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A mining tailing dam rupture in Brazil in November 2015 released millions of tons of mining waste into the Rio Doce ecosystem, leading to long-term aquatic ecosystem impacts. Although multiple lines of evidence indicate tailings associations with potentially toxic elements in estuarine sediments and biological impact and bioaccumulation pathways in fishes, the extent of contamination in base benthic species is still largely unknown. Moreover, Rare Earth Elements (REE) have not received any attention in this regard. This study assessed REE in fiddler crabs (Minuca rapax) sampled from the Rio Doce estuary in 2017, nearly 2 years after the disaster. The ΣREE in crab hepatopancreas and muscle were high (327.83 mg kg -1 w.w. and 33.84 mg kg -1 w.w., respectively, compared to other assessments in crabs, indicating a preference for REE bioaccumulation in the hepatopancreas compared to muscle. Neodimium, La, and Ce were detected at the highest concentrations. The REE from the Rio Doce Basin were, thus, transported and deposited in the estuary with the mine tailings slurry, leading to bioaccumulation in crabs. This may lead to trophic effects and other ecological impacts not readily measured by typical impact assessment studies, revealing an invisible and not typically acknowledged damage to the Rio Doce estuary., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Leachate is a highly complex waste with high toxicological potential that poses a significant threat to the terrestrial environment. Determining leachate physicochemical parameters and identifying xenobiotics alone is, however, not enough to determine the real environmental impacts. In this context, the use of terrestrial model organisms has been highlighted as a tool in ecotoxicological leachate assessments and as a guiding principle in risk assessments. In this context, this review aimed to present the most current state of knowledge concerning leachate toxicity and the bioassays employed in this evaluation concerning terrestrial plants and animals. To this end, a literature search on leachate effects on terrestrial organisms was carried out using ten search terms, in 32 different combinations, at the Web of Science and Scopus databases. A total of 74 eligible articles were selected. The retrieved studies analyzed 42 different plant and animal species and employed nine endpoints, namely phytotoxicity, genotoxicity, bioaccumulation, antioxidant system, cytotoxicity, reproduction, physiological changes, behavior and lethality. A frequent association of toxic leachate effects with metals was observed, mainly Pb, Cd, Cr, Mg, Zn and Cr, which can cause antioxidant system alterations and cyto- and genotoxicity. These elements have also been associated to reproductive effects in earthworms and mice. Specifically concerning plants, most of the retrieved studies employed Allium cepa in toxicity assays, reporting phytotoxic effects frequently associated to metals and soil parameter changes. Animal studies, on the other hand, mostly employed mice and evaluated genotoxicity and antioxidant system effects. Even with the description of toxic leachate effects in both plants and animals, a lack of knowledge is still noted concerning reproductive, physiological, cytotoxic, and behavioral effects in terrestrial species. We, thus, suggest that further studies be carried out on other animals, advancing our understanding on potential environmental leachate effects, also allowing for human health risk assessments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Water body contamination by leachate originated from dumpsites is a concern for municipal solid waste (MSW) management. In this context, this study aimed to evaluate antioxidant system alterations and oxidative and genotoxic effects in Danio rerio (zebrafish) exposed to leachate from a closed dumpsite. Groups comprising 50 fish were exposed (96 h) to different leachate concentrations (5, 15, 30, and 50%) to evaluate effects on liver and brain superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities and reduced glutathione (GSH) and metallothionein (MT) concentrations, as well as malondialdehyde (MDA) and protein carbonylation (PTC) levels. Blood genotoxicity was evaluated by the comet assay. The investigated dumpsite leachate pond presented high chloride concentrations (Cl - ; 2288.4 ± 69.5 mg L -1 ) and high electrical conductivity (EC; 8434.0 mS cm -1 ), indicating the presence of leachate. Concerning Danio rerio exposure, higher SOD (37%), CAT (67%), and GST (39%) activities and higher GSH (57%) concentrations were observed in liver following exposure to 50% leachate, while decreased brain GST (42%) activities and GSH (90%) levels were observed at the same leachate concentration. A significant increase in the olive tail moment (OTM; 280%) indicative of genotoxicity in blood was observed. A principal component analysis indicated that increased enzymatic activities and high levels of both GSH and MT were not sufficient to prevent the accumulation of reactive oxygen species, resulting in PTC and genotoxicity. Therefore, leachate exposure causes sublethal Danio rerio effects, altering the antioxidant system, increasing ROS production, and leading to PTC and genotoxicity. The findings demonstrate the need to further develop sublethal level assessments in zebrafish using leachate from different sources to subsidize risk assessments regarding MSW management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated the mechanism of action of clotrimazole (CTZ) and its adverse effects in a model of endometriosis. After autologous endometrial implantation, 18 rats were randomized into two treatment groups: 200 mg/kg CTZ or vehicle for 15 consecutive days. The lesion growth, implant size, glandular atrophy, nitric oxide (NO) serum levels, number of macrophage cells and inducible nitric oxide synthase (iNOS) immunoreactivity were significantly reduced in the CTZ group compared with the control. CTZ (p < 0.05) reduced the lipid peroxidation and protein carbonylation levels in the liver but did not alter the superoxide dismutase (SOD), glutathione (GSH) or glutathione S-transferase (GST) levels in the brain; however, the drug significantly reduced SOD activity and enhanced GST activity in the liver. These results suggest that CTZ interferes with reactive nitrogen species production by downregulating iNOS expression and thus enhances the antioxidant system to promote atrophy and regression of endometriotic lesions, without adverse effects on the brain and/or liver., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Coupling of UV-C irradiation to different peroxides (H 2 O 2 , S 2 O 8 2- and HSO 5 - ) has great potential to degrade persistent organic compounds due to the formation of HO • or SO 4 •- species. However, an in-depth comparison between the performance of different UV-C/peroxide processes as a function of (i) target compound degradation, (ii) generated transformation products and (iii) lethal/sub lethal toxicity effects has not yet been performed. To this end a comparison study was carried out to evaluate the effectiveness of different UV-C/peroxide processes using the herbicide tebuthiuron (100 or 500 μg L -1 ) as a model pollutant. TBH degradation experiments were performed at lab-scale in real municipal wastewater treatment plant effluent and distilled water. Faster degradation occurred by increasing peroxide concentration from 735 to 2206 μmol L -1 in the municipal wastewater treatment plant effluent, mainly for S 2 O 8 2- . Experiments performed in the presence of peroxide trapping agents - HO • and SO 4 •- (methoxibenzene) or HO • (2-propanol) - revealed that oxidation in the UV-C/S 2 O 8 2- system occurs mainly through SO 4 •- . Lower toxicity for the MWWTP effluent was obtained after oxidative treatments using hydrogen peroxide or monopersulfate as oxidants which react mainly through HO • radicals. Two mechanistic pathways were proposed for tebuthiuron degradation: (i) hydrogen abstraction by HO • (H 2 O 2 and HSO 5 - ) and (ii) electron transfer by SO 4 •- (S 2 O 8 2- ). In addition, one unprecedented transformation product was identified. In conclusion, results emphasize the relevance of comparing the degradation of toxic compounds in the presence of different peroxide sources and matrices and simultaneouly evaluating responses chemical and biological endpoints., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is estimated that approximately 0.4% of the total leachate produced in a landfill is destined for treatment plants, while the rest can reach the soil and groundwater. In this context, this study aimed to perform leachate toxicity evaluations through immune system cytotoxic assessments, genotoxic (comet assay) appraisals and antioxidant system (superoxide dismutase - SOD; catalase - CAT, glutathione-S-transferase - GST; reduced glutathione - GSH and metallothionein - MT) evaluations in Eisenia andrei earthworms exposed to a Brazilian leachate for 77 days. The leachate sample contained high organic matter (COD - 10,630 mg L -1 ) and ammoniacal nitrogen (2398 mg L -1 ), as well as several metals, including Ca, Cr, Fe, Mg, Ni and Zn. Leachate exposure resulted in SOD activity alterations and increased CAT activity and MT levels. Decreased GST activity and GSH levels were also observed. Antioxidant system alterations due to leachate exposure led to increased malondialdehyde levels as a result of lipid peroxidation after the 77 day-exposure. An inflammatory process was also observed in exposed earthworms, evidenced by increased amoebocyte density, and DNA damage was also noted. This study demonstrates for the first time that sublethal effect assessments in leachate-exposed earthworms comprise an important tool for solid waste management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Leachate is difficult to biodegrade, and presents variable physical, chemical and biological characteristics, as well as high toxicological potential for soil, groundwater and water bodies. In this context, untreated leachate toxicity was evaluated through acute and chronic exposures in Eisenia andrei earthworms. Physico-chemical leachate characterizations indicate a complex composition, with high organic matter (COD - 10,634 mg L -1 ) and ammoniacal nitrogen (2388 mg L -1 ) concentrations. Metals with carcinogenic potential, such as Cr, As and Pb, were present at 0.60, 0.14 and 0.01 μg L -1 , respectively and endocrine disrupting compounds were detected in estradiol equivalents of 660 ± 50 ng L -1 . Acute tests with Eisenia andrei indicated an LC 50 (72 h) of 1.3 ± 0.1 μL cm -2 in a filter paper contact test and 53.9 ± 1.3 mL kg -1 in natural soil (14 days). The EC 50 in a behavioral test was estimated as 31.6 ± 6.8 mL kg -1 , indicating an escape effect for concentrations ranging from 35.0 to 70.0 mL kg -1 and habitat loss from 87.5 mL kg -1 of leachate exposure. Chronic exposure (56 days) led to reproduction effects, resulting in a 4-fold decreased cocoon production and 7-fold juvenile decrease. This effect was mainly attributed to the possible presence of endocrine disrupting compounds. An estimated NOAEL of 1.7 mL L -1 and LOAEL of 3.5 mL L -1 were estimated for earthworms exposed to the assessed effluent. Extremely high-risk quotients (RQ ≥ 1) were estimated based on leachate application in irrigation. Thus, adequate municipal solid waste management is paramount, especially with regard to generated by-products, which can result in high toxicological risks for terrestrial organisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Triclocarban (TCC) is a contaminant of emerging concern widely applied as an antimicrobial in personal care products and introduced into the terrestrial environment through the application of biosolids (i.e., treated sewage sludge) in agriculture. Displaying the potential to bioaccumulate in the food chain and a high half-life in the soil, the presence of this compound in the environment may lead to potential ecological risks. In this context, TCC toxicity assessments in Eisenia andrei earthworms were carried out through acute, avoidance and chronic tests following cytotoxicity, antioxidant system, i.e. acatalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), lipid peroxidation (LPO), and DNA damage (comet assay) evaluations. An LC 50 of 3.3 ± 1.6 mg cm -2 in the acute contact test and an EC 50 of 1.92 ± 0.31 mg kg -1 in the avoidance test during 72 h and 48 h, respectively, were obtained. The behavioral test indicates earthworm avoidance from 15.0 mg kg -1 of TCC. During chronic soil exposure, a 44% reduction in earthworm cell viability was observed after 14 days of exposure to 10 mg kg -1 TCC, while an increase in the percentage of amoebocyte cells also ocurred. Chronic exposure to TCC led to reduced CAT and GST activities, decreased GSH levels and increased LPO in exposed organisms. DNA damage was observed after 45 days from a 1 mg kg -1 dose of TCC. Therefore, TCC exhibits toxicological potential to Eisenia andrei earthworms, mainly during long-term exposures. This study provides mechanistic earthworm information towards understanding the environmental and human health implications of TCC exposure and draws attention to correct biosolid management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The first-line chemotherapy treatment for Glioblastoma (GBM) - the most aggressive and frequent brain tumor - is temozolomide (TMZ). The Sonic hedgehog (SHH) pathway is involved with GBM tumorigenesis and TMZ chemoresistance. The role of SHH pathway inhibition in the potentiation of TMZ's effects using T98G, U251, and GBM11 cell lines is investigated herein. The combination of GANT-61 and TMZ over 72 hr suggested a synergistic effect. All TMZ-resistant cell lines displayed a significant decrease in cell viability, increased DNA fragmentation and loss of membrane integrity. For T98G cells, G 2 /M arrest was observed, while U251 cells presented a significant increase in reactive oxygen species production and catalase activity. All the cell lines presented acidic vesicles formation correlated to Beclin-1 overexpression. The combined treatment also enhanced GLI1 expression, indicating the presence of select resistant cells. The selective inhibition of the SHH pathway potentiated the cytotoxic effect of TMZ, thus becoming a promising in vitro strategy for GBM treatment., (© 2019 Wiley Periodicals, Inc.)