of chemicals or mixture rays, and the combination index (CI) was employed to identify the toxicological interactions in the mixtures. It was shown that the three flavor chemicals as well as the binary mixture rays have a significant concentration–response relationship on the lethality of C. elegans. The iSPAN values of the three flavor chemicals and their mixture rays were larger than 3.000, showing very strong toxicity sensitivity to C. elegans. In mixture systems, the toxicity sensitivities of mixture rays with different mixture ratios were also different at different exposure volumes. In addition, it can be seen from the CI heat map that the toxicological interaction not only shows the mixture ratio dependence but also changes with the different exposure volumes, which implies that the mixtures consisting of flavor chemicals with high toxicity sensitivity have complex toxicological interactions. Therefore, in environmental risk assessment, special attention should be paid to chemicals with high toxicity sensitivities.