Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity.

PubMed

Li, Yinbao; Yang, Fan; Chen, Zuanguang; Shi, Lijuan; Zhang, Beibei; Pan, Jianbin; Li, Xinchun; Sun, Duanping; Yang, Hongzhi

2014-01-01

Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

Molecular toxicity of triclosan and carbamazepine to green algae Chlorococcum sp.: A single cell view using synchrotron-based Fourier transform infrared spectromicroscopy.

PubMed

Xin, Xiaying; Huang, Guohe; Liu, Xia; An, Chunjiang; Yao, Yao; Weger, Harold; Zhang, Peng; Chen, Xiujuan

2017-07-01

Although pharmaceuticals and personal care products have been used and introduced into the environment in large quantities, little information on potential ecological risks is currently available considering their effects on living organisms. We verified the feasibility of using synchrotron-based Fourier Transform Infrared (SR-FTIR) spectromicroscopy to explore in vivo toxic effects on single living Chlorococcum sp. cells. The study provided important information to achieve a better understanding of the toxic mechanism of triclosan and carbamazepine on living algae Chlorococcum sp.. Triclosan and carbamazepine had distinctive toxic effects on unicellular living algae. Most strikingly, triclosan had more dramatic toxic effects on biochemical components than carbamazepine. Triclosan can affect algae primarily by inhibiting fatty acid synthesis and causing protein aggregation. The toxicity response was irreversible at higher concentration (100.000 μM), but attenuated at lower concentration (0.391 μM) as time extended. Carbamazepine can produce hydrophobic interactions to affect the phospholipid bilayer and work on specific proteins to disfunction the cell membrane. Carbamazepine-exposed cells developed a resistance while extending exposure time. This is the first demonstration from an ecological standpoint that SR-FTIR can provide an innovative approach to reveal the toxicity of emerging pollutants in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of salinity, pH and temperature on the re-establishment of bioluminescence and copper or SDS toxicity in the marine dinoflagellate Pyrocystis lunula using bioluminescence as an endpoint

USGS Publications Warehouse

Craig, J.M.; Klerks, P.L.; Heimann, K.; Waits, J.L.

2003-01-01

Pyrocystis lunula is a unicellular, marine, photoautotrophic, bioluminescent dinoflagellate. This organism is used in the Lumitox ?? bioassay with inhibition of bioluminescence re-establishment as the endpoint. Experiments determined if acute changes in pH, salinity, or temperature had an effect on the organisms' ability to re-establish bioluminescence, or on the bioassay's potential to detect sodium dodecyl sulfate (SDS) and copper toxicity. The re-establishment of bioluminescence itself was not very sensitive to changes in pH within the pH 6-10 range, though reducing pH from 8 to levels below 6 decreased this capacity. Increasing the pH had little effect on Cu or SDS toxicity, but decreasing the pH below 7 virtually eliminated the toxicity of either compound in the bioassay. Lowering the salinity from 33 to 27??? or less resulted in a substantial decrease in re-establishment of bioluminescence, while increasing the salinity to 43 or 48 ??? resulted in a small decline. Salinity had little influence on the bioassay's quantification of Cu toxicity, while the data showed a weak negative relationship between SDS toxicity and salinity. Re-establishment of bioluminescence showed a direct dependence on temperature, but only at 10??C did temperature have an obvious effect on the toxicity of Cu in this bioassay. ?? 2003 Elsevier Science Ltd. All rights reserved.

The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

PubMed

Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

2014-01-01

Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. Published by Elsevier B.V.

Removal of the precursors of N-nitrosodiethylamine (NDEA), an emerging disinfection byproduct, in drinking water treatment process and its toxicity to adult zebrafish (Danio rerio).

PubMed

Zheng, Jian; Lin, Tao; Chen, Wei

2018-01-01

N-nitrosodiethylamine (NDEA) is one of the emerging nitrogenous disinfection byproducts with probable cytotoxicity, genotoxicity, and carcinogenesis. Its potential toxicological effects have received extensive attention but remain to be poorly understood. In this study, changes in NDEA precursors in drinking water treatment process were studied using the trial of its formation potential (FP), and the toxicity induced by NDEA to adult zebrafish was investigated. NDEA FP in the raw water of Taihu Lake ranged from 46.9 to 68.3 ng/L. The NDEA precursors were removed effectively by O 3 /BAC process. Hydrophilic fraction and low-molecular-weight fraction (<1 kDa) had the highest NDEA FP. The toxicity results demonstrated that the acute lethal concentration of NDEA causing 50% mortality in 96 h (96-h LC50) was 210.4 mg/L, and NDEA was more likely to be accumulated in kidney, followed by liver and gill. NDEA induced oxidative stress and antioxidant defense to zebrafish metabolism system at concentrations over 5 μg/L. After a 42-day exposure, a significant DNA damage was observed in zebrafish liver cells at NDEA concentrations beyond 500 μg/L. This study investigated NDEA properties in both engineering prospective and toxicity evaluation, thus providing comprehensive information on its control in drinking water treatment process and its toxicity effect on zebrafish as a model animal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos.

PubMed

Wang, Wen-Der; Chen, Guan-Ting; Hsu, Hwei-Jan; Wu, Chang-Yi

2015-02-01

Paclobutrazol (PBZ), a trazole-containing fungicide and plant growth retardant, has been widely used for over 30 years to regulate plant growth and promote early fruit setting. Long-term usage of PBZ in agriculture and natural environments has resulted in residual PBZ in the soil and water. Chronic exposure to waterborne PBZ can cause various physiological effects in fish, including hepatic steatosis, antioxidant activity, and disruption of spermatogenesis. We have previously shown that PBZ also affects the rates of zebrafish embryonic survival and hatching, and causes developmental failure of the head skeleton and eyes; here, we further show that PBZ has embryonic toxic effects on digestive organs of zebrafish, and describe the underlying mechanisms. PBZ treatment of embryos resulted in dose-dependent morphological and functional abnormalities of the digestive organs. Real-time RT-PCR and in situ hybridization were used to show that PBZ strongly induces cyp1a1 expression in the digestive system, and slightly induces ahr2 expression in zebrafish embryos. Knockdown of ahr2 with morpholino oligonucleotides prevents PBZ toxicity. Thus, the toxic effect of PBZ on digestive organs is mediated by AhR2, as was previously reported for retene and TCDD. These findings have implications for understanding the potential toxicity of PBZ during embryogenesis, and thus the potential impact of fungicides on public health and the environment. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel bioassay using the barnacle Amphibalanus amphitrite to evaluate chronic effects of aluminium, gallium and molybdenum in tropical marine receiving environments.

PubMed

van Dam, Joost W; Trenfield, Melanie A; Harries, Simon J; Streten, Claire; Harford, Andrew J; Parry, David; van Dam, Rick A

2016-11-15

A need exists for appropriate tools to evaluate risk and monitor potential effects of contaminants in tropical marine environments, as currently impact assessments are conducted by non-representative approaches. Here, a novel bioassay is presented that allows for the estimation of the chronic toxicity of contaminants in receiving tropical marine environments. The bioassay is conducted using planktonic larvae of the barnacle Amphibalanus amphitrite and is targeted at generating environmentally relevant, chronic toxicity data for water quality guideline derivation or compliance testing. The developmental endpoint demonstrated a consistently high control performance, validated through the use of copper as a reference toxicant. In addition, the biological effects of aluminium, gallium and molybdenum were assessed. The endpoint expressed high sensitivity to copper and moderate sensitivity to aluminium, whereas gallium and molybdenum exhibited no discernible effects, even at high concentrations, providing valuable information on the toxicity of these elements in tropical marine waters. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

PubMed

Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

2014-09-01

Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

Teratogenicity of Ochratoxin A and the Degradation Product, Ochratoxin α, in the Zebrafish (Danio rerio) Embryo Model of Vertebrate Development

PubMed Central

Haq, Mehreen; Gonzalez, Nelson; Mintz, Keenan; Jaja-Chimedza, Asha; De Jesus, Christopher Lawrence; Lydon, Christina; Welch, Aaron Z.; Berry, John P.

2016-01-01

Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis of OTA to ochratoxin α (OTα) and phenylalanine is the presumptive product of degradation in most cases. In the current study, we employed the zebrafish (Danio rerio) embryo, as a model of vertebrate development to evaluate, the teratogenicity of OTA and OTα. These studies show that OTA is potently active in the zebrafish embryo toxicity assay (ZETA), and that toxicity is both concentration- and time-dependent with discernible and quantifiable developmental toxicity observed at nanomolar concentrations. On the other hand, OTα had no significant effect on embryo development at all concentrations tested supporting a decreased toxicity of this degradation product. Taken together, these results suggest that ZETA is a useful, and highly sensitive, tool for evaluating OTA toxicity, as well as its degradation products, toward development of effective detoxification strategies. Specifically, the results obtained with ZETA, in the present study, further demonstrate the toxicity of OTA, and support its degradation via hydrolysis to OTα as an effective means of detoxification. PMID:26861395

Teratogenicity of Ochratoxin A and the Degradation Product, Ochratoxin α, in the Zebrafish (Danio rerio) Embryo Model of Vertebrate Development.

PubMed

Haq, Mehreen; Gonzalez, Nelson; Mintz, Keenan; Jaja-Chimedza, Asha; De Jesus, Christopher Lawrence; Lydon, Christina; Welch, Aaron; Berry, John P

2016-02-05

Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis of OTA to ochratoxin α (OTα) and phenylalanine is the presumptive product of degradation in most cases. In the current study, we employed the zebrafish (Danio rerio) embryo, as a model of vertebrate development to evaluate, the teratogenicity of OTA and OTα. These studies show that OTA is potently active in the zebrafish embryo toxicity assay (ZETA), and that toxicity is both concentration- and time-dependent with discernible and quantifiable developmental toxicity observed at nanomolar concentrations. On the other hand, OTα had no significant effect on embryo development at all concentrations tested supporting a decreased toxicity of this degradation product. Taken together, these results suggest that ZETA is a useful, and highly sensitive, tool for evaluating OTA toxicity, as well as its degradation products, toward development of effective detoxification strategies. Specifically, the results obtained with ZETA, in the present study, further demonstrate the toxicity of OTA, and support its degradation via hydrolysis to OTα as an effective means of detoxification.

Coenzyme Q{sub 10} and alpha-tocopherol protect against amitriptyline toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordero, Mario D.; Dpto. Citologia e Histologia Normal y Patologica, Facultad de Medicina. Universidad de Sevilla. 41009 Sevilla; Moreno-Fernandez, Ana Maria

Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q{sub 10} and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q{sub 10},more » decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q{sub 10} and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity.« less

77 FR 47768 - Protection of Stratospheric Ozone: Determination 27 for Significant New Alternatives Policy Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

.... Toxicity and exposure data: Potential health effects of this substitute include respiratory tract... irritation. Ingestion of C7 Fluoroketone is not expected to cause health effects, and there is no anticipated... limit and address potential health risks by following requirements and recommendations in the MSDS and...

Health effects research in direct coal liquefaction. Studies of H-coal distillates: Phase I. PDU samples - the effects of hydrotreatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epler, J.L.; Fry, R.J.M.; Larimer, F.W.

1981-11-01

A multi-divisional effort aimed at the integrated assessment of the health and environmental effects of various coal conversion and shale oil technologies is being carried out. The feasibility of using health effects bioassays to predict the potential biohazard of various H-Coal derived test materials is examined in a coupled chemical and biological approach. The primary focus of the research is the use of preliminary chemical characterizations and preparation for bioassay, followed by testing in short-term assays in order to rapidly ascertain the potential biohazard. Mammalian toxicological assays parallel the testing. Raw and hydrotreated product liquids from process development units ofmore » H-Coal and the pilot plant solvent refined coal process were examined for acute toxicity monitored as population growth impairment of Tetrahymena exposed to aqueous extracts and for mutagenic activity monitored as revertants of Salmonella exposed to metabolically activated chemical class fractions. Medium to high severity hydrotreatment appears to be an effective means of reducing biological activity, presumably by reducing the aromaticity and heteroatom content. Five basic mammalian, acute toxicity tests have been conducted with selected H-coal samples and shale oil derivatives. The data show that H-Coal samples are moderately toxic whereas the toxicity of shale oil derived products is slight and comparable to samples obtained from naturally occurring petroleums. No overt skin or eye toxicity was found. The present data reveal that coal-derived distillates generated by the H-coal process are highly carcinogenic to mouse skin. An extreme form of neurotoxicity associated with dermal exposure to one of the lighter, minimally carcinogenic, materials was noted. (DMC)« less

Toxicity of atmospheric aerosols on marine phytoplankton

USGS Publications Warehouse

Paytan, A.; Mackey, K.R.M.; Chen, Y.; Lima, I.D.; Doney, S.C.; Mahowald, N.; Labiosa, R.; Post, A.F.

2009-01-01

Atmospheric aerosol deposition is an important source of nutrients and trace metals to the open ocean that can enhance ocean productivity and carbon sequestration and thus influence atmospheric carbon dioxide concentrations and climate. Using aerosol samples from different back trajectories in incubation experiments with natural communities, we demonstrate that the response of phytoplankton growth to aerosol additions depends on specific components in aerosols and differs across phytoplankton species. Aerosol additions enhanced growth by releasing nitrogen and phosphorus, but not all aerosols stimulated growth. Toxic effects were observed with some aerosols, where the toxicity affected picoeukaryotes and Synechococcus but not Prochlorococcus.We suggest that the toxicity could be due to high copper concentrations in these aerosols and support this by laboratory copper toxicity tests preformed with Synechococcus cultures. However, it is possible that other elements present in the aerosols or unknown synergistic effects between these elements could have also contributed to the toxic effect. Anthropogenic emissions are increasing atmospheric copper deposition sharply, and based on coupled atmosphere-ocean calculations, we show that this deposition can potentially alter patterns of marine primary production and community structure in high aerosol, low chlorophyll areas, particularly in the Bay of Bengal and downwind of South and East Asia.

The use of high-throughput screening techniques to evaluate mitochondrial toxicity.

PubMed

Wills, Lauren P

2017-11-01

Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity. Mitochondrial toxicants are compounds that cause a decrease in the number of mitochondria within a cell, and/or decrease the ability of mitochondria to perform normal functions including producing adenosine triphosphate (ATP) and maintaining cellular homeostasis. Mitochondrial dysfunction can lead to apoptosis, necrosis, altered metabolism, muscle weakness, neurodegeneration, decreased organ function, and eventually disease or death of the whole organism. The development of HTS techniques to identify mitochondrial toxicants will provide extensive databases with essential connections between mechanistic mitochondrial toxicity and chemical structure. Computational and bioinformatics approaches can be used to evaluate compound databases for specific chemical structures associated with toxicity, with the goal of developing quantitative structure-activity relationship (QSAR) models and mitochondrial toxicophores. Ultimately these predictive models will facilitate the identification of mitochondrial liabilities in consumer products, industrial compounds, pharmaceuticals and environmental hazards. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

PubMed

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (p<0.05); and neonates' heart rate decreased 72.7% (p<0.05). In the chronic toxicity test, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY ...

EPA Pesticide Factsheets

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the “activity” portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical “properties” to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical stru

Protection against neo-formed contaminants (NFCs)-induced toxicity by phytochemicals.

PubMed

Zhao, Mengyao; Wang, Pengpu; Li, Daotong; Shang, Jin; Hu, Xiaosong; Chen, Fang

2017-10-01

Neo-formed compounds (NFCs) are commonly found in all kinds of foods due to the complex reaction between components during processing. Acrylamide, benzo(a)pyrene and heterocyclic aromatic amines are the main types of NFCs in foods enriched with carbohydrate, fats and proteins, respectively. They have exhibited diverse toxicity, such as neurotoxicity, genotoxicity, potentially carcinogenic and reproductive toxicity. In recent years, various phytochemicals have been found to be effective in alleviation of their related toxicities both in vitro and in vivo. This review provides evidences on the protection roles of phytochemicals against the diverse toxicity induced by three NFCs. Moreover, the prevention mechanisms of phytochemicals are summarized. Three potential aspects involving excellent antioxidant activity, DNA protection and enzyme induction contribute to the successful protection mechanism. Meanwhile, the limitations from existing knowledge have been illustrated and the possible perspectives for the further study have also been considered. The information from this review would be useful to provide an easier and better way to improve human health when considering the possibility of using foods enriched with phytochemicals for prevention of the toxicity of exogenous pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanoparticles Made From Xyloglucan-Block-Polycaprolactone Copolymers: Safety Assessment for Drug Delivery.

PubMed

Mazzarino, Letícia; Loch-Neckel, Gecioni; Dos Santos Bubniak, Lorena; Ourique, Fabiana; Otsuka, Issei; Halila, Sami; Curi Pedrosa, Rozangela; Santos-Silva, Maria Cláudia; Lemos-Senna, Elenara; Curti Muniz, Edvani; Borsali, Redouane

2015-09-01

Xyloglucan-block-polycaprolactone (XGO-PCL) copolymer nanoparticles have been proposed as nanocarriers for drug delivery. However, the possible harmful effects of exposure to nanoparticles still remain a concern. Therefore, the aim of this study is to evaluate the potential toxicity of XGO-PCL nanoparticles using in vitro and in vivo assays. Cytotoxicity and genotoxicity studies were conducted on MRC-5 human fetal lung fibroblast cells upon exposure to XGO-PCL nanoparticles. No significant reduction in the cell viability and no DNA damage were observed at the different concentrations tested. Erythrocyte toxicity was assessed by the incubation of nanoparticles with human blood. XGO-PCL nanoparticles induced a hemolytic ratio of less than 1%, indicating good blood compatibility. Finally, the subacute toxicity of XGO-PCL nanoparticles (10 mg/kg/day) was evaluated in BALB/c mice when administered orally or intraperitoneally for 14 days. Results of the in vivo toxicity study showed no clinical signs of toxicity, mortality, weight loss, or hematological and biochemical alterations after treatment with nanoparticles. Also, microscopic analysis of the major organs revealed no histopathological abnormalities, corroborating the previous results. Thus, it can be concluded that XGO-PCL nanoparticles induced no effect indicative of toxicity, indicating their potential use as drug delivery systems. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental Toxicity of Nanoparticles on the Brain.

PubMed

Umezawa, Masakazu; Onoda, Atsuto; Takeda, Ken

2017-01-01

The toxicity of nanoparticles (nanotoxicology) is being investigated to understand both the health impacts of atmospheric ultrafine particles-the size of which is a fraction (<0.1 μm aerodynamic diameter) of that of PM 2.5 (<2.5 μm diameter)-and the safer use of engineered nanomaterials. Developmental toxicity of nanoparticles has been studied since their transfer from pregnant body to fetal circulation and offspring body was first reported. Here we reviewed the developmental toxicity of nanoparticles on the brain, one of the most important organs in maintenance of mental health and high quality of life. Recently the dose- and size-dependency of transplacental nanoparticle transfer to the fetus was reported. It is important to understand both the mechanism of direct effect of nanoparticles transferred to the fetus and offspring and the indirect effect mediated by induction of oxidative stress and inflammation in the pregnant body. Locomotor activity, learning and memory, motor coordination, and social behavior were reported as potential neurobehavioral targets of maternal nanoparticle exposure. Histopathologically, brain perivascular cells, including perivascular macrophages and surrounding astrocytes, have an important role in waste clearance from the brain parenchyma. They are potentially the most sensitive target of maternal exposure to low-dose nanoparticles. Further investigations will show the detailed mechanism of developmental toxicity of nanoparticles and preventive strategies against intended and unintended nanoparticle exposure. This knowledge will contribute to the safer design of nanoparticles through the development of sensitive and quantitative endpoints for prediction of their developmental toxicity.

Nanomedicinal products: a survey on specific toxicity and side effects

PubMed Central

Giannakou, Christina; De Jong, Wim H; Kooi, Myrna W; Park, Margriet VDZ; Vandebriel, Rob J; Bosselaers, Irene EM; Scholl, Joep HG; Geertsma, Robert E

2017-01-01

Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention. PMID:28883724

Sediment contamination of residential streams in the metropolitan kansas city area, USA: Part II. whole-sediment toxicity to the amphipod hyalella azteca

USGS Publications Warehouse

Tao, J.; Ingersoll, C.G.; Kemble, N.E.; Dias, J.R.; Murowchick, J.B.; Welker, G.; Huggins, D.

2010-01-01

This is the second part of a study that evaluates the influence of nonpoint sources on the sediment quality of five adjacent streams within the metropolitan Kansas City area, central United States. Physical, chemical, and toxicity data (Hyalella azteca 28-day whole-sediment toxicity test) for 29 samples collected in 2003 were used for this evaluation, and the potential causes for the toxic effects were explored. The sediments exhibited a low to moderate toxicity, with five samples identified as toxic to H. azteca. Metals did not likely cause the toxicity based on low concentrations of metals in the pore water and elevated concentrations of acid volatile sulfide in the sediments. Although individual polycyclic aromatic hydrocarbons (PAHs) frequently exceeded effect-based sediment quality guidelines [probable effect concentrations (PECs)], only four of the samples had a PEC quotient (PEC-Q) for total PAHs over 1.0 and only one of these four samples was identified as toxic. For the mean PEC-Q for organochlorine compounds (chlordane, dieldrin, sum DDEs), 4 of the 12 samples with a mean PEC-Q above 1.0 were toxic and 4 of the 8 samples with a mean PEC-Q above 3.0 were toxic. Additionally, four of eight samples were toxic, with a mean PEC-Q above 1.0 based on metals, PAHs, polychlorinated biphenyls (PCBs), and organochlorine pesticides. The increase in the incidence of toxicity with the increase in the mean PEC-Q based on organochlorine pesticides or based on metals, PAHs, PCBs, and organochlorine pesticides suggests that organochlorine pesticides might have contributed to the observed toxicity and that the use of a mean PEC-Q, rather than PEC-Qs for individual compounds, might be more informative in predicting toxic effects. Our study shows that stream sediments subject to predominant nonpoint sources contamination can be toxic and that many factors, including analysis of a full suite of PAHs and pesticides of both past and present urban applications and the origins of these organic compounds, are important to identify the causes of toxicity. ?? 2010 Springer Science+Business Media, LLC.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation Dose-Volume Effects in the Stomach and Small Bowel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kavanagh, Brian D., E-mail: Brian.Kavanagh@ucdenver.ed; Pan, Charlie C.; Dawson, Laura A.

2010-03-01

Published data suggest that the risk of moderately severe (>=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely relatedmore » to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.« less

Using zebrafish in systems toxicology for developmental toxicity testing.

PubMed

Nishimura, Yuhei; Inoue, Atsuto; Sasagawa, Shota; Koiwa, Junko; Kawaguchi, Koki; Kawase, Reiko; Maruyama, Toru; Kim, Soonih; Tanaka, Toshio

2016-01-01

With the high cost and the long-term assessment of developmental toxicity testing in mammals, the vertebrate zebrafish has become a useful alternative model organism for high-throughput developmental toxicity testing. Zebrafish is also very favorable for the 3R perspective in toxicology; however, the methodologies used by research groups vary greatly, posing considerable challenges to integrative analysis. In this review, we discuss zebrafish developmental toxicity testing, focusing on the methods of chemical exposure, the assessment of morphological abnormalities, housing conditions and their effects on the production of healthy embryos, and future directions. Zebrafish as a systems toxicology model has the potential to elucidate developmental toxicity pathways, and to provide a sound basis for human health risk assessments. © 2015 Japanese Teratology Society.

Lipid Emulsion in Treatment of Local Anesthetic Toxicity.

PubMed

Collins, Shawn; Neubrander, Judy; Vorst, Zachary; Sheffield, Brad

2015-08-01

Epidural, spinal, regional, local, and intravenous administration of local anesthetics (LAs) is a cornerstone of anesthetic practice. LA toxicity is a grave consequence that is of great significance to anesthesia providers. Outcomes of LA toxicity range from inconvenient symptoms such as tinnitus, twitching, and hypotension to seizures; cardiovascular or respiratory collapse; and death. Lipid emulsion has emerged as a potential "magic bullet" in treating LA toxicity. This literature review provides background information and proposed mechanisms of action for LAs and lipid emulsion as well as animal experiments and a case report that speak to the effectiveness of lipid emulsion in the face of LA toxicity. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Pesticide Toxicity Index: a tool for assessing potential toxicity of pesticide mixtures to freshwater aquatic organisms

USGS Publications Warehouse

Nowell, Lisa H.; Norman, Julia E.; Moran, Patrick W.; Martin, Jeffrey D.; Stone, Wesley W.

2014-01-01

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤ 50% of controls in 44% of samples with Median-PTI values of 0.1–1, and to 0% in 96% of samples with Median-PTI values > 1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

The influence of salinity on copper accumulation and its toxic effects in estuarine animals with differing osmoregulatory strategies.

PubMed

Lee, Jacqueline A; Marsden, Islay D; Glover, Chris N

2010-08-01

Copper is an important ionoregulatory toxicant in freshwater, but its effects in marine and brackish water systems are less well characterised. The effect of salinity on short-term copper accumulation and sublethal toxicity in two estuarine animals was investigated. The osmoregulating crab Hemigrapsus crenulatus accumulated copper in a concentration-dependent, but salinity-independent manner. Branchial copper accumulation correlated positively with branchial sodium accumulation. Sublethal effects of copper were most prevalent in 125% seawater, with a significant increase in haemolymph chloride noted after 96h at exposure levels of 510 microg Cu(II) L(-1). The osmoconforming gastropod, Scutus breviculus, was highly sensitive to copper exposure, a characteristic recognised previously in related species. Toxicity, as determined by a behavioural index, was present at all salinities and was positively correlated with branchial copper accumulation. At 100% seawater, increased branchial sodium accumulation, decreased haemolymph chloride and decreased haemolymph osmolarity were observed after 48h exposure to 221 microg Cu(II) L(-1), suggesting a mechanism of toxicity related to ionoregulation. However, these effects were likely secondary to a general effect on gill barrier function, and possibly mediated by mucus secretion. Significant impacts of copper on haemocyanin were also noted in both animals, highlighting a potentially novel mechanism of copper toxicity to animals utilising this respiratory pigment. Overall these findings indicate that physiology, as opposed to water chemistry, exerts the greatest influence over copper toxicity. An understanding of the physiological limits of marine and estuarine organisms may be critical for calibration of predictive models of metal toxicity in waters of high and fluctuating salinities. Copyright 2010 Elsevier B.V. All rights reserved.

The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma

NASA Astrophysics Data System (ADS)

Dhulekar, Jhilmil

Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the individual effect on cell toxicity of each drug and in combination. Finally, nanoparticles were loaded with the non-toxic drug and delivered with free temozolomide to determine the overall efficacy of the drugs in reducing neuroblastoma cell viability.

Assessment of environmental risks from toxic and nontoxic stressors; a proposed concept for a risk-based management tool for offshore drilling discharges.

PubMed

Smit, Mathijs G D; Jak, Robbert G; Rye, Henrik; Frost, Tone Karin; Singsaas, Ivar; Karman, Chris C

2008-04-01

In order to improve the ecological status of aquatic systems, both toxic (e.g., chemical) and nontoxic stressors (e.g., suspended particles) should be evaluated. This paper describes an approach to environmental risk assessment of drilling discharges to the sea. These discharges might lead to concentrations of toxic compounds and suspended clay particles in the water compartment and concentrations of toxic compounds, burial of biota, change in sediment structure, and oxygen depletion in marine sediments. The main challenges were to apply existing protocols for environmental risk assessment to nontoxic stressors and to combine risks arising from exposure to these stressors with risk from chemical exposure. The defined approach is based on species sensitivity distributions (SSDs). In addition, precautionary principles from the EU-Technical Guidance Document were incorporated to assure that the method is acceptable in a regulatory context. For all stressors a protocol was defined to construct an SSD for no observed effect concentrations (or levels; NOEC(L)-SSD) to allow for the calculation of the potentially affected fraction of species from predicted exposures. Depending on the availability of data, a NOEC-SSD for toxicants can either be directly based on available NOECs or constructed from the predicted no effect concentration and the variation in sensitivity among species. For nontoxic stressors a NOEL-SSD can be extrapolated from an SSD based on effect or field data. Potentially affected fractions of species at predicted exposures are combined into an overall risk estimate. The developed approach facilitates environmental management of drilling discharges and can be applied to define risk-mitigating measures for both toxic and nontoxic stress.

Endo-cannabinoids system and the toxicity of cannabinoids with a biotechnological approach

PubMed Central

Niaz, Kamal; Khan, Fazlullah; Maqbool, Faheem; Momtaz, Saeideh; Ismail Hassan, Fatima; Nobakht-Haghighi, Navid; Rahimifard, Mahban; Abdollahi, Mohammad

2017-01-01

Cannabinoids have shown diverse and critical effects on the body systems, which alter the physiological functions. Synthetic cannabinoids are comparatively innovative misuse drugs with respect to their nature of synthesis. Synthetic cannabinoids therapy in healthy, chain smokers, and alcoholic individuals cause damage to the immune and nervous system, eventually leading to intoxication throughout the body. Relevant studies were retrieved using major electronic databases such as PubMed, EMBASE, Medline, Scopus, and Google Scholar. The extensive use of Cannabis Sativa L. (C. Sativa) and its derivatives/analogues such as the nonpsychoactive dimethyl heptyl homolog (CBG-DMH), and tetrahydrocannabivarin (THCV) amongst juveniles and adults have been enhanced in recent years. Cannabinoids play a crucial role in the induction of respiratory, reproductive, immune and carcinogenic effects; however, potential data about mutagenic and developmental effects are still insufficient. The possible toxicity associated with the prolong use of cannabinoids acts as a tumor promoter in animal models and humans. Particular synthetic cannabinoids and analogues have low affinity for CB1 or CB2 receptors, while some synthetic members like Δ9-THC have high affinity towards these receptors. Cannabinoids and their derivatives have a direct or indirect association with acute and long-term toxicity. To reduce/attenuate cannabinoids toxicity, pharmaceutical biotechnology and cloning methods have opened a new window to develop cannabinoids encoding the gene tetrahydrocannabinolic acid (THCA) synthase. Plant revolution and regeneration hindered genetic engineering in C. Sativa. The genetic culture suspension of C. Sativa can be transmuted by the use of Agrobacterium tumefaciens to overcome its toxicity. The main aim of the present review was to collect evidence of the endo-cannabinoid system (ECS), cannabinoids toxicity, and the potential biotechnological approach of cannabinoids synthesis. PMID:28827985

Enhancing the fathead minnow fish embryo toxicity test: Optimizing embryo production and assessing the utility of additional test endpoints.

PubMed

Roush, Kyle S; Krzykwa, Julie C; Malmquist, Jacob A; Stephens, Dane A; Sellin Jeffries, Marlo K

2018-05-30

The fathead minnow fish embryo toxicity (FET) test has been identified as a potential alternative to toxicity test methods that utilize older fish. However, several challenges have been identified with the fathead minnow FET test, including: 1) difficulties in obtaining appropriately-staged embryos for FET test initiation, 2) a paucity of data comparing fathead minnow FET test performance to the fathead minnow larval growth and survival (LGS) test and 3) a lack of sublethal endpoints that could be used to estimate chronic toxicity and/or predict adverse effects. These challenges were addressed through three study objectives. The first objective was to optimize embryo production by assessing the effect of breeding group composition (number of males and females) on egg production. Results showed that groups containing one male and four females produced the largest clutches, enhancing the likelihood of procuring sufficient numbers of embryos for FET test initiation. The second study objective was to compare the performance of the FET test to that of the fathead minnow LGS test using three reference toxicants. The FET and LGS tests were similar in their ability to predict the acute toxicity of sodium chloride and ethanol, but the FET test was found to be more sensitive than the LGS test for sodium dodecyl sulfate. The last objective of the study was to evaluate the utility and practicality of several sublethal metrics (i.e., growth, developmental abnormalities and growth- and stress-related gene expression) as FET test endpoints. Developmental abnormalities, including pericardial edema and hatch success, were found to offer the most promise as additional FET test endpoints, given their responsiveness, potential for predicting adverse effects, ease of assessment and low cost of measurement. Copyright © 2018 Elsevier Inc. All rights reserved.

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells.

PubMed

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L'azou, Béatrice

2012-09-28

Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO(2) of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO(2). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Environmental mixtures of nanomaterials and chemicals: The Trojan-horse phenomenon and its relevance for ecotoxicity.

PubMed

Naasz, Steffi; Altenburger, Rolf; Kühnel, Dana

2018-04-22

The usage of engineered nanomaterials (NM) offers many novel products and applications with advanced features, but at the same time raises concerns with regard to potential adverse biological effects. Upon release and emission, NM may interact with chemicals in the environment, potentially leading to a co-exposure of organisms and the occurrence of mixture effects. A prominent idea is that NM may act as carriers of chemicals, facilitating and enhancing the entry of substances into cells or organisms, subsequently leading to an increased toxicity. In the literature, the term 'Trojan-horse effect' describes this hypothesis. The relevance of this mechanism for organisms is, however, unclear as yet. Here, a review has been performed to provide a more systematic picture on existing evidence. It includes 151 experimental studies investigating the exposure of various NM and chemical mixtures in ecotoxicological in vitro and in vivo model systems. The papers retrieved comprised studies investigating (i) uptake, (ii) toxicity and (iii) investigations considering both, changes in substance uptake and toxicity upon joint exposure of a chemical with an NM. A closer inspection of the studies demonstrated that the existing evidence for interference of NM-chemical mixture exposure with uptake and toxicity points into different directions compared to the original Trojan-horse hypothesis. We could discriminate at least 7 different categories to capture the evidence ranging from no changes in uptake and toxicity to an increase in uptake and toxicity upon mixture exposure. Concluding recommendations for the consideration of relevant processes are given, including a proposal for a nomenclature to describe NM-chemical mixture interactions in consistent terms. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures of polycyclic aromatic hydrocarbons in zebrafish.

PubMed

Willis, Alison M; Oris, James T

2014-09-01

The present study examined photo-induced toxicity and toxicokinetics for acute exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo-enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of magnitude below effects observed in the absence of UV. Because environmental exposure to PAHs is usually in the form of complex mixtures, the present study examined the photo-induced toxicity of both single compounds and mixtures of PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene, carbazole, and phenanthrene) to examine the hypothesis that phototoxic (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways of mixtures could be predicted from single exposures. Anthracene and pyrene were phototoxic as predicted; however, carbazole exhibited moderate photo-induced toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of each chemical alone was used to compare the toxicity of mixtures in binary, tertiary, and quaternary combinations of these PAHs, and a predictive model for environmental mixtures was generated. The results indicated that the acute toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the magnitude of photo-enhancement. Based on PAH concentrations found in water and circumstances of high UV dose to aquatic systems, there exists potential risk of photo-induced toxicity to aquatic organisms. © 2014 SETAC.

Evaluation of toxic and genotoxic potential of a wet gas scrubber effluent obtained from wooden-based biomass furnaces: A case study in the red ceramic industry in southern Brazil.

PubMed

Bortolotto, Tiago; da Silva, Jaqueline; Sant'Ana, Alex Célio; Tomazi, Kamila Osowski; Geremias, Reginaldo; Angioletto, Elídio; Pich, Claus Tröger

2017-09-01

Red ceramic industry in southern Brazil commonly uses wood biomass as furnace fuel generating great amounts of gas emissions and ash. To avoid their impact on atmospheric environment, wet scrubbing is currently being applied in several plants. However, the water leachate formed could be potentially toxic and not managed as a common water-based effluent, since the resulting wastewater could carry many toxic compounds derived from wood pyrolysis. There is a lack of studies regarding this kind of effluent obtained specifically and strictly from wooden-based biomass furnaces. Therefore, we conducted an evaluation of toxic and genotoxic potentials of this particular type of wet gas scrubber effluent. Physical-chemical analysis showed high contents of several contaminants, including phenols, sulphates and ammoniacal nitrogen, as well as the total and suspended solids. The effluent cause significant toxicity towards microcrustacean Artemia sp. (LC 50 = 34.4%) and Daphnia magna (Toxicity Factor = 6 on average) and to higher plants (Lactuca sativa L. and Allium cepa L.) with acute and sub-acute effects in several parameters. Besides, using plasmid DNA, significant damage was observed in concentrations 12.5% and higher. In cellular DNA, concentrations starting from 12.5% and 6.25% showed significant increase in Damage Index (DI) and Damage Frequency (DF), respectively. The results altogether suggest that the effluent components, such phenols, produced by wood combustion can be volatilized, water scrubbed, resulting in a toxic and genotoxic effluent which could contaminate the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Heavy Metals Toxicity and the Environment

PubMed Central

Tchounwou, Paul B; Yedjou, Clement G; Patlolla, Anita K; Sutton, Dwayne J

2013-01-01

Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity. PMID:22945569

Emerging photovoltaic technologies: Environmental and health issues update

NASA Astrophysics Data System (ADS)

Fthenakis, Vasilis M.; Moskowitz, Paul D.

1997-02-01

New photovoltaic (PV) technologies promise low-cost, reliable PV modules and have the potential for significant PV penetration into the energy market. These prospects for commercialization have attracted renewed interest in the advantageous environmental impact of using PV and also in the potential environmental, health and safety (EHS) burdens in PV manufacturing and decommissioning. In this paper, we highlight recent studies on EHS issues: a) An integrated energy-environmental-economic analysis which shows that large-scale use of PV can significantly contribute to alleviating the greenhouse effect; in the United States alone, it could displace 450 million tons of carbon emissions by the year 2030, b) Recycling of the spent modules and scarp is economically feasible; current research centers on improving the efficiency and economics of recycling CdTe and CIS modules, c) Toxicological studies conducted by the National Institute of Environmental Health Sciences (NIEHS) compared the acute toxicity of CdTe, CIS, and CGS; CdTe was the most toxic, and CGS the least toxic of the three. Additional studies are now comparing the systemic toxicity of these compounds with the toxicity of their precursors.

Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

PubMed

Kee, Kehkooi; Flores, Martha; Cedars, Marcelle I; Reijo Pera, Renee A

2010-09-01

Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells

PubMed Central

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David Lawson

2016-01-01

Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient’s treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research. PMID:27186409

Potential of chromium(III) picolinate for reproductive or developmental toxicity following exposure of male CD-1 mice prior to mating.

PubMed

McAdory, DeAna; Rhodes, Nicholas R; Briggins, Felicia; Bailey, Melissa M; Di Bona, Kristin R; Goodwin, Craig; Vincent, John B; Rasco, Jane F

2011-12-01

Chromium(III) picolinate, [Cr(pic)(3)], is a commonly used nutritional supplement in humans, which has also been approved for use in animals. Health concerns have arisen over the use of [Cr(pic)(3)]. At high [Cr(pic)(3)] doses, developmental toxicity tests in female mice have shown a higher litter incidence of split cervical arch in exposed fetuses, but this was not consistently reproducible. In the current study, male CD-1 mice were used to further assess the potential for reproductive or developmental toxicity. Four weeks prior to mating, the males were fed a diet providing 200 mg/kg/day [Cr(pic)(3)] for comparison with untreated controls. Females were not treated. Each male was mated with two females, which were sacrificed on gestation day 17, and their litters were examined for adverse effects. Mating and fertility indices were not significantly altered by treatment. Male exposure to [Cr(pic)(3)] also had no effect on prenatal mortality, fetal weight, or gross or skeletal morphology. These results suggest that paternal dietary exposure to chromium(III) picolinate has little potential for adverse reproductive effects, even at exposure levels considerably higher than expected human exposures from nutritional supplements (1 mg of Cr per day or less).

An occupational reproductive research agenda for the third millennium.

PubMed Central

Lawson, Christina C; Schnorr, Teresa M; Daston, George P; Grajewski, Barbara; Marcus, Michele; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D; Schrader, Steven M; Shelby, Michael

2003-01-01

There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care. Many other substances are suspected of producing reproductive or developmental toxicity but lack sufficient data. Progress has been limited in identifying hazards and quantifying their potencies and in separating the contribution of these hazards from other etiologic factors. Identifying the causative agents, mechanisms by which they act, and any potential target populations, present the opportunity to intervene and protect the reproductive health of workers. The pace of laboratory studies to identify hazards and to underpin the biologic plausibility of effects in humans has not matched the pace at which new chemicals are introduced into commerce. Though many research challenges exist today, recent technologic and methodologic advances have been made that allow researchers to overcome some of these obstacles. The objective of this article is to recommend future directions in occupational reproductive health research. By bridging interdisciplinary gaps, the scientific community can work together to improve health and reduce adverse outcomes. PMID:12676620

Potential human health effects of acid rain: report of a workshop

PubMed Central

Goyer, Robert A.; Bachmann, John; Clarkson, Thomas W.; Ferris, Benjamin G.; Graham, Judith; Mushak, Paul; Perl, Daniel P.; Rall, David P.; Schlesinger, Richard; Sharpe, William; Wood, John M.

1985-01-01

This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time. PMID:3896772

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

PubMed

Chang, Yue; Feng, LiFang; Miao, Wei

2011-07-01

Dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are persistent in the environment and cause continuous toxic effects in humans and aquatic life. Tetrahymena thermophila has the potential for use as a model for research regarding toxicants. In this study, this organism was used to analyze a genome-wide microarray generated from cells exposed to DDT, TBT and TCDD. To accomplish this, genes differentially expressed when treated with each toxicant were identified, after which their functions were categorized using GO enrichment analysis. The results suggested that the responses of T. thermophila were similar to those of multicellular organisms. Additionally, the context likelihood of relatedness method (CLR) was applied to construct a TCDD-relevant network. The T-shaped network obtained could be functionally divided into two subnetworks. The general functions of both subnetworks were related to the epigenetic mechanism of TCDD. Based on analysis of the networks, a model of the TCDD effect on T. thermophila was inferred. Thus, Tetrahymena has the potential to be a good unicellular eukaryotic model for toxic mechanism research at the genome level.

Epithelial toxicity of alkylglycoside surfactants.

PubMed

Vllasaliu, Driton; Shubber, Saif; Fowler, Robyn; Garnett, Martin; Alexander, Cameron; Stolnik, Snow

2013-01-01

Alkylglycoside surfactants have been proposed as drug delivery excipients with the potential to enhance mucosal drug absorption of therapeutic macromolecules. Previous work reported their drug absorption-promoting potential by demonstrating that several compounds within this class of surfactants improve mucosal absorption of peptides, proteins and other macromolecules. However, detailed investigation of their toxicity has not been conducted. Using Calu-3 epithelial cell layers as a model of the airway mucosa, and liposomes as models of cell membranes, this work investigates the cytotoxicity of dodecylmaltoside, tridecylmaltoside and tetradecylmaltoside, as representative alkylglycosides. A combination of different toxicity assays and other tests indicating cell membrane disruption were used to assess cytotoxicity. The alkylglycosides tested induced a dramatic reduction in cell viability, cell membrane and liposome-disruptive effects, as well as abrogation of transepithelial electrical resistance that did not recover completely. Importantly, these phenomena were noted at concentrations markedly lower than those typically used in the literature studies demonstrating the absorption-enhancing properties of alkylglycosides. This work therefore demonstrates that alkylglycosides exhibit significant toxicity towards airway epithelial cells, most likely resulting from a membrane-damaging effect, highlighting a need for further evaluation of their safety as absorption-enhancing excipients. Copyright © 2012 Wiley Periodicals, Inc.

Treatment of local-anesthetic toxicity with lipid emulsion therapy.

PubMed

Burch, Melissa S; McAllister, Russell K; Meyer, Tricia A

2011-01-15

The use of lipid emulsion to treat local-anesthetic toxicity is discussed. Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia. There is increasing evidence that lipid emulsion may be an effective treatment to reverse the cardiac and neurologic effects of local-anesthetic toxicity. A literature search identified seven case reports of local-anesthetic toxicity in which lipid emulsion was used. Lipid emulsion was found to be successful in the treatment of local-anesthetic toxicity associated with various regional anesthetic techniques and multiple local anesthetics. The majority of patients in the case reports reviewed were unresponsive to initial management of local-anesthetic toxicity with standard resuscitative measures, but all recovered completely after receiving lipid emulsion therapy. The initial dose of lipid emulsion administered varied among the case reports, as well as whether a lipid emulsion infusion was started and at what point during resuscitation. Based on the case reports reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min as soon as local-anesthetic toxicity is suspected seems most beneficial. The pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic toxicity has not been fully elucidated but likely involves increasing metabolism, distribution, or partitioning of the local anesthetic away from receptors into lipid within tissues. Lipid emulsion has been reported useful in the treatment of systemic toxicity caused by local anesthetics. The mechanism of effect is unclear, and evidence for the benefit of lipid therapy in humans is from case reports only.

Food plant toxicants and safety Risk assessment and regulation of inherent toxicants in plant foods.

PubMed

Essers, A J; Alink, G M; Speijers, G J; Alexander, J; Bouwmeister, P J; van den Brandt, P A; Ciere, S; Gry, J; Herrman, J; Kuiper, H A; Mortby, E; Renwick, A G; Shrimpton, D H; Vainio, H; Vittozzi, L; Koeman, J H

1998-05-01

The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial in this approach is analysis of the toxicity of the whole foodstuff. The relationship between the whole foodstuff and the pure toxicant is expressed in the `product correction factor' (PCF). Investigations in humans are essential so that biomarkers of exposure and for effect can be used to analyse the difference between animals and humans and between the food and the pure toxicant. A grid of the variables characterising toxicity is proposed, showing their inter-relationships. A flow diagram for risk estimate is provided, using both toxicological and epidemiological studies.

Effect of pH and ionic strength on exposure and toxicity of encapsulated lambda-cyhalothrin to Daphnia magna.

PubMed

Son, Jino; Hooven, Louisa A; Harper, Bryan; Harper, Stacey L

2015-12-15

Encapsulation of pesticide active ingredients in polymers has been widely employed to control the release of poorly water-soluble active ingredients. Given the high dispersibility of these encapsulated pesticides in water, they are expected to behave differently compared to their active ingredients; however, our current understanding of the fate and effects of encapsulated pesticides is still limited. In this study, we employed a central composite design (CCD) to investigate how pH and ionic strength (IS) affect the hydrodynamic diameter (HDD) and zeta potential of encapsulated λ-cyhalothrin and how those changes affect the exposure and toxicity to Daphnia magna. R(2) values greater than 0.82 and 0.84 for HDD and zeta potential, respectively, irrespective of incubation time suggest those changes could be predicted as a function of pH and IS. For HDD, the linear factor of pH and quadratic factor of pH×pH were found to be the most significant factors affecting the change of HDD at the beginning of incubation, whereas the effects of IS and IS×IS became significant as incubation time increased. For zeta potential, the linear factor of IS and quadratic factor of IS×IS were found to be the most dominant factors affecting the change of zeta potential of encapsulated λ-cyhalothrin, irrespective of incubation time. The toxicity tests with D. magna under exposure conditions in which HDD or zeta potential of encapsulated λ-cyhalothrin was maximized or minimized in the overlying water also clearly showed the worst-case exposure condition to D. magna was when the encapsulated λ-cyhalothrin is either stable or small in the overlying water. Our results show that water quality could modify the fate and toxicity of encapsulated λ-cyhalothrin in aquatic environments, suggesting understanding their aquatic interactions are critical in environmental risk assessment. Herein, we discuss the implications of our findings for risk assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

Toxicity of cypermethrin and deltamethrin insecticides on embryos and larvae of Physalaemus gracilis (Anura: Leptodactylidae).

PubMed

Macagnan, Natani; Rutkoski, Camila F; Kolcenti, Cassiane; Vanzetto, Guilherme V; Macagnan, Luan P; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T

2017-09-01

It is important to establish the toxicity pesticides against non-target species, especially those pesticides used in commercial formulations. Pyrethroid insecticides are widely used in agriculture despite their toxicity to aquatic animals. In this study, we determine the toxicity of commercial formulation of two pyrethroid insecticides, cypermethrin and deltamethrin, in two life stages of Physalaemus gracilis, a frog that breeds in agricultural ecosystems and has potential contact with pyrethroid pesticides. The acute toxicity test (96 h) was carried out with embryos of stage 17:18 and larvae of stages 24:25. Embryos were more resistant to both pesticides than larvae. In embryo mobility assays, we found that both pesticides caused spasmodic contractions, suggestive of neurological effects. In acute toxicity assays, we found that P. gracilis is more resistant to these insecticides than other studied species.

INTEGRATED CHEMICAL INFORMATION TECHNOLOGIES ...

EPA Pesticide Factsheets

A central regulatory mandate of the Environmental Protection Agency, spanning many Program Offices and issues, is to assess the potential health and environmental risks of large numbers of chemicals released into the environment, often in the absence of relevant test data. Models for predicting potential adverse effects of chemicals based primarily on chemical structure play a central role in prioritization and screening strategies yet are highly dependent and conditional upon the data used for developing such models. Hence, limits on data quantity, quality, and availability are considered by many to be the largest hurdles to improving prediction models in diverse areas of toxicology. Generation of new toxicity data for additional chemicals and endpoints, development of new high-throughput, mechanistically relevant bioassays, and increased generation of genomics and proteomics data that can clarify relevant mechanisms will all play important roles in improving future SAR prediction models. The potential for much greater immediate gains, across large domains of chemical and toxicity space, comes from maximizing the ability to mine and model useful information from existing toxicity data, data that represent huge past investment in research and testing expenditures. In addition, the ability to place newer “omics” data, data that potentially span many possible domains of toxicological effects, in the broader context of historical data is the means for opti

Potential toxic effect of trifloxystrobin on cellular microstructure, mRNA expression and antioxidant enzymes in Chlorella vulgaris.

PubMed

Shen, Yu-Feng; Liu, Lei; Gong, Yu-Xin; Zhu, Bin; Liu, Guang-Lu; Wang, Gao-Xue

2014-05-01

This study investigated the effects of trifloxystrobin that one strobilurin used widely in the world as an effective fungicidal agent to control Asian soybean rust on aquatic unicellular algae Chlorella vulgaris. We determined the potential toxic effect of trifloxystrobin on C. vulgaris, and found median inhibition concentration (IC(50)) value 255.58 (95% confidence interval, 207.81-330.29)μgL(-1). In addition, the algal cells were obviously depressed or shrunk at different concentrations by electron microscopy. In the study, a real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL, and one energy gene, ATPs. The results showed that trifloxystrobin reduced the transcript abundances of the three genes and enhanced expression of ATPs after 48 and 96 h. The lowest abundances of psaB, psbC and rbcL transcripts in response to trifloxystrobin exposure were 58%, 79% and 60% of those of the control, respectively. For the potential toxic influences, trifloxystrobin could decrease the soluble protein and total antioxidant contents (T-AOC), and increase superoxide dismutase (SOD) and peroxidase (POD) activity with a gradual concentration-response relationship. Overall, the present study demonstrated that trifloxystrobin could affect the activities of antioxidant enzymes, disrupts photosynthesis in C. vulgaris, and damage cellular structure. Copyright © 2014 Elsevier B.V. All rights reserved.

The toxicity study of functionalized CNT from fermented tapioca on neuroblastoma cell

NASA Astrophysics Data System (ADS)

Nurulhuda, I.; Mazatulikhma, M. Z.; Alrokayan, S.; Khan, H.; Rusop, M.

2018-05-01

Carbon nanotubes known as one of the most interesting types of nanomaterials, especially use in application directly to cells. Somehow the use should take into consideration regarding the potential adverse impact on human health. Current study, the carbon nanotube was synthesized from fermented tapioca and functionalized with polyethylene glycol and directly test on the neuroblastoma cells in vitro. The toxicity effect on cells was assessed by 3(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide assays. It showed a dose-and time-dependent less toxic effect on functionalized carbon nanotube compared to non-functionalized. This leads us to the conclusion that functionalized carbon nanotube can be use for drug delivery in future.

Toxicities of topical ophthalmic anesthetics.

PubMed

McGee, Hall T; Fraunfelder, F W

2007-11-01

Topical ocular anesthesia has been part of ophthalmology for more than a century. The most commonly used drugs today are proparacaine, tetracaine, benoxinate (oxybuprocaine) cocaine and lidocaine. Although generally well tolerated, all these can be toxic, particularly when abused. The most common toxicities are to the ocular surface, but abuse can cause deep corneal infiltrates, ulceration and even perforation. Fortunately, systemic side effects are rare. Cocaine is unique for its higher incidence of systemic side effects and high abuse potential, both of which impede its clinical use. When used appropriately, all these drugs are remarkably safe. They are generally not prescribed for home use, as prolonged abuse of these drugs can be expected to result in serious complications.

Biological response of zebrafish embryos after short-term exposure to thifluzamide

NASA Astrophysics Data System (ADS)

Yang, Yang; Liu, Wenxian; Mu, Xiyan; Qi, Suzhen; Fu, Bin; Wang, Chengju

2016-12-01

Thifluzamide is a new amide fungicide, and its extensive application may have toxic effects on zebrafish. To better understand the underlying mechanism, we investigated in detail the potential toxic effects of thifluzamide on zebrafish embryos. In the present study, embryos were exposed to 0, 0.19, 1.90, and 2.85 mg/L thifluzamide for 4 days. Obvious pathological changes were found upon a histological exam, and negative changes in mitochondrial structure were observed under Transmission Electron Microscopy (TEM), which qualitatively noted the toxic effects of thifluzamide on embryos. Moreover, we quantitatively evaluated the enzyme activities [succinate dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspases], the contents of malonaldehyde (MDA) and interleukin-8 (IL-8) and the expression levels of the related genes. This study suggests that the negative changes in mitochondrial structure and SDH activity might be responsible for oxidative damage, cell apoptosis and inflammation, which would facilitate the action of these factors in cell death and might play a crucial role during toxic events. In addition to providing the first description of the mechanism of the toxic effects of thifluzamide on embryos, this study also represents a step towards using embryos to assess mitochondrial metabolism and disease.

Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: A role for glutathione depletion

PubMed Central

KACHADOURIAN, REMY; LEITNER, VHEATHER M.; DAY, BRIAN J.

2014-01-01

Adjuvant therapies that enhance the anti-tumor effects of cisplatin are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cis-diammineplatinum(II) dichloride (cisplatin, CDDP). We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glu-tathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 μM, 48-h treatment) disrupts the steady-state levels of mitochondrial respiratory complex I, which correlates with elevated mitochondrial reactive oxygen species (ROS) production and cytochrome c release. The flavonoids, 2′,5′-dihydroxychalcone (2′,5′-DHC, 20 μM) and chrysin (20 μM) potentiated the cytotoxicity of cisplatin (20 μM), which could be blocked by supplementation of the media with exogenous GSH (500 μM). Both 2′,5′-DHC and chrysin were more effective than the specific inhibitor of GSH synthesis, L-buthionine sulfoximine (BSO, 20 μM), in inducing GSH depletion and potentiating the cytotoxic effect of cisplatin. These data suggest that the flavonoid-induced potentiation of cisplatin’s toxicity is due, in part, to synergetic pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and the flavonoids by depleting cellular GSH, an important antioxidant defense. PMID:17549417

Toxicity and environmental and economic performance of fly ash and recycled concrete aggregates use in concrete: A review.

PubMed

Kurda, Rawaz; Silvestre, José D; de Brito, Jorge

2018-04-01

This paper presents an overview of previous studies on the environmental impact (EI) and toxicity of producing recycled concrete aggregates (RCA), fly ash (FA), cement, superplasticizer, and water as raw materials, and also on the effect of replacing cement and natural aggregates (NA) with FA and RCA, respectively, on the mentioned aspects. EI and toxicity were analysed simultaneously because considering concrete with alternative materials as sustainable depends on whether their risk assessment is high. Therefore, this study mainly focuses on the cradle-to-gate EI of one cubic meter of concrete, namely abiotic depletion potential (ADP), global warming potential (GWP), ozone depletion potential (ODP), photochemical ozone creation (POCP), acidification potential (AP), eutrophication potential (EP), non-renewable energy (PE-NRe) and renewable energy (PE-Re). In terms of toxicity, leachability (chemical and ecotoxicological characterization) was considered. The results also include the economic performance of these materials, and show that the incorporation of FA in concrete significantly decreases the EI and cost of concrete. Thus, the simultaneous incorporation of FA and RCA decrease the EI, cost, use of landfill space and natural resources extraction. Nonetheless, the leaching metals of FA decrease when they are incorporated in concrete. Relative to FA, the incorporation of RCA does not significantly affect the EI and cost of concrete, but it significantly reduces the use of landfill space and the need of virgin materials.

Safety of Pochonia chlamydosporia var catenulata in acute oral and dermal toxicity/pathogenicity evaluations in rats and rabbits.

PubMed

García, Liseth; Bulnes, Carlos; Melchor, Gleiby; Vega, Ernesto; Ileana, Miranda; de Oca, Nivian Montes; Hidalgo, Leopoldo; Marrero, Eva

2004-10-01

The nematophagous fungus, Pochonia chlamydosporia var. catenulata (Kamyschlco ex Barron & Onions) Zare & W-Gams, was investigated as a potential biocontrol agent in integrated pest management strategy for Meloidogyne incognita (Kofoid and White) Chitwood in vegetable crops in Cuba. An acute oral and dermal toxicity/patogenicity study was performed to determine the safety of this fungus in non-target organisms. In the first study, a 1-dose level of 5 x 10(8) units of the microbial pest control agent/treated rat was used. Mortality or clinical signs were not evident and no adverse effects on body weight, hematology, microbiology and gross or microscopic pathology were observed. Food and water consumption was not significantly different between control and treated groups. In the acute dermal toxicity study, there was neither mortality nor clinical signs of toxicity, and no toxic effects in gross and microscopic pathology were detected. Thus, Pochonia chlamydosporia var. catenulate (Vcc-108, IMI SD 187), administered oral and dermally to rats and rabbits respectively, was safe in toxicity/pathogenicity studies.

Environmental Determinants of Chronic Disease and Medical Approaches: Recognition, Avoidance, Supportive Therapy, and Detoxification

PubMed Central

Sears, Margaret E.; Genuis, Stephen J.

2012-01-01

The World Health Organization warns that chronic, noncommunicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neurocognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bioaccumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives—biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Healthcare practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity. PMID:22315626

Hazards of chemical weapons release during war: new perspectives.

PubMed Central

Reutter, S

1999-01-01

The two major threat classes of chemical weapons are mustard gas and the nerve agents, and this has not changed in over 50 years. Both types are commonly called gases, but they are actually liquids that are not remarkably volatile. These agents were designed specifically to harm people by any route of exposure and to be effective at low doses. Mustard gas was used in World War I, and the nerve agents were developed shortly before, during, and after World War II. Our perception of the potency of chemical weapons has changed, as well as our concern over potential effects of prolonged exposures to low doses and potential target populations that include women and children. Many of the toxicologic studies and human toxicity estimates for both mustard and nerve agents were designed for the purpose of quickly developing maximal casualties in the least sensitive male soldier. The "toxicity" of the chemical weapons has not changed, but our perception of "toxicity" has. PMID:10585902

Field evaluation of an avian risk assessment model

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Borges, S.L.; Bennett, R.S.; Torrez, M.; Williams, B.I.; Leffel, R.

2006-01-01

We conducted two laboratory subacute dietary toxicity tests and one outdoor subacute dietary toxicity test to determine the effectiveness of the U.S. Environmental Protection Agency's deterministic risk assessment model for evaluating the potential of adverse effects to birds in the field. We tested technical-grade diazinon and its D Z N- 50W (50% diazinon active ingredient wettable powder) formulation on Canada goose (Branta canadensis) goslings. Brain acetylcholinesterase activity was measured, and the feathers and skin, feet. and gastrointestinal contents were analyzed for diazinon residues. The dose-response curves showed that diazinon was significantly more toxic to goslings in the outdoor test than in the laboratory tests. The deterministic risk assessment method identified the potential for risk to birds in general, but the factors associated with extrapolating from the laboratory to the field, and from the laboratory test species to other species, resulted in the underestimation of risk to the goslings. The present study indicates that laboratory-based risk quotients should be interpreted with caution.

The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

PubMed

Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

2010-01-01

An ideal preparation for intravenous iron replacement therapy should balance effectiveness and safety. Compounds that release iron rapidly tend to cause toxicity, while large molecules can induce antibody formation and cause anaphylactic reactions. There is therefore a need for an intravenous iron preparation that delivers appropriate amounts of iron in a readily available form but with minimal side effects and thus with an excellent safety profile. In this paper, a review is given on the chemistry, pharmacology, and toxicology of ferric carboxymaltose (FCM, Ferinject), a stable and robust complex formulated as a colloidal solution with a physiological pH. The complex is gradually taken up mainly from the hepatic reticulo-endothelial system (RES), followed by effective delivery of iron to the endogeneous transport system for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also demonstrated a barrier function of the placenta and a low transfer of iron into the milk of lactating rats. Safety pharmacology studies indicated a favourable profile with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A high maximum non-lethal dose was demonstrated in the single-dose toxicity studies. Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose toxicity studies and on the cumulative doses administered, FCM has good safety margins. Reproductive and developmental toxicity studies did not reveal any direct or indirect harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran antibodies and also suggested that FCM does not possess sensitizing potential. Lastly, no evidence of irritation was found in local tolerance studies with FCM. This excellent toxicity profile and the high effectiveness of FCM allow the administration of high doses as a single infusion or bolus injection, which will enhance the cost-effectiveness and convenience of iron replacement therapy. In conclusion, FCM has many of the characteristics of an ideal intravenous iron preparation.

Toxic phytoplankton in San Francisco Bay

USGS Publications Warehouse

Rodgers, Kristine M.; Garrison, David L.; Cloern, James E.

1996-01-01

The Regional Monitoring Program (RMP) was conceived and designed to document the changing distribution and effects of trace substances in San Francisco Bay, with focus on toxic contaminants that have become enriched by human inputs. However, coastal ecosystems like San Francisco Bay also have potential sources of naturally-produced toxic substances that can disrupt food webs and, under extreme circumstances, become threats to public health. The most prevalent source of natural toxins is from blooms of algal species that can synthesize metabolites that are toxic to invertebrates or vertebrates. Although San Francisco Bay is nutrient-rich, it has so far apparently been immune from the epidemic of harmful algal blooms in the world’s nutrient-enriched coastal waters. This absence of acute harmful blooms does not imply that San Francisco Bay has unique features that preclude toxic blooms. No sampling program has been implemented to document the occurrence of toxin-producing algae in San Francisco Bay, so it is difficult to judge the likelihood of such events in the future. This issue is directly relevant to the goals of RMP because harmful species of phytoplankton have the potential to disrupt ecosystem processes that support animal populations, cause severe illness or death in humans, and confound the outcomes of toxicity bioassays such as those included in the RMP. Our purpose here is to utilize existing data on the phytoplankton community of San Francisco Bay to provide a provisional statement about the occurrence, distribution, and potential threats of harmful algae in this Estuary.

Toxicity of harmful cyanobacterial blooms to bream and roach.

PubMed

Trinchet, Isabelle; Cadel-Six, Sabrina; Djediat, Chakib; Marie, Benjamin; Bernard, Cécile; Puiseux-Dao, Simone; Krys, Sophie; Edery, Marc

2013-09-01

Aquatic ecosystems are facing increasing environmental pressures, leading to an increasing frequency of cyanobacterial Harmful Algal Blooms (cHABs) that have emerged as a worldwide concern due to their growing frequency and their potential toxicity to the fauna that threatens the functioning of ecosystems. Cyanobacterial blooms raise concerns due to the fact that several strains produce potent bioactive or toxic secondary metabolites, such as the microcystins (MCs), which are hepatotoxic to vertebrates. These strains of cyanobacteria may be potentially toxic to fish via gastrointestinal ingestion and also by direct absorption of the toxin MC from the water. The purpose of our study was to investigate toxic effects observed in fish taken from several lakes in the Ile-de-France region, where MCs-producing blooms occur. This study comprises histological studies and the measurement of MC concentrations in various organs. The histological findings are similar to those obtained following laboratory exposure of medaka fish to MCs: hepatic lesions predominate and include cell lysis and cell detachment. MC concentrations in the organs revealed that accumulation was particularly high in the digestive tract and the liver, which are known to be classical targets of MCs. In contrast concentrations were very low in the muscles. Differences in the accumulation of MC variants produced by blooms indicate that in order to more precisely evaluate the toxic potential of a specific bloom it is necessary not only to consider the concentration of toxins, but also the variants produced. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation.

PubMed

Shields, Peter G; Berman, Micah; Brasky, Theodore M; Freudenheim, Jo L; Mathe, Ewy; McElroy, Joseph P; Song, Min-Ae; Wewers, Mark D

2017-08-01

The use of electronic cigarettes (e-cigs) is increasing rapidly, but their effects on lung toxicity are largely unknown. Smoking is a well-established cause of lung cancer and respiratory disease, in part through inflammation. It is plausible that e-cig use might affect similar inflammatory pathways. E-cigs are used by some smokers as an aid for quitting or smoking reduction, and by never smokers (e.g., adolescents and young adults). The relative effects for impacting disease risk may differ for these groups. Cell culture and experimental animal data indicate that e-cigs have the potential for inducing inflammation, albeit much less than smoking. Human studies show that e-cig use in smokers is associated with substantial reductions in blood or urinary biomarkers of tobacco toxicants when completely switching and somewhat for dual use. However, the extent to which these biomarkers are surrogates for potential lung toxicity remains unclear. The FDA now has regulatory authority over e-cigs and can regulate product and e-liquid design features, such as nicotine content and delivery, voltage, e-liquid formulations, and flavors. All of these factors may impact pulmonary toxicity. This review summarizes current data on pulmonary inflammation related to both smoking and e-cig use, with a focus on human lung biomarkers. Cancer Epidemiol Biomarkers Prev; 26(8); 1175-91. ©2017 AACR . ©2017 American Association for Cancer Research.

Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation.

PubMed

Alves, L; Paixão, S M

2011-10-01

The acute toxicity of some compounds used in fossil fuels biodesulphurisation studies, on the respiration activity, was evaluated by Gordonia alkanivorans and Rhodococcus erythropolis. Moreover, the effect of 2-hydroxybiphenyl on cell growth of both strains was also determined, using batch (chronic bioassays) and continuous cultures. The IC₅₀ values obtained showed the toxicity of all the compounds tested to both strains, specially the high toxicity of 2-HBP. These results were confirmed by the chronic toxicity data. The toxicity data sets highlight for a higher sensitivity to the toxicant by the strain presenting a lower growth rate, due to a lower cells number in contact with the toxicant. Thus, microorganisms exhibiting faster generation times could be more resistant to 2-HBP accumulation during a BDS process. The physiological response of both strains to 2-HBP pulse in a steady-state continuous culture shows their potential to be used in a future fossil fuel BDS process. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.

1995-12-31

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. Amore » battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs.« less

Reviews of the toxicity behavior of five potential engineered nanomaterials (ENMs) into the aquatic ecosystem.

PubMed

Jahan, Shanaz; Yusoff, Ismail Bin; Alias, Yatimah Binti; Bakar, Ahmad Farid Bin Abu

2017-01-01

Presently, engineered nanomaterials (ENMs) are used in a wide variety of commercial applications, resulting in an uncontrolled introduction into the aquatic environment. The purpose of this review is to summarize the pathways and factors that controlling the transport and toxicity of five extensively used ENMs. These toxicological pathways are of great importance and need to be addressed for sustainable implications of ENMs without environmental liabilities. Here we discuss five potentially utilized ENMs with their possible toxicological risk factors to aquatic plants, vertebrates model and microbes. Moreover, the key effect of ENMs surface transformations by significant reaction with environmental objects such as dissolved natural organic matter (DOM) and the effect of ENMs surface coating and surface charge will also be debated. The transformations of ENMs are subsequently facing a major ecological transition that is expected to create a substantial toxicological effect towards the ecosystem. These transformations largely involve chemical and physical processes, which depend on the properties of both ENMs and the receiving medium. In this review article, the critical issues that controlling the transport and toxicity of ENMs are reviewed by exploiting the latest reports and future directions and targets are keenly discussed to minimize the pessimistic effects of ENMs.

Malathion.

ERIC Educational Resources Information Center

Brenner, Loretta

1992-01-01

Discusses research findings about malathion, a widely used insecticide, concerning potential for human exposure; how malathion works and is used; toxicity; carcinogenicity; mutagenicity; associated birth defects; reproductive effects; effects on vision, diet, behavior, and immune systems; contaminants and analogues, synergists, residues, inert…

Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

PubMed

Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

2016-05-01

High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

Effect of light intensity on the degree of ammonia toxicity on PSII activity of Arthrospira platensis and Chlorella vulgaris.

PubMed

Markou, Giorgos; Muylaert, Koenraad

2016-09-01

Herein the effect of increasing light intensity on the degree of ammonia toxicity and its impact on the photosynthetic performance of Arthrospira and Chlorella was investigated using Chl fluorescence as a technique to characterize their photosystem II (PSII) activity. The results revealed that the increase of light intensity amplifies the ammonia toxicity on PSII. Chl fluorescence transients shown that at a given free ammonia (FA) concentration (100mg-N/L), the photochemistry potential decreased by increasing light intensity. The inhibition of the PSII was not reversible either by re-incubating the cells under dark or under decreased FA concentration. Moreover, the decrease of photochemical and non-photochemical quenching (NPQ) of fluorescence suggest that ammonia toxicity decreases the open available PSII centers, as well the inability of PSII to transfer the generated electrons beyond QA. The collapse of NPQ suggests that ammonia toxicity inhibits the photoprotection mechanism(s) and hence renders PSII more sensitive to photoinhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental Application, Fate, Effects, and Concerns of Ionic Liquids: A Review.

PubMed

Amde, Meseret; Liu, Jing-Fu; Pang, Long

2015-11-03

Ionic liquids (ILs) comprise mostly of organic salts with negligible vapor pressure and low flammability that are proposed as replacements for volatile solvents. ILs have been promoted as "green" solvents and widely investigated for their various applications. Although the utility of these chemicals is unquestionable, their toxic effects have attracted great attention. In order to manage their potential hazards and design environmentally benign ILs, understanding their environmental behavior, fate and effects is important. In this review, environmentally relevant issues of ILs, including their environmental application, environmental behavior and toxicity are addressed. In addition, also presented are the influence of ILs on the environmental fate and toxicity of other coexisting contaminants, important routes for designing nontoxic ILs and the techniques that might be adopted for the removal of ILs.

Ecotoxicity of naproxen and its phototransformation products.

PubMed

Isidori, Marina; Lavorgna, Margherita; Nardelli, Angela; Parrella, Alfredo; Previtera, Lucio; Rubino, Maria

2005-09-15

The occurrence of pharmaceuticals in the environment is of great concern and only few data are available about the adverse effects of such molecules and their derivatives on non-target aquatic organisms. This study was designed to assess the toxic potential of Naproxen, a nonsteroidal anti-inflammatory, Naproxen Na, its freely water soluble sodium salt and their photoproducts in the aquatic environment. Bioassays were performed on algae, rotifers and microcrustaceans to assess acute and chronic toxicity. Furthermore, possible genotoxic effects of photoderivatives were investigated using SOS chromotest and Ames fluctuation test. The results showed that photoproducts were more toxic than the parent compounds both for acute and chronic values, while genotoxic and mutagenic effects were not found. These findings suggested the opportunity to consider derivatives in ecotoxicology assessment of drugs.

Toxicity of environmentally realistic concentrations of chlorpyrifos and terbuthylazine in indoor microcosms.

PubMed

Pereira, Ana Santos; Cerejeira, Maria José; Daam, Michiel A

2017-09-01

Few studies have been conducted into the evaluation of environmentally realistic pesticide mixtures using model ecosystems. In the present study, the effects of single and combined environmentally realistic concentrations of the herbicide terbuthylazine and the insecticide chlorpyrifos were evaluated using laboratory microcosms. Direct toxic effects of chlorpyrifos were noted on copepod nauplii and cladocerans and the recovery of the latter was likely related with the decrease observed in rotifer abundances. Terbuthylazine potentiated the effect of chlorpyrifos on feeding rates of Daphnia magna, presumably by triggering the transformation of chlorpyrifos to more toxic oxon-analogs. Possible food-web interactions resulting from multiple chemical (and other) stressors likely to be present in edge-of-field water bodies need to be further evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment.

PubMed

Ostapchenko, Valeriy G; Chen, Megan; Guzman, Monica S; Xie, Yu-Feng; Lavine, Natalie; Fan, Jue; Beraldo, Flavio H; Martyn, Amanda C; Belrose, Jillian C; Mori, Yasuo; MacDonald, John F; Prado, Vania F; Prado, Marco A M; Jackson, Michael F

2015-11-11

In Alzheimer's disease, accumulation of soluble oligomers of β-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with β-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2α, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for β-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for β-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer's disease. Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress sensing calcium-permeable channel that is thought to contribute to calcium dysregulation associated with neurodegenerative diseases, including Alzheimer's disease. Here we show that oligomeric β-amyloid, the toxic peptide in Alzheimer's disease, facilitates TRPM2 channel activation. In mice designed to model Alzheimer's disease, genetic elimination of TRPM2 normalized deficits in synaptic markers in aged mice. Moreover, the absence of TRPM2 improved age-dependent spatial memory deficits observed in Alzheimer's mice. Our results reveal the importance of TRPM2 for neuronal toxicity and memory impairments in an Alzheimer's mouse model and suggest that TRPM2 could be targeted for the development of therapeutic agents effective in the treatment of dementia. Copyright © 2015 the authors 0270-6474/15/3515158-13$15.00/0.

Inhibition of growth of Zymomonas mobilis by model compounds found in lignocellulosic hydrolysates

PubMed Central

2013-01-01

Background During the pretreatment of biomass feedstocks and subsequent conditioning prior to saccharification, many toxic compounds are produced or introduced which inhibit microbial growth and in many cases, production of ethanol. An understanding of the toxic effects of compounds found in hydrolysate is critical to improving sugar utilization and ethanol yields in the fermentation process. In this study, we established a useful tool for surveying hydrolysate toxicity by measuring growth rates in the presence of toxic compounds, and examined the effects of selected model inhibitors of aldehydes, organic and inorganic acids (along with various cations), and alcohols on growth of Zymomonas mobilis 8b (a ZM4 derivative) using glucose or xylose as the carbon source. Results Toxicity strongly correlated to hydrophobicity in Z. mobilis, which has been observed in Escherichia coli and Saccharomyces cerevisiae for aldehydes and with some exceptions, organic acids. We observed Z. mobilis 8b to be more tolerant to organic acids than previously reported, although the carbon source and growth conditions play a role in tolerance. Growth in xylose was profoundly inhibited by monocarboxylic organic acids compared to growth in glucose, whereas dicarboxylic acids demonstrated little or no effects on growth rate in either substrate. Furthermore, cations can be ranked in order of their toxicity, Ca++ > > Na+ > NH4+ > K+. HMF (5-hydroxymethylfurfural), furfural and acetate, which were observed to contribute to inhibition of Z. mobilis growth in dilute acid pretreated corn stover hydrolysate, do not interact in a synergistic manner in combination. We provide further evidence that Z. mobilis 8b is capable of converting the aldehydes furfural, vanillin, 4-hydroxybenzaldehyde and to some extent syringaldehyde to their alcohol forms (furfuryl, vanillyl, 4-hydroxybenzyl and syringyl alcohol) during fermentation. Conclusions Several key findings in this report provide a mechanism for predicting toxic contributions of inhibitory components of hydrolysate and provide guidance for potential process development, along with potential future strain improvement and tolerance strategies. PMID:23837621

Developmental Toxicology##

EPA Science Inventory

Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

A cell impedance measurement device for the cytotoxicity assay dependent on the velocity of supplied toxic fluid

NASA Astrophysics Data System (ADS)

Kang, Yoon-Tae; Kim, Min-Ji; Cho, Young-Ho

2018-04-01

We present a cell impedance measurement chip capable of characterizing the toxic response of cells depending on the velocity of the supplied toxic fluid. Previous impedance-based devices using a single open-top chamber have been limited to maintaining a constant supply velocity, and devices with a single closed-top chamber present difficulties in simultaneous cytotoxicity assay for varying levels of supply velocities. The present device, capable of generating constant and multiple levels of toxic fluid velocity simultaneously within a single stepwise microchannel, performs a cytotoxicity assay dependent on toxic fluid velocity, in order to find the effective velocity of toxic fluid to cells for maximizing the cytotoxic effect. We analyze the cellular toxic response of 5% ethanol media supplied to cancer cells within a toxic fluid velocity range of 0-8.3 mm s-1. We observe the velocity-dependent cell detachment rate, impedance, and death rate. We find that the cell detachment rate decreased suddenly to 2.4% at a velocity of 4.4 mm s-1, and that the change rates of cell resistance and cell capacitance showed steep decreases to 8% and 41%, respectively, at a velocity of 5.7 mm s-1. The cell death rate and impedance fell steeply to 32% at a velocity of 5.7 mm s-1. We conclude that: (1) the present device is useful in deciding on the toxic fluid velocity effective to cytotoxicity assay, since the cellular toxic response is dependent on the velocity of toxic fluid, and; (2) the cell impedance analysis facilitates a finer cellular response analysis, showing better correlation with the cell death rate, compared to conventional visual observation. The present device, capable of performing the combinational analysis of toxic fluid velocity and cell impedance, has potential for application to the fine cellular toxicity assay of drugs with proper toxic fluid velocity.

A comparison of the toxicity of synergized and technical formulations of permethrin, sumithrin, and resmethrin to trout.

PubMed

Paul, E A; Simonin, H A; Tomajer, T M

2005-02-01

Synthetic pyrethroids often have synergists added to improve effectiveness, yet decisions regarding the use of these pesticides are often based upon toxicity tests using technical material without the synergist, piperonyl butoxide. We conducted toxicity tests with brook trout (Salvelinus fontinalis) and brown trout (Salmo trutta) to compare the toxicity of synergized and technical formulations of permethrin, sumithrin, and resmethrin. We found a significant increase in toxicity in the synergized permethrin formulation using traditional 24, 48, and 96-h tests, relative to tests with the technical formulation. However, there was little difference in toxicity between synergized and technical sumithrin until 48 h had elapsed. Many test fish were strongly intoxicated by either formulation of permethrin or sumithrin, but the synergized formulations of both chemicals affected fish at lower concentrations. Intoxication was potentially severe enough to reduce the survival of these fish in the wild. Following short (6-h) exposures, we also found a larger difference in the number of fish that died or became intoxicated between the synergized and technical formulations of permethrin and sumithrin. Finally, we tested the ability of exposed fish to swim against a current. Fish exposed for 6 h to synergized permethrin and resmethrin had far less swimming stamina than those exposed to technical formulations. We found no difference in the effect on swimming between the synergized and technical formulation of sumithrin. In general, the synergized formulations of these chemicals appeared to cause a faster response than the technical formulations. This response increases the lethal and sublethal impacts of the insecticides. We also found that sumithrin was the least toxic of the three pyrethroids. Since the maximum application rate of sumithrin is half that of the other two pyrethroids, the potential risk to wild trout in streams may be reduced.

Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant

PubMed Central

2017-01-01

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD. PMID:28111421

Cardiotoxicity screening: a review of rapid-throughput in vitro approaches.

PubMed

Li, Xichun; Zhang, Rui; Zhao, Bin; Lossin, Christoph; Cao, Zhengyu

2016-08-01

Cardiac toxicity represents one of the leading causes of drug failure along different stages of drug development. Multiple very successful pharmaceuticals had to be pulled from the market or labeled with strict usage warnings due to adverse cardiac effects. In order to protect clinical trial participants and patients, the International Conference on Harmonization published guidelines to recommend that all new drugs to be tested preclinically for hERG (Kv11.1) channel sensitivity before submitting for regulatory reviews. However, extensive studies have demonstrated that measurement of hERG activity has limitations due to the multiple molecular targets of drug compound through which it may mitigate or abolish a potential arrhythmia, and therefore, a model measuring multiple ion channel effects is likely to be more predictive. Several phenotypic rapid-throughput methods have been developed to predict the potential cardiac toxic compounds in the early stages of drug development using embryonic stem cells- or human induced pluripotent stem cell-derived cardiomyocytes. These rapid-throughput methods include microelectrode array-based field potential assay, impedance-based or Ca(2+) dynamics-based cardiomyocytes contractility assays. This review aims to discuss advantages and limitations of these phenotypic assays for cardiac toxicity assessment.

Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant.

PubMed

Leem, Jong-Han; Chung, Kyu Hyuck

2016-01-01

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs' victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.

Do PCDD/PCDF standard solutions used in dioxin analysis pose a risk as potentially acutely toxic to lab personnel?

PubMed

Malisch, Rainer; Denison, Michael S; Fiedler, Heidelore; Fürst, Peter; Hoogenboom, Ron L A P; Schaechtele, Alexander; Schrenk, Dieter; van den Berg, Martin

2017-10-01

Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential risks were evaluated to determine whether supervision of their use is necessary. Based on LD 50 -data for oral or dermal intake, hazard classification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a substance (category 1) and in commercially available TCDD standard solutions (category 4) is different. As worst case exposure scenario during routine laboratory work it was assumed that a dose of 100 ng TCDD gets onto the skin and is absorbed. This would result in the total body burden of a 70 kg person with 15 kg fat increasing from 10 (upper range of current background levels) to ∼17 pg of toxic equivalents (TEQs) of PCDD/PCDFs per g lipid, a level commonly observed over past decades. Chloracne, the main acute effect occurring weeks after exposure, is observed at much higher blood concentrations than estimated from accidental laboratory exposure. Immunotoxicity, developmental effects and other toxic effects may occur at lower blood levels, but require longer periods to develop. Since acute toxic symptoms don't occur within an "8 h acute time window", no supervision is necessary when working with standard solutions in routine analysis. Nevertheless, precautionary measures are needed regarding long-term adverse health effects and appropriate workplace conditions must exist to ensure that additional occupational exposure to PCDD/PCDFs by laboratory personnel is negligible. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro and in vivo evidence of the cytotoxic and genotoxic effects of metal ions released by orthodontic appliances: A review.

PubMed

Martín-Cameán, Ana; Jos, Ángeles; Mellado-García, Pilar; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

2015-07-01

Intraoral fixed orthodontic appliances are frequently used in the clinical practice of dentistry. They are made from alloys containing different metals at various percentages. The use of these appliances leads to the long-term exposure of patients to these materials, and the potential toxic effects of this exposure raises concerns about patient safety. Thus, the biocompatibility (corrosion behaviour and toxicity) of these materials has to be evaluated prior to clinical use. In the present report, the most recent studies in the scientific literature examining metal ion release from orthodontic appliances and the toxic effects of these ions have been reviewed with a special focus on cytotoxicity and genotoxicity. Previous studies suggest that a case-by-case safety evaluation is required to take into account the increasing variability of materials, their composition and the manufacturing processes. Moreover, in vivo toxicity studies in regard to metal release, cytotoxicity and genotoxicity are still scarce. Therefore, in vitro and in vivo monitoring studies are needed to establish cause-effect relationships between metal ion release and biomarkers of cytotoxicity and genotoxicity. Further investigations could be performed to elucidate the toxic mechanisms involved in the observed effects with a special emphasis on oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

BMY 30047: A novel topically active retinoid with low local and systemic toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, X.; Quigley, J.; Tramposch, K.M.

In the treatment of various dermatological disorders, topically applied retinoids have potential therapeutic use with the advantage of improved localized activity and lower toxicity over systemically administered retinoids. However, most retinoids cause a significant degree of local irritation. In the present study, the ability to produce local activity with low local irritation potential was evaluated with a novel retinoic acid derivative. BMY 30047 (11-cis, 13-cis-12-hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid derivatives in which the carboxyl function of the polar end was modified with the aim of achieving reduced local irritation and systemic toxicity while retainingmore » the local therapeutic effect. BMY 30047 was evaluated and compared with all-trans retinoic acid for topical retinoid activity in several preclinical assay systems, including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13-acetate ester-stimulated ornithine decarboxylase induction in hairless mice and the UV light-induced photodamaged skin model in hairless mice. BMY 30047 was assessed for retinoid-type side effects by evaluating the skin irritation potential in rabbits after repeated topical application, and hypervitaminosis A-inducing potential in mice after i.p. injection. BMY 30047 demonstrated significant topical retinoid activity in several in vivo models with less skin irritation potential relative to the most used clinical concentrations of all-trans retinoic acid. BMY 30047 also showed very little systemic activity and did not produce any evidence of hypervitaminosis A syndrome at systemic doses 20 times greater than the no-effect dose of all-trans retinoic acid.« less

Ecotoxicity of quinoline and hydroxylated derivatives and their occurrence in groundwater of a tar-contaminated field site.

PubMed

Neuwoehner, Judith; Reineke, Anne-Kirsten; Hollender, Juliane; Eisentraeger, Adolf

2009-03-01

In the groundwater of a timber impregnation site higher concentrations of hydroxylated quinolines compared to their parent compounds quinoline and isoquinoline were found. Studying the toxicity of parent compounds and metabolites, genotoxicity was found with metabolic activation in the SOS-Chromotest and Ames fluctuation test only for quinoline. An adverse effect on algae was observed only for the parent compounds quinoline and isoquinoline, while in the Daphnia magna immobilization assay most hydroxylated quinoline derivatives showed toxicity. The highest ecotoxic potential was observed in the Vibrio fischeri luminescence-inhibition assay. Comparing experimental EC50-values with QSAR predicted ones, for all compounds apart from isoquinoline and 2(1H)-quinolinone in the V. fischeri test baseline toxicity or polar nacrosis is indicated. In conclusion, the hydroxylation of quinoline leads to a detoxification of the genotoxic potential, while taken additive mixture toxicity and a safety factor into account parent compounds and metabolites are found of ecotoxicological relevance in the groundwater.

Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, L.J.; Johnson, E.M.; Newman, L.M.

A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

(Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in zebrafish (Danio rerio) and permanent fish cell cultures.

PubMed

Vincze, Krisztina; Gehring, Martin; Braunbeck, Thomas

2014-01-01

2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical used in paper, ink, pesticide, and adhesive industries as a wetting and anti-foaming agent. The physicochemical properties and slow biodegradation rate of TMDD indicate a low bioaccumulation potential but a high prevalence in the environment. As a consequence, TMDD has been detected in several European rivers in the nanogram per liter and lower microgram per liter range; however, its environmental risk to aquatic organisms is considered low. Recent studies almost exclusively focused on acute effects by TMDD, little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to TMDD during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. Our results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range.

Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

PubMed

Mariussen, Espen

2012-09-01

Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

Effects of titanium dioxide nanoparticles derived from consumer products on the marine diatom Thalassiosira pseudonana.

PubMed

Galletti, Andrea; Seo, Seokju; Joo, Sung Hee; Su, Chunming; Blackwelder, Pat

2016-10-01

Increased manufacture of TiO 2 nanoproducts has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO 2 nanoparticles derived from consumer products as opposed to industrial TiO 2 NPs warrant examination in exploring the significance of their release and resultant impacts on the environment. To this end, we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO 2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO 2 and inhibited the growth of the marine diatom T. pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO 2 . Our findings indicate a significant effect, and therefore, further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO 2 derived from consumer products and their physicochemical properties.

Effects of titanium dioxide nanoparticles derived from ...

EPA Pesticide Factsheets

Increased manufacture of TiO2 nano-products has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO2 nanoparticles derived from consumer products as opposed to industrial TiO2 NPs warrants examination in exploring the significance of their release and resultant impacts on the environment. To this end we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO2, and inhibited the growth of the marine diatom Thalassiosira pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO2. Our findings indicate a significant effect, and therefore further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO2 derived from consumer products and their physicochemical properties. Submit to journal Environmental Science and Pollution Research.

Nanoparticle interactions with co-existing contaminants: joint toxicity, bioaccumulation and risk.

PubMed

Deng, Rui; Lin, Daohui; Zhu, Lizhong; Majumdar, Sanghamitra; White, Jason C; Gardea-Torresdey, Jorge L; Xing, Baoshan

2017-06-01

With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants. Here, we review: (1) methods for investigating and evaluating joint effects of NPs and co-contaminants; (2) simultaneous toxicities from NPs co-exposed with organic contaminants, metal/metalloid ions, dissolved organic matter (DOM), inorganic ligands and additional NPs; and (3) the influence of NPs co-exposure on the bioaccumulation of organic contaminants and heavy metal ions, as well as the influence of contaminants on NPs bioaccumulation. In addition, future research needs are discussed so as to better understand risk associated with NPs-contaminant co-exposure.

Multi-walled Carbon Nanotubes Reduce Toxicity of Diphenhydramine to Ceriodaphnia dubia in Water and Sediment Exposures.

PubMed

Myer, Mark H; Black, Marsha C

2017-09-01

Multi-walled carbon nanotubes are adsorptive materials that have potential for remediation of organic contaminants in water. Sediment elutriate exposures were undertaken with Ceriodaphnia dubia to compare the toxic effects of diphenhydramine in the presence and absence of sediment and multi-walled carbon nanotubes. In both sediment and solution-only treatments, addition of 0.318 mg/g of carbon nanotubes significantly decreased 48-h mortality relative to control, with a 78.7%-90.1% reduction in treatments with nanotube-amended sediment and 40.7%-53.3% reduction in nanotube-amended water exposures. The greatest degree of relative mortality reduction occurred in sediments containing higher levels of natural organic matter, indicating a potential additive effect.

Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

NASA Astrophysics Data System (ADS)

Goodchild, John; Agrawal, Sudhir; Civeira, Maria P.; Sarin, Prem S.; Sun, Daisy; Zamecnik, Paul C.

1988-08-01

Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

PubMed Central

Das, Bidyut Kumar

2011-01-01

Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

Effects of naturally occurring and synthetic synergists on the toxicity of three insecticides, a phytochemical and a mycotoxin to the navel orangeworm Amyelois transitella (Lepidoptera: Pyralidae)

USDA-ARS?s Scientific Manuscript database

The navel orangeworm is the most destructive lepidopteran pest of almonds and pistachios in California as well as a serious problem in figs and walnuts. Larval feeding leaves nuts vulnerable to infection by Aspergillus spp., fungi that produce toxic aflatoxins. A potentially safe and sustainable app...

The protective roles of TiO2 nanoparticles against UV-B toxicity in Daphnia magna.

PubMed

Liu, Jie; Wang, Wen-Xiong

2017-09-01

Aquatic environments are increasingly under environmental stress due to ultraviolet (UV) radiation and potential inputs of nanoparticles with intense application of nanotechnology. In this study, we investigated the interaction between UV-B radiation and titanium nanoparticles (TiO 2 -NPs) in a model freshwater cladoceran Daphnia magna. UV-B toxicity to Daphnia magna was examined when the daphnids were exposed to a range of TiO 2 -NPs concentrations with an initial 5 or 10min of 200μW/cm 2 UV-B radiation. In addition, UV-B toxicity was also examined in the presence of TiO 2 -NPs in the body of daphnids. Our results demonstrated that the daphnid mortality under UV-B radiation decreased significantly in the presence of TiO 2 -NPs both in the water and in the body, indicating that TiO 2 -NPs had some protective effects on D. magna against UV-B. Such protective effect was mainly caused by the blockage of UV-B by TiO 2 -NPs adsorption. UV-B produced reactive oxygen species (ROS) in the water and in the daphnids, which was not sufficient to cause mortality of daphnids over short periods of radiation. Previous studies focused on the effects of TiO 2 -NPs on the toxicity of total UV radiation, and did not attempt to differentiate the potential diverse roles of UV-A and UV-B. Our study indicated that TiO 2 -NPs may conversely protect the UV-B toxicity to daphnids. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary supplement adverse events: report of a one-year poison center surveillance project.

PubMed

Haller, Christine; Kearney, Tom; Bent, Stephen; Ko, Richard; Benowitz, Neal; Olson, Kent

2008-06-01

The safety and efficacy of dietary supplements is of growing concern to regulators, health-care providers and consumers. Few scientific data exist on clinical effects and potential toxicities of marketed products. Harmful supplements may not be identified for months or years with existing adverse event monitoring mechanisms. Retrospective review of poison center statistics to capture supplement-associated toxicity also has limitations. We collaborated with the FDA Center for Food Safety and Nutrition (CFSAN) to conduct a 1-year prospective surveillance study of dietary supplement-related poison control center calls in 2006. Prompt follow-up of symptomatic cases, laboratory analysis of implicated dietary supplements, and causality assessment by a case review expert panel were performed. Of 275 dietary supplements calls, 41% involved symptomatic exposures; and two-thirds were rated as probably or possibly related to supplement use. Eight adverse events required hospital admission. Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases. Suspected drug-herb interactions occurred in 6 cases, including yohimbe co-ingested with buproprion (1) and methamphetamine (3), and additive anticoagulant/antiplatelet effects of NSAIDs taken with fish oils (1) and ginkgo (1). Laboratory analysis identified a pharmacologically active substance in 4 cases; supplement toxicity was ruled unlikely when analytical testing was negative in 5 cases. Most supplement-related adverse events were minor. Clinically significant toxic effects were most frequently reported with caffeine and yohimbe-containing products. Active surveillance of poison control center reports of dietary supplement adverse events enables rapid detection of potentially harmful products, which may facilitate regulatory oversight.

Characterization and toxicity of citral incorporated with nanostructured lipid carrier.

PubMed

Nordin, Noraini; Yeap, Swee Keong; Zamberi, Nur Rizi; Abu, Nadiah; Mohamad, Nurul Elyani; Rahman, Heshu Sulaiman; How, Chee Wun; Masarudin, Mas Jaffri; Abdullah, Rasedee; Alitheen, Noorjahan Banu

2018-01-01

The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was -12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined via in vitro and in vivo routes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.

Characterization and toxicity of citral incorporated with nanostructured lipid carrier

PubMed Central

Nordin, Noraini; Yeap, Swee Keong; Zamberi, Nur Rizi; Abu, Nadiah; Mohamad, Nurul Elyani; Rahman, Heshu Sulaiman; How, Chee Wun; Masarudin, Mas Jaffri; Abdullah, Rasedee

2018-01-01

The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was −12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined via in vitro and in vivo routes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity. PMID:29312812

Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

PubMed

Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

2014-01-01

Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states

PubMed Central

Pulido-Reyes, Gerardo; Rodea-Palomares, Ismael; Das, Soumen; Sakthivel, Tamil Selvan; Leganes, Francisco; Rosal, Roberto; Seal, Sudipta; Fernández-Piñas, Francisca

2015-01-01

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and anti-oxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterials. PMID:26489858

Cell culture-based biosensing techniques for detecting toxicity in water.

PubMed

Tan, Lu; Schirmer, Kristin

2017-06-01

The significant increase of contaminants entering fresh water bodies calls for the development of rapid and reliable methods to monitor the aquatic environment and to detect water toxicity. Cell culture-based biosensing techniques utilise the overall cytotoxic response to external stimuli, mediated by a transduced signal, to specify the toxicity of aqueous samples. These biosensing techniques can effectively indicate water toxicity for human safety and aquatic organism health. In this review we account for the recent developments of the mainstream cell culture-based biosensing techniques for water quality evaluation, discuss their key features, potentials and limitations, and outline the future prospects of their development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Applications of diatoms as potential microalgae in nanobiotechnology.

PubMed

Jamali, Ali Akbar; Akbari, Fariba; Ghorakhlu, Mohamad Moradi; de la Guardia, Miguel; Yari Khosroushahi, Ahmad

2012-01-01

Diatoms are single cell eukaryotic microalgae, which present in nearly every water habitat make them ideal tools for a wide range of applications such as oil explora-tion, forensic examination, environmental indication, biosilica pattern generation, toxicity testing and eutrophication of aqueous ecosystems. Essential information on diatoms were reviewed and discussed towards impacts of diatoms on biosynthesis and bioremediation. In this review, we present the recent progress in this century on the application of diatoms in waste degradation, synthesis of biomaterial, biomineraliza-tion, toxicity and toxic effects of mineral elements evaluations. Diatoms can be considered as metal toxicity bioindicators and they can be applied for biomineralization, synthesis of biomaterials, and degradation of wastes.

Toxicity and trophic transfer of P25 TiO2 NPs from Dunaliella salina to Artemia salina: Effect of dietary and waterborne exposure.

PubMed

Bhuvaneshwari, M; Thiagarajan, Vignesh; Nemade, Prateek; Chandrasekaran, N; Mukherjee, Amitava

2018-01-01

The recent increase in nanoparticle (P25 TiO 2 NPs) usage has led to concerns regarding their potential implications on environment and human health. The food chain is the central pathway for nanoparticle transfer from lower to high trophic level organisms. The current study relies on the investigation of toxicity and trophic transfer potential of TiO 2 NPs from marine algae Dunaliella salina to marine crustacean Artemia salina. Toxicity was measured in two different modes of exposure such as waterborne (exposure of TiO 2 NPs to Artemia) and dietary exposure (NP-accumulated algal cells are used to feed the Artemia). The toxicity and accumulation of TiO 2 NPs in marine algae D. salina were also studied. Artemia was found to be more sensitive to TiO 2 NPs (48h LC 50 of 4.21mgL -1 ) as compared to marine algae, D. salina (48h LC 50 of 11.35mgL -1 ). The toxicity, uptake, and accumulation of TiO 2 NPs were observed to be more in waterborne exposure as compared to dietary exposure. Waterborne exposure seemed to cause higher ROS production and antioxidant enzyme (SOD and CAT) activity as compared to dietary exposure of TiO 2 NPs in Artemia. There were no observed biomagnification (BMF) and trophic transfer from algae to Artemia through dietary exposure. Histopathological studies confirmed the morphological and internal damages in Artemia. This study reiterates the possible effects of the different modes of exposure on trophic transfer potential of TiO 2 NPs and eventually the consequences on aquatic environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Reactive oxygen species mediate Terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins.

PubMed

Hung, Jui-Hsiang; Chen, Chia-Yun; Omar, Hany A; Huang, Kuo-Yuan; Tsao, Che-Chia; Chiu, Chien-Chih; Chen, Yi-Ling; Chen, Po-Han; Teng, Yen-Ni

2016-12-01

Terbufos (S-t-butylthiomethyl-O,O-diethyl phosphorodithioate) is a highly toxic organophosphate which is extensively used as an insecticide and nematicide. Chronic exposure to terbufos causes neuronal injury and predisposes to neurodegenerative diseases. Accumulating evidence has shown that the exposure to terbufos, as an occupational risk factor, may also cause reproductive disorders. However, the exact mechanisms of reproductive toxicity remain unclear. The present study aimed to investigate the toxic effect of terbufos on testicular cells and to explore the mechanism of toxicity on a cellular level. The cytotoxic effects of terbufos on mouse immortalized spermatogonia (GC-1), spermatocytes (GC-2), Leydig (TM3), and Sertoli (TM4) cell lines were assessed by MTT assays, caspase activation, flow cytometry, TUNEL assay, Western blot, and cell cycle analysis. The exposure to different concentrations of terbufos ranging from 50 to 800 μM for 6 h caused significant death in all the used testicular cell lines. Terbufos increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and initiated apoptosis, which was confirmed by a dose-dependent increase in the number of TUNEL-positive apoptotic cells. Blocking ROS production by N-acetyl cysteine (NAC) protected GC-1 cells from terbufos-induced cell death. The results demonstrated that terbufos induces ROS, apoptosis, and DNA damage in testicular cell lines and it should be considered potentially hazardous to testis. Together, this study provided potential molecular mechanisms of terbufos-induced toxicity in testicular cells and suggests a possible protective measure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1888-1898, 2016. © 2015 Wiley Periodicals, Inc.

Arsenic toxicity in the human nerve cell line SK-N-SH in the presence of chromium and copper

PubMed Central

HU, LIGANG; GREER, JUSTIN B.; SOLO-GABRIELE, HELENA; FIEBER, LYNNE A.; CAI, YONG

2013-01-01

As, Cr, and Cu represent one potential combination of multiple metals/metalloids exposures since these three elements are simultaneously leached from chromated copper arsenate (CCA)-treated wood, a common product used for building construction, at levels that can be potentially harmful. This study investigated the neurotoxicity of As associated with CCA-treated wood when accompanied by Cr and Cu. The toxicity was evaluated on basis of a cytotoxicity model using human neuroblastoma cell line SK-N-SH. The cells were cultured with CCA-treated wood leachates or with solutions containing arsenate [As(V)], divalent copper [Cu(II)], trivalent chromium [Cr(III)] alone or in different combinations of the three elements. The toxicity was evaluated using variations in cell replication compared to controls after 96 hrs exposure. Among the three elements present in wood leachates, As played the primary role in the observed toxic effects, which exerted through multiple pathways, including the generation of oxidative stress. DOM affected the absorption of metals/metalloids into the test cells, which however did not obviously appear to impact toxicity. As toxicity was enhanced by Cu(II) and inhibited by Cr(III) at concentrations below U.S. EPA’s allowable maximum contaminant levels in drinking waters. Thus assessing As toxicity in real environments is not sufficient if based solely on the result from As. PMID:23473430

The use of multiwell culture plates in the duckweed toxicity test-a case study on Zn nanoparticles.

PubMed

Kalčíková, Gabriela; Marolt, Gregor; Kokalj, Anita Jemec; Gotvajn, Andreja Žgajnar

2018-06-11

Extensive production of nanomaterials of various properties needs to be coupled with rapid toxicity testing in order to provide information about their potential risks to the environment and human health. Miniaturization of toxicity tests may accelerate economical testing of nanomaterials, but is not a common practice. We describe a case study to miniaturize a commonly used toxicity test with plant duckweed Lemna minor. 6-well, 12-well and 24-well culture plates were used to assess their potential use for the duckweed toxicity test with potassium chloride as reference material. The results were compared to the standard test design using 100 mL glass beakers. The comparison showed that the best agreement was with the 6-well vessels. This set-up was further used for toxicity testing of zinc oxide nanoparticles (ZnO NP) and zinc chlorides. Zinc was not adsorbed onto either glass or plastic walls of the miniaturized system. We assume that in both vessels a fast agglomeration and settling of ZnO NP took place. Linear regression and statistical testing indicated a good correlation between the toxicity results obtained in the standard test and miniaturized 6-well vessels. The miniaturization of the test system for assessing the biological effect of nanomaterials on Lemna minor could become an appropriate alternative to the traditionally used high volume vessels. Copyright © 2018. Published by Elsevier B.V.

Toxicity effects of di-(2-ethylhexyl) phthalate to Eisenia fetida at enzyme, cellular and genetic levels

PubMed Central

Chen, Li’ke; Wu, Longhua; Christie, Peter; Zhang, Haibo; Luo, Yongming

2017-01-01

Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester (PAE) that has aroused public concern due to its resistance to degradation and its toxicity as an endocrine-disrupting compound. Effects of different concentrations of DEHP on Eisenia fetida in spiked natural soil have been studied in the body of the earthworm by means of soil cultivation tests 7, 14, 21 and 28 days after exposure. The results indicated that, in general, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, metallothionein (MT) content, the expression of heat shock protein 70 (HSP 70) and all the tested geno-toxicity parameters are promoted as time elapses and with increasing concentration of DEHP. However, peroxidase (POD) activity, neutral red retention time (NRRT) and mitochondrial membrane potential difference values were found to decrease even at a low concentration of DEHP of 1 mg kg-1 soil (p<0.05). Clear toxic effects of DEHP on E. fetida have been generally recognized by means of the disturbance of antioxidant enzyme activity/content and critical proteins, cell membrane and organelle disorder and DNA damage estimated by length of tail, tail DNA ratio, and tail moment parameters. A concentration of DEHP of 3 mg kg-1 may be recommended as a precaution against the potential risk of PAEs in soils and for indicating suitable threshold values for other soil animals and soil micro-organisms. PMID:28319143

Toxicity effects of di-(2-ethylhexyl) phthalate to Eisenia fetida at enzyme, cellular and genetic levels.

PubMed

Ma, Tingting; Zhou, Wei; Chen, Li'ke; Wu, Longhua; Christie, Peter; Zhang, Haibo; Luo, Yongming

2017-01-01

Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester (PAE) that has aroused public concern due to its resistance to degradation and its toxicity as an endocrine-disrupting compound. Effects of different concentrations of DEHP on Eisenia fetida in spiked natural soil have been studied in the body of the earthworm by means of soil cultivation tests 7, 14, 21 and 28 days after exposure. The results indicated that, in general, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, metallothionein (MT) content, the expression of heat shock protein 70 (HSP 70) and all the tested geno-toxicity parameters are promoted as time elapses and with increasing concentration of DEHP. However, peroxidase (POD) activity, neutral red retention time (NRRT) and mitochondrial membrane potential difference values were found to decrease even at a low concentration of DEHP of 1 mg kg-1 soil (p<0.05). Clear toxic effects of DEHP on E. fetida have been generally recognized by means of the disturbance of antioxidant enzyme activity/content and critical proteins, cell membrane and organelle disorder and DNA damage estimated by length of tail, tail DNA ratio, and tail moment parameters. A concentration of DEHP of 3 mg kg-1 may be recommended as a precaution against the potential risk of PAEs in soils and for indicating suitable threshold values for other soil animals and soil micro-organisms.

Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

PubMed

Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

2015-06-01

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

PubMed

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

PubMed Central

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

Impacts of UV radiation and photomodification on the toxicity of PAHs to the higher plant Lemna gibba (duckweed)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiaodong Huang; Dixon, D.G.; Greenberg, B.M.

1993-06-01

The toxicity of polycyclic aromatic hydrocarbons (PAHs) can be enhanced by both biotic and abiotic processes. This is exemplified by light, which, by virtue of the extensive [pi]-orbital systems of PAHs, can be a major factor in PAH toxicity. Light activation of PAHs is known to occur via photosensitization reactions and potentially by photomodification of the chemicals to more toxic species. To examine the modes of PAH action in the light and determine if the photomodified compounds are hazardous, the authors investigated the photoinduced toxicity of anthracene, phenanthrene and benzo[a]pyrene to the aquatic higher plant Lemna gibba (a duckweed). Toxicitymore » end points were inhibition of growth and extent of chlorosis. Light did indeed activated the phytotoxicity of PAHs, with UV radiation more effective than visible light. Dose-response curves based on chemical concentration and light intensity revealed the order of phytotoxic strength to be anthracene > phenanthrene > benzo[a]pyrene. To explore whether photomodified PAHs were contributing to toxicity, the chemicals were irradiated before toxicity testing. The rates of photomodification of the three PAHs were rapid, and the relative velocities were coincident with the order of toxic strength. Furthermore, the photomodified PAHs were more hazardous to Lemna than the intact compounds. Because interpretations of the potential impacts of PAHs in the environment are based mostly on measurements of the structurally intact chemicals, the severity of PAH hazards is possibly underestimated.« less

Haloacetonitriles: metabolism and toxicity.

PubMed

Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

2009-01-01

The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or bioactivation process, depending on the particular HAN and the enzyme involved. HANs can inhibit CYP2E1-mediated metabolism, an effect which may be dependent on a covalent interaction with the enzyme. In addition, HAN compounds inhibit GST-mediated conjugation, but this effect is reversible upon dialysis, indicating that the interaction does not represent covalent binding. No subchronic studies of HAN toxicity are available in the literature. However, studies show that HANs produce developmental toxicity in experimental animals. The nature of developmental toxicity is affected by the type of administration vehicle, which renders interpretation of results more difficult. Skin tumors have been found following dermal application of HANs, but oral studies for carcinogenicity are negative. Pulmonary adenomas were increased following oral administration of HANs, but the A/J strain of mice employed has a characteristically high background rate of such tumors. HANs interact with DNA to produce unscheduled DNA repair, SCE and reverse mutations in Salmonella. HANs did not induce micronuclei or cause alterations in sperm head morphology in mice, but did induce micronuclei in newts. Thus, there is concern for the potential carcinogenicity of HANs. It would be valuable to delineate any relationship between the apparent threshold for micronuclei formation in newts and the potential mechanism of toxicity involving HAN-induced oxidative stress. Dose-response studies in rodents may provide useful information on toxicity mechanisms and dose selection for longer term toxicity studies. Additional studies are warranted before drawing firm conclusions on the hazards of HAN exposure. Moreover, additional studies on HAN-DNA and HAN-protein interaction mechanisms, are needed. Such studies can better characterize the role of metabolism in toxicity of individual HANs, and delineate the role of oxidative stress, both of which enhance the capacity to predict risk. Most needed, now, are new subchronic (and chronic) toxicity studies; the results of such well-planned, controlled, conducted, interpreted and published investigations would be valuable in establishing margins of safety for HANs in human health risk assessment.

Effects of nanoplastics and microplastics on toxicity, bioaccumulation, and environmental fate of phenanthrene in fresh water.

PubMed

Ma, Yini; Huang, Anna; Cao, Siqi; Sun, Feifei; Wang, Lianhong; Guo, Hongyan; Ji, Rong

2016-12-01

Contamination of fine plastic particles (FPs), including micrometer to millimeter plastics (MPs) and nanometer plastics (NPs), in the environment has caught great concerns. FPs are strong adsorbents for hydrophobic toxic pollutants and may affect their fate and toxicity in the environment; however, such information is still rare. We studied joint toxicity of FPs with phenanthrene to Daphnia magna and effects of FPs on the environmental fate and bioaccumulation of 14 C-phenanthrene in fresh water. Within the five sizes particles we tested (from 50 nm to 10 μm), 50-nm NPs showed significant toxicity and physical damage to D. magna. The joint toxicity of 50-nm NPs and phenanthrene to D. magna showed an additive effect. During a 14-days incubation, the presence of NPs significantly enhanced bioaccumulation of phenanthrene-derived residues in daphnid body and inhibited the dissipation and transformation of phenanthrene in the medium, while 10-μm MPs did not show significant effects on the bioaccumulation, dissipation, and transformation of phenanthrene. The differences may be attributed to higher adsorption of phenanthrene on 50-nm NPs than 10-μm MPs. Our findings underlined the high potential ecological risks of FPs, and suggested that NPs should be given more concerns, in terms of their interaction with hydrophobic pollutants in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity.

PubMed

Dunnick, Katherine M; Pillai, Rajalekshmi; Pisane, Kelly L; Stefaniak, Aleksandr B; Sabolsky, Edward M; Leonard, Stephen S

2015-07-01

Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce(3+)/Ce(4+) ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state.

Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

PubMed

Strupp, Christian

2011-01-01

The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral toxic properties.

Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy.

PubMed

Wang, Jun-Ying; Chen, Jie; Yang, Jiang; Wang, Hao; Shen, Xiu; Sun, Yuan-Ming; Guo, Meili; Zhang, Xiao-Dong

2016-01-01

Gold nanoclusters (Au NCs) have exhibited great advantages in medical diagnostics and therapies due to their efficient renal clearance and high tumor uptake. The in vivo effects of the surface chemistry of Au NCs are important for the development of both nanobiological interfaces and potential clinical contrast reagents, but these properties are yet to be fully investigated. In this study, we prepared glutathione-protected Au NCs of a similar hydrodynamic size but with three different surface charges: positive, negative, and neutral. Their in vivo biodistribution, excretion, and toxicity were investigated over a 90-day period, and tumor uptake and potential application to radiation therapy were also evaluated. The results showed that the surface charge greatly influenced pharmacokinetics, particularly renal excretion and accumulation in kidney, liver, spleen, and testis. Negatively charged Au NCs displayed lower excretion and increased tumor uptake, indicating a potential for NC-based therapeutics, whereas positively charged clusters caused transient side effects on the peripheral blood system.

Aquatic toxicity of nine aircraft deicer and anti-icer formulations and relative toxicity of additive package ingredients alkylphenol ethoxylates and 4,5-methyl-1H-henzotriazoles.

PubMed

Corsi, Steven R; Geis, Steven W; Loyo-Rosales, Jorge E; Rice, Clifford P

2006-12-01

Characterization of the effects of aircraft deicer and anti-icer fluid (ADAF) runoff on aquatic organisms in receiving streams is a complex issue because the identities of numerous toxic additives are proprietary and not publicly available. Most potentially toxic and endocrine disrupting effects caused by ADAF are due to the numerous additive package ingredients which vary among manufacturers and types of ADAF formulation. Toxicity investigations of nine ADAF formulations indicate that endpoint concentrations for formulations of different manufacturers are widely variable. Type IV ADAF (anti-icers) are more toxic than Type I (deicers) for the four organisms tested (Vibrio fischeri, Pimephales promelas, Ceriodaphnia dubia, and Selenastrum capricornutum). Acute toxicity endpoint concentrations ranged from 347 to 7700 mg/L as ADAF for Type IV and from 1550 to 45,100 mg/L for Type I formulations. Chronic endpoint concentrations ranged from 70 to 1300 mg/L for Type IV and from 37 to 18,400 mg/L for Type I formulations. Alkylphenol ethoxylates and tolyltriazoles are two known classes of additives. Nonylphenol, nonylphenol ethoxylates, octylphenol, octylphenol ethoxylates, and 4,5-methyl-1H-benzotriazoles were quantified in the nine ADAF formulations, and toxicity tests were conducted with nonylphenol ethoxylates and 4,5-methyl-1H-benzotriazoles. Toxicity units computed for glycol and these additives, with respect to toxicity of the ADAF formulations, indicate that a portion of ADAF toxicity can be explained by the known additives and glycols, but much of the toxicity is due to unidentified additives.

Determination of the acute toxicity of isoniazid to three invasive carp species and rainbow trout in static exposures

USGS Publications Warehouse

Schreier, Theresa M.; Hubert, Terrance D.

2015-01-01

Three invasive fishes of considerable concern to aquatic resource managers are the Hypophthalmichthys nobilis (bighead carp),Hypophthalmichthys molitrix (silver carp), and Ctenopharyngodon idella (grass carp), collectively known as Asian carps. There is a need for an effective chemical control agent for Asian carps. Isoniazid was identified as a potential toxicant for grass carp. The selective toxicity of isoniazid to grass carp was verified as a response to an anecdotal report received in 2013. In addition, the toxicity of isoniazid to bighead carp, silver carp, and Oncorhynchus mykiss (rainbow trout) was evaluated. Isoniazid was not toxic to grass carp at the reported anecdotal concentration, which was 13 milligrams per liter. Isoniazid (130 milligrams per liter) was not selectively toxic to bighead carp, silver carp, or grass carp when compared to rainbow trout.

Biochar reduces copper toxicity in Chenopodium quinoa Willd. In a sandy soil.

PubMed

Buss, Wolfram; Kammann, Claudia; Koyro, Hans-Werner

2012-01-01

Mining, smelting, land applications of sewage sludge, the use of fungicides containing copper (Cu), and other human activities have led to widespread soil enrichment and contamination with Cu and potentially toxic conditions. Biochar (BC) can adsorb several substances, ranging from herbicides to plant-inhibiting allelochemicals. However, the range of potential beneficial effects on early-stage plant growth with regard to heavy metal toxicity is largely unexplored. We investigated the ameliorating properties of a forestry-residue BC under Cu toxicity conditions on early plant growth. Young quinoa plants () were grown in the greenhouse in the presence of 0, 2, and 4% BC application (w/w) added to a sandy soil with 0, 50, or 200 μg g Cu supplied. The plants without BC showed severe stress symptoms and reduced growth shortly after Cu application of 50 μg g and died at 200 μg Cu g. Increasing BC concentrations in the growth medium significantly increased the plant performance without Cu toxicity or under Cu stress. At the 4% BC application rate, the plants with 200 μg g Cu almost reached the same biomass as in the control treatment. In the presence of BC, less Cu entered the plant tissues, which had reduced Cu concentrations in the order roots, shoots, leaves. The amelioration effect also was reflected in the plant-soil system CO gas exchange, which showed clear signs of improvement with BC presence. The most likely ameliorating mechanisms were adsorption of Cu to negatively charged BC surfaces and an improvement of the water supply. Overall, BC seems to be a beneficial amendment with the potential to ameliorate Cu toxicity in sandy soils. Further research with a broad spectrum of different soil types, BCs, and crop plants is required. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Modification of smoke toxicant yields alters the effects of cigarette smoke extracts on endothelial migration: an in vitro study using a cardiovascular disease model.

PubMed

Fearon, Ian M; Acheampong, Daniel O; Bishop, Emma

2012-01-01

Endothelial damage plays a key role in atherosclerosis and this is impacted upon by numerous risk factors including cigarette smoking. A potential measure to reduce the cardiovascular burden associated with smoking is to reduce smoke toxicant exposure. In an in vitro endothelial damage repair assay, endothelial cell migration was inhibited by cigarette smoke particulate matter (PM) generated from several cigarette types. This inhibition was reduced when cells were exposed to PM from an experimental cigarette with reduced smoke toxicant levels. As a number of toxicants induce oxidative stress and since oxidative stress may link cigarette smoke and endothelial damage, we hypothesized that PM effects were dependent on elevated cellular oxidants. However, although PM-induced cellular oxidant production could be inhibited by ascorbic acid or n-acetylcysteine, both these antioxidants were without effect on migration responses to PM. Furthermore, reactive oxygen species production, as indicated by dihydroethidium fluorescence, was not different in cells exposed to smoke from cigarettes with different toxicant levels. In summary, our data demonstrate that a cardiovascular disease-related biological response may be modified when cells are exposed to smoke containing different levels of toxicants. This appeared independent of the induction of oxidative stress.

Toxic effects of two essential oils and their constituents on the mealworm beetle, Tenebrio molitor.

PubMed

Martínez, L C; Plata-Rueda, A; Colares, H C; Campos, J M; Dos Santos, M H; Fernandes, F L; Serrão, J E; Zanuncio, J C

2017-12-14

The study identified insecticidal effects from the cinnamon and clove essential oils in Tenebrio molitor L. (Coleoptera: Tenebrionidae). The lethal concentrations (LC50 and LC90), lethal time, and repellent effect on larvae, pupae, and adults of T. molitor after exposure to six concentrations of each essential oil and toxic compounds were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.19%), trans-3-caren-2-ol (9.92%), benzyl benzoate (9.68%), caryophyllene (9.05%), eugenyl acetate (7.47%), α-phellandrene (7.18%), and α-pinene (6.92%). In clove essential oil, the primary compounds were eugenol (26.64%), caryophyllene (23.73%), caryophyllene oxide (17.74%), 2-propenoic acid (11.84%), α-humulene (10.48%), γ-cadinene (4.85%), and humulene oxide (4.69%). Cinnamon and clove essential oils were toxic to T. molitor. In toxic chemical compounds, eugenol have stronger contact toxicity in larvae, pupae, and adult than caryophyllene oxide, followed by α-pinene, α-phellandrene, and α-humulene. In general, the two essential oils were toxic and repellent to adult T. molitor. Cinnamon and clove essential oils and their compounds caused higher mortality and repellency on T. molitor and, therefore, have the potential for integrated management programs of this insect.

Assessment of Health Effects of Exogenous Urea: Summary and Key Findings.

PubMed

Dickerson, Aisha S; Lee, Janice S; Keshava, Channa; Hotchkiss, Andrew; Persad, Amanda S

2018-05-01

Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.

Assessing Environmental Risks for Established Invasive Weeds: Dalmatian (Linaria dalmatica) and Yellow (L. vulgaris) Toadflax in North America

PubMed Central

Sing, Sharlene E.; Peterson, Robert K. D.

2011-01-01

Environmental risk assessments characterizing potential environmental impacts of exotic weeds are more abundant and comprehensive for potential or new invaders than for widespread and well-established species such as Dalmatian (Linaria dalmatica [L.] Mill.) and yellow (L. vulgaris Mill.) toadflax. Specific effects evaluated in our assessment of environmental risks posed by yellow and Dalmatian toadflax included competitive displacement of other plant species, reservoirs of plant disease, animal and insect use, animal toxicity, human toxicity and allergenicity, erosion, and wildfire. Effect and exposure uncertainties for potential impacts of toadflax on human and ecological receptors were rated. Using publicly available information we were able to characterize ecological and human health impacts associated with toadflax, and to identify specific data gaps contributing to a high uncertainty of risk. Evidence supporting perceived negative environmental impacts of invasive toadflax was scarce. PMID:21845161

Assessing environmental risks for established invasive weeds: Dalmatian (Linaria dalmatica) and yellow (L. vulgaris) toadflax in North America.

PubMed

Sing, Sharlene E; Peterson, Robert K D

2011-07-01

Environmental risk assessments characterizing potential environmental impacts of exotic weeds are more abundant and comprehensive for potential or new invaders than for widespread and well-established species such as Dalmatian (Linaria dalmatica [L.] Mill.) and yellow (L. vulgaris Mill.) toadflax. Specific effects evaluated in our assessment of environmental risks posed by yellow and Dalmatian toadflax included competitive displacement of other plant species, reservoirs of plant disease, animal and insect use, animal toxicity, human toxicity and allergenicity, erosion, and wildfire. Effect and exposure uncertainties for potential impacts of toadflax on human and ecological receptors were rated. Using publicly available information we were able to characterize ecological and human health impacts associated with toadflax, and to identify specific data gaps contributing to a high uncertainty of risk. Evidence supporting perceived negative environmental impacts of invasive toadflax was scarce.

Oral Toxicity and Intestinal Transport Mechanism of Colloidal Gold Nanoparticle-Treated Red Ginseng

PubMed Central

Bae, Song-Hwa; Yu, Jin; Go, Mi-Ran; Kim, Hyun-Jin; Hwang, Yun-Gu; Choi, Soo-Jin

2016-01-01

(1) Background: Application of nanotechnology or nanomaterials in agricultural food crops has attracted increasing attention with regard to improving crop production, quality, and nutrient utilization. Gold nanoparticles (Au-NPs) have been reported to enhance seed yield, germination rate, and anti-oxidant potential in food crops, raising concerns about their toxicity potential. In this study, we evaluated the oral toxicity of red ginseng exposed to colloidal Au-NPs during cultivation (G-red ginseng) in rats and their intestinal transport mechanism. (2) Methods: 14-day repeated oral administration of G-red ginseng extract to rats was performed, and body weight, hematological, serum biochemical, and histopathological values were analyzed. An in vitro model of human intestinal follicle-associated epithelium (FAE) and an intestinal epithelial monolayer system were used for intestinal transport mechanistic study. (3) Results: No remarkable oral toxicity of G-red ginseng extract in rats was found, and Au-NPs did not accumulate in any organ, although Au-NP transfer to G-red ginseng and some increased saponin levels were confirmed. Au-NPs were transcytozed by microfold (M) cells, but not by a paracellular pathway in the intestinal epithelium. (4) Conclusion: These findings suggest great potential of Au-NPs for agricultural food crops at safe levels. Further study is required to elucidate the functional effects of Au-NPs on ginseng and long-term toxicity. PMID:28335336

Linking waterlogging tolerance with Mn²⁺ toxicity: a case study for barley.

PubMed

Huang, X; Shabala, S; Shabala, L; Rengel, Z; Wu, X; Zhang, G; Zhou, M

2015-01-01

Vast agricultural areas are affected by flooding, causing up to 80% yield reduction and resulting in multibillion dollar losses. Up to now, the focus of plant breeders was predominantly on detrimental effects of anoxia, while other (potentially equally important) traits were essentially neglected; one of these is soil elemental toxicity. Excess water triggers a progressive decrease in soil redox potential, thus increasing the concentration of Mn(2+) that can be toxic to plants if above a specific threshold. This work aimed to quantify the relative contribution of Mn(2+) toxicity to waterlogging stress tolerance, using barley as a case study. Twenty barley (Hordeum vulgare) genotypes contrasting in waterlogging stress tolerance were studied for their ability to cope with toxic (1 mm) amounts of Mn(2+) in the root rhizosphere. Under Mn(2+) toxicity, chlorophyll content of most waterlogging-tolerant genotypes (TX9425, Yerong, CPI-71284-48 and CM72) remained above 60% of the control value, whereas sensitive genotypes (Franklin and Naso Nijo) had 35% less chlorophyll than 35% of controls. Manganese concentration in leaves was not related to visual Mn(2+) toxicity symptoms, suggesting that various Mn(2+) tolerance mechanisms might operate in different tolerant genotypes, i.e. avoidance versus tissue tolerance. The overall significant (r = 0.60) correlation between tolerance to Mn(2+) toxicity and waterlogging in barley suggests that plant breeding for tolerance to waterlogging traits may be advanced by targeting mechanisms conferring tolerance to Mn(2+) toxicity, at least in this species. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Emerging toxicities in the treatment of non-small cell lung cancer: ocular disorders.

PubMed

Agustoni, Francesco; Platania, Marco; Vitali, Milena; Zilembo, Nicoletta; Haspinger, Eva; Sinno, Valentina; Gallucci, Rosaria; de Braud, Filippo; Garassino, Marina Chiara

2014-02-01

The treatment of advanced disease (stage IIIb and IV) of non-small cell lung cancer (NSCLC) is based on systemic treatment with platinum-based chemotherapy or biological compounds depending on the disease molecular profile. In the last few years, intensive investigational efforts in anticancer therapy have led to the registration of new active chemotherapeutic agents, combination regimens, and biological drugs, expanding choices for customizing individual treatment. However, the introduction of new drugs in the clinical setting has led to several new toxicities, creating some difficulties in daily management. Among these, ocular toxicity is generally overlooked as more common toxicities such as myelosuppression, stomatitis, diarrhea, vomiting, "hand-foot syndrome", and neurological alterations attract greater attention. Ophthalmic complications from cytotoxic chemotherapeutics are rare, transient, and of mild/moderate intensity but irreversible acute disorders are possible. The best way to prevent potential irreversible visual complications is an awareness of the potential for ocular toxicity because dose reductions or early drug cessation can prevent serious ocular complications in the majority of cases. However, given the novelty of many therapeutic agents and the complexity of ocular pathology, oncologists may be unfamiliar with these adverse effects of anticancer therapy. Although toxicities from chemotherapy are generally intense but short lasting, toxicities related to targeted drugs are often milder but longer lasting and can persist throughout treatment. Here we review the principal clinical presentations of ocular toxicity arising from chemotherapy [1-3], target therapies [4], and newly developed drugs and provide some recommendations for monitoring and management of ocular toxicity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vitro and in silico antioxidant and toxicological activities of Achyrocline satureioides.

PubMed

Salgueiro, Andréia C F; Folmer, Vanderlei; da Rosa, Hemerson S; Costa, Márcio T; Boligon, Aline A; Paula, Fávero R; Roos, Daniel H; Puntel, Gustavo O

2016-12-24

Achyrocline satureioides ("macela or marcela") is a medicinal plant, traditionally collected in "Good Friday" before sunrise. In traditional medicine, dried flowers of A. satureioides are used as anti-dyspeptic, antispasmodic and anti-inflammatory. To evaluate the phytochemical profile and to present an in vitro and in silico approach about toxicity and antioxidant potential of A. satureioides flowers extract and its major phytoconstituents. Plant were collected according to the popular tradition. Extract were obtained by infusion and analyzed from high-performance liquid chromatography. Toxicity was evaluated in Artemia salina and human lymphocytes. Extract antioxidant activity was determined with total antioxidant capacity, DPPH • and ABTS +• scavenging, ferric reducing antioxidant power, deoxyribose degradation assay, and thiobarbituric acid reactive substances (TBA-RS) assay. TBA-RS inhibitions were evaluated in brain of rats for A. satureioides extract and its major phytoconstituents. Predictions of activity spectra for substances and in silico toxicity evaluation from major phytoconstituents were performed via computer simulation. Chromatographic data indicated isoquercitrin, quercetin and caffeic acid as main compounds in flowers extract. Toxicity tests demonstrated a very low toxic potential of A. satureioides. Extract exhibited antioxidant activities in low concentrations. Both extract and major phytochemicals standards showed protection against lipid peroxidation in brain of rats. Computer simulations pointed some biological activities in agreement with traditional use, as well as some experimental results found in this work. Moreover, in silico toxic predictions showed that the A. satureioides major compounds had low probability for toxic risk. Our results indicate that A. satureioides infusion possesses low toxicological potential and an effective antioxidant activity. These findings confirm the traditional use of this plant in the folk medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of nano and bulk ZrO2, TiO2 particles on soil nutrient contents and PGPR.

PubMed

Karunakaran, Gopalu; Suriyaprabha, Rangaraj; Manivasakan, Palanisamy; Yuvakkumar, Rathinam; Rajendran, Venkatachalam; Kannan, Narayanasamy

2013-01-01

Currently, nanometal oxides are used extensively in different industries such as medicine, cosmetics and food. The increased consumption of nanoparticles (NPs) leads the necessity to understand the fate of the nanoparticles in the environment. The present study focused on the ecotoxicological behaviour of bulk and nano ZrO2 (Zirconia) and TiO2 (Titania) particles on PGPR (plant growth promoting rhizobacteria), soil and its nutrient contents. The microbial susceptibility study showed that nano TiO2 had 13 +/- 0.9 mm (B. megaterium), 15 +/- 0.2 mm (P. fluorescens), 16 +/- 0.2 mm (A. vinelandii) and 12 +/- 0.3 mm (B. brevis) zones of inhibition. However, nano and bulk ZrO2 particles were non-toxic to PGPR. In addition, it was found that toxicity varied depends on the medium of reaction. The soil study showed that nano TiO2 was found to be highly toxic, whereas bulk TiO2 was less toxic towards soil bacterial populations at 1000 mg L(-1). In contrast, nano and bulk ZrO2 were found to be inert at 1000 mg L(-1). The observed zeta potential and hydrophobicity of TiO2 particles causes more toxic than ZrO2 in parallel with particle size. However, nano TiO2 decreases the microbial population as well as nutrient level of the soil but not zirconia. Our finding shows that the mechanism of toxicity depends on size, hydrophobic potential and zeta potential of the metal oxide particles. Thus, it is necessary to take safety measures during the disposal and use of such toxic nanoparticles in the soil to prevent their hazardous effects.

Characterizing toxicity of metal-contaminated sediments from mining areas

USGS Publications Warehouse

Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.

2015-01-01

This paper reviews methods for testing the toxicity of metals associated with freshwater sediments, linking toxic effects with metal exposure and bioavailability, and developing sediment quality guidelines. The most broadly applicable approach for characterizing metal toxicity is whole-sediment toxicity testing, which attempts to simulate natural exposure conditions in the laboratory. Standard methods for whole-sediment testing can be adapted to test a wide variety of taxa. Chronic sediment tests that characterize effects on multiple endpoints (e.g., survival, growth, and reproduction) can be highly sensitive indicators of adverse effects on resident invertebrate taxa. Methods for testing of aqueous phases (pore water, overlying water, or elutriates) are used less frequently. Analysis of sediment toxicity data focuses on statistical comparisons between responses in sediments from the study area and responses in one or more uncontaminated reference sediments. For large or complex study areas, a greater number of reference sediments is recommended to reliably define the normal range of responses in uncontaminated sediments – the ‘reference envelope’. Data on metal concentrations and effects on test organisms across a gradient of contamination may allow development of concentration-response models, which estimate metal concentrations associated with specified levels of toxic effects (e.g. 20% effect concentration or EC20). Comparisons of toxic effects in laboratory tests with measures of impacts on resident benthic invertebrate communities can help document causal relationships between metal contamination and biological effects. Total or total-recoverable metal concentrations in sediments are the most common measure of metal contamination in sediments, but metal concentrations in labile sediment fractions (e.g., determined as part of selective sediment extraction protocols) may better represent metal bioavailability. Metals released by the weak-acid extraction of acid-volatile sulfide (AVS), termed simultaneously-extracted metals (SEM), are widely used to estimate the ‘potentially-bioavailable’ fraction of metals that is not bound to sulfides (i.e., SEM-AVS). Metal concentrations in pore water are widely considered to be direct measures of metal bioavailability, and predictions of toxicity based on pore-water metal concentrations may be further improved by modeling interactions of metals with other pore-water constituents using Biotic Ligand Models. Data from sediment toxicity tests and metal analyses has provided the basis for development of sediment quality guidelines, which estimate thresholds for toxicity of metals in sediments. Empirical guidelines such as Probable Effects Concentrations or (PECs) are based on associations between sediment metal concentrations and occurrence of toxic effects in large datasets. PECs do not model bioavailable metals, but they can be used to estimate the toxicity of metal mixtures using by calculation of probable effect quotients (PEQ = sediment metal concentration/PEC). In contrast, mechanistic guidelines, such as Equilibrium Partitioning Sediment Benchmarks (ESBs) attempt to predict both bioavailability and mixture toxicity. Application of these simple bioavailability models requires more extensive chemical characterization of sediments or pore water, compared to empirical guidelines, but may provide more reliable estimates of metal toxicity across a wide range of sediment types.

Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging.

PubMed

Mititelu, Mihai; Wong, Brandon J; Brenner, Marie; Bryar, Paul J; Jampol, Lee M; Fawzi, Amani A

2013-09-01

Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. Retinal toxic effects. Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.

Systematic and comprehensive investigation of the toxicity of curcuminoid‑essential oil complex: A bioavailable turmeric formulation.

PubMed

Aggarwal, Madan L; Chacko, Karampendethu M; Kuruvilla, Binu T

2016-01-01

Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti‑inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid‑essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non‑mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non‑toxic pharmacological formulation.

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway.

PubMed

Kharasch, Evan D; Schroeder, Jesara L; Liggitt, H Denny; Park, Sang B; Whittington, Dale; Sheffels, Pamela

2006-10-01

Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite. Concern exists about potential renal toxicity from volatile anesthetic defluorination, but many anesthetics increase fluoride concentrations without consequence. Methoxyflurane is metabolized by both dechlorination to methoxydifluoroacetic acid (MDFA, which may degrade to fluoride) and O-demethylation to fluoride and dichloroacetatic acid. The metabolic pathway responsible for methoxyflurane nephrotoxicity has not, however, been identified, which was the aim of this investigation. Experiments evaluated methoxyflurane metabolite formation and effects of enzyme induction or inhibition on methoxyflurane metabolism and toxicity. Rats pretreated with phenobarbital, barium sulfate, or nothing were anesthetized with methoxyflurane, and renal function and urine methoxyflurane metabolite excretion were assessed. Phenobarbital effects on MDFA metabolism and toxicity in vivo were also assessed. Metabolism of methoxyflurane and MDFA in microsomes from livers of pretreated rats was determined in vitro. Phenobarbital pretreatment increased methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen and decreased urine osmolality) and induced in vitro hepatic microsomal methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid (1.5-fold), and MDFA (5-fold). In contrast, phenobarbital had no influence on MDFA renal effects in vivo or MDFA metabolism in vitro or in vivo. MDFA was neither metabolized to fluoride nor nephrotoxic. Barium sulfate diminished methoxyflurane metabolism and nephrotoxicity in vivo. Fluoride from methoxyflurane anesthesia derives from O-demethylation. Phenobarbital increases in methoxyflurane toxicity do not seem attributable to methoxyflurane dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite, suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation. Fluoride, one of many metabolites from O-demethylation, may be toxic and/or reflect formation of a different toxic metabolite. These results may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.

Environmental contaminants

USGS Publications Warehouse

Hoffman, D.J.; Rattner, B.A.; Scheunert, I.; Korte, F.; Shore, Richard F.; Rattner, Barnett A.

2001-01-01

The purpose of this chapter is to provide an overview of the ecotoxicology of major classes of environmental contaminants, with respect to sources, environmental chemistry, most likely routes of exposure, potential bioaccumulation and biomagification, mechanisms of toxicity, and effects on potentially vulnerable species of mammalian wildlife. Major contaminants reviewed were selected on the basis of their use patterns, availability and potential toxicity to wild mammals. These included pesticides used in agroecosystems (organochlorines, organophosphorus and carbamate compounds, anticoagulants, herbicides and fungicides), various organic pollutants (chlorobenzenes, chlorophenols, polychlorinated biphenyls, dibenzodioxins and dibenzofurans, and polycyclic aromatic hydrocarbons), heavy metals (lead, mercury, and cadmium), agricultural drainwater mixtures, leachates and radionuclides. Many of the above aspects of ecotoxicology and contaminants will be expanded upon in subsequent chapters of this book as they relate to distinct mammalian species and potential risk.

Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

PubMed

Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

2018-06-06

The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

A review of environmental impacts of salts from produced waters on aquatic resources

USGS Publications Warehouse

Farag, Aïda M.; Harper, David D.

2014-01-01

Salts are frequently a major constituent of waste waters produced during oil and gas production. These produced waters or brines must be treated and/or disposed and provide a daily challenge for operators and resource managers. Some elements of salts are regulated with water quality criteria established for the protection of aquatic wildlife, e.g. chloride (Cl−), which has an acute standard of 860 mg/L and a chronic standard of 230 mg/L. However, data for establishing such standards has only recently been studied for other components of produced water, such as bicarbonate (HCO3−), which has acute median lethal concentrations (LC50s) ranging from 699 to > 8000 mg/L and effects on chronic toxicity from 430 to 657 mg/L. While Cl− is an ion of considerable importance in multiple geographical regions, knowledge about the effects of hardness (calcium and magnesium) on its toxicity and about mechanisms of toxicity is not well understood. A multiple-approach design that combines studies of both individuals and populations, conducted both in the laboratory and the field, was used to study toxic effects of bicarbonate (as NaHCO3). This approach allowed interpretations about mechanisms related to growth effects at the individual level that could affect populations in the wild. However, additional mechanistic data for HCO3−, related to the interactions of calcium (Ca2 +) precipitation at the microenvironment of the gill would dramatically increase the scientific knowledge base about how NaHCO3 might affect aquatic life. Studies of the effects of mixtures of multiple salts present in produced waters and more chronic effect studies would give a better picture of the overall potential toxicity of these ions. Organic constituents in hydraulic fracturing fluids, flowback waters, etc. are a concern because of their carcinogenic properties and this paper is not meant to minimize the importance of maintaining vigilance with respect to potential organic contamination.

Independent University Study to Assess the Performance of a Humate Amendment for Copper Detoxification at the H-12 Outfall at Savannah River Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looney, B.; Harmon, S.; King, J.

2016-09-06

The overarching objective of this study was to evaluate the effectiveness of the copper detoxification process that is in place at the Savannah River Site H-12 Outfall. The testing was performed in two phases; Phase 1 assessed the safety and potential for intrinsic toxicity of the humate amendment being used at the H-12 Outfall, Borregro HA-1, as well as an alternative amendment sodium humic acid. The second phase assessed the effectiveness of Borregro HA-1 in mitigating and reducing toxic effects of copper.

Identification and Avoidance of Potential Artifacts and Misinterpretations in Nanomaterial Ecotoxicity Measurements

PubMed Central

2015-01-01

Novel physicochemistries of engineered nanomaterials (ENMs) offer considerable commercial potential for new products and processes, but also the possibility of unforeseen and negative consequences upon ENM release into the environment. Investigations of ENM ecotoxicity have revealed that the unique properties of ENMs and a lack of appropriate test methods can lead to results that are inaccurate or not reproducible. The occurrence of spurious results or misinterpretations of results from ENM toxicity tests that are unique to investigations of ENMs (as opposed to traditional toxicants) have been reported, but have not yet been systemically reviewed. Our objective in this manuscript is to highlight artifacts and misinterpretations that can occur at each step of ecotoxicity testing: procurement or synthesis of the ENMs and assessment of potential toxic impurities such as metals or endotoxins, ENM storage, dispersion of the ENMs in the test medium, direct interference with assay reagents and unacknowledged indirect effects such as nutrient depletion during the assay, and assessment of the ENM biodistribution in organisms. We recommend thorough characterization of initial ENMs including measurement of impurities, implementation of steps to minimize changes to the ENMs during storage, inclusion of a set of experimental controls (e.g., to assess impacts of nutrient depletion, ENM specific effects, impurities in ENM formulation, desorbed surface coatings, the dispersion process, and direct interference of ENM with toxicity assays), and use of orthogonal measurement methods when available to assess ENMs fate and distribution in organisms. PMID:24617739

Prioritization of reproductive toxicants in unconventional oil and gas operations using a multi-country regulatory data-driven hazard assessment.

PubMed

Inayat-Hussain, Salmaan H; Fukumura, Masao; Muiz Aziz, A; Jin, Chai Meng; Jin, Low Wei; Garcia-Milian, Rolando; Vasiliou, Vasilis; Deziel, Nicole C

2018-08-01

Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence-based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi-national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases. GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple adverse effects. We observed substantial inconsistencies in classification among the 11 databases. By adopting the most stringent classification within and across countries, 43 chemicals were classified as known or presumed human reproductive toxicants (GHS Category 1), while 31 chemicals were classified as suspected human reproductive toxicants (GHS Category 2). The 43 reproductive toxicants were further subjected to analysis for carcinogenic and mutagenic properties. Calculated hazard scores and Cytoscape visualization yielded several high priority chemicals including potassium dichromate, cadmium, benzene and ethylene oxide. Our findings reveal diverging GHS classification outcomes for UOG chemicals across regulatory agencies. Adoption of the most stringent classification with application of hazard scores provides a useful approach to prioritize reproductive toxicants in UOG and other industries for exposure assessments and selection of safer alternatives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Halogenated flame retardants: do the fire safety benefits justify the risks?

PubMed

Shaw, Susan D; Blum, Arlene; Weber, Roland; Kannan, Kurunthachalam; Rich, David; Lucas, Donald; Koshland, Catherine P; Dobraca, Dina; Hanson, Sarah; Birnbaum, Linda S

2010-01-01

Since the 1970s, an increasing number of regulations have expanded the use of brominated and chlorinated flame retardants. Many of these chemicals are now recognized as global contaminants and are associated with adverse health effects in animals and humans, including endocrine and thyroid disruption, immunotoxicity, reproductive toxicity, cancer, and adverse effects on fetal and child development and neurologic function. Some flame retardants such as polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily phased out by manufacturers because of their environmental persistence and toxicity, only to be replaced by other organohalogens of unknown toxicity. Despite restrictions on further production in some countries, consumer products previously treated with banned retardants are still in use and continue to release toxic chemicals into the environment, and the worldwide use of organohalogen retardants continues to increase. This paper examines major uses and known toxic effects of commonly-used organohalogen flame retardants, replacements for those that have been phased out, their combustion by-products, and their effectiveness at reducing fire hazard. Policy and other solutions to maintain fire safety while reducing toxicity are suggested. The major conclusions are: (1) Flammability regulations can cause greater adverse environmental and health impacts than fire safety benefits. (2) The current options for end-of-life disposal of products treated with organohalogens retardants are problematic. (3) Life-cycle analyses evaluating benefits and risks should consider the health and environmental effects of the chemicals, as well as their fire safety impacts. (4) Most fire deaths and most fire injuries result from inhaling carbon monoxide, irritant gases, and soot. The incorporation of organohalogens can increase the yield of these toxic by-products during combustion. (5) Fire-safe cigarettes, fire-safe candles, child-resistant lighters, sprinklers, and smoke detectors can prevent fires without the potential adverse effects of flame retardant chemicals. (6) Alternatives to organohalogen flame retardant chemicals include using less flammable materials, design changes, and safer chemicals. To date, before evaluating their health and environmental impacts, many flame retardant chemicals have been produced and used, resulting in high levels of human exposure. As a growing literature continues to find adverse impacts from such chemicals, a more systematic approach to their regulation is needed. Before implementing new flammability standards, decision-makers should evaluate the potential fire safety benefit versus the health and environmental impacts of the chemicals, materials, or technologies likely to be used to meet the standard. Reducing the use of toxic or untested flame retardant chemicals in consumer products can protect human and animal health and the global environment without compromising fire safety.

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donlon, B.A.; Razo-Flores, E.; Field, J.A.

1995-11-01

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated associated with the industrial production of dyes, explosives, pestides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationship of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed to serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and themore » degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. 41 refs., 3 figs., 1 tab.« less

Tandem screening of toxic compounds on GFP-labeled bacteria and cancer cells in microtiter plates.

PubMed

Montoya, Jessica; Varela-Ramirez, Armando; Shanmugasundram, Muthian; Martinez, Luis E; Primm, Todd P; Aguilera, Renato J

2005-09-23

A 96-well fluorescence-based assay has been developed for the rapid screening of potential cytotoxic and bacteriocidal compounds. The assay is based on detection of green fluorescent protein (GFP) in HeLa human carcinoma cells as well as gram negative (Escherichia coli) and gram positive bacteria (Mycobacterium avium). Addition of a toxic compound to the GFP marked cells resulted in the loss of the GFP fluorescence which was readily detected by fluorometry. Thirty-nine distinct naphthoquinone derivatives were screened and several of these compounds were found to be toxic to all cell types. Apart from differences in overall toxicity, two general types of toxic compounds were detected, those that exhibited toxicity to two or all three of the cell types and those that were primarily toxic to the HeLa cells. Our results demonstrate that the parallel screening of both eukaryotic and prokaryotic cells is not only feasible and reproducible but also cost effective.

Toxicity and Detoxification Effects of Herbal Caowu via Ultra Performance Liquid Chromatography/Mass Spectrometry Metabolomics Analyzed using Pattern Recognition Method

PubMed Central

Yan, Yan; Zhang, Aihua; Dong, Hui; Yan, Guangli; Sun, Hui; Wu, Xiuhong; Han, Ying; Wang, Xijun

2017-01-01

Background: Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful joints, and tumors for thousands of years. However, the toxicity of heart and central nervous system induced by CW still limited the application. Materials and Methods: Metabolomics was performed to identify the sensitive and reliable biomarkers and to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity, and the detoxification by combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by pattern recognition methods. Results: As a result, the metabolites were characterized and responsible for pentose and glucuronate interconversions, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose metabolism, six networks of which were the same to the metabolic pathways of Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was also characterized by CW group. The urinary metabolomics also revealed CW-induced serious toxicity to heart and liver. Thirteen significant metabolites were identified and had validated as phenotypic toxicity biomarkers of CW, five biomarkers of which were commonly owned in Aconitum. The changes of toxicity metabolites obtained from combinatorial intervention of CG, CB, and CR also were analyzed to investigate the regulation degree of toxicity biomarkers adjusted by different combinatorial interventions at 6th month. Conclusion: Metabolomics analyses coupled with pattern recognition methods in the evaluation of drug toxicity and finding detoxification methods were highlighted in this work. SUMMARY Metabolomics was performed to characterize the biochemical potential mechanisms of Caowu toxicityThirteen significant metabolites were identified and validated as phenotypic toxicity biomarkers of CaowuMetabolite changes of toxicity obtained can be adjusted by different combinatorial interventions.Pattern recognition plot reflects the toxicity effects tendency of the urine metabolic fluctuations according to time after treatment of herbal Caowu. Abbreviations used: CW: Caowu (Radix Aconiti kusnezoffii); CHW: Chuanwu (Radix Aconiti); TCM: Traditional Chinese Medicine; CG: Caowu and Gancao; CB: Caowu and Baishao; CR: Caowu and Renshen; QC: Quality control; UPLC: Ultra performance liquid chromatography; MS: Mass spectrometry; PCA: Principal component analysis; PLS-DA: Partial least squares-discriminant analysis; OPLS: Orthogonal projection to latent structures analysis. PMID:29200734

Interactive effects of temperature and drought on cassava growth and toxicity: implications for food security?

PubMed

Brown, Alicia L; Cavagnaro, Timothy R; Gleadow, Ros; Miller, Rebecca E

2016-10-01

Cassava is an important dietary component for over 1 billion people, and its ability to yield under drought has led to it being promoted as an important crop for food security under climate change. Despite its known photosynthetic plasticity in response to temperature, little is known about how temperature affects plant toxicity or about interactions between temperature and drought, which is important because cassava tissues contain high levels of toxic cyanogenic glucosides, a major health and food safety concern. In a controlled glasshouse experiment, plants were grown at 2 daytime temperatures (23 °C and 34 °C), and either well-watered or subject to a 1 month drought prior to harvest at 6 months. The objective was to determine the separate and interactive effects of temperature and drought on growth and toxicity. Both temperature and drought affected cassava physiology and chemistry. While temperature alone drove differences in plant height and above-ground biomass, drought and temperature × drought interactions most affected tuber yield, as well as foliar and tuber chemistry, including C : N, nitrogen and cyanide potential (CNp; total cyanide released from cyanogenic glucosides). Conditions that most stimulated growth and yield (well-watered × high temperature) effected a reduction in tuber toxicity, whereas drought inhibited growth and yield, and was associated with increased foliar and tuber toxicity. The magnitude of drought effects on tuber yield and toxicity were greater at high temperature; thus, increases in tuber CNp were not merely a consequence of reduced tuber biomass. Findings confirm that cassava is adaptable to forecast temperature increases, particularly in areas of adequate or increasing rainfall; however, in regions forecast for increased incidence of drought, the effects of drought on both food quality (tuber toxicity) and yield are a greater threat to future food security and indicate an increasing necessity for processing of cassava to reduce toxicity. © 2016 John Wiley & Sons Ltd.

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro-Filho, Jaime; Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba; Calheiros, Andrea Surrage

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effectsmore » of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine mechanisms involve inhibition of Ca{sup 2+} influx, and IL-13 and eotaxin secretion. • No significant toxicity was observed in mice orally treated with curine for 7 days. • Curine has the potential for the development of anti-asthmatic drugs.« less

Detoxification of sewage sludge by natural attenuation and implications for its use as a fertilizer on agricultural soils.

PubMed

Mazzeo, Dânia Elisa Christofoletti; Casado, Marta; Piña, Benjamin; Marin-Morales, Maria Aparecida

2016-12-01

Sewage Sludges (SS) from wastewater treatment systems constitute a potential alternative to agricultural fertilizers. However, their use is limited by the presence of toxic substances that may represent significant hazards for the environment and for human health. To test the potential of natural processes to attenuate their putative toxic activities, actual SS samples from domestic sewage were buried in holes in a pollution-free environment for different periods of time, up to one year. Aqueous and organic extracts were obtained after each period of natural attenuation, and their respective toxicity was tested for estrogenic and dioxin-like activity by yeast-based bioassays (ER-RYA and AhR-RYA, respectively) and for general toxicity and teratogenicity in zebrafish embryos. Dioxin-like activity was also tested in zebrafish embryos by monitoring the induction of the marker gene cyp1a. Whereas the results showed essentially no estrogenic activity, both dioxin-like activity and embryotoxicity were observed in the initial samples, decreasing significantly after six months of attenuation. Chemical analysis of toxic SS samples showed the presence of low levels of dioxins and furans, and relatively high levels of m- and p-cresol, at concentrations that only partially justify the observed biological effects. Our data indicates the presence of largely uncharacterized hydrophilic compounds with high biological activity in SS, constituting a potential risk of groundwater pollution upon their disposal into the environment. It also shows that this potential impact may be significantly mitigated by attenuation protocols, as the one presented here. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits.

PubMed

Nye, Monica D; Fry, Rebecca C; Hoyo, Cathrine; Murphy, Susan K

2014-01-01

Increasing evidence suggest that epigenetic alterations can greatly impact human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation and disease development by controlling gene expression. In this review we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are being studied in newborns as potential biomarkers of in utero environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms are impacted by early life exposure to iAs and Pb, and the research that is being done to move towards understanding the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early life toxic metal exposure on epigenetic changes and how these changes may result in later development of disease.

Mixture toxicity of six sulfonamides and their two transformation products to green algae Scenedesmus vacuolatus and duckweed Lemna minor.

PubMed

Białk-Bielińska, Anna; Caban, Magda; Pieczyńska, Aleksandra; Stepnowski, Piotr; Stolte, Stefan

2017-04-01

Since humans and ecosystems are continually exposed to a very complex and permanently changing mixture of chemicals, there is increasing concern in the general public about the potential adverse effects they may cause. Among all "emerging pollutants", pharmaceuticals in particular have raised great environmental concern. For these reasons the aim of our study was to evaluate the mixture toxicity of six antimicrobial sulfonamides (SAs) and their two most commonly identified degradation products - sulfanilic acid (SNA) and sulfanilamide (SN) - to limnic green algae Scenedesmus vacuolatus and duckweed Lemna minor. The ecotoxicological data for the single toxicity of SNA and SN towards selected organisms are presented. The concept of Concentration Addition (CA) was applied to estimate the effects, and less than additive effects were observed. In general terms, it seems sufficiently precautionary for the aquatic environment to consider the toxicity of a sulfonamide mixture as additive. The Concentration Addition model proves to be a reasonable worst-case estimation. Such a comparative study on the mixture toxicity of sulfonamides and their transformation products has been presented for the first time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxic behavior of silver and zinc oxide nanoparticles on environmental microorganisms.

PubMed

Dhas, Sindhu Priya; Shiny, Punalur John; Khan, Sudheer; Mukherjee, Amitava; Chandrasekaran, Natrajan

2014-09-01

Silver and zinc oxide nanoparticles (Ag and ZnO NPs) are widely used as antimicrobial agents. However, their potential toxicological impact on environmental microorganisms is largely unexplored. The aim of this work was to investigate the sensitivity and adaptability of five bacterial species isolated from sewage towards Ag and ZnO NPs. The bacterial species were exposed to increasing concentration of nanoparticles and the growth inhibitory effect, exopolysaccharides (EPSs) and extracellular proteins (ECPs) productions were determined. The involvement of surface charge in nanoparticles toxicity was also determined. The bacterial species were constantly exposed to nanoparticles to determine the adaptation behavior toward nanoparticles. The nanoparticles exhibited remarkable growth inhibitory effect on tested bacterial species. The toxicity of nanoparticles was found to be strongly dependent on surface charge effects. Though, these organisms are highly sensitive to Ag and ZnO NPs, the continuous exposure to these nanoparticles leads to moderate adaptation of bacterial species and the adapted bacterial species convert the highly toxic nano form to less toxic microform. Finally we predict that the continuing applications of nanoparticles in consumer products may lead to the development of nanoparticles resistant bacterial strains in future. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environmental sentinel biomonitors: integrated response systems for monitoring toxic chemicals

NASA Astrophysics Data System (ADS)

van der Schalie, William H.; Reuter, Roy; Shedd, Tommy R.; Knechtges, Paul L.

2002-02-01

Operational environments for military forces are becoming potentially more dangerous due to the increased number, use, and misuse of toxic chemicals across the entire range of military missions. Defense personnel may be exposed to harmful chemicals as a result of industrial accidents or intentional or unintentional action of enemy, friendly forces, or indigenous populations. While there has been a significant military effort to enable forces to operate safely and survive and sustain operations in nuclear, biological, chemical warfare agent environments, until recently there has not been a concomitant effort associated with potential adverse health effects from exposures of deployed personnel to toxic industrial chemicals. To provide continuous real-time toxicity assessments across a broad spectrum of individual chemicals or chemical mixtures, an Environmental Sentinel Biomonitor (ESB) system concept is proposed. An ESB system will integrate data from one or more platforms of biologically-based systems and chemical detectors placed in the environment to sense developing toxic conditions and transmit time-relevant data for use in risk assessment, mitigation, and/or management. Issues, challenges, and next steps for the ESB system concept are described, based in part on discussions at a September 2001 workshop sponsored by the U.S. Army Center for Environmental Health Research.

Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity.

PubMed

Hornsby, Lori B; Whitley, Heather P; Hester, E Kelly; Thompson, Melissa; Donaldson, Amy

2010-01-01

To assess patient knowledge regarding acetaminophen dosing, toxicity, and recognition of acetaminophen-containing products. Descriptive, nonexperimental, cross-sectional study. Alabama, January 2007 to February 2008. 284 patients at four outpatient medical facilities. 12-item investigator-administered questionnaire. Degree of patient knowledge regarding acetaminophen safety, dosing recommendations, toxicity, alternative names and abbreviations, and products. Two-thirds of the 284 patients completing the survey reported current or recent use of pain, cold, or allergy medication. Of these, 25% reported knowing the active ingredient. Of patients, 46% and 13% knew that "acetaminophen" and "APAP," respectively, were synonymous with "Tylenol." Several patients (12%) believed that ingesting a harmful amount of acetaminophen was difficult or impossible. One-third of patients correctly identified the maximum daily dose, 10% reported a dose greater than 4 g, 25% were unsure of the dose, and 7% were unsure whether a maximum dose existed. One-half recognized liver damage as the primary toxicity. Results were similar between acetaminophen users and nonusers. Deficiencies were found in patient knowledge regarding acetaminophen recognition, dosing, and potential for toxicity. The development of effective educational initiatives is warranted to ensure patient awareness and limit the potential for acetaminophen overdose.

Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.

PubMed

Schaer, C A; Deuel, J W; Bittermann, A G; Rubio, I G; Schoedon, G; Spahn, D R; Wepf, R A; Vallelian, F; Schaer, D J

2013-11-01

Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.

Effects of water chemistry and surface contact on the toxicity of silver nanoparticles to Bacillus subtilis.

PubMed

Yi, Jun; Cheng, Jinping

2017-07-01

The growing use of silver nanoparticles (AgNPs) has created concerns about its potential impacts on natural microbial communities. In this study, the physicochemical properties of AgNPs and its toxicity on natural bacteria Bacillus subtilis (B. subtilis) were investigated in aqueous conditions. The characterization data showed that AgNPs highly aggregated in aqueous conditions, and the hydrodynamic diameter of AgNPs in aqueous conditions was larger than its primary size. The studied AgNPs was less toxic to B. subtilis in estuarine water as compared to that in Milli-Q water and artificial seawater, which might be due to the observed enhanced aggregation of AgNPs in estuarine water. The toxicity of AgNPs to B. subtilis was greatly reduced when their surface contact was blocked by a dialysis membrane. Scanning electron microscope images showed that exposure contact to AgNPs resulted in damage of the microbial cell wall and enhanced formation of fibrillar structures. These results suggest that particle-cell contact is largely responsible for the observed toxicity of AgNPs in B. subtilis. This study can help to understand the potential impacts of AgNPs to natural microbes, especially in the complex aquatic environments.

Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

PubMed Central

Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy; Sprando, Robert L.

2016-01-01

A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement. PMID:27703475

Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview

PubMed Central

Singh, Divya; Cho, William C.; Upadhyay, Ghanshyam

2016-01-01

The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for drug-induced liver damage. Endorsed medications represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and natural products in the treatment of various disorders led the investigators to look into their potential in countering drug-induced liver toxicity. Several natural products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less adverse reactions of the natural products provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication. PMID:26858648

Glyphosate, a chelating agent-relevant for ecological risk assessment?

PubMed

Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

2018-02-01

Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

The interactive effects of essential ions and salinity on the survival of Mysidopsis bahia in 96-H acute toxicity tests of effluents discharged to marine and estuarine receiving waters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, W.S.; Horne, M.T.

1997-10-01

The importance of salinity in whole effluent toxicity tests using marine organisms has been acknowledged in most testing protocols. However, little if any attention has been given to the specific effects of alteration of the ionic composition of seawater solutions to the test organism. The presence of persistent toxicity in effluents with no apparent toxic agents prompted examination of the potential influence of essential ions on the survival of the opossum shrimp, Mysidopsis bahia, a common effluent toxicity indicator organism. Through stepwise additions of ionic salts to deionized water, the minimum complement of salts to maintain survival of M. bahiamore » during 96-h exposures was determined to be Ca, Mg, K, Br, Na, and Cl. The toxicity curves for Ca, Mg, K, and Br were then determined across test salinity ranging from 10 to 35 parts per thousand. These curves for Ca, Mg, and K revealed that there are significant negative effects on survival when the essential ions are present in either low or high concentrations relative to the levels in natural seawater. Although there were no statistically detectable effects of Br on organism survival over the concentration range tested (5--480 mg/L). Br toxicity at concentrations less than 5 mg/L and greater than 700 mg/L have been shown in other studies. In addition, the tolerance ranges for K, Ca, and Mg were shown to shift significantly with changes in salinity, with lower salinity causing an apparent decrease in tolerance to an excess of essential ions. Tests with toxic effluents from five industrial and municipal sources revealed that adjustment of the ionic balance prior to testing reduced or eliminated toxicity in four of the five whole effluents tested. Suggestions for integrating this information into biomonitoring programs and toxicity identification evaluations are presented.« less

FETAX assay for evaluation of developmental toxicity.

PubMed

Mouche, Isabelle; Malesic, Laure; Gillardeaux, Olivier

2011-01-01

The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larva. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

FETAX Assay for Evaluation of Developmental Toxicity.

PubMed

Mouche, Isabelle; Malésic, Laure; Gillardeaux, Olivier

2017-01-01

The frog embryo teratogenesis assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula-stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larvae. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

A review of developmental and reproductive toxicity of CS2 and H2 S generated by the pesticide sodium tetrathiocarbonate.

PubMed

Silva, Marilyn

2013-04-01

Sodium tetrathiocarbonate (STTC) is an example of a pesticide that when prepared for use in aqueous solution releases two toxic products carbon disulfide (CS2 ) (active ingredient) and hydrogen sulfide (H2 S) in ambient air in equimolar concentrations resulting in potential exposure to workers and bystanders. CS2 and H2 S are pollutants that are generated from several pesticides as well as in industrial settings. Registrant submitted reports and open literature studies for STTC, CS2 and H2 S were reviewed. Previous reports suggest that CS2 was a concern as a developmental and reproductive toxicant. H2 S was also examined since it is a neurotoxicant and potentially harmful to developing fetuses. STTC did not induce developmental or reproductive effects in animal studies. CS2 was a developmental neurobehavioral toxin in rat pups (inhalation no observed effect level [NOEL]=0.01 ppm). Reproductive effects occurred in male and female factory workers after CS2 exposure (NOEL=1 ppm). H2 S had developmental effects in rats at doses at or above those observed for nasal pathology (NOEL=10 ppm) but was not a reproductive or developmental toxin in humans. The database for CS2 indicates a strong potential for developmental neurotoxicity in animals at low doses but it is lacking in acceptable, well-performed studies. There is also a lack of studies performed with CS2 and H2 S as a mixture. © 2013 Wiley Periodicals, Inc.

Comparison of toxicity of class-based organic chemicals to algae and fish based on discrimination of excess toxicity from baseline level.

PubMed

Li, Jin J; Tai, Hong W; Yu, Yang; Wen, Yang; Wang, Xiao H; Zhao, Yuan H

2015-07-01

Toxicity data to fish and algae were used to investigate excess toxicity between species. Results show that chemicals exhibiting excess toxicity to fish also show excess toxicity to algae for most of the compounds. This indicates that they share the same mode of action between species. Similar relationships between logKOW and toxicities to fish and algae for baseline and less inert compounds suggest that they have similar critical body residues in the two species. Differences in excess toxicity for some compounds suggest that there is a difference of physiological structure and metabolism between fish and algae. Some reactive compounds (e.g. polyamines) exhibit greater toxic effects for algae than those for fish because of relatively low bio-uptake potential of these hydrophilic compounds in fish as compared with that in algae. Esters exhibiting greater toxicity in fish than that in algae indicate that metabolism can affect the discrimination of excess toxicity from baseline level. Algae growth inhibition is a very good surrogate for fish lethality. This is not only because overall toxicity sensitivity to algae is greater than that to fish, but also the excess toxicity calculated from algal toxicity can better reflect reactivity of compounds with target molecules than fish toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of the toxicity of the peracetic acid formulations Wofasteril(c) E400, E250 and Lspez to Daphnia magna with emphasis on the effect of hydrogen peroxide

USDA-ARS?s Scientific Manuscript database

Commercial peracetic acid (PAA) formulations are acidic mixtures of PAA, hydrogen peroxide (H2O2), acetic acid (AA), H2O and stabilizers to maintain equilibrium of the concentrations. Different PAA formulations show diverse PAA/H2O2 ratios, leading to potentially different toxicities at the same con...

Sublethal Growth Effects and Mortality to Marine Bivalves and Fish from Long-Term Exposure to Tributyltin.

DTIC Science & Technology

1985-07-01

sublethal toxicity of tributyltin oxide (TBTO) and its putative environmental product, tribu- tyltin sulfide ( TBTS ) to zoeal mud crabs, RIthropanopeus...EXPOSURE TO TRIBUTYLTIN A. Valkirs . B. Davidson Computer Sciences Corporation P. Seligman Naval Ocean Systems Center -5 . - - Naval Ocean Systems...Organotin .,’vwfuf coatingsu~~ study better defines the longterm toxicity and bloaccumnulation potential of tributyltin released from antifouting

Cross-species extrapolation of toxicity information using the ...

EPA Pesticide Factsheets

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two tiered approach for screening chemicals that applied standardized in vitro and in vivo toxicity tests. The Tier 1 screening assays were designed to identify substances that have the potential of interacting with the endocrine system and Tier 2 testing was developed to identify adverse effects caused by the chemical, with documentation of dose-response relationships. While this tiered approach was effective in identifying possible endocrine disrupting chemicals, the cost and time to screen a single chemical was significant. Therefore, in 2012 the EDSP proposed a transition to make greater use of computational approaches (in silico) and high-throughput screening (HTS; in vitro) assays to more rapidly and cost-efficiently screen chemicals for endocrine activity. This transition from resource intensive, primarily in vivo, screening methods to more pathway-based approaches aligns with the simultaneously occurring transformation in toxicity testing termed “Toxicity Testing in the 21st Century” which shifts the focus to the disturbance of the biological pathway predictive of the observable toxic effects. An example of such screening tools include the US Environmental Protection Agency’s

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom.

PubMed

Lazcano-Pérez, Fernando; Zavala-Moreno, Ariana; Rufino-González, Yadira; Ponce-Macotela, Martha; García-Arredondo, Alejandro; Cuevas-Cruz, Miguel; Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Arreguín-Lozano, Barbarín; Arreguín-Espinosa, Roberto

2018-01-01

Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis . The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA 2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. P. caribaeorum venom produced hemolytic and PLA 2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Local and systemic toxicity of JP-8 from cutaneous exposures.

PubMed

McDougal, James N; Rogers, James V

2004-04-01

Jet propellant-8 (JP-8) jet fuel is a version of commercial jet fuel, Jet A, and is a complex mixture of primarily aliphatic (but also aromatic) hydrocarbons that varies in composition from batch to batch. There is potential for dermal exposure to jet fuels with personnel involved in aircraft refueling and maintenance operations as well as ground personnel. Cutaneous exposures have the potential to cause skin irritation, sensitization or skin cancer. JP-8 has been shown to be irritating and causes molecular changes in the skin of laboratory animals. The mechanisms of some of these effects have been investigated in intact skin and cultured skin cells. Hydrocarbons have also been shown to cause skin cancer with repeated application to the skin. Additionally, there is concern about systemic toxicity from dermal exposures to jet fuels, such as JP-8. Assessing risks from systemic absorption of hydrocarbon components is complex because most of the components are present in the mixture in small quantities (less than 1%). The effect of the fuel as a vehicle, different rates of penetration through the skin and different target organ toxicities all complicate the assessment of the hazards of cutaneous exposures. The purpose of this manuscript is to review studies of local and systemic toxicity of JP-8.

Bio-oils from biomass slow pyrolysis: a chemical and toxicological screening.

PubMed

Cordella, Mauro; Torri, Cristian; Adamiano, Alessio; Fabbri, Daniele; Barontini, Federica; Cozzani, Valerio

2012-09-15

Bio-oils were produced from bench-scale slow-pyrolysis of three different biomass samples (corn stalks, poplar and switchgrass). Experimental protocols were developed and applied in order to screen their chemical composition. Several hazardous compounds were detected in the bio-oil samples analysed, including phenols, furans and polycyclic aromatic hydrocarbons. A procedure was outlined and applied to the assessment of toxicological and carcinogenic hazards of the bio-oils. The following hazardous properties were considered: acute toxicity; ecotoxicity; chronic toxicity; carcinogenicity. Parameters related to these properties were quantified for each component identified in the bio-oils and overall values were estimated for the bio-oils. The hazard screening carried out for the three bio-oils considered suggested that: (i) hazards to human health could be associated with chronic exposures to the bio-oils; (ii) acute toxic effects on humans and eco-toxic effects on aquatic ecosystems could also be possible in the case of loss of containment; and (iii) bio-oils may present a marginal potential carcinogenicity. The approach outlined allows the collection of screening information on the potential hazards posed by the bio-oils. This can be particularly useful when limited time and analytical resources reduce the possibility to obtain detailed specific experimental data. Copyright © 2012 Elsevier B.V. All rights reserved.

The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica.

PubMed

Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J; Carroll, Margaret A

2011-01-01

Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain's dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O(2) consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O(2) consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O(2) consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism.

The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica

PubMed Central

Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J.; Carroll, Margaret A.

2011-01-01

Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain’s dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O2 consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O2 consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O2 consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism. PMID:21977482

Toxicological assessment of green petroleum coke.

PubMed

McKee, Richard H; Herron, Deborah; Beatty, Patrick; Podhasky, Paula; Hoffman, Gary M; Swigert, James; Lee, Carol; Wong, Diana

2014-01-01

Green petroleum coke is primarily inorganic carbon with some entrained volatile hydrocarbon material. As part of the petroleum industry response to the high production volume challenge program, the potential for reproductive effects was assessed in a subchronic toxicity/reproductive toxicity screening test in rats (OECD 421). The repeated-dose portion of the study provided evidence for dust accumulation and inflammatory responses in rats exposed to 100 and 300 mg/m(3) but there were no effects at 30 mg/m(3). In the reproductive toxicity screen, the frequency of successful matings was reduced in the high exposure group (300 mg/m(3)) and was not significantly different from control values but was outside the historical experience of the laboratory. The postnatal observations (external macroscopic examination, body weight, and survival) did not indicate any treatment-related differences. Additional tests conducted to assess the potential hazards to aquatic (fish, invertebrates, and algae) and soil dwelling organisms (earthworms and vascular plants) showed few effects at the maximum loading rates of 1000 mg coke/L in aquatic studies and 1000 mg coke/kg soil in terrestrial studies. The only statistically significant finding was an inhibition of algal growth measured as either biomass or growth rate.

Human exposure limits to hypergolic fuels

NASA Technical Reports Server (NTRS)

Garcia, H. D.; James, J. T.; Limero, T. F.

1992-01-01

Over the past four decades, many studies have been conducted on the toxicities of the rocket propellants hydrazine (HZ) and monomethylhydrazine (MH). Numerous technical challenges have made it difficult to unambiguously interpret the results of these studies, and there is considerable divergence between results obtained by different investigators on the inhalation concentrations (MAC's) for each toxic effect inducible by exposure to hypergolic fuels in spacecraft atmospheres, NASA undertook a critical review of published and unpublished investigations on the toxicities of these compounds. The current state of the art practices for similar studies. While many questions remain unanswered, MAC's were determined using the best available data for a variety of toxic endpoints for potential continuous exposure durations ranging from 1 hour to 180 days. Spacecraft MAC's (SMAC's) were set for each compound based on the most sensitive toxic endpoint at each exposure duration.

Short-term soil bioassays may not reveal the full toxicity potential for nanomaterials; bioavailability and toxicity of silver ions (AgNO₃) and silver nanoparticles to earthworm Eisenia fetida in long-term aged soils.

PubMed

Diez-Ortiz, Maria; Lahive, Elma; George, Suzanne; Ter Schure, Anneke; Van Gestel, Cornelis A M; Jurkschat, Kerstin; Svendsen, Claus; Spurgeon, David J

2015-08-01

This study investigated if standard risk assessment hazard tests are long enough to adequately provide the worst case exposure for nanomaterials. This study therefore determined the comparative effects of the aging on the bioavailability and toxicity to earthworms of soils dosed with silver ions and silver nanoparticles (Ag NP) for 1, 9, 30 & 52 weeks, and related this to the total Ag in the soil, Ag in soil pore water and earthworm tissue Ag concentrations. For ionic Ag, a classical pattern of reduced bioavailability and toxicity with time aged in the soil was observed. For the Ag NP, toxicity increased with time apparently driven by Ag ion dissolution from the added Ag NPs. Internal Ag in the earthworms did not always explain toxicity and suggested the presence of an internalised, low-toxicity Ag fraction (as intact or transformed NPs) after shorter aging times. Our results indicate that short-term exposures, without long-term soil aging, are not able to properly assess the environmental risk of Ag NPs and that ultimately, with aging time, Ag ion and Ag NP effect will merge to a common value. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biotic ligand modeling approach: Synthesis of the effect of major cations on the toxicity of metals to soil and aquatic organisms.

PubMed

Ardestani, Masoud M; van Straalen, Nico M; van Gestel, Cornelis A M

2015-10-01

The biotic ligand model (BLM) approach is used to assess metal toxicity, taking into account the competition of other cations with the free metal ions for binding to the biotic ligand sites of aquatic and soil organisms. The bioavailable fraction of metals, represented by the free metal ion, is a better measure than the total concentration for assessing their potential risk to the environment. Because BLMs are relating toxicity to the fraction of biotic ligands occupied by the metal, they can be useful for investigating factors affecting metal bioaccumulation and toxicity. In the present review, the effects of major cations on the toxicity of metals to soil and aquatic organisms were comprehensively studied by performing a meta-analysis of BLM literature data. Interactions at the binding sites were shown to be species- and metal-specific. The main factors affecting the relationships between toxicity and conditional binding constants for metal binding at the biotic ligand appeared to be Ca(2+) , Mg(2+) , and protons. Other important characteristics of the exposure medium, such as levels of dissolved organic carbon and concentrations of other cations, should also be considered to obtain a proper assessment of metal toxicity to soil and aquatic organisms. © 2015 SETAC.

Relation between different metal pollution criteria in sediments and its contribution on assessing toxicity.

PubMed

Alves, Cristina M; Ferreira, Carlos M H; Soares, Helena M V M

2018-05-14

Several tools have been developed and applied to evaluate the metal pollution status of sediments and predict their potential ecological risk assessment. To date, a comprehensive relationship between the information given by these sediment tools for predicting metal bioavailability and the effective toxicity observed is lacking. In this work, the possible inter-correlations between the data outcoming from using several qualitative evaluation tools of the sediment contamination (contamination factor, CF, the enrichment factor, EF, or the geoaccumulation index, Igeo), metal speciation on sediments (evaluated by the modified BCR sequential extraction procedure) and free metal concentrations in pore waters were studied. It was also our aim to evaluate if these assessment tools could be used for predicting the pore waters toxicity data as toxicity proxy. Principal component analysis and cluster analysis revealed that two quality indices used (CF and EF) were highly correlatable with the more labile fractions from BCR sediment speciation. However, neither of these parameters did correlate with the toxicity of pore waters measured by the chronic toxicity (72 h) in Pseudokirchneriella subcapitata. In contrast, the toxic effects of the given total metal load in sediments were better evaluated by using an additive metal approach using pore water free metal concentrations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of Speciation of Thorium on Toxic Effects to Green Algae Chlorella pyrenoidosa.

PubMed

Peng, Can; Ma, Yuhui; Ding, Yayun; He, Xiao; Zhang, Peng; Lan, Tu; Wang, Dongqi; Zhang, Zhaohui; Zhang, Zhiyong

2017-04-10

Thorium (Th) is a natural radioactive element present in the environment and has the potential to be used as a nuclear fuel. Relatively little is known about the influence and toxicity of Th in the environment. In the present study, the toxicity of Th to the green algae Chlorella pyrenoidosa ( C. pyrenoidosa ) was evaluated by algal growth inhibition, biochemical assays and morphologic observations. In the cultural medium (OECD TG 201), Th(NO₃)₄ was transformed to amorphous precipitation of Th(OH)₄ due to hydrolysis. Th was toxic to C. pyrenoidosa , with a 96 h half maximum effective concentration (EC 50 ) of 10.4 μM. Scanning electron microscopy shows that Th-containing aggregates were attached onto the surface of the algal cells, and transmission electron microscopy indicates the internalization of nano-sized Th precipitates and ultrastructural alterations of the algal cells. The heteroagglomeration between Th(OH)₄ precipitation and alga cells and enhanced oxidative stress might play important roles in the toxicity of Th. To our knowledge, this is the first report of the toxicity of Th to algae with its chemical species in the exposure medium. This finding provides useful information on understanding the fate and toxicity of Th in the aquatic environment.

Effect-Based Tools for Monitoring and Predicting the Ecotoxicological Effects of Chemicals in the Aquatic Environment

PubMed Central

Connon, Richard E.; Geist, Juergen; Werner, Inge

2012-01-01

Ecotoxicology faces the challenge of assessing and predicting the effects of an increasing number of chemical stressors on aquatic species and ecosystems. Herein we review currently applied tools in ecological risk assessment, combining information on exposure with expected biological effects or environmental water quality standards; currently applied effect-based tools are presented based on whether exposure occurs in a controlled laboratory environment or in the field. With increasing ecological relevance the reproducibility, specificity and thus suitability for standardisation of methods tends to diminish. We discuss the use of biomarkers in ecotoxicology including ecotoxicogenomics-based endpoints, which are becoming increasingly important for the detection of sublethal effects. Carefully selected sets of biomarkers allow an assessment of exposure to and effects of toxic chemicals, as well as the health status of organisms and, when combined with chemical analysis, identification of toxicant(s). The promising concept of “adverse outcome pathways (AOP)” links mechanistic responses on the cellular level with whole organism, population, community and potentially ecosystem effects and services. For most toxic mechanisms, however, practical application of AOPs will require more information and the identification of key links between responses, as well as key indicators, at different levels of biological organization, ecosystem functioning and ecosystem services. PMID:23112741

Effect of H+ ion activity and Ca2+ on the toxicity of metals in the environment.

PubMed Central

Hutchinson, T C; Collins, F W

1978-01-01

The role of acidity in determining and restricting plant distribution and performance is discussed. In soils especially, a key effect of H+ ion concentration is on the solubility of potentially toxic heavy metals such as aluminum, managenese, zinc, iron, copper, and nickel. Al has been reported from many studies since the 1920's as the key determining toxic factor in acid soils. Some acid-tolerant species have been shown to be especially tolerant of Al, and mechanisms of tolerance have been suggested. Mn is also a commonly toxic factor at soil pH less than 5.0. Calcium has been shown to alleviate Mn toxicity. Low pH soils are also generally low in Ca, K, Na, and P; all essential major elements for plant growth. In lakes and marine situations acidic waters are uncommon as the waters are buffered. Calcium is again ameliorative of metal toxicities. The pH, redox, and valency state are critical in determining nutrient availability and metal speciation. Recent increases in the H+ ion content of precipitation have caused increased acidities of freshwater lakes in Scandinavia and eastern North America, which have depleted biota, including fish populations. PMID:31277

Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater

PubMed Central

Juárez, Ángela Beatriz; Dragani, Valeria; Saenz, Magalí Elizabeth; Moretton, Juan

2014-01-01

Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. PMID:25214834

Leaching characteristics, ecotoxicity, and risk assessment based management of mine wastes

NASA Astrophysics Data System (ADS)

Kim, J.; Ju, W. J.; Jho, E. H.; Nam, K.; Hong, J. K.

2016-12-01

Mine wastes generated during mining activities in metal mines generally contain high concentrations of metals that may impose toxic effects to surrounding environment. Thus, it is necessary to properly assess the mining-impacted landscapes for management. The study investigated leaching characteristics, potential environmental effects, and human health risk of mine wastes from three different metal mines in South Korea (molybdenum mine, lead-zinc mine, and magnetite mine). The heavy metal concentrations in the leachates obtained by using the Korean Standard Test Method for Solid Wastes (STM), Toxicity Characteristics Leaching Procedure (TCLP), and Synthetic Precipitation Leaching Procedure (SPLP) met the Korea Waste Control Act and the USEPA region 3 regulatory levels accordingly, even though the mine wastes contained high concentrations of metals. Assuming that the leachates may get into nearby water sources, the leachate toxicity was tested using Daphnia Magna. The toxic unit (TU) values after 24 h and 48 h exposure of all the mine wastes tested met the Korea Allowable Effluent Water Quality Standards (TU<1). The column leaching test showed that the lead-zinc mine waste may have long-term toxic effects (TU>1 for the eluent at L/S of 30) implying that the long-term effect of mine wastes left in mining areas need to be assessed. Considering reuse of mine wastes as a way of managing mine wastes, the human health risk assessment of reusing the lead-zinc mine waste in industrial areas was carried out using the bioavailable fraction of the heavy metals contained in the mine wastes, which was determined by using the Solubility/Bioavailability Research Consortium method. There may be potential carcinogenic risk (9.7E-05) and non-carcinogenic risk (HI, Hazard Index of 1.0E+00) as CR≧1.0E-05 has carcinogenic risk and HI≧1.0E+00 has non-carcinogenic risk. Overall, this study shows that not only the concentration-based assessment but ecological toxic effect and human health risk based assessments can be utilized for mining-impacted landscapes management.

Preparation of five 3-MCPD fatty acid esters, and the effects of their chemical structures on acute oral toxicity in Swiss mice.

PubMed

Liu, Man; Liu, Jie; Wu, Yizhen; Gao, Boyan; Wu, Pingping; Shi, Haiming; Sun, Xiangjun; Huang, Haiqiu; Wang, Thomas Ty; Yu, Liangli Lucy

2017-02-01

3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg -1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3-MCPDEs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Linking embryo toxicity with genotoxic responses in the freshwater snail Physa acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and exposure to binary mixtures with benzo(a)pyrene.

PubMed

Sánchez-Argüello, Paloma; Aparicio, Natalia; Fernández, Carlos

2012-06-01

Genotoxic effects on fauna after waterborne pollutant exposure have been demonstrated by numerous research programmes. Less effort has been focused on establishing relationship between genotoxicity and long-term responses at higher levels of biological organization. Taking into account that embryos may be more sensitive indicators of reproductive impairment than alterations in fertility, we have developed two assays in multiwell plates to address correlations between embryo toxicity and genotoxicity. The potential teratogenicity was assessed by analyzing abnormal development and mortality of Physa acuta at embryonic stage. Genotoxicity was measured by the micronucleus (MN) test using embryonic cells. Our results showed that linkage between genotoxicity and embryo toxicity depends on mechanisms of action of compounds under study. Embryo toxic responses showed a clear dose-related tendency whereas no clear dose-dependent effect was observed in micronucleus induction. The higher embryo toxicity was produced by benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was the lower embryo toxic compound. Binary mixtures with BaP always resulted in higher embryo toxicity than single exposures but antagonistic effects were observed for MN induction. Benzo(a)pyrene produced the higher MN induction at 0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol A significantly reduced hatchability at 0.5mg/L while MN induction appeared with higher treatments than those that start causing teratogenicity. Much higher concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN formation. In conclusion, while validating one biomarker of genotoxicity and employing one ecologically relevant effect, we have evaluated the relative sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity test is a starting point for the development of a life cycle test with freshwater snails even for undertaking multigeneration studies focused on transgenerational effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Inhibition of autophagy contributes to the toxicity of cadmium telluride quantum dots in Saccharomyces cerevisiae.

PubMed

Fan, Junpeng; Shao, Ming; Lai, Lu; Liu, Yi; Xie, Zhixiong

2016-01-01

Cadmium telluride quantum dots (CdTe QDs) are used as near-infrared probes in biologic and medical applications, but their cytological effects and mechanism of potential toxicity are still unclear. In this study, we evaluated the toxicity of CdTe QDs of different sizes and investigated their mechanism of toxicity in the yeast Saccharomyces cerevisiae. A growth inhibition assay revealed that orange-emitting CdTe (O-CdTe) QDs (half inhibitory concentration [IC50] =59.44±12.02 nmol/L) were more toxic than green-emitting CdTe QDs (IC50 =186.61±19.74 nmol/L) to S. cerevisiae. Further studies on toxicity mechanisms using a transmission electron microscope and green fluorescent protein tagged Atg8 processing assay revealed that O-CdTe QDs could partially inhibit autophagy at a late stage, which differs from the results reported in mammalian cells. Moreover, autophagy inhibited at a late stage by O-CdTe QDs could be partially recovered by enhancing autophagy with rapamycin (an autophagy activator), combined with an increased number of living cells. These results indicate that inhibition of autophagy acts as a toxicity mechanism of CdTe QDs in S. cerevisiae. This work reports a novel toxicity mechanism of CdTe QDs in yeast and provides valuable information on the effect of CdTe QDs on the processes of living cells.

Impacts of low-molecular-weight organic acids on aquatic behavior of graphene nanoplatelets and their induced algal toxicity and antioxidant capacity.

PubMed

Wang, Zhuang; Gao, Yucheng; Wang, Se; Fang, Hao; Xu, Defu; Zhang, Fan

2016-06-01

Knowledge of the interaction between graphene-based materials and low-molecular-weight organic acids (LOAs) is essential to understand fate and effects of graphene-based materials in the aquatic environment, but this interaction remains poorly elucidated. In this study, the effects of LOAs on the physicochemical properties of graphene nanoplatelets (GNPs) in an aqueous medium and on the GNP toxicity to algae were studied. The unicellular green alga Scenedesmus obliquus was exposed to GNP suspensions in the presence of benzoic acid or gallic acid at various concentrations. The GNPs had smaller hydrodynamic sizes and the GNP suspensions were more stable and had higher or lower surface zeta potentials in the presence of LOAs than when LOAs were not present. The toxic effects in S. obliquus cultures incubated with GNP suspensions containing LOAs were related to the LOA concentration, and the presence of LOAs caused three effects: stimulation, alleviation, and synergistic inhibition. The intensities of the effects mainly correlated with the LOA concentration, the extent of agglomeration, and particle-induced oxidative stress. The results indicate that the environmental fates and toxicities of GNPs are strongly affected by the binding of GNPs to LOAs.

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not.

PubMed

Akan, Pinar; Kizildag, Servet; Ormen, Murat; Genc, Sermin; Oktem, Mehmet Ali; Fadiloglu, Meral

2009-01-15

Pregnenolone (P), the main precursor of the steroids, and its sulfate ester, pregnenolone sulfate (PS), are the major neurosteroids produced in the neural tissue. Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although it has been suggested that the inhibition of P and PS synthesis can delay neuronal cell death. The potential roles of P and PS in vital neuronal functions and in amyloid beta peptide (Abeta) toxicity are not clearly identified. This work aims to investigate the effects of P and PS on cell viability and Abeta peptide toxicity in a concentration and exposure time-dependent manner in rat PC-12 cells. The cells were treated with 20muM Abeta peptide 25-35 and variable concentrations of P and PS ranging from 0.5muM to 100muM. To examine the effects of steroid treatment on Abeta peptide toxicity, 0.5muM (low) and 50muM (high) neurosteroids were used. The cell viability and lactate dehydrogenase release of cells were evaluated after 24, 48 and 72h. Morphological changes of cells were also examined. The treatment with higher than 1muM concentrations of P and PS significantly decreased the cell viability comparing to untreated cells. At lower concentrations, P and PS had no toxic actions until 72h. The Abeta treatment resulted in a significant decrease in cell viability comparing to untreated cells. P showed a dose-dependent protective effect against Abeta peptide in PC-12 cells. But its sulfate ester did not have the same effect on Abeta peptide toxicity, even it significantly decreased cell viability in Abeta-treated cells. Consequently, the discrepant effects of P and PS on Abeta peptide toxicity may provide insight on the pathogenesis of Alzheimer's disease.

Monitoring genetic damage to ecosystems from hazardous waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, S.L.

1992-03-01

Applications of ecological toxicity testing to hazardous waste management have increased dramatically over the last few years, resulting in a greater awareness of the need for improved biomonitoring techniques. Our laboratory is developing advanced techniques to assess the genotoxic effects of environmental contamination on ecosystems. We have developed a novel mutagenesis assay using the nematode Caenorhabditis elegans, which is potentially applicable for multimedia studies in soil, sediment, and water. In addition, we are conducting validation studies of a previously developed anaphase aberration test that utilizes sea urchin embryos. Other related efforts include field validation studies of the new tests, evaluationmore » of their potential ecological relevance, and analysis of their sensitivity relative to that of existing toxicity tests that assess only lethal effects, rather than genetic damage.« less

PPARα-dependent increase of mouse urine output by gemfibrozil and fenofibrate.

PubMed

Song, Danjun; Luo, Min; Dai, Manyun; Bu, Shizhong; Wang, Weihua; Zhang, Burong; Gonzalez, Frank J; Liu, Aiming

2017-02-01

While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity. A therapeutically equivalent dose of gemfibrozil was more effective than fenofibrate in increasing urine output. This regulatory effect was not observed in Pparα-null mice. In contrast, hepatomegaly induced by fenofibrate was more pronounced than that of gemfibrozil. No significant toxicity was observed in liver or kidney in the 2-month treatment with gemfibrozil. These data demonstrated PPARα mediates the increased urine output by fibrates. Considering the relative action on hepatomegaly and the regulatory effect on urine output, gemfibrozil may be the preferable drug to increase urine output. These results revealed a new pharmacodynamic effect of clinically prescribed PPARα agonists and suggested the potential value of gemfibrozil in modification of blood pressure.

Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

PubMed

Chen, Xiao-Xin; Leung, George Pak-Heng; Zhang, Zhang-Jin; Xiao, Jian-Bo; Lao, Li-Xing; Feng, Feng; Mak, Judith Choi-Wo; Wang, Ying; Sze, Stephen Cho-Wing; Zhang, Kalin Yan-Bo

2017-09-01

Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Status and future concerns of clinical and environmental aluminum toxicology.

PubMed

Flaten, T P; Alfrey, A C; Birchall, J D; Savory, J; Yokel, R A

1996-08-30

A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroencephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 micrograms/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects. Increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialties. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity.

Molecular Modeling for Screening Environmental Chemicals for Estrogenicity: Use of the Toxicant-Target Approach

EPA Science Inventory

There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the pre...

THE EFFECTS OF FUNCTIONALIZED AND NON-FUNCTIONALIZED CARBON NANOTUBES ON ROOT ELONGATION OF SELECTED CROP SPECIES

EPA Science Inventory

Single-walled carbon nanotubes (SWNT) have many potential beneficial uses with additional applications constantly being investigated. However, these unique properties create a potential cause for concern of toxicity, not only in humans and animals, but also in plants. Root elong...

Use of High-Throughput Cell-Based and Model Organism Assays for Understanding the Potential Toxicity of Engineered Nanomaterials

EPA Science Inventory

The rapidly expanding field of nanotechnology is introducing a large number and diversity of engineered nanomaterials into research and commerce with concordant uncertainty regarding the potential adverse health and ecological effects. With costs and time of traditional animal to...

Effects of three related amides on microecosystem stability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flum, T.F.; Shannon, L.J.

1987-04-01

Three related amides (diuron, 2-(octyloxy) acetanilide, and salicylanilide) were evaluated for toxicity to aquatic microcosm communities. Effects were measured at the ecosystem level using changes in pH, Eh (redox potential), and dissolved oxygen as indicators of toxicity. These values were used to calculate the resistance, resilience, and relative instability of the microecosystems to each compound at comparable dose levels of approximately 2500 micrograms/liter. Such measures have often been used in a theoretical context, but have not received wide practical application. The systems showed low resistance and no resilience to diuron, high resistance and low resilience to 2-(octyloxy) acetanilide, and nomore » response to salicylanilide. At a higher exposure level (9800 micrograms/liter salicylanilide), the systems showed low resistance and high resilience. Both this approach and more traditional dose-response measures of toxicity indicated that diuron was clearly the most toxic compound, followed by 2-(octyloxy) acetanilide and salicylanilide. While microcosm toxicity tests were slightly less sensitive than some single species tests, they provided important additional information on the extent of perturbations and the rate of ecosystem recovery.« less

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models.

PubMed

Seremet, Oana Cristina; Olaru, Octavian Tudorel; Gutu, Claudia Maria; Nitulescu, George Mihai; Ilie, Mihaela; Negres, Simona; Zbarcea, Cristina Elena; Purdel, Carmen Nicoleta; Spandidos, Demetrios A; Tsatsakis, Aristides M; Coleman, Michael D; Margina, Denisa Marilena

2018-06-01

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC‑MS method, using a retention time (TR)‑5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson 's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC‑MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans.

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models

PubMed Central

Seremet, Oana Cristina; Olaru, Octavian Tudorel; Gutu, Claudia Maria; Nitulescu, George Mihai; Ilie, Mihaela; Negres, Simona; Zbarcea, Cristina Elena; Purdel, Carmen Nicoleta; Spandidos, Demetrios A.; Tsatsakis, Aristides M.; Coleman, Michael D.; Margina, Denisa Marilena

2018-01-01

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC-MS method, using a retention time (TR)-5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC-MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans. PMID:29620235

Toxicity Assessment of Silica Coated Iron Oxide Nanoparticles and Biocompatibility Improvement by Surface Engineering

PubMed Central

Malvindi, Maria Ada; De Matteis, Valeria; Galeone, Antonio; Brunetti, Virgilio; Anyfantis, George C.; Athanassiou, Athanassia; Cingolani, Roberto; Pompa, Pier Paolo

2014-01-01

We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects. PMID:24465736

An assessment of the potential toxicity of runoff from an urban roadscape during rain events.

PubMed

Waara, Sylvia; Färm, Carina

2008-05-01

The potential negative impact of urban storm water on aquatic freshwater ecosystems has been demonstrated in various studies with different types of biological methods. There are a number of factors that influence the amount and bioavailability of contaminants in storm water even if it is derived from an area with a fairly homogenous land use such as a roadscape where a variation in toxicity during rain events might be expected. There are only a few previous investigations on the toxicity of highway runoff and they have not explored these issues extensively. The main objective of this study is therefore to characterize the potential toxicity of highway runoff during several rain events before it enters a detention pond in Västerås, Sweden, using laboratory bioassays with test organisms representing various functional groups in an aquatic ecosystem. The results are to be used for developing a monitoring program, including biological methods. The storm water was sampled before the entrance to a detention pond, which receives run-off from a highway with approximately 20,000 vehicles a day. The drainage area, including the roadscape and vegetated areas, is 4.3 ha in size. Samples for toxicity tests were taken with an automatic sampler or manually during storm events. In total, the potential toxicity of 65 samples representing 15 different storm events was determined. The toxicity was assessed with 4 different test organisms; Vibrio fischeri using the Microtox comparison test, Daphnia magna using Daphtoxkit-F agna, Thamnocephalus platyurus using the ThamnotoxkitF and Lemna minor, duckweed using SS 028313. Of the 65 samples, 58 samples were tested with DaphniatoxkitF agna, 57 samples with the Microtox comparison test, 48 samples with ThamnotoxkitF and 20 samples with Lemna minor, duckweed. None of the storm water samples were toxic. No toxicity was detected with the Lemna minor test, but in 5 of the 23 samples tested in comparison to the control a growth stimulation of 22-46% was observed. This is in accordance with the chemical analysis of the storm water, which indicated rather large concentrations of tot-N and tot-P. In addition to the growth stimulation, morphological changes were observed in all the 5 samples from the winter event that was sampled. The lack of toxicity observed in our study might be due to a lower traffic intensity (20,000 vehicles/day) at the site and the trapping of pollutants in the vegetated areas of the roadscape, resulting in much smaller loads of pollutants in the storm water than in some previous studies. Ecotoxicological evaluations of storm water including run off from rain events from urban roadscape studies clearly reveal that toxicity may or may not be detected depending upon site, storm condition and the test organism chosen. However, storm water might not be as polluted as previously reported nor may the first flush be such a widespread phenomenon as we originally expected. In this study, there was also a good correlation between pollutant load measured and the lack of toxicity. The test organisms chosen in this study are commonly used in effluent control programs in Sweden and other countries, which makes it possible to compare the results with those from other effluents. In this study, only acute toxicity tests were used and further studies using chronic toxicity tests, assays for genotoxic compounds or in situ bioassays might reveal biological effects at this site. Furthermore, most of the samples were taken in spring, summer or fall and it is possible that winter conditions might alter the constituents in the storm water and, thus, the toxicity of the samples. Considering the complex nature of run off from urban roadscapes, it will be virtually impossible to evaluate properly the potential hazard of particular storm water and the efficiency of a particular treatment strategy from only physical and chemical characterizations of the effluent. Therefore, despite the lack of toxicity detected in this study, it is recommended that toxicity tests or other biological methods should be included in evaluations of the effects of runoff from roadscapes.

Toxicity assessment in marine sediment for the Terra Nova environmental effects monitoring program (1997-2010)

NASA Astrophysics Data System (ADS)

Whiteway, Sandra A.; Paine, Michael D.; Wells, Trudy A.; DeBlois, Elisabeth M.; Kilgour, Bruce W.; Tracy, Ellen; Crowley, Roger D.; Williams, Urban P.; Janes, G. Gregory

2014-12-01

This paper discusses toxicity test results on sediments from the Terra Nova offshore oil development. The Terra Nova Field is located on the Grand Banks approximately 350 km southeast of Newfoundland (Canada). The amphipod (Rhepoxynius abronius) survival and solid phase luminescent bacteria (Vibrio fischeri, or Microtox) assays were conducted on sediment samples collected from approximately 50 stations per program year around Terra Nova during baseline (1997), prior to drilling, and in 2000, 2001, 2002, 2004, 2006, 2008 and 2010 after drilling began. The frequency of toxic responses in the amphipod toxicity test was low. Of the ten stations that were toxic in environmental effects monitoring (EEM) years, only one (station 30(FE)) was toxic in more than one year and could be directly attributed to Terra Nova project activities. In contrast, 65 (18%) of 364 EEM samples were toxic to Microtox. Microtox toxicity in EEM years was not related to distance from Terra Nova drill centres or concentrations of >C10-C21 hydrocarbons or barium, the primary constituents of the synthetic-based drill muds used at Terra Nova. Of the variables tested, fines and strontium levels showed the strongest (positive) correlations with toxicity. Neither fines nor strontium levels were affected by drill cuttings discharge at Terra Nova, except at station 30(FE) (and that station was not toxic to Microtox). Benthic macro-invertebrate abundance, richness and diversity were greater in toxic than in non-toxic sediments. Therefore, Microtox responses indicating toxicity were associated with positive biological responses in the field. This result may have been an indirect function of the increased abundance of most invertebrate taxa in less sandy sediments with higher gravel content, where fines and strontium levels and, consequently, toxicity to Microtox were high; or chemical substances released by biodegradation of organic matter, where invertebrates are abundant, may be toxic to Microtox. Given the lack of association between Microtox results and discharge from Terra Nova, coupled with the confounding effects of other variables, the usefulness of Microtox toxicity tests within the context of environmental monitoring for the Terra Nova and, potentially, other offshore oil operations needs to be questioned. The amphipod toxicity tests showed that sediments in the vicinity of discharges of synthetic-based drilling mud cuttings are rarely toxic.

Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

PubMed

Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Degradation of rotenone in yam bean seeds ( Pachyrhizus sp.) through food processing.

PubMed

Catteau, Lucy; Lautié, Emmanuelle; Koné, Oumou; Coppée, Marie; Hell, Kerstin; Pomalegni, Charles Bertrand; Quetin-Leclercq, Joëlle

2013-11-20

The purpose of this research is to screen different processes that could potentially decrease or even eliminate rotenone, a toxic isoflavonoid, from Pachyrhizus seeds. Yam bean seeds have very interesting nutritional characteristics, especially their high protein and lipid contents, and could potentially increase food security in under-nourished populations. However, they contain rotenone, a natural molecule previously used as an insecticide inhibiting the respiratory mitochondrial chain. It was also proven to be toxic to mammals as chronic exposure leads to the development of Parkinson-like symptoms in rats. As the thermosensitivity of rotenone had been reported, this study tested different processes (drying, roasting, boiling, frying, alcohol extraction), tegument removal, and traditional Beninese culinary recipes. Rotenone was then quantified in end-products by a validated method, associating microwave extraction, solid phase extraction (SPE), and HPLC-UV. With these processes a rotenone removal of up to 80% was obtained. The most effective methods were the drying and roasting of the seeds and the maceration of their flour in local alcohol. Rotenone degradation and elimination were confirmed by cytotoxic assays, effectively inducing a decrease in sample toxicity.

Default mode network as a potential biomarker of chemotherapy-related brain injury

PubMed Central

Kesler, Shelli R.

2014-01-01

Chronic medical conditions and/or their treatments may interact with aging to alter or even accelerate brain senescence. Adult onset cancer, for example, is a disease associated with advanced aging and emerging evidence suggests a profile of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer is currently the primary model for studying these “chemobrain” effects. Given the widespread changes to brain structure and function as well as the common impairment of integrated cognitive skills observed following breast cancer chemotherapy, it is likely that large-scale brain networks are involved. Default mode network (DMN) is a strong candidate considering its preferential vulnerability to aging and sensitivity to toxicity and disease states. Additionally, chemotherapy is associated with several physiologic effects including increased inflammation and oxidative stress that are believed to elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the development of treatments for chemotherapy-related cognitive decline. For example, certain nutritional interventions could potentially reduce the metabolic changes (e.g. amyloid beta toxicity) associated with DMN disruption. PMID:24913897

Allium-test as a tool for toxicity testing of environmental radioactive-chemical mixtures

NASA Astrophysics Data System (ADS)

Oudalova, A. A.; Geras'kin, S. A.; Dikareva, N. S.; Pyatkova, S. V.

2017-01-01

Bioassay-based approaches have been propagated to assess toxicity of unknown mixtures of environmental contaminants, but it was rarely applied in cases of chemicals with radionuclides combinations. Two Allium-test studies were performed to assess environmental impact from potential sources of combined radioactive-chemical pollution. Study sites were located at nuclear waste storage facilities in European and in Far-Eastern parts of Russia. As environmental media under impact, waters from monitor wells and nearby water bodies were tested. Concentrations of some chemicals and radionuclides in the samples collected enhanced the permitted limits. Cytogenetic and cytotoxic effects were used as biological endpoints, namely, frequency and spectrum of chromosome aberrations and mitotic abnormalities in anatelophase cells as well as mitotic activity in Allium root tips. Sample points were revealed where waters have an enhanced mutagenic potential. The findings obtained could be used to optimize monitoring system and advance decision making on management and rehabilitation of industrial sites. The Allium-test could be recommended and applied as an effective tool for toxicity testing in case of combined contamination of environmental compartments with radionuclides and chemical compounds.

Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages.

PubMed

Li, Qian; Wang, Peipei; Chen, Ling; Gao, Hongwen; Wu, Lingling

2016-09-01

Zebrafish (Danio rerio) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC50 were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish (D. rerio) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC50 values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.

Assessment of antimutagenic and genotoxic potential of senna (Cassia angustifolia Vahl.) aqueous extract using in vitro assays.

PubMed

Silva, C R; Monteiro, M R; Rocha, H M; Ribeiro, A F; Caldeira-de-Araujo, A; Leitão, A C; Bezerra, R J A C; Pádula, M

2008-02-01

Senna (Cassia angustifolia Vahl.) is widely used as a laxative, although potential side effects, such as toxicity and genotoxicity, have been reported. This study evaluated genotoxic and mutagenic effects of senna aqueous extract (SAE) by means of four experimental assays: inactivation of Escherichia coli cultures; bacterial growth inhibition; reverse mutation test (Mutoxitest) and DNA strand break analysis in plasmid DNA. Our results demonstrated that SAE produces single and double strand breaks in plasmid DNA in a cell free system. On the other hand, SAE was not cytotoxic or mutagenic to Escherichia coli strains tested. In effect, SAE was able to avoid H(2)O(2)-induced mutagenesis and toxicity in Escherichia coli IC203 (uvrA oxyR) and IC205 (uvrA mutM) strains, pointing to a new antioxidant/antimutagenic action of SAE.

A question about the potential cardiac toxicity of escitalopram.

PubMed

Howland, Robert H

2012-04-01

Previous reviews have focused on the potential cardiac toxicity of the racemic drug citalopram (Celexa(®)). Evaluating the safety of escitalopram (Lexapro(®)) is an important issue to consider, since it is the S-enantiomer of citalopram. Escitalopram has a small effect on the QTc interval. A prolonged QTc was seen in 2% to 14% of escitalopram overdose cases, without serious cardiac sequelae. The QTc prolongation effect of citalopram in beagle dogs has been attributed to the minor metabolite racemic didemethylcitalopram (DDCT). Whether the escitalopram minor metabolite S-DDCT has this effect is not known. Concentrations of S-DDCT are lower than DDCT, but for a broad range of doses of escitalopram and citalopram, the S-DDCT and DDCT concentrations are well below the QTc prolonging concentrations reported in dogs. There is no strong evidence from human and animal studies that the cardiac safety of escitalopram is significantly superior to that of citalopram. Copyright 2012, SLACK Incorporated.

Toxicity evaluations of nanoclays and thermally degraded byproducts through spectroscopical and microscopical approaches

PubMed Central

Wagner, Alixandra; Eldawud, Reem; White, Andrew; Agarwal, Sushant; Stueckle, Todd A.; Sierros, Konstantinos A.; Rojanasakul, Yon; Gupta, Rakesh K.; Dinu, Cerasela Zoica

2016-01-01

Background Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is incorporated into polymers to form nanocomposites with enhanced mechanical strength, barrier, and flammability properties used for food packaging, automotive, and medical devices. However, with implementation in such consumer applications, the interaction of montmorillonite-based composites or derived byproducts with biological systems needs to be investigated. Methods Herein we examined the potential of Cloisite Na+ (pristine) and Cloisite 30B (organically modified montmorillonite nanoclay) and their thermally degraded byproducts’ to induce toxicity in model human lung epithelial cells. The experimental set-up mimicked biological exposure in manufacturing and disposal areas and employed cellular treatments with occupationally relevant doses of nanoclays previously characterized using spectroscopical and microscopical approaches. For nanoclay-cellular interactions and for cellular analyses respectively, biosensorial-based analytical platforms were used, with induced cellular changes being confirmed via live cell counts, viability assays, and cell imaging. Results Our analysis of byproducts’ chemical and physical properties revealed both structural and functional changes. Real-time high throughput analyses of exposed cellular systems confirmed that nanoclay induced significant toxic effects, with Cloisite 30B showing time-dependent decreases in live cell count and cellular viability relative to control and pristine nanoclay, respectively. Byproducts produced less toxic effects; all treatments caused alterations in the cell morphology upon exposure. Conclusions Our morphological, behavioral, and viability cellular changes show that nanoclays have the potential to produce toxic effects when used both in manufacturing or disposal environments. General significance The reported toxicological mechanisms prove the extensibility of a biosensorial-based platform for cellular behavior analysis upon treatment with a variety of nanomaterials. PMID:27612663

Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.

PubMed

Jira, David; Janousek, Stanislav; Pikula, Jiri; Vitula, Frantisek; Kejlova, Kristina

2012-01-01

Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.

Potential toxicity of pesticides measured in midwestern streams to aquatic organisms

USGS Publications Warehouse

Battaglin, W.; Fairchild, J.

2002-01-01

Society is becoming increasingly aware of the value of healthy aquatic ecosystems as well as the effects that man’s activities have on those ecosystems. In recent years, many urban and industrial sources of contamination have been reduced or eliminated. The agricultural community also has worked towards reducing off-site movement of agricultural chemicals, but their use in farming is still growing. A small fraction, estimated at <1 to 2% of the pesticides applied to crops are lost from fields and enter nearby streams during rainfall events. In many cases aquatic organisms are exposed to mixtures of chemicals, which may lead to greater non-target risk than that predicted based on traditional risk assessments for single chemicals. We evaluated the potential toxicity of environmental mixtures of 5 classes of pesticides using concentrations from water samples collected from ∼50 sites on midwestern streams during late spring or early summer runoff events in 1989 and 1998. Toxicity index values are calculated as the concentration of the compound in the sample divided by the EC50 or LC50 of an aquatic organism. These index values are summed within a pesticide class and for all classes to determine additive pesticide class and total pesticide toxicity indices. Toxicity index values greater than 1.0 indicate probable toxicity of a class of pesticides measured in a water sample to aquatic organisms. Results indicate that some samples had probable toxicity to duckweed and green algae, but few are suspected of having significant toxicity to bluegill sunfish or chorus frogs.

Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

PubMed

Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

2003-01-01

This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

Modified Whole Effluent Toxicity Test to Assess and Decouple Wastewater Effects from Environmental Gradients

PubMed Central

Sauco, Sebastián; Gómez, Julio; Barboza, Francisco R.; Lercari, Diego; Defeo, Omar

2013-01-01

Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET) that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM) to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd) and salinity controls (SC: without canal water). CWd were prepared by diluting the water effluent (sampled during the pesticide application period) with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses. PMID:23755304

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Ultrasound covers and sonographic gels are embryo-toxic and could be replaced by non-toxic polyethylene bags and paraffin oil.

PubMed

Van der Auwera, I; D'Hooghe, T M

1998-08-01

The objective of this study was to test the hypothesis that ultrasound covers and sonographic gels, used during vaginal ultrasound, are toxic for mouse embryonic development in vitro. A prospective randomized design was used on pronucleate ova of F1 hybrid CBA x C57Bl female mice. The mice were superovulated with pregnant mare's serum gonadotrophin and human chorionic gonadotrophin and mated with CBA x C57Bl males. The pronucleate ova were randomly divided between culture media with the addition of commercially available ultrasound covers and sonographic gels in different concentrations. As controls and potential alternatives, plastic polyethylene bags and paraffin oil were tested simultaneously. Embryo-toxicity was assessed by documenting cleavage capacity, blastocyst formation and embryo degeneration in vitro. Exposure of culture medium to the ultrasound covers and sonographic gels tested resulted in a severely reduced cleavage capacity, a high incidence of embryo degeneration and absent or impaired blastocyst formation. This toxic effect could be reduced by high dilutions in vitro. In contrast, plastic polyethylene bags and paraffin oil had no influence on in-vitro development of mouse ova. We conclude that commercially available ultrasound latex covers and sonographic gels are toxic for mouse embryos and can potentially influence embryonic development during infertility treatment. It is safer to perform vaginal ultrasonic measurements using non-toxic paraffin oil (as contact fluid) and plastic polyethylene bags (as ultrasonic cover).

In vitro toxic effects of reduced graphene oxide nanosheets on lung cancer cells

NASA Astrophysics Data System (ADS)

Tabish, Tanveer A.; Pranjol, Md Zahidul I.; Hayat, Hasan; Rahat, Alma A. M.; Abdullah, Trefa M.; Whatmore, Jacqueline L.; Zhang, Shaowei

2017-12-01

The intriguing properties of reduced graphene oxide (rGO) have paved the way for a number of potential biomedical applications such as drug delivery, tissue engineering, gene delivery and bio-sensing. Over the last decade, there have been escalating concerns regarding the possible toxic effects, behaviour and fate of rGO in living systems and environments. This paper reports on integrative chemical-biological interactions of rGO with lung cancer cells, i.e. A549 and SKMES-1, to determine its potential toxicological impacts on them, as a function of its concentration. Cell viability, early and late apoptosis and necrosis were measured to determine oxidative stress potential, and induction of apoptosis for the first time by comparing two lung cancer cells. We also showed the general trend between cell death rates and concentrations for different cell types using a Gaussian process regression model. At low concentrations, rGO was shown to significantly produce late apoptosis and necrosis rather than early apoptotic events, suggesting that it was able to disintegrate the cellular membranes in a dose dependent manner. For the toxicity exposures undertaken, late apoptosis and necrosis occurred, which was most likely resultant from limited bioavailability of unmodified rGO in lung cancer cells.

Mechanism of deoxynivalenol effects on the reproductive system and fetus malformation: Current status and future challenges.

PubMed

Yu, Miao; Chen, Liangkai; Peng, Zhao; Nüssler, Andreas K; Wu, Qinghua; Liu, Liegang; Yang, Wei

2017-06-01

Deoxynivalenol (DON) is a toxic fungal secondary metabolite produced by molds of the Fusarium genus, and it is known to cause a spectrum of diseases both in humans and animals, such as emesis, diarrhea, anorexia, immunotoxicity, hematological disorders, impairment of maternal reproduction, and fetal development. The recently revealed teratogenic potential of DON has received much attention. In various animal models, it has been shown that DON led to skeletal deformities of the fetus. However, the underlying mechanisms are not yet fully understood, and toxicological data are also scarce. Several animal research studies highlight the potential link between morphological abnormalities and changes of autophagy in the reproductive system. Because autophagy is involved in fetal development, maintenance of placental function, and bone remodeling, this mechanism has become a high priority for future research. The general aim of the present review is to deliver a comprehensive overview of the current state of knowledge of DON-induced reproductive toxicity in different animal models and to provide some prospective ideas for further research. The focus of the current review is to summarize toxic and negative effects of DON exposure on the reproductive system and the potential underlying molecular mechanisms in various animal models. Copyright © 2017 Elsevier B.V. All rights reserved.

Stormwater-related transport of the insecticides bifenthrin, fipronil, imidacloprid, and chlorpyrifos into a tidal wetland, San Francisco Bay, California.

PubMed

Weston, Donald P; Chen, Da; Lydy, Michael J

2015-09-15

Suisun Marsh, in northern San Francisco Bay, is the largest brackish marsh in California, and provides critical habitat for many fish species. Storm runoff enters the marsh through many creeks that drain agricultural uplands and the urban areas of Fairfield and Suisun City. Five creeks were sampled throughout a major storm event in February 2014, and analyzed for representatives of several major insecticide classes. Concentrations were greatest in creeks with urban influence, though sampling was done outside of the primary season for agricultural pesticide use. Urban creek waters reached maximum concentrations of 9.9 ng/l bifenthrin, 27.4 ng/l fipronil, 11.9 ng/l fipronil sulfone, 1462 ng/l imidacloprid, and 4.0 ng/l chlorpyrifos. Water samples were tested for toxicity to Hyalella azteca and Chironomus dilutus, and while few samples caused mortality, 70% of the urban creek samples caused paralysis of either or both species. Toxic unit analysis indicated that bifenthrin was likely responsible for effects to H. azteca, and fipronil and its sulfone degradate were responsible for effects to C. dilutus. These results demonstrate the potential for co-occurrence of multiple insecticides in urban runoff, each with the potential for toxicity to particular species, and the value of toxicity monitoring using multiple species. In the channels of Suisun Marsh farther downstream, insecticide concentrations and toxicity diminished as creek waters mixed with brackish waters entering from San Francisco Bay. Only fipronil and its degradates remained measurable at 1-10 ng/l. These concentrations are not known to present a risk based on existing data, but toxicity data for estuarine and marine invertebrates, particularly for fipronil's degradates, are extremely limited. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

PubMed Central

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-01-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

Summary report of bioassays for the city of Hollywood water plant membrane reject water as it mixed with WWTP effluent in an ocean outfall environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fergen, R.E.; Vinci, P.; Bloetscher, F.

1999-07-01

A special bioassay study was conducted to review the impact of the City of Hollywood's Membrane Softening Water Treatment Plant (WRP) reject water as it mixes with the City's Wastewater Treatment Plant (WWTP) effluent. Three sampling periods occurred during 1997. The purpose of this study was to determine potential toxicity of the WTP reject water, pre-chlorinated effluent, and combined effluent, and to demonstrate if the combined effluent was acceptable for ocean discharge on the basis of no potential toxicity. Effluent was acceptable for ocean discharge on the basis of no potential toxicity. Effluent samples were collected at six sampling points;more » three were in the plant, while the other three were along the outfall pipeline. Definitive, static renewal bioassay tests were performed using Mysidopsis bahia and Menidia beryllina as indicators of potential toxicity. The bioassay tests at 30% effluent concentration indicate that there is not potential toxicity for the pre-chlorinated WTP effluent, WTP reject water, dechlorinate combined effluent at the plant, and chlorinated combined effluent at Holland Park, the riser, and the terminus. The results indicate that the WTP reject water (100%) is not toxic to Menidia beryllina but was toxic to Mysidopsis bahia. When combined with the WWRP effluent, the reject water's impact on the potential toxicity of the commingled effluent was insignificant. All of the tests indicate the combined effluents are not toxic to the species tested at the 30% effluent level. Therefore, potential toxicity concerns were not demonstrated for this outfall discharge and did not prevent FDEP from issuing a permit to the City of Hollywood for the disposal of the combined effluent. Furthermore, these results, in combination with the previous results, indicated that individual bioassay testing for the reject water for regulatory compliance is not required.« less

Toxic effects of electrolyte and trace mineral administration in the intensive care unit.

PubMed

Besunder, J B; Smith, P G

1991-07-01

Electrolytes and trace minerals are administered routinely to ICU patients to correct deficiencies or as specific therapy for various conditions. Complications are usually related to the rate of infusion, rapidity of correction of a deficiency state, or iatrogenic poisoning with the agent. Adverse effects associated with Na+ administration included volume overload, CPM, and central nervous system bleeds. The toxic effects of K+, Ca2+, and Mg2+ are primarily related to their effects on the myocardium, nervous system, and muscle. Other than precipitating or maintaining a metabolic acidosis, Cl- administration is relatively nontoxic. Its accompanying anion (i.e., ammonium or arginine), however, may contribute significantly to patient morbidity and, possibly, mortality. Side effects observed with phosphate administration include hypocalcemia, metastatic calcification, and hypernatremia or hyperkalemia. Most of these toxicities are avoidable if appropriate precautions are taken and appropriate monitoring implemented. Finally, when administering any of these agents, the intensivist should be familiar with their toxicologic profiles and management of potential complications.

Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wenming; Meng, Mei; Zhang, Bin

Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantlymore » suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.« less

Environmental complex mixture toxicity assessment.

PubMed

Gardner, H S; Brennan, L M; Toussaint, M W; Rosencrance, A B; Boncavage-Hennessey, E M; Wolfe, M J

1998-12-01

Trichloroethylene (TCE) was found as a contaminant in the well supplying water to an aquatic testing laboratory. The groundwater was routinely screened by a commercial laboratory for volatile and semivolatile compounds, metals, herbicides, pesticides, and polychlorinated biphenyls using U.S. Environmental Protection Agency methods. Although TCE was the only reportable peak on the gas chromatograph, with average concentrations of 0.200 mg/l, other small peaks were also present, indicating the possibility that the contamination was not limited to TCE alone. A chronic 6-month carcinogenicity assay was conducted on-site in a biomonitoring trailer, using the Japanese medaka fish (Oryzias latipes) in an initiation-promotion protocol, with diethylnitrosamine (DEN) as the initiator and the TCE-contaminated groundwater as a promoter. Study results indicated no evidence of carcinogenic potential of the groundwater without initiation. There was, however, a tumor-promotional effect of the groundwater after DEN initiation. A follow-up laboratory study was conducted using reagent grade TCE added to carbon-filtered groundwater to simulate TCE concentrations comparable to those found in the contaminated groundwater. Study results indicated no promotional effects of TCE. These studies emphasize the necessity for on-site bioassays to assess potential environmental hazards. In this instance, chemical analysis of the groundwater identified TCE as the only reportable contaminant, but other compounds present below reportable limits were noted and may have had a synergistic effect on tumor promotion observed with the groundwater exposure. Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species but cannot take into account the possible toxic effects of mixtures of compounds.

Evaluation of ecotoxicological effects of benzophenone UV filters: Luminescent bacteria toxicity, genotoxicity and hormonal activity.

PubMed

Zhang, Qiuya; Ma, Xiaoyan; Dzakpasu, Mawuli; Wang, Xiaochang C

2017-08-01

The widespread use of organic ultraviolet (UV) filters in personal care products raises concerns about their potentially hazardous effects on human and ecosystem health. In this study, the toxicities of four commonly used benzophenones (BPs) UV filters including benzophenone (BP), 2-Hydroxybenzophenone (2HB), 2-Hydroxy-4-methoxybenzophenone (BP3), and 2-Hydroxy-4-methoxybenzophenone-5-sulfonicacid (BP4) in water were assayed in vitro using Vibrio fischeri, SOS/umu assay, and yeast estrogen screen (YES) assay, as well as in vivo using zebrafish larvae. The results showed that the luminescent bacteria toxicity, expressed as logEC 50 , increased with the lipophilicity (logKow) of BPs UV filters. Especially, since 2HB, BP3 and BP4 had different substituent groups, namely -OH, -OCH 3 and -SO 3 H, respectively, these substituent functional groups had a major contribution to the lipophilicity and acute toxicity of these BPs. Similar tendency was observed for the genotoxicity, expressed as the value of induction ratio=1.5. Moreover, all the target BPs UV filters showed estrogenic activity, but no significant influences of lipophilicity on the estrogenicity were observed, with BP3 having the weakest estrogenic efficiency in vitro. Although BP3 displayed no noticeable adverse effects in any in vitro assays, multiple hormonal activities were observed in zebrafish larvae including estrogenicity, anti-estrogenicity and anti-androgenicity by regulating the expression of target genes. The results indicated potential hazardous effects of BPs UV filters and the importance of the combination of toxicological evaluation methods including in vitro and in vivo assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment in rats of the reproductive toxicity of gasoline from a gasoline vapor recovery unit.

PubMed

McKee, R H; Trimmer, G W; Whitman, F T; Nessel, C S; Mackerer, C R; Hagemann, R; Priston, R A; Riley, A J; Cruzan, G; Simpson, B J; Urbanus, J H

2000-01-01

Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial products. Although numerous toxicology studies have been conducted, the potential for reproductive toxicity has not been directly assessed. Accordingly, a two-generation reproductive toxicity study in rats was conducted to provide base data for hazard assessment and risk characterization. The test material, vapor recovery unit gasoline (68514-15-8), is the volatile fraction of formulated gasoline and the material with which humans are most likely to come in contact. The study was of standard design. Exposures were by inhalation at target concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure concentration was approximately 50% of the lower explosive limit and several orders of magnitude above anticipated exposure during refueling. There were no treatment-related clinical or systemic effects in the parental animals, and no microscopic changes other than hyaline droplet nephropathy in the kidneys of the male rats. None of the reproductive parameters were affected, and there were no deleterious effects on offspring survival and growth. The potential for endocrine modulation was also assessed by analysis of sperm count and quality as well as time to onset of developmental landmarks. No toxicologically important differences were found. Therefore, the NOAEL for reproductive toxicity in this study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a male rat-specific effect and not relevant to human health risk assessment.

Impact of black carbon on the bioaccessibility of organic contaminants in soil.

PubMed

Semple, Kirk T; Riding, Matthew J; McAllister, Laura E; Sopena-Vazquez, Fatima; Bending, Gary D

2013-10-15

The ability of carbonaceous geosorbents (CGs) such as black carbon (BC) to extensively sorb many common environmental contaminants suggests that they potentially possesses qualities useful to the sequestration of harmful xenobiotics within contaminated land. Presently, however, there is limited understanding of the implications for the bioaccessibility, mobility and environmental risk of organic contaminants while sorbed to BC in soil and sediment, in addition to the inherent toxicity of BC itself to terrestrial flora and fauna. We review both the processes involved in and factors influencing BC sorption characteristics, and ultimately consider the impacts BC will have for bioavailability/bioaccessibility, toxicity and risk assessment/remediation of contaminated land. We conclude that while the application of BC is promising, additional work on both their toxicity effects and long-term stability is required before their full potential as a remediation agent can be safely exploited. Copyright © 2013 Elsevier B.V. All rights reserved.

Cardiovascular effects of bupivacaine and the role of this agent in preemptive dental analgesia.

PubMed

Younessi, O J; Punnia-Moorthy, A

1999-01-01

Inappropriately high blood concentrations of bupivacaine have been reported to cause toxicity and even death. The potential for cardiovascular toxicity and the difficulty with which this may be reversed has made the dental practitioners reluctant to use this agent. Nevertheless, cardiovascular toxicity from its use in and around the mouth is exceedingly rare. This study was undertaken to assess bupivacaine's cardiotoxic potential in the practice of oral and maxillofacial surgery. Results showed a dose-dependent decrease in systolic blood pressure, but no other statistically significant cardiovascular change was noted. Preemptive treatment of postsurgical pain has been the subject of numerous trials. Bupivacaine administered preoperatively has been suggested to prevent central nervous system "conditioning," thus decreasing the perceived postoperative pain. However, there was no statistical support for any reduction in the perceived postoperative pain in the treatment groups in this study.

Toxicological Implications and Inflammatory Response in Human Lymphocytes Challenged with Oxytetracycline

PubMed Central

Di Cerbo, A.; Palatucci, A. T.; Rubino, V.; Centenaro, S.; Giovazzino, A.; Fraccaroli, E.; Cortese, L.; Ruggiero, G.; Guidetti, G.; Canello, S.

2015-01-01

ABSTRACT Antibiotics are widely used in zoo technical and veterinary practices as feed supplementation to ensure wellness of farmed animals and livestock. Several evidences have been suggesting both the toxic role for tetracyclines, particularly for oxytetracycline (OTC). This potential toxicity appears of great relevance for human nutrition and for domestic animals. This study aimed to extend the evaluation of such toxicity. The biologic impact of the drug was assessed by evaluating the proinflammatory effect of OTC and their bone residues on cytokine secretion by in vitro human peripheral blood lymphocytes. Our results showed that both OTC and OTC‐bone residues significantly induced the T lymphocyte and non‐T cell secretion of interferon (IFN)‐γ, as cytokine involved in inflammatory responses in humans as well as in animals. These results may suggest a possible implication for new potential human and animal health risks depending on the entry of tetracyclines in the food‐processing chain. PMID:26537863

[Potentially toxic antibiotics concentrations after administration using impregnated dressing in a severe burned patient: A case report].

PubMed

Dupouey, Julien; Wiramus, Sandrine; Albanese, Jacques; Guilhaumou, Romain; Blin, Olivier

2016-10-01

Severe burned patients present high risk of skins infections, frequently due to Pseudomonas aeruginosa. Impregnated dressings with amikacin or colistin could be a good alternative to obtain effective concentration directly at the infected site. Therapeutic drug monitoring for these antibiotics is currently recommended after an intravenous administration to obtain effective and non-toxic plasmatic concentrations. However, data are lacking about systemic exposition and risk of toxicity after an administration with impregnated dressings. We report the case of a severe burned patient with cutaneous infection treated with amikacin and colistin impregnated dressings, for which plasmatic pharmacokinetic profiles were performed. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Graphene oxide alleviates the ecotoxicity of copper on the freshwater microalga Scenedesmus obliquus.

PubMed

Hu, Changwei; Hu, Naitao; Li, Xiuling; Zhao, Yongjun

2016-10-01

The extensive industrial application of graphene oxide (GO), has increased its exposure risk to various aquatic organisms and its potential to affect the toxicity of other environmental pollutants. In this study, we investigated the combined toxicity of GO and copper on the freshwater microalga Scenedesmus obliquus, using the MIXTOX model. The effects of low concentration (1mg/L) exposure to GO were investigated with environmentally relevant concentrations of copper by using a 12-d subacute toxicity test, with pre- and post-GO treatment. Results showed that there were significant antagonistic effects between GO and copper on S. obliquus, and GO was found to reduce ecotoxicity of copper even at low and environmentally relevant concentrations (1mg/L). Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Substrate Salinity on Early Seedling survival and Growth of Scirpus robustus Pursh and Spartina alterniflora Loisel

EPA Science Inventory

Rooted aquatic plants are being used increasingly as test species in estuarine sediment toxicity evaluations. Effects of naturally occurring substrate constituents on most potential test species however, are not well understood even though their effects could impact the data int...

76 FR 8157 - National Ambient Air Quality Standards for Carbon Monoxide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... alternative mechanisms of CO- induced effects independent of limited oxygen availability (2000 AQCD, section 5... Concentrations B. Health Effects Information 1. Carboxyhemoglobin as Biomarker and Mechanism of Toxicity 2. Nature of Effects 3. At-Risk Populations 4. Potential Impacts on Public Health C. Human Exposure and Dose...

Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees.

PubMed

Lopes, Leonardo Q S; Santos, Cayane G; de Almeida Vaucher, Rodrigo; Gende, Liesel; Raffin, Renata P; Santos, Roberto C V

2016-08-01

The American Foulbrood Disease (AFB) is a fatal larval bee infection. The etiologic agent is the bacterium Paenibacillus larvae. The treatment involves incineration of all contaminated materials, leading to high losses. The Glycerol Monolaurate (GML) is a known antimicrobial potential compound, however its use is reduced due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages like improved stability and solubility in water. The present study aimed to evaluate the antimicrobial activity against P. larvae and the toxicity in bees of GML nanoparticles. The nanocapsules were produced and presented mean diameter of 210 nm, polydispersity index of 0.044, and zeta potential of -23.4 mV demonstrating the acceptable values to predict a stable system. The microdilution assay showed that it is necessary 142 and 285 μg/mL of GML nanocapsules to obtain a bacteriostatic and bactericidal effect respectively. The time-kill curve showed the controlled release of compound, exterminating the microorganism after 24 h. The GML nanocapsules were able to kill the spore form of Paenibacillus larvae while the GML do not cause any effect. The assay in bees showed that the GML has a high toxicity while the GML nanoparticles showed a decrease on toxic effects. Concluding, the formulation shows positive results in the action to combat AFB besides not causing damage to bees. Copyright © 2016 Elsevier Ltd. All rights reserved.

Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster.

PubMed

Sudati, Jéssie Haigert; Vieira, Francielli Araújo; Pavin, Sandra Sartoretto; Dias, Glaecir Roseni Mundstock; Seeger, Rodrigo Lopes; Golombieski, Ronaldo; Athayde, Margareth Linde; Soares, Félix Antunes; Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

2013-07-01

In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500 μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase (TH) gene. The expression of SOD and CAT mRNAs was normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melanogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD). Copyright © 2013 Elsevier Inc. All rights reserved.

Toxic effects of three strobilurins (trifloxystrobin, azoxystrobin and kresoxim-methyl) on mRNA expression and antioxidant enzymes in grass carp (Ctenopharyngodon idella) juveniles.

PubMed

Liu, Lei; Jiang, Chao; Wu, Zhuo-Qi; Gong, Yu-Xin; Wang, Gao-Xue

2013-12-01

The strobilurins are used widely in the world as effective fungicidal agents to control Asian soybean rust. In this study, the early life stage of grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China, was chosen to measure the acute toxicity of three common strobilurin-derived fungicides (trifloxystrobin (TFS), azoxystrobin (AZ) and kresoxim-methyl (KM)). As endpoints, normal developmental parameters (lethal concentration (LC₅₀) and average heart rate), expression of relative genes, and three antioxidant enzyme activities in the developing juveniles were recorded during a 48 h exposure. The results revealed that values of LC₅₀ were TFS 0.051 (0.046-0.058) mg L⁻¹, AZ 0.549 (0.419-0.771) mg L⁻¹ and KM 0.338 (0.284-0.407) mg L⁻¹ for juveniles. For the potential toxicity mechanisms, these three fungicides increased catalase (CAT) and peroxidase (POD) activity and decreased superoxide dismutase (SOD) activity, significantly inhibited expressions of three growth-related genes (IGF-1, IGF-2 and GHR) and two energy-related-genes (CCK and PYY), and caused pronounced up-regulation a stress-gene (HSP70). The present study demonstrated potential toxic effects of TFS, AZ and KM on the early development of C. idella. Overall, three strobilurins (TFS, AZ and KM) might cause serious damages to the aquatic species; therefore, their pollution supervision in water ecological environment should be strengthened.

Selenium Administration Alleviates Toxicity of Chromium(VI) in the Chicken Brain.

PubMed

Hao, Pan; Zhu, Yiran; Wang, Shenghua; Wan, Huiyu; Chen, Peng; Wang, Yang; Cheng, Ziqiang; Liu, Yongxia; Liu, Jianzhu

2017-07-01

Selenium (Se) can play a protective role against heavy metal toxicity. This experiment aims to evaluate the effect of Se supplementation at different doses on the chicken brains. Oxidative stress was induced in the chicken brains by chromium(VI). A total of 105 Hyland brown male chickens were randomly divided into seven groups, including the control group, poisoned group [6%LD 50 K 2 Cr 2 O 7 body weight (B.W.)], and detoxification groups K 2 Cr 2 O 7 (6%LD 50 ) + Se (0.31, 0.63, 1.25, 2.50, and 5.00 Na 2 SeO 3 mg/kg B.W.) orally in water for 42 days. The chickens were detected by the activities of mitochondrial membrane potential, 2'-benzoyloxycinnamaldehyde, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and Ca 2+ -ATPase. Cr(VI) administration caused histopathological damage. In addition, changes in oxidative stress indicators were observed in the chicken's brains. Se supplement increased the levels of GSH, mitochondrial membrane potential (MMP), and Ca 2+ -ATPase and reduced MDA activity in the detoxification groups. However, the high-dose Se supplementation groups of 2.50 and 5.00 mg/kg reduced the activities of GSH, MMP, and Ca 2+ -ATPase; increased the brain-body ratio; and increased SOD activity. In conclusion, Cr(VI) exposure caused oxidative stress. Se exerted a remission effect on toxic responses in the chicken brains. However, a high Se concentration was synergistic to the toxic effect of Cr(VI).

In vitro inflammatory effects of hard metal (WC-Co) nanoparticle exposure.

PubMed

Armstead, Andrea L; Li, Bingyun

Identifying the toxicity of nanoparticles (NPs) is an important area of research as the number of nanomaterial-based consumer and industrial products continually rises. In addition, the potential inflammatory effects resulting from pulmonary NP exposure are emerging as an important aspect of nanotoxicity. In this study, the toxicity and inflammatory state resulting from tungsten carbide-cobalt (WC-Co) NP exposure in macrophages and a coculture (CC) of lung epithelial cells (BEAS-2B) and macrophages (THP-1) at a 3:1 ratio were examined. It was found that the toxicity of nano-WC-Co was cell dependent; significantly less toxicity was observed in THP-1 cells compared to BEAS-2B cells. It was demonstrated that nano-WC-Co caused reduced toxicity in the CC model compared to lung epithelial cell monoculture, which suggested that macrophages may play a protective role against nano-WC-Co-mediated toxicity in CCs. Nano-WC-Co exposure in macrophages resulted in increased levels of interleukin (IL)-1β and IL-12 secretion and decreased levels of tumor necrosis factor alpha (TNFα). In addition, the polarizing effects of nano-WC-Co exposure toward the M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophage phenotypes were investigated. The results of this study indicated that nano-WC-Co exposure stimulated the M1 phenotype, marked by high expression of CD40 M1 macrophage surface markers.

A toxic organic solvent-free technology for the preparation of PEGylated paclitaxel nanosuspension based on human serum albumin for effective cancer therapy

PubMed Central

Yin, Tingjie; Dong, Lihui; Cui, Bei; Wang, Lei; Yin, Lifang; Zhou, Jianping; Huo, Meirong

2015-01-01

Clinically, paclitaxel (PTX) is one of most commonly prescribed therapies against a wide range of solid neoplasms. Despite its success, the clinical applicability of PTX (Taxol®) is severely hampered by systemic toxicities induced by Cremophor EL. While attempts to bypass the need for Cremophor EL have been developed through platforms such as Abraxane™, nab™ relies heavily on the use of organic solvents, namely, chloroform. The toxicity introduced by residual chloroform poses a potential risk to patient health. To mitigate the toxicities of toxic organic solvent-based manufacture methods, we have designed a method for the formulation of PTX nanosuspensions (PTX-PEG [polyethylene glycol]-HSA [human serum albumin]) that eliminates the dependence on toxic organic solvents. Coined the solid-dispersion technology, this technique permits the dispersion of PTX into PEG skeleton without the use of organic solvents or Cremophor EL as a solubilizer. Once the PTX-PEG dispersion is complete, the dispersion can be formulated with HSA into nanosuspensions suitable for intravenous administration. Additionally, the incorporation of PEG permits the prolonged circulation through the steric stabilization effect. Finally, HSA-mediated targeting permits active receptor-mediated endocytosis for enhanced tumor uptake and reduced side effects. By eliminating the need for both Cremophor EL and organic solvents while simultaneously increasing antitumor efficacy, this method provides a superior alternative to currently accepted methods for PTX delivery. PMID:26715846

Long-Term Effects of Dredging Operations Program. Long-Term Evaluation of Plants and Animals Colonizing Contaminated Estuarine Dredged Material Placed in Both Upland and Wetland Environments

DTIC Science & Technology

1991-09-01

MP D-91-5, September 1991 References Beckett, P. H. T., and Davis, R. D. 1977. Upper critical levels of toxic elements in plants. New Phytology 79:95...and ryegrass. New Phytology 80:23-42. Davis, R. D., Beckett, P. H. T., and Wollan, E. 1978. Critical levels of twenty potentially toxic elements in

Development of Monitors for Assessing Exposure of Military Personnel to Toxic Chemicals.

DTIC Science & Technology

2000-01-01

Residues " S ampler Preparation 7 Transfer and Analysis 7 Temperature Effects on PIMS Sampling Rate 8 Environmental Air Sampling 8 Results and...of exposure and potential toxicity to personnel. While progress has been made in improving active water and air sampling technology, such devices...streams, 3) the apparatus is also applicable for use in air sampling deployments in indoor and outdoor scenarios, and 4) the apparatus is commercially

76 FR 77703 - Hexythiazox; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... the relationship of the results of the studies to human risk. EPA has also considered available... effects including potential carcinogenicity of hexythiazox. Specific information on the studies received...-level (NOAEL) and the lowest-observed-adverse-effect- level (LOAEL) from the toxicity studies can be...

Health Effects Assessment for Acenaphthene

EPA Science Inventory

Because of the lack of data for the carcinogenicity and threshold toxicity of acenaphthene risk assessment values cannot be derived. The ambient water quality criterion of 0.2 mg/l is based on organoleptic data, which has no known relationship to potential human health effects. A...

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY ...

EPA Pesticide Factsheets

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, SAR model development, or building of chemical relational databases (CRD). The Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: 1) to adopt and encourage the use of a common standard file format (SDF) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; 2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data s

Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.

1995-12-31

The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size ofmore » the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.« less

Toxicological evaluation and anti-inflammatory potential of an ethanolic extract from Bromelia balansae (Bromeliaceae) fruit.

PubMed

da Silva Balin, Paola; Zanatta, Flavia Carina; Jorge, Bárbara Campos; Leitão, Maicon; Kassuya, Roberto Mikio; Cardoso, Claudia Andrea Lima; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2018-05-03

Bromelia balansae is a relatively unexplored medicinal species that is used for nutritional purposes and in folk medicine to treat cough or wounds. This study assessed the anti-inflammatory activity of the ethanolic extract obtained from Bromelia balansae fruit (EEBB) as well as the toxicological potential of this extract after single and repeated exposure. Male rats (Wistar) were gavaged with 2000 mg/kg of extract from the fruit of B. balansae for the acute toxicity test and with 25, 100, or 400 mg/kg of EEBB for the subacute toxicity test. The anti-inflammatory effect of EEBB was evaluated in vivo (30, 100, or 300 mg/kg) by carrageenan (Cg) induced-oedema and pleurisy in Swiss mice. A single oral dose of EEBB did not result in toxicity, demonstrating that the LD 50 of this extract was greater than 2000 mg/kg. In the subacute toxicity test, the tested doses produced no significant changes in the haematological, biochemical or histopathological parameters of treated animals. Similarly, there were no statistically significant differences in the sperm parameters. A dose of 300 mg/kg of EEBB significantly reduced oedema formation, Cg-induced mechanical hypersensitivity and cold sensitivity, as well as leukocyte migration in the pleurisy model. These results show that EEBB has an anti-inflammatory potential without causing acute or subacute toxicity. These data may contribute to the advancement of biopharmaceutical applications for this species. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of symbiotic bacteria on chemical sensitivity of Daphnia magna.

PubMed

Manakul, Patcharaporn; Peerakietkhajorn, Saranya; Matsuura, Tomoaki; Kato, Yasuhiko; Watanabe, Hajime

2017-07-01

The crustacean zooplankton Daphnia magna has been widely used for chemical toxicity tests. Although abiotic factors have been well documented in ecotoxicological test protocols, biotic factors that may affect the sensitivity to chemical compounds remain limited. Recently, we identified symbiotic bacteria that are critical for the growth and reproduction of D. magna. The presence of symbiotic bacteria on Daphnia raised the question as to whether these bacteria have a positive or negative effect on toxicity tests. In order to evaluate the effects of symbiotic bacteria on toxicity tests, bacteria-free Daphnia were prepared, and their chemical sensitivities were compared with that of Daphnia with symbiotic bacteria based on an acute immobilization test. The Daphnia with symbiotic bacteria showed higher chemical resistance to nonylphenol, fenoxycarb, and pentachlorophenol than bacteria-free Daphnia. These results suggested potential roles of symbiotic bacteria in the chemical resistance of its host Daphnia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2011-01-01

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination.

PubMed

Bai, Shahla Hosseini; Ogbourne, Steven M

2016-10-01

Glyphosate has been the most widely used herbicide during the past three decades. The US Environmental Protection Agency (EPA) classifies glyphosate as 'practically non-toxic and not an irritant' under the acute toxicity classification system. This classification is based primarily on toxicity data and due to its unique mode of action via a biochemical pathway that only exists in a small number of organisms that utilise the shikimic acid pathway to produce amino acids, most of which are green plants. This classification is supported by the majority of scientific literature on the toxic effects of glyphosate. However, in 2005, the Food and Agriculture Organisation (FAO) reported that glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern, mainly as a result of accumulation of residues in the food chain. The FAO further states that the dietary risk of glyphosate and AMPA is unlikely if the maximum daily intake of 1 mg kg(-1) body weight (bw) is not exceeded. Research has now established that glyphosate can persist in the environment, and therefore, assessments of the health risks associated with glyphosate are more complicated than suggested by acute toxicity data that relate primarily to accidental high-rate exposure. We have used recent literature to assess the possible risks associated with the presence of glyphosate residues in food and the environment.

Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice.

PubMed

Ting, Yuwen; Chiou, Yi-Shiou; Jiang, Yike; Pan, Min-Hsiung; Lin, Zhengyu; Huang, Qingrong

2015-08-01

Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging group of bioactive compounds with wide arrays of disease prevention functionalities. To understand the potential oral toxicity, tangeretin, being one of the most abundant polymethoxyflavones from natural sources, was used as model compound for the safety evaluation. Acute oral toxicity study was conducted using both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of tangeretin in oil suspension from single gavage administration. No evidence of death was observed during 14-day post-administration period. Alterations of the hepatic cell and clinical chemistry profile increased dose dependently and exhibited distinct injury recovery pattern among different sexes. To determine the potential safety concern related to emulsification, the sub-acute toxicity of tangeretin in emulsion was evaluated and compared with un-processed oil suspension when conducting the sub-acute toxicity study over 28days. In the sub-acute study, emulsion system did not induce a significant increase of toxicity response. However, the daily low-dose application of tangeretin showed U-shaped dose-response pattern in regard to hepatic alteration. The result from this study can serve as a good safety reference for future application of polymethoxyflavone as a functional ingredient in food. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxics Use Reduction in the Home: Lessons Learned from Household Exposure Studies

PubMed Central

Dunagan, Sarah C.; Dodson, Robin E.; Rudel, Ruthann A.; Brody, Julia G.

2010-01-01

Workers and fence-line communities have been the first to benefit from the substantial reductions in toxic chemical use and byproducts in industrial production resulting from the Massachusetts Toxics Use Reduction Act (TURA). As TURA motivates reformulation of products as well as retooling of production processes, benefits could extend more broadly to large-scale reductions in everyday exposures for the general population. Household exposure studies, including those conducted by Silent Spring Institute, show that people are exposed to complex mixtures of indoor toxics from building materials and a myriad of consumer products. Pollutants in homes are likely to have multiple health effects because many are classified as endocrine disrupting compounds (EDCs), with the ability to interfere with the body's hormone system. Product-related EDCs measured in homes include phthalates, halogenated flame retardants, and alkylphenols. Silent Spring Institute's chemical analysis of personal care and cleaning products confirms many are potential sources of EDCs, highlighting the need for a more comprehensive toxics use reduction (TUR) approach to reduce those exposures. Toxics use reduction targeted at EDCs in consumer products has the potential to substantially reduce occupational and residential exposures. The lessons that have emerged from household exposure research can inform improved chemicals management policies at the state and national levels, leading to safer products and widespread health and environmental benefits. PMID:21516227

[The protective effect of dexpanthenol in nasal sprays. First results of cytotoxic and ciliary-toxic studies in vitro].

PubMed

Klöcker, N; Verse, T; Rudolph, P

2003-03-01

In Germany more than 60 million units of nasal decongestants are prescribed or sold over the counter. The cytotoxic and ciliary-toxic potential of alpha-sympathomimetic decongestants is well established. Furthermore, in many of the marketed products preservatives are added, predominantly benzalchonium-chloride, which can lead to a further alteration of cell- and ciliary function. Recently a protective effect of dexpanthenol was found for the human nasal mucosa. The objective of the present studies was to prove the hypothesis that dexpanthenol is able to neutralise the toxic effects of both alpha-sympathomimetic decongestants, in particular those of xylometazoline, and those of benzalconium-chloride. Therefore, systematic cytotoxic and ex vivo in vitro ciliary-toxic studies were performed. After exposition to xylometazoline in concentrations of 0.1 % and 0.05 %, the influence of dexpanthenol (5 %) and benzalconium-chloride (0,01 %) was assessed by determination of a) cell growth of FL-cells of human amnion origin, and b) ciliary beat frequency of human nasal mucosa. All tests were performed placebo-controlled. Both hypotheses were confirmed. Dexpanthenol (5 %) reduces statistically significantly the concentration-dependent toxic effects of xylometazoline, and benzalchonium-cloride regarding cell growth and ciliary beat frequency (p < 0.001). The combination of xylometazoline with dexpanthenol, while benzalconium-chloride is eliminated, resulted in a further significant increase of cell growth and ciliary beat frequency (p < 0.001), similar to control. The additive application of dexpanthenol (5 %) with nasal decongestants and/or with preserved nasal sprays seems to be able to reduce the cell- and ciliary-toxic effects of these substances.

Mercury Exposure and Heart Diseases

PubMed Central

Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia

2017-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system. PMID:28085104

Mercury Exposure and Heart Diseases.

PubMed

Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia

2017-01-12

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

A high throughput passive dosing format for the Fish Embryo Acute Toxicity test.

PubMed

Vergauwen, Lucia; Schmidt, Stine N; Stinckens, Evelyn; Maho, Walid; Blust, Ronny; Mayer, Philipp; Covaci, Adrian; Knapen, Dries

2015-11-01

High throughput testing according to the Fish Embryo Acute Toxicity (FET) test (OECD Testing Guideline 236) is usually conducted in well plates. In the case of hydrophobic test substances, sorptive and evaporative losses often result in declining and poorly controlled exposure conditions. Therefore, our objective was to improve exposure conditions in FET tests by evaluating a passive dosing format using silicone O-rings in standard 24-well polystyrene plates. We exposed zebrafish embryos to a series of phenanthrene concentrations until 120h post fertilization (hpf), and obtained a linear dilution series. We report effect values for both mortality and sublethal morphological effects based on (1) measured exposure concentrations, (2) (lipid normalized) body residues and (3) chemical activity. The LC50 for 120hpf was 310μg/L, CBR50 (critical body residue) was 2.72mmol/kg fresh wt and La50 (lethal chemical activity) was 0.047. All values were within ranges expected for baseline toxicity. Impaired swim bladder inflation was the most pronounced morphological effect and swimming activity was reduced in all exposure concentrations. Further analysis showed that the effect on swimming activity was not attributed to impaired swim bladder inflation, but rather to baseline toxicity. We conclude that silicone O-rings (1) produce a linear dilution series of phenanthrene in the 120hpf FET test, (2) generate and maintain aqueous concentrations for reliable determination of effect concentrations, and allow for obtaining mechanistic toxicity information, and (3) cause no toxicity, demonstrating its potential as an extension of the FET test when testing hydrophobic chemicals. Copyright © 2015 Elsevier Ltd. All rights reserved.

The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish.

PubMed

Chen, Pei-Jen; Wu, Wan-Lin; Wu, Kevin Chia-Wen

2013-08-01

Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly being used for enhanced treatment of water or wastewater processes; however, the fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear. We investigated bioaccumulation and lethal-to-sublethal toxic effects on early life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25-200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)-stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and developmental toxic effects in embryos, with lesser and the least effects with Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity in the oxygenic solution, which led to a combination of hypoxia and production of reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI. The antioxidant balance was differentially altered by induced intracellular ROS in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI and its oxidized products in early life stages of medaka fish using different organizational levels of biomarker assays. The toxicity results implicate a potential eco-toxicological impact of nZVI on the aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Toxicity of ferric chloride sludge to aquatic organisms.

PubMed

Sotero-Santos, Rosana B; Rocha, Odete; Povinelli, Jurandyr

2007-06-01

Iron-rich sludge from a drinking water treatment plant (DWTP) was investigated regarding its toxicity to aquatic organisms and physical and chemical composition. In addition, the water quality of the receiving stream near the DWTP was evaluated. Experiments were carried out in August 1998, February 1999 and May 1999. Acute toxicity tests were carried out on a cladoceran (Daphnia similis), a midge (Chironomus xanthus) and a fish (Hyphessobrycon eques). Chronic tests were conducted only on D. similis. Acute sludge toxicity was not detected using any of the aquatic organisms, but chronic effects were observed upon the fecundity of D. similis. Although there were relatively few sample dates, the results suggested that the DWTP sludge had a negative effect on the receiving body as here was increased suspended matter, turbidity, conductivity, chemical oxygen demand (COD) and hardness in the water downstream of the DWTP effluent discharge. The ferric chloride sludge also exhibited high heavy metal concentrations revealing a further potential for pollution and harmful chronic effects on the aquatic biota when the sludge is disposed of without previous treatment.

[Toxic effect of DDT, chlordane and water from the Ignacio Ramírez dam (Mexico), on Daphnia magna (Crustacea: Daphnidae)].

PubMed

Martínez-Tabche, L; Romero Solís, M; López López, E; Galar Martínez, M

1999-12-01

Chlorodiphenylnitrichloroethane (DDT) and chlordane (CLO) are currently used in Mexico to control malaria and termites. From 1990 to 1996 a total of 27 ton of DDT and 508 of CLO were imported. We establish a methodology to determine their environmental impact in a Mexican dam (Ignacio Ramírez). The toxic effect of DDT and CLO were evaluated on the o-demethylase (OD) and acethycholinesterase activities (AchA) of the cladoceran Daphnia magna exposed to different concentrations of the insecticides solved in water from three sites. Their effect on the AchA and OD activities, and so the CL50 were used as exposure bioindicators to determine the more polluted sites. The physicochemical characteristics of water and the biodiversity of the dam test sites were considered. The station near the floodgate has toxicity potential because enzymatic activities were modified. We suggest the use of AchA and OD activities measure in the cladoceran to evaluate the toxicity of a water body polluted by organochlorate insecticides.

Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata.

PubMed

Aruoja, Villem; Dubourguier, Henri-Charles; Kasemets, Kaja; Kahru, Anne

2009-02-01

Toxicities of ZnO, TiO2 and CuO nanoparticles to Pseudokirchneriella subcapitata were determined using OECD 201 algal growth inhibition test taking in account potential shading of light. The results showed that the shading effect by nanoparticles was negligible. ZnO nanoparticles were most toxic followed by nano CuO and nano TiO2. The toxicities of bulk and nano ZnO particles were both similar to that of ZnSO4 (72 h EC50 approximately 0.04 mg Zn/l). Thus, in this low concentration range the toxicity was attributed solely to solubilized Zn2+ ions. Bulk TiO2 (EC50=35.9 mg Ti/l) and bulk CuO (EC50=11.55 mg Cu/l) were less toxic than their nano formulations (EC50=5.83 mg Ti/l and 0.71 mg Cu/l). NOEC (no-observed-effect-concentrations) that may be used for risk assessment purposes for bulk and nano ZnO did not differ (approximately 0.02 mg Zn/l). NOEC for nano CuO was 0.42 mg Cu/l and for bulk CuO 8.03 mg Cu/l. For nano TiO2 the NOEC was 0.98 mg Ti/l and for bulk TiO2 10.1 mg Ti/l. Nano TiO2 formed characteristic aggregates entrapping algal cells that may contribute to the toxic effect of nano TiO2 to algae. At 72 h EC50 values of nano CuO and CuO, 25% of copper from nano CuO was bioavailable and only 0.18% of copper from bulk CuO. Thus, according to recombinant bacterial and yeast Cu-sensors, copper from nano CuO was 141-fold more bioavailable than from bulk CuO. Also, toxic effects of Cu oxides to algae were due to bioavailable copper ions. To our knowledge, this is one of the first systematic studies on effects of metal oxide nanoparticles on algal growth and the first describing toxic effects of nano CuO towards algae.

Evaluating the Spatial Distribution of Toxic Air Contaminants in Multiple Ecosystem Indicators in the Sierra Nevada-Southern Cascades

NASA Astrophysics Data System (ADS)

Nanus, L.; Simonich, S. L.; Rocchio, J.; Flanagan, C.

2013-12-01

Toxic air contaminants originating from agricultural areas of the Central Valley in California threaten vulnerable sensitive receptors including surface water, vegetation, snow, sediments, fish, and amphibians in the Sierra Nevada-Southern Cascades region. The spatial distribution of toxic air contaminants in different ecosystem indicators depends on variation in atmospheric concentrations and deposition, and variation in air toxics accumulation in ecosystems. The spatial distribution of organic air toxics and mercury at over 330 unique sampling locations and sample types over two decades (1990-2009) in the Sierra Nevada-Southern Cascades region were compiled and maps were developed to further understand spatial patterns and linkages between air toxics deposition and ecological effects. Potential ecosystem impacts in the Sierra Nevada-Southern Cascades region include bioaccumulation of air toxics in both aquatic and terrestrial ecosystems, reproductive disruption, and immune suppression. The most sensitive ecological end points in the region that are affected by bioaccumulation of toxic air contaminants are fish. Mercury was detected in all fish and approximately 6% exceeded human consumption thresholds. Organic air toxics were also detected in fish yielding variable spatial patterns. For amphibians, which are sensitive to pesticide exposure and potential immune suppression, increasing trends in current and historic use pesticides are observed from north to south across the region. In other indicators, such as vegetation, pesticide concentrations in lichen increase with increasing elevation. Current and historic use pesticides and mercury were also observed in snowpack at high elevations in the study area. This study shows spatial patterns in toxic air contaminants, evaluates associated risks to sensitive receptors, and identifies data gaps. Future research on atmospheric modeling and information on sources is needed in order to predict which ecosystems are the most sensitive to toxic air contaminants in the Sierra Nevada-Southern Cascades region.