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Sample records for subchronic toxic effects

  1. Acute and Sub-Chronic Toxicity Potential Effects of Alchornea ...

    African Journals Online (AJOL)

    The open field test showed that sub-chronic administration increased rearing behavior significantly at the dose of 250 mg/kg/28 days but had no effect on grooming. In conclusion, the ethanolic extract has no toxicological effect as observed on hematological, biochemical and histopathological parameters even at the ...

  2. Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats

    OpenAIRE

    Ibrahim, Abdelazim; Eldaim, Mabrouk A. Abd; Abdel-Daim, Mohamed M.

    2015-01-01

    Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated grou...

  3. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Directory of Open Access Journals (Sweden)

    Basak Ozlem Perk

    2013-01-01

    Full Text Available The fruit of Physalis peruviana L. (PPL has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  4. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Science.gov (United States)

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  5. Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice

    Institute of Scientific and Technical Information of China (English)

    Qixiao Zhai; Tianqi Li; Leilei Yu; Yue Xiao; Saisai Feng; Jiangping Wu; Jianxin Zhao; Hao Zhang; Wei Chen

    2017-01-01

    Oral exposure to toxic metals such as cadmium (Cd),lead (Pb),copper (Cu) and aluminum (Al) can induce various adverse health effects in humans and animals.However,the effects of these metals on the gut microbiota have received limited attention.The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner.Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice,whereas no significant changes were observed in groups treated with other metals.Cd exposure significantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae.Pb exposure significantly decreased the abundances of eight genera:unclassified and uncultured Ruminococcaceae,unclassified Lachnospiraceae,Ruminiclostridium_9,Rikenellaceae_RC9_gut_group,Oscillibacter,Anaerotruncus and Lachnoclostridium.Cu exposure affected abundances of the genera Alistipes,Bacteroides,Ruminococcaceae_UCG-014,Allobaculum,Mollicutes_RFg_norank,Rikenellaceae_RC9_gut_group,Ruminococcaceae_unclassified and Turicibacter.Al exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus.Exposure to any metal for eight weeks significantly decreased the abundance of Akkermansia.These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.

  6. Subchronic and acute preclinical toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae)

    International Nuclear Information System (INIS)

    Garcia Gonzalez, Mildred; Coto Morales, Teresita; Ocampo, Rafael; Pazos, Liliana

    2006-01-01

    The effects of the aqueous extract of Petiveria alliacea, leaves were tested on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice, of 20 to 25 g mean weight. Treatments were in all cases doses of 1000 and 2000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed in both tests. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1000 mg/kg dose but not for the higher 2000 mg/kg doses. After administering the dose once after a starving period of six hours, no significant differences in intestinal motility could be found. (author) [es

  7. Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae).

    Science.gov (United States)

    García-González, Mildred; Morales, Teresita Coto; Ocampo, Rafael; Pazos, Liliana

    2006-12-01

    We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1,000 and 2,000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1,000 mg/kg dose but not for the higher 2,000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found.

  8. [Subchronic toxicity testing of mold-ripened cheese].

    Science.gov (United States)

    Schoch, U; Lüthy, J; Schlatter, C

    1984-08-01

    The biological effects of known mycotoxins of Penicillium roqueforti or P. camemberti and other still unknown, but potentially toxic metabolites in mould ripened cheese (commercial samples of Blue- and Camembert cheese) were investigated. High amounts of mycelium (equivalents of 100 kg cheese/man and day) were fed to mice in a subchronic feeding trial. The following parameters were determined: development of body weight, organ weights, hematology, blood plasma enzymes. No signs of adverse effects produced by cheese mycotoxins could be detected after 28 days. No still unknown toxic metabolites could be demonstrated. From these results no health hazard from the consumption of mould ripened cheese, even in high amounts, appears to exist.

  9. Effect of subchronic zinc toxicity on rat salivary glands and serum composition.

    Science.gov (United States)

    Mizari, Nazer; Hirbod-Mobarakeh, Armin; Shahinpour, Shervin; Ghalichi-Tabriz, Mostafa; Beigy, Maani; Yamini, Ali; Dehpour, Ahmad Reza

    2012-11-01

    Zinc plays an important role in a wide variety of metabolic processes in animal systems. The role of zinc in preservative treatment, fungicidal action and medicine, and addition of supplementary zinc have increased the probability of zinc toxicity, specially the chronic type. It is known that the composition and quantity of saliva influence the oral health. Regarding people's exposure to zinc in routine life and the importance of saliva, our purpose was to investigate the effects of oral zinc intoxication on secretory function in rat salivary glands and also on serum composition. In this study, there were five groups of female rats. Four groups received zinc acetate dehydrate through their drinking water. After 3 months of experiment, the chemical characteristics and flow rate of saliva and weight of salivary glands were determined. The effects of zinc on hematological and chemical factors of plasma were assessed too. Flow rate of submandibular glands was significantly lower in experimental groups and there were significant changes in Na(+), Ca(2+) and K(+) concentration both in saliva and in plasma. The serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, glucose levels in the plasma and urine creatinine levels were also altered in experimental groups in comparison with the control group. Our results show that zinc toxicity will affect the quantity and quality of saliva probably through changes in the various neurologic pathways to the salivary glands or effects on acinar cells of the salivary glands. Furthermore, our results showed that zinc toxicity will affect the liver and renal function.

  10. Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae

    Directory of Open Access Journals (Sweden)

    Mildred García-González

    2006-12-01

    Full Text Available We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1 000 and 2 000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week. Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1 000 mg/kg dose but not for the higher 2 000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found. Rev. Biol. Trop. 54 (4: 1323-1326. Epub 2006 Dec. 15Se evaluaron los efectos del estracto acuoso de las hojas de Petiveria alliacea, en la toxicidad aguda y toxicidad subcrónica, hematocritos, niveles de glucosa en la sangre y motilidad intestinal del ratón macho albino NGP, con un peso promedio de 20 a 25g. En todos los casos los tratamientos fueron dosis de 1 000 y 2 000 mg/kg de peso del animal y un tratamiento control con 0.5 ml de agua destilada, usando 10 animales por tratamiento y administrado oralmente cinco días por semana. Los períodos experimentales fueron de 18 y 70 días para toxicidad aguda y toxicidad subcrónica, respectivamente. No se observaron signos de mortalidad ni de toxidad en ambas pruebas. Con la dosis de 1 000 mg/kg hubo un leve pero significativo incremento en los niveles de glucosa durante las primeras tres semanas, pero no con la dosis más alta de 2 000 mg/kg. Después de administrar las dosis luego de un período de hambre de seis horas, no se encontraron diferencias significativas en la motilidad intestinal

  11. Subchronic toxicity study of corn silk with rats.

    Science.gov (United States)

    Wang, Cuina; Zhang, Tiehua; Liu, Jun; Lu, Shuang; Zhang, Cheng; Wang, Erlei; Wang, Zuozhao; Zhang, Yan; Liu, Jingbo

    2011-09-01

    Corn silk is a traditional herbal medicine in China, which has been used in many parts of the world for the treatment of edema as well as for cystitis, gout, kidney stones, nephritis, prostatitis and similar ailments. However, there is little scientific evidence about its safety. As a part of its safety assessment, a subchronic toxicity was performed in this paper. The subchronic toxicity was investigated in male and female Wistar rats by dietary administration at concentrations of 0.5%, 2.0% and 8.0% (w/w) for 90 days. Overall health, body weight, food consumption, hematology, blood chemistry, organ weights, gross and microscopic appearance of tissues were compared between test and control groups. A number of significant differences were seen between groups, but none of them was considered to be adverse. Based on the present study, the no-observed-adverse-effect level (NOAEL) of corn silk is at least 8.0% which corresponds to a mean daily corn silk intake of approximately 9.354 and 10.308 g/day/kg body weight for males and females, respectively. The results obtained in the present study suggest that consumption of corn silk has no adverse effects and support the safety of corn silk for humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.

    Science.gov (United States)

    Abu, Nadiah; Zamberi, Nur Rizi; Yeap, Swee Keong; Nordin, Noraini; Mohamad, Nurul Elyani; Romli, Muhammad Firdaus; Rasol, Nurulfazlina Edayah; Subramani, Tamilselvan; Ismail, Nor Hadiani; Alitheen, Noorjahan Banu

    2018-01-27

    Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.

  13. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    Science.gov (United States)

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  14. Subchronic oral toxicity of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Kim Yong

    2010-08-01

    Full Text Available Abstract Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm over a period of 13 weeks (90 days in F344 rats following Organization for Economic Cooperation and Development (OECD test guideline 408 and Good Laboratory Practices (GLP. Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group: vehicle control, low-dose (30 mg/kg, middle-dose (125 mg/kg, and high-dose (500 mg/kg. After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level of 30 mg/kg and LOAEL (lowest observable adverse effect level of 125 mg/kg are suggested from the present study.

  15. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures.

    Science.gov (United States)

    Pauluhn, Jürgen

    2010-01-01

    Wistar rats were nose-only exposed to multiwalled carbon nanotubes (MWCNT, Baytubes) in a subchronic 13-week inhalation study. The focus of study was on respiratory tract and systemic toxicity, including analysis of MWCNT biokinetics in the lungs and lung-associated lymph nodes (LALNs). The time course and concentration dependence of pulmonary effects were examined by bronchoalveolar lavage (BAL) and histopathology up to 6 months postexposure. Particular emphasis was directed to the comparative characterization of MWCNT structures prior to and after micronization and dry powder dispersion into inhalation chambers. These determinations were complemented by additional analyses in digested BAL cells. Animals were exposed on 6 h/day, 5 days per week for 13 consecutive weeks to 0, 0.1, 0.4, 1.5, and 6 mg/m(3). The subchronic exposure to respirable solid aerosols of MWCNT was tolerated without effects suggestive of systemic toxicity. Kinetic analyses demonstrated a markedly delayed clearance of MWCNT from lungs at overload conditions. Translocation into LALNs occurred at 1.5 and 6 mg/m(3) and required at least 13 weeks of study to become detectable. At these exposure levels, the lung and LALN weights were significantly increased. Sustained elevations in BAL polymorphonuclear neutrophils and soluble collagen occurred at these concentrations with borderline effects at 0.4 mg/m(3). Histopathology revealed principal exposure-related lesions at 0.4 mg/m(3) and above in the upper respiratory tract (goblet cell hyper- and/or metaplasia, eosinophilic globules, and focal turbinate remodeling) and the lower respiratory tract (inflammatory changes in the bronchioloalveolar region and increased interstitial collagen staining). Granulomatous changes and a time-dependent increase of a bronchioloalveolar hyperplasia occurred at 6 mg/m(3). All end points examined were unremarkable at 0.1 mg/m(3) (no-observed-adverse-effect-level). In summary, this study demonstrates that the induced

  16. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

    Science.gov (United States)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

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    A. V. Voronkov

    2016-01-01

    Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

  18. Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

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    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

    Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

  19. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  20. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    International Nuclear Information System (INIS)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-01-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

  1. [Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

    Science.gov (United States)

    Li, Min; Piao, Jianhua; Yang, Xiaoguang

    2010-07-01

    To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

  2. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  3. Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

    International Nuclear Information System (INIS)

    McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A.

    2007-01-01

    Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca 2+ , changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

  4. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

    Science.gov (United States)

    Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

    2017-06-01

    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Acute and subchronic toxicity studies of the original drug FS-1

    Directory of Open Access Journals (Sweden)

    Assem Kalykova

    2016-01-01

    Full Text Available Interest in iodine complexes has increased significantly in recent years because of their wide spectrum of biological activity. The FS-1 is an ion nanostructured complex formed by proteins and/or polypeptides, carbohydrates, salts of alkali and alkaline earth metals with intercalated iodine. Patented in 2014, it is intended for the treatment of infectious diseases of bacterial origin including nosocomial infections and multidrug resistant tuberculosis. The aim of the study was to determine its acute and subchronic toxicity. The study of acute and subchronic toxicity was performed on adult Wistar rats according to OECD guidelines. The data on acute toxicity showed LD50 > 2,000 mg/kg after a single intragastric administration. Twenty-eight days of FS-1 administration at a dose of 500 mg/kg resulted in toxic effects. At a dose of 250 mg/kg, the toxic effects were temporary and a return to normal followed after the recovery period. Doses of 100 mg/kg had no adverse effects on the rats.

  6. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    Science.gov (United States)

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  7. Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

    Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

  8. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    Science.gov (United States)

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

  9. Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

    Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

  10. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    International Nuclear Information System (INIS)

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-01-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted

  11. Acute and sub-chronic oral toxicity studies of methanol extract of ...

    African Journals Online (AJOL)

    Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Norhafizah Mohtarrudin, Arifah Abdul Kadir, Manraj Singh Cheema, Zuraini Ahmad, Ching Siew Mooi, Siti Farah Md. Tohid ...

  12. Acute and Sub-chronic (28-day) Oral Toxicity Studies of ...

    African Journals Online (AJOL)

    Erah

    was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats. Methods: In the acute test, the ... associated with navel in children [4], and in the treatment of ... Ethical Committee for Teaching and. Research (ref no.

  13. Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

    Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

  14. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

    International Nuclear Information System (INIS)

    Seacat, Andrew M.; Thomford, Peter J.; Hansen, Kris J.; Clemen, Lisa A.; Eldridge, Sandra R.; Elcombe, Cliff R.; Butenhoff, John L.

    2003-01-01

    Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (< twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (μg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370

  15. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2012-09-01

    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  16. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models

    International Nuclear Information System (INIS)

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.; Chen, Wei

    2016-01-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD_5_0 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. - Highlights: • The acute and subchronic toxicity of PFOS was systematically investigated. • The acute oral LD_5_0 value for PFOS in C57BL/6J mice was 0.579 g/kg body weight. • PFOS disrupted the homeostasis of antioxidative systems. • PFOS induced hepatocellular apoptosis and triggered liver injury. - PFOS disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis, and triggered liver injury.

  17. Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and kidney following subchronic exposure.

    Science.gov (United States)

    Mitra, Sumonto; Gera, Ruchi; Singh, Vikas; Khandelwal, Shashi

    2014-02-01

    Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to its bio-accumulative property. Isolated studies of TBT toxicity on different organs are available but consolidated information is greatly lacking. We planned this study to delineate the effect of subchronic (1 month) exposure to low dose TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration was found to be significantly increased in liver, kidney and blood, and marginally in lungs. Organo-somatic indices were seen to be altered with little effect on serum biochemical markers (liver and kidney function, and general parameters). Reactive oxygen species but not lipid peroxidation content was observed to be significantly elevated both in the tissues and serum. TBTC was found to act as a hyperlipidemic agent and it also affected heme biosynthetic pathway. Hematological analysis showed that TBTC exposure resulted in minor alterations in RBC parameters. Histological studies demonstrated marked tissue damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex-vivo conditions. Antioxidants were evidently more efficient in comparison to the calcium inhibitors, implying major role of oxidative stress pathways in TBTC toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. [Nutritional components and sub-chronic toxicity of genetically modified rice expressing human lactoferrin].

    Science.gov (United States)

    Hu, Yichun; Piao, Jianhua; Yang, Xiaoguang

    2012-01-01

    To compare the nutritional components of genetically modified rice expressing human lactoferrin (hLf) with its parental rice, and to observe the sub-chronic toxicity of hLf rice. The nutritional components of hLf rice and its parental rice were determined by the National Standard Methods. Eighty weanling Wistar rats were randomly divided into 4 groups based on their gender and body weight: group A (hLf rice high-dose group with 71.45% rice), group B (hLf rice medium-dose group with 35. 725% rice), group C (parental rice group with 71.01% rice) and group D (AIN-93G diet group), and the latter two groups were used as the control. Body weight, dietary intake, blood routine test, blood biochemical examination, organ coefficient, bone density and the pathology of organs were investigated at the end of a 90-day feeding experiment. Except for human lactoferrin and Fe, there was no difference of main nutritional components, minerals and vitamins between groups. The differences of some indicators of blood routine (WBC, HGB, RBC and MCH), blood biochemistry (AST and GLU), organ coefficient and bone density between group A and B (hLf rice) with group C (parental rice) or group D (AIN-93G) were significant, while no difference of other indicators. Although some differences were observed, all indicators were still in the normal reference range. Therefore, there was no sign of toxic and adverse effects for hLf rice on rats.

  19. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    Science.gov (United States)

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO2) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO2 -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO2 test particles (d50 = 145 nm - 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO2 particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO2 test particles (d50 = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO2 particles (d50 = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD50 for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies - each with different TiO2 particulate-types, demonstrated an absence of

  1. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    Science.gov (United States)

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  2. Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

    Science.gov (United States)

    Simon, Ryan R; Vo, Trung D; Levine, Robert

    2016-10-01

    Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    Science.gov (United States)

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. hepatorenal toxicity studies of sub-chronic administration of calyx

    African Journals Online (AJOL)

    DR. AMINU

    significant (p>0.05) increase in concentrations of total protein and albumin were observed in ... suggest that high dose of calyx extracts of H.sabdariffa may be toxic to liver and kidney. .... monitoring liver damage (Wada and Snell, 1962).

  6. Biochemical biomarker responses of green-lipped mussel, Perna canaliculus, to acute and subchronic waterborne cadmium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Chandurvelan, Rathishri, E-mail: rch118@uclive.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Marsden, Islay D., E-mail: islay.marsden@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Gaw, Sally, E-mail: sally.gaw@canterbury.ac.nz [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Glover, Chris N., E-mail: chris.glover@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

    2013-09-15

    Highlights: •Biochemical biomarkers were measured to assess effects of Cd on Perna canaliculus. •Biochemical responses varied between acute and subchronic exposure to Cd. •MTLP induction correlated strongly with Cd accumulation. •Alkaline phosphatase and glycogen levels decreased during subchronic Cd exposure. •Duration of Cd exposure influenced biochemical biomarker responses in mussels. -- Abstract: The biochemical responses of the green-lipped mussel, Perna canaliculus, to waterborne cadmium (Cd) were investigated in order to delineate toxic mechanisms, and the impacts of exposure dose and duration, of this important toxicant in a potential sentinel species. Mussels were exposed for either 96 h (acute: 0, 2000, 4000 μg L{sup −1} Cd) or for 28 d (subchronic: 0, 200, 2000 μg L{sup −1} Cd), and the digestive gland, gill and haemolymph were examined for impacts. Biochemical responses measured included those associated with metal detoxification (metallothionein-like protein; MTLP), oxidative stress (catalase, lipid peroxidation), cellular homeostasis (alkaline phosphatase, Na{sup +}, K{sup +}-ATPase; NKA), and energy utilisation (glycogen, haemolymph protein). Following acute exposure, digestive gland glycogen and gill NKA activity were significantly altered by Cd exposure relative to levels in mussels exposed to Cd-free seawater. Subchronic Cd exposure resulted in a significant increase in MTLP levels in both the gill and the digestive gland. This increase was correlated strongly with the levels of Cd accumulation measured in these tissues (R = 0.957 for gill, 0.964 for digestive gland). Catalase activity followed a similar pattern, although the correlation with tissue Cd accumulation was not as strong (R = 0.907 for gill, 0.708 for digestive gland) as that for MTLP. Lipid peroxidation increased in the digestive gland at Days 7 and 14 at both subchronic Cd levels tested, but this effect had largely dissipated by Days 21 and 28 (with the exception of

  7. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  8. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

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    Ayman Goudah

    2015-05-01

    Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  9. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

    Science.gov (United States)

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A

    2015-05-01

    The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  10. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

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    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  11. Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

    International Nuclear Information System (INIS)

    Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2014-01-01

    Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems. (papers)

  12. Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

    Science.gov (United States)

    Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2014-06-01

    Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.

  13. Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

    Science.gov (United States)

    Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

    2012-04-01

    The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    Science.gov (United States)

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Subchronic toxicity evaluation of anthraquinone in Fischer 344 rats.

    Science.gov (United States)

    Dodd, Darol E; Layko, Debra K; Cantwell, Katherine E; Willson, Gabrielle A; Thomas, Russell S

    2013-01-01

    Female F344 rats were exposed to anthraquinone (AQ) by dietary feed at concentrations of 0, 50, 150, 469, 938, 1875, or 3750 ppm for 2 or 13 weeks. End points evaluated included clinical observations, body weights, serum chemistry, blood AQ, gross pathology, organ weights, and select tissue histopathology. Mean body weight and food consumption were 5% to 10% lower than control values in rats of the ≥938 ppm group during study weeks 2 through 13. Occasional decreases in body weight means were also observed in rats of the 150 and 469 ppm groups. Increases in liver, kidney, and spleen weights were observed in rats exposed to AQ diet concentrations ≥150 ppm for 13 weeks. Urinary bladder weights were increased at ≥469 ppm. Liver and spleen weights were also increased following 2 weeks of exposure. Liver weight increases were clearly dependent on AQ concentration. At 2 weeks, decreases in serum aspartate aminotransferase (AST), blood urea nitrogen, and creatinine concentrations were observed in higher AQ exposure groups, and AST was decreased at 13 weeks (≥1875 ppm). Microscopic alterations were observed in the liver (mild centrilobular hypertrophy), spleen (mild hematopoietic cell proliferation and pigmentation), and kidneys (minimal hyaline droplets) of rats exposed to AQ for 13 weeks. Blood AQ concentrations ranged from 0.75 to 14.8 µg/mL in rats of the 150 to 3750 ppm groups, respectively, and were similar in value following either 2 weeks or 13 weeks of exposure. A no observed adverse effect level of 469 ppm AQ (31.3 mg/kg/d) was selected based on the absence of liver histopathology.

  16. Toxicity effect of sub-chronic oral administration of class bitters® - a polyherbal formula on serum electrolytes and hematological indices in male Wistar albino rats

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    Kingsley C. Patrick-Iwuanyanwu

    2015-11-01

    Full Text Available The indiscriminate administration of readyto- use herbal formulations has become a major concern due to their potential health risk. The study investigated the effect of class bitters® (CB - a polyherbal formula prepared with Mondia whitei, Khaya senegalensis, Capparis erythrocarpus, Thoningia sanguinea and Xylopia aethiopica on serum electrolytes and hematological parameters in male Wistar albino rats. Two doses (500 and 1000 mg kg–1 of the polyherbal drugs were administered orally to male Wistar albino rats for a period of 9 weeks. The results showed that administration of 500 and 1000 mg kg–1 body weight of CB recorded a marked increase in the levels of sodium and chlorum when compared with control. However, there was a marked reduction in the levels of potassium and hydrogen carbonate. The results of the study also showed a significant (P≤0.05 decrease in the level of hematological parameters such as hemoglobin (Hb, packed cell volume (PCV, red blood cells (RBCs and platelets levels in the male Wistar albino rats, when compared with control. The marked decrease in Hb, PCV, RBCs and platelets concentrations observed in experimental rats in this study suggest that CB may have an adverse effect on erythropoiesis. These observations therefore showed that long-term administration of CB might cause renal disease and anemia.

  17. Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles

    Science.gov (United States)

    Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

    2015-01-01

    Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile. PMID:26491315

  18. Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

  19. Acute and subchronic toxicity study of the water extract from root of Imperata cylindrica (Linn. Raeusch. in rats

    Directory of Open Access Journals (Sweden)

    Siharat Chunlaratthanaphorn

    2007-03-01

    Full Text Available The water extract from root of Imperata cylindrica (Linn. Raeusch. was studied for acute and subchronic toxicities. The extract at a single dose of 5,000 mg/kg was administered orally to female and male rats (5 male, 5 female. After 14 days, signs and behavioral changes, mortality, gross and histopathological changes of internal organs were examined. The extract did not produce signs of toxicity. For the subchronic toxicity test, the extract at doses of 300, 600 and 1,200 mg/kg body weight was orally administered to rats daily for 90 days (10 male, 10 female. The observation of signs, behavior and health status showed no abnormality in the test groups as compared with the controls. At the end of the study, necropsy and histopathology examination were performed in all animals in the control group, the test groups and the satellite group in which the extract was discontinued for another 28 days. Body and organ weights, hematological and blood clinical chemistry were also examined. The results suggest that the water extract of Imperata cylindrica (Linn. Raeusch does not cause acute and subchronic toxicities in rats.

  20. Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

    Science.gov (United States)

    Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

    1999-12-01

    The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

  1. Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

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    Pongri Adarki

    2017-09-01

    Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

  2. Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

    Science.gov (United States)

    Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Matsushita, Kohei; Nishikawa, Akiyoshi; Imaida, Katsumi; Ogawa, Kumiko

    2017-01-01

    3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

  3. Acute and Subchronic Toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from Chloroform Bay Leaf Extract (Eugenia Polyantha W.) with Palm Kernel Oil as A Carrier

    Science.gov (United States)

    Prihapsara, F.; Mufidah; Artanti, A. N.; Harini, M.

    2018-03-01

    The present study was aimed to study the acute and subchronic toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with Palm Kernel Oil as carrier. In acute toxicity test, five groups of rat (n=5/groups) were orally treated with Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with doses at 48, 240, 1200 and 6000 mg/kg/day respectively, then the median lethal dose LD50, advers effect and mortality were recorded up to 14 days. Meanwhile, in subchronic toxicity study, 4 groups of rats (n=6/group) received by orally treatment of SNEDDS from chloroform bay leaf extract with doses at 91.75; 183.5; 367 mg/kg/day respectively for 28 days, and biochemical, hematological and histopatological change in tissue such as liver, kidney, and pancreatic were determined. The result show that LD50 is 1045.44 mg/kg. Although histopathological examination of most of the organs exhibited no structural changes, some moderate damage was observed in high‑ dose group animals (367 mg/kg/day). The high dose of SNEDDS extract has shown mild signs of toxicity on organ function test.

  4. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    Science.gov (United States)

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Subchronic toxicity of Nile tilapia with different exposure routes to Microcystis aeruginosa: Histopathology, liver functions, and oxidative stress biomarkers

    Directory of Open Access Journals (Sweden)

    H. M. R. Abdel-Latif

    2017-08-01

    Full Text Available Background: Toxic cyanobacterial blooms (Microcystis aeruginosa contains microcystins [MCs] have been reported to induce clinicopathological alterations as well as different oxidative stress in aquatic biota. Aim: Three-week subchronic exposure experiment was carried out on Nile tilapia, to determine their effects on fish behavior, tissues, liver functions, antioxidant enzymes, and lipid peroxidation. Materials and Methods: Fish were exposed to four main treatments; orally fed diet plus toxic cells of M. aeruginosa (containing 3500 μg/g MC-LR, immersion in 500 μg MC-LR/L, intraperitoneal injection of M. aeruginosa MC-LR with a dose of 0.1 ml of extracted toxin at a dose of 200 μg/kg bwt, and the fourth one served as a control group, then the fish were sacrificed at the end of 3rd week of exposure. Results: The results revealed no recorded mortality with obvious behavioral changes and an enlarged liver with the congested gall bladder. Histopathology demonstrated fragmentation, hyalinization, and necrosis of the subcutaneous musculature marked fatty degeneration, and vacuolation of hepatopancreatic cells with adhesion of the secondary gill lamellae associated with severe leukocytic infiltration. Furthermore, liver functions enzymes (aspartate aminotransferase and alanine aminotransferase, and the activities of glutathione peroxidase, glutathione reductase, lipid peroxidase, and catalase enzymes were significantly increased in all treatments starting from the 2nd week as compared to the control levels. Conclusion: In this context, the study addresses the possible toxicological impacts of toxic M. aeruginosa contain MC-LR to Nile tilapia, and the results investigated that MC-LR is toxic to Nile tilapia in different routes of exposure as well as different doses.

  6. Effect of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to hematological parameters in rat

    Science.gov (United States)

    Bachri, M. S.; Yuliani, S.; Sari, A. K.

    2017-11-01

    Nutmeg is dried kernel of broadly ovoid seed of Myristica fragrans Houtt. It has been mentioned in ethnomedical literature as aphrodisiac, stomachic, carminative, tonic, and nervous stimulant. In order to establish the safety of nutmeg, the effect of the repeated administration of nutmeg is needed. The study was aimed to determine the toxic effect of subchronic administration of nutmeg ethanolic extract to hematological parameters in rat. A total of 28 male adult Wistar rats divided into 4 groups. Group I as control was given by 0.5% CMC-suspension, group II, III, and IV were given by 50, 100, and 200 mg/kg bw, respectively, of nutmeg ethanolic extract. The treatments were administered daily for 31 days. On day 31 bloods were taken from orbital sinus. The hematological parameter consisted of the numbers of erythrocyte and leukocyte as well as hemoglobin and total protein levels were measured. The data were statistically analyzed by one way Anova followed by LSD test. All of observed hematological parameters in rats showed that there were no significant difference between the nutmeg ethanolic extract treated groups and control group. The result indicated that the subchronic administration of 50, 100, and 200 mg/kg bw of nutmeg ethanolic extract did not cause the change of hematological parameters in rat.

  7. Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae in Male Rats

    Directory of Open Access Journals (Sweden)

    Abidemi J. Akindele

    2018-01-01

    Full Text Available Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o. for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05 reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01 increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001 reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05 the level of total cholesterol (400 mg/kg and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg. Significant (p < 0.05 increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic

  8. Safety assessment of McB-E60 (extract of a Momordica sp.: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Narendra S. Deshmukh

    Full Text Available Momordica charantia plant is consumed as a foodstuff in some south Asian curries while its extract preparations have been traditionally used for lowering blood glucose levels in patients with diabetes mellitus. Nutritional Health Institute Laboratories (NHIL, LLC, Florida informed that it patented a new plant McB, as an interhybrid of three plants of Momordica genus. The objective of the present study was to investigate potential adverse effects, if any, of McB-E60 (extract of a Momordica sp. in rats following subchronic administration. Sprague-Dawley rats (10/sex/group were administered via oral gavage 0 (control, 250, 500 and 1000 mg/kg body weight (bw/day of McB-E60 for 90 days. Additional 28-day recovery groups were maintained at control and high dose levels. No mortality or significant and adverse changes in clinical signs, neurological signs, body weight gain or feed intake were noted. No toxicologically significant changes in hematology, clinical chemistry, urinalysis and organ weights were noted. Gross and microscopic pathology examinations did not reveal treatment-related abnormalities. Any changes noted were incidental and within historical control ranges. Based on the results of this study, the No-Observed-Effect Level (NOEL for McB-E60 (extract of a Momordica sp. was determined as greater than 1000 mg/kg bw/day, the highest dose tested. Keywords: Dietary supplement, Safety, Toxicity

  9. How subchronic and chronic health effects can be neglected for GMOs, pesticides or chemicals.

    Science.gov (United States)

    Séralini, Gilles-Eric; de Vendômois, Joël Spiroux; Cellier, Dominique; Sultan, Charles; Buiatti, Marcello; Gallagher, Lou; Antoniou, Michael; Dronamraju, Krishna R

    2009-06-17

    Chronic health effects are increasing in the world such as cancers, hormonal, reproductive, nervous, or immune diseases, even in young people. During regulatory toxicological subchronic tests to prevent these on mammalian health, prior commercialization of chemicals, including pesticides and drugs, or GMOs, some statistically significant findings may be revealed. This discussion is about the need to investigate the relevant criteria to consider those as biologically significant. The sex differences and the non linear dose or time related effects should be considered in contrast to the claims of a Monsanto-supported expert panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in particular to reveal hormone-dependent diseases and first signs of toxicities.

  10. A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats

    Directory of Open Access Journals (Sweden)

    Toyohisa Katsumata

    2014-01-01

    Full Text Available Astaxanthin is believed to be beneficial to human health because it possesses strong antioxidant properties. A natural astaxanthin-rich carotenoid extract (ARE was produced by a well-controlled fermentation of a natural bacteria Paracoccus carotinifaciens, followed by the extraction and enrichment of the final product comprising mixture of carotenoids that is predominantly astaxanthin. The aim of this study was to evaluate the sub-chronic toxicity of the ARE using 6 week old Sprague-Dawley SPF rats [Crl:CD(SD]. The test article was suspended in olive oil and administered daily to the rats by oral gavage for 13 weeks at doses of 0 (olive oil, 250, 500 or 1000 mg/kg/day. Each group consisted of 10 animals of each sex. No deaths occurred and no treatment-related changes were observed in the detailed clinical observations, manipulative tests, grip strength, motor activity, body weights, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology. Dark-red feces were observed throughout the administration period in all treated groups due to excretion of the colored test article. Based on these results, it was concluded that the no observed adverse effect level (NOAEL for ARE was at least 1000 mg/kg/day for male and female rats, respectively.

  11. Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

    Directory of Open Access Journals (Sweden)

    Marjan Razavi

    2013-01-01

    Full Text Available Objective(s: In this study, the effects of crocin against subchronic toxicity of diazinon (DZN on systolic blood pressure (SBP and heart rate (HR were evaluated in rats. Materials and Methods: Rats were equally divided into 7 groups; control (corn oil, DZN (15 mg/kg, crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN, vitamin E (200 IU/kg plus DZN and crocin (50 mg/kg treated groups.  Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week and crocin (once a day were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method, malondealdehyde (MDA levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method; SBP and HR (tail cuff method were evaluated at the end of 4th week. Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001. Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001 in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01 and increased HR (P< 0.001 in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

  12. Assessment of the Toxicity of Sub-chronic Low and High Doses of the Bio-insecticide Spinosad on the Liver, Kidney and the Cerebellum in Male Albino Mice

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    Sabry A El-Naggar

    2017-06-01

    Full Text Available ABSTRACT Spinosad (SPD is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1 served as a control, second group (G2 received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3 received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT, triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

  13. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  14. Acute and sub-chronic oral toxicity studies of the extracts from herbs ...

    African Journals Online (AJOL)

    AJL

    2012-06-14

    Jun 14, 2012 ... Thailand registered PN in the list of herbal medical ... Pharmacy, Silpakorn University, Nakorn Pathom, Thailand. The ... automated blood analyzer (Hitachi Science Systems Ltd., Ibaraki, ..... toxic effects of the extracts in both concurrent control and ..... uric acid levels might be necessary when patients are.

  15. Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Cobbina, Samuel J.; Chen, Yao [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Zhou, Zhaoxiang; Wu, Xueshan; Zhao, Ting [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China); Zhang, Zhen [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Feng, Weiwei; Wang, Wei [School of Food and Biological Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Li, Qian [School of Pharmacy, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Wu, Xiangyang, E-mail: wuxy@ujs.edu.cn [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Yang, Liuqing, E-mail: yangliuqing@ujs.edu.cn [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China)

    2015-08-30

    Highlights: • Low dose single and mixtures of toxic metals had adverse effect on mice. • Metal mixtures exhibited higher toxicities compared to individual metals. • Mixtures of low dose Pb + Hg + Cd induced neuronal degeneration in brain of mice. • Exposure to Pb + Hg + As + Cd showed renal tubular necrosis in kidney. - Abstract: Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on toxicity of low dose mixtures. In this study, lead (Pb) (0.01 mg/L), mercury (Hg) (0.001 mg/L), cadmium (Cd) (0.005 mg/L) and arsenic (As) (0.01 mg/L) were administered individually and as mixtures to 10 groups of 40 three-week old mice (20 males and 20 females), for 120 days. The study established that low dose exposures induced toxicity to the brain, liver, and kidney of mice. Metal mixtures showed higher toxicities compared to individual metals, as exposure to low dose Pb + Hg + Cd reduced brain weight and induced structural lesions, such as neuronal degeneration in 30-days. Pb + Hg + Cd and Pb + Hg + As + Cd exposure induced hepatocellular injury to mice evidenced by decreased antioxidant activities with marginal increases in MDA. These were accentuated by increases in ALT, AST and ALP. Interactions in metal mixtures were basically synergistic in nature and exposure to Pb + Hg + As + Cd induced renal tubular necrosis in kidneys of mice. This study underlines the importance of elucidating the toxicity of low dose metal mixtures so as to protect public health.

  16. Sub-chronic toxicity study of a novel herbal-based formulation (Semelil on dogs

    Directory of Open Access Journals (Sweden)

    Farzamfar B

    2008-04-01

    Full Text Available Semelil (ANGIPARSTM, a novel herbal-based compound containing extract of Melilotus officinalis, was formulated for treatment of chronic wounds, especially diabetic foot ulcer. The purpose of this study was to investigate safety and toxicity effects of intramuscular administration of Semelil in dogs. "nPreliminary one-month study with Semelil was performed on 8 male and female dogs divided into 2 groups, test and control, four animals each. Semelil was administered intramuscularlyat a dose of 0.07 ml/kg body wt. once a day to the animals of the test group, while the control group received sterile saline. During experiments, general state of the animals including the dynamics of body weight changes, appetite, motor activity and behavior, hair condition, ECG parameters, rectal temperature of animals and data of hematological and biochemical tests were monitored for signs of toxicity and side-effects. Finally, morphology and histology analyses were performed using standard methods."nNo adverse health or toxicity effects were observed through the course of the study. No damaging consequences of Semelil injections on the functional state of main organs of the experimental animals were found. This observation gave a good evidence of a favorable safety profile compatible with potential therapeutic use of Semelil.

  17. Does a concomitant exposure to lead influence unfavorably the naphthalene subchronic toxicity and toxicokinetics?

    Science.gov (United States)

    Katsnelson, Boris A; Minigaliyeva, Ilzira A; Degtyareva, Tamara D; Privalova, Larisa I; Beresneva, Tatyana A

    2014-01-01

    Rats were given 20 times during 40 d either naphthalene per gavage or the same and lead acetate intraperitoneally in single doses corresponding to 5% of the respective 50% lethal doses. The concomitant exposure to lead not only added some typical indicators of lead toxicity to the moderate naphthalene intoxication picture but also exaggerated some less specific indices for intoxication. However, a number of such indices testified to attenuation of naphthalene's adverse effects under the impact of lead. Lead also lowered urinary excretion of both total and conjugated naphthalene, while the free- to total naphthalene ratio in urine sharply increased. These results corroborate implicitly the initial hypothesis that lead, being an inhibitor of cytochrome P450, hinders phase I of the naphthalene biotransformation and, thus, the formation of derivates which can be more toxic but are capable of entering into reactions of conjugation with resulting detoxication and elimination of naphthalene from the body. © 2013 SETAC.

  18. Subchronic toxicity studies of t-butyl alcohol in rats and mice.

    Science.gov (United States)

    Lindamood, C; Farnell, D R; Giles, H D; Prejean, J D; Collins, J J; Takahashi, K; Maronpot, R R

    1992-07-01

    The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

  19. Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

    Science.gov (United States)

    Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

    2017-06-01

    In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

  20. Health effects of subchronic exposure to environmental levels of diesel exhaust.

    Science.gov (United States)

    Reed, M D; Gigliotti, A P; McDonald, J D; Seagrave, J C; Seilkop, S K; Mauderly, J L

    2004-04-01

    Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 microg/m(3)). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of

  1. Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

    Science.gov (United States)

    Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

    2010-03-26

    In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

    Science.gov (United States)

    Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

    2018-03-01

    Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

  3. The sub-chronic toxicity of regular White Spirit in rats.

    Science.gov (United States)

    Carrillo, Juan-Carlos; Adenuga, M David; Mckee, Richard H

    2014-10-01

    Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3). Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Subchronic toxicity evaluation of γ-aminobutyric acid (GABA) in rats.

    Science.gov (United States)

    Takeshima, Kazuhito; Yamatsu, Atsushi; Yamashita, Yusuke; Watabe, Kazuya; Horie, Noriko; Masuda, Kazuyuki; Kim, Mujo

    2014-06-01

    γ-Aminobutyric acid (GABA) is an amino acid compound contained in vegetables such as tomatoes and also widely distributed in mammals. GABA acts as an inhibitory neurotransmitter and promotes parasympathetic activity to provide several beneficial effects, for instance, relaxation, anti-stress, and insomnia. GABA, produced via a fermentation process, has been available as a functional food ingredient. As part of a program to assess its safety, GABA was administered by oral gavage at doses of 500, 1250, and 2500mg/kg body weight to groups of 10 male and 10 female Sprague-Dawley rats for 13weeks. Treatment was not associated with the test substance-related mortality and appeared to be well tolerated. There were no toxicologically and statistically significant changes in urinalysis, hematology, clinical chemistry parameters, and in necropsy findings. A few statistically significant changes in food consumption and body weights were noted in the male groups while any significant changes were not noted in female groups. There was no effect of treatment on organ weights or on the results of the histopathological examinations. The results of toxicity evaluation support the safety use of GABA and the potential use as a functional food ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    Science.gov (United States)

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

    Science.gov (United States)

    Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

    2017-06-01

    Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

    International Nuclear Information System (INIS)

    Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres; Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L.; Kodavanti, Urmila P.

    2016-01-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

  8. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Henriquez, Andres [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2016-09-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

  9. Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats

    Directory of Open Access Journals (Sweden)

    Job Tchoumtchoua

    2014-01-01

    Full Text Available Amphimas pterocarpoides Harms (Leguminosae is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent and without biological relevance indicate a wide margin of safety for the traditional use of AP.

  10. Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no

  11. Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

    NARCIS (Netherlands)

    Til, H.P.; Bär, A.

    1998-01-01

    The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs

  12. Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment

    International Nuclear Information System (INIS)

    Xie Liqiang; Xie Ping; Ozawa, Kazuhiko; Honma, Takamitsu; Yokoyama, Atsushi; Park, Ho-Dong

    2004-01-01

    A sub-chronic toxicity experiment was conducted to examine tissue distribution and depuration of two microcystins (microcystin-LR and microcystin -RR) in the phytoplanktivorous filter-feeding silver carp during a course of 80 days. Two large tanks (A, B) were used, and in Tank A, the fish were fed naturally with fresh Microcystis viridis cells (collected from a eutrophic pond) throughout the experiment, while in Tank B, the food of the fish were M. viridis cells for the first 40 days and then changed to artificial carp feed. High Performance Liquid Chromatography (HPLC) was used to measure MC-LR and MC-RR in the M. viridis cells, the seston, and the intestine, blood, liver and muscle tissue of silver carp at an interval of 20 days. MC-RR and MC-LR in the collected Microcystis cells varied between 268-580 and 110-292 μg g -1 DW, respectively. In Tank A, MC-RR and MC-LR varied between 41.5-99.5 and 6.9-15.8 μg g -1 DW in the seston, respectively. The maximum MC-RR in the blood, liver and muscle of the fish was 49.7, 17.8 and 1.77 μg g -1 DW, respectively. No MC-LR was detectable in the muscle and blood samples of the silver carp in spite of the abundant presence of this toxin in the intestines (for the liver, there was only one case when a relatively minor quantity was detected). These findings contrast with previous experimental results on rainbow trout. Perhaps silver carp has a mechanism to degrade MC-LR actively and to inhibit MC-LR transportation across the intestines. The depuration of MC-RR concentrations occurred slowly than uptakes in blood, liver and muscle, and the depuration rate was in the order of blood>liver>muscle. The grazing ability of silver carp on toxic cyanobacteria suggests an applicability of using phytoplanktivorous fish to counteract cyanotoxin contamination in eutrophic waters. - Silver carp are tolerant of cyanobacterial toxins, and might be used to control toxic algal blooms in highly eutrophic lakes

  13. Effect of Sub-Chronic Administration of Tetracera potatoria Roots ...

    African Journals Online (AJOL)

    Triglyceride levels were non-significantly reduced in T. potatoria treated rats but were increased from 74.0±3.8 mg/dl (control) to 139.3±4.8 mg/dl in rats administered with BA (40 mg/kg). In conclusion, sub-acute administration of T. potatoria root was relatively nontoxic, but BA showed relatively more toxicity to blood cells ...

  14. Health Effects of Subchronic Inhalation of Simulated Downwind Coal Combustion Emissions

    Energy Technology Data Exchange (ETDEWEB)

    Joe Mauderly

    2009-01-07

    The purpose of this project was to conduct a comprehensive laboratory-based evaluation of selected respiratory and cardiac health hazards of subchronic (up to 6 months) inhalation of simulated key components of 'downwind plume' emissions of coal combustion. This project was performed as an integral part of a joint government-industry program termed the 'National Environmental Respiratory Center' (NERC), which is aimed at disentangling the roles of different physical-chemical air pollutants and their sources in the health effects associated statistically with air pollution. The characterization of the exposure atmosphere and the health assays were identical to those employed in the NERC protocols used to evaluate other pollution source emissions, such as diesel, gasoline, and wood combustion. The project had two phases, each encompassing multiple tasks. Guidelines for the composition of the exposure atmosphere were set by consensus of an expert workshop. Development of the capability to generate the exposure atmosphere and pilot studies of the comparative exposure composition using two coal types were accomplished in Phase 1. In Phase 2, the toxicological study was conducted using Powder River Basin Sub-bituminous coal. NETL provided 50% support for the work in Phase 1 and had intended to provide 20% support for the work in Phase 2. Phase 1 is completed and Phase 2 is in the final stages. All animal exposures were completed without incident, and the composition of the exposure atmospheres met the targets. All of the health sample collections are completed, but some samples remain to be analyzed. Data summaries and final statistical analysis of results remain to be completed. The goal is to submit all publications before the end of FY-08. Repeated exposure to simulated downwind coal emissions caused some significant health effects, but the number of effects tended to be fewer than those caused by the other NERC exposures (diesel and gasoline

  15. Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

    Science.gov (United States)

    Nghonjuyi, Ndaleh Wozerou; Tiambo, Christian Keambou; Taïwe, Germain Sotoing; Toukala, Jean Paul; Lisita, Frederico; Juliano, Raquel Soares; Kimbi, Helen Kuokuo

    2016-02-03

    Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low

  16. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yanli [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Feng, Yongdong [Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 400030 (China); Li, Yanling [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Xu, Yiping; Shi, Nian [Department of hygienic toxicology, School of Public Health, Huazhong University of Science and Technology, Wuhan 400030 (China); Hu, Guo-fu [Molecular Oncology Research Institute, Tufts Medical Center, Tufts University, Boston 02111 (United States); Wu, Yunxia, E-mail: wuyunxia@hust.edu.cn [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China)

    2017-01-15

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  17. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    International Nuclear Information System (INIS)

    Wu, Yanli; Feng, Yongdong; Li, Yanling; Xu, Yiping; Shi, Nian; Hu, Guo-fu; Wu, Yunxia

    2017-01-01

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg −1 ·d −1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg −1 ·d −1 for females and 16 mg·kg − 1·d −1 for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  18. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

    International Nuclear Information System (INIS)

    Lee, Min-Ho; Kim, Mingoo; Lee, Byung-Hoon; Kim, Ju-Han; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-Il; Chung, Heekyoung; Kong, Gu; Lee, Mi-Ock

    2008-01-01

    Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

  19. Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

    Science.gov (United States)

    Mattila, M J; Koski, J; Strömberg, C

    1987-02-01

    Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.

  20. Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

    Science.gov (United States)

    Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

    2008-03-01

    The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

  1. Antioxidant status in oral subchronic toxicity of fipronil and fluoride co-exposure in buffalo calves.

    Science.gov (United States)

    Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

    2016-02-01

    The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels. © The Author(s) 2013.

  2. Subacute and subchronic oral toxicity of p-chlorotoluene in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Terrill, J.B.; Robinson, M.; Wolfe, G.W.; Billups, L.H.

    1990-01-01

    P-Chlorotoluene was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dose levels of 200, 600 and 1800 mg/kg/day and 50, 200 and 800 mg/kg/day, respectively. In the 14-day study 8 of 10 animals of each sex in the high-dose group died due to treatment. Other treatment-related signs for these animals included an adverse effect upon body weight, and clinical signs of salivation, tremors and prostration. In the 200 and 600 mg/kg/day groups there were no apparent treatment-related effects. In the 90-day study, 4 of 10 males and 2 of 10 females in the high-dose group died due to treatment. Other signs for this treatment group included an adverse effect upon body weight, and clinical signs of languid behavior, prostration, tremors, sensitive to touch, epistaxis and respiratory distress. Increases in alkaline phosphatase and creatinine (males only), and increases in adrenal (absolute and relative, females), kidney (relative, both sexes) and liver (relative, both sexes) weights were also noted.

  3. Health effects of subchronic inhalation exposure to gasoline engine exhaust.

    Science.gov (United States)

    Reed, M D; Barrett, E G; Campen, M J; Divine, K K; Gigliotti, A P; McDonald, J D; Seagrave, J C; Mauderly, J L; Seilkop, S K; Swenberg, J A

    2008-10-01

    Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.

  4. Subchronic toxicity study in vivo and allergenicity study in vitro for genetically modified rice that expresses pharmaceutical protein (human serum albumin).

    Science.gov (United States)

    Sheng, Yao; Qi, Xiaozhe; Liu, Yifei; Guo, Mingzhang; Chen, Siyuan; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

    2014-10-01

    Genetically modified (GM) crops that express pharmaceutical proteins have become an important focus of recent genetic engineering research. Food safety assessment is necessary for the commercial development of these crops. Subchronic toxicity study in vivo and allergenicity study in vitro were designed to evaluate the food safety of the rice variety expressing human serum albumin (HSA). Animals were fed rodent diets containing 12.5%, 25.0% and 50.0% GM or non-GM rice for 90 days. The composition analysis of the GM rice demonstrated several significant differences. However, most of the differences remained within the ranges reported in the literature. In the animal study, a range of indexes including clinical observation, feed efficiency, hematology, serum chemistry, organ weights and histopathology were examined. Random changes unrelated to the GM rice exposure, within the range of historical control values and not associated with any signs of illness were observed. The results of heat stability and in vitro digestion of HSA indicated no evidence of potential allergenicity of the protein. Overall, the results of these studies suggest that the GM rice appears to be safe as a dietary ingredient when it is used at up to 50% in the diet on a subchronic basis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats.

    Science.gov (United States)

    Domingues, Alexandre; Barbisan, Luis Fernando; Martins, Priscila Raquel; Spinardi-Barbisan, Ana Lúcia Tozzi

    2011-05-01

    Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substitute urea herbicide widely used on agricultural crops with potential mutagenic, teratogenic, reproductive and carcinogenic effects. Nonetheless, its toxic potential on the immune system needs a detailed assessment. Thus, in order to evaluate the adverse effect of this herbicide on lymphohematopoietic organs and macrophage activity, male Wistar rats were orally treated with Diuron at 125, 1250 and 2500 ppm for 14, 28 or 90 days. General signs of toxicity were observed in Diuron-treated groups (1250 and 2500 ppm), including reduced food intake and body weight gain, as well as higher relative weights for spleen, kidneys and liver (28 and 90-day toxicity studies) and elevated serum levels of ALT, albumin, total protein, creatinine and urea (28-day toxicity study). Diuron exposure caused a severe depletion of splenic white pulp compartments and cellularity, followed by a decreased number of CD4(+) T lymphocytes, increased extramedullary hematopoiesis and deposition of hemosiderin in red pulp. Despite alteration in macrophage spreading, the macrophagic activity was not significantly affected by the herbicide. Under these experimental conditions, the results suggest that Diuron exerts systemic and target-organ toxicity, mainly at higher concentration. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Xiaofang Zhang

    2016-11-01

    Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

  7. Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead.

    Science.gov (United States)

    Varaksin, Anatoly N; Katsnelson, Boris A; Panov, Vladimir G; Privalova, Larisa I; Kireyeva, Ekaterina P; Valamina, Irene E; Beresneva, Olga Yu

    2014-02-01

    Rats were exposed intraperitoneally (3 times a week up to 20 injections) to either Cadmium and Lead salts in doses equivalent to their 0.05 LD50 separately or combined in the same or halved doses. Toxic effects were assessed by more than 40 functional, biochemical and morphometric indices. We analysed the results obtained aiming at determination of the type of combined toxicity using either common sense considerations based on descriptive statistics or two mathematical models based (a) on ANOVA and (b) on Mathematical Theory of Experimental Design, which correspond, respectively, to the widely recognised paradigms of effect additivity and dose additivity. Nevertheless, these approaches have led us unanimously to the following conclusions: (1) The above paradigms are virtually interchangeable and should be regarded as different methods of modelling the combined toxicity rather than as reflecting fundamentally differing processes. (2) Within both models there exist not merely three traditionally used types of combined toxicity (additivity, subadditivity and superadditivity) but at least 10 variants of it depending on exactly which effect is considered and on its level, as well as on the dose levels and their ratio. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

    .c. injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p. injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii temporal dynamics of eCB and eicosanoid (eiC levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

  9. The effect of subchronic fluoxetine treatment on learning and memory in adolescent rats

    DEFF Research Database (Denmark)

    Sass, Amdi; Wörtwein, Gitta

    2012-01-01

    Selective serotonin re-uptake inhibitors are increasingly used for the treatment of adolescents with behavioural disorders. However, the effect of this class of drugs during this sensitive period of brain development has not been extensively investigated. In this study we examine the effect of su...... in dorsal dentate gyrus and subgranular zone in young adulthood. This calls for further studies examining the long-term effects of this class of antidepressants on adolescent brain development and behaviour....... of subchronic treatment with the selective serotonin re-uptake inhibitor, fluoxetine (10mg/kg/day, i.p.) throughout adolescence (postnatal day 28-60) on learning and memory in the rat. Learning and memory were assessed at two time points: during adolescence, while the animals were being treated with fluoxetine...... and in young adulthood, 40 days after the termination of fluoxetine treatment. Fluoxetine treated rats were compared to a saline injected control group with respect to spatial navigation in the water maze, object recognition and object-in-place recognition memory. Additionally open field behaviour was examined...

  10. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

    Science.gov (United States)

    Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

    2017-08-01

    The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice.

    Science.gov (United States)

    de Oliveira, R V; Dall'Igna, O P; Tort, A B L; Schuh, J F; Neto, P F; Santos Gomes, M W; Souza, D O; Lara, D R

    2005-03-01

    N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder.

  12. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene and tetryl in rats. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, T.V.; Daniel, F.B.

    1994-09-01

    Toxic effects of 1,3-Dinitrobenzene (1,3-DNB) in male and female F344 rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of 1,3-DNB (0, 2.5, 10, 25, 75 and 150 mg/kg diet) for fourteen days. The average daily 1 ,3-DNB doses consumed were 0.21, 0.87, 2.02, 6.28 and 11.82 mg/kg b.w. for females and 0.21, 0.80, 1.98, 5.77 and 10.56 for males. Food consumption was significantly decreased in high dose animals of both sexes. Final body weights were not altered but relative organ weights were significantly changed in the 150 and 75 mg dose groups involving the spleen (males and females) and testes (males). Hematology and clinical chemistry studies indicated significantly increased values in both sexes relating to reticulocytes and methemoglobin in the 150 and 75 mg/kg dose groups while the red blood cell count, hemoglobin level and % hematocrit were decreased in these same groups. In addition, the levels of bilirubin, protein and albumin were increased in high dose males, Histopathological evaluations suggested that the susceptible organs for 1,3-DNB toxicity were kidneys (hyaline droplets), spleen (erythroid cell hyperplasia), brain (malacia and microgliosis), testes (seminiferous tubular degeneration). These changes were noted mainly in the 150 and 75 mg/kg dose groups except those changes involving the brain (150 mg/kg group only).

  13. Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

    Science.gov (United States)

    Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi

    2016-09-01

    The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P healthy control mice fed semi-purified and non-purified diets, respectively. These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

  14. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    International Nuclear Information System (INIS)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze

    2006-01-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  15. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  16. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

    2003-03-01

    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  17. Effects of Subchronic Treatment with Ibuprofen and Nimesulide on Spatial Memory and NMDAR Subunits Expression in Aged Rats.

    Science.gov (United States)

    Ozturk Bilgin, Ozlem; Kumbul Doguc, Duygu; Altuntas, Irfan; Sutcu, Recep; Delibas, Namık

    2013-01-01

    Several studies point to an important function of cyclooxygenase (COX) and prostaglandin signaling in models of synaptic plasticity which is associated with N-methyl-D-aspartate receptors (NMDARs). Cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by NMDA dependent synaptic activity. Nonsteroid Antiinflammatory Drugs (NSAIDs) exert their antiinflammatory effect by the inhibion of COX have controversial effects on learning and memory. We administered ibuprofen as a non-selective COX-2 inhibitor and nimesulide as a selective COX-2 inhibitor for 8 weeks for determining the cognitive impact of subchronic administration of NSAIDs to aged rats. Wistar albino rats (16 mo, n = 30) were separated into control (n = 10), ibuprofen (n = 10) and nimesulide (n = 10) treated groups. First we evaluated hippocampus-dependent spatial memory in the radial arm maze (RAM) and than we evaluated the expression of the NMDAR subunits, NR2A and NR2B by western blotting to see if their expressions are effected by subchronic administration with these drugs. Ibuprofen and nimesulide treated rats completed the task in a statistically significant shorter time when compared with control group (p RAM. Furthermore, no statistically significant difference was detected for the protein expressions of NR2A and NR2B of the subjects. Oral administration of ibuprofen and nimesulide for 8 weeks showed no impairment but partly improved spatial memory.

  18. Effects of subchronic phencyclidine (PCP treatment on social behaviors, and operant discrimination and reversal learning in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Jonathan L Brigman

    2009-02-01

    Full Text Available Subchronic treatment with the psychotomimetic phencyclidine (PCP has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal in C57BL/6J mice on 1 social behaviors using a sociability/social novelty-preference paradigm, and 2 pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains that produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.

  19. Subchronic toxicity of Baltic herring oil and its fractions in the rat II: Clinical observations and toxicological parameters

    NARCIS (Netherlands)

    Stern, N.H.; Oberg, M.; Casabona, H.; Trossvik, C.; Manzoor, E.; Johansson, N.; Lind, M.; Orberg, J.; Feinstein, R.; Johansson, A.; Chu, I.; Poon, R.; Yagminas, A.; Brouwer, A.; Jones, B.; Hakansson, H.

    2002-01-01

    This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified

  20. The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats.

    NARCIS (Netherlands)

    Kam, E.L. van der; Coolen, J.C.; Ellenbroek, B.A.; Cools, A.R.

    2005-01-01

    The aim of this study was to investigate the effects of mild acute and mild sub-chronic challenges on alcohol intake and preference in the genetically selected ratlines of apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) animals. Animals from both lines were subjected to

  1. Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Narges El Golli

    2016-04-01

    Full Text Available The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes and promoted changes in kidney biomarkers. In order to explore the possible mechanism involved, oxidative-stress assessment was performed. Results identified critical oxidative alterations in all tested organs, as shown by the promotion of lipid peroxidation and the modification of endogenous antioxidant-defense enzymes. Thus, tartrazine is able to induce in adult rats’ hematotoxicity, immunotoxicity, and liver and kidney injuries by changing the whole balance between oxidants and antioxidants.

  2. Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries

    Directory of Open Access Journals (Sweden)

    Helena Lenasi

    2005-07-01

    Full Text Available Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh were obtained in the absence and presence of the endothelial NO synthase (eNOS inhibitor N ω nitro L-arginine (L-NA and the cyclo-oxygenase (COX inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and

  3. Fourteen-Day Subchronic Oral Toxicity Study of 4-Nitrophenyl Methyl (Phenyl) Phosphinate in Male and Female Rats.

    Science.gov (United States)

    1982-09-01

    because of concern about the susceptibility of the compound to hydrolysis. If the compound were microencapsulated , one could then mix it with the diet... Enzymatic Activity in Serum...............32 Table 8 - Effect of MPP on Cholinesterase Activity in Plasma ........ 33 Red Blood Cell and Brain I A...4 w) c - U,- APEN I D S C N NC a N Lewis--30 TABLE 7 Egfeat of MPP* on Enzymatic Activity in Serum Aspartate Alanlne Lactate Creatine Amino- Amino

  4. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sasser, L. B.; Miller, R. A.; Kalkwarf, D, R.; Buschbom, R. L.; Cushing, J. A.

    1989-06-30

    Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.

  5. Avaliação da toxicidade subcrônica do extrato bruto seco de Anacardium occidentale Linn em cães = Evaluation of the subchronic toxicity of the crude dry extract of Anacardium occidentale Linn in dogs

    Directory of Open Access Journals (Sweden)

    Arquimedes Fernandes Monteiro de Melo

    2006-01-01

    accordance with the effective law. The present work evaluated the subchronic toxicity of the CDE in dogs of indefinite pedigree. Data showed an increase of alanine transaminase (ALT and aspartate transaminase (AST levels, which may indicate transitory hepatotoxicity.

  6. The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Micovic Zarko

    2016-09-01

    Full Text Available Hyperhomocysteinemia (HHC, both basal and after methionine load, may occur due to genetic disorders or deficiencies of nutrients that affect the remethylation or trans-sulphuration pathways during methionine metabolism. HHC is involved in the pathogenesis of many illnesses as a result of its prooxidative effect and its impairment of antioxidative protection. The aim was to examine the effects of subchronic methionine overload on the body weight and standard biochemical parameters in rat serum and to examine whether simultaneous subchronic intraperotoneal administration of methionine alone or together with L-cysteine or N-acetyl-cysteine resulted in a change in the body weight and biochemical parameters in the rat serum. The research was conducted during a three-week period (male Wistar albino rats, n=36, body weight of approximately 160 g, age of 15-20 days, and the animals were divided into a control group and three experimental groups of 8-10 animals each: a control group (0.9% sodium chloride 0.1-0.2 ml/day; b methionine (0.8 mmol/kg/bw/day (MET group; c methionine (0.8 mmol/kg/bw/day + L-cysteine (7 mg/kg/bw/day (L-cys+MET group; and d methionine (0.8 mmol/kg/bw/day + N-acetyl-L-cysteine (50 mg/kg/bw/day (NAC+MET group. In addition to the body weight monitoring, the levels of total homocysteine and the standard biochemical parameters in blood samples (plasma or serum were determined. The results indicated that monitoring the homocysteine levels and standard biochemical parameters in blood could be used for analysis and could provide an excellent guideline for distinguishing between toxic and non-toxic doses of methionine intake, which may be meaningful for clinical applications.

  7. Effect of head-only sub-chronic GSM exposure on spatial memory of rats

    International Nuclear Information System (INIS)

    Ammari, Mohamed; Brillaud, Elsa; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; Seze, Rene de; Faculte des Sciences de Bizerte, Jarzouna

    2008-01-01

    Full text: Introduction: Low power electromagnetic fields (EMF) are suspected to produce deficit memory in rats. The study of Dubreuil et al (2003) showed that a short-term (10-15 days) exposure 'head-only' to GSM 900 MHz radio frequencies does not produce a deficit memory in adult rats. The aim of our experiment was to determine if head-only sub-chronic exposure (2 months) of rats to GSM signal for 45 min at a SAR = 1.5 W/Kg and for 15 min at 6 W/Kg induce deficit in spatial memory of rats in radial maze test. Materials and methods: Exposure system: Animals were placed in Plexiglas rockets with an individual loop antenna placed above the rat's head. Four animals were exposed at the time. Loop antennas were connected to a generator and emitted a GSM signal (900 MHz, pulsed at 217 Hz, 1/8 duty factor) 5 days / week for 8 weeks. Experimental group: 30 Sprague-Dawley male rats were randomly assigned to 5 different groups: a) 6 rats exposed 15 min at SAR = 6 W/Kg; b) 6 rats exposed 45 min at SAR = 1.5 W/g; c) 6 rats sham controls (3 for 5 min and 3 for 45 min, SAR = 0 W/Kg); d) 6 rats without any treatment and manipulation (cage control); e) 6 rats were injected (i.p) S.B.H 0.1 mg/Kg (Sigma Aldrich) as positive control group. Behavioural procedure: The radial maze protocol consists of two consecutive phases: the training task (10 days) and the test task (8 days). In the first phase, rats were trained to visit the 8 arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-min intra-trial delay was introduced after four visited arms. After the intra-delay, the rat was placed in the maze to finish the test task, which is visiting four other arms he had not visited. During the training task, exposure took place before the behavioural task. During the test task, exposure or sham-exposure took place during the intra-delay. Results and discussion: In all experiments, performance of exposed rats (1.5 and 6 W/Kg) was compared with that of

  8. Effects of Subchronic Exposure to N,N-Diethyl-m-toluamide on Selected Biomarkers in Common Carp (Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Andrea Slaninova

    2014-01-01

    Full Text Available DEET (N,N-diethyl-m-toluamide is the most common active ingredient in the insect repellents commonly detected in European groundwater. The aim of this study was to investigate the effect of subchronic DEET exposure on biochemical and haematological parameters, antioxidant enzymes, including catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and the amount of thiobarbituric acid reactive substances (TBARS in common carp (Cyprinus carpio L.. Two specific proinflammatory and anti-inflammatory cytokine genes were selected to assess an immunological status of the fish. Fish were exposed for 28 days to three concentrations of DEET (1.0 µg/L, 0.1 mg/L, and 1.0 mg/L where 1 µg/L is corresponding to the concentration found in the environment. DEET had a significant (P<0.05 effect on increased RBC, decreased mean corpuscular volume (MCV, and mean corpuscular haemoglobin value (MCH compared to control groups in the concentration of 1 mg/L. A significant decline (P<0.05 in triacylglycerols (TAG in plasma was found in the concentration of 1 mg/L compared to the control groups. The parameters of oxidative stress in tissues of common carp were weekly affected and immunological parameters were not affected.

  9. Effects of Subchronic Exposure to N,N-Diethyl-m-toluamide on Selected Biomarkers in Common Carp (Cyprinus carpio L.)

    Science.gov (United States)

    Slaninova, Andrea; Modra, Helena; Hostovsky, Martin; Sisperova, Eliska; Blahova, Jana; Matejova, Iveta; Vicenova, Monika; Faldyna, Martin; Zelnickova, Lenka; Tichy, Frantisek; Svobodova, Zdenka

    2014-01-01

    DEET (N,N-diethyl-m-toluamide) is the most common active ingredient in the insect repellents commonly detected in European groundwater. The aim of this study was to investigate the effect of subchronic DEET exposure on biochemical and haematological parameters, antioxidant enzymes, including catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and the amount of thiobarbituric acid reactive substances (TBARS) in common carp (Cyprinus carpio L.). Two specific proinflammatory and anti-inflammatory cytokine genes were selected to assess an immunological status of the fish. Fish were exposed for 28 days to three concentrations of DEET (1.0 µg/L, 0.1 mg/L, and 1.0 mg/L) where 1 µg/L is corresponding to the concentration found in the environment. DEET had a significant (P < 0.05) effect on increased RBC, decreased mean corpuscular volume (MCV), and mean corpuscular haemoglobin value (MCH) compared to control groups in the concentration of 1 mg/L. A significant decline (P < 0.05) in triacylglycerols (TAG) in plasma was found in the concentration of 1 mg/L compared to the control groups. The parameters of oxidative stress in tissues of common carp were weekly affected and immunological parameters were not affected. PMID:24795897

  10. Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

    Science.gov (United States)

    Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2016-12-24

    Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. The effects of subchronic exposure to ketoprofen on early developmental stages of common carp

    Czech Academy of Sciences Publication Activity Database

    Prášková, E.; Štěpánová, S.; Chromcová, L.; Plhalová, L.; Voslářová, E.; Pištěková, V.; Prokeš, Miroslav; Svobodová, Z.

    2013-01-01

    Roč. 82, č. 3 (2013), s. 343-347 ISSN 0001-7213 Institutional support: RVO:68081766 Keywords : embryo-larval toxicity test * NSAIDs * environmental concentration Subject RIV: EG - Zoology Impact factor: 0.448, year: 2013

  12. 1997 Toxic Hazards Research Annual Report

    Science.gov (United States)

    1998-05-01

    evaluate the potential for CF 3I to produce reproductive toxicity and to provide additional information on the effect of CF 3I exposure on the...questions raised on the effects of CF 3I exposure following the recently completed acute and subchronic inhalation toxicity studies (Dodd et al., 1997a...individuals from potential toxic consequences resulting from exposure to combustion products of advanced composite materials (ACM), this laboratory has

  13. Effects of sub-chronic exposure to SO{sub 2} on lipid and carbohydrate metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lovati, M.R. [Institute of Pharmacological Sciences, Milan (Italy); Manzoni, C. [Institute of Pharmacological Sciences, Milan (Italy); Daldossi, M. [Institute of Pharmacological Sciences, Milan (Italy); Spolti, S. [Institute of Pharmacological Sciences, Milan (Italy); Sirtori, C.R. [Institute of Pharmacological Sciences, Milan (Italy)

    1996-01-01

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO{sub 2} have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO{sub 2} on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO{sub 2} at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO{sub 2} exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO{sub 2} resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO{sub 2} exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO{sub 2} exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals. (orig.)

  14. Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats

    International Nuclear Information System (INIS)

    Theumer, M.G.; Lopez, A.G.; Masih, D.T.; Chulze, S.N.; Rubinstein, H.R.

    2003-01-01

    Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in animals by a subchronic administration of both toxins mixtures. We have studied the nutritional and immunological alterations induced in rats fed during 90 days with a diet without mycotoxins, containing 40 ppb AFB1, and with a diet containing a mixture of 40 ppb AFB1 and 100 ppm FB1. Animals fed with the mixture of toxins obtained lower body weight than the control ones. The mitogenic response of spleen mononuclear cells (SMC) in vivo was higher in animals fed with AFB1. In in vitro studies, lower proliferations of SMC pre-exposed to AFB1 and to the mixture of toxins were detected. The SMC of animals fed with AFB1 produced lower levels of IL-2, higher of IL-4 and equal levels of IL-10. The SMC of animals fed with both toxins produced higher levels of IL-4, lower of IL-10 and equal levels of IL-2. The SMC preincubated with an AFB1-FB1 mixture produced higher concentrations of IL-4, lower of IL-10 and equal levels of IL-2. The peritoneal macrophages of animals that consumed AFB1 released less H 2 O 2 , while animals fed with the mixture of toxins produced higher levels. In in vitro studies, macrophages pre-exposed to the mixture of toxins released less H 2 O 2 . These results show different immunobiological effects produced by a mixture of mycotoxins in comparison to the individual action of the same toxins

  15. Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats

    Energy Technology Data Exchange (ETDEWEB)

    Theumer, M G; Lopez, A G; Masih, D T; Chulze, S N; Rubinstein, H R

    2003-04-15

    Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in animals by a subchronic administration of both toxins mixtures. We have studied the nutritional and immunological alterations induced in rats fed during 90 days with a diet without mycotoxins, containing 40 ppb AFB1, and with a diet containing a mixture of 40 ppb AFB1 and 100 ppm FB1. Animals fed with the mixture of toxins obtained lower body weight than the control ones. The mitogenic response of spleen mononuclear cells (SMC) in vivo was higher in animals fed with AFB1. In in vitro studies, lower proliferations of SMC pre-exposed to AFB1 and to the mixture of toxins were detected. The SMC of animals fed with AFB1 produced lower levels of IL-2, higher of IL-4 and equal levels of IL-10. The SMC of animals fed with both toxins produced higher levels of IL-4, lower of IL-10 and equal levels of IL-2. The SMC preincubated with an AFB1-FB1 mixture produced higher concentrations of IL-4, lower of IL-10 and equal levels of IL-2. The peritoneal macrophages of animals that consumed AFB1 released less H{sub 2}O{sub 2}, while animals fed with the mixture of toxins produced higher levels. In in vitro studies, macrophages pre-exposed to the mixture of toxins released less H{sub 2}O{sub 2}. These results show different immunobiological effects produced by a mixture of mycotoxins in comparison to the individual action of the same toxins.

  16. The Effect of Subchronic Administration of the Aqueous and Hydro-alcoholic Extracts of Crocus sativus from Estahbanat, Fars Province, on Mice

    Directory of Open Access Journals (Sweden)

    M Emamghoreishi

    2012-02-01

    Full Text Available Background & aim: In Iranian traditional medicine, Crocus sativus L. has been defined as an exultant plant. The present study was undertaken to determine the effect of subchronic administration of aqueous and hydro-alcoholic extracts of Crocus sativus on mice. Methods: The effect of subchronic i.p. administration of different doses of the aqueous extract (50, 100, 200, 400 mg/kg or water and the hydro-alcoholic extract (100, 200, 400, 800 mg/kg or water of Crocus sativus stigma on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test in mice. Fluoxetine (20 mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. The collected data was analyzed using One-way ANOVA. Results: The aqueous extract at doses of 50 and 100 mg/kg produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. The hydro-alcoholic extract did not show significant effects on immobility, climbing and swimming behaviors of all studied doses, compared to control group. The aqueous extract of all studied doses and the hydro-alcoholic extract at dose of 1600 mg/kg decreased spontaneous activity. Conclusion: The results of this study suggests that the aqueous, but not hydro-alcoholic, extract of Crocus sativus stigma from Estahbanat in Fars province, in subchronic administration possess an antidepressant-like activity which may be mediated through norepinephrine system.

  17. Haematogical changes induced by subchronic glyphosate exposure ...

    African Journals Online (AJOL)

    The aim of this study was to determine the haematological changes induced by subchronic glyphosate exposure in Wistar rats and the ameliorative effect of zinc. Sixty adult male and female Wistar rats were used for the study. Twelve of them were used for the LD50 which was evaluated to be 3750 mg kg-1 with clinical ...

  18. Toxicological evaluation of subchronic use of pioglitazone in mice

    Directory of Open Access Journals (Sweden)

    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  19. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Park HS

    2014-12-01

    Full Text Available Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+ nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+ NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with

  20. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Science.gov (United States)

    2010-07-01

    ... from the mother's repeated exposure to vehicle/engine emissions before and during her pregnancy. By... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells in... grown to confluence in cell culture. The guideline for the SCE assay is found in § 79.65. (iv...

  1. Reproduction and subchronic feeding study of carnauba wax in rats.

    Science.gov (United States)

    Parent, R A; Re, T A; Babish, J G; Cox, G E; Voss, K A; Becci, P J

    1983-02-01

    The reproductive performance of Wistar rats fed carnauba wax at levels of 0.1, 0.3 or 1% in the diet and the effects of subchronic administration of carnauba wax at these dose levels on the resultant progeny were studied. Reproductive indices, body-weight gain, food consumption, haematological and clinical chemical data, ophthalmic, gross and histopathological examinations were used to study the possible toxic or pathological effects. Serum free fatty acid levels were found to be decreased in male and female rats fed carnauba wax at dietary levels of 0.3 and 1.0%. No other effects of feeding carnauba wax at levels up to 1.0% of the diet were observed.

  2. Acute, subacute and subchronic toxicological studies of carissa carandas leaves (ethanol extract): a plant active against cardiovascular diseases

    International Nuclear Information System (INIS)

    Shamim, S.

    2014-01-01

    The Purpose of this research study was to examine the toxicological effects of aqueous: ethanol (1:1) extract of Carissa carandas leaves extracts in rats. Methodolgy: Acute toxicity studies were conducted to check the LD50 values in experimental animals. Autopsy after acute toxicity revealed that no gross changes were observed in organs like liver, spleen, heart and kidney among the animals of group N (control) and S (treated). The appearance of organs of Group S animals was comparable with that of Group N animals. Results: No signs of toxicity and mortality were observed in treated group after sub acute toxicity as compared to the control group. The histopathological studies after subchronic toxicity in doses of 1750 mg/kg (p.o.) and 5000 mg/kg (p.o) showed no toxic effects on organs like liver, heart, kidney and spleen. While chronic toxicity in dose 5000 mg/kg (p.o.) showed some histological changes. (author)

  3. Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.

    Science.gov (United States)

    Park, Eun-Jung; Choi, Je; Kim, Jae-Ho; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-10-01

    Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs.

  4. Sub-chronic exposure to fluoxetine in juvenile oysters (Crassostrea gigas): uptake and biological effects.

    Science.gov (United States)

    Di Poi, Carole; Evariste, Lauris; Séguin, Alexis; Mottier, Antoine; Pedelucq, Julie; Lebel, Jean-Marc; Serpentini, Antoine; Budzinski, Hélène; Costil, Katherine

    2016-03-01

    The bioconcentration potential of fluoxetine (FLX) and its biological effects were investigated in juvenile Pacific oyster exposed for 28 days to environmentally relevant concentrations of FLX (1 ng L(-1), 100 ng L(-1) and up to 10 μg L(-1)). FLX bioaccumulated in oyster flesh resulting in 28-day bioconcentration factors greater than 2,000 and 10,000 by referring to wet and dry weights, respectively. Nevertheless, FLX did not induce oyster mortality, delayed gametogenesis, or lead to adverse histopathological alterations. At the two highest concentrations, despite non-optimal trophic conditions, FLX stimulated shell growth but only in a transient manner, suggesting a role of serotonin in the regulation of feeding and metabolism in bivalves. Those high concentrations seemed to drive bell-shaped responses of catalase and glutathione S-transferase activities throughout the exposure period, which may indicate the activation of antioxidant enzyme synthesis and then an enhanced catabolic rate or direct inhibition of those enzymes. However, no clear oxidative stress was detected because no strong differences in thiobarbituric acid-reactive substance (TBARS) content (i.e. lipid peroxidation) were observed between oyster groups, suggesting that cellular defence mechanisms were effective. These results demonstrate the importance of considering additional biomarkers of oxidative stress to obtain a comprehensive overview of the FLX-induced changes in marine bivalves exposed under realistic conditions. Considering the battery of biomarkers used, FLX appears to induce little or no effects on oyster physiology even at a concentration of 10 μg L(-1). These results do not confirm the lowest observed effect concentration (LOEC) values reported by some authors in other mollusc species.

  5. Effects of oral, subchronic cadmium administration on fertility prenatal and postnatal progeny development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Baranski, B.; Stetkiewicz, I.; Sitarek, K.; Szymczak, W.

    1983-12-01

    Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.

  6. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  7. Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.

    Science.gov (United States)

    Pilar-Cuéllar, F; Vidal, R; Pazos, A

    2012-02-01

    5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  8. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

  9. Toxic Stress: Effects, Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Hillary A. Franke

    2014-11-01

    Full Text Available Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrative approach to the prevention and treatment of toxic stress necessitates individual, community and national focus.

  10. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  11. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    International Nuclear Information System (INIS)

    Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

    2014-01-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

  12. Effects of subchronic inhalation exposure of rats to emissions from a diesel engine burning soybean oil-derived biodiesel fuel.

    Science.gov (United States)

    Finch, G L; Hobbs, C H; Blair, L F; Barr, E B; Hahn, F F; Jaramillo, R J; Kubatko, J E; March, T H; White, R K; Krone, J R; Ménache, M G; Nikula, K J; Mauderly, J L; Van Gerpen, J; Merceica, M D; Zielinska, B; Stankowski, L; Burling, K; Howell, S

    2002-10-01

    There is increasing interest in diesel fuels derived from plant oils or animal fats ("biodiesel"), but little information on the toxicity of biodiesel emissions other than bacterial mutagenicity. F344 rats were exposed by inhalation 6 h/day, 5 days/wk for 13 wk to 1 of 3 dilutions of emissions from a diesel engine burning 100% soybean oil-derived fuel, or to clean air as controls. Whole emissions were diluted to nominal NO(x) concentrations of 5, 25, or 50 ppm, corresponding to approximately 0.04, 0.2, and 0.5 mg particles/m(3), respectively. Biologically significant, exposure-related effects were limited to the lung, were greater in females than in males, and were observed primarily at the highest exposure level. There was a dose-related increase in the numbers of alveolar macrophages and the numbers of particles in the macrophages, as expected from repeated exposure, but no neutrophil response even at the highest exposure level. The macrophage response was reduced 28 days after cessation of the exposure. Among the high-level females, the group mean lung weight/body weight ratio was increased, and minimal, multifocal bronchiolar metaplasia of alveolar ducts was observed in 4 of 30 rats. Lung weights were not significantly increased, and metaplasia of the alveolar ducts was not observed in males. An increase in particle-laden macrophages was the only exposure-related finding in lungs at the intermediate and low levels, with fewer macrophages and fewer particles per macrophage at the low level. Alveolar histiocytosis was observed in a few rats in both exposed and control groups. There were statistically significant, but minor and not consistently exposure-related, differences in body weight, nonpulmonary organ weights, serum chemistry, and glial fibrillary acidic protein in the brain. There were no significant exposure-related effects on survival, clinical signs, feed consumption, ocular toxicity, hematology, neurohistology, micronuclei in bone marrow, sister

  13. Neuroprotective effect of bee venom is mediated by reduced astrocyte activation in a subchronic MPTP-induced model of Parkinson's disease.

    Science.gov (United States)

    Kim, Mi Eun; Lee, Joo Yeon; Lee, Kyung Moon; Park, Hee Ra; Lee, Eunjin; Lee, Yujeong; Lee, Jun Sik; Lee, Jaewon

    2016-08-01

    Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP(+) treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders.

  14. The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: A randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Laura Amy Massee

    2015-05-01

    Full Text Available Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa’s effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n=40, age M= 24.13 years, SD = 4.47 years was conducted to investigate the effects of both acute (same-day and sub-chronic (daily for four-weeks 250mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-minute cycles of the Cognitive Demand Battery (CDB encompassing two serial subtraction tasks (Serial Threes and Sevens, a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerised Cognitive Assessment Battery (SUCCAB was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763. Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN126130006 26763&ddlSearch=Registered

  15. The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

    Science.gov (United States)

    Massee, Laura A; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

    2015-01-01

    Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

  16. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    Science.gov (United States)

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2013-01-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

  17. Effect of subchronic administration of methyl parathion on in vivo protein synthesis in pregnant rats and their conceptuses

    International Nuclear Information System (INIS)

    Gupta, R.C.; Thornburg, J.E.; Stedman, D.B.; Welsch, F.

    1984-01-01

    Pregnant rats received daily po doses of the organophosphate methyl parathion (MPTH) from Day 6 through Day 15 or 19 of gestation at doses causing no (1.0 mg/kg) or minimal (1.5 mg/kg) signs of maternal toxicity. Following the dose of MPTH on Day 15 or 19, in vivo protein synthesis was measured 0.5, 1.0, and 2.0 hr after sc injection of L-[1- 14 C]valine at a dose of 5 microCi/mmol/100 g body wt. The specific activity of [ 14 C]valine in the free amino acid pool and protein bound pool was significantly reduced in various regions of maternal brain and in maternal viscera, placenta, and whole embryos (Day 15), and in fetal brain and viscera (Day 19). The inhibitory effect of MPTH on net protein synthesis was dose dependent, greater on Day 19 than 15 of gestation and more pronounced in fetal than in maternal tissues

  18. ACUTE AND SUBCHRONIC TOXICITY STUDIES OF KERNEL ...

    African Journals Online (AJOL)

    Administrator

    to fine powder using pestle and mortar, sieved to pass through 80- meish sieve and ... and down procedure of Organization for Economic and Cultural ... Significantly different from the control (P < 0.05) using one way analysis of variance.

  19. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    Science.gov (United States)

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Subchronic exposure to deoxynivalenol exerts slight effect on the immune system and liver morphology of growing rabbits

    Directory of Open Access Journals (Sweden)

    Mariam Kachlek

    2017-01-01

    Full Text Available As the most common grain contaminant worldwide, deoxynivalenol is of high importance despite its low toxicity compared to other trichothecene mycotoxins. Data on the effects of deoxynivalenol in rabbits are scarce. Thus, the aim of this study was to investigate the effects of dietary deoxynivalenol fed at a high level (10 mg/kg of feed on the productive performance, blood indices, immunological variables, histopathological changes, and genotoxicity in rabbits. Forty-eight Pannon White rabbits were exposed to contaminated diets for three weeks. Despite its high concentration, deoxynivalenol did not affect the feed intake, body weight, and body weight gain. Liver and kidney function was not affected, as shown by the clinical chemistry indices. Conversely, in two rabbits the toxin caused mild fibrosis of the liver, without degenerative changes of the hepatocytes. No genotoxicity could be observed either. Gut cytokines and the phagocytic activity of the macrophages did not differ significantly. The percentage of neutrophils was significantly lower, whereas that of eosinophils was significantly higher in the toxin-fed group. Deoxynivalenol did not cause significant changes in gut and villus morphology. In 4 out of the 6 deoxynivalenol-treated animals, the ratio of lymphoblast proliferation and simultaneous apoptosis shifted towards apoptosis in the gut-associated lymphoid tissue. In the central part of the lymphoid follicles of the spleen, lymphocyte depletion and follicular atrophy could be detected. It can be concluded that rabbits are less sensitive to deoxynivalenol, but the findings confirm that this Fusarium toxin is capable of modulating the immune response.

  1. Avaliação da toxicidade subcrônica do extrato bruto seco de Anacardium occidentale Linn em cães - DOI: 10.4025/actascihealthsci.v28i1.1112 Evaluation of the subchronic toxicity of the crude dry extract of Anacardium occidentale Linn in dogs - DOI: 10.4025/actascihealthsci.v28i1.1112

    Directory of Open Access Journals (Sweden)

    Isabely de Souza Vera Cruz

    2006-03-01

    accordance with the effective law. The present work evaluated the subchronic toxicity of the CDE in dogs of indefinite pedigree. Data showed an increase of alanine transaminase (ALT and aspartate transaminase (AST levels, which may indicate transitory hepatotoxicity

  2. Sub-chronic indomethacin treatment and its effect on the male reproductive system of albino rats: possible protective role of black tea extract.

    Science.gov (United States)

    Bagoji, Ishwar B; Hadimani, Gavishiddappa A; Yendigeri, Saeed M; Das, Kusal K

    2017-05-01

    Indomethacin is commonly used as a nonsteroidal anti-inflammatory drug (NSAID) to treat inflammation, arthritis and joint pains. Unfortunately, it has a wide range of adverse effects on the physiological system, including gonads. This study aimed to assess possible beneficial effects of black tea extract (BTE) against indomethacin-induced alteration of gonadal hormone levels in male rats. Adult male rats were divided into Group I (control), Group II (indomethacin, 5 mg/kg body weight [bwt.]; i.p., 21 days), Group III (BTE, 2.5 g tea leaf/dL of water, i.e. 2.5% of aqueous BTE, orally, 21 days) and Group IV (indomethacin+BTE, 21 days). Sperm count and motility, serum luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone, along with histopathology of testes were studied. One-way ANOVA, followed by post-hoc t-test were conducted. Indomethacin-treated rats showed significant decrease in testicular weight, sperm count, sperm motility, serum gonadotropins and testosterone concentrations. Histopathology of the testes showed tortuous and distorted seminiferous tubules, marked thickening of the tubular basement membrane, reduced spermatogenesis process (>30%) and marked decrease in the number of interstitial cells of Leydig in indomethacin-treated rats. Interestingly, rats supplemented with BTE showed remarkable improvements in testicular weight gain, sperm count and motility, serum gonadotropins and testosterone concentrations, along with testicular histopathology. The results suggest that BTE might have potential ameliorative effects against sub-chronic indomethacin-induced alteration of gonadal hormone levels in male albino rats.

  3. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    International Nuclear Information System (INIS)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-01-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 μg/m 3 . At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 μg/m 3 , but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 μg/m 3 exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate

  4. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

    Science.gov (United States)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-09-15

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

  5. Toxicity and antinociceptive effects of Hamelia patens

    Directory of Open Access Journals (Sweden)

    Angel Josabad Alonso-Castro

    Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

  6. Toxic effects of fluoride on organisms.

    Science.gov (United States)

    Zuo, Huan; Chen, Liang; Kong, Ming; Qiu, Lipeng; Lü, Peng; Wu, Peng; Yang, Yanhua; Chen, Keping

    2018-04-01

    Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. On toxic effects of scientific journals

    Indian Academy of Sciences (India)

    ... 'top' journals are endowed with sufficient insight to set the trends of future science. It seems even less obvious that funding agencies should blindly follow the fashion trends set by the publishers. The perverse relationships between private publishers and public funding agencies may have a toxic effect on science policy.

  8. Linking Arsenic Metabolism and Toxic Effects

    Science.gov (United States)

    Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

  9. Sub-chronic effects of a Phthirusa pyrifolia aqueous extract on reproductive function and comparative hormone levels in male rats

    Directory of Open Access Journals (Sweden)

    Romero Marcos Pedrosa Brandão-Costa

    2016-03-01

    Conclusions: These results suggest that the high amounts of flavonoids shown to be in the extract may be responsible for its hepato-protective effects and suggest a possible decrease in the libido and reproduction of rats.

  10. EFFECTS OF SUBCHRONIC EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES ON ELECTROCARDIOGRAM AND HEART RATE VARIABILITY IN SPONTANEOUSLY HYPERTENSIVE RATS

    Science.gov (United States)

    Epidemiological studies have linked air pollution exposure to adverse respiratory health effects, especially in individuals with inflammatory airways disease. Symptomatic asthmatics appear to be at greatest risk. We previously demonstrated that exposure of rats to particulate...

  11. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, Craig A., E-mail: craig.a.mcfarland@us.army.mi [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Quinn, Michael J [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Boyce, John [Biotechnics, LLC, Hillsborough, NC 27278 (United States); LaFiandra, Emily M; Bazar, Matthew A [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States); Johnson, Mark S [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States)

    2011-02-15

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD{sub 50} values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at {>=}15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: Oral LD{sub 50} (mg/kg) values were 1406 for male and 1867 for female lizards. Dose-dependent hepatocellular transdifferentiation was observed at {>=}5 mg/kg-d. Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  12. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    McFarland, Craig A.; Quinn, Michael J.; Boyce, John; LaFiandra, Emily M.; Bazar, Matthew A.; Talent, Larry G.; Johnson, Mark S.

    2011-01-01

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD 50 values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: → Oral LD 50 (mg/kg) values were 1406 for male and 1867 for female lizards. → Dose-dependent hepatocellular transdifferentiation was observed at ≥5 mg/kg-d. → Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. → Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  13. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, Christoph, E-mail: steinbach@frov.jcu.cz [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Fedorova, Ganna [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Prokes, Miroslav [Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., Kvetna 8, 603 65 Brno (Czech Republic); Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic)

    2013-09-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L{sup −1} to μg L{sup −1}. In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC{sub 50} values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L{sup −1} for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L{sup −1}. Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L{sup −1} of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of

  14. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    International Nuclear Information System (INIS)

    Steinbach, Christoph; Fedorova, Ganna; Prokes, Miroslav; Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour

    2013-01-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L −1 to μg L −1 . In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC 50 values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L −1 for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L −1 . Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L −1 of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of common carp. • The

  15. Persistent toxic substances: sources, fates and effects.

    Science.gov (United States)

    Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

    2012-01-01

    Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

  16. Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP: effects of modafinil and relevance to cognitive deficits in schizophrenia?

    Directory of Open Access Journals (Sweden)

    John P Redrobe

    2010-11-01

    Full Text Available Phencyclidine (PCP induces a behavioural syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p. or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP-treatment. Acute treatment with modafinil (64 mg/kg, p.o. ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c., risperidone (0.2 mg/kg, i.p. and donepezil (3 mg/kg, p.o. were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.

  17. Subchronic exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies

    International Nuclear Information System (INIS)

    Bloch-Shilderman, Eugenia; Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-01-01

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 μg/kg/day, 0.05 LD 50 ) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition (∼ 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction (∼ 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures

  18. Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

    Science.gov (United States)

    Lyoussi, Badiaa; Cherkaoui Tangi, Khadija; Morel, Nicole; Haddad, Mohamed; Quetin-Leclercq, Joelle

    2018-01-01

    The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC 50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD 50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

  19. Evaluation of multiwalled carbon nanotubes toxicity in two fish species.

    Science.gov (United States)

    Cimbaluk, Giovani Valentin; Ramsdorf, Wanessa Algarte; Perussolo, Maiara Carolina; Santos, Hayanna Karla Felipe; Da Silva De Assis, Helena Cristina; Schnitzler, Mariane Cristina; Schnitzler, Danielle Caroline; Carneiro, Pedro Gontijo; Cestari, Marta Margarete

    2018-04-15

    Carbon Nanotubes are among the most promising materials for the technology industry. Their unique physical and chemical proprieties may reduce the production costs and improve the efficiency of a large range of products. However, the same characteristics that have made nanomaterials interesting for industry may be responsible for inducing toxic effects on the aquatic organisms. Since the carbon nanotubes toxicity is still a controversial issue, we performed tests of acute and subchronic exposure to a commercial sample of multiwalled carbon nanotubes in two fish species, an exotic model (Danio rerio) and a native one (Astyanax altiparanae). Using the alkaline version of the comet assay on erythrocytes and the piscine micronucleous, also performed on erythrocytes, it was verified that the tested carbon nanotubes sample did not generate apparent genotoxicity by means of single/double DNA strand break or clastogenic/aneugenic effects over any of the species, independently of the exposure period. Although, our findings indicate the possibility of the occurrence of CNTs-DNA crosslinks. Apparently, the sample tested induces oxidative stress after subchronic exposure as shown by activity of superoxide dismutase and catalase. The data obtained by the activity levels of acetylcholinesterase suggests acute neurotoxicity in Astyanax altiparanae and subchronic neurotoxicity in Danio rerio. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  1. Environmental Mercury and Its Toxic Effects

    Directory of Open Access Journals (Sweden)

    Kevin M. Rice

    2014-03-01

    Full Text Available Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

  2. Allyl nitrile: Toxicity and health effects.

    Science.gov (United States)

    Tanii, Hideji

    2017-03-28

    Allyl nitrile (3-butenenitrile) occurs naturally in the environment, in particular, in cruciferous vegetables, indicating a possible daily intake of the compound. There is no report on actual health effects of allyl nitrile in humans, although it is possible that individuals in the environment are at a risk of exposure to allyl nitrile. However, little is known about its quantitative assessment for the environment and bioactivity in the body. This study provides a review of previous accumulated studies on allyl nitrile. Published literature on allyl nitrile was examined for findings on toxicity, metabolism, risk of various cancers, generation, intake estimates, and low-dose effects in the body. High doses of allyl nitrile produce toxicity characterized by behavioral abnormalities, which are considered to be produced by an active metabolite, 3,4-epoxybutyronitrile. Cruciferous vegetables have been shown to have a potential role in reducing various cancers. Hydrolysis of the glucosinolate sinigrin, rich in cruciferous vegetables, results in the generation of allyl nitrile. An intake of allyl nitrile is estimated at 0.12 μmol/kg body weight in Japan. Repeated exposure to low doses of allyl nitrile upregulates antioxidant/phase II enzymes in various tissues; this may contribute to a reduction in neurotoxicity and skin inflammation. These high and low doses are far more than the intake estimate. Allyl nitrile in the environment is a compound with diverse bioactivities in the body, characterized by inducing behavioral abnormalities at high doses and some antioxidant/phase II enzymes at low doses.

  3. Joint toxic effects on Caenorhabditis elegans

    NARCIS (Netherlands)

    Jonker, M.J.

    2003-01-01

    In polluted areas organisms are generally exposed to mixtures of toxic chemicals rather than a single toxicant only. Since the number of mixture toxicity studies with regard to soil systems is limited, the research in this thesis was focused on investigating ecotoxicological consequences of

  4. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    International Nuclear Information System (INIS)

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-01-01

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  5. Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats

    Directory of Open Access Journals (Sweden)

    Li-Chan Yang

    2018-01-01

    Full Text Available Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE in male and female Sprague-Dawley (SD rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. Based on results, the no-observed-adverse-effect level of DTTE is greater than 2400 mg/kg in SD rats.

  6. Dietary intake and health effects of selected toxic elements

    OpenAIRE

    Silva, André Luiz Oliveira da; Barrocas, Paulo R.G.; Jacob, Silvana do Couto; Moreira, Josino Costa

    2005-01-01

    Anthropogenic activities have being contributing to the spread of toxic chemicals into the environment, including several toxic metals and metalloids, increasing the levels of human exposure to many of them. Contaminated food is an important route of human exposure and may represent a serious threat to human health. This mini review covers the health effects caused by toxic metals, especially Cd, Hg, Pb and As, the most relevant toxic elements from a human health point of view. As atividad...

  7. Toxic Effects of Cannabis and Cannabinoids: Animal Data

    Directory of Open Access Journals (Sweden)

    Pierre Beaulieu

    2005-01-01

    Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  8. Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

    International Nuclear Information System (INIS)

    Hendriksen, Peter J.M.; Freidig, Andreas P.; Jonker, Diana; Thissen, Uwe; Bogaards, Jan J.P.; Mumtaz, Moiz M.; Groten, John P.; Stierum, Rob H.

    2007-01-01

    The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest-Observed-Adverse-Effect-Level (LOAEL) or at a two- or threefold lower concentration individually or in binary or ternary mixtures. The compounds had strong antagonistic effects on each other's gene expression changes, which included several genes encoding Phase I and II metabolizing enzymes. On the other hand, the mixtures affected the expression of 'novel' genes that were not or little affected by the individual compounds. The three compounds exhibited a synergistic interaction on gene expression changes at the LOAEL in the liver and both at the sub-LOAEL and LOAEL in the kidney. Many of the genes induced by mixtures but not by single compounds, such as Id2, Nr2f6, Tnfrsf1a, Ccng1, Mdm2 and Nfkb1 in the liver, are known to affect cellular proliferation, apoptosis and tissue-specific function. This indicates a shift from compound specific response on exposure to individual compounds to a more generic stress response to mixtures. Most of the effects on cell viability as concluded from transcriptomics were not detected by classical toxicological endpoints illustrating the benefit of increased sensitivity of assessing gene expression profiling. These results emphasize the benefit of applying toxicogenomics in mixture interaction studies, which yields biomarkers for joint toxicity and eventually can result in an interaction model for most known toxicants

  9. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

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

    2009-01-01

    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

  10. Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice

    DEFF Research Database (Denmark)

    Roursgaard, Martin; Jensen, Keld A; Poulsen, Steen Seier

    2011-01-01

    This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compo...

  11. Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

    Science.gov (United States)

    Sertié, J A A; Woisky, R G; Wiezel, G; Rodrigues, M

    2005-05-01

    Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

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

    International Nuclear Information System (INIS)

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Prince, H.H.; Ringer, R.K.

    1995-01-01

    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. A 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

  13. Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

    Science.gov (United States)

    Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

    1998-01-01

    The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate

  14. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview

    Directory of Open Access Journals (Sweden)

    Katsnelson BA

    2015-04-01

    Full Text Available Boris A Katsnelson,1 Larisa I Privalova,1 Marina P Sutunkova,1 Vladimir B Gurvich,1 Nadezhda V Loginova,1 Ilzira A Minigalieva,1 Ekaterina P Kireyeva,1 Vladimir Y Shur,2 Ekaterina V Shishkina,2 Ya B Beikin,3 Oleg H Makeyev,4 Irene E Valamina4 1The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia; 2The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia; 3The City Clinical Diagnostics Centre, Ekaterinburg, Russia; 4The Ural State Medical University, Ekaterinburg, Russia Abstract: The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 µm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently

  15. Effects of subchronic benzo(a)pyrene exposure on neurotransmitter receptor gene expression in the rat hippocampus related with spatial learning and memory change.

    Science.gov (United States)

    Qiu, Chongying; Cheng, Shuqun; Xia, Yinyin; Peng, Bin; Tang, Qian; Tu, Baijie

    2011-11-18

    Exposure of laboratory rats to Benzo(a)pyrene (BaP), an environmental contaminant with its high lipophilicify which is widely dispersed in the environment and can easily cross the blood brain barrier presenting in the central nervous system, is associated with impaired learning and memory. The purpose of the research was to examine whether subchronic exposure to BaP affects spatial learning and memory, and how it alters normal gene expression in hippocampus, as well as selection of candidate genes involving neurotransmitter receptor attributed to learning and memory. Morris water maze (MWM) was used to evaluate behavioral differences between BaP-treated and vehicle-treated groups. To gain a better insight into the mechanism of BaP-induced neurotoxicity on learning and memory, we used whole genome oligo microarrays as well as Polymerase Chain Reaction (PCR) to assess the global impact of gene expression. Male Sprague-Dawley rats were intraperitoneally injected with 6.25mg/kg of BaP or vehicle for 14 weeks. The results from the Morris water maze (MWM) test showed that rats treated with BaP exhibited significantly higher mean latencies as compared to vehicle controls. BaP exposure significantly decreased the number of crossing the platform and the time spent in the target area. After the hippocampus was collected from each rat, total RNA was isolated. Microarray and PCR revealed that exposure to BaP affected mRNA expression of neurotransmitter receptors. The web tool DAVID was used to analyze the significantly enriched gene ontology (GO) and KEGG pathways in the differentially expressed genes. Analysis showed that the most significantly affected gene ontology category was behavior. Furthermore, the fourth highest significantly affected gene ontology category was learning and memory. KEGG molecular pathway analysis showed that "neuroactive ligand-receptor interaction" was affected by BaP with highest statistical significance, and 9 candidate neurotransmitter receptor

  16. Use of hydra for chronic toxicity assessment of waters intended for human consumption

    International Nuclear Information System (INIS)

    Arkhipchuk, Victor V.; Blaise, Christian; Malinovskaya, Maria V.

    2006-01-01

    Methods developed with the cnidarian, Hydra attenuata (Pallas), have proven effective for screening acute toxicity in aqueous samples, whereas their use in revealing (sub)chronic toxic effects have had mitigated success. We therefore sought to explore manifestations of hydra mortality and abnormal morphological changes, as well as the reproductive capacity of hydras to further enhance the bioassay sensitivity and to assess (sub)chronic toxicity. These parameters were recorded following the onset of experiments after 8, 12 and 19-21 days of hydra exposure. Results obtained with potable waters (30 brands of bottled waters and artesian waters from 9 wells) showed chronic sublethal and lethal effects or reproduction rate inhibition for most samples. The effectiveness of the hydra toxicity test was demonstrated in comparison with other widely used bioassays. Our previous and present investigations suggest that hydra is a reliable and relevant test organism for the assessment of acute and chronic water toxicity. - Hydra is a reliable and relevant test organism for the assessment of acute and chronic toxicity of waters intended for human consumption

  17. Safety evaluation of genetically modified DAS-40278-9 maize in a subchronic rodent feeding study.

    Science.gov (United States)

    Zou, Shiying; Lang, Tianqi; Liu, Xu; Huang, Kunlun; He, Xiaoyun

    2018-07-01

    Genetically modified (GM) maize, DAS-40278-9, expresses the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The aad-1 gene, which expresses the AAD-1 protein, was derived from Gram-negative soil bacterium, Sphingobium herbicidovorans. A 90-day sub-chronic toxicity study was conducted on rats as a component of the safety evaluation of DAS-40278-9 maize. Rats were given formulated diets containing maize grain from DAS-40278-9 or a non-GM near isogenic control comparator at an incorporation rate of 12.5%, 25%, or 50% (w/w), respectively for 90 days. In addition, another group of rats was fed a basic rodent diet. Animals were evaluated by cage-side and hand-held detailed clinical observations, ophthalmic examinations, body weights/body weight gains, feed consumption, hematology, serum chemistry, selected organ weights, and gross and histopathological examinations. Under the condition of this study, DAS-40278-9 maize did not cause any treatment-related effects in rats compared with rats fed diets containing non-GM maize. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Quantal health effects of three toxic agents combined

    International Nuclear Information System (INIS)

    Seiler, F.A.

    1988-01-01

    Quantal health effects such as cancer, correlated with the combined action of three toxic agents, are considered. Data on the combined effects of two agents are scarce and no such data exist for three toxicants, yet concerns have arisen about simultaneous exposure of radiation workers to three different agents. Using models developed from the analysis of health effects involving two toxicants, equations for the combined effects of three agents are derived from a more general formalism. An application of practical interest is the incidence of cancer of the esophagus and its correlation with concurrent exposures to alcohol, tobacco, and either low- or high-LET radiation. (author)

  19. Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

    Directory of Open Access Journals (Sweden)

    Čolović Mirjana B.

    2013-01-01

    Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

  20. The toxic effects of chlorophenols and associated mechanisms in fish

    International Nuclear Information System (INIS)

    Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun

    2017-01-01

    Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

  1. The toxic effects of chlorophenols and associated mechanisms in fish

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun, E-mail: huangdj@lzu.edu.cn

    2017-03-15

    Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

  2. Quantal health effects for a combination of several toxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Seiler, F A

    1988-12-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  3. Quantal health effects for a combination of several toxic agents

    International Nuclear Information System (INIS)

    Seiler, F.A.

    1988-01-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  4. Toxic effect of heavy metals on aquatic environment | Baby ...

    African Journals Online (AJOL)

    Toxic effect of heavy metals on aquatic environment. ... International Journal of Biological and Chemical Sciences ... The indiscriminate discharge of industrial effluents, raw sewage wastes and other waste pollute most of the environments and ...

  5. Principles for prevention of toxic effects from metals

    DEFF Research Database (Denmark)

    Landrigan, Philip J.; Kotelchuk, David; Grandjean, Philippe

    2007-01-01

    of the Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc...

  6. Evaluation of toxic effects of metformin hydrochloride and ...

    African Journals Online (AJOL)

    olayemitoyin

    Drug Metabolism and Toxicology Research Laboratories, Department of ... This study was designed to investigate the toxic effect of MET and GB in the Liver, kidney and testis of rats. Twenty one ..... glibenclamide on male reproductive system,.

  7. Comparative toxicity effect of bush tea leaves ( Hyptis suaveolens ...

    African Journals Online (AJOL)

    Hyptis suaveolens) were compared for their toxicity effect on the larvae of the yellow fever mosquito Aedes aegypti collected from disused tyres beside College of Natural Sciences building University of Agriculture, Abeokuta, Nigeria.

  8. Studying the effect of CO2-induced acidification on sediment toxicity using acute amphipod toxicity test.

    Science.gov (United States)

    Basallote, M Dolores; De Orte, Manoela R; DelValls, T Ángel; Riba, Inmaculada

    2014-01-01

    Carbon capture and storage is increasingly being considered one of the most efficient approaches to mitigate the increase of CO2 in the atmosphere associated with anthropogenic emissions. However, the environmental effects of potential CO2 leaks remain largely unknown. The amphipod Ampelisca brevicornis was exposed to environmental sediments collected in different areas of the Gulf of Cádiz and subjected to several pH treatments to study the effects of CO2-induced acidification on sediment toxicity. After 10 days of exposure, the results obtained indicated that high lethal effects were associated with the lowest pH treatments, except for the Ría of Huelva sediment test. The mobility of metals from sediment to the overlying seawater was correlated to a pH decrease. The data obtained revealed that CO2-related acidification would lead to lethal effects on amphipods as well as the mobility of metals, which could increase sediment toxicity.

  9. The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.

    Science.gov (United States)

    Brown, Alastair; Thatje, Sven; Hauton, Chris

    2017-09-05

    Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.

  10. Ultrastructural analysis of early toxic effects produced by bee venom phospholipase A2 and melittin in Sertoli cells in rats.

    Science.gov (United States)

    Tilinca, Mariana; Florea, Adrian

    2018-01-01

    In this study, we aimed to investigate the testicular toxicity of two molecules derived from bee venom (BV): phospholipase A2 (PlA2) and melittin (Mlt). Ultrastructural effects of purified BV PlA2 and Mlt were assessed consecutive to repeated dose (30 days) and acute toxicity studies. For the subchronic treatment, PlA2 and Mlt were injected in daily doses equivalent to those released by a bee sting (105 μg PlA2/kg/day and 350 μg Mlt/kg/day), while in the acute treatment their doses corresponded to those released by 100 bee stings (9.3 mg PlA2/kg and 31 mg Mlt/kg). Both PlA2 and Mlt affected the Leydig cells and the cells in seminiferous tubules, the Sertoli cells first of all. PlA2 injection resulted in detachment of the Sertoli cells from the surrounding cells, and extracellular vacuolations, cytoplasmic vacuolations in their basal region and in branches as well, detachment of spermatids, residual bodies and sometimes even spermatocytes into the lumen, changes that had a higher magnitude after the acute treatment. Mlt injection induced similar ultrastructural alterations, but more severe, including degeneration of cellular organelles and cellular necrosis, resulting into rarefaction of the seminiferous epithelium; the ultrastructural changes had a higher magnitude after the 30 repeated dose treatment. We concluded that either of the two molecules tested here, PlA2 and Mlt, were Sertoli cells toxicants at the used doses, and they participated both in the BV testicular toxicity. We consider the observed changes as part of a preceding mechanism of the more severe alterations produced by the BV. It also remains possible that these early unspecific changes reported here could represent the response of the SCs not only to the components of bee venom, but to molecules of other venoms as well. The Sertoli cells were the primary target of PlA2 and Mlt in the spermatogenic epithelium, and their alteration led to further degenerative changes of the germ cells. Since

  11. Hepatorenal toxicity studies of sub-chronic administration of calyx ...

    African Journals Online (AJOL)

    Group A, was fed with growers mesh and distilled water as control. Groups B to F were administered orally with the aqueous extract at 1, 2, 3, 4 and 5g /kg body weight respectively and the treatment period was 28 days. A decreased in weights of the animals were observed at all dose levels. The activities of liver maker ...

  12. Subchronic oral toxicity studies with erythritol in mice and rats

    NARCIS (Netherlands)

    Til, H.P.; Kuper, C.F.; Falke, H.E.; Bär, A.

    1996-01-01

    Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10

  13. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    given orally to male and female rats at doses of 250 mg/kg, 500 mg/kg and 1000 ... There were no significant differences in body weight and organ weight between ... major vital organs (liver, kidney, stomach, spleen, brain and heart) tested.

  14. Acute and Subchronic Oral Toxicity of Aqueous Extract of Ageratum ...

    African Journals Online (AJOL)

    However, histological studies revealed that the extract caused dose-dependent lesions, resulting in hepatorenal changes correlated with a high level of transaminases activity and hyperleukocytosis at 800 mg/kg dose level. The hemoglobin and hematocrit concentrations were also high in all groups treated with the extract.

  15. Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

    Science.gov (United States)

    Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

    2018-01-01

    Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Effectiveness of bioremediation in reducing toxicity in oiled intertidal sediments

    International Nuclear Information System (INIS)

    Lee, K.; Tremblay, G.H.

    1995-01-01

    A 123-day field study was conducted with in situ enclosures to compare the effectiveness of bioremediation strategies based in inorganic and organic fertilizer additions to accelerate the biodegradation rates and reduce the toxicity of Venture trademark condensate stranded within sand-beach sediments. Comparison of the two fertilizer formulations with identical nitrogen and phosphorus concentrations showed that the organic fertilizer stimulated bacterial productivity within the oiled sediments to the greatest extent. However, detailed chemical analysis indicated that inorganic fertilizer additions were the most effective in enhancing condensate biodegradation rates. The Microtox reg-sign Solid-Phase Test (SPT) bioassay was determined to be sensitive to Venture Condensate in laboratory tests. Subsequent application of this procedure to oiled sediment in the field showed a reduction in sediment toxicity over time. However, the Microtox reg-sign bioassay procedure did not identify significant reductions in sediment toxicity following bioremediation treatment. An observed increase in toxicity following periodic additions of the organic fertilizer was attributed to rapid biodegradation rates of the fertilizer, which resulted in the production of toxic metabolic products

  17. The toxic effect of alunimium in vines

    International Nuclear Information System (INIS)

    Le Roux, E.G.; Peisach, M.; Pineda, C.A.; Pougnet, M.A.B.

    1988-01-01

    The split-root technique was used to study the effect of varying the growth media on the elemental content of nutrient elements in the roots of grape vines. The varieties 2-1 (R99 x Jacquez) and Sauvignon blanc (Vitis vinifera) were grown in Hoagland water culture with and without added aluminium. The elemental concentrations of Mg, Al, Si, P, S, Cl, K and Ca in the dried roots were determined by PIXE. Roots grown in Al-rich media were deficient in Mg and Ca, but enriched in Al. There was a correlation between Al and Si but the uptake differed in the two varieties. (author) 7 refs.; 4 figs

  18. Antioxidant, Antibacterial and Cell Toxicity Effects of Polyphenols

    African Journals Online (AJOL)

    Z. Ghouila, S. Laurent, S. Boutry, L. Vander Elst, F. Nateche, R. N. Muller, A. Baaliouamer

    2017-01-01

    Jan 1, 2017 ... At 100 μg/mL, GSE induced a moderate toxicity of the order of ... the many phytochemical compounds consumed in our diet, polyphenols are the most ... action of grape seed extract in many health related areas due to its antioxidant effect [11]. In ...... antibacterial activities of southern Serbian red wines.

  19. The effects on health of radiological and chemical toxicity

    International Nuclear Information System (INIS)

    Toledano, M.; Flury-Herard, A.

    2003-01-01

    Future trends in the protection against the effects on health of radiological and/or chemical toxicity will certainly be based on improved knowledge of specific biological mechanisms and individual sensitivity. Progress in these areas will most likely be made at the interfaces between research, health care and biomedical monitoring. (authors)

  20. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    edoja

    2013-07-31

    Jul 31, 2013 ... Full Length Research Paper. Neuroprotective effect of creatine against propionic acid toxicity in neuroblastoma SH-SY5Y cells in culture. Afaf El-Ansary*, Ghada Abu-Shmais and Abeer Al-Dbass. Biochemistry Department, College of Science, King Saud University, P.O. Box 22452, Zip code 11495, Riyadh, ...

  1. Protective effect of zinc against cadmium toxicity on pregnant rats ...

    African Journals Online (AJOL)

    ZINO

    2013-04-17

    Apr 17, 2013 ... fetuses were used to isolate a total RNA for quantification of Msx1, Cx43, Bcl2 and Bax genes. The results show the toxic effect ... caspase-mitochondria pathways (Li et al., 2000), indicating that apoptosis could .... RNA isolation and real-time reverse transcription polymerase chain reaction. Total RNA was ...

  2. Health effects of toxicants: Online knowledge support

    Science.gov (United States)

    Judson, Richard; de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva

    2016-01-01

    Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. PMID:26506572

  3. The toxic effects of ionizing radiations

    International Nuclear Information System (INIS)

    Draghita Payet, A.C.

    2006-06-01

    The sources of radiations to which the human body is subjected are of natural or artificial origin and the irradiation of the human body can take place either by internal or external way. The ionizing radiations act at several levels of the human body, the main thing being the molecule of DNA. The ionizing radiations have no specificity, the effects on the human body can be: somatic, genetic or hereditary, teratogen. In the case of a human being irradiation, we proceed to the diagnosis and to the treatment of the irradiated person, however, to decrease the incidence of injuries we use the radiation protection. The treatment if necessary will be established according to the irradiation type. (N.C.)

  4. Health effects of toxicants: Online knowledge support.

    Science.gov (United States)

    Wexler, Philip; Judson, Richard; de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva

    2016-01-15

    Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. Published by Elsevier Inc.

  5. Mercury and its toxic effects on fish

    Directory of Open Access Journals (Sweden)

    Patricia Morcillo

    2017-04-01

    Full Text Available Mercury (Hg and its derivative compounds have been parts of widespread pollutants of the aquatic environment. Since Hg is absorbed by fish and passed up the food chain to other fish-eating species, it does not only affect aquatic ecosystems but also humans through bioaccumulation. Thus, the knowledge of toxicological effects of Hg on fish has become one of the aims in research applied to fish aquaculture. Moreover, the use of alternative methods to animal testing has gained great interest in the field of Toxicology. This review addresses the systemic pathophysiology of individual organ systems associated with Hg poisoning on fish. Such data are extremely useful to the scientific community and public officials involved in health risk assessment and management of environmental contaminants as a guide to the best course of action to restore ecosystems and, in turn, to preserve human health.

  6. Toxic effect of lithium in mouse brain

    International Nuclear Information System (INIS)

    Dixit, P.K.; Smithberg, M.

    1988-01-01

    The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into 14 CO 2 /mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed

  7. Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats.

    Science.gov (United States)

    Hasumura, Mai; Imai, Toshio; Cho, Young-Man; Ueda, Makoto; Hirose, Masao; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2011-01-01

    Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

  8. Nanomedicinal products: a survey on specific toxicity and side effects

    Directory of Open Access Journals (Sweden)

    Brand W

    2017-08-01

    Full Text Available Walter Brand,1,* Cornelle W Noorlander,1,* Christina Giannakou,2,3 Wim H De Jong,2 Myrna W Kooi,1 Margriet VDZ Park,2 Rob J Vandebriel,2 Irene EM Bosselaers,4 Joep HG Scholl,5 Robert E Geertsma2 1Centre for Safety of Substances and Products, 2Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 3Department of Toxicogenomics, Maastricht University, Maastricht, 4Section Pharmacology, Toxicology and Pharmacokinetics, Medicines Evaluation Board (CBG-MEB, Utrecht, 5Research & Analysis Department, Netherlands Pharmacovigilance Centre Lareb, ‘s-Hertogenbosch, the Netherlands *These authors contributed equally to this work Abstract: 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

  9. POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF ULTRAFINE PARTICLE TOXIC EFFECTS IN HUMANS

    Directory of Open Access Journals (Sweden)

    JASMINA JOVIĆ-STOŠIĆ

    2008-03-01

    Full Text Available Epidemiological and clinical studies suggested the association of the particulate matter ambient air pollution and the increased morbidity and mortality, mainly from respiratory and cardiovascular diseases. The size of particles has great influence on their toxicity, because it determines the site in the respiratory tract where they deposit. The most well established theory explaining the mechanisms behind the increased toxicity of ultrafine particles (UFP, < 0.1 µm is that it has to do with the increased surface area and/or the combination with the increased number of particles. Biological effects of UFP are also determined by their shape and chemical composition, so it is not possible to estimate their toxicity in a general way. General hypothesis suggested that exposure to inhaled particles induces pulmonary alveolar inflammation as a basic pathophysiological event, triggering release of various proinflammatory cytokines. Chronic inflammation is a very important underlying mechanism in the genesis of atherosclerosis and cardiovascular diseases. UFP can freely move through the circulation, but their effects on the secondary organs are not known yet, so more studies on recognizing toxicological endpoints of UFP are needed. Determination of UFP toxicity and the estimation of their internal and biologically active dose are necessary for the evidence based conclusions connecting air pollution by UFP and human diseases.

  10. Effects of sub-chronic exposure to zinc nanoparticles on tissue accumulation, serum biochemistry and histopathological changes in tilapia (Oreochromis niloticus)

    Science.gov (United States)

    Kaya, Hasan; Duysak, Müge; Akbulut, Mehmet; Yılmaz, Sevdan; Gürkan, Mert; Arslan, Zikri; Demir, Veysel; Ateş, Mehmet

    2016-01-01

    Zinc nanoparticles (ZnNPs) are among the least investigated NPs and thus their toxicological effects are not known. In this study, tilapia (Oreochromis niloticus) were exposed to 1 and 10 mg/L suspensions of small size (SS, 40–60 nm) and large size (LS, 80–100 nm) ZnNPs for 14 days under semi-static conditions. Total Zn levels in the intestine, liver, kidney, gill, muscle tissue and brain were measured. Blood serum glucose (GLU), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were examined to elucidate the physiological disturbances induced by ZnNPs. Organ pathologies were examined for the gills, liver and kidney to identify injuries associated with exposure. Significant accumulation was observed in the order of intestine, liver, kidney and gills. Zn levels exhibited time- and concentration-dependent increase in the organs. Accumulation in kidney was also dependent on particle size; NPs SS-ZnNPs were trapped more effectively than LS-ZnNPs. No significant accumulation occurred in the brain (p>0.05) while Zn levels in muscle tissue increased only marginally (p≥0.05). Significant disturbances were noted in serum GOT and LDH (p0.05). Histopathological tubular deformations and mononuclear cell infiltrations were observed in kidney sections. In addition, an increase in melano-macrophage aggregation intensity was identified on the 7th day in treatments exposed to LS-ZnNPs. Mononuclear cell infiltrations were identified in liver sections for all treatments. Both ZnNPs caused basal hyperplasia in gill sections. Fusions appeared in the gills after the 7th day in fish treated with 10 mg/L suspensions of SS-ZnNPs. In addition, separations in the secondary lamella epithelia were observed. The results indicated that exposure to ZnNPs could lead to disturbances in blood biochemistry and cause histopathological injuries in the tissues of O. niloticus. PMID:27464841

  11. The fungicide mancozeb induces toxic effects on mammalian granulosa cells

    International Nuclear Information System (INIS)

    Paro, Rita; Tiboni, Gian Mario; Buccione, Roberto; Rossi, Gianna; Cellini, Valerio; Canipari, Rita; Cecconi, Sandra

    2012-01-01

    The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant. Highlights: ► The fungicide mancozeb affects oocyte spindle morphology and fertilization rate. ► We investigated the toxic effects of mancozeb on mouse and human granulosa cells. ► Granulosa cells modify their morphology and expression level of p53. ► Mancozeb induces a premalignant-like status in exposed cells.

  12. The fungicide mancozeb induces toxic effects on mammalian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Paro, Rita [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy); Tiboni, Gian Mario [Department of Medicine and Aging, Section of Reproductive Sciences, University “G. D' Annunzio”, Chieti-Pescara (Italy); Buccione, Roberto [Tumor Cell Invasion Laboratory, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti (Italy); Rossi, Gianna; Cellini, Valerio [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy); Canipari, Rita [Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Histology and Embryology, School of Pharmacy and Medicine, “Sapienza” University of Rome, Rome (Italy); Cecconi, Sandra, E-mail: sandra.cecconi@cc.univaq.it [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy)

    2012-04-15

    The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant. Highlights: ► The fungicide mancozeb affects oocyte spindle morphology and fertilization rate. ► We investigated the toxic effects of mancozeb on mouse and human granulosa cells. ► Granulosa cells modify their morphology and expression level of p53. ► Mancozeb induces a premalignant-like status in exposed cells.

  13. Past, present and emerging toxicity issues for jet fuel

    International Nuclear Information System (INIS)

    Mattie, David R.; Sterner, Teresa R.

    2011-01-01

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  14. Safety evaluation of transgenic low-gliadin wheat in Sprague Dawley rats: An alternative to the gluten free diet with no subchronic adverse effects.

    Science.gov (United States)

    Ozuna, Carmen Victoria; Barro, Francisco

    2017-09-01

    Gluten-associated pathologies have increased in recent years and there is a greater demand for low or gluten-free products. Transgenic low-gliadin wheat lines showed low T-cell response, good bread-making properties, and excellent sensory assets. The aim of this study was to evaluate the safety of the whole-wheat flour from one transgenic low-gliadin line (named E82) in a 90-day feeding study. In this study males (n = 50) and females (n = 50) SD rats were used. They were fed with doses of 1.42, 2.83 and 5.67 g/kg/day of the transgenic E82 line, 5.67 g/kg/day of the WT and a blank group. We found that there were no significant differences in the development of animals. Biochemistry for liver and kidney function were similar for males and females of all groups. Other haematological and metabolic blood parameters, as well as organ weight did not show significant differences in the five groups of animals. In the histopathological study performed for the higher dose of transgenic E82 line, WT and blank group no abnormalities were observed. The whole-wheat flour of E82 line administered to rats at tested doses for 90 days did not have any adverse effects and there was no difference with the rats which ate WT wheat. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. II. Effect on hepatic glutathione level

    Directory of Open Access Journals (Sweden)

    Danuta Plewka

    2012-09-01

    Full Text Available Background: Feature of modern existing hazards both environmental and occupational is cumulative exposure often leading to unexpected response of the organism resulting, among other things, in interactions with cytochrome P450 system involved in biotransformation of trichloroethylene and paracetamol. Hepatotoxity of paracetamol is closely connected with hepatic glutathione level. „In therapy of acute paracetamol poisoning application of N-acetylcysteine as a factor, which protects GSH level in cells, is recommended.” Materials and method: Tests were performed on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In rat liver total level of glutathione was determined i.e. reduced and oxidized form. Results: Paracetamol just after completion of the exposure affected the glutathione level. Trichloroethylene throughout the period of observation stimulated growth of glutathione level in liver. N-acetylcysteine didn’t have any influence on the level of investigated tripeptyde. Conclusions: N-acetylcysteine removes negative effect of paracetamol especially when it’s applied with 2-hour delay. After exposure for trichloethylene immediate application of N-acetylcysteine caused noticeable lowering of glutathione level. Cumulative exposure for three xenobiotics had positive influence for glutathione level in rat liver.

  16. Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Sherry; Chen, Jin Ching; Hsu, Chin Wei; Chang, Walter H, E-mail: whchang@cycu.edu.t [Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan (China); Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan (China)

    2009-09-16

    Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg{sup -1} body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

  17. Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.

    Science.gov (United States)

    Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M; Morris, Brian J; Pratt, Judith A

    2008-05-01

    We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.

  18. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Liver Effects

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1, but not with degree of induction in hepatocellular proliferation. In sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver protein levels of Cyp2e1, Adh and Aldh2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. PMID:25424544

  19. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  20. Acute And Toxicity Effect of The Aqueous Extract

    African Journals Online (AJOL)

    Administrator

    antidiarrhoeal, antimalarial and antitrypanosomal activities of plants-based products support this ... Experimental design for Acute toxicity Study: The acute toxicity study was .... Lorke, D. (1983). A new approach to practical acute toxicity testing.

  1. EFFECTS OF SILICON ON ALLEVIATING ARSENIC TOXICITY IN MAIZE PLANTS

    Directory of Open Access Journals (Sweden)

    Airon José da Silva

    2015-02-01

    Full Text Available Arsenic is a metalloid highly toxic to plants and animals, causing reduced plant growth and various health problems for humans and animals. Silicon, however, has excelled in alleviating stress caused by toxic elements in plants. The aim of this study was to investigate the effects of Si in alleviating As stress in maize plants grown in a nutrient solution and evaluate the potential of the spectral emission parameters and the red fluorescence (Fr and far-red fluorescence (FFr ratio obtained in analysis of chlorophyll fluorescence in determination of this interaction. An experiment was carried out in a nutrient solution containing a toxic rate of As (68 μmol L-1 and six increasing rates of Si (0, 0.25, 0.5, 1.0, 1.5, and 2.0 mmol L-1. Dry matter production and concentrations of As, Si, and photosynthetic pigments were then evaluated. Chlorophyll fluorescence was also measured throughout plant growth. Si has positive effects in alleviating As stress in maize plants, evidenced by the increase in photosynthetic pigments. Silicon application resulted in higher As levels in plant tissue; therefore, using Si for soil phytoremediation may be a promising choice. Chlorophyll fluorescence analysis proved to be a sensitive tool, and it can be successfully used in the study of the ameliorating effects of Si in plant protection, with the Fr/FFr ratio as the variable recommended for identification of temporal changes in plants.

  2. Review on the effects of toxicants on freshwater ecosystem functions

    International Nuclear Information System (INIS)

    Peters, K.; Bundschuh, M.; Schäfer, R.B.

    2013-01-01

    We reviewed 122 peer-reviewed studies on the effects of organic toxicants and heavy metals on three fundamental ecosystem functions in freshwater ecosystems, i.e. leaf litter breakdown, primary production and community respiration. From each study meeting the inclusion criteria, the concentration resulting in a reduction of at least 20% in an ecosystem function was standardized based on median effect concentrations of standard test organisms (i.e. algae and daphnids). For pesticides, more than one third of observations indicated reductions in ecosystem functions at concentrations that are assumed being protective in regulation. Moreover, the reduction in leaf litter breakdown was more pronounced in the presence of invertebrate decomposers compared to studies where only microorganisms were involved in this function. High variability within and between studies hampered the derivation of a concentration–effect relationship. Hence, if ecosystem functions are to be included as protection goal in chemical risk assessment standardized methods are required. -- Highlights: •Quantitative review of 122 studies on effects of toxicants on ecosystem functions. •Variation between studies hampered derivation of concentration–effect relationships. •Adverse effects of pesticide were observed below thresholds corresponding to regulation. •Effects on leaf breakdown were greater when invertebrates were involved. -- Concentrations assumed as protective in chemical regulation cause adverse effects in three fundamental ecosystem functions

  3. Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Rauscher, J.D.

    1988-01-01

    Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects of Se and Cu on planarians.

  4. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    Directory of Open Access Journals (Sweden)

    A.M. Kammon

    2011-02-01

    Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

  5. Effect of malachite green toxicity on non target soil organisms.

    Science.gov (United States)

    Gopinathan, R; Kanhere, J; Banerjee, J

    2015-02-01

    Although malachite green (MG), is banned in Europe and US for its carcinogenic and teratogenic effect, the dye being cheap, is persistently used in various countries for fish farming, silk, dye, leather and textile industries. Current research, however, fails to elucidate adequate knowledge concerning the effects of MG in our ecosystem. In the present investigation, for the first time, an attempt has been made to study the effects of MG on soil biota by testing Bacillus subtilis, Azotobacter chroococcum, Saccharomyces cerevisiae, Penicillium roqueforti, Eisenia fetida and seeds of three crop plants of different families. Various tests were conducted for determining cytotoxicity, genotoxicity, acute toxicity, morphological and germination effect. Our data confirmed MG toxicity on fungi and bacteria (gram positive and gram negative organisms) showing elevated level of ROS. Genotoxicity caused in the microorganisms was detected by DNA polymorphism and fragmentation. Also, scanning electron microscopy data suggests that the inhibitory effect of MG to these beneficial microbes in the ecosystem might be due to pore formation in the cell and its eventual disruption. Filter paper and artificial soil test conducted on earthworms demonstrated a LC 50 of 2.6 mg cm(-2) and 1.45 mg kg(-1) respectively with severe morphological damage. However, seed germination of Mung bean, Wheat and Mustard was found to be unaffected in presence of MG up to 100 mL(-1) concentration. Thus, understanding MG toxicity in non target soil organisms and emphasis on its toxicological effects would potentially explicate its role as an environmental contaminant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Effects of benzoic acid and cadmium toxicity on wheat seedlings

    Directory of Open Access Journals (Sweden)

    Kavita Yadav

    2013-06-01

    Full Text Available Benzoic acid (BA and Cd exhibit cumulative effects on plants due to their accumulation in the soil. The present study reports the effects of BA an allelochemical, Cd and their combinations on seed germination, seedling growth, biochemical parameters, and response of antioxidant enzymes in Triticum aestivum L. The experiment was conducted in sand supplemented with Hoagland nutrient solution. Benzoic acid was applied at concentrations of 0.5, 1.0, and 1.5 mM with or without Cd (7 mg L-1 to observe effects of allelochemical and Cd alone and in combination on wheat. Both stresses exhibited inhibitory effect on growth and metabolism of wheat seedlings. The allelochemical in single and combined treatments with Cd decreased seedling growth as compared to Cd stress. The two stresses significantly enhanced malondialdehyde content of wheat seedlings. The activity of other antioxidant enzymes, viz. superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX, and guaiacol peroxidase (POX were also recorded. SOD increased in seedlings under the two stresses. CAT more prominently ameliorates the toxic effects of H2O2 as compared with APX and POX and protected wheat seedlings from oxidative stress. Allelochemical buttressed the toxic effect of Cd on wheat seedlings.

  7. Effect of radiosterilization of some antihistamines on their toxicity

    International Nuclear Information System (INIS)

    El-Sayed, M.E.; Roushdy, H.M.; Naiema, M.; Seham, H.M.H.

    1985-01-01

    The effect of gamma irradiation of pgeniramine maleate and menhydrinate solutions at the radiation levels of 15,25 and 50KGY on their toxicity has been investigated. Irradiation of pheniramine maleate and dimenhydrinate solutions at dose levels of 15,25 and 50KGY resulted in no significant change in neither the gross toxicity of the two drugs nor in their LD 50's on rats. Pheniramine maleate and dimenhydrinate whether irradiated or not, resulted in no significant increase in serum GPT or alkaline phosphatase activities when given at a dose of 15mg/Kg suggesting no significant alteration to liver function in rats. Higher doses of the two antihistaminics, namely, the minimal lethal doses and the LD 50's induced hydropic degeneration of liver cells, lymphocytic infiltration of the portal tract and focal areas of necrosis of hepatic cells mostly in the central lobule. Fatty infiltration was observed with dimenhydrinate. Radiation treatment of those antihistamines up to 50KGY resulting in no alteration in their toxicity projects the high radiation stability of pheniramine maleate and dimenhydrinate and confirms gamma irradiation is a successful method for their sterilization

  8. [Toxicity effects of phthalate substitute plasticizers used in toys].

    Science.gov (United States)

    Hirata-Koizumi, Mutsuko; Takahashi, Mika; Matsumoto, Mariko; Kawamura, Tomoko; Ono, Atsushi; Hirose, Akihiko

    2012-01-01

    Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently. We therefore collected and evaluated the toxicological information on di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexanedicarboxylic acid, diisononyl ester (DINCH), diisononyl adipate (DINA), 2,2,4-trimetyl-1,3-pentanediol diisobutyrate (TXIB), tri-n-butyl citrate (TBC) and acetyl tri-n-butyl citrate (ATBC) which were detected at a relatively high frequency in toys. The collected data have shown that chronic exposure to DEHT affects the eye and nasal turbinate, and DINCH exerts effects on the thyroid and kidney in rats. DINA and TXIB have been reported to have hepatic and renal effects in dogs or rats, and ATBC slightly affected the liver in rats. The NOAELs for repeated dose toxicity are relatively low for DINCH (40 mg/kg bw/day) and TXIB (30 mg/kg bw/day) compared with DEHT, DINA and ATBC. DEHT, TXIB and ATBC have been reported to have reproductive/developmental effects at relatively high doses in rats. For DINA and TBC, available data are insufficient for assessing the hazards, and therefore, adequate toxicity studies should be conducted. In the present review, the toxicity information on 6 alternatives to phthalate plasticizers is summarized, focusing on the effects after oral exposure, which is the route of most concern.

  9. Effects of biochar addition on toxic element concentrations in plants

    DEFF Research Database (Denmark)

    Peng, Xin; Deng, Yinger; Peng, Yan

    2018-01-01

    Consuming food contaminated by toxic elements (TEs) could pose a substantial risk to human health. Recently, biochar has been extensively studied as an effective soil ameliorant in situ because of its ability to suppress the phytoavailability of TEs. However, despite the research interest......, the effects of biochar applications to soil on different TE concentrations in different plant parts remain unclear. Here, we synthesize 1813 individual observations data collected from 97 articles to evaluate the effects of biochar addition on TE concentrations in plant parts. We found that (1) the experiment...... type, biochar feedstock and pyrolysis temperature all significantly decreased the TE concentration in plant parts; (2) the responses of Cd and Pb concentrations in edible and indirectly edible plant parts were significantly more sensitive to the effect of biochar than the Zn, Ni, Mn, Cr, Co and Cu...

  10. Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhuri, Shubhra, E-mail: SCHAUDHURI@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); McCullough, Sandra S., E-mail: mcculloughsandras@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Hennings, Leah, E-mail: lhennings@uams.edu [Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Brown, Aliza T., E-mail: brownalizat@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Li, Shun-Hwa [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Simpson, Pippa M., E-mail: psimpson@mcw.edu [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Hinson, Jack A., E-mail: hinsonjacka@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); James, Laura P., E-mail: jameslaurap@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States)

    2012-10-15

    Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A{sub 2}, and cytosolic and secretory PLA{sub 2} activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E{sub 2} expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE{sub 2} expression and hepatocyte regeneration, likely through a mechanism involving PLA{sub 2}. -- Highlights: ► Trifluoperazine reduced acetaminophen toxicity and lowered HIF-1α induction. ► Trifluoperazine had no effect on the metabolism of acetaminophen. ► Trifluoperazine reduced hepatocyte regeneration. ► Trifluoperazine reduced phospholipase A{sub 2} activity and prostaglandin E{sub 2} levels.

  11. Toxic effects of silica nanoparticles on zebrafish embryos and larvae.

    Directory of Open Access Journals (Sweden)

    Junchao Duan

    Full Text Available Silica nanoparticles (SiNPs have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 µg/mL during 4-96 hours post fertilization (hpf. Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 µg/mL SiNPs produced substantial hyperactivity while the higher doses (100 and 200 µg/mL SiNPs elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

  12. Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

    Science.gov (United States)

    Li, Xia; Jiang, Xinwei; Sun, Jianxia; Zhu, Cuijuan; Li, Xiaoling; Tian, Lingmin; Liu, Liu; Bai, Weibin

    2017-06-01

    Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported. © 2017 New York Academy of Sciences.

  13. Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

    Energy Technology Data Exchange (ETDEWEB)

    Balmuri, Sricharani Rao [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Selvaraj, Uthra [Department of Biotechnology, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Kumar, Vadivel Vinod [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Anthony, Savarimuthu Philip, E-mail: philip@biotech.sastra.edu [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Tsatsakis, Aristides Michael [Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003 (Greece); Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Golokhvast, Kirill Sergeevich [Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Raman, Thiagarajan, E-mail: raman@biotech.sastra.edu [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Centre for Research in Infectious Diseases (CRID), School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India)

    2017-01-15

    Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights:

  14. Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

    International Nuclear Information System (INIS)

    Balmuri, Sricharani Rao; Selvaraj, Uthra; Kumar, Vadivel Vinod; Anthony, Savarimuthu Philip; Tsatsakis, Aristides Michael; Golokhvast, Kirill Sergeevich; Raman, Thiagarajan

    2017-01-01

    Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH) 2 without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd 2+ ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd 2+ ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd 2+ from sources such as cigarette smoke. - Highlights: • Toxicity of Cd

  15. Behavioral effects of ketamine and toxic interactions with psychostimulants

    Directory of Open Access Journals (Sweden)

    Yamamoto Keiichi

    2006-03-01

    Full Text Available Abstract Background The anesthetic drug ketamine (KT has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p. KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC and methamphetamine (MA, were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p. dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p. dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p. or MA (4 mg/kg, i.p. caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms in the elevated plus-maze test. For the COC (30 mg/kg or MA (4 mg/kg groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.- or MA (15 mg/kg, i.p.-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single

  16. Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

    Science.gov (United States)

    Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

    2016-05-01

    Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

  17. Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon Nanotubes.

    Science.gov (United States)

    Manke, Amruta; Luanpitpong, Sudjit; Rojanasakul, Yon

    Given their remarkable properties, carbon nanotubes (CNTs) have made their way through various industrial and medicinal applications and the overall production of CNTs is expected to grow rapidly in the next few years, thus requiring an additional recruitment of workers. However, their unique applications and desirable properties are fraught with concerns regarding occupational exposure. The concern about worker exposure to CNTs arises from the results of recent animal studies. Short-term and sub-chronic exposure studies in rodents have shown consistent adverse health effects such as pulmonary inflammation, granulomas, fibrosis, genotoxicity and mesothelioma after inhalation or instillation of several types of CNTs. Furthermore, physicochemical properties of CNTs such as dispersion, functionalization and particle size can significantly affect their pulmonary toxicity. Risk estimates from animal studies necessitate implementation of protective measures to limit worker exposure to CNTs. Information on workplace exposure is very limited, however, studies have reported that CNTs can be aerosolized and attain respirable airborne levels during synthesis and processing activities in the workplace. Quantitative risk assessments from sub-chronic animal studies recommend the health-based need to reduce exposures below the recommended exposure limit of 1 µg/m 3 . Practice of prevention measures including the use of engineering controls, personal protective equipment, health surveillance program, safe handling and use, as well as worker training can significantly minimize worker exposure and improve worker health and safety.

  18. STUDY OF THE TOXIC EFFECTS OF CYPERMETHRIN IN EXPERIMENTAL ANIMALS

    Directory of Open Access Journals (Sweden)

    Syed Mehmood Hasan

    2016-06-01

    Full Text Available This study focuses on the toxic effects of a commercially available pesticide, cypermethrin (CM, on animals. This pesticide was administered in the form of aerosol spray through a nebulizer. The study was performed in four different groups and a constant dose of the pesticide was administered once, twice, thrice and four times a day to the respective group for a period of 30 days. The animals were then dissected to study the pesticide effects on different organs. The organs were preserved in 10% formalin. The tissues were processed by basic histopathological method and the slides were prepared for observation. The results were recorded on a performa and were quantified by a unique scoring system. It is concluded that the injurious effects to the mentioned organs were dose and frequency dependent.

  19. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    OpenAIRE

    McDonald Jacob; Surace Michael J; Levesque Shannon; Block Michelle L

    2011-01-01

    Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 a...

  20. Selenium toxicity: cause and effects in aquatic birds

    Science.gov (United States)

    Spallholz, J.E.; Hoffman, D.J.

    2002-01-01

    There are several manners in which selenium may express its toxicity: (1) an important mechanism appears to involve the formation of CH3Se- which either enters a redox cycle and generates superoxide and oxidative stress, or forms free radicals that bind to and inhibit important enzymes and proteins. (2) Excess selenium as selenocysteine results in inhibition of selenium methylation metabolism. As a consequence, concentrations of hydrogen selenide, an intermediate metabolite, accumulate in animals and are hepatotoxic, possibly causing other selenium-related adverse effects. (3) It is also possible that the presence of excess selenium analogs of sulfur-containing enzymes and structural proteins play a role in avian teratogenesis. l-selenomethionine is the most likely major dietary form of selenium encountered by aquatic birds, with lesser amounts of l-selenocysteine ingested from aquatic animal foods. The literature is suggestive that l-selenomethionine is not any more toxic to adult birds than other animals. l-Selenomethionine accumulates in tissue protein of adult birds and in the protein of egg white as would be expected to occur in animals. There is no suggestion from the literature that the levels of l-selenomethionine that would be expected to accumulate in eggs in the absence of environmental concentration of selenium pose harm to the developing embryo. For several species of aquatic birds, levels of Se as selenomethionine in the egg above 3 ppm on a wet weight basis result in reduced hatchability and deformed embryos. The toxicity of l-selenomethionine injected directly into eggs is greater than that found from the entry of l-selenomethionine into the egg from the normal adult diet. This suggests that there is unusual if not abnormal metabolism of l-selenomethionine in the embryo not seen when l-selenomethionine is present in egg white protein where it likely serves as a source of selenium for glutathione peroxidase synthesis in the developing aquatic chick.

  1. Aloe vera: A review of toxicity and adverse clinical effects.

    Science.gov (United States)

    Guo, Xiaoqing; Mei, Nan

    2016-04-02

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.

  2. Evaluation of MWNT toxic effects on daphnia and zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Olasagasti, Maider; Rainieri, Sandra [AZTI-TECNALIA, Parque Tecnologico de Bizkaia 609, 48160 Derio (Spain)], E-mail: srainieri@azti.es; Alvarez, Noelia; Vera, Carolina [INASMET-TECNALIA, Mikeletegi pasealekua, 2, Parque Tecnologico, 20009 San Sebastian (Spain)

    2009-05-01

    Organisms of daphnia (Daphnia magna) and zebrafish (Danio rerio) embryos were exposed to a range of different concentrations of COOH-functionalized MWCNT suspended in an aqueous solution of Tween 20. Immobilization of daphnia and growth retardation, inhibition and malformation of zebrafish embryos were the endpoints tested after 24 and 48 hours. Immobilization of daphnia could be observed from 3 to 16 ppm and an increasing mortality of zebrafish embryo was detected at all the concentration tested. To identify more subtle toxic effects, we took advantage of the extensive information available on the zebrafish genome and monitored by RT-PCR the expression patterns of different zebrafish genes that could act as toxicity bio-markers. At some of the concentrations tested, changes in the expression profiles of the genes examined were detected. Our results suggest that MWCNT could potentially represent a risk to human health and environment, therefore a wider range of concentrations and further testing of this molecules should be carried out to define possible limitations in their use.

  3. Mercury accumulation and its distribution to metallothionein in mouse brain after sub-chronic pulse exposure to mercury vapor

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Sawada, M.; Shimada, A. [Department of Veterinary Pathology, Tottori University, 4-101 Koyamacho, Minami, Tottori 680-0945 (Japan); Satoh, M. [Department of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan); Tohyama, C. [Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

    2004-09-01

    Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m{sup 3} for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m{sup 3} for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains. (orig.)

  4. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  5. Toxic effect of khat (Catha edulis on memory: Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Birhane Alem Berihu

    2017-01-01

    Full Text Available Background: People use khat (Catha edulis for its pleasant stimulant effect of physical activity, consciousness, motor, and mental functions. Although there are reports assessing the effect of khat on memory, there was no study based on formal systematic review and meta-analysis. Objective: We have therefore conducted this meta-analysis to determine the level of evidence for the effect of khat (C. edulis Forsk on memory discrepancy. Methods: MEDLINE, Cochrane Library, PubMed, Academic Search Complete, SPORTDiscus, ScienceDirect, Scopus, Web of Science, and Google Scholar were searched to retrieve the papers for this review. Keywords utilized across database search were khat, cat, chat, long-term memory, short-term memory, memory deficit, randomized control trial, and cross-sectional survey. The search was limited to studies in humans and rodents; published in English language. Result: Finding of various studies included in our meta-analysis showed that the effect of acute, and subchronic exposure to khat showed that short-term memory appears to be affected depending on the duration of exposure. However, does not have any effect on long-term memory. Conclusion: Although a number of studies regarding the current topic are limited, the evidenced showed that khat (C. edulis induced memory discrepancy.

  6. The effect of toxic loads on effluent purification systems

    Energy Technology Data Exchange (ETDEWEB)

    Cillie, G.C.; Hart, O.O.; Davies, T.R.; Hassett, A.J.

    1977-04-01

    Deterioration of the performance of biological wastewater treatment plants at Daspoort Sewage Works, Pretoria, South Africa, during 1975 was attributed to toxic material in the sewage. Unusually high concentrations of mercury, phenol, chromium, and an organophosphorus compound were detected. These substances singly or in combination could have been responsible for the deterioration. Data from the biological plants and research units at Daspoort are collected and reviewed to evaluate the water quality effects of the period of low performance. Encystation by peritrichous ciliates caused high bacteria counts in biofilter effluents. Nitrification declined rapidly and recovery was delayed, while carbon oxidation was affected to a limited extent. The water product was of the same quality throughout, even when the influent was little better than settled sewage. (12 graphs, 4 references, 3 tables)

  7. Toxic effects of chlorinated cake flour in rats.

    Science.gov (United States)

    Cunningham, H M; Lawrence, G A; Tryphonas, L

    1977-05-01

    Four experiments were conducted using weanling Wistar rats to determine whether chlorinated cake flour or its constituents were toxic. Levels of 0.2 and 1.0% chlorine added to unbleached cake flour significantly (p less than 0.01) reduced growth rate by 20.7 and 85.2% and increased liver weight relative to body weight by 16.7 and 25.3%, respectively. Lipids extracted from flour chlorinated at the same levels had similar effects. Rat chow diets containing 0.2 and 0.6% chlorine in the form of chlorinated wheat gluten reduced growth rate and increased liver weight as a percentage of body weight. A rat chow diet containing 0.2% chlorine as chlorinated flour lipids increased absolute liver weight by 40%, kidney by 20%, and heart by 10% compared to pair-fed controls.

  8. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    Science.gov (United States)

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Toxic effects of ultraviolet radiation on the skin

    International Nuclear Information System (INIS)

    Matsumura, Yasuhiro; Ananthaswamy, Honnavara N.

    2004-01-01

    Ultraviolet (UV) irradiation present in sunlight is an environmental human carcinogen. The toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The major acute effects of UV irradiation on normal human skin comprise sunburn inflammation (erythema), tanning, and local or systemic immunosuppression. At the molecular level, UV irradiation causes DNA damage such as cyclobutane pyrimidine dimers and (6-4) photoproducts, which are usually repaired by nucleotide excision repair (NER). Chronic exposure to UV irradiation leads to photoaging, immunosuppression, and ultimately photocarcinogenesis. Photocarcinogenesis involves the accumulation of genetic changes, as well as immune system modulation, and ultimately leads to the development of skin cancers. In the clinic, artificial lamps emitting UVB (280-320 nm) and UVA (320-400 nm) radiation in combination with chemical drugs are used in the therapy of many skin diseases including psoriasis and vitiligo. Although such therapy is beneficial, it is accompanied with undesirable side effects. Thus, UV radiation is like two sides of the same coin--on one side, it has detrimental effects, and on the other side, it has beneficial effects

  10. A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

    Science.gov (United States)

    Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

    2011-12-01

    Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

  11. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

    OpenAIRE

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora ...

  12. Blueberry (Vaccinium ashei Reade) extract ameliorates ovarian damage induced by subchronic cadmium exposure in mice: Potential δ-ALA-D involvement.

    Science.gov (United States)

    Izaguirry, Aryele Pinto; Soares, Melina Bucco; Vargas, Laura Musacchio; Spiazzi, Cristiano Chiapinotto; Dos Santos Brum, Daniela; Noremberg, Simone; Mendez, Andreas Sebastian Loureiro; Santos, Francielli Weber

    2017-01-01

    Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 β-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017. © 2015 Wiley Periodicals, Inc.

  13. Intestinal lymphangiectasis and lipidosis in rats following subchronic exposure to indole-3-carbinol via oral gavage.

    Science.gov (United States)

    Boyle, Michael C; Crabbs, Torrie A; Wyde, Michael E; Painter, J Todd; Hill, Georgette D; Malarkey, David E; Lieuallen, Warren G; Nyska, Abraham

    2012-06-01

    To investigate the toxicity and carcinogenic potential of indole-3-carbinol (I3C), the National Toxicology Program has conducted 13-week subchronic studies in Fisher 344 rats and B6C3F1 mice, and chronic 2-year bioassays in Sprague-Dawley rats and B6C3F1 mice. While the chronic study results are not yet available, subchronic study results and short-term special evaluations of interim sacrifices in the 2-year rat bioassay are presented. F344 rats were orally gavaged ≤300 mg I3C/kg body weight 5 days a week for 13 weeks. Rats treated with ≥150 mg/kg demonstrated a dose-related dilation of lymphatics (lymphangiectasis) of the duodenum, jejunum, and mesenteric lymph nodes. Material within dilated lacteals stained positively for Oil Red O and Sudan Black, consistent with lipid. Electron microscopic evaluation confirmed extracellular lipid accumulation within the villar lamina propria, lacteals, and within villar macrophages. Analyses of hepatic and pulmonary CYP1A enzymes demonstrated dose-dependent I3C induction of CYP1A1 and 1A2. B6C3F1 mice orally gavaged ≤250 mg I3C/kg body weight did not demonstrate histopathological changes; however, hepatic CYP induction was similar to that in rats. The histopathologic changes of intestinal lymphangiectasis and lipidosis in this study share similarities with intestinal lymphangiectasia as observed in humans and dogs. However, the resultant clinical spectrum of protein-losing enteropathy was not present.

  14. Impaired ecosystem process despite little effects on populations: modeling combined effects of warming and toxicants.

    Science.gov (United States)

    Galic, Nika; Grimm, Volker; Forbes, Valery E

    2017-08-01

    Freshwater ecosystems are exposed to many stressors, including toxic chemicals and global warming, which can impair, separately or in combination, important processes in organisms and hence higher levels of organization. Investigating combined effects of warming and toxicants has been a topic of little research, but neglecting their combined effects may seriously misguide management efforts. To explore how toxic chemicals and warming, alone and in combination, propagate across levels of biological organization, including a key ecosystem process, we developed an individual-based model (IBM) of a freshwater amphipod detritivore, Gammarus pseudolimnaeus, feeding on leaf litter. In this IBM, life history emerges from the individuals' energy budgets. We quantified, in different warming scenarios (+1-+4 °C), the effects of hypothetical toxicants on suborganismal processes, including feeding, somatic and maturity maintenance, growth, and reproduction. Warming reduced mean adult body sizes and population abundance and biomass, but only in the warmest scenarios. Leaf litter processing, a key contributor to ecosystem functioning and service delivery in streams, was consistently enhanced by warming, through strengthened interaction between the detritivorous consumer and its resource. Toxicant effects on feeding and maintenance resulted in initially small adverse effects on consumers, but ultimately led to population extinction and loss of ecosystem process. Warming in combination with toxicants had little effect at the individual and population levels, but ecosystem process was impaired in the warmer scenarios. Our results suggest that exposure to the same amount of toxicants can disproportionately compromise ecosystem processing depending on global warming scenarios; for example, reducing organismal feeding rates by 50% will reduce resource processing by 50% in current temperature conditions, but by up to 200% with warming of 4 °C. Our study has implications for

  15. Evaluation of toxic and interactive toxic effects of three agrochemicals and copper using a battery of microbiotests.

    Science.gov (United States)

    Kungolos, A; Emmanouil, C; Tsiridis, V; Tsiropoulos, N

    2009-08-01

    Three commonly used test organisms of different trophic levels (Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna) were exposed to selected agrochemicals (fosthiazate, metalaxyl-M, imidacloprid) and copper, in single doses or in binary mixtures. The toxicity of each single compound varied up to two orders of magnitude, depending on the test species examined. V. fischeri was the most sensitive test organism regarding fosthiazate and metalaxyl-M, indicating an IC(50) value of 0.20 mg/L (0.17-0.25 mg/L) and 0.88 mg/L (0.35-1.57 mg/L), respectively. Imidacloprid was the least toxic compound, indicating an EC(50) value on D. magna of 64.6 mg/L (43.3-122.5 mg/L) and an IC(50) value on V. fischeri of 226 mg/L (159-322 mg/L), while for imidacloprid at a concentration of 1000 mg/L the effect on P. subcapitata was lower than 50%. Copper was the most toxic compound towards all test organisms exhibiting the highest toxic effect on P. subcapitata, with an IC(50) value of 0.05 mg/L (0.003-0.008 mg/L). The toxic effects of the binary mixtures have been compared to the theoretically expected effect, resulting from a simple mathematical model based on the theory of probabilities. The independent action model was used in order to predict the theoretically expected effect. The interactive effects were mostly antagonistic or additive, while in few cases (interactive effects of metalaxyl-M and copper on V. fischeri) a synergistic mode of action was observed for some concentration combinations. Experiments showed that interactive effects of chemicals may vary depending on the test species used as well as on the chemicals and their respective concentrations. Although most of the concentrations of chemicals tested in this study are higher than the ones usually found in natural environment, the evaluation of their interactive toxic effects using a battery of bioassays may comprise a useful tool for the estimation of the environmental hazard of chemicals.

  16. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    OpenAIRE

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right p...

  17. Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP.

    Science.gov (United States)

    de Heer, Eric W; Dekker, Jack; van Eck van der Sluijs, Jonna F; Beekman, Aartjan Tf; van Marwijk, Harm Wj; Holwerda, Tjalling J; Bet, Pierre M; Roth, Joost; Hakkaart-Van Roijen, Leona; Ringoir, Lianne; Kat, Fiona; van der Feltz-Cornelis, Christina M

    2013-05-24

    The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This study is a placebo controlled double blind, three armed randomized multi centre trial. Patients with (sub)chronic pain and a depressive disorder are randomized to either a) collaborative care with duloxetine, b) collaborative care with placebo or c) duloxetine alone. 189 completers are needed to attain sufficient power to show a clinically significant effect of 0.6 SD on the primary outcome measures (PHQ-9 score). Data on depression, anxiety, mental and physical health, medication adherence, medication tolerability, quality of life, patient-doctor relationship, coping, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months. This study enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Furthermore, a comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting. Also, this study will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study. Moreover, patients included in this study are screened for pain symptoms, differentiating between nociceptive

  18. Effect Of Environmental Load On The Toxicity Of Bottom Sediments

    Directory of Open Access Journals (Sweden)

    Šestinová Oľga

    2015-06-01

    Full Text Available This study is devoted to Ecotoxicity tests, Terrestrial Plant Test (modification of OECD 208, Phytotoxkit microbiotest on Sinapis alba and chronic tests of Earthworm (Eisenia veneta, modification of OECD Guidelines for the testing of chemicals 317, Bioaccumulation in Terrestrial Oligochaetes on polluted sediments. Earthworms can accelerate the removal of contaminants from soil. The study materials are river sediments, which were obtained from a monitoring station - the Water reservoir the Ružín No.1 particularly, the river Hornád, Hnilec and sample from sludge bed Rudňany. The samples of sediment were used to assess of the potential phytotoxic effect of heavy metals on higher plants. Total mortality was established in earthworms using chronic toxicity test after 7 and 28 exposure days. Based on the phytotoxicity testing, phytotoxic effects of the metals contaminated sediments from the sludge bed Rudňany on S. alba seeds was observed. The largest concentration differences were recorded in the sample R7 after 7 days earthworms exposure. The earthworms mortality was not influenced by sediment neither after 7 nor 28 exposure days The spectra of samples H, HO and R showed broad peak at 1 419 - 1 512 cm−1 characteristic for carbonate radical. In the spectra of the samples (R and R7 the vibration of C-H groups at 2 926 and 2 921 cm−1, respectively were also observed, demonstrating the presence of organic matter. Our research will continue with determination of metals concentration in earthworms.

  19. Do diosgenin ameliorate urinary bladder toxic effect of ...

    African Journals Online (AJOL)

    SWEET

    2012-01-26

    Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

  20. Effects of synthetic and natural toxicants on livestock.

    Science.gov (United States)

    Shull, L R; Cheeke, P R

    1983-07-01

    Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

  1. The influence of single application of paracetamol and/or N-acetylcysteine on rats subchronic exposed to trichloroethylene vapours. I. Effect on hepatic moonooxygenase system dependent of cytochrome P450

    Directory of Open Access Journals (Sweden)

    Andrzej Plewka

    2012-06-01

    Full Text Available Background: There is a number of factors which potentially affect occurrence of toxic change in liver after overdosing of paracetamol. Hepatic metabolism of trichloroethylene has primary impact on hepatotoxic effect of this solvent. This means that the combined exposure to these xenobiotics can be particularly harmful for human. The influence of N-acetylcysteine (NAC as a protective factor after paracetamol intoxication was studies. Materials and method: Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the hepatic microsomal fraction activity of the components of cytochrome P450- dependent monooxygenases was determined Results: Paracetamol slightly stimulated cytochrome P450 having no effect on reductase activity cooperating with it. Cytochrome b5 and its reductase were inhibited by this compound. Trichloroethylene was the inhibitor of compounds of II microsomal electron transport chain. N-acetylcysteine inhibited activity of reductase of NADH-cytochrome b5. Conclusions: Tested doses of the xenobiotics influenced on II microsomal electron transport chain. Protective influence of N-acetylcysteine was better if this compound was applied 2 hours after exposure on xenobiotics

  2. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

  3. Molecular mechanisms of toxic effects of fotemustine in rat hepatocytes and subcellular rat liver fractions.

    NARCIS (Netherlands)

    Brakenhoff, J.P.G.; Commandeur, J.N.M.; Wormhoudt, L.W.; Groot, E.J.; Vermeulen, N.P.E.

    1996-01-01

    Fotemustine is a clinically used DNA-alkylating 2-chloroethyl-substituted N-nitrosourea, which sometimes shows signs of haematotoxicity and reversible liver and renal toxicity as toxic side-effects. Mechanistic data on these side-effects are scarce and incomplete. In this study, firstly the

  4. Toxic effects of isoproturon on periphyton communities a microcosm study

    Science.gov (United States)

    Schmitt-Jansen, Mechthild; Altenburger, Rolf

    2005-02-01

    Coastal and estuarine ecosystems are increasingly exposed to herbicide contamination. To study the potential risks of these pollutants, the establishment of periphyton communities under exposure of a concentration series of isoproturon in a range of 0.0024-0.312 mg L -1 was investigated in a microcosm study. After two weeks of growth, chronic effects on biomass development, measured as Chl a fluorescence, taxonomic composition and photosynthetic capacity of PS II of attached microalgae were analysed using a pulse-amplitude modulated (PAM) fluorescence-based method. Algal classes were differentiated according to their pigment systems using four excitation wavelengths. Biomass remained constant up to pre-exposure concentrations of 0.02 mg L -1 isoproturon but decreased within one order of magnitude at the highest test concentration. Algal classes shifted from diatoms to chlorophytes at pre-exposure concentrations of 0.02-0.39 mg L -1. Community structure of diatoms representing the dominant group of attached algae at lower test concentrations was studied by microscopic analysis revealing that species numbers were highest at lowest test concentrations as compared to controls. At higher test concentrations Navicula halophila dominated with 89% of the diatom biomass but was abnormally shaped. Pollution-induced community tolerance (PICT) of periphyton to isoproturon was determined by short-term inhibition tests of photosynthesis. Pre-exposed communities increased their effect concentrations (EC 50) up to threefold within the 0.039 mg L -1 pre-treatment. Our results suggest that attached microalgal communities have a high potential of tolerance development to isoproturon at lower levels of contamination due to the replacement of sensitive species by more tolerant algae, although these species seemed to be affected too. We conclude that herbicide concentrations in river basins, estuaries or coastal zones may change community structure and primary production of

  5. Effect of Microbial inoculation in combating the aluminium toxicity effect on growth of Zea mays.

    Science.gov (United States)

    Arora, P; Singh, G; Tiwari, A

    2017-07-31

    The present study is aimed at improving the aluminium tolerance in maize crop employing the potential of microbial inoculants in conferring resistance to these toxicities via production of certain chelating compounds like siderophores, exopolysachharides and organic acids. Acid soils have now-a-days become one of the key factors for limiting growth of many agriculturally important crops. Aluminium  is one of the major elements present in acid soils and is mainly responsible for toxicity in the soil. This aluminium is rapidly soluble in soil water and hence absorbed by plant roots under conditions where soil pH is below 5. This toxicity leads to severe root growth inhibition, thereby limiting the production of maize crops. It was observed that use of microbial inoculums can be helpful in elimination of these toxic compounds and prevent the inhibition of root growth . It was found that the soils contaminated with aluminium toxicity decreased the root length of maize plant significantly by 65% but Bacillus and Burkholderia inoculation increased this root length significantly by 1.4- folds and 2- folds respectively thereby combating the effect of aluminium toxicity. Aluminium concentration was found maximum in roots of plants which were grown under aluminium stress condition. But this aluminium accumulation decreased ̴ 2-folds when Burkholderia was used as seed inoculants under aluminium stress conditions. Also, at 60mM aluminium accumulation, phosphorus solubilisation in roots was found to be increased upto 30% on Burkholderia inoculation. However, Bacillus inoculation didn't show any significant difference in either of the case. Thus, the inoculation of seeds with Burkholderia isolates could prove to be a boon in sequestering aluminium toxicity in Zea mays.

  6. Subchronic mycotoxicoses in rats. Histopathological changes and modulation of the sphinganine to sphingosine (Sa/So) ratio imbalance induced by Fusarium verticillioides culture material, due to the coexistence of aflatoxin B1 in the diet.

    Science.gov (United States)

    Theumer, M G; López, A G; Aoki, M P; Cánepa, M C; Rubinstein, H R

    2008-03-01

    Mycotoxicoses are diseases caused by consumption of diets contaminated with mycotoxins, a special class of fungal secondary metabolites. Fumonisin B1 (FB1) and aflatoxin B1 (AFB1), the main toxins synthesized by toxicogenic stocks of Fusarium spp. and Aspergillus spp., respectively, can coexist in grains and in its by-products. We investigated a probable synergism of a fumonisins-containing Fusarium verticillioides culture material and AFB1 in the induction of hepatocyte apoptosis in rats subchronically fed on a mixture of them. Furthermore, the possibility of modifications in the fumonisins-induced Sa/So ratio imbalance in tissues and urine from rats poisoned with this mycotoxin, due to the presence of AFB1 in the diet, was evaluated. The co-exposure to fumonisins and AFB1 produced a higher liver toxicity, with respect to their individual administration, inducing apoptosis and mitotic hepatocytes. There was an inversion of the typical Sa/So ratio in rats fed on the culture material as well as in those subjected to a diet co-contamined with fumonisins and AFB1. Moreover, the later had a synergistic effect in the induction of Sa/So variations in kidneys. Therefore, the mixture of fumonisins and AFB1 induced toxic responses which could not be considered a sum of the effects caused individually by these mycotoxins.

  7. Past, present and emerging toxicity issues for jet fuel.

    Science.gov (United States)

    Mattie, David R; Sterner, Teresa R

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Effects-driven chemical fractionation of heavy fuel oil to isolate compounds toxic to trout embryos.

    Science.gov (United States)

    Bornstein, Jason M; Adams, Julie; Hollebone, Bruce; King, Thomas; Hodson, Peter V; Brown, R Stephen

    2014-04-01

    Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic. © 2013 SETAC.

  9. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Effects of toxic metals and chemicals on biofilm and biocorrosion.

    Science.gov (United States)

    Fang, Herbert H P; Xu, Li-Chong; Chan, Kwong-Yu

    2002-11-01

    Microbes in marine biofilms aggregated into clusters and increased the production of extracellular polymeric substances (EPS), by over 100% in some cases, when the seawater media containing toxic metals and chemicals, such as Cd(II), Cu(II), Pb(II), Zn(II), AI(III), Cr(III), glutaraldehyde, and phenol. The formation of microbial cluster and the increased production of EPS, which contained 84-92% proteins and 8-16% polysaccharides, accelerated the corrosion of the mild steel. However, there was no quantitative relationship between the degree of increased corrosion and the toxicity of metals/chemicals towards sulfate-reducing bacteria, or the increased EPS production.

  11. Introducing Toxics

    OpenAIRE

    David C. Bellinger

    2013-01-01

    With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present ...

  12. Acute toxicity effects of the aqueous leaf extract of Anogeissus ...

    African Journals Online (AJOL)

    Using the intraperitoneal route, the rats showed dose-dependent signs of toxicity ranging from inappetence, depression, unsteady gait, tremors, and respiratory distress to death. The I/P LD50 was 1400 mg/kg body weight. No gross changes were observed in the organs of rats that died following extract administration.

  13. Protective effect of zinc over lead toxicity on testes

    International Nuclear Information System (INIS)

    Rafique, M.; Shaikh, S.P.; Tahir, F.

    2010-01-01

    To determine the effects of lead and zinc on testes. Study Design: Randomized control trial. Place and Duration of Study: Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, from August 2003 to December 2005. Methodology: Sixty adult (90 days old) albino rats were obtained from animal house JPMC for the study and divided into 3 groups. Group A received injection normal saline 1 cc intraperitoneally daily for 8 weeks. Group B received lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily. Group C received zinc chloride in a dose of 1 mg/kg body weight before half an hour of injection of lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily so that to provide pre-treatment. On the day of completion of treatment the animals were sacrificed testes removed and fixed in Bouin's fluid. Testes were dehydrated in the ascending strength of alcohol, 5 mu m thick sections were cut and stained with PAS Iron Hematoxylin. Student's t-test was used for statistical analysis with significance at p < 0.05. Results: The mean diameter of seminiferous tubule was 291.91+-1.18, 198.53 +- 1.67 and 288.77 +- 1.11 mu m in groups A, B and C respectively. Diameter of seminiferous tubules decreased by 31.99% in group B (p < 0.001; CI 89.023 to 97.736) as compared group A and while group B comparing with group C, the diameter of seminiferous tubules was decreased by 31.25% (p-value = 0.076; CI -94.264 to -86.203). Mean thickness of germinal epithelium was 96.19 +- 1.01, 50.69 +- 1.20 and 94.94 +- 0.54 mu m in groups A, B and C respectively. Thickness of germinal epithelium decreased by 47.30 in group B (P < 0.001; CI 42.503 to 48.496) as compared to group A and while comparing group B with group C, the thickness of germinal epithelium was decreased by 46.61% (p=-44.25; CI -46.704 to -41.787). Conclusion: Zinc prevented toxic effects of lead on germinal epithelium in the albino rats. (author)

  14. In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves.

    Science.gov (United States)

    Fonseca, Aldilane Gonçalves; Ribeiro Dantas, Luzia Leiros Sena Fernandes; Fernandes, Júlia Morais; Zucolotto, Silvana Maria; Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira; Rocha, Hugo Alexandre Oliveira; Lemos, Telma Maria Araújo Moura

    2018-01-01

    The species Kalanchoe brasiliensis , known as "Saião , " has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis . The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo , the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

  15. In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae Leaves

    Directory of Open Access Journals (Sweden)

    Aldilane Gonçalves Fonseca

    2018-01-01

    Full Text Available The species Kalanchoe brasiliensis, known as “Saião,” has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis. The action of the extract (concentrations from 0.1 to 1000 uL/100 uL in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal and 786-0 (kidney carcinoma, showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo, the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

  16. Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia

    DEFF Research Database (Denmark)

    Løhmann, Ditte J A; Abrahamsson, Jonas; Ha, Shau-Yin

    2016-01-01

    Treatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first...

  17. How might selenium moderate the toxic effects of mercury in stream fish of the Western USA?

    Science.gov (United States)

    The ability of selenium (Se) to moderate mercury (Hg) toxicity is well established in the literature. Mercury exposures that might otherwise produce toxic effects are counteracted by Se, particularly when Se:Hg molar ratios approach or exceed 1. We analyzed whole body Se and Hg c...

  18. Toxic effects of formalin-treated cadaver on medical students, staff ...

    African Journals Online (AJOL)

    Background: Formaldehyde can be toxic, allergenic and carcinogenic. Evaporation of formaldehyde from formalin-treated cadavers in the anatomy dissection rooms can produce high exposure. This study was conducted to assess acute and chronic toxic effects of formalin-treated cadavers on medical students, staff ...

  19. Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats.

    Science.gov (United States)

    Toscano, Cindy Medici; Simões, Maylla Ronacher; Alonso, Maria Jesus; Salaices, Mercedes; Vassallo, Dalton Valentim; Fioresi, Mirian

    2017-07-01

    Lead is considered a causative factor for hypertension and other cardiovascular diseases. To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β 1 -adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days. Blood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β 1 -adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process. These findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys.

    Science.gov (United States)

    Benlasher, Emad; Geng, Xiuyu; Nguyen, Ngoc Thanh Xuan; Tardieu, Didier; Bailly, Jean-Denis; Auvergne, Alain; Guerre, Philippe

    2012-03-01

    Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.

  1. The molecular basis of simple relationships between exposure concentration and toxic effects with time.

    Science.gov (United States)

    Tennekes, Henk A; Sánchez-Bayo, Francisco

    2013-07-05

    Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure. Empirical evidence demonstrates that the Druckrey-Küpfmüller toxicity model, which was validated for chemical carcinogens in the early 1960s, is also applicable to a wide range of toxic compounds in ecotoxicology. According to this model, the character of a poison is primarily determined by the reversibility of critical receptor binding. Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure, and whenever the effects are also irreversible (e.g. death) they are reinforced over time; these chemicals have time-cumulative toxicity. Compounds having non-specific receptor binding, or involving slowly reversible binding to some receptors that do not contribute to toxicity, may also be time-dependent; however, their effects depend primarily on the exposure concentration, with time playing a minor role. Consequently, the mechanism of toxic action has important implications for risk assessment. Traditional risk approaches cannot predict the impacts of toxicants with time-cumulative toxicity in the environment. New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment. An example is shown to explain how the risk of time-dependent toxicants is underestimated when using current risk assessment protocols. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. ALUMINUM TOXICITY VS SALICYLIC ACID EFFECTS IN PEARL MILLET METHYLOME.

    OpenAIRE

    Baba Ngom; Edward Mamati; Ibrahima Sarr; Josphert Kimatu.

    2018-01-01

    Aluminum toxicity is one of most distributed plant abiotic stress in the world, causing root inhibition and therefore crop losses. Plants continuously adapt its defense to abiotic stresses through different mechanisms including DNA methylation. The methylome variation is influenced by external cues from environment or by hormonal signals. Salicylic acid is one of the most important hormones in plants, directing growth and defense. Its application is seen having the capacity to elicit plant de...

  3. Benzimidazole for the prevention of toxic effects of air pollutants on plants

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, I; Fukuda, M; Kitano, H; Shinohara, T

    1974-02-02

    Tobacco plants were sprayed with benzimidazole before being exposed to 30 ppM of photochemical oxidants for a period of two hours. The plants were observed 48 hours after exposure and found to have suffered no toxic effects from the oxidants. It may be concluded that benzimidazole is an effective agent for preventing the toxic effects of air pollutants, such as photochemical oxidants on plants.

  4. Toxic effects of combined effects of anthracene and UV radiation on Brachionus plicatilis

    Science.gov (United States)

    Gao, Ceng; Zhang, Xinxin; Xu, Ningning; Tang, Xuexi

    2017-05-01

    Anthracene is a typical polycyclic aromatic hydrocarbon, with photo activity, can absorb ultraviolet light a series of chemical reactions, aquatic organisms in the ecosystem has a potential light induced toxicity. In this paper, the effects of anthracene and UV radiation on the light-induced toxicity of Brachionus plicatilis were studied. The main methods and experimental results were as follows: (1) The semi-lethal concentration of anthracene in UV light was much lower than that in normal light, The rotifers have significant light-induced acute toxicity. (2) Under UV irradiation, anthracene could induce the increase of ROS and MDA content in B. plicatilis, and the activity of antioxidant enzymes in B. plicatilis significantly changed, Where SOD, GPx activity was induced within 24 hours of the beginning of the experiment. And the content of GPX and CAT was inhibited after 48 hours. Therefore, the anthracite stress induced by UV radiation could more strongly interfere with the ant oxidative metabolism of B. plicatilis, and more seriously cause oxidative damage, significant light-induced toxicity.

  5. The Effect of Digestive Capacity on the Intake Rate of Toxic and Non-Toxic Prey in an Ecological Context.

    Directory of Open Access Journals (Sweden)

    Thomas Oudman

    Full Text Available Digestive capacity often limits food intake rate in animals. Many species can flexibly adjust digestive organ mass, enabling them to increase intake rate in times of increased energy requirement and/or scarcity of high-quality prey. However, some prey species are defended by secondary compounds, thereby forcing a toxin limitation on the forager's intake rate, a constraint that potentially cannot be alleviated by enlarging digestive capacity. Hence, physiological flexibility may have a differential effect on intake of different prey types, and consequently on dietary preferences. We tested this effect in red knots (Calidris canutus canutus, medium-sized migratory shorebirds that feed on hard-shelled, usually mollusc, prey. Because they ingest their prey whole and crush the shell in their gizzard, the intake rate of red knots is generally constrained by digestive capacity. However, one of their main prey, the bivalve Loripes lucinalis, imposes a toxin constraint due to its symbiosis with sulphide-oxidizing bacteria. We manipulated gizzard sizes of red knots through prolonged exposure to hard-shelled or soft foods. We then measured maximum intake rates of toxic Loripes versus a non-toxic bivalve, Dosinia isocardia. We found that intake of Dosinia exponentially increased with gizzard mass, confirming earlier results with non-toxic prey, whereas intake of Loripes was independent of gizzard mass. Using linear programming, we show that this leads to markedly different expected diet preferences in red knots that try to maximize energy intake rate with a small versus a large gizzard. Intra- and inter-individual variation in digestive capacity is found in many animal species. Hence, the here proposed functional link with individual differences in foraging decisions may be general. We emphasize the potential relevance of individual variation in physiology when studying trophic interactions.

  6. Toxic effect of metal cation binary mixtures to the seaweed Gracilaria domingensis (Gracilariales, Rhodophyta).

    Science.gov (United States)

    Mendes, Luiz Fernando; Stevani, Cassius Vinicius; Zambotti-Villela, Leonardo; Yokoya, Nair Sumie; Colepicolo, Pio

    2014-01-01

    The macroalga Gracilaria domingensis is an important resource for the food, pharmaceutical, cosmetic, and biotechnology industries. G. domingensis is at a part of the food web foundation, providing nutrients and microelements to upper levels. As seaweed storage metals in the vacuoles, they are considered the main vectors to magnify these toxic elements. This work describes the evaluation of the toxicity of binary mixtures of available metal cations based on the growth rates of G. domingensis over a 48-h exposure. The interactive effects of each binary mixture were determined using a toxic unit (TU) concept that was the sum of the relative contribution of each toxicant and calculated using the ratio between the toxicant concentration and its endpoint. Mixtures of Cd(II)/Cu(II) and Zn(II)/Ca(II) demonstrated to be additive; Cu(II)/Zn(II), Cu(II)/Mg(II), Cu(II)/Ca(II), Zn(II)/Mg(II), and Ca(II)/Mg(II) mixtures were synergistic, and all interactions studied with Cd(II) were antagonistic. Hypotheses that explain the toxicity of binary mixtures at the molecular level are also suggested. These results represent the first effort to characterize the combined effect of available metal cations, based on the TU concept on seaweed in a total controlled medium. The results presented here are invaluable to the understanding of seaweed metal cation toxicity in the marine environment, the mechanism of toxicity action and how the tolerance of the organism.

  7. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

    OpenAIRE

    Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

    2012-01-01

    This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after...

  8. Toxicity and health effects of vehicle emissions in Shanghai

    Science.gov (United States)

    Ye, Shun-Hua; Zhou, Wei; Song, Jian; Peng, Bao-Cheng; Yuan, Dong; Lu, Yuan-Ming; Qi, Ping-Ping

    In China, the number of vehicles is increasing rapidly with the continuous development of economy, and vehicle emission pollution in major cities is more serious than ever. In this article, we summarized the results of a series of short-term assays, animal experiments and epidemiology investigations on the genotoxicity, immunotoxicity, respiratory toxicity and health effects of vehicle emissions in Shanghai, including gasoline exhausts (gas condensate and particles), diesel exhaust particles (DEP) and scooter exhaust particles (SEP). The results showed that: (1) Both gases and particulate phases of the exhausts of different kinds of vehicles showed strong mutagenicity in Ames test (TA98 and TA100 strains), rat hepatocyte unscheduled DNA synthesis (UDS) assay, and mouse micronucleus assay, and vehicle emissions could induce the transformation of Syrian hamster embryo (SHE) cells. DEP and SEP could induce the transformation of human diploid cell strain (KMB-13) cells, immunohistochemistry assay showed that c-myc and p21 proteins were highly expressed in the transformed cells. DEP and SEP could also inhibit the gap junctional intercellular communication (GJIC) of BALB/C3T3 cells (2) Vehicle emissions could decrease the number of macrophages in the lung (bronchial alveolar lavage fluid) (BALF) of male SD rats. Vehicle emissions could also increase the proportion of polymorphonuclear leukocytes (PMN), the content of cetyneuraminic acid (NA), the activity of lactate dehydrogenase (LDH), alkali phosphate (AKP), acid phosphate (ACP) in the lung BALF of the animals. (3) In epidemiology investigation, the proportion of those who have respiratory symptoms and chronic obstructive pulmonary diseases (COPD) in the workers who were exposed to DEP ( n=806) were much higher than those of the controls ( n=413). The OR (odd ratio) values of angina, nasal obstruction, phlegm, short of breath and COPD were 2.27, 3.08, 3.00, 3.19 and 2.32, respectively, and the proportion of those who

  9. Toxicity and health effects of vehicle emissions in Shanghai

    Energy Technology Data Exchange (ETDEWEB)

    Shunhua Ye; Wei Zhou; Jian Song; Baocheng Peng; Dong Yuan; Yuanming Lu; Pingping Qi [Shanghai Medical University (China). Dept. of Environmental Health

    2000-07-01

    In China, the number of vehicles is increasing rapidly with the continuous development of economy, and vehicle emission pollution in major cities is more serious than ever. In this article, we summarized the results of a series of short-term assays, animal experiments and epidemiology investigations on the genotoxicity, immunotoxicity, respiratory toxicity and health effects of vehicle emissions in Shanghai, including gasoline exhausts (gas condensate and particles), diesel exhaust particles (DEP) and scooter exhaust particles (SEP). The results showed that: (1) Both gases and particulate phases of the exhausts of different kinds of vehicles showed strong mutagenicity in Ames test (TA98 and TA100 strains), rat hepatocyte unscheduled DNA synthesis (UDS) assay, and mouse micronucleus assay, and vehicle emissions could induce the transformation of Syrian hamster embryo (SHE) cells. DEP and SEP could induce the transformation of human diploid cell strain (KMB-13) cells, immunohistochemistry assay showed that c-myc and p21 proteins were highly expressed in the transformed cells. DEP and SEP could also inhibit the gap junctional intercellular communication (GJIC) of BALB/C3T3 cells (2) Vehicle emissions could decrease the number of macrophages in the lung (bronchial alveolar lavage fluid) (BALF) of male SD rats. Vehicle emissions could also increase the proportion of polymorphonuclear leukocytes (PMN), the content of cetyneuraminic acid (NA), the activity of lactate dehydrogenase (LDH), alkali phosphate (AKP), acid phosphate (ACP) in the lung BALF of the animals. (3) In epidemiology investigation, the proportion of those who have respiratory symptoms and chronic obstructive pulmonary diseases (COPD) in the workers who were exposed to DEP (n = 806) were much higher than those of the controls (n = 413). The OR (odd ratio) values of angina, nasal obstruction, phlegm, short of breath and COPD were 2.27, 3.08, 3.00, 3.19 and 2.32, respectively, and the proportion of those who

  10. Hematotoxicity and genotoxicity of mercuric chloride following subchronic exposure through drinking water in male rats.

    Science.gov (United States)

    Boujbiha, Mohamed Ali; Ben Salah, Ghada; Ben Feleh, Abdelraouf; Saoudi, Mongi; Kamoun, Hassen; Bousslema, Ali; Ommezzine, Asma; Said, Khaled; Fakhfakh, Faiza; El Feki, Abdelfattah

    2012-07-01

    Erythrocytes are a convenient model to understand the subsequent oxidative deterioration of biological macromolecules in metal toxicities. The present study examined the variation of hematoxic and genotoxic parameters following subchronic exposure of mercuric chloride via drinking water and their possible association with oxidative stress. Male rats were exposed to 50 ppm (HG1) and 100 ppm (HG2) of mercuric chloride daily for 90 days. A significant dose-dependent decrease was observed in red blood cell count, hemoglobin, hematocrit, and mean cell hemoglobin concentration in treated groups (HG1 and HG2) compared with controls. A significant dose-dependent increase was observed in lipid peroxidation; therefore, a significant variation was found in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, mercuric chloride treatment showed a significant dose-dependent increase in frequency of total chromosomal aberration and in percentage of aberrant bone marrow metaphase of treated groups (p mercury treatment may be the major cause for chromosomal aberration as free radicals lead to DNA damage. These data will be useful in screening the antioxidant activities of natural products, which may be specific to the bone marrow tissue.

  11. Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

    Science.gov (United States)

    Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

    2009-07-01

    The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L.

  12. Webinar Presentation: Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?

    Science.gov (United States)

    This presentation, Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Food and Children's Health held on Dec. 9, 2015.

  13. Specific toxic effect of dinoflagellate Heterocapsa circularisquama on the rotifer Brachionus plicatilis.

    Science.gov (United States)

    Kim, D; Sato, Y; Oda, T; Muramatsu, T; Matsuyama, Y; Honjo, T

    2000-12-01

    Heterocapsa circularisquama (Dinophyceae), a noxious red tide dinoflagellate, is known to have a specifically lethal effect on shellfish, especially bivalves such as pearl oyster (Pinctada fucata), but no detrimental effects of this alga on fishes have not been observed so far. In this study, we found that H. circularisquama was toxic to a microzooplankton, a rotifer (Brachionus plicatilis) in a cell concentration-dependent manner, while the cultured supernatant or ultrasonic ruptured H. circularisquama had no significant toxic effect on the rotifer. Since no such toxic effects on the rotifer were observed in Chattonella marina, Heterosigma akashiwo, or Cochlodinium polykrikoides, other species of harmful red tide plankton, H. circularisquama may have a strictly specific toxic mechanism against the rotifer as well as bivalves.

  14. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

    2011-01-01

    BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving

  15. Webinar Presentation: Epidemiologic Studies of the Effects of Toxic Exposures on Brain and Behavior: Neuropsychological Assessment

    Science.gov (United States)

    This presentation, Epidemiologic Studies of the Effects of Toxic Exposures on Brain and Behavior: Neuropsychological Assessment, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Interdisciplinary Approaches to Neurodevelopment.

  16. In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves

    Directory of Open Access Journals (Sweden)

    Cheng-Zhang Wang

    2015-12-01

    Full Text Available Polyprenols of Ginkgo biloba L. leaves (GBP are a new type of lipid with 14–24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt. Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 μg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2 on the four standard Salmonella strains (p > 0.05 in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats’ organ weight and the ratio of viscera

  17. Use of passive samplers for improving oil toxicity and spill effects assessment

    International Nuclear Information System (INIS)

    Letinski, Daniel; Parkerton, Thomas; Redman, Aaron; Manning, Ryan; Bragin, Gail; Febbo, Eric; Palandro, David; Nedwed, Tim

    2014-01-01

    Highlights: • Methods to quantify dissolved hydrocarbons needed to link oil exposures to toxicity. • Solid phase microextraction (SPME) fibers used to measure dissolved hydrocarbons. • SPME results reliably predicted acute toxicity for range of dispersed oils. • Oil droplets and chemical dispersant did not significantly contribute to toxicity. • SPME analysis improves oil exposure assessment in lab and field studies. - Abstract: Methods that quantify dissolved hydrocarbons are needed to link oil exposures to toxicity. Solid phase microextraction (SPME) fibers can serve this purpose. If fibers are equilibrated with oiled water, dissolved hydrocarbons partition to and are concentrated on the fiber. The absorbed concentration (C polymer ) can be quantified by thermal desorption using GC/FID. Further, given that the site of toxic action is hypothesized as biota lipid and partitioning of hydrocarbons to lipid and fibers is well correlated, C polymer is hypothesized to be a surrogate for toxicity prediction. To test this method, toxicity data for physically and chemically dispersed oils were generated for shrimp, Americamysis bahia, and compared to test exposures characterized by C polymer . Results indicated that C polymer reliably predicted toxicity across oils and dispersions. To illustrate field application, SPME results are reported for oil spills at the Ohmsett facility. SPME fibers provide a practical tool to improve characterization of oil exposures and predict effects in future lab and field studies

  18. The effects of characteristics of substituents on toxicity of the nitroaromatics: HiT QSAR study

    Science.gov (United States)

    Kuz'min, Victor E.; Muratov, Eugene N.; Artemenko, Anatoly G.; Gorb, Leonid; Qasim, Mohammad; Leszczynski, Jerzy

    2008-10-01

    The present study applies the Hierarchical Technology for Quantitative Structure-Activity Relationships (HiT QSAR) for (i) evaluation of the influence of the characteristics of 28 nitroaromatic compounds (some of which belong to a widely known class of explosives) as to their toxicity; (ii) prediction of toxicity for new nitroaromatic derivatives; (iii) analysis of the effects of substituents in nitroaromatic compounds on their toxicity in vivo. The 50% lethal dose concentration for rats (LD50) was used to develop the QSAR models based on simplex representation of molecular structure. The preliminary 1D QSAR results show that even the information on the composition of molecules reveals the main tendencies of changes in toxicity. The statistic characteristics for partial least squares 2D QSAR models are quite satisfactory ( R 2 = 0.96-0.98; Q 2 = 0.91-0.93; R 2 test = 0.89-0.92), which allows us to carry out the prediction of activity for 41 novel compounds designed by the application of new combinations of substituents represented in the training set. The comprehensive analysis of toxicity changes as a function of substituent position and nature was carried out. Molecular fragments that promote and interfere with toxicity were defined on the basis of the obtained models. It was shown that the mutual influence of substituents in the benzene ring plays a crucial role regarding toxicity. The influence of different substituents on toxicity can be mediated via different C-H fragments of the aromatic ring.

  19. Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

    OpenAIRE

    Hodges, A.B; Ladenheim, B; McCoy, M.T; Beauvais, G; Cai, N; Krasnova, I.N; Cadet, J.L

    2011-01-01

    Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dos...

  20. Toxicity of middle distillates from dermal exposure.

    Science.gov (United States)

    Koschier, F J

    1999-02-01

    /developmental toxicity (OECD Guideline 421) or neurotoxicity (TSCA Guidelines on subchronic inhalation and neurotoxicity studies). These studies demonstrated that the highest dose level of kerosine does not induce reproductive/developmental or neurotoxicity effects by skin exposure in rodent studies. The dermal NOEL for HDS kerosine in rats was > or = 494 mg/kg for both neurotoxicity, and reproductive/developmental toxicity.

  1. Mobility, bioavailability, and toxic effects of cadmium in soil samples

    International Nuclear Information System (INIS)

    Prokop, Z.; Cupr, P.; Zlevorova-Zlamalikova V.; Komarek, J.; Dusek, L.; Holoubek, I.

    2003-01-01

    Total concentration is not a reliable indicator of metal mobility or bioavailability in soils. The physicochemical form determines the behavior of metals in soils and hence the toxicity toward terrestrial biota. The main objectives of this study were the application and comparison of three approaches for the evaluation of cadmium behavior in soil samples. The mobility and bioavailability of cadmium in five selected soil samples were evaluated using equilibrium speciation (Windermere humic aqueous mode (WHAM)), extraction procedures (Milli-Q water, DMSO, and DTPA), and a number of bioassays (Microtox, growth inhibition test, contact toxicity test, and respiration). The mobility, represented by the water-extractable fraction corresponded well with the amount of cadmium in the soil solution, calculate using the WHAM (r 2 =0.96, P<0.001). The results of the ecotoxicologica evaluation, which represent the bioavailable fraction of cadmium, correlated well with DTPA extractability and also with the concentration of free cadmium ion, which is recognized as the most bioavailable metal form. The results of the WHAM as well as the results of extraction experiments showed a strong binding of cadmium to organic matter and a weak sorption of cadmium to clay minerals

  2. Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Praveen Kumar

    2014-01-01

    Full Text Available Withania somnifera (Ashwagandha, also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM resulted in normalization of glial fibrillary acidic protein (GFAP expression as well as heat shock protein (HSP70, mortalin, and neural cell adhesion molecule (NCAM expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx levels, catalase, and superoxide dismutase (SOD but not reduced glutathione (GSH contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

  3. Inflammatory effects of the toxic cyanobacterium Geitlerinema amphibium.

    Science.gov (United States)

    Dogo, Camila Ranzatto; Bruni, Fernanda Miriane; Elias, Fabiana; Rangel, Marisa; Pantoja, Patricia Araujo; Sant'anna, Célia Leite; Lima, Carla; Lopes-Ferreira, Monica; de Carvalho, Luciana Retz

    2011-11-01

    Toxic cyanobacteria in public water reservoirs may cause severe health issues for livestock and human beings. Geitlerinema amphibium, which is frequently found in São Paulo City's drinking water supplies, showed toxicity in the standard mouse bioassay, while displaying signs of intoxication and post-mortem findings different from those showed by animals intoxicated by known cyanotoxins. We report here the alterations caused by G. amphibium methanolic extract on mouse microcirculatory network, as seen by in vivo intravital microscopy, besides observations on leukocyte migration, cytokine quantitation, and results of toxicological essays. Our data showed that G. amphibium methanolic extract displayed time- and dose-dependent pro-inflammatory activity, and that at lower doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling, caused partial venular stasis, as well as induced an increase in leukocyte counts in the peripheral blood and peritoneal washings. At higher doses (500 and 1000 mg/kg b.w.), the extract caused ischemic injury leading to animal death. As confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium methanolic extract did not contain lipopolysaccharides. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Toxic effects of pesticide mixtures at a molecular level: Their relevance to human health

    International Nuclear Information System (INIS)

    Hernández, Antonio F.; Parrón, Tesifón; Tsatsakis, Aristidis M.; Requena, Mar; Alarcón, Raquel; López-Guarnido, Olga

    2013-01-01

    Highlights: ► Toxic effects of pesticide mixtures can be independent, dose addition or interaction. ► Metabolic interactions involve inhibition or induction of detoxifying enzymes. ► Organophosphates can potentiate pyrethroid, carbaryl and triazine toxicity. ► Synergism occurs when two active pesticides elicit greater than additive toxicity. ► Endocrine disruptors have the potential for additivity rather than synergism. - Abstract: Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the

  5. Discrimination of uranium chemo-toxic and radio-toxic effects: definition of biological markers for evaluating professional risks in nuclear industry

    International Nuclear Information System (INIS)

    Darolles, Carine

    2010-01-01

    Uranium (U) is a heavy metal that is also considered as an alpha emitter. Thus the origin of U toxicity is both chemical and radiological. The identification of bio-markers to discriminate chemical and radiological toxicity for a given U compound is required to assess accurately the health effects of isotopic mixtures such as depleted U in 235 U with a low specific activity. Data from the literature show that the best candidates are cytogenetic markers. In the present work, the assessment of bio-markers of U contamination was performed on three cellular models (mouse fibroblasts, rat lymphocytes and human lymphocytes) that were exposed to different isotopic mixtures of U. The cytokinesis-block micronucleus (MN) centromere assay was performed to discriminate the chemo-toxic and radio-toxic effects of U. This study showed that the evaluation of micronuclei in bi-nucleated cells could not assess U genotoxicity accurately. Instead, the assessment of centromere-negative micronuclei and nucleo-plasmic bridges correlated with the radio-toxic effects of U. The evaluation of centromere-positive micronuclei and micronuclei in mono-nucleated cells correlated with the chemo-toxic effects of U. These cytogenetic markers should be validated on different biological models and could be proposed to discriminate radiological and chemical toxicity of a given isotopic mixture of U. These four cytogenetic markers could be a useful complement of the classical dosimetric bio-markers for the assessment of internal uranium contamination. (author)

  6. E-submission Format for Sub-chronic and Chronic Studies

    Science.gov (United States)

    The purpose of this document is to suggest the format for final reports and to provide instructions for creation of Adobe PDF electronic submission documents for electronic submission of sub-chronic and chronic studies for pesticides.

  7. Chronic uranium exposure and growth toxicity for phytoplankton. Dose-effect relationship: first comparison of chemical and radiological toxicity

    International Nuclear Information System (INIS)

    Gilbin, R.; Pradines, C.; Garnier-Laplace, J.

    2004-01-01

    The bioavailability of uranium for freshwater organisms, as for other dissolved metals, is closely linked to chemical speciation in solution (U aqueous speciation undergoes tremendous changes in the presence of ligands commonly found in natural waters e.g. carbonate, phosphate, hydroxide and natural organic matter). For the studied chemical domain, short-term uranium uptake experiments have already shown that the free uranyl ion concentration [UO 2 2+ ] is a good predictor of uranium uptake by the green algae Chlamydomonas reinhardtii, as predicted by the Free Ion Activity Model. In agreement with these results, acidic pH and low ligands concentrations in water enhance uranium bioavailability and consequently its potential chronic effects on phytoplankton. Moreover, uranium is known to be both radio-toxic and chemo-toxic. The use of different isotopes of uranium allows to expose organisms to different radiological doses for the same molar concentration: e.g. for a given element concentration (chemical dose), replacing depleted U by U-233 obviously leads to an enhanced radiological delivered dose to organisms (x10 4 ). In this work we established relationships between uranium doses (depleted uranium and 233-U ) and effect on the growth rate of the green algae Chlamydomonas reinhardtii. Uranium bioaccumulation was also monitored. Growth rate was measured both in classical batch (0-72 hrs) and continuous (turbidostat) cultures, the latter protocol allowing medium renewal to diminish exudates accumulation and speciation changes in the medium. The differences in effects will be, if possible, related to the development of defence mechanisms against the formation of reactive oxygen species (forms of glutathione) and the production of phyto-chelatins (small peptides rich in cystein that play an important role in the homeostasis and the detoxication of metals in cells). (author)

  8. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats

    NARCIS (Netherlands)

    Jonker, D.; Kuper, C.F.; Fraile, N.; Estrella, A.; Rodríguez Otero, C.

    2003-01-01

    Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal

  9. Investigations with beagles about toxicity and radioprotective effect of the chemical radioprotection substance WR 2721

    International Nuclear Information System (INIS)

    Wagner, M.; Sedlmeier, H.; Wustrow, T.; Messerschmidt, O.

    1980-01-01

    The toxicity of the chemical radioprotection substance WR 2721 (S-2-(3-aminopropylamino)ethyl-thiophosphate) was examined in 25 beagles. The study showed that the toxicity of the substance increases as the dose gets higher. Between the doses 200 and 250 mg/kg of body weight, the increase of toxicity was significantly greater than could be expected on the basis of the dose difference. Until a dose of 200 mg/kg, the authors found no side effects which would have disturbed vital functions, but higher doses led to marked symptoms of intoxication. (orig.) [de

  10. Effectiveness and Mechanisms of Antagonism of Toxic Effects of Cyanide by Alpha-Keto Acids.

    Science.gov (United States)

    1986-12-31

    until the miss-w near death. Lethal blood levels of cyanide in alpha-KG treated animl. as levels of 5-7 mcg cyani0e, which so 5-7 times the expected...lethal levels . rwm these studies, alpha-KC is effettive in antagonising administered dos of CH of five time the lethal dose before the toxic effects are...parameters in the dog .................. 26 Table 6 The effects of cyanide on 2,3 diphosphoglyceric acid .......... 28 Table 7 Stability of solution of ci

  11. Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure

    International Nuclear Information System (INIS)

    Felser, Andrea; Lindinger, Peter W.; Schnell, Dominik; Kratschmar, Denise V.; Odermatt, Alex; Mies, Suzette; Jenö, Paul; Krähenbühl, Stephan

    2014-01-01

    Highlights: • Benzbromarone impairs the electron transport chain and uncouples mitochondria. • Benzbromarone impairs mitochondrial β-oxidation by inhibiting fatty acid activation. • Benzbromarone disrupts the mitochondrial network and induces apoptosis. - Abstract: Benzbromarone is an uricosuric structurally related to amiodarone and a known mitochondrial toxicant. The aim of the current study was to improve our understanding in the molecular mechanisms of benzbromarone-associated hepatic mitochondrial toxicity. In HepG2 cells and primary human hepatocytes, ATP levels started to decrease in the presence of 25–50 μM benzbromarone for 24–48 h, whereas cytotoxicity was observed only at 100 μM. In HepG2 cells, benzbromarone decreased the mitochondrial membrane potential starting at 50 μM following incubation for 24 h. Additionally, in HepG2 cells, 50 μM benzbromarone for 24 h induced mitochondrial uncoupling,and decreased mitochondrial ATP turnover and maximal respiration. This was accompanied by an increased lactate concentration in the cell culture supernatant, reflecting increased glycolysis as a compensatory mechanism to maintain cellular ATP. Investigation of the electron transport chain revealed a decreased activity of all relevant enzyme complexes. Furthermore, treatment with benzbromarone was associated with increased cellular ROS production, which could be located specifically to mitochondria. In HepG2 cells and in isolated mouse liver mitochondria, benzbromarone also reduced palmitic acid metabolism due to an inhibition of the long-chain acyl CoA synthetase. In HepG2 cells, benzbromarone disrupted the mitochondrial network, leading to mitochondrial fragmentation and a decreased mitochondrial volume per cell. Cell death occurred by both apoptosis and necrosis. The study demonstrates that benzbromarone not only affects the function of mitochondria in HepG2 cells and human hepatocytes, but is also associated with profound changes in mitochondrial

  12. Effects of estrogen coadministration on epoxiconazole toxicity in rats.

    Science.gov (United States)

    Stinchcombe, Stefan; Schneider, Steffen; Fegert, Ivana; Rey Moreno, Maria Cecilia; Strauss, Volker; Gröters, Sibylle; Fabian, Eric; Fussell, Karma C; Pigott, Geoffrey H; van Ravenzwaay, Bennard

    2013-06-01

    Epoxiconazole (EPX; CAS-No. 133855-98-8) is a triazole class-active substance of plant protection products. At a dose level of 50 mg/kg bw/day, it causes a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (gestation day [GD] 7-18 or 21), as reported previously (Taxvig et al., 2007, 2008) and confirmed in these studies. Late fetal resorptions occurred in the presence of significant maternal toxicity such as clear reduction of corrected body weight gain, signs of anemia, and, critically, a marked reduction of maternal estradiol plasma levels. Furthermore, estradiol supplementation at dose levels of 0.5 or 1.0 μg/animal/day of estradiol cyclopentylpropionate abolished the EPX-mediated late fetal resorptions. No increased incidences of external malformations were found in rats cotreated with 50 mg/kg bw/day EPX and estradiol cyclopentylpropionate, indicating that the occurrence of malformations was not masked by fetal mortality under the study conditions. Overall, the study data indicate that fetal mortality observed in rat studies with EPX is not the result of direct fetal toxicity but occurs indirectly via depletion of maternal estradiol levels. The clarification of the human relevance of the estrogen-related mechanism behind EPX-mediated late fetal resorptions in rats warrants further studies. In particular, this should involve investigation of the placenta (Rey Moreno et al., 2013), since it is the materno-fetal interface and crucial for fetal maintenance. The human relevance is best addressed in a species which is closer to humans with reference to placentation and hormonal regulation of pregnancy, such as the guinea pig (Schneider et al., 2013). © 2013 Wiley Periodicals, Inc.

  13. Subchronic feeding study of carnauba wax in beagle dogs.

    Science.gov (United States)

    Parent, R A; Cox, G E; Babish, J G; Gallo, M A; Hess, F G; Becci, P J

    1983-02-01

    Carnauba wax fed at levels of 0.1, 0.3 and 1% in the diet to beagle dogs for 28 wk did not produce evidence of toxicity or pathological effects. Body weight gain, food consumption, clinical chemical, haematological, and urine analysis data, and organ weights of animals fed carnauba wax were comparable with those of control animals. Ophthalmic, gross and histopathological examinations revealed no significant treatment-related findings.

  14. Spatial dynamics of a nutrient-phytoplankton system with toxic effect on phytoplankton.

    Science.gov (United States)

    Chakraborty, Subhendu; Tiwari, P K; Misra, A K; Chattopadhyay, J

    2015-06-01

    The production of toxins by some species of phytoplankton is known to have several economic, ecological, and human health impacts. However, the role of toxins on the spatial distribution of phytoplankton is not well understood. In the present study, the spatial dynamics of a nutrient-phytoplankton system with toxic effect on phytoplankton is investigated. We analyze the linear stability of the system and obtain the condition for Turing instability. In the presence of toxic effect, we find that the distribution of nutrient and phytoplankton becomes inhomogeneous in space and results in different patterns, like stripes, spots, and the mixture of them depending on the toxicity level. We also observe that the distribution of nutrient and phytoplankton shows spatiotemporal oscillation for certain toxicity level. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. How can we investigate the effects of small amounts of toxic substances?

    International Nuclear Information System (INIS)

    Taylor, D.M.

    1991-01-01

    Today there is increasing concern about the possible toxic effects of tiny amounts of toxic substances in the environment of workplace. Because the incidence of effects at such levels of toxic material is likely to be very low their investigation becomes very difficult and will require new approaches to toxicological research. Only through the use of in vitro cell systems and the most modern theoretical and experimental methods in biochemistry, chemistry and molecular biolgoy can we hope to elucidate the mechanisms underlying the causation and expression of environmentally-induced diseases. Much of this research will be at the fundamental level but it must be so oriented that the information obtained is directly applicable to the realistic estimation of the risks to mankind and other living creatures from natural and man made toxicants. (orig.) [de

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

    Science.gov (United States)

    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

  17. Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

    International Nuclear Information System (INIS)

    Sandre, C.; Moulin, C.; Bresson, C.; Gault, N.; Poncy, J. L.; Lefaix, J. L.

    2010-01-01

    Cobalt (Co) is an essential trace element well known as a constituent of vitamin B 12 , but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, 58 Co and 60 Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl 2 ) with or without gamma-ray doses to mimic contamination by 60 Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

  18. Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

    Energy Technology Data Exchange (ETDEWEB)

    Gault, N. [CEA Fontenay aux Roses, DSV/IRCM/SCSR/LRTS, 92265 Fontenay aux Rose (France); Sandre, C.; Moulin, B.; Bresson, C. [CEA, DEN, SECR, Laboratoire de Speciation des Radionucleides et des Molecules, F-91191 Gif-sur-Yvette (France); Poncy, J.L. [CEA Bruyeres Le Chatel, DSV/IRCM/SREIT/LRT, 91680 Bruyeres Le Chatel (France); Lefaix, J.L. [CEA Caen, DSV/IRCM/SRO/LARIA, 14070 Caen (France)

    2010-07-01

    Cobalt (Co) is an essential trace element well known as a constituent of vitamin B12, but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, {sup 58}Co and {sup 60}Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl{sub 2}) with or without {gamma}-ray doses to mimic contamination by {sup 60}Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate {gamma}-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

  19. Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

    Energy Technology Data Exchange (ETDEWEB)

    Sandre, C.; Moulin, C.; Bresson, C. [CEA Saclay, DEN, SECR, Lab Speciat Radionucleides and Mol, F-91191 Gif Sur Yvette (France); Gault, N. [CEA Fontenay Roses, DSV IRCM SCSR LRTS, F-92265 Fontenay Aux Roses (France); Poncy, J. L. [CEA Bruyeres Le Chatel, DSV IRCM SREIT LRT, F-91680 Bruyeres Le Chatel (France); Lefaix, J. L. [CEA Caen, DSV IRCM SRO LARIA, F-14070 Caen (France)

    2010-07-01

    Cobalt (Co) is an essential trace element well known as a constituent of vitamin B{sub 12}, but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, {sup 58}Co and {sup 60}Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl{sub 2}) with or without gamma-ray doses to mimic contamination by {sup 60}Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

  20. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy

    International Nuclear Information System (INIS)

    Carvalho, Rui A.; Sousa, Rui P.B.; Cadete, Virgilio J.J.; Lopaschuk, Gary D.; Palmeira, Carlos M.M.; Bjork, James A.; Wallace, Kendall B.

    2010-01-01

    Doxorubicin (Adriamycin ® ) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR). 13 C-isotopomer analysis of isolated perfused hearts from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.

  1. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    Science.gov (United States)

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

  2. Behavioral, endocrine, and neuronal alterations in zebrafish (Danio rerio) following sub-chronic coadministration of fluoxetine and ketamine.

    Science.gov (United States)

    Pittman, Julian; Hylton, Andrew

    2015-12-01

    Most existing pharmacological treatments have focused on the "monoamine hypothesis" for targeted drug design for major depressive disorder (MDD). Many of these medications have a delayed onset-of-action and limited efficacy. Antidepressants with principal targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. Growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Ketamine (Ketalar®) is a non-competitive glutamatergic antagonist classically used to induce sedation. However, preliminary clinical evidence has been promising with regard to its rapidly acting antidepressant profile. Zebrafish (Danio rerio) have emerged as a promising new animal model to screen the effects of numerous psychotropic compounds. This study aimed to determine if a sub-chronic low (sub-anesthetic) dose of ketamine could be used to augment the antidepressant effects of the widely used antidepressant fluoxetine (Prozac®) in adult zebrafish, employing an ethanol withdrawal model. Sub-chronic exposure to dosages of 100μg/L fluoxetine and 20mg/L of ketamine reduced anxiety/depression-like behaviors, leads to upregulation of serotonin synthesis and elevated whole-body cortisol levels. These results demonstrate the utility of zebrafish as a model for neuropharmacological research, and the possible efficacy of fluoxetine and ketamine coadministration. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Olakunle James Onaolapo

    2013-01-01

    Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  4. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

    Science.gov (United States)

    Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

    2013-01-01

    This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  5. Immunological changes following a combined effect of chromic small dose γ-irradiation and toxic agents

    International Nuclear Information System (INIS)

    Shubik, V.M.; Zykova, I.A.

    1981-01-01

    Immunologic changes under conditions of durable effect of low dose γ-radiation on people in the case of combining radiation with the effect of low concentrations of toxic substances, are studied. Under the above effect, the appearance of deviations from the side of immunologic status is possible. Taking into account the important role of the immunity system in homeostasis preservation and the formation of a series of pathological states it is advisable to use figures, and characteristics inherent in the state of the cell immunity to autoallergic processes to estimate a combined effect of radiation and toxic substances on the organism of people [ru

  6. A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

    Science.gov (United States)

    Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

    2017-11-01

    Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Toxic effect of ciprofloxacin on some biochemical variables in chicks

    Directory of Open Access Journals (Sweden)

    Y. Z. Salih

    2010-01-01

    Full Text Available The aim of the present study was to examine the acute and sub acute toxicity of ciprofloxacin on lipids metabolism ofchicks which included determination of cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, and albuminlevels in serum of chicks. The biochemical changes induced by giving ciprofloxacin as a single dose (200 and 400 mg/kg.body weight intraperitoneally included significant increases of cholesterol, triglyceride and low density lipoprotein levels inserum, whereas albumin level significantly decreased, and there was no significant changes in high density lipoprotein levelsas compared with control group. Repeated treatment with ciprofloxacin (100 mg/kg. body weight intra peritoneal for 14 dayscaused significant increase in cholesterol level, albumin level significantly decreased as compared with control group, whereasit did not change significantly high density lipoprotein and triglyceride levels, repeated treatment of ciprofloxacin also showedsignificant decrease of the body weights of the chicks as compared with control group. The results suggest that there are toxiceffects of ciprofloxacin on lipids metabolism as seen through changes in cholesterol, triglyceride, albumin and low densitylipoprotein level.

  8. Artificial saliva effect on toxic substances release from acrylic resins

    Directory of Open Access Journals (Sweden)

    Kostić Milena

    2015-01-01

    Full Text Available Background/Aim. Acrylic-based resins are intensively used in dentistry practice as restorative or denture-base materials. The purpose of this study was to analyze the surface structure of denture base resins and the amount of released potentially toxic substances (PTS immediately upon polymerization and incubation in different types of artificial saliva. Methods. Storage of acrylic samples in two models of artificial saliva were performed in a water bath at the temperature of 37 ± 1°C. Analysis of the surface structure of samples was carried out using scanning electronic microscopy analysis immediately after polymerization and after the 30-day incubation. The amounts of PTS per day, week and month extracts were measured using high-pressure liquid chromatography. Results. Surface design and amount of PTS in acrylic materials were different and depended on the types and duration of polymerization. The surfaces of tested acrylates became flatter after immersing in solutions of artificial saliva. The degree of acrylic materials release was not dependent on the applied model of artificial saliva. Conclusion. In order to improve biological features of acrylic resin materials, it was recommended that dentures lined with soft or hard coldpolymerized acrylates should be kept at least 1 to 7 days in water before being given to a patient. So, as to reach high degree of biocompatibility preparation of prosthetic restorations from heat-polymerized acrylate was unnecessary. [Projekat Ministarstva nauke Republike Srbije, br. 41017

  9. Does lipophilicity of toxic compounds determine effects on drought tolerance of the soil collembolan Folsomia candida?

    International Nuclear Information System (INIS)

    Skovlund, Gitte; Damgaard, Christian; Bayley, Mark; Holmstrup, Martin

    2006-01-01

    The ability of Collembola to survive drought stress is crucial for their distribution in the terrestrial environment. Previous studies have suggested that several toxic compounds affect the drought tolerance of Folsomia candida in a synergistic manner and that these compounds have the feature in common that they elicit their toxicity by causing membrane damage. We hypothesised that the detrimental effect of toxic chemicals on drought tolerance in F. candida depends on the lipophilicity (log K ow ) of the compound because a higher log K ow would mean a closer interaction with membranes. In this study the three chemicals 4-nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with the lowest log K ow , was the most potent with respect to reducing drought tolerance followed by pyrene, suggesting that interactions between drought tolerance and chemical stress do not depend on lipophilicity alone. - Toxic stress may reduce drought tolerance of Collembola

  10. Effect of soil properties on the toxicity of Pb: assessment of the appropriateness of guideline values.

    Science.gov (United States)

    Romero-Freire, A; Martin Peinado, F J; van Gestel, C A M

    2015-05-30

    Soil contamination with lead is a worldwide problem. Pb can cause adverse effects, but its mobility and availability in the terrestrial environment are strongly controlled by soil properties. The present study investigated the influence of different soil properties on the solubility of lead in laboratory spiked soils, and its toxicity in three bioassays, including Lactuca sativa root elongation and Vibrio fischeri illumination tests applied to aqueous extracts and basal soil respiration assays. Final aim was to compare soil-dependent toxicity with guideline values. The L. sativa bioassay proved to be more sensitive to Pb toxicity than the V. fischeri and soil respiration tests. Toxicity was significantly correlated with soil properties, with soil pH, carbonate and organic carbon content being the most important factors. Therefore, these variables should be considered when defining guideline values. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Overlapping toxic effect of long term thallium exposure on white mustard (Sinapis alba L.) photosynthetic activity.

    Science.gov (United States)

    Mazur, Radosław; Sadowska, Monika; Kowalewska, Łucja; Abratowska, Agnieszka; Kalaji, Hazem M; Mostowska, Agnieszka; Garstka, Maciej; Krasnodębska-Ostręga, Beata

    2016-09-02

    Heavy metal exposure affect plant productivity by interfering, directly and indirectly, with photosynthetic reactions. The toxic effect of heavy metals on photosynthetic reactions has been reported in wide-ranging studies, however there is paucity of data in the literature concerning thallium (Tl) toxicity. Thallium is ubiquitous natural trace element and is considered the most toxic of heavy metals; however, some plant species, such as white mustard (Sinapis alba L.) are able to accumulate thallium at very high concentrations. In this study we identified the main sites of the photosynthetic process inhibited either directly or indirectly by thallium, and elucidated possible detoxification mechanisms in S. alba. We studied the toxicity of thallium in white mustard (S. alba) growing plants and demonstrated that tolerance of plants to thallium (the root test) decreased with the increasing Tl(I) ions concentration in culture media. The root growth of plants exposed to Tl at 100 μg L(-1) for 4 weeks was similar to that in control plants, while in plants grown with Tl at 1,000 μg L(-1) root growth was strongly inhibited. In leaves, toxic effect became gradually visible in response to increasing concentration of Tl (100 - 1,000 μg L(-1)) with discoloration spreading around main vascular bundles of the leaf blade; whereas leaf margins remained green. Subsequent structural analyses using chlorophyll fluorescence, microscopy, and pigment and protein analysis have revealed different effects of varying Tl concentrations on leaf tissue. At lower concentration partial rearrangement of the photosynthetic complexes was observed without significant changes in the chloroplast structure and the pigment and protein levels. At higher concentrations, the decrease of PSI and PSII quantum yields and massive oxidation of pigments was observed in discolored leaf areas, which contained high amount of Tl. Substantial decline of the photosystem core proteins and disorder of the

  12. Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

    International Nuclear Information System (INIS)

    Fuma, S.; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G.

    2003-01-01

    The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of γ-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation

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

    Science.gov (United States)

    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

  14. Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

    Science.gov (United States)

    Zhang, Yi; Tay, JooHwa

    2015-04-09

    Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors to h...

  16. Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

    Science.gov (United States)

    Kudryasheva, N S; Rozhko, T V

    2015-04-01

    The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Consequences of subchronic exposure to ethanolic extract from fruits and leaves of Schinus molle var. areira L. in mice.

    Science.gov (United States)

    Bras, Cristina; Domínguez, Sergio; Codón, Stella; Minetti, Alejandra; Ferrero, Adriana

    2010-10-28

    Several extracts of Schinus molle var. areira L. plant proved to be useful for the treatment of different pathologies and for the control of insect pest. Due to these potential uses, it is necessary to study their safety. In this work, we evaluated the effects of subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira in mice. The plant extract was added to the diet at 1 g/kg body weight/day for 90 days. At the end of the exposure, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, several biochemical and histopathological studies were realized. The exposure to extract from leaves produced an increase in the number of rearings in the open field and of urine pools in the functional observational battery. On the other hand, the exposure to extract from fruits produced an increase in the neutrophil count and a decrease in the lymphocyte count and in the total cholesterol levels. None of the exposures affected the different organs evaluated. Our results suggest that subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira should be potentially useful in the treatment of lipid pathologies and safe to use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. The Study on Acute Subacute Toxicity and Anti-cancer Effect of K-herbal-acupuncture

    Directory of Open Access Journals (Sweden)

    Kwang-Ho, Kim

    2003-02-01

    Full Text Available Objectives : The purpose of this study was to investigate Acute· Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K- herbal-acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. LD50 of K-Herbal-acupuncture was limited 4×10-3ml/kg~2×10-3ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(p<0.05 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (p<0.05 6. In subacute toxicity test of complete blood count test (CBC of rat, HCT was decreased in treatments, compared with the normal group.(p<0.05 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (p<0.05 8. Median survival time was increased about 45% in treatment groups compared with the control group.(p<0.05 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(p<0.005 11. In making an examination of metastatic cancer with the naked eye, melanoma

  19. Mixtures of benzo(a)pyrene, dichlorodiphenyltrichloroethane and tributyltin are more toxic to neotropical fish Rhamdia quelen than isolated exposures.

    Science.gov (United States)

    Oliveira, Heloísa H P; Liebel, Samuel; Rossi, Stéfani C; Azevedo, Ana C B; Barrera, Ellie A L; Garcia, Juan Ramon Esquivel; Grötzner, Sônia Regina; Neto, Francisco Filipak; Randi, Marco A F; Ribeiro, Ciro A O

    2015-12-01

    activation of cell defenses after the sub-chronic exposure. TBT increased melanomacrophages counting in the 5-day experiment and the mixtures increased it in the 5 and 15-day experiments. Overall, the majority of the biomarkers pointed to a more toxic effect when these contaminants were combined, leading to unexpected toxicities compared to individual exposure scenarios. These findings are relevant considering environmental exposure conditions, since organisms are often exposed to different combinations of contaminants. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Protective Effect of Vitamins E and C on Endosulfan-Induced Reproductive Toxicity in Male Rats

    Directory of Open Access Journals (Sweden)

    Hussain Kargar

    2012-09-01

    Full Text Available Background: The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats.Methods: Fifty adult male Sprague–Dawley rats were randomly divided into five groups (n=10 each. The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day, vitamin E (200 mg/kg/day, or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH, plasma testosterone and malondialdehyde (MDA levels in the testis were determined. Results: Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan.Conclusion: The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  1. Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male rats.

    Science.gov (United States)

    Takhshid, Mohammad Ali; Tavasuli, Ali Reza; Heidary, Yazdan; Keshavarz, Mojtaba; Kargar, Hussain

    2012-09-01

    The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats. Fifty adult male Sprague-Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan. The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  2. Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

    Energy Technology Data Exchange (ETDEWEB)

    Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

    1994-02-01

    Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

  3. Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

    Science.gov (United States)

    Segal, L; Penman, M G; Piriou, Y

    2018-01-01

    The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

  4. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    Science.gov (United States)

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

  5. Effects of soil properties on copper toxicity to earthworm Eisenia fetida in 15 Chinese soils.

    Science.gov (United States)

    Duan, Xiongwei; Xu, Meng; Zhou, Youya; Yan, Zengguang; Du, Yanli; Zhang, Lu; Zhang, Chaoyan; Bai, Liping; Nie, Jing; Chen, Guikui; Li, Fasheng

    2016-02-01

    The bioavailability and toxicity of metals in soil are influenced by a variety of soil properties, and this principle should be recognized in establishing soil environmental quality criteria. In the present study, the uptake and toxicity of Cu to the earthworm Eisenia fetida in 15 Chinese soils with various soil properties were investigated, and regression models for predicting Cu toxicity across soils were developed. The results showed that earthworm survival and body weight change were less sensitive to Cu than earthworm cocoon production. The soil Cu-based median effective concentrations (EC50s) for earthworm cocoon production varied from 27.7 to 383.7 mg kg(-1) among 15 Chinese soils, representing approximately 14-fold variation. Soil cation exchange capacity and organic carbon content were identified as key factors controlling Cu toxicity to earthworm cocoon production, and simple and multiple regression models were developed for predicting Cu toxicity across soils. Tissue Cu-based EC50s for earthworm cocoon production were also calculated and varied from 15.5 to 62.5 mg kg(-1) (4-fold variation). Compared to the soil Cu-based EC50s for cocoon production, the tissue Cu-based EC50s had less variation among soils, indicating that metals in tissue were more relevant to toxicity than metals in soil and hence represented better measurements of bioavailability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth.

    Science.gov (United States)

    Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

    2016-01-01

    Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca(2+)]c and induce the disappearance of the [Ca(2+)]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca(2+)]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth.

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

    Directory of Open Access Journals (Sweden)

    Can Peng

    2017-04-01

    Full Text Available 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(NO34 was transformed to amorphous precipitation of Th(OH4 due to hydrolysis. Th was toxic to C. pyrenoidosa, with a 96 h half maximum effective concentration (EC50 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(OH4 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.

  8. The effect of soil properties on the toxicity of silver to the soil nitrification process.

    Science.gov (United States)

    Langdon, Kate A; McLaughlin, Mike J; Kirby, Jason K; Merrington, Graham

    2014-05-01

    Silver (Ag) is being increasingly used in a range of consumer products, predominantly as an antimicrobial agent, leading to a higher likelihood of its release into the environment. The present study investigated the toxicity of Ag to the nitrification process in European and Australian soils in both leached and unleached conditions. Overall, leaching of soils was found to have a minimal effect on the final toxicity data, with an average leaching factor of approximately 1. Across the soils, the toxicity was found to vary by several orders of magnitude, with concentrations of Ag causing a 50% reduction in nitrification relative to the controls (EC50) ranging from 0.43 mg Ag/kg to >640 mg Ag/kg. Interestingly, the dose-response relationships in most of the soils showed significant stimulation in nitrification at low Ag concentrations (i.e., hormesis), which in some cases produced responses up to double that observed in the controls. Soil pH and organic carbon were the properties found to have the greatest influence on the variations in toxicity thresholds across the soils, and significant relationships were developed that accounted for approximately 90% of the variability in the data. The toxicity relationships developed from the present study will assist in future assessment of potential Ag risks and enable the site-specific prediction of Ag toxicity. © 2014 SETAC.

  9. In vitro toxicity analysis of nanoscale aluminum: Particle size and shape effects

    Science.gov (United States)

    Palazuelos Jorganes, Maria

    2007-12-01

    Nanostructured materials promise to revolutionize many key areas of science and technology. As our ability to manipulate matter at the nanoscale increases, there is a need to assess the effects of these materials on human health and the environment. Materials at the nanoscale are interesting and useful because they possess properties that are different from the equivalent bulk or molecular scale. These same properties can make toxicological profiles very different from those of the same materials on a different scale. There is a rising consensus that toxicity analysis of nanomaterials should start from a thorough physicochemical characterization of the materials under investigation in order to be able to establish a proper correlation between the nanoparticles characteristics and their effects and behavior in physiological environments. This research is a clear example of the necessity of comprehensive studies when investigating the toxicity of nanomaterials. Aluminum nanoparticles are being extensively used for their very unique energetic properties. These materials offer a very promising market that is fostering many startup companies which are expected to consolidate on strong technological positions. Aluminum is generally recognized as a non-toxic material to humans and it is widely used for applications which imply direct human contact. The effect of aluminum nanoparticles in human health is still an unknown. My research consisted of an in vitro toxicity screening of aluminum materials from nano to micron size, including spherical irregularly shaped particles. Several issues relating to size, shape, detection and characterization of nanoparticles in the different environments relevant to in vitro toxicity analysis were addressed and suitable protocols were developed. Lung human epithelial cells were exposed to different concentrations of these materials and the effects were analyzed by means of various toxicity tests. Some of the materials investigated caused

  10. Toxic effect of visible light on Drosophila lifespan depending upon diet protein content.

    Science.gov (United States)

    Shen, Jie; Zhu, Xiang; Gu, Yitian; Zhang, Chiqian; Huang, Jiahong; Qing, Xiao

    2018-03-01

    We investigated the toxic effect of visible light on Drosophila lifespan in both sexes. The toxic effect of ultraviolet (UV) light on organisms is well known. However, the effects of illumination with visible light remain unclear. Here, we found that visible light could be toxic to Drosophila survival, depending on the protein content in diet. In addition, further analysis revealed significant interaction between light and sex, and showed that strong light shortened life span by causing opposite direction changes in mortality rate parameters in females versus males. Our findings suggest that photoageing may be a general phenomenon, and support the theory of sexual antagonistic pleiotropy in aging intervention. The results caution that exposure to visible light could be hazardous to life span and suggest that identification of the underlying mechanism would allow better understanding of aging intervention.

  11. Aflatoxin B1 Induced Systemic Toxicity in Poultry and Rescue Effects of Selenium and Zinc.

    Science.gov (United States)

    Mughal, Muhammad Jameel; Peng, Xi; Kamboh, Asghar Ali; Zhou, Yi; Fang, Jing

    2017-08-01

    Among many challenges, exposure to aflatoxins, particularly aflatoxin B 1 (AFB 1 ), is one of the major concerns in poultry industry. AFB 1 intoxication results in decreased meat/egg production, hepatotoxicity, nephrotoxicity, disturbance in gastrointestinal tract (GIT) and reproduction, immune suppression, and increased disease susceptibility. Selenium (Se) and zinc (Zn), in dietary supplementation, offer easy, cost-effective, and efficient ways to neutralize the toxic effect of AFB 1 . In the current review, we discussed the impact of AFB 1 on poultry industry, its biotransformation, and organ-specific noxious effects, along with the action mechanism of AFB 1 -induced toxicity. Moreover, we explained the biological and detoxifying roles of Se and Zn in avian species as well as the protection mechanism of these two trace elements. Ultimately, we discussed the use of Se and Zn supplementation against AFB 1 -induced toxicity in poultry birds.

  12. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Eduard Kolesár

    2015-02-01

    Full Text Available The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studies describe the effects of natural compound amygdalin on female and male reproductive systems focused on process of steroidogenesis, spermatozoa motility and morphological abnormalities of spermatozoa. In accordance to the previous studies on amygdalin its benefit is controversial.

  13. Toxic effects of cadmium on Morus alba L. and Bombyx moril L.

    NARCIS (Netherlands)

    Wang, K.R.; Gong, H.; Wang, Y.; Zee, van der S.E.A.T.M.

    2004-01-01

    A 3-year micro-plot experiment of mulberry cultivation with Cd-polluted soil and silkworm breeding experiments by feeding with exogenous or endogenous ¿Cd-polluted mulberry leaves were conducted to evaluate the toxic effects of Cd on mulberry and silkworms. There was no apparent harmful effect on

  14. Effects of inorganic lead on Western fence lizards (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    Salice, Christopher J., E-mail: chris.salice@ttu.ed [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Suski, Jamie G., E-mail: jamie.suski@ttu.ed [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Bazar, Matthew A., E-mail: matthew.bazar@us.army.mi [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G., E-mail: larry.talent@okstate.ed [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States)

    2009-12-15

    Although anthropogenic pollutants are thought to threaten reptilian species, there are few toxicity studies on reptiles. We evaluated the toxicity of Pb as lead acetate to the Western fence lizard (Sceloporus occidentalis). The acute lethal dose and sub-acute (14-day) toxicity studies were used to narrow exposure concentrations for a sub-chronic (60-day) study. In the sub-chronic study, adult and juvenile male lizards were dosed via gavage with 0, 1, 10 and 20 mg Pb/kg-bw/day. Mortality was limited and occurred only at the highest dose (20 mg Pb/kg-bw/d). There were statistically significant sub-lethal effects of 10 and 20 mg Pb/kg-bw/d on body weight, cricket consumption, organ weight, hematological parameters and post-dose behaviors. Of these, Pb-induced changes in body weight are most useful for ecological risk assessment because it is linked to fitness in wild lizard populations. The Western fence lizard is a useful model for reptilian toxicity studies. - The Western fence lizard, Sceloporus occidentalis, is sensitive to Pb and is a useful laboratory model for ecotoxicological testing of reptiles.

  15. Effects of inorganic lead on Western fence lizards (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    Salice, Christopher J.; Suski, Jamie G.; Bazar, Matthew A.; Talent, Larry G.

    2009-01-01

    Although anthropogenic pollutants are thought to threaten reptilian species, there are few toxicity studies on reptiles. We evaluated the toxicity of Pb as lead acetate to the Western fence lizard (Sceloporus occidentalis). The acute lethal dose and sub-acute (14-day) toxicity studies were used to narrow exposure concentrations for a sub-chronic (60-day) study. In the sub-chronic study, adult and juvenile male lizards were dosed via gavage with 0, 1, 10 and 20 mg Pb/kg-bw/day. Mortality was limited and occurred only at the highest dose (20 mg Pb/kg-bw/d). There were statistically significant sub-lethal effects of 10 and 20 mg Pb/kg-bw/d on body weight, cricket consumption, organ weight, hematological parameters and post-dose behaviors. Of these, Pb-induced changes in body weight are most useful for ecological risk assessment because it is linked to fitness in wild lizard populations. The Western fence lizard is a useful model for reptilian toxicity studies. - The Western fence lizard, Sceloporus occidentalis, is sensitive to Pb and is a useful laboratory model for ecotoxicological testing of reptiles.

  16. Differential effects of the ascorbyl and tocopheryl derivative on the methamphetamine-induced toxic behavior and toxicity

    International Nuclear Information System (INIS)

    Ito, Shinobu; Mori, Tomohisa; Kanazawa, Hideko; Sawaguchi, Toshiko

    2007-01-01

    A previous study showed that high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. Furthermore, the combination of methamphetamine and morphine increased lethality in mice. We recently surmised that the rise in SIB and mortality induced by methamphetamine and/or morphine may be related to oxidative stress. The present study was designed to determine whether an antioxidant could inhibit SIB or mortality directly induced by methamphetamine and/or morphine. The SIB induced by 20 mg/kg of methamphetamine was abolished by the administration of Na L-ascorbyl-2-phosphate (APS: 300 mg/kg), but not Na DL-α-tocopheryl phosphate (TPNa: 200 mg/kg). In contrast, APS (300 mg/kg) and TPNa (200 mg/kg) each significantly attenuated the lethality induced by methamphetamine and morphine. The present study showed that the signal intensity of superoxide adduct was increased by 20 mg/kg of methamphetamine in the heart and lungs, and methamphetamine plus morphine tended to increase superoxide adduct in all of the tissues measured by ESR spin trap methods. Adduct signal induced in brain by methamphetamine administration increased in significance, but in mouse administrated methamphetamine plus morphine. There are differential effects of administration of methamphetamine and coadministration of methamphetamine plus morphine on adduct signal. These results suggest that APS and TPNa are effective for reducing methamphetamine-induced toxicity and/or toxicological behavior. While APS and TPNa each affected methamphetamine- and/or morphine-induced toxicology and/or toxicological behavior, indicating that both drugs have antioxidative effects, their effects differed

  17. Disentangling the effects of low pH and metal mixture toxicity on macroinvertebrate diversity

    Science.gov (United States)

    Fornaroli, Riccardo; Ippolito, Alessio; Tolkkinen, Mari J.; Mykrä, Heikki; Muotka, Timo; Balistrieri, Laurie S.; Schmidt, Travis S.

    2018-01-01

    One of the primary goals of biological assessment of streams is to identify which of a suite of chemical stressors is limiting their ecological potential. Elevated metal concentrations in streams are often associated with low pH, yet the effects of these two potentially limiting factors of freshwater biodiversity are rarely considered to interact beyond the effects of pH on metal speciation. Using a dataset from two continents, a biogeochemical model of the toxicity of metal mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative importance of both pH and metals as limiting factors for macroinvertebrate communities. Current environmental quality standards for metals proved to be protective of stream macroinvertebrate communities and were used as a starting point to assess metal mixture toxicity. A model of metal mixture toxicity accounting for metal interactions was a better predictor of macroinvertebrate responses than a model considering individual metal toxicity. We showed that the direct limiting effect of pH on richness was of the same magnitude as that of chronic metal toxicity, independent of its influence on the availability and toxicity of metals. By accounting for the direct effect of pH on macroinvertebrate communities, we were able to determine that acidic streams supported less diverse communities than neutral streams even when metals were below no-effect thresholds. Through a multivariate quantile model, we untangled the limiting effect of both pH and metals and predicted the maximum diversity that could be expected at other sites as a function of these variables. This model can be used to identify which of the two stressors is more limiting to the ecological potential of running waters.

  18. Disentangling the effects of low pH and metal mixture toxicity on macroinvertebrate diversity.

    Science.gov (United States)

    Fornaroli, Riccardo; Ippolito, Alessio; Tolkkinen, Mari J; Mykrä, Heikki; Muotka, Timo; Balistrieri, Laurie S; Schmidt, Travis S

    2018-04-01

    One of the primary goals of biological assessment of streams is to identify which of a suite of chemical stressors is limiting their ecological potential. Elevated metal concentrations in streams are often associated with low pH, yet the effects of these two potentially limiting factors of freshwater biodiversity are rarely considered to interact beyond the effects of pH on metal speciation. Using a dataset from two continents, a biogeochemical model of the toxicity of metal mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative importance of both pH and metals as limiting factors for macroinvertebrate communities. Current environmental quality standards for metals proved to be protective of stream macroinvertebrate communities and were used as a starting point to assess metal mixture toxicity. A model of metal mixture toxicity accounting for metal interactions was a better predictor of macroinvertebrate responses than a model considering individual metal toxicity. We showed that the direct limiting effect of pH on richness was of the same magnitude as that of chronic metal toxicity, independent of its influence on the availability and toxicity of metals. By accounting for the direct effect of pH on macroinvertebrate communities, we were able to determine that acidic streams supported less diverse communities than neutral streams even when metals were below no-effect thresholds. Through a multivariate quantile model, we untangled the limiting effect of both pH and metals and predicted the maximum diversity that could be expected at other sites as a function of these variables. This model can be used to identify which of the two stressors is more limiting to the ecological potential of running waters. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Effect of cypermethrin toxicity on enzyme activities in the freshwater ...

    African Journals Online (AJOL)

    Shahid

    2014-03-05

    Mar 5, 2014 ... ... and floods to large water bodies like ponds and rivers and change the water ... from the processing of sheep skin, wood industry and knitwear ... there is little information on the comprehensive effects of ... deep freezer prior to analysis. ..... insecticide monocrotophas and its effects on behaviour of an air-.

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

    Science.gov (United States)

    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.

  1. Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing

    Science.gov (United States)

    Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling

    2016-10-01

    Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

  2. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    OpenAIRE

    Aicha Fassi Fihri; Noori S. Al-Waili; Redouan El-Haskoury; Meryem Bakour; Afaf Amarti; Mohammad J. Ansari; Badiaa Lyoussi

    2016-01-01

    Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: tr...

  3. The Effect of Toxic Cyanobacteria on Human and Animal Health

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  4. Predicting_Systemic_Toxicity_Effects_ArchTox_2017_Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was...

  5. Toxic effect of naphta exposure on respiratory system among ...

    African Journals Online (AJOL)

    EJIRO

    stem, liver, kidney and skin, however, the effects of these organic solvents to ... inhalation of the vapor that is volatile in air can affect the health (Singh ..... Care . 160: 2028-2033. Bradley WG (1999). Neurology in Clinical Practice. Butterworth-.

  6. Is the OECD acute worm toxicity test environmentally relevant? The effect of mineral form on calculated lead toxicity

    International Nuclear Information System (INIS)

    Davies, N.A.Nicola A.; Hodson, M.E.Mark E.; Black, S.Stuart

    2003-01-01

    The current OECD acute worm toxicity test does not relate well to ambient conditions. - In a series of experiments the toxicity of lead to worms in soil was determined following the draft OECD earthworm reproduction toxicity protocol except that lead was added as solid lead nitrate, carbonate and sulphide rather than as lead nitrate solution as would normally be the case. The compounds were added to the test soil to give lead concentrations of 625-12500 μg Pb g -1 of soil. Calculated toxicities of the lead decreased in the order nitrate>carbonate>sulphide, the same order as the decrease in the solubility of the metal compounds used. The 7-day LC 50 (lethal concentration when 50% of the population is killed) for the nitrate was 5321±275 μg Pb g -1 of soil and this did not change with time. The LC 50 values for carbonate and sulphide could not be determined at the concentration ranges used. The only parameter sensitive enough to distinguish the toxicities of the three compounds was cocoon (egg) production. The EC 50 s for cocoon production (the concentration to produce a 50% reduction in cocoon production) were 993, 8604 and 10246 μg Pb g -1 of soil for lead nitrate, carbonate and sulphide, respectively. Standard toxicity tests need to take into account the form in which the contaminant is present in the soil to be of environmental relevance

  7. TOXIC EFFECT OF PESTICIDES ON THE BIOTA OF FRESHWATER RESERVOIRS OF UKRAINE (A REVIEW

    Directory of Open Access Journals (Sweden)

    N. Kolesnyk

    2015-12-01

    Full Text Available Purpose. To analyze scientific sources on the studies of toxic and lethal concentrations of pesticides on phytoplankton, zooplankton, zoobenthos and fish in current conditions of Ukraine. Findings. A review of works of a variety of scientists showed that pesticides with different chemical origins have disastrous effects on everyone without the exception of freshwater biota organisms. The article highlights the peculiarities of the toxic effects of pesticides of major chemical groups, which are used or stored in Ukraine. Their toxic and lethal concentrations for the major species of phytoplankton, zooplankton, zoobenthos and ichthyofauna reservoirs are considered. The data on basic features of behavioral reactions of aquatic organisms on poisoning by pesticides are provided. The basic structural and systemic diosrders of homeostasis of the organisms of aquatic biota are described. The effect of pesticides on phytoplankton needs further research, however, is was found that they have common feature as the disturbace of photosynthesis process and accumulation. In turn, this provoques kills in water bodies and poisoning of phytoplanctivorous fish. Zooplanktonic organisms are highly sensitive to pesticides; hence they can be used as an indicator of the state of fresh water. It was found that, pesticides depending on their concentration have different toxic effects on zooplankton organisms. The effect of pesticides on benthic organisms was little investigated. It is known that benthic communities respond to the presence of pesticide by changes in species composition, number of species, abundance and biomass of benthos in general and individual taxonomic groups of benthic invertebrates. The toxicity of pesticides for fish depends on their chemical nature, the form of the preparation, dose, fish species and age, water temperature and the content of oxygen and salts. In particular, juvenile fish are much more sensitive to the chemicals, and an increase in

  8. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

    Directory of Open Access Journals (Sweden)

    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  9. Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

    Science.gov (United States)

    Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

    2017-09-01

    Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

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

    Science.gov (United States)

    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 ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  12. Combined Effects of Muricid Extract and 5-Fluorouracil on Intestinal Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Roger Yazbeck

    2015-01-01

    Full Text Available Chemotherapy drugs, such as 5-fluorouracil (5FU, are the standard approach for cancer and are associated with several peripheral toxicities. We previously demonstrated that Muricidae marine molluscs exhibit chemopreventive properties. This study investigated the combined effect of muricid extract derived from Dicathais orbita, with 5FU, on intestinal toxicity in rats. Groups of rats were orally gavaged water, muricid extract, or sunflower oil, with or without 5FU (150 mg/kg. Metabolic data was collected daily and small intestinal brush border enzyme activity was measured by sucrose breath test (SBT. Blood was collected by cardiac puncture for whole blood analysis. Intestinal biopsies were taken for histopathology. Neutrophil activity was measured by myeloperoxidase activity. No additional toxicity effects were observed in rats receiving the combination of 5FU and muricid extract compared to 5FU alone, as indicated by SBT, histopathology, and myeloperoxidase activity. Intestinal integrity was protected from 5FU-induced damage in the sunflower oil vehicle group, compared to controls, as measured by SBT, villus height, and crypt depth. We concluded that combination of muricid extract and 5FU did not confer any additional intestinal toxicity, further supporting its potential as a chemopreventive food product. In this model system, sunflower oil partially protected against 5FU-induced intestinal toxicity.

  13. Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

    Science.gov (United States)

    Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

    2005-11-30

    Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

  14. Toxic Gas Removal by Dielectric Discharge with Corona Effect

    International Nuclear Information System (INIS)

    Moreno, H.; Pacheco, M.; Mercado, A.; Cruz, A.; Pacheco, J.; Yousfi, M.; Eichwald, O.; Benhenni, M.

    2006-01-01

    In this work, a theoretical and experimental study on SO2 and NOx removal by non-thermal plasma technology, more specifically a dielectric barrier (DBD) discharge combined with the Corona effect, is presented. Results obtained from a theoretical study describe the chemical kinetic model of SO2 and NOx removal processes; the effect of OH radicals in removal of both gases is noteworthy. Experimental results of de-SO2 process are reported. Also, optical emission spectroscopy study was applied on some atomic helium lines to obtain temperature of electrons in the non-thermal plasma

  15. Evaluation on the Toxic Effects of NanoAg to Catalase.

    Science.gov (United States)

    Zhang, Bin; Zhai, Wenxin; Liu, Rutao; Yu, Zehua; Shen, Hengmei; Hu, Xinxin

    2015-02-01

    Protein is the functional actor of life. Research on protein damage induced by nanomaterials may give insight into the toxicity mechanisms of nanoparticles. Studying nano silver over the impact of the structure and function of catalase (CAT) at the molecular level, is of great significance for a comprehensive evaluation of their toxic effects. The toxic effects of nanoAg on catalase were thoroughly investigated using steady state and time resolved fluorescence quenching measurements, ultraviolet-visible absorption spectroscopy, resonance light scattering spectroscopy (RLS), circular dichroism spectroscopy (CD) and transmission electron microscopy (TEM). NanoAg could decrease the amount of alpha-helix and increase the beta sheet structure, leading to loose the skeleton structure of catalase. The characteristic fluorescence of catalase was obviously quenched, which showed the exposal of internal hydrophobic amino acids enhanced, and its quenching type is dynamic quenching. The result of RLS and TEM showed that the distribution and size of nanoAg become more uniform and smaller after their interaction, resulting in a decrease of RLS intensity. NanoAg could make the activity of catalase rise. By changing the structure of catalase, nanoAg increases its enzymatic activity to a certain extent, breaking down its balance in vivo, thereby affecting the normal physiological activities. NanoAg has obvious toxic effects on catalase. This paper provided a new perspective and method for the toxic effects of nanoAg to biological macromolecules; provided basic data and reference gist for the hygienics and toxicology studies of nanoAg. It is conducive to the toxicity prevention and control work of nanoAg, promoting nano-technology applied to human production and living better.

  16. Toxic effects of sublethal concentrations of diethyl Phthalate on the ...

    African Journals Online (AJOL)

    An investigation on the effect of Diethyl phthalate (DEP) on the gill of the African catfish Clarias gariepinus was carried out in the laboratory. Seventy-five (75) catfish fingerlings were subjected to continuous exposure to sublethal concentrations of DEP (30, 40, 60 and 80 ìg/L) for a period of four weeks. The gills of the catfish ...

  17. Toxic effects of neem products ( Azadirachta indica A. Juss) on ...

    African Journals Online (AJOL)

    Treatment and comparative analysis of the properties of aqueous extracts of seed kernel of Azadirachta indica A. Juss (neem) was carried out on Aedes aegypti larvae. The aim of this work was to evaluate lethal effects of neem products (1% Suneem, formulated neem oil and neem powder) on A. aegypti larvae. Assays ...

  18. Bioaccumulation and toxic effects of some heavy metals in ...

    African Journals Online (AJOL)

    The contamination of the aquatic systems with heavy metals from natural anthropogenic sources has become a global problem which poses threats to ecosystems and natural communities. Hence this study reviews the effects of heavy metals in freshwater fishes. Fishes bioaccumulate heavy metals (including cadmium, zinc ...

  19. Ecological effects of ionizing radiation and other toxic agents on the aquatic microcosm

    International Nuclear Information System (INIS)

    Fuma, Shoichi; Ishii, Nobuyoshi; Tanaka, Nobuyuki; Takeda, Hiroshi; Miyamoto, Kiriko; Yanagisawa, Kei; Kawabata, Zen'ichiro

    2004-01-01

    The purpose of this study was comparative evaluation of effects of ionizing radiation and other various toxic agents on aquatic microbial communities. For this purpose, the authors investigated effects of γ-rays, ultraviolet (UV) radiation, acidification, aluminum, manganese, nickel, copper and gadolinium on the microcosm, i.e., the experimental model ecosystem consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Eseherichia coli as a decomposer. Effects of toxic agents in the microcosm were not only direct effects but also community-level effects due to interactions among the constituting species or between organisms and toxic agents. In general, the degrees of effects observed in the microcosm could be categorized as follows: no effects; recognizable effects, i.e., decrease or increase in the cell densities of at least one species; severe effects, i.e., extinction of one or two species; and destructive effects, i.e., extinction of all species. These results were analyzed by the ecological effect index (EEI), in which differences in the cell densities between exposed and control microcosm were represented by the Euclidean distance function. A 50% effect doses for the microcosm (ED M50 ), at which the EEI became 50%, were evaluated to be 530 Gy for γ-rays, 2100 J m -2 for UV, 4100 μM for manganese, 45 μM for nickel, 110 μM for copper and 250 μM for gadolinium. (author)

  20. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    Directory of Open Access Journals (Sweden)

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  1. Near fatal 5-FU gut toxicity post surgery--remarkable effect of high-dose sucralfate.

    Science.gov (United States)

    Toh, James Wei Tatt; Morris, David; Chen, Zhuoran; Chen, Cindy

    2015-06-01

    The objective of this review article and case report was to investigate the effectiveness of high-dose sucralfate on severe life-threatening 5-fluorouracil (5-FU) gut toxicity, with reference to, but not limited to dihydropyrimidine dehydrogenase (DPD) deficiency. A search was conducted on PubMed from 1950 to July 2013 for original studies on 5-FU gut toxicity and sucralfate. Studies were limited to human trials and English language and all articles included in this study were assessed with the application of predetermined selection criteria. Each article was then reviewed independently by two reviewers. A case report from our own centre was included in this review. From 33 results, 6 manuscripts were identified including 4 randomized controlled trial. One trial evaluated the use of sucralfate to alleviate stomatitis in patients with 5-FU-based chemotherapy. The other three trials evaluated the role of sucralfate in radiation toxicity. There was one case report which showed gastroscopy confirmed normalization of severe dysplastic erosive gastroduodenitis attributed to hepatic arterial infusion of 5-FU following a 2-month course of sucralfate and cimetidine and one case series showing clinical and sigmoidoscopically demonstrated improvement in ulcerative colitis in majority of patients receiving sucralfate enemas. There was no current literature specifically focussed on the role of sucralfate in 5-FU gut toxicity. Our case report describes the clinical course and successful treatment with sucralfate of a patient with Pseudomyxoma peritonei (PMP) who experienced 5-FU gut toxicity resulting in life-threatening bleeding due to presumed DPD deficiency post intraperitoneal 5-FU administration. This review article showed a lack of literature concerning the use of sucralfate in 5-FU gut toxicity. In our patient's case, sucralfate had a crucial role in the management of near fatal 5-FU gut toxicity, and further evaluation is required.

  2. Studies of the ionizing radiation effects on the effluents acute toxicity due to anionic surfactants

    International Nuclear Information System (INIS)

    Moraes, Maria Cristina Franco de

    2004-01-01

    Several studies have shown the negative effects of surfactants, as detergents active substance, when discharged on biological sewage wastewater treatment plants. High toxicity may represent a lower efficiency for biological treatment. When surfactants are in aquatic environment they may induce a loss of grease revetment on birds (feather). Depending on the surfactant concentration, several damages to all biotic systems can happen. Looking for an alternative technology for wastewater treatment, efficient for surfactant removal, the present work applied ionizing radiation as an advanced oxidation process for affluents and effluents from Suzano Treatment Station. Such wastewater samples were submitted to radiation using an electron beam from a Dynamic Electron Beam Accelerator from Instituto de Pesquisas Energeticas e Nucleares. In order to assess this proposed treatment efficacy, it was performed acute toxicity evaluation with two test-organisms, the crustacean Daphnia similis and the luminescent bacteria Vibrio fischeri. The studied effluents were: one from a chemical industry (IND), three from sewage plant (affluents - GG, GM and Guaio) and the last biologically treated secondary effluent (EfF), discharged at Tiete river. The applied radiation doses varied from 3 kGy to 50 kGy, being 50 kGy enough for surfactant degradation contained at industrial effluent. For GG, GM and Guaio samples, doses of 6 kGy and 10 kGy were efficient for surfactant and toxicity reduction, representing an average removal that varied from 71.80% to 82.76% and toxicity from 30% to 91% for most the effluents. The final effluent was less toxic than the others and the radiation induced an average 11% removal for anionic surfactant. The industrial effluents were also submitted to an aeration process in order to quantify the contribution of surfactant to the whole sample toxicity, once it was partially removed as foam and several fractions were evaluated for toxicity. (author)

  3. Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview

    Directory of Open Access Journals (Sweden)

    Sai Sandeep Singh Rowdhwal

    2018-01-01

    Full Text Available Di-2-ethylhexyl phthalate (DEHP is extensively used as a plasticizer in many products, especially medical devices, furniture materials, cosmetics, and personal care products. DEHP is noncovalently bound to plastics, and therefore, it will leach out of these products after repeated use, heating, and/or cleaning of the products. Due to the overuse of DEHP in many products, it enters and pollutes the environment through release from industrial settings and plastic waste disposal sites. DEHP can enter the body through inhalation, ingestion, and dermal contact on a daily basis, which has raised some concerns about its safety and its potential effects on human health. The main aim of this review is to give an overview of the endocrine, testicular, ovarian, neural, hepatotoxic, and cardiotoxic effects of DEHP on animal models and humans in vitro and in vivo.

  4. Characterization of cholinesterases in Chironomus riparius and the effects of three herbicides on chlorpyrifos toxicity.

    Science.gov (United States)

    Pérez, Joanne; Monteiro, Marta S; Quintaneiro, Carla; Soares, Amadeu M V M; Loureiro, Susana

    2013-11-15

    In this study, the toxicities of four pesticides (the herbicides atrazine, terbuthylazine, metolachlor and the insecticide chlorpyrifos) previously detected in the Alqueva reservoir/dam (south of Portugal) were evaluated individually and in binary combinations of the herbicides and the insecticide using fourth-instar larvae of the aquatic midge Chironomus riparius. Chlorpyrifos induced toxicity to midges in all the 48 h toxicity bioassays performed. The swimming behaviour of the larvae was impaired, with EC50 values ranging from 0.15 to 0.17 μg/L. However, neither s-triazine (atrazine and terbuthylazine) herbicides nor metolachlor alone at concentrations up to 200 μg/L caused significant toxicity to C. riparius. When combined with both s-triazine herbicides, chlorpyrifos toxicity was enhanced by approximately 2-fold when tested in a binary mixture experimental setup, at the 50% effective concentration levels. To evaluate how chlorpyrifos toxicity was being increased, the cholinesterases (ChE) were characterized biochemically using different substrates and selective inhibitors. The results obtained suggested that the main enzyme present in this species is acetylcholinesterase (AChE) and therefore it was assayed upon C. riparius exposures to all pesticides individually and as binary mixtures. Although atrazine and terbuthylazine are not effective inhibitors of AChE, the potentiation of chlorpyrifos toxicity by the two s-triazine herbicides was associated with a potentiation in the inhibition of AChE in midges; both s-triazine herbicides at 200 μg/L increased the inhibition of the AChE activity by 7 and 8-fold, respectively. A strong correlation was observed between swimming behaviour disturbances of larvae and the inhibition of the AChE activity. In contrast, metolachlor did not affect chlorpyrifos toxicity at any of the concentrations tested. Therefore, the herbicides atrazine and terbuthylazine can act as synergists in the presence of chlorpyrifos, increasing

  5. Hepato-toxic effect of diuron in albino rats.

    Science.gov (United States)

    Agrawal, R C; Kumar, S

    1999-05-01

    Tumour initiating/promoting effect of diuron, a widely used substituted urea herbicide, was studied in rats using liver tumour model. Chronic exposure to diuron at a dose of 250 mg/kg body wt resulted in high mortality and weight loss in treated animals. The animals which received diuron + HCH treatment showed an increase in size and weight of liver as compared to controls. Liver tumours were not observed in any of the treated group whereas some significant histological changes were seen in diuron treated rat liver. Diuron thus has been found to be hepatotoxic albeit neither tumour initiating nor promoting in rat liver tumorigenesis assay system.

  6. Toxic effects of lead on neuronal development and function

    International Nuclear Information System (INIS)

    Freedman, R.; Olson, L.; Hoffer, B.J.

    1990-01-01

    The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. The goal of the authors research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. To study neuronal development in a system that minimizes such difficulties, the authors have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development in the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Using this system, they have discovered that lead induces a hypernoradrenergic innervation of central nervous system tissue. The increased innervation is observed not only structurally, but also functionally. Since norepinephrine is an inhibitory neurotransmitter, this ingrowth may explain the profound slowing of discharge of cerebellar neurons recorded in grafts of lead-treated animals. Studies in other tissues suggest that increased axonal ingrowth may be a general problem of lead intoxication that encompasses many brain areas, as well as peripheral sympathetic systems

  7. Manganese toxicity effects on nodulation and nitrogen fixation of beans (Phaseolus vulgaris L. ), in acid soils

    Energy Technology Data Exchange (ETDEWEB)

    Doebereiner, J

    1966-02-01

    Three greenhouse experiments were conducted to study manganese toxicity effects on the nitrogen fixing symbiosis of beans (Phaseolus vulgaris). Addition of 40 ppm of manganese to two acid soils affected nodulation and nitrogen fixation. Dependent on the Rhizobion strain either nodule numbers or efficiency in nitrogen fixation were reduced; the efficiency of one Rhizobium-host combination was more affected than another. Under less severe conditions of manganese toxicity, reduction of nodule numbers or of efficiency in nitrogen fixation could be compensated by an increase of nodule size. In the absence of manganese toxicity nodulation and nitrogen fixation of beans were abundant in a soil with pH 4.4. Naturally occurring manganese toxicity in a gray hydromorphic soil was eliminated by liming. The total nitrogen content of bean plants which were dependent on symbiotic nitrogen fixation decreased linearly with the logarithm of the manganese concentration in the plants. This did not happen when the plants were grown with mineral nitrogen. The role of manganese toxicity in the well known sensitivity to acid soil conditions of certain legumes and the importance of selection of manganese tolerant Rhizobium strains for the inoculation of beans in acid tropical soils, are discussed. 25 references, 1 figure, 6 tables.

  8. Toxic effects of several phthalate esters on the embryos and larvae of abalone Haliotis diversicolor supertexta

    Science.gov (United States)

    Yang, Zhihui; Zhang, Xiangjing; Cai, Zhonghua

    2009-05-01

    As the most widely used plasticizers in the world, phthalate esters (PAEs) are potential endocrine disruption compounds (EDCs). In the present study, the toxicity of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) on embryogenesis and larvae development of the marine univalve Haliotis diversicolor supertexta was examined in laboratory. The results show that the malformation of embryos appeared during the experiment, such as embryos died or lysed, small transparent flocculent rings studded on the periphery of the embryo, and the larvae could failed to hatch. In embryo toxic test, embryos incubated at the highest concentration of DMP, DEP and DBP solutions showed significantly high abnormal rate compared with the control, while DEHP solutions displayed no significant difference. In larval toxic test, in all concentrations of DMP, DEP and DBP solutions, larval settlement rates were low significantly than that of the control. Similarly, DEHP solutions show nearly no effect on the larval settlement. The order of toxicity on embryos and larvae is DBP>DEP>DMP>DEHP. Being a simple and easy stimulation to indoor spawn, sensitive to environmental factors, and short culture time, the embryos of H. diversicolor supertexta can be used to indicate toxicity of the PAEs.

  9. Effect of pH on the toxicity and bioconcentration of sulfadiazine on Daphnia magna

    DEFF Research Database (Denmark)

    Anskjær, Gitte Gotholdt; Rendal, Cecilie; Kusk, Kresten Ole

    2013-01-01

    The antimicrobial sulfonamide sulfadiazine has in the last decades been detected in environmental water bodies, both surface and ground water. Since pH in the environment may vary considerably, this study examined the toxicity of the amphoter sulfadiazine towards Daphnia magna at pH levels of 6.......0, 7.5 and 8.5, thus taking the impact of speciation into consideration, contrary to earlier eco-toxicity studies conducted at standard conditions. Toxicity tests were performed using the standard ISO 6341 test procedure modified to accommodate the three pH levels and the toxicity was expressed as EC50....... After 48h the EC50 was determined to be 27.2, 188 and 310mgL−1 at pH 6.0, 7.5 and 8.5, respectively, thus demonstrating a significant effect of pH on the toxicity of sulfadiazine. Furthermore, the bioconcentration factor (dry weight) was determined to be 50 and 36 at pH 6.0 and 8.5, respectively...

  10. Sub-acute toxicity and biochemical effects of extracts of Anaphe ...

    African Journals Online (AJOL)

    Ataxia syndrome which is characterized by sudden onset of severe muscular tremor and gait ataxia has been shown to be associated with the consumption of the larvae of Anaphe venata in South Western part of Nigeria. In this report, the sub -acute toxicity and biochemical effects of polar and nonpolar extracts of Anaphe ...

  11. Toxic and radiosensitizina effect of reduced nitroimidazoles on E.COLI B/r cells

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Semin, Yu.A.; Petrova, K.M.; Kutmin, A.I.

    1983-01-01

    The spectrophotometric method was used to study the rate of chemical reduction of misonidazole and metronidazole by NH 4 Cl and Zn in the atmosphere of argon and oxygen. Reduction of drugs increased their toxicity for hypoxic and oxygenated E. coli B/r. The reduced metronidazole is a more effective radiosensitizer of hypoxic E. coli B/r than the original compound

  12. The effect of mixotrophic chrysophyte on toxic and colony-forming cyanobacteria

    NARCIS (Netherlands)

    Van Donk, E.; Cerbin, S.; Wilken, S.; Helmsing, N.R.; Ptacnik, R.; Verschoor, A.M.

    2009-01-01

    1. In order to test the effect of Ochromonas sp., a mixotrophic chrysophyte, on cyanobacteria, grazing experiments were performed under controlled conditions. We studied grazing on three Microcystis aeruginosa strains, varying in toxicity and morphology, as well as on one filamentous cyanobacterium,

  13. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    Directory of Open Access Journals (Sweden)

    Aicha Fassi Fihri

    2016-06-01

    Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

  14. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

    Science.gov (United States)

    Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

    2016-01-01

    Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

  15. The Use of Paramecium to Observe the Toxic Effect of Cigarette Smoke.

    Science.gov (United States)

    Bardell, David

    1986-01-01

    Describes a laboratory experiment in which Paramecium caudatum was used to demonstrate the toxic effect of cigarette smoke on the cilia of epithelium cells lining the trachea and bronchi of smokers. Provides background information and explains the procedure, including how to make a simple mechanical smoking device. (TW)

  16. The effects of smoke hand grenades on human lung cells and bacteria for toxicity screening purposes

    NARCIS (Netherlands)

    Hulst, M. van; Klerk, W.P.C. de; Langenberg, J.P.; Tuinman, I.L.; Alblas, M.J.

    2013-01-01

    Exposure to signaling smoke is almost impossible to avoid, and may have adverse health effects. Hand grenades with signaling smoke are used during training and/or military operations. To obtain the most realistic results when estimating the toxicity of the smoke, not only the smoke–forming

  17. Sublethal Toxic effects of spent Oil Based Drilling Mud and Cuttings ...

    African Journals Online (AJOL)

    Sublethal toxic effects of spent oil based drilling mud collected from an abandoned oil drilling site in Mpanak, Akwa Ibom State, Nigeria were assessed in the earthworm Aporrectodea longa. The test annelid was exposed to sub-lethal Concentration of 0ppm SPP; 62,500ppm SPP; 125, 000ppm SPP; 250,000ppm SPP and ...

  18. Sulfur dioxide : Relevance of toxic and nutritional effects for Chinese cabbage

    NARCIS (Netherlands)

    Yang, Liping; Stulen, Ineke; De Kok, Luit J.

    2006-01-01

    Shoots of Chinese cabbage formed a sink for atmospheric SO2 and there was a linear relation between the rate of uptake and the atmospheric SO2 level (0.03-1.4 mu l l(-1)). Chinese cabbage appeared to be rather susceptible to the toxic effects of SO2. Shoot biomass production was reduced upon

  19. Toxicity bioassay and effects of sub-lethal exposure of malathion on ...

    African Journals Online (AJOL)

    Ksu-network

    2012-04-26

    Apr 26, 2012 ... glutamate pyruvic transaminase. Non-target animals including fish are greatly affected by the indiscriminate use of these pesticides. Fish appear to posses the same biochemical pathways to deal with the toxic effects of endogenous and exogenous agents as mammalian species does (Lackner, 1998).

  20. GLOBOX : A spatially differentiated global fate, intake and effect model for toxicity assessment in LCA

    NARCIS (Netherlands)

    Wegener Sleeswijk, Anneke; Heijungs, Reinout

    GLOBOX is a model for the calculation of spatially differentiated LCA toxicity characterisation factors on a global scale. It can also be used for human and environmental risk assessment. The GLOBOX model contains equations for the calculation of fate, intake and effect factors, and equations for

  1. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity

    DEFF Research Database (Denmark)

    Høgberg, Lotte Christine Groth; Bania, Theodore C; Lavergne, Valéry

    2016-01-01

    BACKGROUND: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid......-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. RESULTS: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human...... case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context...

  2. Lead toxicity in rice: effects, mechanisms, and mitigation strategies--a mini review.

    Science.gov (United States)

    Ashraf, Umair; Kanu, Adam Sheka; Mo, Zhaowen; Hussain, Saddam; Anjum, Shakeel Ahmad; Khan, Imran; Abbas, Rana Nadeem; Tang, Xiangru

    2015-12-01

    Lead (Pb) is a major environmental pollutant that affects plant morpho-physiological and biochemical attributes. Its higher levels in the environment are not only toxic to human beings but also harmful for plants and soil microbes. We have reviewed the uptake, translocation, and accumulation mechanisms of Pb and its toxic effects on germination, growth, yield, nutrient relation, photosynthesis, respiration, oxidative damage, and antioxidant defense system of rice. Lead toxicity hampers rice germination, root/shoot length, growth, and final yield. It reduces nutrient uptake through roots, disrupts chloroplastic ultrastructure and cell membrane permeability, induces alterations in leaves respiratory activities, produces reactive oxygen species (ROS), and triggers some enzyme and non-enzymatic antioxidants (as defense to oxidative damage). In the end, biochar amendments and phytoremediation technologies have been proposed as soil remediation approaches for Pb tainted soils.

  3. Effect of lead toxicity on aquatic macrophyte Elodea canadensis Michx.

    Science.gov (United States)

    Dogan, Muhittin; Saygideger, Saadet Demirors; Colak, Ugur

    2009-08-01

    Effects of Pb accumulation on the contents of chlorophylls (a and b), carotenoid, ascorbic acid (AsA), non-protein SH groups and protein were investigated in aquatic macrophyte Elodea canadensis. Pb accumulation in E. canadensis tissues increased with increasing metal concentrations. The increases at 1, 10 and 100 mg/L Pb are about 12.0, 44.6 and 71.1 times greater than control, respectively. Contents of chlorophylls, carotenoid and protein were adversely affected by Pb accumulation. Induction of non-protein SH groups and AsA showed that Pb accumulation caused oxidative stress. It is also possible that increased non-protein SH groups by Pb accumulation may be due to their role in Pb detoxification.

  4. Toxicity of silica nanoparticles and the effect of protein corona

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus; Jespersen, Lars Vesterby; Wang, Jing

    2010-01-01

      The cytotoxicity of silica nanoparticles (NPs) was investigated in the human lung cell line, A549. Silica NPs of different sizes (DLS size; 16-42 nm) were used to determine appropriate dose metrics whereas the effect of the NP corona was tested by coating the NPs with bovine serum albumin (BSA......). The NPs were characterized by TEM and DLS as monodisperse and non-aggregated in solution and the NP suspensions were free of metal and endotoxin impurities as tested by ICP-MS and the LAL test. Cellular uptake and binding of the silica NPs was indirectly assessed by flow cytometry side scatter and SEM...... upon silica NP exposure. The silica NP surface area was found to be the best dose metric for predicting cytotoxicity and IL-8 release. Generally, the NPs were only cytotoxic at high concentrations and BSA-coating of the NPs significantly decreased the cytotoxicity and cellular IL-8 secretion. All...

  5. Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

    Energy Technology Data Exchange (ETDEWEB)

    Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2016-01-01

    Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late

  6. Protective effect of riboflavin on cisplatin induced toxicities: a gender-dependent study.

    Science.gov (United States)

    Naseem, Imrana; Hassan, Iftekhar; Alhazza, Ibrahim M; Chibber, Sandesh

    2015-01-01

    The toxicity exerted by the anticancer drug, cisplatin in vivo is functional to many factors such as dose, duration, gender and age etc. The present study is aimed to investigate if ameliorative potential of riboflavin on cisplatin induced toxicity is gender dependent. Eighty four adult mice from male and female sex were divided into seven groups (n=6) for both sexes. They were treated with riboflavin (2mg/kg), cisplatin (2mg/kg) and their two different combinations (cisplatin at 2mg/kg with 1mg/kg and 2mg/kg of riboflavin) under photoillumination with their respective controls for the combination groups without photoillumination. After treatment, all groups were sacrificed and their kidney, liver and serum were collected for biochemical estimations, comet assay and histopathology. In the present investigation, it was evident from antioxidant and detoxification studies (SOD, CAT, GSH, GST, MDA and carbonyl level) that the female mice exhibited better tolerance towards cisplatin inducted toxicity and the ameliorative effect of riboflavin against cisplatin toxicity was found stronger in their combination groups as compared to the male groups as the activity of all antioxidant enzymes were found better concomitant with lower level of MDA and carbonyl contents in the female combination groups than their male counterparts. Furthermore, single cell gel electrophoresis and histopathological examination confirmed that restoration of normal nuclear and cellular integrity was more prominent in female with respect to the males after treatment in the combination groups in a dose-dependent manner. Hence, this study reveals that cisplatin is more toxic in male mice and the ameliorative effect of riboflavin against cisplatin toxicity is stronger in female mice. Copyright © 2014. Published by Elsevier GmbH.

  7. Matrix effect on paralytic shellfish toxins quantification and toxicity estimation in mussels exposed to Gymnodinium catenatum.

    Science.gov (United States)

    Botelho, M J; Vale, C; Mota, A M; Rodrigues, S M; Costa, P R; Simões Gonçalves, M L S

    2010-12-01

    Paralytic shellfish toxins were quantified in whole tissues of the mussel Mytilus galloprovincialis exposed to blooms of the dinoflagellate Gymnodinium catenatum in Portuguese coastal waters. A validated liquid chromatography method with fluorescence detection, involving pre-chromatographic oxidation was used to quantify carbamoyl, N-sulfocarbamoyl and decarbamoyl toxins. In order to test for any matrix effect in the quantification of those toxins, concentrations obtained from solvent and matrix matched calibration curves were compared. A suppression of the fluorescence signal was observed in mussel extract or fraction in comparison to solvent for the compounds dcGTX2 + 3, GTX2 + 3 and GTX1 + 4, while an enhancement was found for C1 + 2, dcSTX, STX, B1, dcNEO and NEO. These results showed that a matrix effect varies among compounds. The difference of concentrations between solvent and matrix matched calibration curves for C1 + 2 (median = 421 ng g⁻¹) exceeded largely the values for the other quantified compounds (0.09-58 ng g⁻¹). Those differences were converted into toxicity differences, using Oshima toxicity equivalence factors. The compounds C1 + 2 and dcNEO were the major contributors to the differences of total toxicity in the mussel samples. The differences of total toxicity were calculated in ten mussel samples collected during a 10-week blooming period in Portuguese coastal lagoon. Values varied between 53 and 218 µg STX equivalents kg⁻¹. The positive differences mean that the estimated toxicity using solvent calibration curves exceed the values taking into account the matrix. For the toxicity interval 200-800 µg STX equivalents kg⁻¹ an increase was found between 44 and 28%.

  8. Combined effect of salt and drought on boron toxicity in Puccinellia tenuiflora.

    Science.gov (United States)

    Liu, Chunguang; Dai, Zheng; Xia, Jingye; Chang, Can; Sun, Hongwen

    2018-08-15

    Boron toxicity is a worldwide problem, usually accompanied by salt (NaCl) and drought. The combined stresses may induce complex toxicity to the plant. The aim of the present study was to investigate how the combined stresses of salt and drought affect B toxicity in plants. Puccinellia tenuiflora seedlings were planted in vermiculite. A three (B) × three (salt) × three (drought) factorial experiment (for a total of 27 treatments) was conducted. After a 30-day cultivation, plants were harvested to determine dry weight and the concentrations of B, Na + , K + , Ca 2+ , and Mg 2+ . Plant growth was inhibited by B toxicity, which was alleviated by salt and drought. B stress enhanced B uptake and transport of the plant, which was inhibited by salt and drought. B stress had a little effect on K + and Na + concentration and caused Ca 2+ and Mg 2+ accumulation in the plant. Salt addition increased Na + concentration and inhibited Ca 2+ and Mg 2+ accumulation. Drought addition inhibited Na + accumulation and enhanced Ca 2+ and Mg 2+ accumulation. The combined stresses of salt and drought had a greater alleviation on the inhibition of dry weight caused by B than individual salt and drought. Besides, the combined stresses of salt and drought also enhanced B uptake and inhibited B transport. The results indicate that salt, drought, and the combined stresses of salt and drought all can alleviate B toxicity in P. tenuiflora, the main mechanism of which is the restriction of B and Na + uptake caused by salt and drought. The combined stresses of salt and drought have a greater effect on B toxicity than individual salt and drought. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Comparative effect of collaborative care, pain medication, and duloxetine in the treatment of major depressive disorder and comorbid (Sub)chronic pain: Results of an exploratory randomized, placebo-controlled, multicenter trial (CC:PAINDIP)

    NARCIS (Netherlands)

    de Heer, Eric W.; Dekker, Jack; Beekman, Aartjan T.F.; van Marwijk, Harm W.J.; Holwerda, Tjalling J.; Bet, Pierre M.; Roth, Joost; Timmerman, Lotte; van der Feltz-Cornelis, Christina M.

    2018-01-01

    Objective: Evidence exists for the efficacy of collaborative care (CC) for major depressive disorder (MDD), for the efficacy of the consequent use of pain medication against pain, and for the efficacy of duloxetine against both MDD and neuropathic pain. Their relative effectiveness in comorbid MDD

  10. Structural and toxic effect investigation of vanadium pentoxide

    Energy Technology Data Exchange (ETDEWEB)

    Yuvakkumar, R., E-mail: yuvakkumar@gmail.com [Nanomaterials Laboratory, Department of Physics, Alagappa University, Karaikudi 630 004, Tamil Nadu (India); Department of Nanomaterials Engineering, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Hong, S.I., E-mail: sihong@cnu.ac.kr [Department of Nanomaterials Engineering, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2016-08-01

    A facile inorganic complex synthesis route has been developed to synthesis V{sub 2}O{sub 5} nanostructures. The effects of varying incubation time on the crystallinity and morphology of the V{sub 2}O{sub 5} phase has been investigated. The obtained XRD result clearly revealed the pure orthorhombic V{sub 2}O{sub 5} crystalline phase. Raman antiphase bridging V−O and chaining V−O stretching modes peaks at 686 and 521 cm{sup −1} attributed orthorhombic V{sub 2}O{sub 5} characteristics. The V2{sub p3/2} peak at the binding energies of 517 eV and V2{sub p1/2} peak at 524 eV assigned to V{sup 5+} oxidation state. Bioinspired V{sub 2}O{sub 5} nanostructures as a biocompatible material for anticancer agents show excellent cytotoxicity at higher V{sub 2}O{sub 5} concentration. - Highlights: • Sustainable and eco-friendly approach of vanadium pentoxide formation • Excellent cytotoxicity at higher V{sub 2}O{sub 5} concentration • Varying incubation on V{sub 2}O{sub 5} crystallinity and morphology was investigated.

  11. BISPHENOL A AND ITS POTENTIAL TOXIC EFFECTS ON LIVING ORGANISMS

    Directory of Open Access Journals (Sweden)

    Irena Šutiaková

    2012-10-01

    Full Text Available Bisphenol A (BPA, 2, 2,-bis (4-hydroxyphenyl propane, CAS No. 80-05-7, is an industrial chemical that is made by combining acetone and phenol. Food is acknowledged to be a main source of exposure to BPA as a consequence of BPA migration from food containers. Several studies have reported BPA migrations from can surface coatings or plastics into foods and food-simulating liquids at high temperatures, and with repeated use of plastic products. Evaluation of BPA confirmed a no-observable adverse effect level (NOAEL of 5 mg/kg/body weight/day and established a maximum total daily intake (TDI of 0.05 mg/kg body weight. A metabolism of BPA is characterized mainly by phase II conjugation reactions in the gastrointestinal tract and in the liver. The presence of BPA in the environment can cause serious health problems (endocrine disruptions, neurotoxic, genotoxic and other problems. However, there are controversial opinions about BPA. Based on current knowledge of literature the need for further experimental studies in addressing health of human and animal populations living in different ecosystems may be still useful.

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

    Science.gov (United States)

    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 (ptest, 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.

  13. Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals.

    Science.gov (United States)

    Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

    2009-06-01

    The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose-response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2(n) factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.

  14. Effect of Associated Bacteria on the Growth and Toxicity of Alexandrium catenella

    Science.gov (United States)

    Uribe, Paulina; Espejo, Romilio T.

    2003-01-01

    Saprophytic bacteria in cultures of the marine dinoflagellate Alexandrium catenella were removed to assess their effect on growth and paralytic shellfish poisoning toxin production of this dinoflagellate. The actual axenic status was demonstrated by the lack of observable bacteria both immediately after treatment and following extended incubation in the absence of antibiotics. Bacteria were measured by counting CFU and also by epifluorescence microscopy and PCR amplification of bacterial 16S-23S spacer ribosomal DNA to detect noncultivable bacteria. Removal of bacteria did not have any effect on the growth of the dinoflagellate except for the inhibition of A. catenella disintegration after reaching the stationary phase. Toxicity was determined in dinoflagellate cell extracts by different methods: high-performance liquid chromatography (HPLC); an electrophysiological test called the Electrotest, which measures the inhibition of saxitoxin-sensitive Na+ channels expressed in a cell line; and a mouse bioassay, which measures the toxic effect on the whole mammal neuromuscular system. A lower toxicity of the dinoflagellates in axenic culture was observed by these three methods, though the difference was significant only by the mouse bioassay and HPLC methods. Altogether the results indicate that axenic cultures of A. catenella are able to produce toxin, though the total toxicity is probably diminished to about one-fifth of that in nonaxenic cultures. PMID:12514056

  15. A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone

    International Nuclear Information System (INIS)

    Hatch, G.E.; Koren, H.; Aissa, M.

    1989-01-01

    Present models for predicting the pulmonary toxicity of O 3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O 3 mass balance and species comparisons of mechanisms that protect tissue against O 3 . The goal of the study described was to identify a method to directly compare O 3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O 3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18 O-labeled O 3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O 3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O 3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18 O 3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O 3 to alveoli of animals or humans

  16. Monitoring the effectiveness of remediation techniques using sediment toxicity tests with the amphipod Eohaustorius estuarius

    International Nuclear Information System (INIS)

    Doe, K.G.; Jackman, P.M.; Lee, K.

    2002-01-01

    The results of a controlled oil release experiment of weathered crude oil was presented. The released oil was applied to a tidal saltwater marsh at Conrod's Beach, Nova Scotia, Canada. The study included 3 replicate blocks which included 2 unoiled treatments and 4 oiled treatments for each block. One unoiled site had no treatment, the second unoiled site had nutrient addition to examine the effect of nutrients. The oiled treatments included natural attenuation, nutrient addition, nutrient addition with plants, and nutrient addition with a garden aerator to introduce oxygen. A standard lab procedure was used to analyze the sediments to determine the effectiveness of the technique as well as the toxic effects on the survival of the amphipod Eohaustorius estuarius. Test results indicated that the unoiled sites were non-toxic, with a slight decrease in survival in the treatment with nutrient addition. All the oiled sites were very toxic at first, but toxicity decreased gradually with time. Treatment with nutrient addition with a garden aerator proved to be the most complete and fastest detoxification method. 8 refs., 4 tabs., 2 figs

  17. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  18. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

    Science.gov (United States)

    Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

  19. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  20. Comparative Effect of Collaborative Care, Pain Medication, and Duloxetine in the Treatment of Major Depressive Disorder and Comorbid (SubChronic Pain: Results of an Exploratory Randomized, Placebo-Controlled, Multicenter Trial (CC:PAINDIP

    Directory of Open Access Journals (Sweden)

    Eric W. de Heer

    2018-04-01

    Full Text Available ObjectiveEvidence exists for the efficacy of collaborative care (CC for major depressive disorder (MDD, for the efficacy of the consequent use of pain medication against pain, and for the efficacy of duloxetine against both MDD and neuropathic pain. Their relative effectiveness in comorbid MDD and pain has never been established so far. This study explores the effectiveness of CC with pain medication and duloxetine, and CC with pain medication and placebo, compared with duloxetine alone, on depressive and pain symptoms. This study was prematurely terminated because of massive reorganizations and reimbursement changes in mental health care in the Netherlands during the study period and is therefore of exploratory nature.MethodsThree-armed, randomized, multicenter, placebo-controlled trial at three specialized mental health outpatient clinics with patients who screened positive for MDD. Interventions lasted 12 weeks. Pain medication was administered according to an algorithm that avoids opiate prescription as much as possible, where paracetamol, COX inhibitors, and pregabalin are offered as steps before opiates are considered. Patients who did not show up for three or more sessions were registered as non-compliant. Explorative, intention-to-treat and per protocol, multilevel regression analyses were performed. The trial is listed in the trial registration (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1089; NTR number: NTR1089.ResultsSixty patients completed the study. Patients in all treatment groups reported significantly less depressive and pain symptoms after 12 weeks. CC with placebo condition showed the fastest decrease in depressive symptoms compared with the duloxetine alone group (b = −0.78; p = 0.01. Non-compliant patients (n = 31 did not improve over the 12-week period, in contrast to compliant patients (n = 29. Pain outcomes did not differ between the three groups.ConclusionIn MDD and pain, patient

  1. Evaluating the toxic effects of three priority hazardous and noxious substances (HNS) to rotifer Brachionus plicatilis.

    Science.gov (United States)

    Zheng, Lei; Pan, Luqing; Lin, Pengfei; Miao, Jingjing; Wang, Xiufen; Lin, Yufei; Wu, Jiangyue

    2017-12-01

    Hazardous and noxious substances (HNS) spill in the marine environment is an issue of growing concern, and it will mostly continue to do so in the future owing to the increase of high chemical traffic. Nevertheless, the effects of HNS spill on marine environment, especially on aquatic organisms are unclear. Consequently, it is emergent to provide valuable information for the toxicities to marine biota caused by HNS spill. Accordingly, the acute toxicity of three preferential HNS and sub-lethal effects of acrylonitrile on Brachionus plicatilis were evaluated. The median lethal concentration (LC 50 ) at 24 h were 47.2 mg acrylonitrile L -1 , 276.9 mg styrene L -1 , and 488.3 mg p-xylene L -1 , respectively. Sub-lethal toxicity effects of acrylonitrile on feeding behavior, development, and reproduction parameters of B. plicatilis were also evaluated. Results demonstrated that rates of filtration and ingestion were significantly reduced at 2.0, 4.0, and 8.0 mg L -1 of acrylonitrile. Additionally, reproductive period, fecundity, and life span were significantly decreased at high acrylonitrile concentrations. Conversely, juvenile period was significantly increased at the highest two doses and no effects were observed on embryonic development and post-reproductive period. Meanwhile, we found that ingestion rate decline could be a good predictor of reproduction toxicity in B. plicatilis and ecologically relevant endpoint for toxicity assessment. These data will be useful to assess and deal with marine HNS spillages.

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

    Science.gov (United States)

    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.

  3. Ecological effects of low toxicity oil-based mud drilling in the Beatrice oilfield

    Energy Technology Data Exchange (ETDEWEB)

    Addy, J M; Hartley, J P; Tibbetts, P J.C.

    1984-12-01

    To investigate the effects of drilling discharges on the seabed fauna, surveys were carried out in the Beatrice oilfield after drilling 13 wells with water-based muds, and then after one and five further wells had been drilled using low toxicity oil-based muds. Localized benthic effects were found after the water-based mud drilling. After the use of oil-based muds, the nature of the effects was different, although there was little increase in the area involved. Possible reasons for this are discussed and burial and organic enrichment are suggested as the major influences. It is concluded that the use of low toxicity oil-based mud at Beatrice has resulted in only limited benthic effects, suggesting that the use of these muds is environmentally acceptable.

  4. Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

    Science.gov (United States)

    Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

    2016-10-01

    A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

  5. Effect of titanium dioxide nanoparticles on the bioavailability, metabolism, and toxicity of pentachlorophenol in zebrafish larvae

    International Nuclear Information System (INIS)

    Fang, Qi; Shi, Xiongjie; Zhang, Liping; Wang, Qiangwei; Wang, Xianfeng; Guo, Yongyong; Zhou, Bingsheng

    2015-01-01

    Highlights: • Effects of n-TiO 2 on toxicity of PCP in zebrafish larvae were investigated. • Co-exposure n-TiO 2 enhanced metabolism of PCP to tetrachlorohydroquinone in larvae. • Co-exposure n-TiO 2 increased oxidative damage and developmental toxicity in larvae. • NPs may influence toxicity of associated organic pollutants in the aquatic environment. - Abstract: This study investigated the influence of titanium dioxide nanoparticles (n-TiO 2 ) on the bioavailability, metabolism, and toxicity of pentachlorophenol (PCP) in fish. Zebrafish (Danio rerio) embryos or larvae (2-h post-fertilization) were exposed to PCP (0, 3, 10, and 30 μg/L) alone or in combination with n-TiO 2 (0.1 mg/L) until 6 days post-fertilization. Results showed that n-TiO 2 treatment alone did not induce lipid peroxidation, DNA damage, as well as the generation of reactive oxygen species (ROS) in the larvae. As compared with PCP treatment, the co-exposure of PCP and n-TiO 2 enhanced the induction of ROS generation, eventually leading to lipid peroxidation and DNA damage. The nuclear factor erythroid 2-related factor 2 gene transcriptions were significantly upregulated in both PCP treatment alone and in combination with n-TiO 2 . Chemical analysis and histological examination showed that n-TiO 2 adsorb PCP, and n-TiO 2 are taken up by developing zebrafish larvae; however, PCP content was not enhanced in the presence of n-TiO 2 , but the metabolism of PCP to tetrachlorohydroquinone was enhanced in larvae. The results indicate that n-TiO 2 enhanced the metabolism of PCP and caused oxidative damage and developmental toxicity, suggesting that NPs can influence the fate and toxicity of associated organic pollutants in the aquatic environment

  6. Effect of titanium dioxide nanoparticles on the bioavailability, metabolism, and toxicity of pentachlorophenol in zebrafish larvae

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Qi [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Shi, Xiongjie [College of Life Sciences, Wuhan University, Wuhan 430072 (China); Zhang, Liping [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Qiangwei; Wang, Xianfeng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Guo, Yongyong [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhou, Bingsheng, E-mail: bszhou@ihb.ac.cn [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2015-02-11

    Highlights: • Effects of n-TiO{sub 2} on toxicity of PCP in zebrafish larvae were investigated. • Co-exposure n-TiO{sub 2} enhanced metabolism of PCP to tetrachlorohydroquinone in larvae. • Co-exposure n-TiO{sub 2} increased oxidative damage and developmental toxicity in larvae. • NPs may influence toxicity of associated organic pollutants in the aquatic environment. - Abstract: This study investigated the influence of titanium dioxide nanoparticles (n-TiO{sub 2}) on the bioavailability, metabolism, and toxicity of pentachlorophenol (PCP) in fish. Zebrafish (Danio rerio) embryos or larvae (2-h post-fertilization) were exposed to PCP (0, 3, 10, and 30 μg/L) alone or in combination with n-TiO{sub 2} (0.1 mg/L) until 6 days post-fertilization. Results showed that n-TiO{sub 2} treatment alone did not induce lipid peroxidation, DNA damage, as well as the generation of reactive oxygen species (ROS) in the larvae. As compared with PCP treatment, the co-exposure of PCP and n-TiO{sub 2} enhanced the induction of ROS generation, eventually leading to lipid peroxidation and DNA damage. The nuclear factor erythroid 2-related factor 2 gene transcriptions were significantly upregulated in both PCP treatment alone and in combination with n-TiO{sub 2}. Chemical analysis and histological examination showed that n-TiO{sub 2} adsorb PCP, and n-TiO{sub 2} are taken up by developing zebrafish larvae; however, PCP content was not enhanced in the presence of n-TiO{sub 2}, but the metabolism of PCP to tetrachlorohydroquinone was enhanced in larvae. The results indicate that n-TiO{sub 2} enhanced the metabolism of PCP and caused oxidative damage and developmental toxicity, suggesting that NPs can influence the fate and toxicity of associated organic pollutants in the aquatic environment.

  7. An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

    Science.gov (United States)

    Hoffmann, Krista Callinan; Deanovic, Linda; Werner, Inge; Stillway, Marie; Fong, Stephanie; Teh, Swee

    2016-10-01

    A novel 2-tiered analytical approach was used to characterize and quantify interactions between type I and type II pyrethroids in Hyalella azteca using standardized water column toxicity tests. Bifenthrin, permethrin, cyfluthrin, and lambda-cyhalothrin were tested in all possible binary combinations across 6 experiments. All mixtures were analyzed for 4-d lethality, and 2 of the 6 mixtures (permethrin-bifenthrin and permethrin-cyfluthrin) were tested for subchronic 10-d lethality and sublethal effects on swimming motility and growth. Mixtures were initially analyzed for interactions using regression analyses, and subsequently compared with the additive models of concentration addition and independent action to further characterize mixture responses. Negative interactions (antagonistic) were significant in 2 of the 6 mixtures tested, including cyfluthrin-bifenthrin and cyfluthrin-permethrin, but only on the acute 4-d lethality endpoint. In both cases mixture responses fell between the additive models of concentration addition and independent action. All other mixtures were additive across 4-d lethality, and bifenthrin-permethrin and cyfluthrin-permethrin were also additive in terms of subchronic 10-d lethality and sublethal responses. Environ Toxicol Chem 2016;35:2542-2549. © 2016 SETAC. © 2016 SETAC.

  8. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  9. Introducing Toxics

    Directory of Open Access Journals (Sweden)

    David C. Bellinger

    2013-04-01

    Full Text Available With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present their work in as much detail as they wish. Toxics will publish original research papers, conventional reviews, meta-analyses, short communications, theoretical papers, case reports, commentaries and policy perspectives, and book reviews (Book reviews will be solicited and should not be submitted without invitation. Toxins and toxicants concern individuals from a wide range of disciplines, and Toxics is interested in receiving papers that represent the full range of approaches applied to their study, including in vitro studies, studies that use experimental animal or non-animal models, studies of humans or other biological populations, and mathematical modeling. We are excited to get underway and look forward to working with authors in the scientific and medical communities and providing them with a novel venue for sharing their work. [...

  10. Disentangling the effects of polymer coatings on silver nanoparticle agglomeration, dissolution, and toxicity to determine mechanisms of nanotoxicity

    International Nuclear Information System (INIS)

    Zook, Justin M.; Halter, Melissa D.; Cleveland, Danielle; Long, Stephen E.

    2012-01-01

    Silver nanoparticles (AgNPs) are frequently coated with a variety of polymers, which may affect various interdependent mechanisms of toxicity or antimicrobial action, including agglomeration and dissolution rates. Here, we systematically measure how citrate, dextran, 5 and 20 kDa poly(ethylene glycol) (PEG), and poly(vinyl pyrrolidone) coatings affect AgNP agglomeration, dissolution, and toxicity. In addition, to disentangle the coatings’ effects on agglomeration from their other effects, we produce multiple stable agglomerate sizes of several of the coated ∼23 nm AgNPs ranging from singly-dispersed to mean agglomerate sizes of several hundred nanometers. These dispersions allow us to independently study the effects of agglomeration and polymer coating on dissolution rate and hemolytic toxicity. We find that both hemolytic toxicity and dissolution rate are highest for the 5 kDa PEG coating, and toxicity and dissolution rate decrease significantly with increasing agglomerate size independent of coating. This correlation between toxicity and dissolution rate suggests that both polymer coating and agglomeration may affect hemolytic toxicity largely through their effects on dissolution. Because both the AgNP dissolution rate and hemolysis decrease only moderately compared to the large increases in agglomerate size, AgNPs’ hemolytic toxicity may be caused by their large surface area and consequently high dissolution rate, rather than from other size-specific effects. At the silver concentrations used in this work, silver dissolved from AgNPs is expected to be primarily in the form of AgCl NPs, which are therefore more likely than Ag + ions to be the primary drivers of hemolytic toxicity. In addition, all AgNPs we tested are much more toxic to horse red blood cells than sheep red blood cells, highlighting the complexity of toxic responses and the need to test toxicity in multiple biological systems.

  11. Disentangling the effects of polymer coatings on silver nanoparticle agglomeration, dissolution, and toxicity to determine mechanisms of nanotoxicity

    Science.gov (United States)

    Zook, Justin M.; Halter, Melissa D.; Cleveland, Danielle; Long, Stephen E.

    2012-10-01

    Silver nanoparticles (AgNPs) are frequently coated with a variety of polymers, which may affect various interdependent mechanisms of toxicity or antimicrobial action, including agglomeration and dissolution rates. Here, we systematically measure how citrate, dextran, 5 and 20 kDa poly(ethylene glycol) (PEG), and poly(vinyl pyrrolidone) coatings affect AgNP agglomeration, dissolution, and toxicity. In addition, to disentangle the coatings' effects on agglomeration from their other effects, we produce multiple stable agglomerate sizes of several of the coated 23 nm AgNPs ranging from singly-dispersed to mean agglomerate sizes of several hundred nanometers. These dispersions allow us to independently study the effects of agglomeration and polymer coating on dissolution rate and hemolytic toxicity. We find that both hemolytic toxicity and dissolution rate are highest for the 5 kDa PEG coating, and toxicity and dissolution rate decrease significantly with increasing agglomerate size independent of coating. This correlation between toxicity and dissolution rate suggests that both polymer coating and agglomeration may affect hemolytic toxicity largely through their effects on dissolution. Because both the AgNP dissolution rate and hemolysis decrease only moderately compared to the large increases in agglomerate size, AgNPs' hemolytic toxicity may be caused by their large surface area and consequently high dissolution rate, rather than from other size-specific effects. At the silver concentrations used in this work, silver dissolved from AgNPs is expected to be primarily in the form of AgCl NPs, which are therefore more likely than Ag+ ions to be the primary drivers of hemolytic toxicity. In addition, all AgNPs we tested are much more toxic to horse red blood cells than sheep red blood cells, highlighting the complexity of toxic responses and the need to test toxicity in multiple biological systems.

  12. Disentangling the effects of polymer coatings on silver nanoparticle agglomeration, dissolution, and toxicity to determine mechanisms of nanotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zook, Justin M., E-mail: jzook@nist.gov; Halter, Melissa D.; Cleveland, Danielle; Long, Stephen E. [National Institute of Standards and Technology, Material Measurement Laboratory (United States)

    2012-10-15

    Silver nanoparticles (AgNPs) are frequently coated with a variety of polymers, which may affect various interdependent mechanisms of toxicity or antimicrobial action, including agglomeration and dissolution rates. Here, we systematically measure how citrate, dextran, 5 and 20 kDa poly(ethylene glycol) (PEG), and poly(vinyl pyrrolidone) coatings affect AgNP agglomeration, dissolution, and toxicity. In addition, to disentangle the coatings' effects on agglomeration from their other effects, we produce multiple stable agglomerate sizes of several of the coated {approx}23 nm AgNPs ranging from singly-dispersed to mean agglomerate sizes of several hundred nanometers. These dispersions allow us to independently study the effects of agglomeration and polymer coating on dissolution rate and hemolytic toxicity. We find that both hemolytic toxicity and dissolution rate are highest for the 5 kDa PEG coating, and toxicity and dissolution rate decrease significantly with increasing agglomerate size independent of coating. This correlation between toxicity and dissolution rate suggests that both polymer coating and agglomeration may affect hemolytic toxicity largely through their effects on dissolution. Because both the AgNP dissolution rate and hemolysis decrease only moderately compared to the large increases in agglomerate size, AgNPs' hemolytic toxicity may be caused by their large surface area and consequently high dissolution rate, rather than from other size-specific effects. At the silver concentrations used in this work, silver dissolved from AgNPs is expected to be primarily in the form of AgCl NPs, which are therefore more likely than Ag{sup +} ions to be the primary drivers of hemolytic toxicity. In addition, all AgNPs we tested are much more toxic to horse red blood cells than sheep red blood cells, highlighting the complexity of toxic responses and the need to test toxicity in multiple biological systems.

  13. Ameliorative effect of Zingiber officinale on diazinon -induced testicular toxicity: A biochemical, histopathological, and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    S. Yaghubi Beklar

    2017-11-01

    Full Text Available Background and objectives: Diazinon (O,O-diethyl O-2-isopropyl-6- methyl pyrimidinyl-4-g-1- phosphorothioate is one of  the organophosphate insecticides for different agricultural and gardening uses, which can be highly toxic. Zingiber officinale(ginger, a spice and herbal medicine, has antioxidant and anti-inflammatory properties. This study has investigated the effects of ginger against DZN-induced testicular toxicity. Methods: Thirty two adult male mice were randomly divided into four groups. The control group; ginger group (200 mg/kg; DZN group (10 mg/kg and ginger + DZN group. Ginger and DZN were received for 30 consecutive days by gavage and DZN treat one hour after receiving ginger. Sperm parameters, testosterone levels, biochemical, histopathological and immunohistochemical assays of testis were evaluated. Results: The results revealed that treatment with DZN caused significant damage of sperm parameters (sperm motility, count, viability rate and abnormalities, increased oxidative stress (increased MDA and decreased GSH level, significant histopathological changes and decreased Johnsen’s Score, testosterone level and increased caspase-3 immunoreactivity. Ginger preserved sperm parameters and mitigated the toxic effects of DZN. Also, pretreatment with ginger significantly reduced caspase-3 immunoreactivity. Conclusion: Our results concluded that ginger probably with its antioxidant activity and scavenging free radicals protect against DZN-induced testicular toxicity.

  14. Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review.

    Science.gov (United States)

    Guzmán-Guillén, Remedios; Puerto, María; Gutiérrez-Praena, Daniel; Prieto, Ana I; Pichardo, Silvia; Jos, Ángeles; Campos, Alexandre; Vasconcelos, Vitor; Cameán, Ana M

    2017-05-23

    Cyanobacterial toxins, particularly microcystins (MCs) and cylindrospermopsin (CYN), are responsible for toxic effects in humans and wildlife. In order to counteract or prevent their toxicity, various strategies have been followed, such as the potential application of chemoprotectants. A review of the main substances evaluated for this aim, as well as the doses and their influence on cyanotoxin-induced toxicity, has been performed. A search of the literature shows that research on MCs is much more abundant than research on CYN. Among chemoprotectants, antioxidant compounds are the most extensively studied, probably because it is well known that oxidative stress is one of the toxic mechanisms common to both toxins. In this group, vitamin E seems to have the strongest protectant effect for both cyanotoxins. Transport inhibitors have also been studied in the case of MCs, as CYN cellular uptake is not yet fully elucidated. Further research is needed because systematic studies are lacking. Moreover, more realistic exposure scenarios, including cyanotoxin mixtures and the concomitant use of chemoprotectants, should be considered.

  15. Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia

    International Nuclear Information System (INIS)

    Jin Yaping; Sun Guifan; Li Xin; Li Gexin; Lu Chunwei; Qu Long

    2004-01-01

    Arsenic toxicity is a global health problem affecting millions of people. The objectives of this study were to determine if the toxic effects on primary cultured rat astroglia would be induced by different arsenicals. Based on alamarBlue assay and the single cell gel electrophoresis (SCGE, comet assay), the cell viability and DNA damage in the cells exposed to different arsenicals were evaluated. Treatment of astroglia with methylated arsenicals, that is, pentavalent monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), resulted in no obvious changes in cell viability and DNA damage at micromolar concentrations. However, treatment of astroglia with inorganic arsenicals, that is, arsenite and arsenate, caused decreased cell viability and increased DNA damage at micromolar levels, and showing a dose-related decrease in mean alamarBlue reduced rate and a dose-related increase in mean comet length. Our study is therefore highly suggestive for a link between inorganic exposure and cellular toxicity or DNA damage. Based on the results of this study, the toxic effects induced by arsenite were stronger than those induced by arsenate

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

    Science.gov (United States)

    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.

  17. Anthelmintic effect of thymol and thymol acetate on sheep gastrointestinal nematodes and their toxicity in mice

    Directory of Open Access Journals (Sweden)

    Weibson Paz Pinheiro André

    Full Text Available Abstract Thymol is a monoterpene and acetylation form of this compound can reduce the toxicity and enhance its biological effects. The objective of this study was to evaluate the effect of thymol and thymol acetate (TA on egg, larva and adult Haemonchus contortus and the cuticular changes, acute toxicity in mice and the efficacy on sheep gastrointestinal nematodes. In vitro tests results were analyzed by analysis of variance (ANOVA and followed by comparison with Tukey test or Bonferroni. The efficacy of in vivo test was calculated by the BootStreet program. In the egg hatch test (EHT, thymol (0.5 mg/mL and TA (4 mg/mL inhibited larval hatching by 98% and 67.1%, respectively. Thymol and TA (8 mg/mL inhibited 100% of larval development. Thymol and TA (800 µg/mL reduced the motility of adult worms, by 100% and 83.4%, respectively. Thymol caused cuticular changes in adult worm teguments. In the acute toxicity test, the LD50 of thymol and TA were 1,350.9 mg/kg and 4,144.4 mg/kg, respectively. Thymol and TA reduced sheep egg count per gram of faeces (epg by 59.8% and 76.2%, respectively. In in vitro tests thymol presented better anthelmintic activity than TA. However TA was less toxic and in in vivo test efficacy was similar.

  18. Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity

    Science.gov (United States)

    Gunsolus, Ian L.; Mousavi, Maral P. S.; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L.

    2015-01-01

    The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag+ influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM’s chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution. PMID:26047330

  19. The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

    DEFF Research Database (Denmark)

    Jørgensen, Bettina Merete Pyndt; Redrobe, Paul; Brønnum Pedersen, Tina

    The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gut microbiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gut microbiota on behavior in this model, and therefore it might be relavant to include the information...

  20. Effects of soil organic matter content on cadmium toxicity in Eisenia fetida: implications for the use of biomarkers and standard toxicity tests.

    Science.gov (United States)

    Irizar, A; Rodríguez, M P; Izquierdo, A; Cancio, I; Marigómez, I; Soto, M

    2015-01-01

    Bioavailability is affected by soil physicochemical characteristics such as pH and organic matter (OM) content. In addition, OM constitutes the energy source of Eisenia fetida, a well established model species for soil toxicity assessment. The present work aimed at assessing the effects of changes in OM content on the toxicity of Cd in E. fetida through the measurement of neutral red uptake (NRU) and mortality, growth, and reproduction (Organisation for Economic Co-operation and Development [OECD] Nos. 207 and 222). Complementarily, metallothionein (MT) and catalase transcription levels were measured. To decrease variability inherent to natural soils, artificial soils (Organization for Economic Cooperation and Development 1984) with different OM content (6, 10, and 14%) and spiked with Cd solutions at increasing concentrations were used. Low OM in soil decreased soil ingestion and Cd bioaccumulation but also increased Cd toxicity causing lower NRU of coelomocytes, 100 % mortality, and stronger reproduction impairment, probably due to the lack of energy to maintain protection mechanisms (production of MT).Cd bioaccumulation did not reflect toxicity, and OM played a pivotal role in Cd toxicity. Thus, OM content should be taken into account when using E. fetida in in vivo exposures for soil health assessment.

  1. Effect of toxic metals on indigenous soil ß-subgroup proteobacterium ammonia oxidizer community structure and protection against toxicity by inoculated metal-resistant bacteria

    NARCIS (Netherlands)

    Stephen, J.R.; Chang, Y.J.; MacNaughton, S.J.; Kowalchuk, G.A.; Leung, K.T.; Flemming, C.A.; White, D.C.

    1999-01-01

    Contamination of soils with toxic metals is a major problem on military, industrial, and mining sites worldwide. Of particular interest to the field of bioremediation is the selection of biological markers for the end point of remediation, In this microcosm study, we focus on the effect of addition

  2. Modified whole effluent toxicity test to assess and decouple wastewater effects from environmental gradients.

    Directory of Open Access Journals (Sweden)

    Sebastián Sauco

    Full Text Available 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.

  3. Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity

    International Nuclear Information System (INIS)

    Kudryasheva, N.S.; Rozhko, T.V.

    2015-01-01

    The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1 – absence of effects (stress recognition), 2 – activation (adaptive response), and 3 – inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. - Highlights: • Luminous bacteria demonstrate nonlinear dose-effect relation in radioactive solutions. • Response to low-dose radiation includes 3 stages: threshold, activation, inhibition. • ROS are responsible for low-dose effects of alpha-emitting radionuclides. • Luminous marine bacteria are a convenient tool to study radiation hormesis

  4. Two stressors and a community - Effects of hydrological disturbance and a toxicant on freshwater zooplankton

    Energy Technology Data Exchange (ETDEWEB)

    Stampfli, Nathalie C. [Department of System Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig (Germany); Quantitative Landscape Ecology, Institute for Environmental Sciences, University of Koblenz-Landau, Fortstrasse 7, 76829 Landau (Germany); Knillmann, Saskia [Department of System Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig (Germany); Department of Ecosystem Analyses, Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Liess, Matthias [Department of System Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig (Germany); Noskov, Yury A. [Institute of Systematics and Ecology of Animals, Russian Academy of Sciences, Siberian Branch, Frunze St. 11, 630091 Novosibirsk (Russian Federation); Schaefer, Ralf B. [Quantitative Landscape Ecology, Institute for Environmental Sciences, University of Koblenz-Landau, Fortstrasse 7, 76829 Landau (Germany); Beketov, Mikhail A., E-mail: mikhail.beketov@ufz.de [Department of System Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig (Germany)

    2013-02-15

    Climate change models predict an increase in the frequency and intensity of extreme fluctuations in water level in aquatic habitats. Therefore, it is necessary to understand the combined effects of hydrological fluctuations and toxicants on aquatic biological communities. We investigated the individual and combined effects of the insecticide esfenvalerate and recurring fluctuations in water level on zooplankton communities in a system of 55 outdoor pond microcosms. The communities were exposed to esfenvalerate contamination as a single pulse (at 0.03, 0.3, or 3 {mu}g/L) and gradual removal of water and its subsequent replacement over three cycles and monitored until 84 days after contamination. The results showed that the sensitivities of the community and its constituent populations to the toxicant were increased by the hydrological stress. Specifically, for both the community structure and abundance of Daphnia spp. the lowest-observed-effect concentrations (LOEC) were 0.03 and 0.3 {mu}g/L for the series with fluctuating and constant water levels, respectively. Despite these differences in sensitivity, the interactive effects of the two stressors were found to be additive for both the community structure and the abundance of the most affected species. Presumably, it was not possible to detect synergism due to the strong individual effects of the water level fluctuations. Recovery times in the series exposed to the highest pesticide concentration were 64 and 55 days under fluctuating and constant water level regimes, respectively. Competition and water quality are suggested to be the major factors that underlie the observed effects of fluctuations in the water level. For the ecological risk assessment of toxicants, the present results suggest that (i) community sensitivity may vary substantially, depending on the environmental context, and (ii) this variability can be assessed experimentally to derive safety factors (coefficients used to avoid unexpected effects

  5. Effects of water chemistry on the dissolution of ZnO nanoparticles and their toxicity to Escherichia coli

    International Nuclear Information System (INIS)

    Li Mei; Lin Daohui; Zhu Lizhong

    2013-01-01

    The dissolution of ZnO nanoparticles (nano-ZnO) plays an important role in the toxicity of nano-ZnO to the aquatic organisms. The effects of water chemistry such as pH, ionic components, and dissolved organic matter (DOM) on the dissolution of nano-ZnO and its toxicity to Escherichia coli (E. coli) were investigated in synthetic and natural water samples. The results showed that the toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also the coexisting cations which could reduce the toxicity of Zn 2+ . Increasing solution pH, HPO 4 2− , and DOM reduced the concentration of free Zn 2+ released from nano-ZnO, and thus lowered the toxicity of nano-ZnO. In addition, both Ca 2+ and Mg 2+ dramatically reduced the toxicity of Zn 2+ to E. coli. These results highlight the importance of water chemistry on the toxicity evaluation of nano-ZnO in natural waters. - Highlights: ► The effects of water chemistry on the toxicity of nano-ZnO were investigated. ► Increasing solution pH, HPO 4 2− , and DOM reduced nano-ZnO toxicity to E. coli. ► Ca 2+ and Mg 2+ could dramatically reduce the toxicity of nano-ZnO to E. coli. ► Free Zn 2+ ions and water hardness together controlled nano-ZnO toxicity in waters. - The toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also Ca 2+ and Mg 2+ which could reduce the toxicity of Zn 2+ .

  6. Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Pollack, Alan; Levy, Larry; Starkschall, George; Lei Dong; Rosen, Isaac; Kuban, Deborah A.

    2002-01-01

    Purpose: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74-78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24-102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity. Results: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p 3 of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p=0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p<0.05 for all comparisons). Conclusion: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications

  7. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, ch