Is Actara® a less toxic neonicotinoid formulation? A multigenerational study using the non-target organism Chironomus xanthus.

Neonicotinoids are highly consumed systemic insecticides that mimic acetylcholine (ACh) with a specific mode of action at the nicotinic acetylcholine receptors (nAChRs). The insecticide Actara® (active ingredient thiamethoxam- TMX) is a commercial formulation widely used for the control of various agricultural pest species. However, negative effects of TMX have been observed in non-target organisms. This work aimed to evaluate the biological effects of the commercial formulation Actara® on the aquatic non-target and non-biting larvae of Chironomus xanthus (Diptera). The lethal (LC50) and sublethal (body length, head capsule width, cumulative emergence, and mean time to emergence-EmT50) effects were determined in two subsequent generations (P and F1). The estimated 48 h LC50 for C. xanthus larvae exposed to Actara® was 73.02 µg TMX/L. By looking at the sublethal effects of Actara on the life cycle parameters of C. xanthus, we determined that none of the concentrations used induced a significantly different response in the organisms, compared to the control treatment (NOEC > 2 µg TMX/L). However, the head capsule width in the parental (P) generation exposed to Actara (≥ 0.9 µg TMX/L) was significantly bigger than the head capsule width of control animals. Overall, our results highlight that, at environmentally relevant concentrations, the commercial formulation Actara® is non-toxic to C. xanthus.

Systematic Review of Nano- and Microplastics' (NMP) Influence on the Bioaccumulation of Environmental Contaminants: Part II-Freshwater Organisms.

Nano- and microplastic fragments (NMPs) exist ubiquitously in all environmental compartments. The literature-based evidence suggests that NMPs interact with other environmental contaminants in freshwater ecosystems through sorption mechanisms, thereby playing a vector role. Chemically bound NMPs can translocate throughout the environment, reaching long distances from the contaminant discharge site. In addition, they can be ab/adsorbed by freshwater organisms. Although many studies show that NMPs can increase toxicity towards freshwater biota through the carrier role, little is known regarding their potential to influence the bioaccumulation of environmental contaminants (EC) in freshwater species. This review is part II of a systematic literature review regarding the influence of NMPs on bioaccumulation. Part I deals with terrestrial organisms and part II is devoted to freshwater organisms. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA ScR) was used for the literature search and selection. Only studies that assessed the bioaccumulation of EC in the presence of NMPs and compared this with the bioaccumulation of the isolated EC were considered. Here, we discuss the outcome of 46 papers, considering NMPs that induced an increase, induced a decrease, or caused no effect on bioaccumulation. Lastly, knowledge gaps are identified, and future directives for this area of research are discussed.

Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms.

Since the late 70s, the continuous pharmaceuticals` input into the environment has raised concerns regarding the eventual risk posed by such compounds to human and environmental health. A major group of pharmaceuticals in terms of environmental impact are the antineoplastic agents (AAs). Herein, we followed a systematic review method to retrieve antineoplastic agents (AAs') ecotoxicological information regarding freshwater species. In this analysis, data from diverse taxonomic groups, from microorganisms to vertebrate species, looked at different levels of biological organization, including cell lines. Furthermore, this review gathers ecotoxicological parameters (EC50 and LC50) for imatinib (IM), cisplatin (CisPt), and 5-fluorouracil (5-FU) in species sensitivity distribution (SSD) curves and estimates the hazard concentration (HC5) considering the protection of 95% of the ecological community. Lastly, we suggest how we can improve AAs' Environmental Risk Assessment (ERA), considering potential adoptable toxicity endpoints, test duration, AAs metabolites testing, and AAs mixture exposure.

A Systematic Review of Nano- and Microplastic (NMP) Influence on the Bioaccumulation of Environmental Contaminants: Part I-Soil Organisms.

Nano- and microplastics (NMPs) are a group of contaminants that cause concern due to their abundance in the environment, high persistence, and interaction with other contaminants. This review aims to understand the role of NMP in the bioaccumulation of environmental contaminants. For that, a comprehensive literature search was conducted to identify publications that compared the uptake of contaminants in the presence and absence of NMP. In this part I, twenty-eight publications of the terrestrial compartment were analyzed. Two main taxonomic groups were studied, namely, earthworms and terrestrial plants. In earthworms, most studies observed an increase in the bioaccumulation of the contaminants, while in plants, most studies observed a decrease in the bioaccumulation. Changes in bioavailable fractions of contaminants due to NMP presence was the main reason pointed out by the authors for their outcomes. Moreover, biological aspects were also found to be important in defining how NMPs affect bioaccumulation. Dermal damage and changes in contaminant-degrading bacteria in the gut of earthworms caused an increase in bioaccumulation, and root pore blockage was a common reason for the decrease in the bioaccumulation of contaminants in plants. Nevertheless, such effects were mainly observed at high, unrealistic NMP concentrations. Finally, knowledge gaps were identified, and the limitations of this systematic review were presented.

What does not kill it makes it stronger! The tolerance of the F1 larvae of Chironomus xanthus to a neonicotinoid insecticide formulation.

Thiamethoxam (TMX) is a systemic neonicotinoid that acts as a partial agonist of the nicotinic acetylcholine receptors (nAChRs). However, target species have shown resistance to formulations based on such neonicotinoids, which can also be expected for non-target insects. This research aimed to study the effects of a formulation based on TMX [Cruiser® 350 FS (CRZ)] on the life traits of Chironomus xanthus filial generation (F1) and compare it with the parental generation (P). Environmentally relevant concentrations of CRZ significantly decreased larvae growth P generation , also slowing and decreasing their emergence. Larvae of the F1 generation were less sensitive than their parents, suggesting that the progeny were able to thrive and perform basic physiological functions better than the parental generation. Our results highlight that insect resistance to neonicotinoids may be associated with the better performance of the filial generation, which is related to the change in affinities of the active ingredient for the sub-units constituting the nAChRs subtypes of F1 organisms, inherited from P organisms that were able to survive and reproduce. Moreover, further studies using biochemical and omics tools should be performed to disentangle the specific changes occurring at the nAChRs throughout insect development.

The multigenerational effects of clothianidin on Chironomus xanthus: Larvae exposed to this acetylcholine super agonist show no clear resistance.

Clothianidin (CLO) is an insecticide belonging to the second-generation class of neonicotinoids. In this study, we evaluated how CLO affects the survival and the complete life cycle of the tropical insect Chironomus xanthus, a non-target species, considering the Parental (P) and Filial (F1) generations. We found a 48 h-lethal concentration (LC50) of CLO of 3.78 µg/L. The lowest observed effect concentrations (LOECs) were: i) for body growth and head capsule width in P generation = 47.3 ng/L CLO; ii) for body growth and head capsule width in F1 generation larvae = 80 and 36.4 ng/L CLO, respectively; iii) for cumulative emergence it was 80 ng/L CLO in the P generation, while there was no significant difference in the F1 generation; iv) for total developmental time for males and females = 61.53 ng/L in P generation; v) in the F1 generation, the LOEC was determined to be 36.4 ng/L for males and 80 ng/L for females; vi) The number of total hatched eggs and total hatched eggs/female had LOECs of 36.4 ng/L CLO for both generations. Our study reveals that environmentally relevant concentrations of the CLO-based insecticide are highly toxic to C. xanthus. It also shows that the F1 generation, resulting from parents exposed to CLO was not clearly resistant to the insecticide. This fact might be explained by the different effects observed for males and females of F1 generation. Understanding the sub-types of acetylcholine receptors present on target and non-target insect species and toxicological effects of neonicotinoids seems to be desirable for the insecticide industry to deal with insect pests and the environmental protection of non-target organisms.

Metabolomic profiling and correlations of supercritical extracts of guarana.

A previous optimization of supercritical extraction from guarana seeds was performed applying orthogonal array design (OA9(34)). The antioxidant and antimicrobial activities of these extracts, as well as metabolomic profiling and correlations from the compounds by statistical analysis were determined. Extracts 1 (40% ethanol; 20 min; 40 °C and 100 bar), 2 (40% methanol; 60 min; 40 °C and 200 bar), and 8 (40% methanol; 40 min; 60 °C and 100 bar) had the highest combined values of antioxidant capacity for the DPPH, FRAP, ABTS and xanthine oxidase system methods, and were identified by chemometric analysis. Similar chemical profiles of the extracts were obtained by LC-DAD-MS, and were identified: methyl-xanthine, (epi)catechin and dimers and trimers of type A and B proanthocyanidins. The heat map analysis showed positive correlation between antioxidant methods DPPH, FRAP and ABTS and with flavan-3-ols and proanthocyanidins. Extract 3 was active against Gram-negative and -positive bacteria and Candida tropicalis.

Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms.

Pharmaceutical compounds represent a class of emerging contaminants present in the environment. Their intense (and increasing) use in human and veterinary medicine leads to their discharge, mainly via human excretion, into wastewater treatment plants where their removal is inefficient. A specific class of pharmaceuticals used to fight cancer, known as antineoplastic or anticancer drugs, has gained increased attention regarding their possible environmental hazard due to their pharmacological properties, which include the nonselective targeting of DNA replication mechanisms and cell division processes, potentially inducing cell apoptosis. To date, there is limited information concerning the effects of anticancer drugs and/or their metabolites in species inhabiting freshwater environments, let alone marine and estuarine compartments. In the present review, we aimed to assemble information regarding the impact that anticancer drugs have on biological traits of marine species, to identify gaps in the current environmental hazard assessment, and to make recommendations to promote an efficient environmental hazard assessment of anticancer drugs in the marine environment. Environ Toxicol Chem 2022;41:1793-1807. © 2022 SETAC.

Toxicokinetics of silver in the goldfish Carassius auratus under simultaneous waterborne and diet-borne exposures to silver nanoparticles.

Silver nanoparticles (AgNPs) are applied in many products as antimicrobial agents and can be found in the environment. In this study, the uptake and elimination kinetics of silver nanoparticles in fish (Carassius auratus), via simultaneous water and dietary exposure, was investigated and compared with ionic silver (AgNO3). Silver concentration in the tissues of C. auratus after the uptake phase was similar between nanoparticles and ionic treatments. Upon exposure to nanoparticles, Ag concentration in the different tissues of C. auratus was significantly different (Ag[liver] > Ag[intestine] > Ag[gill] > Ag[muscle]). The liver presented the highest amount of Ag among all organs, and no elimination was detected throughout the elimination period. Our results suggest that once uptake of Ag occurs in fish, the elimination takes very long which may pose ecological implications for bioaccumulation.

Green toxicology approach involving polylactic acid biomicroplastics and neotropical tadpoles: (Eco)toxicological safety or environmental hazard?

Different and alternative renewable-source materials, commonly called bioplastics, have been proposed due to the high production and consumption of petroleum-derived plastics and to their high toxicity in the biota. However, their toxicological safety has not yet been assessed in a comprehensive way; therefore, their effects on several animal groups remain completely unknown. Thus, we aimed at testing the following hypothesis: the exposure of Physalaemus cuvieri tadpoles to polylaic acid biomicroplastic (PLA BioMP) at environmentally relevant concentrations (760 and 15,020 µg/L) induces physiological changes in them. Based on the collected data, biopolymer uptake changed tadpoles' growth and development features, reduced their lipid reserves (it was inferred by decreased triglyceride levels), as well as increased reactive oxygen and nitric oxide species production after 14-day exposure. The proportional increase in total glutathione levels, and in superoxide dismutase and catalase activity, was not enough to counterbalance the production of reactive species. In addition, the two tested concentrations caused cholinesterase effect, which was marked by increased acetylcholinesterase and butyrylcholinesterase. This finding is indicative of the neurotoxic action of PLA BioMP. To the best of our knowledge, this is the first report on the harmful consequences of exposing amphibian representatives to the herein tested biopolymers. Therefore, this finding encourages further studies and contributes to demystify the idea that bioplastics are "harmless" to the aquatic biota in freshwater environments.

Polyethylene glycol acute and sub-lethal toxicity in neotropical Physalaemus cuvieri tadpoles (Anura, Leptodactylidae).

Although many polymers are known by their toxicity, we know nothing about the impact of polyethylene glycol (PEG) on anurofauna. Its presence in different products and disposal in aquatic environments turn assessments about its impact on amphibians an urgent matter. Accordingly, we tested the hypothesis that short-time exposure (72 h) of tadpoles belonging to the species Physalaemus cuvieri (Anura, Leptodactylidae) to PEG induces oxidative stress and neurotoxicity on them. We observed that polymer uptake in P. cuvieri occurred after exposure to 5 and 10 mg/L of PEG without inducing changes in their nitrite levels neither at the levels of substances reactive to thiobarbituric acid. However, hydrogen peroxide and reactive oxygen species production was higher in animals exposed to PEG, whose catalase and superoxide dismutase levels were not enough to counterbalance the production of these reactive species. Therefore, this finding suggests physiological changes altering REDOX homeostasis into oxidative stress. In addition, the increased activity of acetylcholinesterase and butyrylcholinesterase, and reduction in superficial neuromasts, confirmed PEG's neurotoxic potential. To the best of our knowledge, this is the first report on PEG's biological impact on a particular amphibian species. The study has broadened the understanding about ecotoxicological risks associated with water pollution by these polymers, as well as motivated further investigations on its impacts on amphibians' health and on the dynamics of their natural populations.

Ceria Nanoparticles Decrease UVA-Induced Fibroblast Death Through Cell Redox Regulation Leading to Cell Survival, Migration and Proliferation.

Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.

Metformin effect on driving cell survival pathway through inhibition of UVB-induced ROS formation in human keratinocytes.

Human skin functions go beyond serving only as a mechanical barrier. As a complex organ, the skin is capable to cope with external stressors cutaneous by neuroendocrine systems to control homeostasis. However, constant skin exposure to ultraviolet (UV) radiation causes progressive damage to cellular skin constituents, mainly due excessive reactive oxygen species (ROS) production. The present study shows new approaches of metformin (MET) as an antioxidant agent. Currently, MET is the first line treatment of type 2 diabetes and has attracted attention, based on its broad mechanism of action. Therefore, we evaluated MET antioxidant potential in cell-free systems and in UVB irradiated human keratinocyte HaCaT cells. In cell-free system assays MET did not show intrinsic scavenging activity on DPPH radicals or superoxide (O2-) xanthine/luminol/xanthine oxidase-generated. Cell-based results demonstrated that MET was able to reduce UVB-induced intracellular ROS and NADPH oxidase-dependent superoxide (O2-) production. MET posttreatment of HaCaT cells reduced ERK 1/2 phosphorylation, NADPH oxidase activity, and cell death by apoptosis. These findings suggest that the protection mechanism of MET may be through the inhibition of ROS formation enzyme. These results showed that MET might be a promising antioxidant agent against UV radiation induced skin damage.

Initial beach litter survey in a conservation unit (Santa Isabel Biological Reserve, Sergipe) from northeast Brazil.

This study aimed to evaluate the presence and distribution of litter on four beaches in a conservation unit in northeast Brazil (Santa Isabel Biological Reserve; SIBR), and at the tourist beach of Pirambu (PB). Samplings occurred during low tide in March 2018 and May 2018. We observed that PB contained a higher number of litter items (March = 12.5 ± 1.2 items m-1; May = 6.1 ± 2.1 items m-1) when compared to SIBR beaches with a general average of 1.7 ± 0.8 items·m-1 (March) and 2.1 ± 1.1 items·m-1 (May). Plastics were the most quantified items (~ 80% in PB and ~ 90% in SIBR). SIBR beaches were considered moderately clean. Despite access restriction on the SIBR beaches, the considerable amount of litter found in those beaches (mainly near the villages) calls attention to the importance of waste management improvements in Sergipe cities.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

In vitro evaluation of the protective effects of plant extracts against amyloid-beta peptide-induced toxicity in human neuroblastoma SH-SY5Y cells.

Alzheimer's disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aß) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia, Limonium brasiliense, Paullinia cupana, Poincianella pluviosa, Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aß25-35 toxicity in SH-SY5Y cells. The effect of the EAF of S. adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 (S. adstringens, P. pluviosa and L. brasiliense) protected SH-SY5Y cells from Aß25-35-induced toxicity. The EAF of S. adstringens at 15.62 µg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aß25-35-induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S. adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aß25-35, which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa and S. adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.

The extended production of UV-induced reactive oxygen species in L929 fibroblasts is attenuated by posttreatment with Arrabidaea chica through scavenging mechanisms.

Ultraviolet radiation (UVR) exposure causes various injurious effects to human skin by generating reactive oxygen species (ROS). Excessive ROS production can lead to oxidative stress which may damage cellular components like lipids and proteins and causing photoaging. The use of natural photochemopreventive agents with antioxidant properties is an important alternative to improve the effectiveness of sunscreens and reduce skin photodamage. A crude extract (CE) from the leaves of Arrabidaea chica underwent partition by a liquid-liquid method. The hexane fraction (FH), chloroform fraction (FC), and ethyl acetate fraction (FEA) were obtained. The antioxidant capacity of the CE, FH, FC, and FEA was studied in a cell-free system using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and the xanthine/luminol/xanthine oxidase system. The FC had the best antioxidant activity. We also evaluated the photochemoprotective effect of A. chica in protecting L929 fibroblasts against UV-A- and UV-B-induced cell damage. A. chica inhibited the extended production of ROS up to 3h. Posttreatment with the CE and FC attenuated UV-induced cell damage through scavenging mechanisms, including the quenching of intracellular ROS and mitochondrial O2- and preventing lipid peroxidation. These results suggest that A. chica may be a promising non-sunscreen photoprotector that can improve the effectiveness of commercial sunscreens.

Bioaccumulation of silver in Daphnia magna: Waterborne and dietary exposure to nanoparticles and dissolved silver.

Silver nanoparticles (Ag-NP) are incorporated into commercial products as antimicrobial agents, which potentiate their emission to the environment. The toxicity of Ag-NP has been associated with the release of Ag ions (Ag+), which are more toxic to aquatic organisms than Ag-NP. In this study, a toxicokinetics approach was applied to compare the potential of Daphnia magna to accumulate Ag from either Ag-NP or AgNO3 through different exposure routes: a) water, b) diet and c) water and diet. A one-compartment kinetics model was applied to describe the development of Ag body concentrations over time and derive uptake (k1w; k1d) and elimination (k2) rate constants. Under water-only exposure, AgNO3 induced higher Ag uptake rate constants and bioconcentration factors when compared to Ag-NP. For dietary exposure, no differences in Ag concentrations in D. magna, along with the kinetics parameters, were found for both Ag forms. Simultaneous water and dietary exposures to Ag-NP induced higher Ag concentrations in D. magna compared to AgNO3. In this combined exposure, uptake from water explains most for the increase in Ag body concentration in D. magna for Ag-NP exposure, whereas uptake from the diet was the major contributor for the increase in Ag concentration in D. magna under AgNO3 exposure. Biomagnification was not observed for any of the exposure routes applied in this study, neither for Ag-NP nor for AgNO3.

Co-exposure of ZnO nanoparticles and UV radiation to Daphnia magna and Danio rerio: Combined effects rather than protection.

The application of nanoparticles (NPs) in consumer products has been increasing over the past few years. Their release into the environment is likely to happen at any stage of production or during the use of products containing NPs. Zinc oxide NPs (ZnO-NP) are among the most-used NPs on the market due to its intrinsic properties, such as ultraviolet (UV) absorption. The aim of the present study was to assess the combined effects of ZnO-NP and UV radiation on 2 freshwater species: Daphnia magna and Danio rerio. The initial hypothesis was that the presence of ZnO-NP in the aquatic media would decrease the damaging effects of UV radiation for both species. The endpoints assessed for D. magna were immobilization, feeding inhibition, and reproduction output. For D. rerio, egg development was studied during 96 h and mortality, hatching delay, and abnormal development were the endpoints recorded. Combined exposures were designed based on the single toxicity of both stressors and analyzed based on the independent action concept and exploring possible deviations for synergism/antagonism, dose level, and dose ratio. Combined exposures with D. magna induced synergism on reproduction, decreasing the number of neonates produced more than expected based on both stressors' individual toxicity. Single exposures of D. rerio embryos to both stressors induced negative effects. The combined exposures caused a dose-ratio deviation pattern on mortality and hatching, with a synergism observed when ZnO-NP was the dominant stressor, changing to antagonism when UV radiation dominated the combined exposure. Regarding the results attained, studying ZnO toxicity under laboratory conditions may underestimate the risks when considering the potential interaction on effects when combined with UV radiation.