Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

Science.gov (United States)

Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

2017-01-01

Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute and chronic toxicity studies of the water extract from dried ...

African Journals Online (AJOL)

Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results ...

Oral ketamine for children with chronic pain: a pilot phase 1 study

Science.gov (United States)

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

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.

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 ...

Sub-acute toxicity evaluation of ethanol extract of rheumatic tea ...

African Journals Online (AJOL)

Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on body weight, ...

The chronic toxicity of molybdate to marine organisms. I. Generating reliable effects data

Energy Technology Data Exchange (ETDEWEB)

Heijerick, D.G., E-mail: Dagobert.heijerick@arche-consulting.be [ARCHE - Assessing Risks of Chemicals, Stapelplein 70 Bus 104, Gent (Belgium); Regoli, L. [International Molybdenum Association, 4 Heathfield Terrace, London, W4 4JE (United Kingdom); Stubblefield, W. [Oregon State University, Department of Environmental and Molecular Toxicology, 421 Weniger Hall, Corvallis, OR 97331 (United States)

2012-07-15

A scientific research program was initiated by the International Molybdenum Association (IMOA) which addressed identified gaps in the environmental toxicity data for the molybdate ion (MoO{sub 4}{sup 2-}). These gaps were previously identified during the preparation of EU-REACH-dossiers for different molybdenum compounds (European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances; EC, 2006). Evaluation of the open literature identified few reliable marine ecotoxicological data that could be used for deriving a Predicted No-Effect Concentration (PNEC) for the marine environment. Rather than calculating a PNEC{sub marine} using the assessment factor methodology on a combined freshwater/marine dataset, IMOA decided to generate sufficient reliable marine chronic data to permit derivation of a PNEC by means of the more scientifically robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Nine test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na{sub 2}MoO{sub 4}{center_dot}2H{sub 2}O) according to published standard testing guidelines that are acceptable for a broad range of regulatory purposes. The selected test organisms were representative for typical marine trophic levels: micro-algae/diatom (Phaeodactylum tricornutum, Dunaliella tertiolecta), macro-alga (Ceramium tenuicorne), mysids (Americamysis bahia), copepod (Acartia tonsa), fish (Cyprinodon variegatus), echinoderms (Dendraster exentricus, Strongylocentrotus purpuratus) and molluscs (Mytilus edulis, Crassostrea gigas). Available NOEC/EC{sub 10} levels ranged between 4.4 mg Mo/L (blue mussel M. edulis) and 1174 mg Mo/L (oyster C. gigas). Using all available reliable marine chronic effects data that are currently available, a HC{sub 5,50%} (median hazardous concentration affecting 5% of the species) of 5.74 (mg Mo)/L was derived with the statistical extrapolation approach, a

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.

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.

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.

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.

Chronic toxicity of ZnO nanoparticles, non-nano ZnO and ZnCl{sub 2} to Folsomia candida (Collembola) in relation to bioavailability in soil

Energy Technology Data Exchange (ETDEWEB)

Kool, Pauline L., E-mail: pauline.kool@falw.vu.nl [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Diez Ortiz, Maria [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Pole de Recherche ROVALTAIN en Toxicologie Environnementale et Ecotoxicologie, Batiment Rhovalparc, BP 15173, 26958 Valence Cedex 9 (France); Gestel, Cornelis A.M. van [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

2011-10-15

The chronic toxicity of zinc oxide nanoparticles (ZnO-NP) to Folsomia candida was determined in natural soil. To unravel the contribution of particle size and free zinc to NP toxicity, non-nano ZnO and ZnCl{sub 2} were also tested. Zinc concentrations in pore water increased with increasing soil concentrations, with Freundlich sorption constants K{sub f} of 61.7, 106 and 96.4 l/kg (n = 1.50, 1.34 and 0.42) for ZnO-NP, non-nano ZnO and ZnCl{sub 2} respectively. Survival of F. candida was not affected by ZnO-NP and non-nano ZnO at concentrations up to 6400 mg Zn/kg d.w. Reproduction was dose-dependently reduced with 28-d EC50s of 1964, 1591 and 298 mg Zn/kg d.w. for ZnO-NP, non-nano ZnO and ZnCl{sub 2}, respectively. The difference in EC50s based on measured pore water concentrations was small (7.94-16.8 mg Zn/l). We conclude that zinc ions released from NP determine the observed toxic effects rather than ZnO particle size. - Highlights: > ZnO nanoparticles and non-nano ZnO were equally toxic to Folsomia candida in soil. > Pore water from soil spiked with ZnO nanoparticles showed saturation with zinc suggesting aggregation. > Pore water based EC50 values for ZnO nanoparticles and ZnCl{sub 2} were similar. > ZnO nanoparticle toxicity in soil was most probably due to Zn dissolution from the nanoparticles. - ZnO nanoparticle toxicity to springtails in soil can be explained from Zn dissolution but not from particle size.

[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.

On the mechanism of nanoparticulate CeO{sub 2} toxicity to freshwater algae

Energy Technology Data Exchange (ETDEWEB)

Angel, Brad M., E-mail: Brad.Angel@csiro.au [Centre for Environmental Contaminants Research, CSIRO Land and Water Flagship, Locked Bag 2007, Kirrawee, NSW 2232 (Australia); Vallotton, Pascal [Digital Productivity Flagship, CSIRO, North Ryde, NSW 1670 (Australia); Apte, Simon C. [Centre for Environmental Contaminants Research, CSIRO Land and Water Flagship, Locked Bag 2007, Kirrawee, NSW 2232 (Australia)

2015-11-15

Highlights: • Nanoparticulate CeO{sub 2} less toxic than micron-sized CeO{sub 2}. • UV light filters prevented ROS generation by CeO{sub 2}. • ROS not toxic mechanism: CeO{sub 2} toxicity was similar in presence and absence of ROS. • Strong sorption of nanoparticulate CeO{sub 2} to Pseudokirchneriella subcapitata in synthetic fresh water. • CeO{sub 2} sorption to cells was prevented and toxicity mitigated in the presence of DOC. - Abstract: The factors affecting the chronic (72-h) toxicity of three nanoparticulate (10–34 nm) and one micron-sized form of CeO{sub 2} to the green alga, Pseudokirchneriella subcapitata were investigated. To characterise transformations in solution, hydrodynamic diameters (HDD) were measured by dynamic light scatter, zeta potential values by electrophoretic mobility, and dissolution by equilibrium dialysis. The protective effects of humic and fulvic dissolved organic carbon (DOC) on toxicity were also assessed. To investigate the mechanisms of algal toxicity, the CytoViva hyperspectral imaging system was used to visualise algal–CeO{sub 2} interactions in the presence and absence of DOC, and the role of reactive oxygen species (ROS) was investigated by ‘switching off’ ROS production using UV-filtered lighting conditions. The nanoparticulate CeO{sub 2} immediately aggregated in solution to HDDs measured in the range 113–193 nm, whereas the HDD and zeta potential values were significantly lower in the presence of DOC. Negligible CeO{sub 2} dissolution over the time course of the bioassay ruled out potential toxicity from dissolved cerium. The nanoparticulate CeO{sub 2} concentration that caused 50% inhibition of algal growth rate (IC50) was in the range 7.6–28 mg/L compared with 59 mg/L for micron-sized ceria, indicating that smaller particles were more toxic. The presence of DOC mitigated toxicity, with IC50s increasing to greater than 100 mg/L. Significant ROS were generated in the nanoparticulate CeO{sub 2

Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

International Nuclear Information System (INIS)

Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

2007-01-01

Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

Acute oral toxicity test of chemical compounds in silkworms.

Science.gov (United States)

Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

2016-02-01

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

Energy Technology Data Exchange (ETDEWEB)

Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

2010-03-26

As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

ZnO and TiO{sub 2} nanoparticles as novel antimicrobial agents for oral hygiene: a review

Energy Technology Data Exchange (ETDEWEB)

Khan, Shams Tabrez, E-mail: shamsalig75@gmail.com; Al-Khedhairy, Abdulaziz A. [King Saud University, Department of Zoology, College of Science (Saudi Arabia); Musarrat, Javed [AMU, Department of Agricultural Microbiology, Faculty of Agricultural Sciences (India)

2015-06-15

Oral cavity is inhabited by more than 25,000 different bacterial phylotypes; some of them cause systemic infections in addition to dental and periodontal diseases. Emergence of multiple antibiotic resistance among these bacteria necessitates the development of alternative antimicrobial agents that are safe, stable, and relatively economic. This review focuses on the significance of metal oxide nanoparticles, especially zinc oxide and titanium dioxide nanoparticles as supplementary antimicrobials for controlling oral infections and biofilm formation. Indeed, the ZnO NPs and TiO{sub 2} NPs have exhibited significant antimicrobial activity against oral bacteria at concentrations which is not toxic in in vivo toxicity assays. These nanoparticles are being produced at an industrial scale for use in a variety of commercial products including food products. Thus, the application of ZnO and TiO{sub 2} NPs as nanoantibiotics for the development of mouthwashes, dental pastes, and other oral hygiene materials is envisaged. It is also suggested that these NPs could serve as healthier, innocuous, and effective alternative for controlling both the dental biofilms and oral planktonic bacteria with lesser side effects and antibiotic resistance.

Potential fluoride toxicity from oral medicaments: A review.

Science.gov (United States)

Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

2017-08-01

The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

Directory of Open Access Journals (Sweden)

Akram Ghadirkhomi

2016-08-01

Full Text Available Objective: Pinus eldarica (P. eldarica is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50 of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels.  There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (pConclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg.

Potential fluoride toxicity from oral medicaments: A review

Directory of Open Access Journals (Sweden)

Rizwan Ullah

2017-08-01

Full Text Available The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

Oral Chromium Exposure and Toxicity

Science.gov (United States)

Sun, Hong; Brocato, Jason

2015-01-01

Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

Science.gov (United States)

Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

2016-11-01

Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Acute and chronic toxicity of Roundup Weathermax and Ignite 280 SL to larval Spea multiplicata and S. bombifrons from the Southern High Plains, USA

Energy Technology Data Exchange (ETDEWEB)

Dinehart, Simon K., E-mail: simon.dinehart@okstate.ed [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States); Smith, Loren M.; McMurry, Scott T. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States); Smith, Philip N.; Anderson, Todd A. [Institute of Environmental and Human Health, Texas Tech University, Box 41163, Lubbock, TX 79409 (United States); Haukos, David A. [U.S. Fish and Wildlife Service, MS 2125, Texas Tech University, Lubbock, TX 79409 (United States)

2010-08-15

Pesticides have been implicated in widespread amphibian declines. We assessed acute and chronic toxicity of two widely used herbicides to larval New Mexico (Spea multiplicata) and Plains (S. bombifrons) spadefoots from cropland and native grassland playas. Roundup WeatherMAX (WM) toxicity estimates (48- and 216-h LC{sub 50}; 48-h LC{sub 1}) for both species were similar to environmental concentrations expected from accidental overspray. Chronic (30-day) exposure to WM at predicted environmental concentrations (2.0 and 2.8 mg glyphosate acid equivalents/L) reduced survival of both species. Ignite 280 SL (IG) toxicity estimates (48-h LC{sub 50} and LC{sub 1}) for both species were above predicted environmental concentrations of 1.0 mg glufosinate/L. Chronic exposure to predicted environmental concentrations of IG did not reduce survival of either species. Toxicity test results suggest that at predicted environmental concentrations IG would not cause extensive mortalities among larval New Mexico and Plains spadefoots. However, WM may cause extensive mortality among larvae of these species. - Roundup WeatherMAX may cause extensive mortality among larval New Mexico and Plains spadefoots; it is unlikely that exposure to Ignite 280 SL would result in extensive mortalities.

Potential fluoride toxicity from oral medicaments: A review

OpenAIRE

Rizwan Ullah; Muhammad Sohail Zafar; Nazish Shahani

2017-01-01

The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, tox...

Toxicity of oral radiotherapy in patients with acquired immunodeficiency syndrome

International Nuclear Information System (INIS)

Cooper, J.S.; Fried, P.R.

1987-01-01

Although radiotherapy is a standard form of management of head and neck tumors, treatment of the oral cavity in patients who have the acquired immunodeficiency syndrome has produced unacceptable toxicity. Five such patients are described as a warning of enhanced toxicity of oral radiotherapy in this patient population

Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

Science.gov (United States)

Şeremet, Oana Cristina; Bărbuceanu, Florica; Ionică, Floriana Elvira; Margină, Denisa Marilena; GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Ilie, Mihaela; Gonciar, Veaceslav; Negreş, Simona; ChiriŢă, Cornel

2016-01-01

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

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

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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

Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice

Science.gov (United States)

Kalantari, Heibatullah; Salimi, Anayatollah; Rezaie, Anahita; Jazayeri Shushtari, Fereshteh; Goudarzi, Mehdi

2015-01-01

Background: The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. Objectives: The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Materials and Methods: Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. Results: The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0

[Association between oral hygiene, chronic diseases, and oral squamous cell carcinoma].

Science.gov (United States)

Huang, Jiangfeng; He, Baochang; Chen, Fa; Liu, Fangping; Yan, Lingjun; Hu, Zhijian; Lin, Lisong; He, Fei; Cai, Lin

2015-08-01

To investigate the association between oral hygiene, chronic diseases, and oral squamous cell carcinoma. We performed a case-control study with 414 cases and 870 controls in Fujian during September 2010 to January 2015. Patients were newly diagnosed oral squamous cell carcinoma cases according to the pathologic diagnoses, control subjects were enrolled from community population. Epidemiological data were collected by in-person interviews using a standard questionnaire. The contents of the questionnaire included demography character, history of tobacco smoking and alcohol drinking, dietary habits, oral hygiene status, family history of cancer, etc. Using unconditional logistic regression analysis to estimate adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI) for oral hygiene and chronic diseases. We also stratified by sex, smoking and drinking to explore possible difference in association between subgroups. The multivariate logistic regression analysis indicated that number of teeth (20-27 and oral ulceration were the risk factors of oral squamous cell carcinoma, the adjusted OR (95% CI) values were 2.01 (1.49-2.73), 3.51 (2.39-5.15), 2.33 (1.79-3.04), 3.96 (2.11-7.44), respectively; brushing tooth once per bay, brushing tooth more than once per day, regular oral health examination at least 5 years per time were the protective factors of oral squamous cell carcinoma, the adjusted OR (95% CI) values were 0.24 (0.13-0.43), 0.13 (0.07-0.24), 0.37 (0.26-0.53), respectively. The stratification analysis indicated that recurrent oral ulceration could increase the risk of oral squamous cell carcinoma for non-smokers and non-drinking, the adjusted OR (95% CI) value was 5.21 (2.42-11.18) and 4.71 (2.37-9.36); and a risky effect of hypertension on risk of oral squamous cell carcinoma was observed for non-smokers and non-drinking, the adjusted OR (95% CI) values were 1.70 (1.10-2.61) and 1.58 (1.07-2.34). Oral hygiene and chronic diseases could affect the

Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

African Journals Online (AJOL)

Erah

2010-10-21

Oct 21, 2010 ... Histopathological assessment of liver sections of treated-rats showed normal ... Keywords: Alchornea cordifolia, Rats, Subacute oral toxicity, Neutrophils, Hepatocytes, Hydropic ..... albino rats against acetaminophen-induced.

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

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.

A chronic toxicity test protocol using Caridina nilotica (Decapoda ...

African Journals Online (AJOL)

Salinization of freshwater resources is an increasing global problem, yet there is a paucity of chronic salinity tolerance data linked to very few chronic toxicity test protocols. This research aimed to generate a chronic toxicity test protocol and protective salinity tolerance data for the indigenous South African freshwater shrimp ...

Acute Oral Toxicity of 3-Chloro-4,4-dimethyl-2-oxazolidinone (Compound 1) in ICR Mice

Science.gov (United States)

1990-10-01

number) FIELD GROUP SUB-GROUP Acute Oral Toxicity, N- Chloramine , Mouse, Mammalian Toxicology, Water Disinfectant , 3-Chloro-4, 4 -dimethyl-2...Amer Ind Hyg Assoc Q 1943; 10:93-96. 7. Mora EC, Kohl HH, Wheatley WB, et al. Properties or a new chloramine disinfectant and detoxicant. Poultry Sci...ORGANIZATION Mammalian Toxicology (If applicable) US Army Biomedical Research Division of Toxicology SGRD-ULE- T and Development Laboratory 6c. ADDRESS

Chronic Exposure to Deoxynivalenol Has No Influence on the Oral Bioavailability of Fumonisin B1 in Broiler Chickens

Science.gov (United States)

Antonissen, Gunther; Devreese, Mathias; Van Immerseel, Filip; De Baere, Siegrid; Hessenberger, Sabine; Martel, An; Croubels, Siska

2015-01-01

Both deoxynivalenol (DON) and fumonisin B1 (FB1) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and integrity, by affecting the intestinal surface area and function of the tight junctions. This might influence the oral bioavailability of FB1, and possibly lead to altered toxicity of this mycotoxin. A toxicokinetic study was performed with two groups of 6 broiler chickens, which were all administered an oral bolus of 2.5 mg FBs/kg BW after three-week exposure to either uncontaminated feed (group 1) or feed contaminated with 3.12 mg DON/kg feed (group 2). No significant differences in toxicokinetic parameters of FB1 could be demonstrated between the groups. Also, no increased or decreased body exposure to FB1 was observed, since the relative oral bioavailability of FB1 after chronic DON exposure was 92.2%. PMID:25690690

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

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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.

Toxicity of nanoparticulate and bulk ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} to the nematode Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Wang Huanhua; Wick, Robert L. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Stockbridge Hall, Amherst, MA 01003 (United States); Xing Baoshan [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Stockbridge Hall, Amherst, MA 01003 (United States)], E-mail: bx@pssci.umass.edu

2009-04-15

Limited information is available on the environmental behavior and associated potential risk of manufactured oxide nanoparticles (NPs). In this research, toxicity of nanoparticulate and bulk ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} were examined to the nematode Caenorhabditis elegans with Escherichia coli as a food source. Parallel experiments with dissolved metal ions from NPs were also conducted. The 24-h median lethal concentration (LC{sub 50}) and sublethal endpoints were assessed. Both NPs and their bulk counterparts were toxic, inhibiting growth and especially the reproductive capability of the nematode. The 24-h LC{sub 50} for ZnO NPs (2.3 mg L{sup -1}) and bulk ZnO was not significantly different, but significantly different between Al{sub 2}O{sub 3} NPs (82 mg L{sup -1}) and bulk Al{sub 2}O{sub 3} (153 mg L{sup -1}), and between TiO{sub 2} NPs (80 mg L{sup -1}) and bulk TiO{sub 2} (136 mg L{sup -1}). Oxide solubility influenced the toxicity of ZnO and Al{sub 2}O{sub 3} NPs, but nanoparticle-dependent toxicity was indeed observed for the investigated NPs. - ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} nanoparticles are more toxic than their bulk counterparts to the nematode, Caenorhabditis elegans.

Acute and sub-acute toxicity of Pithecellobium dulce (Roxb. Benth. stem bark hydroalcoholic extract on Wistar rats

Directory of Open Access Journals (Sweden)

Gérard A. Toudji

2017-10-01

Full Text Available Context: Pithecellobium dulce (PD is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. Aims: To evaluate the acute and sub-acute toxicity of P. dulce stem bark hydroethanolic extract in Wistar rats. Methods: In the acute test, a single dose of 5 g/kg body weight was administered to Wistar rats afterwards they were observed individually 4 hours post-dosing, and at least once daily for 14 consecutive days. The sub-acute toxicity was evaluated by daily oral administration of 0.5 and 1 g/kg extract, for 28 days. Biochemical and hematological parameters assessment as well as body and organ weights of the rats were carried out. Results: The limit dose of 5 g/kg did not cause any mortality or signs of acute toxicity on the rats during the experimentation period. In the sub-acute test, uterus-ovary-trompe (UOT weight decreased dose-dependently: Control group (0.82 ± 0.03 g; Extract 0.5 g/kg (0.57 ± 0.06 g; Extract 1g/kg (0.48 ± 0.01 g (p ˂ 0.01. Extract lowered urea values in female group treated with 1 g/kg (p < 0.01. Lymphocytes percentage was dose dependently increased in treated male groups: Control group (53.00 ± 0.58%; extract 0.5 g/kg (58.67 ± 0.67% and extract 1 g/kg (60.67 ± 2.41%. Conclusions: These findings suggest that PD is relatively safe when administered orally in rats but is slightly atrophic for female reproductive organs.

Acute toxicity from baking soda ingestion.

Science.gov (United States)

Thomas, S H; Stone, C K

1994-01-01

Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

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.

Subacute (90 days) oral toxicity studies of Kombucha tea.

Science.gov (United States)

Vijayaraghavan, R; Singh, M; Rao, P V; Bhattacharya, R; Kumar, P; Sugendran, K; Kumar, O; Pant, S C; Singh, R

2000-12-01

Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

Anti-inflammatory activity and sub-acute toxicity of artemetin.

Science.gov (United States)

Sertié, J A; Basile, A C; Panizza, S; Matida, A K; Zelnik, R

1990-02-01

The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

African Journals Online (AJOL)

fisiologia

2012-09-18

Sep 18, 2012 ... In the acute toxicity of Nv-EtOH, behavioral and physiological alterations were not observed neither animal's death in the doses of 2.0 g/kg intraperitoneally and 5.0 g/kg orally, respectively indicating low toxicity of the extract. In this experiment, it was observed that the. Nv-EtOH has LD50 > 5000 mg/kg.

Added Sugar Consumption and Chronic Oral Disease Burden among Adolescents in Brazil.

Science.gov (United States)

Carmo, C D S; Ribeiro, M R C; Teixeira, J X P; Alves, C M C; Franco, M M; França, A K T C; Benatti, B B; Cunha-Cruz, J; Ribeiro, C C C

2018-05-01

Chronic oral diseases are rarely studied together, especially with an emphasis on their common risk factors. This study examined the association of added sugar consumption on "chronic oral disease burden" among adolescents, with consideration of obesity and systemic inflammation pathways through structural equation modeling. A cross-sectional study was conducted of a complex random sample of adolescent students enrolled at public schools in São Luís, Brazil ( n = 405). The outcome was chronic oral disease burden, a latent variable based on the presence of probing depth ≥4 mm, bleeding on probing, caries, and clinical consequences of untreated caries. The following hypotheses were tested: 1) caries and periodontal diseases among adolescents are correlated with each other; 2) added sugar consumption and obesity are associated with chronic oral disease burden; and 3) chronic oral disease burden is linked to systemic inflammation. Models were adjusted for socioeconomic status, added sugar consumption, oral hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All estimators of the latent variable chronic oral disease burden involved factor loadings ≥0.5 and P values disease burden values. Obesity was associated with high IL-6 levels (SC = 0.232, P = 0.001). Visible plaque index was correlated with chronic oral disease burden (SC = 0.381, P periodontal diseases are associated with each other and with added sugar consumption, obesity, and systemic inflammation reinforces the guidance of the World Health Organization that any approach intended to prevent noncommunicable diseases should be directed toward common risk factors.

Photothermal effects and toxicity of Fe{sub 3}O{sub 4} nanoparticles via near infrared laser irradiation for cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Dunn, Andrew W. [The Materials Science and Engineering Program, Dept. of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221 (United States); Ehsan, Sadat M.; Mast, David [Department of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States); Pauletti, Giovanni M. [The James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267 (United States); Xu, Hong [Nano Biomedical Research Center, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhang, Jiaming; Ewing, Rodney C. [Department of Geological and Environmental Sciences, Stanford University, Stanford, CA 94305 (United States); Shi, Donglu, E-mail: donglu.shi@uc.edu [The Materials Science and Engineering Program, Dept. of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221 (United States); Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200120 (China)

2015-01-01

The photothermal effect of magnetite (Fe{sub 3}O{sub 4}) nanoparticles was characterized by photonic absorption in the near-infrared (NIR) region. Upon laser irradiation at 785 nm, the Fe{sub 3}O{sub 4} nanoparticles generate localized hyperthermia in tumorous lesions, which is an effective strategy for cancer therapy; however, uncoated magnetite possesses an innate toxicity which can lead to drawbacks in the clinical setting. To reduce innate toxicity, a poly(acrylic acid) (PAA) coating on the nanoparticles was investigated in order to determine the alterations to stability and the degree of toxicity in an attempt to create a higher utility vector. It was found that the PAA coating significantly reduced the innate toxicity of the uncoated magnetite. Furthermore, the efficacy of PAA-coated magnetite nanoparticles (PAA-Fe{sub 3}O{sub 4}) was investigated for treating MDA-MB-231 (human mammary gland adenocarcinoma) cultures in viable concentration ranges (0.1–0.5 mg/ml). An appropriate PAA-Fe{sub 3}O{sub 4} concentration range was then established for inducing significant cell death by hyperthermic ablation, but not through innate toxicity. - Highlights: • Uncoated magnetite NPs possess high innate toxicity in MDA-MB-231 cultures. • PAA coating significantly reduces innate toxicity and stabilizes magnetite NPs. • Thermal ablation begins at 0.2 mg/ml for PAA-Fe{sub 3}O{sub 4} at 785 nm NIR laser, 38.5 kW/m{sup 2}. • 38.5 kW/m{sup 2} does not significantly affect MDA-MB-231 viability in-vitro.

The Correlation between Chronic Periodontitis and Oral Cancer.

Science.gov (United States)

Krüger, Maximilian; Hansen, Torsten; Kasaj, Adrian; Moergel, Maximilian

2013-01-01

Infections are increasingly considered as potential trigger for carcinogenesis apart from risk factors like alcohol and tobacco. The discussion about human papilloma virus (HPV) in oral squamous cell carcinoma (OSCC) points at a general role of infection for the development of oral carcinomas. Furthermore, first studies describe a correlation between chronic periodontitis and OSCC, thus, characterizing chronic inflammation as being a possible trigger for OSCC. In front of this background, we present four well-documented clinical cases. All patients showed a significant anatomical relation between OSCC and clinical signs of chronic periodontitis. The interindividual differences of the clinical findings lead to different theoretical concepts: two with coincidental appearance of OSCC and chronic periodontitis and two with possible de novo development of OSCC triggered by chronic inflammation. We conclude that the activation of different inflammatory cascades by chronic periodontitis negatively affects mucosa and bone. Furthermore, the inflammatory response has the potential to activate carcinogenesis. Apart from a mere coincidental occurrence, two out of four patients give first clinical hints for a model wherein chronic periodontitis represents a potential risk factor for the development of OSCC.

The Correlation between Chronic Periodontitis and Oral Cancer

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Maximilian Krüger

2013-01-01

Full Text Available Infections are increasingly considered as potential trigger for carcinogenesis apart from risk factors like alcohol and tobacco. The discussion about human papilloma virus (HPV in oral squamous cell carcinoma (OSCC points at a general role of infection for the development of oral carcinomas. Furthermore, first studies describe a correlation between chronic periodontitis and OSCC, thus, characterizing chronic inflammation as being a possible trigger for OSCC. In front of this background, we present four well-documented clinical cases. All patients showed a significant anatomical relation between OSCC and clinical signs of chronic periodontitis. The interindividual differences of the clinical findings lead to different theoretical concepts: two with coincidental appearance of OSCC and chronic periodontitis and two with possible de novo development of OSCC triggered by chronic inflammation. We conclude that the activation of different inflammatory cascades by chronic periodontitis negatively affects mucosa and bone. Furthermore, the inflammatory response has the potential to activate carcinogenesis. Apart from a mere coincidental occurrence, two out of four patients give first clinical hints for a model wherein chronic periodontitis represents a potential risk factor for the development of OSCC.

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

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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

Quantitative analysis of potentially toxic metals in alginates for dental use

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A. S. BRAGA

2009-01-01

Full Text Available

Alginate is one the materials most employed in practice to make dental impressions. Substances like zinc, cadmium and lead silicate, which are included in several alginate brands with the aim of improving their physical, chemical and mechanical properties, are a source of serious concern as regards their toxicity. The most serious chronic effect of oral exposure to cadmium is renal toxicity. Assimilation of lead has deleterious effects on the gastrointestinal tract, hematopoietic system, cardiovascular system, central and peripheral nervous systems, kidneys, immune system, and reproductive system. Chronic oral exposures to zinc have resulted in hypochromic and microcyte anemia in some individuals. The aim of the present study was to measure the cadmium, lead and zinc contents of seven brands of alginate for dental use on sale in Brazil. The samples were weighed and placed in the Teflon cups of a closedsystem microwave oven. Aqua regia (4mL concentrated HCl:HNO<sub>3sub>, 3:1 v/v and hydrofluoric acid (2mL concentrated HF were added to the samples, which were then subjected to heating. The samples were then cooled to room temperature and diluted to 25 mL in deionized water in a volumetric glass flask. The samples were diluted in duplicate and analyzed against a reagent blank. The analyses were performed in an atomic absorption flame spectrophotometer. Neither lead nor cadmium was detected. Zinc contents ranged from 0.001% to 1.36% by weight. The alginates exhibited low contents of the metals under study and gave no cause for concern regarding toxicity; even so, it is advisable to monitor potentially toxic materials continually and to analyze their plasmatic levels in the professionals working with them. Keywords: Cadmium, lead, zinc, alginates, intoxication, irreversible hydrocolloid.

Non-oral gram-negative facultative rods in chronic periodontitis microbiota.

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van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadrach M; Rams, Thomas E

2016-05-01

The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. Subgingival biofilm specimens from 102 untreated and 101 recently treated adults with chronic periodontitis in the Netherlands were plated onto MacConkey III and Dentaid selective media with air-5% CO2 incubation for isolation of non-oral GNFR, and onto enriched Oxoid blood agar with anaerobic incubation for recovery of selected periodontal bacterial pathogens. Suspected non-oral GNFR clinical isolates were identified to a species level with the VITEK 2 automated system. A total of 87 (42.9%) out of 203 patients yielded subgingival non-oral GNFR. Patients recently treated with periodontal mechanical debridement therapy demonstrated a greater prevalence of non-oral GNFR (57.4% vs 28.4%, P chronic periodontitis patients yielded cultivable non-oral GNFR in periodontal pockets, particularly among those recently treated with periodontal mechanical debridement therapy. Since non-oral GNFR species may resist mechanical debridement from periodontal pockets, and are often not susceptible to many antibiotics frequently used in periodontal practice, their subgingival presence may complicate periodontal treatment in species-positive patients and increase risk of potentially dangerous GNFR infections developing at other body sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

LD/sub 50/ and selenium concentration in organs of rabbit following oral application of sodium selenite and toxicity verification of Ursoselevit-Praemix

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Berschneider, F.; Hess, M.; Neuffer, K.; Willer, S.

1976-07-01

LC/sub 50/24 hr/ was established in the first of a series of experiments on 72 rabbits for orally applied sodium selenite. The dosage was 8.62 mg/kg live weight, the confidence interval being (1 - ..cap alpha.. = 0.95) +/- 0.13 mg/kg. The value was four times as high following intravenous application. Complete lethality was recorded from 15 mg Na/sub 2/SeO/sub 3//kg live weight within 21 hours. Thirty-six animals were involved in the second experiment of the series. They had 50 or 100 percent Ursoselevit-Praemix (30 ppm Se) in their rations. Body mass development of the test animals was superior to that recorded from the controls in the first 50 days, after which limit the former declined strongly in a few days. Their general condition worsened. Postmortem finding, following slaughter, included catarrhal enteritis, toxic liver dystrophy, scattered pulpous tumors in the spleen, and interstitial nephritis. In the third experiment (50 percent Ursoselevit-Praemix with 60 ppm Se in the rations), the test animals developed better than the controls during the first two months, after which point they exhibited the same clinical symptoms as those observed in the second experiment, stopped putting on weight, and eventually turned cachectic. The pathomorphological findings were identical with those obtained from the second experiment. The selenium concentrations in the organs of the test animals all were much higher than those of the controls. Their amounts in excess to base values were up to eleven times in the blood, nine times in the liver, twelve times in the kidneys, and 13 times in the muscles. 11 references, 2 figures, 2 tables.

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

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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.

Oral rehabilitation of a patient with sub - total maxillectomy

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Romesh Soni

2011-01-01

Full Text Available This clinical report describes oral rehabilitation of a patient with sub-total maxillectomy with palatine process of maxilla and horizontal plate of palatine bone intact to retain the maxillary obturator. Clinical examination has been performed to know the amount of favorable undercuts to be used for retention of the obturator for better functional efficiency. Successful prosthetic reconstruction of hemimaxillectomy defect is a challenging procedure that requires multidisciplinary expertise to achieve acceptable functional speech and swallowing outcomes. This article describes the oral rehabilitation of a patient with sub-total maxillectomy with a maxillary obturator. Oral rehabilitation of sub-total maxillectomy patient is a challenging task. Obturation of the defect depends on volume of the defect, and positioning of remaining hard and soft tissues to be used to retain, stabilize, and support the prosthesis. A maxillary obturator for edentulous patient must provide for retention, stability, support, patient comfort, and cleanliness.

Oral rehabilitation of a patient with sub - total maxillectomy.

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Soni, Romesh; Jindal, Shitu; Singh, B P; Mittal, Neelam; Chaturvedi, T P; Prithviraj, D R

2011-01-01

This clinical report describes oral rehabilitation of a patient with sub-total maxillectomy with palatine process of maxilla and horizontal plate of palatine bone intact to retain the maxillary obturator. Clinical examination has been performed to know the amount of favorable undercuts to be used for retention of the obturator for better functional efficiency. Successful prosthetic reconstruction of hemimaxillectomy defect is a challenging procedure that requires multidisciplinary expertise to achieve acceptable functional speech and swallowing outcomes. This article describes the oral rehabilitation of a patient with sub-total maxillectomy with a maxillary obturator. Oral rehabilitation of sub-total maxillectomy patient is a challenging task. Obturation of the defect depends on volume of the defect, and positioning of remaining hard and soft tissues to be used to retain, stabilize, and support the prosthesis. A maxillary obturator for edentulous patient must provide for retention, stability, support, patient comfort, and cleanliness.

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

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

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Tipping, E., E-mail: et@ceh.ac.u [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Lofts, S. [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Hooper, H. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom); Frey, B. [Swiss Federal Research Institute WSL, 8903 Birmensdorf (Switzerland); Spurgeon, D.; Svendsen, C. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom)

2010-07-15

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 {mu}g (g soil){sup -1} and 3.3 {mu}g (g soil organic matter){sup -1} being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 {mu}g (g soil organic matter){sup -1}. We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg{sup 2+} in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg{sup 2+}]{sub crit} = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg{sup 2+} concentration.

Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

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Wuen Yew Teoh

2013-01-01

Full Text Available Gynura bicolor (Compositae which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116, one human breast adenocarcinoma cell line (MCF7, and one human normal colon cell line (CCD-18Co were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay, possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.

Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

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Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-02-01

Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to

Oral protein calorie supplementation for children with chronic disease.

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Francis, Damian K; Smith, Joanne; Saljuqi, Tawab; Watling, Ruth M

2015-05-27

Poor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009. To examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems. Trials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted.Most recent search of the Group's Trials Register: 24 February 2015. Randomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease. We independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials. Four studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease. Overall there was a low risk of bias for blinding and incomplete outcome data.Two studies had a high

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

Sub-acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

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Shin Yee Fung

2016-08-01

Full Text Available Lignosus also known as Tiger Milk Mushroom, is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500 and 1000 mg/kg to the SD rats once daily, consecutively for 28 days. Body weight of the rats was recorded and general behavior, adverse effects and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL dose is more than 1000 mg/kg.

Acute and Sub-Acute Oral Toxicity Evaluation of Astragalus hamosus Seedpod Ethanolic Extract in Wistar Rats

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Mohammadmehdi Hassanzadeh-Taheri

2018-03-01

Full Text Available Background: Oral consumption of Astragalus hamosus L. (AH seedpod has been widely prescribed in traditional medicine system. However, its toxicity evaluation has never been investigated. Hence, the current study was performed to evaluate the toxicological profile of AH seedpod in acute and subacute assessments based on the OECD-guidelines 425 and 407 in male and female Wistar rats. Methods: In the acute study, ethanolic extract of AH at a single dose of 2000 mg/kg was orally administrated to six female rats. In the subacute assay, AH at the three different oral doses (75, 150 and 300 mg/kg were administrated to both male and female rats for 28 consecutive days. Results: No death or behavioural changes were observed in the treated animals. In subacute test, in both sexes, no changes in organ weights observed. Biochemically, compared to the control, AH at the dose of 300 mg/kg slightly increased (p<0.05 uric acid and creatinine and declined total cholesterol levels in both male and female rats. However, there is no statistically difference in other parameters such as albumin, triglyceride, blood urea, aspartate aminotransferase and alanine aminotransferase between AH treated groups and untreated controls. Hematologic parameters showed that AH at the maximum dose decreased red blood cells count only in male rats. Histopathological evaluation of liver and kidney exhibited no noticeable alterations in AH treated animals. Conclusion: It could be concluded that high excessive and long term consumption of AH may lead to renal dysfunction and deficiency in hematopoietic system.

Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

International Nuclear Information System (INIS)

Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C.

1990-01-01

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02)

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

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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.

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.

A CONTROVERSIAL ON THE DIAGNOSIS OF CHRONIC BULLOUS TYPE MUCOCUTANEOUS DISEASE INVOLVING ORAL MUCOSA (A CASE REPORT

Directory of Open Access Journals (Sweden)

Isadora Gracia

2006-04-01

Full Text Available A case of chronic bullous type mucocutaneous disease involving oral mucosa was reported from a 56 years old man with never healing oral ulcers and wound on the perianal skin for three years. There were also red and black spots on the limb and back skin and a lesion on nail. Painful oral lesion consisted of mucous erosion, desquamative gingivitis, and sloughing area on palate and tongue. The patient is diabetic. The first perianal skin diagnosis was granulomatous candidasis with differential diagnosis pemphigus vegetates and acuminarum condiloma. However the histopathologic examination did not support these diagnosis. After several histopathologic examinations, the latest perianal skin diagnosis was lichen planus with differential diagnosis granulomatous vasculitis, bowenoid papulosis and pyodema gangrenosum. Other skin diagnosis was erythema multiforme. Oral diagnosis was mucous membrane pemphigoid with differential diagnosis lichen planus, Behçet's syndrome and erythema multiforme. Oral histopathologic examinations showed a sub-epithelial blister, which supported mucous membrane pemphigoid. A lip balm, prednisone 5 mg oral rinse and multivitamins were given but oral improvement started after blood sugar level was controlled. Conclusion: It is not yet known whether skin and oral mucous lesions are from the same disease or not.

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

Science.gov (United States)

Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

2016-10-01

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

Energy Technology Data Exchange (ETDEWEB)

Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

2016-10-15

Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

Photodegradation and toxicity changes of antibiotics in UV and UV/H{sub 2}O{sub 2} process

Energy Technology Data Exchange (ETDEWEB)

Fang, Yuan [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China); Hu Chun, E-mail: huchun@rcees.ac.cn [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China); Xuexiang, Hu; Dongbin, Wei; Yong, Chen; Jiuhui, Qu [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China)

2011-01-30

The photodegradation of three antibiotics, oxytetracycline (OTC), doxycycline (DTC), and ciprofloxacin (CIP) in UV and UV/H{sub 2}O{sub 2} process was investigated with a low-pressure UV lamp system. Experiments were performed in buffered ultrapure water (UW), local surface water (SW), and treated water from local municipal drinking water treatment plant (DW) and wastewater treatment plant (WW). The efficiency of UV/H{sub 2}O{sub 2} process was affected by water quality. For all of the three selected antibiotics, the fastest degradation was observed in DW, and the slowest degradation occurred in WW. This phenomenon can be explained by R{sub OH,UV}, defined as the experimentally determined {center_dot}OH radical exposure per UV fluence. The R{sub OH,UV} values represent the background {center_dot}OH radical scavenging in water matrix, obtained by the degradation of para-chlorobenzoic acid (pCBA), a probe compound. In natural water, the indirect degradation of CIP did not significantly increase with the addition of H{sub 2}O{sub 2} due to its effective degradation by UV direct photolysis. Moreover, the formation of several photoproducts and oxidation products of antibiotics in UV/H{sub 2}O{sub 2} process was identified using GC-MS. Toxicity assessed by Vibrio fischer (V. fischer), was increased in UV photolysis, for the photoproducts still preserving the characteristic structure of the parent compounds. While in UV/H{sub 2}O{sub 2} process, toxicity increased first, and then decreased; nontoxic products were formed by the oxidation of {center_dot}OH radical. In this process, detoxification was much easier than mineralization for the tested antibiotics, and the optimal time for the degradation of pollutants in UV/H{sub 2}O{sub 2} process would be determined by parent compound degradation and toxicity changes.

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

Development of a chronic sediment toxicity test for marine benthic amphipods

International Nuclear Information System (INIS)

DeWitt, T.H.; Redmond, M.S.; Sewall, J.E.; Swartz, R.C.

1992-12-01

The results of the research effort culminated in the development of a research method for assessing the chronic toxicity of contaminated marine and estuarine sediments using the benthic amphipod, Leptocheirus plumulosus. The first chapter describes the efforts at collecting, handling, and culturing four estuarine amphipods from Chesapeake Bay, including L. plumulosus. This chapter includes maps of the distribution and abundance of these amphipods within Chesapeake Bay and methodologies for establishing cultures of amphipods which could be readily adopted by other laboratories. The second chapter reports the development of acute and chronic sediment toxicity test methods for L. plumulosus, its sensitivity to non-contaminant environmental variables, cadmium, two polynuclear aromatic hydrocarbons, and contaminated sediment from Baltimore Harbor, MD. The third chapter reports the authors attempts to develop a chronic sediment toxicity test with Ampelisca abdita

Quantitative structure–activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes)

Energy Technology Data Exchange (ETDEWEB)

Lin, Hongkang [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Morandi, Garrett D. [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Brown, R. Stephen [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Snieckus, Victor; Rantanen, Toni [Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Jørgensen, Kåre B. [Department of Mathematics and Natural Sciences, University of Stavanger, 4036 Stavanger (Norway); Hodson, Peter V., E-mail: peter.hodson@queensu.ca [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada)

2015-02-15

Highlights: • Medaka embryos were exposed to alkyl chrysenes and benzo[a]anthracenes (BAA). • Concentrations were kept constant by partition controlled delivery. • Chrysene was not toxic within solubility limits, in contrast to BAA. • Alkylation increased the toxicity of chrysene and BAA. • Toxicity was related to hydrophobicity and to specific modes of action. - Abstract: Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and log K{sub ow} values provided a rough estimation of structure–activity relationships for alkyl-PAHs, but K{sub ow} alone did not provide

Non-oral gram-negative facultative rods in chronic periodontitis microbiota

NARCIS (Netherlands)

van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadnach; Rams, Thomas E

OBJECTIVE: The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. METHODS:

Chronic toxicity of copper and ammonia to juvenile freshwater mussels (Unionidae)

Science.gov (United States)

Wang, N.; Ingersoll, C.G.; Greer, I.E.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; Brumbaugh, W.G.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

2007-01-01

The objectives of the present study were to develop methods for conducting chronic toxicity tests with juvenile mussels under flow-through conditions and to determine the chronic toxicity of copper and ammonia to juvenile mussels using these methods. In two feeding tests, two-month-old fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris) were fed various live algae or nonviable algal mixture for 28 d. The algal mixture was the best food resulting in high survival (???90%) and growth. Multiple copper and ammonia toxicity tests were conducted for 28 d starting with two-month-old mussels. Six toxicity tests using the algal mixture were successfully completed with a control survival of 88 to 100%. Among copper tests with rainbow mussel, fatmucket, and oyster mussel (Epioblasma capsaeformis), chronic value ([ChV], geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) ranged from 8.5 to 9.8 ??g Cu/L for survival and from 4.6 to 8.5 ??g Cu/L for growth. Among ammonia tests with rainbow mussel, fatmucket, and wavy-rayed lampmussel (L. fasciola), the ChV ranged from 0.37 to 1.2 mg total ammonia N/L for survival and from 0.37 to 0.67 mg N/L for growth. These ChVs were below the U.S. Environmental Protection Agency 1996 chronic water quality criterion (WQC) for copper (15 ??g/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20??C). Results indicate that toxicity tests with two-month-old mussels can be conducted for 28 d with >80% control survival; growth was frequently a more sensitive endpoint compared to survival; and the 1996 chronic WQC for copper and the 1999 chronic WQC for total ammonia might not be adequately protective of the mussel species tested. However, a recently revised 2007 chronic WQC for copper based on the biotic ligand model may be more protective in the water tested. ?? 2007 SETAC.

Preclinical Safety Assessment of Standardized Extract of Centella asiatica (L.) Urban Leaves

OpenAIRE

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad

2015-01-01

Context: Centella asiatica (CA) leaves extract has been shown therapeutic potential. However, safety information is lacking. Aims: To evaluate acute oral toxicity (AOT), sub-chronic toxicity, and mutagenic potential of standardized extract of CA (L.) Urban leaves (INDCA). Materials and Methods: For the acute toxicity study, INDCA was orally administered to Sprague-Dawley rats at a dose range of 0?2000 mg/kg. For the repeated dose toxicity study, the rats of either sex were orally administered...

Lower doses venlafaxine-associated toxic hepatitis in a patient with chronic hepatitis

International Nuclear Information System (INIS)

Sencan, I.; Sahin, I.; Ozcetin, A.

2003-01-01

Toxic hepatitis is observed with high doses of Venlafaxine. But toxic hepatitis has not been yet reported at lower doses of Venlafaxine such as 37.5 mg per day. In this case report, a case of Venlafaxine associated toxic hepatitis with lower doses in patient with history of chronic hepatitis is presented. We suggest that liver function should be regularly monitored in patients with history of chronic hepatitis receiving Venlafaxine even at lower doses and even when their liver enzymes are normal. (author)

Oral toxicity of fipronil insecticide against the stingless bee Melipona scutellaris (Latreille, 1811).

Science.gov (United States)

Lourenço, Clara Tavares; Carvalho, Stephan Malfitano; Malaspina, Osmar; Nocelli, Roberta Cornélio Ferreira

2012-10-01

For a better evaluation of the model using Apis mellifera in toxicology studies with insecticides, the oral acute toxicity of the insecticide fipronil against the stingless bee Melipona scutellaris was determined. The results showed that fipronil was highly toxic to M. scutellaris, with a calculated LC(50) (48 h) value of 0.011 ng a.i./μL of sucrose solution and an estimated oral LD(50) (48 h) of 0.6 ng a.i./bee. Our results showed that M. scutellaris bee is more sensitive to fipronil than the model specie A. mellifera.

Chronic myeloproliferative disorders: A rarest case with oral manifestations and dental management

Directory of Open Access Journals (Sweden)

Pritesh B Ruparelia

2012-01-01

Full Text Available Chronic myeloproliferative disorders (CMPD are rarest hematological disorders (malignant myeloid neoplasms. The three most common chronic myeloproliferative disorders are polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis. Clinical manifestations (including oral manifestations of these disorders are overlapping with each other and with other hematologic disorders, which makes the diagnosis of CMPD a challenging task. In this article we report a rare to rarest case of CMPD at dental outpatient department, its oral manifestations and its management in dental clinics.

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).

Association between chronic periodontitis and oral health-related quality of life in Sri Lankan adults.

Science.gov (United States)

Wellapuli, Nimali; Ekanayake, Lilani

2016-12-01

To determine the impact of chronic periodontitis on oral health-related quality of life in Sri Lankan adults. A cross-sectional study was conducted among 1,400 participants, 35-60 years of age, residing in the Colombo district of Sri Lanka. Data were collected using two interviewer-administered questionnaires and an oral examination. The prevalence, extent and severity of oral impacts increased with the increase in severity of chronic periodontitis. The most commonly experienced impacts were within the domain of physical pain. The adjusted Poisson regression model indicated that chronic periodontitis was significantly associated with the prevalence of oral impacts. The prevalence of oral impacts was 48% and 69% higher in those with moderate and severe periodontitis, respectively, compared with those with no/mild periodontitis. Oral health-related quality of life deteriorates with the increase in severity of chronic periodontitis. © 2016 FDI World Dental Federation.

Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

International Nuclear Information System (INIS)

Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

2008-01-01

Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity

Summary of safety evaluation toxicity studies of glufosinate ammonium.

Science.gov (United States)

Ebert, E; Leist, K H; Mayer, D

1990-05-01

This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations*

Science.gov (United States)

Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; de Souza, Mair Pedro; Orti-Raduan, Érica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease. PMID:25054751

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations.

Science.gov (United States)

Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; Souza, Mair Pedro de; Orti-Raduan, Erica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

Science.gov (United States)

Sireeratawong, Seewaboon; Itharat, Arunporn; Khonsung, Parirat; Lertprasertsuke, Nirush; Jaijoy, Kanjana

2013-01-01

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

Directory of Open Access Journals (Sweden)

Ehsan Zayerzadeh

2016-07-01

Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

Determination and toxicity evaluation of the generated products in sulfamethoxazole degradation by UV/CoFe{sub 2}O{sub 4}/TiO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Gong, Han; Chu, Wei, E-mail: wei.chu@polyu.edu.hk

2016-08-15

Highlights: • Four pathways were determined in sulfamethoxazole degradation by UV/CoFe{sub 2}O{sub 4}/TiO{sub 2}. • Four intermediates were newly detected during sulfamethoxazole degradation. • Planktons were used in the toxicity evaluation of generated intermediates. • The toxicity of sulfanilamide as a harmful intermediate was studied. - Abstract: The photodegradation of sulfamethoxazole (SMX) under UV radiation with a recyclable catalyst CoFe{sub 2}O{sub 4}/TiO{sub 2} was examined. The reaction mechanism during the treatment was determined. The toxicity of the degradation intermediates to aquatic organisms, including the green alga Chlorella vulgaris and the brine shrimp Artemia salina was investigated. SMX was completely removed and about 50% TOC was degraded in 5 h. Sixteen intermediates were detected, from which four of them were reported for the first time in this study. Four main decay pathways, i.e., hydroxylation, cleavage of S−N bond, nitration of amino group, and isomerization were proposed. About 45% of the total mass sulfur source transformed to sulfate ion, and around 25%, 1%, and 0.25% of the total nitrogen transformed to ammonium, nitrogen, and nitrite ions. The toxicity of the treated solution was significantly reduced compared to that of the parent compound SMX. A variation of the algae growth was observed, which was due to the combination of generation of toxic intermediates (i.e., sulfanilamide) and the release of inorganic substances and carbon source as additional nutrients. The adverse effect on the clearance rate of the brine shrimp was also observed, but it can be eliminated if longer degradation time is used.

Immunohistochemical Analysis of Vimentin in Oral Sub mucous Fibrosis

International Nuclear Information System (INIS)

Nayak, M. T.; Singh, A.; Desai, R. S.; Vanaki, S. S.

2013-01-01

Oral sub mucous fibrosis (OSF), a precancerous condition, is characterized by abnormal accumulation of collagen fibers in oral sub mucosa. Vimentin is a Class 2 intermediate filament (IF) and primarily expressed in cells of mesenchymal origin. Vimentin is also found to be involved in cell growth, cell cycling, and tumour differentiation. Objective. The purpose of the study was to compare the expression of vimentin in various histological grades of OSF. Materials and Methods. To assess the immunohistochemical expression of vimentin in 20 mild cases of OSF, 20 severe cases of OSF, and ten cases of normal oral buccal mucosa. Results. The overall staining intensity of vimentin significantly increased statistically (P<0.01) in OSF cases over normal control. A significant increase in the staining intensity of vimentin was also noted in the fibroblasts of severe cases of OSF (P=0.03). Conclusion. Considering the marked vimentin expression in the present study, future studies should include cytoskeleton IF and other filaments in the fibroblasts of OSF.

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

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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.

Co-existence of Oral Lichen Planes & Chronic Liver Disease - A Coincidence?

Directory of Open Access Journals (Sweden)

Jyoti Gupta

2003-01-01

Full Text Available "Oral cavity is the reflection of an individual′s general health" .Many systemic diseases have manifestations in the oral cavity. Systemic influences,such as endocrinal, immtlnological, nutritional and psychological states have an important role in thebalance between oral health and disease. This also holds good for a well known mucocutaneous disorder - "Oral Lichen Planus". The present study is carried out to deteremine any co-relation between oral lichen planes and chronic liver diseases.

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

International Nuclear Information System (INIS)

Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V.

2012-01-01

The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ( 99m Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99m Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis

Science.gov (United States)

2012-01-01

2 Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis Takeshi Yamanaka1...species biofilm in the oral cavity can cause persistent chronic periodontitis along with the importance of dental plaque formation and maturation...independent manner could be pathogenic for periodontal tissues and can cause chronic periodontitis lesions. 2.1 Initial colonizers on the tooth surface

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.

Effects of sub acute oral administration of aqueous extract of ...

African Journals Online (AJOL)

The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

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 ...

The chronic toxicity of molybdate to freshwater organisms. I. Generating reliable effects data

Energy Technology Data Exchange (ETDEWEB)

De Schamphelaere, K.A.C., E-mail: karel.deschamphelaere@Ugent.be [Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University (Belgium); Stubblefield, W. [Oregon State University, Department of Environmental and Molecular Toxicology, 421 Weniger Hall, Corvallis, OR 97331 (United States); Rodriguez, P. [Centro de Investigacion Minera y Metalurgica (CIMM), Santiago (Chile); Vleminckx, K. [Department for Molecular Biomedical Research, Ghent University (Belgium); Janssen, C.R. [Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University (Belgium)

2010-10-15

The European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) (EC, 2006) requires the characterization of the chronic toxicity of many chemicals in the aquatic environment, including molybdate (MoO{sub 4}{sup 2-}). Our literature review on the ecotoxicity of molybdate revealed that a limited amount of reliable chronic no observed effect concentrations (NOECs) for the derivation of a predicted no-effect concentration (PNEC) existed. This paper presents the results of additional ecotoxicity experiments that were conducted in order to fulfill the requirements for the derivation of a PNEC by means of the scientifically most robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Ten test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na{sub 2}MoO{sub 4}.2H{sub 2}O) according to internationally accepted standard testing guidelines or equivalent. The 10% effective concentrations (EC10, expressed as measured dissolved molybdenum) for the most sensitive endpoint per species were 62.8-105.6 (mg Mo)/L for Daphnia magna (21 day-reproduction), 78.2 (mg Mo)/L for Ceriodaphnia dubia (7 day-reproduction), 61.2-366.2 (mg Mo)/L for the green alga Pseudokirchneriella subcapitata (72 h-growth rate), 193.6 (mg Mo)/L for the rotifer Brachionus calyciflorus (48 h-population growth rate), 121.4 (mg Mo)/L for the midge Chironomus riparius (14 day-growth), 211.3 (mg Mo)/L for the snail Lymnaea stagnalis (28 day-growth rate), 115.9 (mg Mo)/L for the frog Xenopus laevis (4 day-larval development), 241.5 (mg Mo)/L for the higher plant Lemna minor (7 day-growth rate), 39.3 (mg Mo)/L for the fathead minnow Pimephales promelas (34 day-dry weight/biomass), and 43.2 (mg Mo)/L for the rainbow trout Oncorhynchus mykiss (78 day-biomass). These effect concentrations are in line with the few reliable data currently available in the open literature. The data

Interactions between nano-TiO{sub 2} and the oral cavity: Impact of nanomaterial surface hydrophilicity/hydrophobicity

Energy Technology Data Exchange (ETDEWEB)

Teubl, Birgit J.; Schimpel, Christa [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010 (Austria); Leitinger, Gerd [Institute of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010 (Austria); Center for Medical Research, Medical University of Graz, 8010 (Austria); BioTechMed, Graz 8010 (Austria); Bauer, Bettina [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010 (Austria); Fröhlich, Eleonore [Center for Medical Research, Medical University of Graz, 8010 (Austria); BioTechMed, Graz 8010 (Austria); Zimmer, Andreas [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010 (Austria); BioTechMed, Graz 8010 (Austria); Roblegg, Eva, E-mail: eva.roblegg@uni-graz.at [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010 (Austria); BioTechMed, Graz 8010 (Austria)

2015-04-09

Highlights: • Hydrophilic as well as hydrophobic TiO{sub 2} NPs agglomerated under oral physiological conditions. • Particles penetrated the upper and lower buccal epithelium, independent on the degree of hydrophilicity. • Most of the hydrophobic particles were found in vesicular structures, while hydrophilic particles were freely distributed in the cytoplasm. • Hydrophilic particles had a higher potential to trigger toxic effects (e.g., ROS) than hydrophobic particles. - Abstract: Titanium dioxide (TiO{sub 2}) nanoparticles are available in a variety of oral applications, such as food additives and cosmetic products. Thus, questions about their potential impact on the oro-gastrointestinal route rise. The oral cavity represents the first portal of entry and is known to rapidly interact with nanoparticles. Surface charge and size contribute actively to the particle–cell interactions, but the influence of surface hydrophilicity/hydrophobicity has never been shown before. This study addresses the biological impact of hydrophilic (NM 103, rutile, 20 nm) and hydrophobic (NM 104, rutile, 20 nm) TiO{sub 2} particles within the buccal mucosa. Particle characterization was addressed with dynamic light scattering and laser diffraction. Despite a high agglomeration tendency, 10% of the particles/agglomerates were present in the nanosized range and penetrated into the mucosa, independent of the surface properties. However, significant differences were observed in intracellular particle localization. NM 104 particles were found freely distributed in the cytoplasm, whereas their hydrophobic counterparts were engulfed in vesicular structures. Although cell viability/membrane integrity was not affected negatively, screening assays demonstrated that NM 104 particles showed a higher potential to decrease the physiological mitochondrial membrane potential than NM 103, resulting in a pronounced generation of reactive oxygen species.

A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus and snowdrop lectin shows oral toxicity to target insects

Directory of Open Access Journals (Sweden)

Fitches Elaine

2006-03-01

Full Text Available Abstract Background Despite evidence suggesting a role in plant defence, the use of plant lectins in crop protection has been hindered by their low and species-specific insecticidal activity. Snowdrop lectin (Galanthus nivalis agglutinin; GNA is transported to the haemolymph of insects after oral ingestion, and can be used as a basis for novel insecticides. Recombinant proteins containing GNA expressed as a fusion with a peptide or protein, normally only toxic when injected into the insect haemolymph, have the potential to show oral toxicity as a result of GNA-mediated uptake. Results A gene encoding a toxin, ButaIT, from the red scorpion (Mesobuthus tamulus was synthesised and assembled into expression constructs. One construct contained ButaIT alone, whereas the other contained ButaIT fused N-terminally to a GNA polypeptide (ButaIT/GNA. Both recombinant proteins were produced using the yeast Pichia pastoris as an expression host, and purified. Recombinant ButaIT and ButaIT/GNA were acutely toxic when injected into larvae of tomato moth (Lacanobia oleracea, causing slow paralysis, leading to mortality or decreased growth. ButaIT/GNA was chronically toxic when fed to L. oleracea larvae, causing decreased survival and weight gain under conditions where GNA alone was effectively non-toxic. Intact ButaIT/GNA was detected in larval haemolymph from insects fed the fusion protein orally, demonstrating transport of the linked polypeptide across the gut. Proteolysis of the fusion protein was also observed. ButaIT/GNA was significantly more toxic that GNA alone when fed to the homopteran Nilaparvata lugens (rice brown planthopper in liquid artificial diet. Conclusion The ButaIT/GNA recombinant fusion protein is toxic to lepidopteran larvae both when injected and when fed orally, showing the utility of GNA as a carrier to transport potentially toxic peptides and proteins across the insect gut. Although ButaIT has been claimed to be lepidopteran

The Acute Oral Toxicity of Commonly Used Pesticides in Iran, to Honeybees (Apis Mellifera Meda

Directory of Open Access Journals (Sweden)

Rasuli Farhang

2015-06-01

Full Text Available The honey bee is credited with approximately 85% of the pollinating activity necessary to supply about one-third of the world’s food supply. Well over 50 major crops depend on these insects for pollination. The crops produce more abundantly when honey bees are plentiful. Worker bees are the ones primarily affected by pesticides. Poisoning symptoms can vary depending on the developmental stage of the individual bee, and the kind of chemical employed. The oral toxicity of these insecticides: (phosalone and pirimicarb, acaricide (propargite, insecticide and acaricide (fenpropathrin, fungicides, and bactericides (copper oxychloride and the Bordeaux mixture, were evaluated for the purposes of this research. The results showed that fenpropathrin had high acute oral toxicity (LC50-24h and LC50-48 were 0.54 and 0.3 ppm, respectively. Propargite had 7785 ppm (active ingredient for LC50-24h and 6736 ppm (active ingredient for LC50-48h in honeybees and is therefore, non-toxic to Apis mellifera. On the other hand, copper oxychloride had minimum acute oral toxicity to honeybees (LC50-24h and LC50-48 were 4591.5 and 5407.9 ppm, respectively and was therefore considered non-toxic. Also, the Bordeaux mixture was safe to use around honeybees. Phosalone and primicarb were considered highly and moderately toxic to honeybees, respectively.

Derivation of an oral toxicity reference value for nickel.

Science.gov (United States)

Haber, Lynne T; Bates, Hudson K; Allen, Bruce C; Vincent, Melissa J; Oller, Adriana R

2017-06-15

Nickel (Ni) is in the earth's crust and can be found in environmental compartments such as water, soil, and air, as well as food. This paper presents an assessment of the oral nickel toxicity data in support of non-cancer health-based oral exposure limits or toxicity reference values (TRVs). This paper derives TRVs for three populations of interest: adults, toddlers, and people who have been dermally sensitized to nickel. The adult/lifetime TRV of 20 μg Ni/kg-day is based on post-implantation loss/perinatal mortality in a 2-generation reproductive study in rats. Several recent assessments by regulatory agencies have used the same study and endpoint, but the dose-response modeling conducted here was more appropriate for the study design. Toxicokinetic data from rats and humans indicate that the applied uncertainty factors are very conservative. Because the endpoint relates to fetal exposure and is not relevant to toddlers, a toddler TRV was derived based on decreased body weight in young rats; this TRV was also 20 μg Ni/kg-day. A separate TRV of 4 μg Ni/kg in addition to Ni in food was derived for protection of nickel-sensitized populations from flare-up of dermatitis, based on studies of single exposures in humans under conditions that maximize oral absorption. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Indicators of Ceriodaphnia dubia chronic toxicity test performance and sensitivity

Energy Technology Data Exchange (ETDEWEB)

Rosebrock, M.M.; Bedwell, N.J.; Ausley, L.W. [North Carolina Division of Environmental Management, Raleigh, NC (United States)

1994-12-31

The North Carolina Division of Environmental Management has begun evaluation of the sensitivity of test results used for measuring chronic whole effluent toxicity in North Carolina wastewater discharges. Approximately 67% of 565 facilities required to monitor toxicity by an NPDES permit perform a Ceriodaphnia dubia chronic, single effluent concentration (pass/fail) analysis. Data from valid Ceriodaphnia dubia chronic pass/fail tests performed by approximately 20 certified biological laboratories and submitted by North Carolina NPDES permittees were recorded beginning January 1992. Control and treatment reproduction data from over 2,500 tests submitted since 1992 were analyzed to determine the minimum significant difference (MSD) at a 99% confidence level for each test and the percent reduction from the control mean that the MSD represents (%MSD) for each certified laboratory. Initial results for the 20 laboratories indicate that the average intralaboratory percent MSD ranges 12.72% (n = 367) to 34.91% (n = 7) with an average of 23.08%. Additionally, over 3,800 tests were analyzed to determine the coefficient of variation (CV) for control reproduction for each test and the average for each certified biological laboratory. Preliminary review indicates that average interlaboratory control reproduction CV values range from 10.59% (n = 367) to 31.08% (n = 572) with a mean of 20.35%. The statistics investigated are indicators of intra/interlaboratory performance and sensitivity of Ceriodaphnia chronic toxicity analyses.

Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae.

Science.gov (United States)

Zhu, Wanyi; Schmehl, Daniel R; Mullin, Christopher A; Frazier, James L

2014-01-01

Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L.) health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax--fluvalinate, coumaphos, chlorothalonil, and chloropyrifos--tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common 'inert' ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae.

Directory of Open Access Journals (Sweden)

Wanyi Zhu

Full Text Available Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L. health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax--fluvalinate, coumaphos, chlorothalonil, and chloropyrifos--tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common 'inert' ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

Oral Candida Carriage and Morphotype Differentiation in Chronic Periodontitis Patients with and without Diabetes in the Indian Sub-Continent

Directory of Open Access Journals (Sweden)

Gomathinayagam Venkatesan

2015-11-01

Full Text Available The aim of this study was to assess the oral Candida carriage and morphotype differentiation of Candida species in chronic periodontitis patients, with and without diabetes mellitus. This cross sectional study included 30 subjects in the age range of 40–60 years, who were divided into two groups: 15 chronic periodontitis only (CP patients, and 15 chronic periodontitis patients with diabetes (CPD. Clinical measurements included plaque index (PI, gingival index (GI, probing depth (PD, clinical attachment level (CAL, and fasting blood sugar level (FBS. The unstimulated whole saliva samples were collected for fungal analysis. Candida carriage was analyzed by measuring colony forming units (CFU following the culture of samples. Qualitative morphotype differentiation of Candida species from yeast to hyphal form was analyzed using Periodic acid-Schiff (PAS staining. There was no statistically significant difference between CP and CPD groups for the periodontal parameters. However, a significantly higher Candida species CFU count was found in CPD (0.33 ± 0.23 as compared to CP (0.05 ± 0.04 group. This pilot study suggests that the occurrence of Candida species is higher in the saliva of chronic periodontitis patients with diabetes as compared to patients with chronic periodontitis alone.

Meta-analysis of aquatic chronic chemical toxicity data

Science.gov (United States)

Chronic toxicity data from the open literature and from tests submitted for pesticide registration were extracted and assembled into a database, AquaChronTox, with a flexible search interface. Data were captured at a treatment and, when available, replicate level to support conc...

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

Science.gov (United States)

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2011-04-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

Energy Technology Data Exchange (ETDEWEB)

Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V. [Division of Pharmaceutical Technology, Defence Research Laboratory, Assam (India); Department of Life Sciences, Defense Research Development and Organization, New Delhi (India)

2012-07-01

The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ({sup 99m} Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of {sup 99m}Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

Directory of Open Access Journals (Sweden)

P Chattopadhyay

2012-01-01

Full Text Available The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.

Toxicity of selenium (Na sub 2 SeO sub 3 ) and mercury (HgCl sub 2 ) on the planarian Dugesia gonocephala

Energy Technology Data Exchange (ETDEWEB)

Congiu, A.M.; Casu, S.; Ugazio, G. (Istituto di Genetica (Italy))

1989-10-01

The toxicity of selenium (Na{sub 2}SeO{sub 3}) and mercury (HgCl{sub 2}) was determined by using a freshwater planarian which is particularly sensitive to pollution, and belongs to a fissiparous breed of Dugesia gonocephala. The mortality and fissiparity frequency of the subjects were studied. They were exposed to intense treatments (48 hours) or for medium to long periods of time (21 days) to either the single compounds or a combination of both, and were fed or fasting. The lethal effect of sodium selenite is correlated to the food intake, whereas the toxicity of mercurous chloride is probably the result of a fixative effect which does not depend on feeding. The 21-day treatment with the first compound has a non-negligible lethal effect which is probably due to an accumulation phenomenon. At doses where an antioxidant effect prevails, fissiparity is stimulated. On the other hand, the second compound reduces reproduction frequency to half the base values. Compared to the Paracentrotus lividus, the Dugesia gonocephala offers various advantages concerning toxicological experiments; besides being easier to handle in the laboratory, it is available all year round and is not subject to seasonal cycles. It is also more susceptible to the toxic effect of mercury, which is a common and highly toxic pollutant, than the sea urchin.

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

Science.gov (United States)

Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

2015-01-01

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

Chronic plaque psoriasis: streptococcus pyogenes throat carriage rate and therapeutic response to oral antibiotics in comparison with oral methotrexate

International Nuclear Information System (INIS)

Raza, N.; Usman, M.; Hameed, A.

2007-01-01

To determine the throat carriage rate of Streptococcus pyogenes in patients having chronic plaque psoriasis and the effect of antibiotics as compared with that of oral methotrexate. Forty patients and 40 age and gender-matched controls were selected. Throat swab for culture of Streptococcus pyogenes was taken from each patient and control. All patients were treated with oral Penicillin V 250 mg, 6 hourly, and oral Rifampicin, 600 mg daily, for 10 days. Pre- and post therapy 'Psoriasis Area and Severity Index' (PASI) were compared. Thirty of these 40 patients were later given oral methotrexate, 5-10 mg weekly, for 04 weeks and pre- and post-therapy PASI were compared. Chi-square and paired-samples t-test were used for data analysis. Throat swab cultures were positive for Streptococcus pyogenes in 05 (12.5%) patients and none (0%) of the controls (p=0.02). Mean pre- and postantibiotic therapy PASI were 15.92 + 05.94 and 15.19 + 06.17 respectively (p=0.078). Mean pre- and postmethotrexate PASI were 15.81+ 5.55 and 8.79 + 4.19 respectively (p <0.01). Throat carriage of Streptococcus pyogenes is common in patients with chronic plaque psoriasis. Short-term antibiotic treatment has no role in routine treatment of chronic plaque psoriasis. However, it would be worthwhile to consider the effects of long term antibiotics on chronic plaque psoriasis. (author)

Oral disorders in patients with chronic renal failure. Narrative review

Directory of Open Access Journals (Sweden)

Carolina Hernández

2016-02-01

Full Text Available Chronic renal failure (CRF is one of the best known renal diseases. It is characterized by a deterioration in the overall renal function and is associated with other conditions such as hypertension, diabetes mellitus, uropathy, chronic glomerulonephritis and autoimmune diseases. Patients with CRF show alterations of the masticatory system that are specific to the disease and other type of disorders as a result of treatment. Oral health in dialysis and transplant patients tends to be poor, which makes them more likely to develop pathological conditions in the oral cavity, potentially increasing morbidity, mortality and affecting the quality of life of patients. Among the lesions we can find dysgeusia, periodontitis, candidiasis, gingival bleeding, petechiae, and joint alterations. Gingivitis and xerostomia associated to long-term use medications can cause oral lesions. Children with CRF show two oral conditions of interest: high incidence of dental anomalies and low caries activity. In patients receiving a kidney transplant, previous dental treatment is critical because the immune status of the patient will be affected not only by the toxemia, but by the immunosuppressive drugs used to prevent transplant rejection. Therefore, the dentist plays an important role in training parents and/or guardians, doctors and paramedics on the treatment of oral lesions in these patients

Oral protein calorie supplementation for children with chronic disease

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Francis, Damian K; Smith, Joanne; Saljuqi, Tawab; Watling, Ruth M

2015-01-01

Background Poor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009. Objectives To examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems. Search methods Trials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted. Most recent search of the Group's Trials Register: 24 February 2015. Selection criteria Randomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease. Data collection and analysis We independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials. Main results Four studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

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Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

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

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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

Metal mixture toxicity to aquatic biota in laboratory experiments: Application of the WHAM-F{sub TOX} model

Energy Technology Data Exchange (ETDEWEB)

Tipping, E., E-mail: et@ceh.ac.uk; Lofts, S.

2013-10-15

Highlights: •Metal accumulation by living organisms is successfully simulated with WHAM. •Modelled organism-bound metal provides a measure of toxic exposure. •The toxic potency of individual bound metals is quantified by fitting toxicity data. •Eleven laboratory mixture toxicity data sets were parameterised. •Relatively little variability amongst individual test organisms is indicated. -- Abstract: The WHAM-F{sub TOX} model describes the combined toxic effects of protons and metal cations towards aquatic organisms through the toxicity function (F{sub TOX}), a linear combination of the products of organism-bound cation and a toxic potency coefficient (α{sub i}) for each cation. Organism-bound, metabolically-active, cation is quantified by the proxy variable, amount bound by humic acid (HA), as predicted by the WHAM chemical speciation model. We compared published measured accumulations of metals by living organisms (bacteria, algae, invertebrates) in different solutions, with WHAM predictions of metal binding to humic acid in the same solutions. After adjustment for differences in binding site density, the predictions were in reasonable line with observations (for logarithmic variables, r{sup 2} = 0.89, root mean squared deviation = 0.44), supporting the use of HA binding as a proxy. Calculated loadings of H{sup +}, Al, Cu, Zn, Cd, Pb and UO{sub 2} were used to fit observed toxic effects in 11 published mixture toxicity experiments involving bacteria, macrophytes, invertebrates and fish. Overall, WHAM-F{sub TOX} gave slightly better fits than a conventional additive model based on solution concentrations. From the derived values of α{sub i}, the toxicity of bound cations can tentatively be ranked in the order: H < Al < (Zn–Cu–Pb–UO{sub 2}) < Cd. The WHAM-F{sub TOX} analysis indicates much narrower ranges of differences amongst individual organisms in metal toxicity tests than was previously thought. The model potentially provides a means to

[Behavioral-cognitive disorders due to chronic exposure to industrial and environmental toxic substances].

Science.gov (United States)

Mangone, Carlos A; Genovese, Osvaldo; Abel, Carlos

2006-01-01

A review of neurotoxics is made, given the low tendency to investigate for chronic exposure to environmental and industrial potential central nervous system toxic substances (heavy metals, insecticides, organic solvents and carbon monoxide) in the history of a patient consulting for behavioral - cognitive complains, and considering the potential overturn of the disease if a correct diagnosis and early treatment is made. to determine the onset of the cognitive - behavioral features, presentation pattern, diagnosis and treatment of such neurotoxics (NT). systematized search in Cochrane and Medline reviews, Embase and Lilacs. chronic exposure to neurotoxics can produce personality changes (sleeping problems, excitation, depression, delusions and hallucinations) as well as cognitive problems (memory, learning, language and cognitive reaction problems). NT may cause changes in the neuron morphology and its sub cellular structures, affecting its normal biochemistry and physiology (proteins and neurotransmitters synthesis). The clinical history, diagnosis and treatment of each neurotoxic are discussed. The NT must be taken in consideration among the possible different etiologies when a patient with a bizarre behavioral cognitive syndrome is examined.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

Science.gov (United States)

Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

Science.gov (United States)

Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

2015-08-01

Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. © 2015 SETAC.

Oral health in patients with chronic kidney disease - emphasis on periodontitis

OpenAIRE

Nylund, Karita

2017-01-01

ORAL HEALTH IN PATIENTS WITH CHRONIC KIDNEY DISEASE - EMPHASIS ON PERIODONTITIS Background: Periodontitis is a common bacteria-induced chronic inflammatory disease with mild symptoms. It leads to destruction of the periodontium and finally to tooth loss in a susceptible patient. Periodontitis is associated with many systemic diseases such as diabetes, atherosclerosis, cardiovascular diseases, and chronic kidney disease (CKD) through low-grade systemic inflammation. However, no causality c...

Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

Science.gov (United States)

Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

2015-11-01

The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal toxicity caused by oral use of medicinal plants: the yacon example.

Science.gov (United States)

de Oliveira, Rejane Barbosa; de Paula, Daniela Aparecida Chagas; Rocha, Bruno Alves; Franco, João José; Gobbo-Neto, Leonardo; Uyemura, Sérgio Akira; dos Santos, Wagner Ferreira; Da Costa, Fernando Batista

2011-01-27

Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs). The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys. The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic

Oral acute toxicity study of selected botanical pesticide plants used ...

African Journals Online (AJOL)

African Journal of Environmental Science and Technology ... The extracts were administered orally and the animals were observed for 24 h. ... Chronic studies should be carried out to assess whether these extracts have serious effects on experimental animals exposed to them at small doses for a long period of time.

Acute and chronic toxicity of boron to a variety of freshwater organisms.

Science.gov (United States)

Soucek, David J; Dickinson, Amy; Koch, Brian T

2011-08-01

Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far. Copyright © 2011 SETAC.

40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

Science.gov (United States)

2010-07-01

... on the chronic toxicity of chemical substances and mixtures (“chemicals”) subject to environmental... with the test design into retention chambers within the test and the control chambers. Mysids in the... and experimental history. Mysids used for establishing laboratory cultures may be purchased...

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.

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

Science.gov (United States)

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

Oral hygiene in patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Pedersen, Preben Ulrich; Uhrenfeldt, Lisbeth; Larsen, Palle

2017-01-01

SCOPING REVIEW OBJECTIVE: It is hypothesized that systematic oral hygiene may reduce airway infections in patients with chronic obstructive pulmonary disease (COPD). Before considering doing a systematic review, a scoping review is necessary to explore and map literature on the subject and identify......-invasive interventions that have been carried out to improve oral hygiene and relieve and/or reduce respiratory tract infections, exacerbation and/or hospital readmission in patients with diagnosed with COPD. A further objective is to undertake a comprehensive search to identify qualitative literature reporting...... on the experiences of oral hygiene in people diagnosed with COPD and/or their relatives and/or healthcare providers (HCPs).Specifically, the scoping review questions are as follows....

Plasma enzymatic antioxidant levels in non smoke tobacco consuming Oral sub mucous fibrosis (OSMF

Directory of Open Access Journals (Sweden)

Teklal Patel, Vikram Kulkarni

2013-04-01

Full Text Available Background: Globally Oral Cancer is the sixth most common cause death with India accounts for 86% of the world’s oral cancer cases. Chronic tobacco quid consumption often results in a progressive premalignant condition called Oral Sub mucous Fibrosis (OSMF whose malignant transformation rate of is around 7.6%. Free radicals released during the metabolism of tobacco and Areca nut my involved in the initiation and propagation of mucosal fibrosis. Objective: the objective of the present study is to measure antioxidant enzymes and lipid peroxidation levels in OSMF to assess oxidative stress like environment in OSMF patients. Materials and methods: for this study we invited 38 newly diagnosed OSMF patients both male and female consuming tobacco in the form of quid and the same number of age matched healthy non tobacco consuming were selected as a control group. In both groups plasma superoxide dismutase, Glutathione peroxidase, catalase levels and lipid peroxidation rate was measured. Results and conclusion: we observed very low antioxidant enzyme levels in OSMF patients when compared with healthy controls (P<0.01 and at the same time also observed very high lipid peroxidation rate in the study population (P<0.01 compare to control group indicating prevalence of oxidative stress like environment in tobacco consuming population, which might play a vital role in the initiation and propagation of various precancerous conditions like OSMF.

Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

Science.gov (United States)

Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

2017-11-01

Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

Early and late oral features of chronic graft-versus-host disease

Directory of Open Access Journals (Sweden)

Alessandra Oliveira Ferrari Gomes

2014-01-01

Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

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Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Division of Drug Safety Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993 (United States); Moland, Carrie L.; Branham, William S. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); George, Nysia I. [Division Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

2013-01-01

Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

Acute toxicity of metals and reference toxicants to a freshwater ostracod, Cypris subglobosa Sowerby, 1840 and correlation to EC{sub 50} values of other test models

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Khangarot, B.S., E-mail: bkhangarot@hotmail.com [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India); Das, Sangita [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India)

2009-12-30

The ostracod Cypris subglobosa Sowerby, 1840 static bioassay test on the basis of a 48 h of 50% of immobilization (EC{sub 50}) has been used to measure the toxicity of 36 metals and metalloids and 12 reference toxicants. Among the 36 metals and metalloids, osmium (Os) was found to be the most toxic in the test while boron (B), the least toxic. The EC{sub 50} values of this study revealed positive linear relationship with the established test models of cladoceran (Daphnia magna), sludge worm (Tubifex tubifex), chironomid larvae (Chironomus tentans), protozoan (Tetrahymena pyriformis), fathead minnow (Pimephales promelas), bluegill sunfish (Lepomis macrochirus), and aquatic macrophyte duckweed (Lemna minor). Correlation coefficients (r{sup 2}) for 17 physicochemical properties of metals or metal ions and EC{sub 50}s (as pM) were examined by linear regression analysis. The electronegativity, ionization potential, melting point, solubility product of metal sulfides (pK{sub sp}), softness parameter and some other physicochemical characteristics were significantly correlated with EC{sub 50}s of metals to C. subglobosa. The reproducibility of toxicity test was determined using 12 reference toxicants. The coefficient of variability of the EC{sub 50}s ranged from 6.95% to 55.37% and variability was comparable to that noticed for D. magna and other aquatic test models. The study demonstrated the need to include crustacean ostracods in a battery of biotests to detect the presence of hazardous chemicals in soils, sewage sludges, sediments and aquatic systems.

Prediction of Acute Mammalian Toxicity Using QSAR Methods: A Case Study of Sulfur Mustard and Its Breakdown Products

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John Wheeler

2012-07-01

Full Text Available Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR, has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD<sub>50sub> for determining relative toxicity of a number of substances. In general, the smaller the LD<sub>50sub> value, the more toxic the chemical, and the larger the LD<sub>50sub> value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s of interest, during emergency responses, LD<sub>50sub> values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD<sub>50sub> models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD<sub>50sub> values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

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Hussin Muhammad

2012-04-01

Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

Association of Oral Lichen Planus with Chronic C Hepatitis. Review of the Data in Literature

Science.gov (United States)

GHEORGHE, Carmen; MIHAI, Lelia; PARLATESCU, Ioanina; TOVARU, Serban

2014-01-01

The relationship between chronic hepatitis C virus infection (HCV) and oral lichen planus (OLP) is a current topic in the field of oral medicine. Many studies of this association have been made over time. The geographic variation of the hepatitis C prevalence proved to be an important factor influencing the statistical results of the studies analyzing the association of the oral plan lichen with the hepatitis C virus. Approaching this issue is not to be neglected. Treatment outcomes in patients with oral lichen planus associated with chronic hepatitis C virus are often unsatisfactory compared to patients suffering from idiopathic oral lichen planus. Also, the evolution of oral lesions is often fluctuating, with repeated periods of relapse according to the degree of liver function decompensation. Background therapy for liver disease itself may influence lichen planus lesions. Thus, during therapy with interferon and ribavirin oral lesions may appear or become acute. PMID:25553136

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

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

Particle-specific toxicity and bioavailability of cerium oxide (CeO{sub 2}) nanoparticles to Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Yang, Xinping; Pan, Haopeng [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Wang, Peng, E-mail: p.wang3@uq.edu.au [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); The University of Queensland, School of Agriculture and Food Sciences, St. Lucia, Queensland 4072 (Australia); Zhao, Fang-Jie [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom)

2017-01-15

Highlights: • The phytotoxicity and uptake of CeO{sub 2} NPs were examined in Arabidopsis. • CeO{sub 2} NPs stimulated plant growth at low doses but were toxic at high doses. • The toxicity was due to the NPs per se, rather than from the dissolved Ce ions. • A similar up-translocation factor was found for CeO{sub 2} NPs, bulk CeO{sub 2} and Ce ions. - Abstract: The use of manufactured cerium oxide nanoparticles (CeO{sub 2}-NPs) in consumer products has increased markedly over the past decade, and their release into natural ecosystems is unavoidable. This study investigated the phytotoxicity and uptake of CeO{sub 2}-NPs in Arabidopsis thaliana grown in an agar medium. Although low concentrations of CeO{sub 2}-NPs had stimulatory effects on plant growth, at higher concentrations, CeO{sub 2}-NPs reduced growth and had adverse effects on the antioxidant systems and photosystem. Importantly, the toxicity resulted from the nanoparticles per se, rather than from the dissolved Ce ions. CeO{sub 2}-NPs were taken up and subsequently translocated to shoot tissues, and transmission electron microscopy (TEM) showed the presence of a large number of needle-like particle aggregations in the intercellular regions and the cytoplasm of leaf cells. The up-translocation factor to shoots was independent of the concentrations of Ce in the roots and the supplied forms of Ce (i.e. CeO{sub 2}-NPs, CeO{sub 2}-bulk, and ionic Ce), suggesting that endocytosis is likely to be a general mechanism responsible for the translocation of these Ce compounds. These findings provide important information regarding the toxicity and uptake of CeO{sub 2}-NPs in plants, which needs to be considered in environmental risk assessment for the safe use and disposal of CeO{sub 2}-NPs.

Oral bioaccessibility of toxic metals in contaminated oysters and relationships with metal internal sequestration.

Science.gov (United States)

Gao, Shi; Wang, Wen-Xiong

2014-12-01

The Hong Kong oysters Crassostrea hongkongensis are widely farmed in the estuarine waters of Southern China, but they accumulate Cu and Zn to alarmingly high concentrations in the soft tissues. Health risks of seafood consumption are related to contaminants such as toxic metals which are bioaccessible to humans. In the present study, we investigated the oral bioaccessibility of five toxic metals (Ag, Pb, Cd, Cu and Zn) in contaminated oysters collected from different locations of a large estuary in southern China. In all oysters, total Zn concentration was the highest whereas total Pb concentration was the lowest. Among the five metals, Ag had the lowest oral bioaccessibility (38.9-60.8%), whereas Cu and Zn had the highest bioaccessibility (72.3-93.1%). Significant negative correlation was observed between metal bioaccessibility and metal concentration in the oysters for Ag, Cd, and Cu. We found that the oral bioaccessibility of the five metals was positively correlated with their trophically available metal fraction (TAM) in the oyster tissues, and negatively correlated with metal distribution in the cellular debris. Thus, metal partitioning in the TAM and cellular debris controlled the oral bioaccessibility to humans. Given the dependence of oral bioaccessibility on tissue metal contamination, bioaccessibility needs to be incorporated in the risk assessments of contaminated shellfish. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

Science.gov (United States)

Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

2016-05-01

The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe. © 2015 SETAC.

Treating chronic arsenic toxicity with high selenium lentil diets

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Sah, Shweta [Department of Ecosystem and Public Health, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4Z6 (Canada); Vandenberg, Albert [Department of Plant Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8 (Canada); Smits, Judit, E-mail: judit.smits@ucalgary.ca [Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6 (Canada)

2013-10-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

Treating chronic arsenic toxicity with high selenium lentil diets

International Nuclear Information System (INIS)

Sah, Shweta; Vandenberg, Albert; Smits, Judit

2013-01-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

Combined effects of chronic hyperglycaemia and oral aluminium intoxication on testicular tissue and some male reproductive parameters in Wistar rats.

Science.gov (United States)

Akinola, O B; Biliaminu, S A; Adedeji, O G; Oluwaseun, B S; Olawoyin, O M; Adelabu, T A

2016-09-01

Exposure to either environmental toxicants or chronic hyperglycaemia could impair male reproductive function. However, the extent to which exposure to such toxicants, in the presence of pre-existing metabolic dysfunction, could affect male reproduction is unclear. Streptozotocin-induced diabetic Wistar rats (12 weeks old) were exposed to oral aluminium chloride at 250 ppm for 30 days; followed by evaluation of caudal epididymal sperm count and motility, assay for serum follicle stimulating hormone (FSH), testosterone (T) and oestradiol; and assessment of testicular histology. Moreover, blood glucose was evaluated by the glucose oxidase method. In rats treated with streptozotocin (STZ) or aluminium (Al) alone, erosion of testicular parenchyma and stroma was observed. This effect was most severe in diabetic rats simultaneously exposed to Al; coupled with reduced caudal epididymal sperm count that was least in this (STZ+Al) group (18.75 × 10(6)  ml(-1) ) compared with controls (61.25 × 10(6)  ml(-1) ; P < 0.05), STZ group or Al group. Moreover, these reproductive perturbations (in the STZ+Al group) were associated with reduced sperm motility and significantly reduced serum FSH (P < 0.05); but elevated serum T and oestradiol (P < 0.05), compared with control. These suggest that diabetes-induced testicular lesion is exacerbated by simultaneous oral Al toxicity in Wistar rats. © 2015 Blackwell Verlag GmbH.

Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

DEFF Research Database (Denmark)

Wollenberger, Leah; Halling-Sørensen, B.; Kusk, Kresten Ole

2000-01-01

The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC...

Multi-dimensionality of chronic pain of the oral cavity and face

Science.gov (United States)

2013-01-01

Orofacial pain in its broadest definition can affect up to 7% of the population. Its diagnosis and initial management falls between dentists and doctors and in the secondary care sector among pain physicians, headache neurologists and oral physicians. Chronic facial pain is a long term condition and like all other chronic pain is associated with numerous co-morbidities and treatment outcomes are often related to the presenting co-morbidities such as depression, anxiety, catastrophising and presence of other chronic pain which must be addressed as part of management . The majority of orofacial pain is continuous so a history of episodic pain narrows down the differentials. There are specific oral conditions that rarely present extra orally such as atypical odontalgia and burning mouth syndrome whereas others will present in both areas. Musculoskeletal pain related to the muscles of mastication is very common and may also be associated with disc problems. Trigeminal neuralgia and the rarer glossopharyngeal neuralgia are specific diagnosis with defined care pathways. Other trigeminal neuropathic pain which can be associated with neuropathy is caused most frequently by trauma but secondary causes such as malignancy, infection and auto-immune causes need to be considered. Management is along the lines of other neuropathic pain using accepted pharmacotherapy with psychological support. If no other diagnostic criteria are fulfilled than a diagnosis of chronic or persistent idiopathic facial pain is made and often a combination of antidepressants and cognitive behaviour therapy is effective. Facial pain patients should be managed by a multidisciplinary team. PMID:23617409

Oral Health Challenges for Sub-Saharan Africa | Danfillo | Nigerian ...

African Journals Online (AJOL)

Oral Health Challenges for Sub-Saharan Africa. IS Danfillo. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

Phytochemical, sub-acute toxicity, and antibacterial evaluation of Cordia sebestena leaf extracts.

Science.gov (United States)

Osho, Adeleke; Otuechere, Chiagoziem A; Adeosun, Charles B; Oluwagbemi, Tolu; Atolani, Olubunmi

2016-03-01

In Nigeria, Cordia sebestena (Boraginaceae), an understudied medicinal plant, is used in traditional medicine for the treatment of gastrointestinal disorders. In this study, we investigated the chemical composition, antibacterial potential, and sub-acute toxicity of C. sebestena leaves. Ethyl acetate extracts were analyzed using thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectrophotometry. The antibacterial potential of the extracts was tested against five standard bacteria, namely Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Clinical observations and blood parameters were used to evaluate the possible toxicity of C. sebestena. The TLC profile yielded 39 fractions, which were pooled to nine combined sub-fractions (A-I). The FTIR spectrum of sub-fraction H indicated the presence of aliphatic C-H stretching vibration at 2922 and 2850 cm-1, C=O stretch at 1734 and 1708 cm-1, and C=C stretch of aromatics and aliphatics at 1464 and (shoulder) 1618 cm-1, respectively. The fractions of the C. sebestena ethyl acetate leaf extract showed antibacterial potential across board, but fraction H had the highest antibacterial activity against B. cereus and S. aureus. The study also indicated the relatively low toxicity profile of the ethyl acetate leaf extract of C. sebestena in the liver of rats. The study showed that C. sebestena leaves have strong antibacterial potential and low toxicity, thereby underlying the scientific basis for their folkloric use in the management of microbial infections and its associated complications.

Psychological treatment of patients with chronic toxic encephalopathy : Lessons from studies of chronic fatigue and whiplash

NARCIS (Netherlands)

van Hout, MSE; Wekking, EM; Berg, IJ; Deelman, BG

2003-01-01

Background. Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed

Effect of some drugs on radioprotective effectiveness, toxicity and distribution of 35S-Aminopropyl-aminoethyl-thiophosphate orally administered to mice

International Nuclear Information System (INIS)

Grechka, I.I.; Belavina, L.P.; Kalistpatov, G.V.; Zherebchenko, P.G.

1979-01-01

Studied was the influence of adreno- adn cholinolytics and cholinomimetic substances on radioprotective effectiveness and toxicity of aminopropyl-aminoehtyl-thiophosphate (APAETP) and distribution thereof among organs after oral and intraperitoneal administration. Atropine and INPEA decrease the toxicity and radioprotectiVe efficiency of APAETP when administered orally and do not influence these properties after intraperitoneal in ection. Deposition of the labelled radioprotector within the organs after oral administration is also indicative that atropine and INPEA can delay the transfer of APAETP from the stomach to the intenstine

Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy

International Nuclear Information System (INIS)

Vargas, Carlos; Martinez, Alvaro; Kestin, Larry L.; Yan Di; Grills, Inga; Brabbins, Donald S.; Lockman, David M.; Liang Jian; Gustafson, Gary S.; Chen, Peter Y.; Vicini, Frank A.; Wong, John W.

2005-01-01

Purpose We analyzed our experience treating localized prostate cancer with image-guided off-line correction with adaptive high-dose radiotherapy (ART) in our Phase II dose escalation study to identify factors predictive of chronic rectal toxicity. Materials and Methods From 1999-2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated in our Phase II 3D conformal dose escalation ART study to a median dose of 75.6 Gy (range, 63.0-79.2 Gy), minimum dose to confidence limited-planning target volume (cl-PTV) in 1.8 Gy fractions (median isocenter dose = 79.7 Gy). Seventy-four patients (22%) also received neoadjuvant/adjuvant androgen deprivation therapy. A patient-specific cl-PTV was constructed using 5 computed tomography scans and 4 sets of electronic portal images by applying an adaptive process to assure target accuracy and minimize PTV margin. For each case, the rectum (rectal solid) was contoured from the sacroiliac joints or rectosigmoid junction (whichever was higher) to the anal verge or ischial tuberosities (whichever was lower), with a median volume of 81.2 cc. The rectal wall was defined using the rectal solid with an individualized 3-mm wall thickness (median volume = 29.8 cc). Rectal wall dose-volume histogram was used to determine the prescribed dose. Toxicity was quantified using the National Cancer Institute Common Toxicity Criteria 2.0. Multiple dose-volume endpoints were evaluated for their association with chronic rectal toxicity. Results Median follow-up was 1.6 years. Thirty-four patients (crude rate 10.3%) experienced Grade 2 chronic rectal toxicity at a median interval of 1.1 years. Nine patients (crude rate = 2.7%) experienced Grade ≥3 chronic rectal toxicity (1 was Grade 4) at a median interval of 1.2 years. The 3-year rates of Grade ≥2 and Grade ≥3 chronic rectal toxicity were 20% and 4%, respectively. Acute toxicity predicted for chronic: Acute Grade 2-3 rectal toxicity (p 40% respectively. The volume

Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

Directory of Open Access Journals (Sweden)

Seol-Hee Moon

Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

Histopathological effects of lethal and sub-lethal concentrations of ...

African Journals Online (AJOL)

The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

Criteria for solvent-induced chronic toxic encephalopathy: a systematic review

NARCIS (Netherlands)

van der Hoek, J. A.; Verberk, M. M.; Hageman, G.

2000-01-01

In 1985, a WHO Working Group presented diagnostic criteria and a classification for solvent-induced chronic toxic encephalopathy (CTE). In the same year, the "Workshop on neurobehavioral effects of solvents" in Raleigh, N.C., USA introduced a somewhat different classification for CTE. The objective

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Psychological treatment of patients with chronic toxic encephalopathy: lessons from studies of chronic fatigue and whiplash

NARCIS (Netherlands)

van Hout, Moniek S. E.; Wekking, Ellie M.; Berg, Ina J.; Deelman, Betto G.

2003-01-01

Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed treatment outcome

BCR SIGNALING INHIBITORS: AN OVERVIEW OF TOXICITIES ASSOCIATED WITH IBRUTINIB AND IDELALISIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Directory of Open Access Journals (Sweden)

Lorenzo Falchi

2016-02-01

Full Text Available The B-cell receptor signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment landscape of chronic lymphocytic leukemia (CLL and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology of these agents, as well as clinical experience regarding their use for the treatment of patients with CLL. Our foci will be both the most common and the most clinically significant toxicities associated with these drugs.

BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia

Science.gov (United States)

Falchi, Lorenzo; Baron, Jessica M.; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

2016-01-01

The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs. PMID:26977270

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

Degradation of 5-FU by means of advanced (photo)oxidation processes: UV/H{sub 2}O{sub 2}, UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2} — Comparison of transformation products, ready biodegradability and toxicity

Energy Technology Data Exchange (ETDEWEB)

Lutterbeck, Carlos Alexandre, E-mail: lutterbeck@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul — UNISC, Av. Independência, 2293, CEP 96815-900 Santa Cruz do Sul, Rio Grande do Sul (Brazil); Wilde, Marcelo Luís, E-mail: wilde@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Baginska, Ewelina, E-mail: ewelina.baginska@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Leder, Christoph, E-mail: cleder@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Machado, Ênio Leandro, E-mail: enio@unisc.br [Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul — UNISC, Av. Independência, 2293, CEP 96815-900 Santa Cruz do Sul, Rio Grande do Sul (Brazil); and others

2015-09-15

The present study investigates the degradation of the antimetabolite 5-fluorouracil (5-FU) by three different advanced photo oxidation processes: UV/H{sub 2}O{sub 2}, UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2}. Prescreening experiments varying the H{sub 2}O{sub 2} and TiO{sub 2} concentrations were performed in order to set the best catalyst concentrations in the UV/H{sub 2}O{sub 2} and UV/TiO{sub 2} experiments, whereas the UV/Fe{sup 2+}/H{sub 2}O{sub 2} process was optimized varying the pH, Fe{sup 2+} and H{sub 2}O{sub 2} concentrations by means of the Box–Behnken design (BBD). 5-FU was quickly removed in all the irradiation experiments. The UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2} processes achieved the highest degree of mineralization, whereas the lowest one resulted from the UV/H{sub 2}O{sub 2} treatment. Six transformation products were formed during the advanced (photo)oxidation processes and identified using low and high resolution mass spectrometry. Most of them were formed and further eliminated during the reactions. The parent compound of 5-FU was not biodegraded, whereas the photolytic mixture formed in the UV/H{sub 2}O{sub 2} treatment after 256 min showed a noticeable improvement of the biodegradability in the closed bottle test (CBT) and was nontoxic towards Vibrio fischeri. In silico predictions showed positive alerts for mutagenic and genotoxic effects of 5-FU. In contrast, several of the transformation products (TPs) generated along the processes did not provide indications for mutagenic or genotoxic activity. One exception was TP with m/z 146 with positive alerts in several models of bacterial mutagenicity which could demand further experimental testing. Results demonstrate that advanced treatment can eliminate parent compounds and its toxicity. However, transformation products formed can still be toxic. Therefore toxicity screening after advanced treatment is recommendable. - Highlights: • Full primary elimination of 5-FU was

Regenerative toxicology: the role of stem cells in the development of chronic toxicities.

Science.gov (United States)

Canovas-Jorda, David; Louisse, Jochem; Pistollato, Francesca; Zagoura, Dimitra; Bremer, Susanne

2014-01-01

Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.

The neonicotinoid imidachloprid shows high chronic toxicity to mayfly nymphs

NARCIS (Netherlands)

Roessink, I.; Merga, L.B.; Zweers, A.J.; Brink, van den P.J.

2013-01-01

The present study evaluated the acute and chronic toxicity of imidacloprid to a range of freshwater arthropods. Mayfly and caddisfly species were most sensitive to short-term imidacloprid exposures (10 tests), whereas the mayflies showed by far the most sensitive response to long-term exposure of

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.

The effect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice.

Science.gov (United States)

Sharma, Veena; Sharma, Arti; Kansal, Leena

2010-03-01

Lead is a common environmental occupational toxic metal, known to have indirect oxidative effects. Considering the antioxidant properties of garlic, this study was undertaken to evaluate the therapeutic efficacy of garlic extracts in terms of normalization of altered hematological, biochemical and immunological parameters, and depletion of inorganic lead burden in blood, kidney and brain tissues. Chronic lead nitrate ingestion showed a significant decline in total erythrocyte count, total leukocyte count, hemoglobin concentration, lymphocyte and monocyte content, while neutrophil content increased in lead nitrate treated group. Pb(NO(3))(2) exposure elicited a significant escalation in thiobarbituric acid reactive substances level and depletion in reduced glutathione content and antioxidant enzymes namely, superoxide dismutase and catalase in kidney and brain. Activities of aspartate transaminase, alanine transaminase, acid phosphatase and alkaline phosphatase augmented significantly in kidney and brain of lead exposed mice. Lead nitrate treatment decreased protein content while cholesterol and lead burden increased significantly. A decrease in viability of macrophage, phagocytic index, immunoglobulin level and plaque count were the salient features observed in lead exposed animals. However, oral administration of garlic extracts to Pb(NO(3))(2) treated groups attenuated the deranged parameters to some extent. This indicates that garlic can be a protective regimen for lead toxicity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

Science.gov (United States)

Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

2014-01-01

Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

Directory of Open Access Journals (Sweden)

Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

Science.gov (United States)

Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

2018-02-01

Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

The management of chronic traumatic ulcer in oral cavity

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Maharani Laillyza Apriasari

2012-06-01

Full Text Available Background: The traumatic ulcer is one of the most common oral mucosal lesions. The etiology of traumatic ulcer may result from mechanical trauma, as well as chemical, electrical, or thermal stimulus, may also be involved in addition, fractured, malposed, or malformed teeth. The clinical manifestation of traumatic ulcer are ulcer, have a yellowish floor, fibrinous center, red and inflammatory margin without induration. Purpose: The purpose of this case report is to present how to manage the patient with the chronic traumatic ulcer in oral cavity. Case: This case report is about the patient with chronic ulcer in oral cavity. Intra oral examination showed on the right tongue margin appeared the major ulcer, single, diameter 1,5 cm, pain, white color, induration and irreguler margin around the ulcer. The patient had been suffering it for 5 months. She had come to a lot of dentist and the oral maxillofacial surgery, but they could not heal the ulcer. The dental occlusion of the patient, especially 17 and 47 then 15 and 45 teeth was looked bitten the right tongue. It underlied to get the clinical diagnosis as the chronic traumatic ulcer. Case management: The main therapy of traumatic ulcer is eliminiting the etiology factor, so that decided to do teeth extraction 45 and 47 that was looked linguversion position on 45 degrees. Before doing the teeth extraction, the patient was referred to take complete blood count (CBC, blood glucose examination and biopsy. The monitoring of the ulcer must be done until 2 weeks after the teeth extraction. If the lesion was persistent, it is suspected as malignancy. Conclusion: It can be concluded that the main management of chronic traumatic ulcer in oral cavity is removing the etiology factors. If the ulcer is still persistent after 2 weeks from the etiology factor had been removing, it is suspected as the malignancy that is needed biopsy examination to get the final diagnosis.Latar belakang: Ulkus traumatikus adalah

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

International Nuclear Information System (INIS)

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

2006-01-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

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 ...

The chronic toxicity of molybdate to marine organisms. I. Generating reliable effects data

International Nuclear Information System (INIS)

Heijerick, D.G.; Regoli, L.; Stubblefield, W.

2012-01-01

A scientific research program was initiated by the International Molybdenum Association (IMOA) which addressed identified gaps in the environmental toxicity data for the molybdate ion (MoO 4 2− ). These gaps were previously identified during the preparation of EU-REACH-dossiers for different molybdenum compounds (European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances; EC, 2006). Evaluation of the open literature identified few reliable marine ecotoxicological data that could be used for deriving a Predicted No-Effect Concentration (PNEC) for the marine environment. Rather than calculating a PNEC marine using the assessment factor methodology on a combined freshwater/marine dataset, IMOA decided to generate sufficient reliable marine chronic data to permit derivation of a PNEC by means of the more scientifically robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Nine test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na 2 MoO 4 ·2H 2 O) according to published standard testing guidelines that are acceptable for a broad range of regulatory purposes. The selected test organisms were representative for typical marine trophic levels: micro-algae/diatom (Phaeodactylum tricornutum, Dunaliella tertiolecta), macro-alga (Ceramium tenuicorne), mysids (Americamysis bahia), copepod (Acartia tonsa), fish (Cyprinodon variegatus), echinoderms (Dendraster exentricus, Strongylocentrotus purpuratus) and molluscs (Mytilus edulis, Crassostrea gigas). Available NOEC/EC 10 levels ranged between 4.4 mg Mo/L (blue mussel M. edulis) and 1174 mg Mo/L (oyster C. gigas). Using all available reliable marine chronic effects data that are currently available, a HC 5,50% (median hazardous concentration affecting 5% of the species) of 5.74 (mg Mo)/L was derived with the statistical extrapolation approach, a value that can be used for national and

Toxicity studies of medicinal plants used in sub-Saharan Africa.

Science.gov (United States)

Boukandou Mounanga, Marlaine; Mewono, Ludovic; Aboughe Angone, Sophie

2015-11-04

In sub-Saharan Africa, traditional medicine is widely used in rural and urban areas also. This is essentially due to the prohibitive cost of pharmaceutical-based medicine and the low incomes of a major part of the population. In addition, the efficacies of many of these traditional and plant-based medicines are proven, but the fact remains that certain plants used in traditional medicine have toxic effects. It is in this perspective that we investigated by bibliographic literature on the toxicity of plants used in traditional medicine. It is crucial to gain knowledge on these plant-based medicines prepared and prescribed by practitioners, particularly in terms of toxicity, composition, specific efficacy of disease and to advise practitioners of this alternative medicine on the protection and security of patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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.

Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

Directory of Open Access Journals (Sweden)

Davide Conrotto

2014-01-01

Full Text Available Background. Chronic graft versus host disease (cGVHD is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

Chronic toxicity of nickel-spiked freshwater sediments: variation in toxicity among eight invertebrate taxa and eight sediments

Science.gov (United States)

Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.; Ivey, Chris D.; Kunz, James L.; Kemble, Nile E.; Schlekat, Christian E.; Garman, Emily R.

2013-01-01

This study evaluated the chronic toxicity of Ni-spiked freshwater sediments to benthic invertebrates. A 2-step spiking procedure (spiking and sediment dilution) and a 2-stage equilibration period (10 wk anaerobic and 1 wk aerobic) were used to spike 8 freshwater sediments with wide ranges of acid-volatile sulfide (AVS; 0.94–38 µmol/g) and total organic carbon (TOC; 0.42–10%). Chronic sediment toxicity tests were conducted with 8 invertebrates (Hyalella azteca, Gammarus pseudolimnaeus, Chironomus riparius, Chironomus dilutus, Hexagenia sp., Lumbriculus variegatus, Tubifex tubifex, and Lampsilis siliquoidea) in 2 spiked sediments. Nickel toxicity thresholds estimated from species-sensitivity distributions were 97 µg/g and 752 µg/g (total recoverable Ni; dry wt basis) for sediments with low and high concentrations of AVS and TOC, respectively. Sensitive species were tested with 6 additional sediments. The 20% effect concentrations (EC20s) for Hyalella and Gammarus, but not Hexagenia, were consistent with US Environmental Protection Agency benchmarks based on Ni in porewater and in simultaneously extracted metals (SEM) normalized to AVS and TOC. For Hexagenia, sediment EC20s increased at less than an equimolar basis with increased AVS, and toxicity occurred in several sediments with Ni concentrations in SEM less than AVS. The authors hypothesize that circulation of oxygenated water by Hexagenia led to oxidation of AVS in burrows, creating microenvironments with high Ni exposure. Despite these unexpected results, a strong relationship between Hexagenia EC20s and AVS could provide a basis for conservative site-specific sediment quality guidelines for Ni.

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

Science.gov (United States)

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients.

Science.gov (United States)

Rauscher, Sandrine; Lafrance, Jean-Philippe; Pichette, Vincent; Bell, Robert Z; Desforges, Katherine; Lepage, Laurence; Ouellet, Georges; Ouimet, Denis; Leblanc, Martine; Lamarche, Caroline; Bezzaoucha, Sarah; Vallee, Michel

2017-02-01

The optimal vitamin D 3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D 3 . The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D 3 , to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests. The mean dose of active vitamin D 3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance. According to our study, calcitriol in equal dosage is more effective than alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D 3 for the treatment of SHPT in chronic hemodialysis patients.

Oral rehabilitation of a patient with sub - total maxillectomy

OpenAIRE

Romesh Soni; Shitu Jindal; B P Singh; Neelam Mittal; T P Chaturvedi; D R Prithviraj

2011-01-01

This clinical report describes oral rehabilitation of a patient with sub-total maxillectomy with palatine process of maxilla and horizontal plate of palatine bone intact to retain the maxillary obturator. Clinical examination has been performed to know the amount of favorable undercuts to be used for retention of the obturator for better functional efficiency. Successful prosthetic reconstruction of hemimaxillectomy defect is a challenging procedure that requires multidisciplinary expertise t...

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.

Behavior and chronic toxicity of two differently stabilized silver nanoparticles to Daphnia magna

DEFF Research Database (Denmark)

Sakka, Yvonne; Skjolding, Lars Michael; Mackevica, Aiga

2016-01-01

While differences in silver nanoparticle (AgNP) colloidal stability, surface potential, or acute aquatic toxicity for differently stabilized AgNP have often been reported, these have rarely been studied in long-term ecotoxicity tests. In the current study, we investigated the chronic toxicity of Ag...... types of AgNP during a typical media exchange period in the D. magna test for chronic toxicity. As expected, the sterically stabilized AgNP were more stable in the test medium, also in the presence of food; however, a higher uptake of silver after 24 h exposure of the charge stabilized AgNP was found...... compared to the detergent-stabilized AgNP (0.046 ± 0.006 μg Ag μg DW−1 and 0.023 ± 0.005 μg Ag μg DW−1, respectively). In accordance with this, the higher reproductive effects and mortality were found for the charge-stabilized than for the sterically-stabilized silver nanoparticles in 21-d tests...

Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

Directory of Open Access Journals (Sweden)

Letícia Flohr

2012-01-01

Full Text Available Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3 induced the highest toxicity level to Daphnia magna(CE50,48 h=2.21%. A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min=12.08%. All samples of pulp and paper wastes, and a textile waste (sample TX2 induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

Toxicity assessment of TiO{sub 2} nanoparticles in zebrafish embryos under different exposure conditions

Energy Technology Data Exchange (ETDEWEB)

Clemente, Z., E-mail: zairaclemente@yahoo.com.br [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Programa de Pós-graduação em Biologia Funcional e Molecular, UNICAMP, Campinas, SP (Brazil); Castro, V.L.S.S. [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Moura, M.A.M. [Laboratório da Ciência das Plantas Daninhas, Instituto Biológico, APTA/SAA, Campinas, SP (Brazil); Jonsson, C.M. [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Fraceto, L.F. [Programa de Pós-graduação em Biologia Funcional e Molecular, UNICAMP, Campinas, SP (Brazil); Departamento de Engenharia Ambiental, UNESP, Sorocaba, SP (Brazil)

2014-02-15

Highlights: •Nano-TiO{sub 2} accelerated hatching of the larvae. •Exposure to anatase/rutile mixture under UV light altered the equilibrium and survival of the larvae. •Nano-TiO{sub 2} caused alterations in the activities of CAT and GST. -- Abstract: The popularity of TiO{sub 2} nanoparticles (nano-TiO{sub 2}) lies in their wide range of nanotechnological applications, together with low toxicity. Meanwhile, recent studies have shown that the photocatalytic properties of this material can result in alterations in their behavior in the environment, causing effects that have not yet been fully elucidated. The objective of this study was to evaluate the toxicity of two formulations of nano-TiO{sub 2} under different illumination conditions, using an experimental model coherent with the principle of the three Rs of alternative animal experimentation (reduction, refinement, and replacement). Embryos of the fish Danio rerio were exposed for 96 h to different concentrations of nano-TiO{sub 2} in the form of anatase (TA) or an anatase/rutile mixture (TM), under either visible light or a combination of visible and ultraviolet light (UV). The acute toxicity and sublethal parameters evaluated included survival rates, malformation, hatching, equilibrium, and overall length of the larvae, together with biochemical biomarkers (specific activities of catalase (CAT), glutathione S-transferase (GST), and acid phosphatase (AP)). Both TA and TM caused accelerated hatching of the larvae. Under UV irradiation, there was greater mortality of the larvae of the groups exposed to TM, compared to those exposed to TA. Exposure to TM under UV irradiation altered the equilibrium of the larvae. Alterations in the activities of CAT and GST were indicative of oxidative stress, although no clear dose-response relationship was observed. The effects of nano-TiO{sub 2} appeared to depend on both the type of formulation and the illumination condition. The findings contribute to elucidation of the

Toxicity studies of the water extract from the calyces of Hibiscus ...

African Journals Online (AJOL)

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and ...

A re-evaluation of PETROTOX for predicting acute and chronic toxicity of petroleum substances.

Science.gov (United States)

Redman, Aaron D; Parkerton, Thomas F; Leon Paumen, Miriam; Butler, Josh D; Letinski, Daniel J; den Haan, Klass

2017-08-01

The PETROTOX model was developed to perform aquatic hazard assessment of petroleum substances based on substance composition. The model relies on the hydrocarbon block method, which is widely used for conducting petroleum substance risk assessments providing further justification for evaluating model performance. Previous work described this model and provided a preliminary calibration and validation using acute toxicity data for limited petroleum substance. The objective of the present study was to re-evaluate PETROTOX using expanded data covering both acute and chronic toxicity endpoints on invertebrates, algae, and fish for a wider range of petroleum substances. The results indicated that recalibration of 2 model parameters was required, namely, the algal critical target lipid body burden and the log octanol-water partition coefficient (K OW ) limit, used to account for reduced bioavailability of hydrophobic constituents. Acute predictions from the updated model were compared with observed toxicity data and found to generally be within a factor of 3 for algae and invertebrates but overestimated fish toxicity. Chronic predictions were generally within a factor of 5 of empirical data. Furthermore, PETROTOX predicted acute and chronic hazard classifications that were consistent or conservative in 93 and 84% of comparisons, respectively. The PETROTOX model is considered suitable for the purpose of characterizing petroleum substance hazard in substance classification and risk assessments. Environ Toxicol Chem 2017;36:2245-2252. © 2017 SETAC. © 2017 SETAC.

Acute and chronic systemic chromium toxicity.

Science.gov (United States)

Gad, S C

1989-10-01

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

Science.gov (United States)

Walker, Calvin C., James T. Winstead, Steven S. Foss, Janis C. Kurtz, James Watts, Jeanne E. Scott and William S. Fisher. In press. Acute and Chronic Toxicity of Brevetoxin to Oysters and Grass Shrimp (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November ...

Acute oral toxicity test and phytochemistry of some west african ...

African Journals Online (AJOL)

(SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1,2,4 and 8, PN; 2.5, 5, 10 and 20, OC; 5,10,20 and 40, FC; 1,2,4 and 8, HE; 4,8,16,32) of the aqueous extract of each plant (g/kg body weight) after 12hours fasting. Results: The dry ...

Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

Energy Technology Data Exchange (ETDEWEB)

Kim Tiam, Sandra, E-mail: sandra.kimtiam@gmail.com [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Laviale, Martin [Departamento de Biologia and CESAM – Centro de Estudos do Ambiente e do Mar Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Sorbonne Universités, UPMC Univ Paris 06, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer (France); CNRS, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer France (France); Feurtet-Mazel, Agnès [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Jan, Gwilherm [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Gonzalez, Patrice [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Mazzella, Nicolas; Morin, Soizic [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France)

2015-08-15

Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F{sub 0}), optimal and effective quantum yields of photosystem II (F{sub v}/F{sub m} and Φ{sub PSII}). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L{sup −1}), its main degradation product (DCPMU) (from 1.0 to 1014 μg L{sup −1}) and norflurazon (from 0.6 to 585 μg L{sup −1}) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR{sub max} and I{sub k}) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F{sub 0} and F{sub v}/F{sub m}) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors.

FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia.

Science.gov (United States)

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Nolen, Jacqueline G; Roger, Simon D

2014-11-01

The optimal iron therapy regimen in patients with non-dialysis-dependent chronic kidney disease (CKD) is unknown. Ferinject® assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre, prospective and randomized study of 626 patients with non-dialysis-dependent CKD, anaemia and iron deficiency not receiving erythropoiesis-stimulating agents (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric carboxymaltose (FCM), targeting a higher (400-600 µg/L) or lower (100-200 µg/L) ferritin or oral iron therapy. The primary end point was time to initiation of other anaemia management (ESA, other iron therapy or blood transfusion) or haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52. The primary end point occurred in 36 patients (23.5%), 49 patients (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a greater proportion of patients achieved an Hb increase ≥1 g/dL with high-ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of adverse events and serious adverse events were similar in all groups. Compared with oral iron, IV FCM targeting a ferritin of 400-600 µg/L quickly reached and maintained Hb level, and delayed and/or reduced the need for other anaemia management including ESAs. Within the limitations of this trial, no renal toxicity was observed, with no difference in cardiovascular or infectious events. NCT00994318. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

NARCIS (Netherlands)

van Hout, Moniek S. E.; Schmand, Ben; Wekking, Ellie M.; Hageman, Gerard; Deelman, Betto G.

2003-01-01

Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

NARCIS (Netherlands)

van Hout, MSE; Schmand, B; Wekking, EM; Hageman, G; Deelman, BG

Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

Oral lichen planus may enhance the expression of Th17-associated cytokines in local lesions of chronic periodontitis.

Science.gov (United States)

Wang, Hui; Han, Qi; Luo, Zhenhua; Xu, Caixia; Liu, Jiajia; Dan, Hongxia; Xu, Yi; Zeng, Xin; Chen, Qianming

2014-07-01

This study aims to compare the expression levels of interleukin (IL)-17 and IL-23 in local periodontal tissues from patients with both chronic periodontitis and oral lichen planus (CP-OLP), patients with chronic periodontitis (CP) only, patients with oral lichen planus (OLP) only, and healthy controls (HC). The periodontal tissues were collected from 15 CP-OLP patients, 15 CP patients, 15 OLP patients, and 10 healthy controls. Immunohistochemistry (IHC) and real-time quantitative PCR (qPCR) was performed to investigate the protein and mRNA expression level of IL-17 and IL-23 in periodontal lesions from these four groups. IHC statistical analysis showed that the expression level of IL-17- and IL-23p19-positive cells significantly increased in CP-OLP group compared with that in CP (P periodontal tissues from periodontitis patients with oral lichen planus, which might aggravate the inflammatory response in local lesions. Oral lichen planus and chronic periodontitis may have interaction in disease pathogenesis, while IL-17 detection in local lesions may be helpful in identifying the disease severity in periodontitis patients with oral lichen planus.

Acute and chronic toxicity of effluent water from an abandoned uranium mine.

Science.gov (United States)

Antunes, S C; Pereira, R; Gonçalves, F

2007-08-01

Inactive or abandoned mines represent a significant source of environmental, chemical, physical, and aesthetic impact. Among concerning situations, the occurrence of abandoned or semi-abandoned mine-associated ponds (for sedimentation of solids, for effluent neutralization, or for washing the ore) is a common feature in this type of system. These ponds are a source of contamination for the groundwater resources and adjacent soils, because they lack appropriate impermeabilization. The use of this water for agriculture may also pose chronic risks to humans. In Portugal, these problems have been diagnosed and some remediation projects have been developed. The purpose of our study was to evaluate the acute and chronic toxicity of water samples collected from the aquatic system surrounding an abandoned uranium mine (Cunha Baixa, Mangualde, Central Portugal). The present study focuses on the water compartment, whose toxicity was evaluated by means of standard toxicity assays using two Daphnia species (D. longispina and D. magna). Three different ponds were used in the characterization of the aquatic system from Cunha Baixa mine: a reference pond (Ref), a mine effluent treatment pond (T), and a mine pit pond (M). Metal analyses performed in the water samples from these ponds showed values that, in some cases, were much higher than maximum recommendable values established (especially Al, Mn) by Portuguese legislation for waters for crop irrigation. Acute toxicity was only observed in the mine pit pond, with EC(50) values of 28.4% and 50.4% for D. longispina and D. magna, respectively. The significant impairment of chronic endpoints, translated in reductions in the population growth rate for both species, gives rise to concerns regarding the potential risks for aquatic zooplanktonic communities, from local receiving waters, potentially exposed to point source discharges of the treated and nontreated effluent from Cunha Baixa uranium mine.

Effect of gamma irradiation on acute oral toxicity of ethanolic extract of red ginger (zingiber officinale)

International Nuclear Information System (INIS)

Ermin Katrin; Winarti Andayani; Susanto; Hendig Winarno

2014-01-01

Red ginger is widely used in traditional medicine to treat various types of diseases. Evaluation of the toxic properties of red ginger is very important to know the negative harmful impact to human health. Therefore, before it is consumed by humans, it is needed to conduct acute oral toxicity of red ginger extract in mice. Thin rhizome of red ginger in poly ethylene plastic packaging was irradiated by gamma rays at a dose of 10 kGy with a dose rate of 10 kGy/h. The ethanol extract of unirradiated as well as irradiated red ginger was then tested for the acute oral toxicity using OECD Guideline test method. The results showed that throughout the 14 days of treatment there was a change in behavior pattern, clinical symptoms and body weight of control mice and treatment groups. Histopathological examination of kidneys, heart, liver, lungs and spleen of the dose less than 1250 mg/kg body weight showed normal condition and no significant side effects observation. While central venous damage and a reduced number of hepatocyte cells in male mice occurred in the test dose higher than 2000 mg/kg body weight, whereas in female mice it occurred in the test group dose higher than 1250 mg/kg bw. Based on renal histology of male and female mice at doses higher than 1250 mg/kg body weight, there were damage to Bowman's capsule, glomerulus, proximal vessel and distal vessels. LD50 of unirradiated and irradiated with 10 kGy of ethanol extract of red ginger were 1887 mg/kg body weight and 2639 mg/kg body weight, respectively, and it can be categorized as moderately toxic. Oral administration of ethanol extract of red ginger with dose of 1250 mg/kg body weight gave an effect in mice organs. From these results it can be concluded that oral administration of both unirradiated and irradiated with a dose 10 kGy of ethanol extract consider safe at a dose less than 1250 mg/kg body weigh. (author)

Acute oral toxicity test and phytochemistry of some West African medicinal plants.

Science.gov (United States)

Awobajo, F O; Omorodion-Osagie, E; Olatunji-Bello, I I; Adegoke, O A; Adeleke, T I

2009-01-01

Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. LD50 and phytochemistry of four medicinal plants of West Africa were investigated. Thirty male and non pregnant female Swiss albino mice weighing 20grams each were used for this study. They were divided into the Control (C), Oldenlandia corymbosa L. aqueous leaf-extract treated (OCG), Parquetina nigrescens aqueous leaf extract treated (PNG), Hybanthus enneaspermus aqueous leaf extract treated (HEG), Ficus carica leaf extract treated (FCG) and Sesamum indicum aqueous seeds extract treated group (SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1, 2, 4 and 8, PN; 2.5, 5, 10 and 20, OC; 5, 10, 20 and 40, FC; 1, 2, 4 and 8, HE; 4, 8, 16, 32) of the aqueous extract of each plant (g/kg body weight) after 12 hours fasting. The dry aqueous leaf extracts of HE, OC, PN, FC all have dark brown colour and pH ranging from 6.1 to 7.2 while the seed extract of SI has a light brown color with pH of 7.0. Flavonoids, cardiac glycosides, anthocyanosides, saponin, and reducing sugar were present in all extracts, while cyanogenic glycoside was present only in HE. LD50 determination results obtained using Thompson and Finney methods were as follows; OC; 14.14 +/- 0.27 and 10.56 +/- 0.20, PN; 12.60 +/- 0.10 and 13.10 +/- 0.10, HE; 8.14 +/- 0.30 and 8.24 +/- 0.35, FC; 3.36 +/- 0.26 and 4.00 +/- 0.04, SI; 4.00 +/- 0.10 and 3.10 +/- 0.22 respectively (LD50 values are in g/kg body weight. The results of this study have provided an oral LD50 from where a safe dose can be chosen for further research into the merits of the consumption of these medicinal plants.

Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

International Nuclear Information System (INIS)

Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

2010-01-01

2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

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.)

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]).

Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

Science.gov (United States)

Davoudi, Bahar

More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

Science.gov (United States)

Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schroeder, Jennifer R; Schwope, David M; Kelly, Deanna L; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

2013-01-01

Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers. Thirteen male chronic daily cannabis smokers (mean ± SD age 24.6± 3.7 years, self-reported smoking frequency of 5.5 ± 5.9 (range 1-24) joint-equivalents daily at study entry) were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg daily) starting the afternoon after admission. The St. Mary's Hospital Sleep Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active metabolite) concentrations were measured in venous blood samples collected every evening. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression. Higher evening THC and 11-OH-THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day. In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly (3.54 and 5.34 minutes per night, respectively) but significantly during the study. These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations. Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment. (Am J Addict 2013;22:510-514). Copyright © American Academy of Addiction Psychiatry.

The H{sub 1}–H{sub 2} domain of the α{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

Energy Technology Data Exchange (ETDEWEB)

Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li, E-mail: wangyongli@gmail.com

2012-07-01

The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α{sub 1} or α{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 μM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ► We prepared two antibodies against the H{sub 1}-H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

Oral Fosfomycin for the Treatment of Acute and Chronic Bacterial Prostatitis Caused by Multidrug-Resistant Escherichia coli

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George G. Zhanel

2018-01-01

Full Text Available Acute and chronic bacterial prostatitis in outpatients is commonly treated with oral fluoroquinolones; however, the worldwide dissemination of multidrug-resistant (MDR Escherichia coli has resulted in therapeutic failures with fluoroquinolones. We reviewed the literature regarding the use of oral fosfomycin in the treatment of acute and chronic prostatitis caused by MDR E. coli. All English-language references on PubMed from 1986 to June 2017, inclusive, were reviewed from the search “fosfomycin prostatitis.” Fosfomycin demonstrates potent in vitro activity against a variety of antimicrobial-resistant E. coli genotypes/phenotypes including ciprofloxacin-resistant, trimethoprim-sulfamethoxazole-resistant, extended-spectrum β-lactamase- (ESBL- producing, and MDR isolates. Fosfomycin attains therapeutic concentrations (≥4 μg/g in uninflamed prostatic tissue and maintains a high prostate/plasma ratio up to 17 hours after oral administration. Oral fosfomycin’s clinical cure rates in the treatment of bacterial prostatitis caused by antimicrobial-resistant E. coli ranged from 50 to 77% with microbiological eradication rates of >50%. An oral regimen of fosfomycin tromethamine of 3 g·q 24 h for one week followed by 3 g·q 48 h for a total treatment duration of 6–12 weeks appeared to be effective. Oral fosfomycin may represent an efficacious and safe treatment for acute and chronic prostatitis caused by MDR E. coli.

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF{sub 4}] and [omim][BF{sub 4}], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone

Energy Technology Data Exchange (ETDEWEB)

Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos, E-mail: sdailianis@upatras.gr

2015-07-15

Highlights: • The toxic effects of [bmim][BF{sub 4}] and [omim][BF{sub 4}] on mussels were investigated. • Both ILs could induce lethal and nonlethal effects on Mytilus galloprovincialis. • Different extent of IL-mediated adverse effects was observed in mussel hemocytes. • The alkyl chain length and lipophilicity of ILs are crucial for their toxicity. • Acetone influences the oxidative and genotoxic effects of [omim][BF{sub 4}]. - Abstract: This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF{sub 4}] (1-butyl-3-methylimidazolium) and [omim][BF{sub 4}] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF{sub 4}] or [omim][BF{sub 4}], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96 h, in order to determine the concentration that causes 50% mussel mortality (LC{sub 50} values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF{sub 4}] was more toxic than [bmim][BF{sub 4}] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF{sub 4}]-treated mussels, compared to those occurring in [bmim][BF{sub 4}] in all cases. Similarly, [bmim][BF{sub 4}]-mediated oxidative and genotoxic effects were observed only in the highest

Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

Science.gov (United States)

Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

2013-01-01

Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

Toxicological analysis and effectiveness of oral Kalanchoe pinnata on a human case of cutaneous leishmaniasis.

Science.gov (United States)

Torres-Santos, E C; Da Silva, S A G; Costa, S S; Santos, A P P T; Almeida, A P; Rossi-Bergmann, B

2003-08-01

Leishmaniasis is an extremely difficult disease to treat. Previously, it was shown that oral Kalanchoe pinnata (Kp) leaf extract is strongly effective against murine leishmaniasis. Here, it is shown that the serum levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), urea and alkaline phosphatase were unchanged in mice orally treated with supraoptimal Kp doses for 30 days, indicating the absence of chronic toxicity to the liver, heart or kidney. Additionally, evidence is presented that human leishmaniasis may also be controlled with oral Kp. A 36-year-old man with an active cutaneous leishmaniasis was orally treated with 30 g wet weight of Kp leaves/day for 14 days. During the Kp treatment, the lesion stopped growing and slightly decreased. No adverse reactions or toxicity was observed. This study reports for the first time that Kalanchoe pinnata contains substances potentially active and safe for the oral treatment of human cutaneous leishmaniasis. Copyright 2003 John Wiley & Sons, Ltd.

Effect of oral preparation of astragalus membranaceous on serum SOD levels in aged patients with chronic bronchial asthma

International Nuclear Information System (INIS)

Sun Zhiyong

2005-01-01

Objective: To investigate the therapeutic effect of oral liquid preparation of astragalus membranaceous in aged patients with chronic bronchial asthma with special reference on the serum SOD levels. Methods: Serum SOD levels were measured with RIA in 42 aged patients with chronic bronchial asthma both before and after a course of treatment with oral liquid preparation of astragalus membranaceous (10ml b. i. d for 3 months) as well as in 35 controls. Results: The patients general condition was greatly improved after the treatment. Before treatment, the serum SOD levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Oral liquid preparation of astragalus membranaceous was therapeutically useful for chronic bronchial asthma in aged patients with correction of the serum SOD levels. (authors)

P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

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Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

2013-12-15

Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

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.

Experimental oral transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus.

Directory of Open Access Journals (Sweden)

Gordon B Mitchell

Full Text Available Chronic wasting disease (CWD, a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrP(CWD in the recto-anal mucosa associated lymphoid tissue (RAMALT of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrP(CWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M, 129 (G/S, 138 (S/N and 169 (V/M. These findings demonstrate that (i a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii certain reindeer PRNP polymorphisms may be protective against CWD infection.

Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart. Coville

Directory of Open Access Journals (Sweden)

Anna C. Almeida

Full Text Available ABSTRACT: This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922 and Staphylococcus aureus (ATCC 25923 in the concentration of 200, 400 and 600μL/mL. The results indicated that 600μL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.

Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

Science.gov (United States)

Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

2014-05-01

Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

Toxicity and biodistribution of orally administered casein nanoparticles.

Science.gov (United States)

Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

2017-08-01

In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

Energy Technology Data Exchange (ETDEWEB)

Holland, J.M.

2001-01-16

Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

Chronic toxicity of selected polycyclic aromatic hydrocarbons to algae and crustaceans using passive dosing.

Science.gov (United States)

Bragin, Gail E; Parkerton, Thomas F; Redman, Aaron D; Letinksi, Daniel J; Butler, Josh D; Paumen, Miriam Leon; Sutherland, Cary A; Knarr, Tricia M; Comber, Mike; den Haan, Klaas

2016-12-01

Because of the large number of possible aromatic hydrocarbon structures, predictive toxicity models are needed to support substance hazard and risk assessments. Calibration and evaluation of such models requires toxicity data with well-defined exposures. The present study has applied a passive dosing method to generate reliable chronic effects data for 8 polycyclic aromatic hydrocarbons (PAHs) on the green algae Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia. The observed toxicity of these substances on algal growth rate and neonate production were then compared with available literature toxicity data for these species, as well as target lipid model and chemical activity-based model predictions. The use of passive dosing provided well-controlled exposures that yielded more consistent data sets than attained by past literature studies. Results from the present study, which were designed to exclude the complicating influence of ultraviolet light, were found to be well described by both target lipid model and chemical activity effect models. The present study also found that the lack of chronic effects for high molecular weight PAHs was consistent with the limited chemical activity that could be achieved for these compounds in the aqueous test media. Findings from this analysis highlight that variability in past literature toxicity data for PAHs may be complicated by both poorly controlled exposures and photochemical processes that can modulate both exposure and toxicity. Environ Toxicol Chem 2016;35:2948-2957. © 2016 SETAC. © 2016 SETAC.

Can chronic exposure to imidacloprid, clothianidin, and thiamethoxam mixtures exert greater than additive toxicity in Chironomus dilutus?

Science.gov (United States)

Maloney, E M; Morrissey, C A; Headley, J V; Peru, K M; Liber, K

2018-07-30

Widespread agricultural use of neonicotinoid insecticides has resulted in frequent detection of mixtures of these compounds in global surface waters. Recent evidence suggests that neonicotinoid mixtures can elicit synergistic toxicity in aquatic insects under acute exposure conditions, however this has not been validated for longer exposures more commonly encountered in the environment. Therefore, we aimed to characterize the chronic (28-day) toxicity of imidacloprid, clothianidin, and thiamethoxam mixtures under different doses and mixture ratios to determine if the assumption of synergistic toxicity would hold under more environmentally realistic exposure settings. The sensitive aquatic insect Chironomus dilutus was used as a representative test species, and successful emergence was used as a chronic endpoint. Applying the MIXTOX modeling approach, predictive parametric models were fitted using single-compound toxicity data and statistically compared to observed toxicity in subsequent mixture tests. Imidacloprid-clothianidin, clothianidin-thiamethoxam and imidacloprid-clothianidin-thiamethoxam mixtures did not significantly deviate from concentration-additive toxicity. However, the cumulative toxicity of the imidacloprid-thiamethoxam mixture deviated from the concentration-additive reference model, displaying dose-ratio dependent synergism and resulting in up to a 10% greater reduction in emergence from that predicted by concentration addition. Furthermore, exposure to select neonicotinoid mixtures above 1.0 toxic unit tended to shift sex-ratios toward more male-dominated populations. Results indicate that, similar to acute exposures, the general assumption of joint additivity cannot adequately describe chronic cumulative toxicity of all neonicotinoid mixtures. Indeed, our observations of weak synergism and sex-ratio shifts elicited by some mixture combinations should be considered in water quality guideline development and environmental risk assessment practices

Structure elucidation and toxicity analyses of the radiolytic products of aflatoxin B{sub 1} in methanol-water solution

Energy Technology Data Exchange (ETDEWEB)

Wang, Feng [Institute of Agro-food Science and Technology of Chinese Academy of Agricultural Sciences, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Key Opening Laboratory of Agricultural Products Processing and Quality Control, Ministry of Agriculture, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Graduate School of Chinese Academy of Agricultural Sciences, 12th Zhongguancun South Road, Hai Dian District, Beijing 100081 (China); Xie, Fang [Institute of Agro-food Science and Technology of Chinese Academy of Agricultural Sciences, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Key Opening Laboratory of Agricultural Products Processing and Quality Control, Ministry of Agriculture, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Xue, Xiaofeng [Bee Research Institute of Chinese Academy of Agricultural Sciences, 1st Xiangshan North Ditch, Hai Dian District, Beijing 100093 (China); Wang, Zhidong; Fan, Bei [Institute of Agro-food Science and Technology of Chinese Academy of Agricultural Sciences, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Key Opening Laboratory of Agricultural Products Processing and Quality Control, Ministry of Agriculture, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Ha, Yiming, E-mail: wxfay2011@hotmail.com [Institute of Agro-food Science and Technology of Chinese Academy of Agricultural Sciences, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China); Key Opening Laboratory of Agricultural Products Processing and Quality Control, Ministry of Agriculture, 2nd Yuanmingyuan West Road, Hai Dian District, Beijing 100193 (China)

2011-09-15

Highlights: {yields} Radiolytic products of aflatoxin B{sub 1} were produced under gamma irradiation. {yields} Seven key radiolytic products were structure-elucidated. {yields} Free-radical species in radiolytic solution resulted in the formation of products. {yields} Based on the structure-activity relationship analysis, the toxicity of radiolytic products was significantly reduced compared with that of AFB{sub 1}. {yields} The addition reaction on furan ring double bond was the reason for the reduced toxicity. - Abstract: The identification of the radiolytic products of mycotoxins is a key issue in the feasibility study of gamma ray radiation detoxification. Methanol-water solution (60:40, v/v) spiked with aflatoxin B{sub 1} (AFB{sub 1}; 20 mg L{sup -1}) was irradiated with Co{sup 60} gamma ray to generate radiolytic products. Liquid chromatography-quadruple time-of-flight mass spectrometry was applied to identify the radiolytic products of AFB{sub 1}. Accurate mass and proposed molecular formulas with a high-matching property of more than 20 radiolytic products were obtained. Seven key radiolytic products were proposed based on the molecular formulas and tandem mass spectrometry spectra. The analyses of toxicity and formation pathways were proposed based on the structure of the radiolytic products. The addition reaction caused by the free-radical species in the methanol-water solution resulted in the formation of most radiolytic products. Based on the structure-activity relationship analysis, the toxicity of radiolytic products was significantly reduced compared with that of AFB{sub 1} because of the addition reaction that occurred on the double bond in the terminal furan ring. For this reason, gamma irradiation is deemed an effective tool for the detoxification of AFB{sub 1}.

Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to aluminum and aluminum fluoride.

Science.gov (United States)

Sharma, Shweta; Sharma, K P; Sharma, Subhasini

2016-12-01

Aluminum is ingested through foods, water, air, and even drugs. Its intake is potentiated further through foods and tea prepared in aluminum utensils and Al salt added in the drinking water for removal of suspended impurities and also fluoride in the affected areas. The ameliorating role of a blue green alga Spirulina is well documented to various pollutants in the animal models. We, therefore, examined its protective role (230 mg/kg body weight) on the hematology of male Swiss albino mice treated with aluminum (sub-acute = 78.4 mg/kg body weight for 7 days, sub-chronic = 7.8 mg/kg body weight for 90 days) and aluminum fluoride (sub-acute = 103 mg/kg body weight, sub-chronic = 21 mg/kg body weight), along with their recovery after 90 days of sub-chronic exposure. This study revealed significant reduction in the values of RBC (5-18 %), Hb (15-17 %), PCV (8-14 %), and platelets (26-36 %), and increase in WBC (54-124 %) in the treated mice, particularly after sub-acute exposure. Aluminum fluoride was comparatively more toxic than aluminum. Further, Spirulina supplement not only alleviated toxicity of test chemicals in Swiss albino mice but also led to their better recovery after withdrawal.

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.

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 ...

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

Science.gov (United States)

Shankar, Priyanka; Ghosh, Sudip; Bhaskarachary, K; Venkaiah, K; Khandare, Arjun L

2013-07-14

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

Science.gov (United States)

Sadekar, S; Ghandehari, H

2012-05-01

This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

Science.gov (United States)

Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

2015-04-01

Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

International Nuclear Information System (INIS)

Romanelli, Maria Fernanda

2004-01-01

Surfactants are synthetic organic compounds widely used in cosmetic, food, textile, dyers and paper production industries and in particular detergents and others cleaning products industries. The world consumption is nearly 8 million tons per year. One of the main environmental issues coming from the use of these compounds is their toxicity that compromises the biological treatment of effluents and the quality of receiving waters. The objective of this work was the application of ionizing radiation by electron beam in the degradation and reduction of acute and chronic toxicities of surfactants sodium dodecylsulfate (SDS), dodecyl p-benzenesulfonate acid (LAS) and sodium dodecyl p-benzenesulfonate (LAS). This treatment technology has been studied as a pre-treatment for effluents containing toxic and non-biodegradable compounds, before the biological treatment. Two acute toxicity assays were employed, one with the micro-crustacean Daphnia similis and the other with the luminescent bacterium Vibrio fischeri along with a chronic toxicity assay with the micro-crustacean Ceriodaphnia dubia (just for SDS and acid LAS) for the non-irradiated and irradiated samples and radiation doses 3.0 kGy, 6.0 kGy, 9.0 kGy and 12.0 kGy. Physical-chemical parameters were evaluated for the following up the degradation of the surfactant molecules. The reductions of acute toxicity varied between 72.49% and 90.98% for SDS, 18.22% and 78.98% for acid LAS and 82.66% and 94.26% for sodium LAS. For the chronic toxicity, the reduction percentages varied between 64.03% and 83.01% for SDS and 47.48% and 64.91% for acid LAS. When one considers the application of the electron beam as a pre-treatment of effluents containing high concentrations of surfactants, the toxicity is an essential parameter allowing the further biological treatment of these effluents. (author)

Electron Microscopic Analysis of Surface Inorganic Substances on Oral and Combustible Tobacco Products.

Science.gov (United States)

Halstead, Mary M; Watson, Clifford H; Pappas, R Steven

2015-01-01

Although quantitative trace toxic metal analyses have been performed on tobacco products, little has been published on inorganic particulate constituents on and inside the products. We analyzed these constituents using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). The nature of SEM-EDS instrumentation makes it an ideal choice for inorganic particulate analyses and yields relevant information to potential exposures during consumption of oral tobacco products, and possibly as a consequence of smoking. Aluminum silicates, silica and calcium compounds were common inorganic particulate constituents of tobacco products. Aluminum silicates and silica from soil were found on external leaf surfaces. Phytolithic silica, found in the lumen of the plant leaf, is of biogenic origin. Calcium oxalate was also apparently of biogenic origin. Small mineral deposits on tobacco could have health implications. Minerals found on the surfaces of smokeless tobacco products could possibly abrade the oral mucosa and contribute to the oral inflammatory responses observed with smokeless tobacco product use. If micron and sub-micron size calcium particles on cigarette filler were transported in mainstream smoke, they could potentially induce a pulmonary irritant inflammation when inhaled. The transport of aluminum silicate and silica in smoke could potentially also contribute to chronic inflammatory disease. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study.

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He, Songlin; Wei, Shicheng; Wang, Jinhua; Ji, Ping

2018-03-01

This population-based, cross-sectional study explored the association between chronic periodontitis and oral health-related quality of life (OHRQoL) in Chinese adults, independently of sociodemographic factors and other common oral conditions. The present study was carried out in a sample population of 480 adults aged 35 to 74 years from Chongqing municipality. A multi-stage stratified random sampling approach was adopted to select participants. The Chinese version of the short-form oral health impact profile (OHIP-14) was used to assess OHRQoL. Chronic periodontitis was trichotomized into mild, moderate, and severe periodontitis. Logistic regression models were adopted to explore the association between the severity of chronic periodontitis and OHIP-14 scores. After adjustment for sociodemographic factors and other common clinical conditions, participants with severe and moderate chronic periodontitis, respectively, had 1.63- (95% CI: 1.41 to 1.98) and 1.42-fold (95% CI: 1.29 to 1.63) higher odds for the OHIP-14 scores being above the median compared with participants without chronic periodontitis. However, participants with mild periodontitis did not have significantly higher odds for the OHIP-14 scores being above the median than participants without chronic periodontitis. Certain sociodemographic variables, including higher age, lower education level, number of missing teeth, and current smoker, had negative associations with OHRQoL. Chronic periodontitis was associated with poorer OHRQoL in Chinese adults. In addition, the impairment in OHRQoL showed a significant correlation with the severity of chronic periodontitis. © 2018 American Academy of Periodontology.

Comparative chronic toxicity of homo- and heterocyclic aromatic compounds to benthic and terrestrial invertebrates: Generalizations and exceptions.

NARCIS (Netherlands)

Leon Paumen, M.; de Voogt, P.; van Gestel, C.A.M.; Kraak, M.H.S.

2009-01-01

The aim of the present study was to elucidate consistent patterns in chronic polycyclic aromatic compound (PAC) toxicity to soil and sediment inhabiting invertebrates. Therefore we examined our experimental dataset, consisting of twenty-one chronic effect concentrations for two soil invertebrates

Comparative chronic toxicity of homo- and heterocyclic aromatic compounds to benthic and terrestrial invertebrates: Generalizations and exceptions

NARCIS (Netherlands)

León Paumen, M.; de Voogt, P.; van Gestel, C.A.M.; Kraak, M.H.S.

2009-01-01

The aim of the present study was to elucidate consistent patterns in chronic polycyclic aromatic compound (PAC) toxicity to soil and sediment inhabiting invertebrates. Therefore we examined our experimental dataset, consisting of twenty-one chronic effect concentrations for two soil invertebrates

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

Energy Technology Data Exchange (ETDEWEB)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

2016-09-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

Safety assessment of chronic oral exposure to iron oxide nanoparticles

International Nuclear Information System (INIS)

Chamorro, Susana; Vaquero, María Pilar; Brenes, Agustín; Gutiérrez, Lucía; Salas, Gorka; Luengo, Yurena; Verdoy, Dolores; José Teran, Francisco

2015-01-01

Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe 2 O 3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe 2 O 3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe 2 O 3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses. (paper)

Malignant transformation of oral lichen planus by a chronic inflammatory process. Use of topical corticosteroids to prevent this progression?

Science.gov (United States)

Otero-Rey, Eva Maria; Suarez-Alen, Fatima; Peñamaria-Mallon, Manuel; Lopez-Lopez, Jose; Blanco-Carrion, Andres

2014-11-01

Oral lichen planus is a potentially malignant disorder with a capacity, although low, for malignant transformation. Of all the factors related to the process of malignant transformation, it is believed that the chronic inflammatory process plays a key role in the development of oral cancer. This inflammatory process is capable of providing a microenvironment based on different inflammatory cells and molecules that affect cellular growth, proliferation and differentiation. The objectives of our study are: to review the available evidence about the possible relationship between the chronic inflammatory process present in oral lichen planus and its malignant transformation, to discuss the potential therapeutic implications derived from this relationship and to study the role that topical corticosteroids play in the control of oral lichen planus inflammation and its possible progression to malignant transformation. The maintenance of a minimum dose of topical corticosteroids could prevent the inflammatory progression of oral lichen planus to oral cancer.

Role of oral microbiome on oral cancers, a review.

Science.gov (United States)

Gholizadeh, Pourya; Eslami, Hosein; Yousefi, Mehdi; Asgharzadeh, Mohammad; Aghazadeh, Mohammad; Kafil, Hossein Samadi

2016-12-01

The oral cavity is inhibited by many of the bacterial species. Some of them have a key role in the development of oral disease. Interrelationships between oral microbiome and systemic conditions such as head-and-neck cancer have become increasingly appreciated in recent years. Emerging evidence also suggests a link between periodontal disease and oral cancer, and the explanation being that chronic inflammation could be a major factor in both diseases. Squamous cell carcinoma is that the most frequently occurring malignancy of the oral cavity and adjacent sites, representing over 90% of all cancers. The incidence of oral cancer is increasing, significantly among young people and women. Worldwide there are 350,000-400,000 new cases diagnosed every year. Bacteria, viruses, and fungi are strongly implicated as etiological factors in certain cancers. In this review we will discuss the association between the development of oral cancer in potentially malignant oral lesions with chronic periodontitis, chronic Porphyromonas gingivalis, Fusobacterium nucleatum, candida, other microbes and described mechanisms which may be involved in these carcinoma. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acute and chronic toxic effects of bisphenol A on Chlorella pyrenoidosa and Scenedesmus obliquus.

Science.gov (United States)

Zhang, Wei; Xiong, Bang; Sun, Wen-Fang; An, Shuai; Lin, Kuang-Fei; Guo, Mei-Jin; Cui, Xin-Hong

2014-06-01

The acute and chronic toxic effects of Bisphenol A (BPA) on Chlorella pyrenoidosa (C. pyrenoidosa) and Scenedesmus obliquus (S. obliquus) were not well understood. The indoor experiments were carried out to observe and analyze the BPA-induced changes. Results of the observations showed that in acute tests BPA could significantly inhibit the growth of both algae, whereas chronic exposure hardly displayed similar trend. Superoxide dismutase (SOD) and Catalase (CAT) activities of both algae were promoted in all the treatments. Chlorophyll a synthesis of the two algae exhibited similar inhibitory trend in short-term treatments, and in chronic tests C. pyrenoidosa hardly resulted in visible influence, whereas in contrast, dose-dependent inhibitory effects of S. obliquus could be clearly observed. The experimental results indicated that the growth and Chlorophyll a syntheses of S.obliquus were more sensitive in response to BPA than that of C. pyrenoidosa, whereas for SOD andCAT activities, C. pyrenoidosa was more susceptible. This research provides a basic understanding of BPA toxicity to aquatic organisms. Copyright © 2012 Wiley Periodicals, Inc.

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

International Nuclear Information System (INIS)

Tipping, E.; Lofts, S.; Hooper, H.; Frey, B.; Spurgeon, D.; Svendsen, C.

2010-01-01

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 μg (g soil) -1 and 3.3 μg (g soil organic matter) -1 being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 μg (g soil organic matter) -1 . We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg 2+ in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg 2+ ] crit = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg 2+ concentration.

In Vitro Antifungal Susceptibility of Oral Candida Isolates from Patients Suffering from Caries and Chronic Periodontitis.

Science.gov (United States)

De-la-Torre, Janire; Ortiz-Samperio, María Esther; Marcos-Arias, Cristina; Marichalar-Mendia, Xabier; Eraso, Elena; Echebarria-Goicouria, María Ángeles; Aguirre-Urizar, José Manuel; Quindós, Guillermo

2017-06-01

Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

[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.

Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

International Nuclear Information System (INIS)

Sato, Atsushi; Imaizumi, Masue; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Iinuma, Kazuie; Minegishi, Masayoshi

2006-01-01

Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

A Novel Chronic Opioid Monitoring Tool to Assess Prescription Drug Steady State Levels in Oral Fluid.

Science.gov (United States)

Shaparin, Naum; Mehta, Neel; Kunkel, Frank; Stripp, Richard; Borg, Damon; Kolb, Elizabeth

2017-11-01

Interpretation limitations of urine drug testing and the invasiveness of blood toxicology have motivated the desire for the development of simpler methods to assess biologically active drug levels on an individualized patient basis. Oral fluid is a matrix well-suited for the challenge because collections are based on simple noninvasive procedures and drug concentrations better correlate to blood drug levels as oral fluid is a filtrate of the blood. Well-established pharmacokinetic models were utilized to generate oral fluid steady state concentration ranges to assess the interpretive value of the alternative matrix to monitor steady state plasma oxycodone levels. Paired oral fluid and plasma samples were collected from patients chronically prescribed oxycodone and quantitatively analyzed by liquid chromatography tandem mass spectrometry. Steady state plasma concentration ranges were calculated for each donor and converted to an equivalent range in oral fluid. Measured plasma and oral fluid oxycodone concentrations were compared with respective matrix-matched steady state ranges, using each plasma steady state classification as the control. A high degree of correlation was observed between matrices when classifying donors according to expected steady state oxycodone concentration. Agreement between plasma and oral fluid steady state classifications was observed in 75.6% of paired samples. This study supports novel application of basic pharmacokinetic knowledge to the pain management industry, simplifying and improving individualized drug monitoring and risk assessment through the use of oral fluid drug testing. Many benefits of established therapeutic drug monitoring in plasma can be realized in oral fluid for patients chronically prescribed oxycodone at steady state. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

Energy Technology Data Exchange (ETDEWEB)

Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Zheng, Suqing [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Huang, Jeffrey T.-J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Honda, Tadashi [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Dinkova-Kostova, Albena T., E-mail: a.dinkovakostova@dundee.ac.uk [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States)

2015-09-25

The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in

ProTox: a web server for the in silico prediction of rodent oral toxicity.

Science.gov (United States)

Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

2014-07-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

Science.gov (United States)

Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

2015-08-01

Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases.

Science.gov (United States)

Cardoso, Elsa Maria; Reis, Cátia; Manzanares-Céspedes, Maria Cristina

2018-01-01

Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

NARCIS (Netherlands)

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-01-01

OBJECTIVES: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

NARCIS (Netherlands)

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-01-01

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

NARCIS (Netherlands)

Thebaut, Alice; Nemeth, Antal; Le Mouhaer, Jeannie; Scheenstra, Rene; Baumann, Ulrich; Koot, Bart; Gottrand, Frederic; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-01-01

Objectives:d-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

DEFF Research Database (Denmark)

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60...... % (monkfish). Arsenic (> 64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73 %) and iodine (71 %) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according...

Chronic disease management in Sub-Saharan Africa: whose business is it?

Science.gov (United States)

Bischoff, Alexander; Ekoe, Tetanye; Perone, Nicolas; Slama, Slim; Loutan, Louis

2009-08-01

Public health specialists and clinicians alike agree that Humanity faces a global pandemic of chronic diseases in the 21(st) century. In this article we discuss the implications of this pandemic on another global issue, the health workforce. Because both issues are particularly acute in Sub-Saharan Africa (SSA), we will focus on this region and use Cameroon as a case in point. We first gauge the epidemic of chronic conditions in SSA. We then discuss the implications of chronic conditions for the reshaping of health systems and the health workforce. We conclude by making a strong case for the building up and strengthening the health workforce, insisting on the crucial role of nurses, their training, and involvement in chronic disease management.

Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Nexø, Ebba

1986-01-01

The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral...

Chronic toxicity of unresolved complex mixtures (UCM) of hydrocarbons in marine sediments

Energy Technology Data Exchange (ETDEWEB)

Scarlett, A.; Galloway, T.S. [Plymouth Univ., Drake Circus (United Kingdom). School of Biological Sciences; Rowland, S.J. [Plymouth Univ., Drake Circus (United Kingdom). School of Earth, Ocean and Environmental Sciences

2007-08-15

Background, Aim and Scope: Unresolved complex mixtures (UCM) of hydrocarbons, containing many thousands of compounds which cannot be resolved by conventional gas chromatography (GC), are common contaminants of sediments but little is known of their potential to affect sediment-dwelling organisms. Evidence exists for reduced health status in mussels, arising from aqueous exposure to aromatic UCM components acting through a narcotic mode of action. However, UCM contaminants in sediments may not be sufficiently bioavailable to elicit toxic effects. The aim of our study was therefore to measure the sublethal effects of chronic exposure to model UCM-dominated oils at environmentally realistic concentrations and compare this to effects produced by a UCM containing weathered crude oil. A further aim was to determine which, if any, fractions of the oils were responsible for any observed toxicity. Materials and Methods: Whole oils were spiked into estuarine sediment to give nominal concentrations of 500 {mu}g g-1 dry weight. Juveniles of the estuarine amphipod Corophium volutator were exposed to the contaminated sediment for 35 days and their survival, growth rate and reproductive success quantified. Using an effect-directed fractionation approach, the oils were fractionated into aliphatic and two aromatic fractions by open column chromatography and their toxicity assessed by further chronic exposures using juvenile C. volutator. Results: The growth rates of amphipods were reduced following exposure to the oils although this was only statistically significant for the weathered oil; reproductive success was reduced by all oil exposures. Sediment spiked with UCM fractions also caused reduced growth and reproduction but no particular fraction was found to be responsible for the observed toxicity. Survivorship was not affected by any oil or fraction. Discussion: The study showed that chronic exposure to sediments contaminated by UCM-dominated oils could have population level

Enhancement of parathion toxicity to quail by heat and cold exposure

Science.gov (United States)

Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.

1987-01-01

Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26.degree. C) or exposed to elevated (37.degree. C) or reduced (4.degree. C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a two-fold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26.degree. C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., birds is substantially influenced by environmental temperature.

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

NARCIS (Netherlands)

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; Heuvel, van den Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, António

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60%

Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

Science.gov (United States)

Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

2015-11-01

The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences

NARCIS (Netherlands)

Brink, Van den P.J.; Smeden, Van J.M.; Bekele, R.S.; Dierick, Wiebe; Gelder, De Daphne M.; Noteboom, Maarten; Roessink, Ivo

2016-01-01

Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to

Oral toxicity of silver ions, silver nanoparticles and colloidal silver--a review.

Science.gov (United States)

Hadrup, Niels; Lam, Henrik R

2014-02-01

Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached. Copyright © 2013 Elsevier Inc. All rights reserved.

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish

Energy Technology Data Exchange (ETDEWEB)

Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

Chronic toxicologic study of the ethanolic extract of the aerial parts of Jatropha gossypiifolia in rats

Directory of Open Access Journals (Sweden)

Saulo R. Mariz

Full Text Available This work presents the observed changes in Wistar rats under long treatment (thirteen weeks with different oral doses of the ethanolic extract (EE from Jatropha gossypiifolia L., Euphorbiaceae. The most significant toxic signs indicated a reduction of the activity in the central nervous system and digestive disturbances. The histopathological analysis shows hepatotoxity and pulmonary damages. The lethality was 46.6% among males under the higher experimental dose (405 mg/kg and 13.3% both in females under the higher dose and among the animals treated with 135 mg/kg of the product. These data show the significant oral chronic toxicity of EE of J. gossypiifolia in rats.

Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

DEFF Research Database (Denmark)

Hadrup, Niels; Lam, Henrik Rye

2014-01-01

Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

Toxicity assessment of metoprolol and its photodegradation mixtures obtained by using different type of TiO{sub 2} catalysts in the mammalian cell lines

Energy Technology Data Exchange (ETDEWEB)

Četojević-Simin, Dragana D., E-mail: ddaaggeerr@gmail.com [University of Novi Sad, Faculty of Medicine, Oncology Institute of Vojvodina, Dr Goldmana 4, 21204 Sremska Kamenica (Serbia); Armaković, Sanja J., E-mail: sanja.armakovic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia); Šojić, Daniela V., E-mail: daniela.sojic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia); Abramović, Biljana F., E-mail: biljana.abramovic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia)

2013-10-01

Toxicity of metoprolol (MET) alone and in mixtures with its photocatalytic degradation intermediates obtained by using TiO{sub 2} Wackherr and Degussa P25 under UV irradiation in the presence of O{sub 2} was evaluated in vitro in a panel of three histologically different cell lines: rat hepatoma (H-4-II-E), human colon adenocarcinoma (HT-29) and human fetal lung (MRC-5). Both catalysts promoted a time-dependent increase in the toxicity of the photodegradation products, and those obtained using Degussa P25 photocatalyst were more toxic. The most pronounced and selective toxic action of MET and products of its photodegradation was observed in the hepatic cell line. The higher toxicity of the mixtures obtained using Degussa P25 catalyst could be explained by a different mechanism of MET degradation, i.e. by the presence or higher concentrations of some intermediates. Although the concentrations of intermediates obtained using TiO{sub 2} Wackherr catalyst were higher, they did not affect significantly the growth of the examined cell lines, indicating their lower toxicity. This suggests that a treatment aiming at complete mineralization should be performed bearing in mind that the type of catalyst, the concentration of target molecule, and the duration of the process are significant factors that determine the nature and toxicity of the resulting mixtures. Although the EC{sub 50} values of MET obtained in mammalian cell lines were higher compared to the bioassays for lower trophic levels, the time-dependent promotion of toxicity of degradation mixtures should be attributed to the higher sensitivity of mammalian cell bioassays. - Highlights: • Toxicity study of metoprolol and its photocatalytic degradation mixtures • Toxicity evaluation in vitro in H-4-II-E, HT-29 and MRC-5 cell lines • TiO{sub 2} Wackherr and Degussa P25 promoted a time-dependent increase in toxicity. • The higher toxicity of degradation mixtures obtained using Degussa P25 • Most pronounced and

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.

Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms

Energy Technology Data Exchange (ETDEWEB)

Comber, S.D.W. [WRc-NSF, Henley Road, Medmenham, Marlow, Buckinghamshire, SL7 2HD (United Kingdom)]. E-mail: sean.comber@atkinsglobal.com; Conrad, A.U. [Weinberg Group, Blue Tower, Box 16, B-1050 Brussels (Belgium); Hoess, S. [ECOSSA, Thierschstrasser 43, 80538, Muenchen (Germany); Webb, S. [CEFIC, Ave E. Van Nieuwenhuyse 4, B-1160 Brussels (Belgium); Marshall, S. [Unilever Research, Environment Centre, Bebington, Wirral, Merseyside, L63 3JW (United Kingdom)

2006-11-15

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs >100 mg/kg dry weight). No observed effect concentrations (NOECs) of 81 mg/kg dw (Lumbriculus) and 100 mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20 days in sediment. - This paper provides sediment toxicity data for LAS, essential for a detailed and accurate environment risk assessment.

Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms

International Nuclear Information System (INIS)

Comber, S.D.W.; Conrad, A.U.; Hoess, S.; Webb, S.; Marshall, S.

2006-01-01

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs >100 mg/kg dry weight). No observed effect concentrations (NOECs) of 81 mg/kg dw (Lumbriculus) and 100 mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20 days in sediment. - This paper provides sediment toxicity data for LAS, essential for a detailed and accurate environment risk assessment

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

Science.gov (United States)

Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

2016-02-01

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

Haloacetonitriles: metabolism and toxicity.

Science.gov (United States)

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

2009-01-01

The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

Science.gov (United States)

Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

2012-03-01

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

Science.gov (United States)

Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

2013-11-01

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests

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Débora Rebechi

2014-09-01

Full Text Available Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests. Organophosphate compounds are used in agro-systems, and in programs to control pathogen vectors. Because they are continuously applied, organophosphates often reach water sources and may have an impact on aquatic life. The effects of acute and chronic exposure to the organophosphate insecticide malathion on the midge Chironomus sancticaroli are evaluated. To that end, three biochemical biomarkers, acetylcholinesterase (AChE, alpha (EST-α and beta (EST-β esterase were used. Acute bioassays with five concentrations of malathion, and chronic bioassays with two concentrations of malathion were carried out. In the acute exposure test, AChE, EST-α and EST-β activities declined by 66, 40 and 37%, respectively, at 0.251 µg L-1 and more than 80% at 1.37, 1.96 and 2.51 µg L-1. In chronic exposure tests, AChE and EST-α activities declined by 28 and 15% at 0.251 µg L-1. Results of the present study show that low concentrations of malathion can influence larval metabolism, indicating high toxicity for Chironomus sancticaroli and environmental risk associated with the use of organophosphates.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

International Nuclear Information System (INIS)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Impact of aggressive periodontitis and chronic periodontitis on oral health-related quality of life.

Science.gov (United States)

Llanos, Alexandre Hugo; Silva, Carlos Guillermo Benítez; Ichimura, Karina Tamie; Rebeis, Estela Sanches; Giudicissi, Marcela; Romano, Marcelo Munhóes; Saraiva, Luciana

2018-01-01

The purpose of this cross-sectional study was to investigate the effect of different forms of periodontal diseases on Oral Health-Related Quality of Life (OHRQoL). Fifty-two patients with Aggressive Periodontitis (AP) or Chronic Periodontitis (CP) were included: nine patients with Localized Aggressive Periodontitis (LAP), thirty-three patients with Generalized Aggressive Periodontitis (GAP) and ten patients with Generalized Chronic Periodontitis (GCP). Oral Health Impact Profile questionnaires (OHIP-14) were distributed after a clinical examination that measured the following periodontal parameters: tooth loss, bleeding on probing (BoP), probing depth (PD), gingival recession (REC) and clinical attachment level (CAL). The global OHIP-14 score means were 10.6 for LAP, 16.5 for GAP, and 17.5 for GCP. A statistically significant difference (p periodontitis. LAP, GAP and GCP have an impact on patient quality of life when measured using the OHIP-14. Patients with GAP and GCP had poorer OHRQoL than LAP patients.

Acute and chronic aquatic toxicity of aromatic extracts. Summary of relevant test data

Energy Technology Data Exchange (ETDEWEB)

Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Leon Paumen, M.; Dmytrasz, B.; Del Castillo, F.

2013-09-15

This report describes the experimental procedures and the results obtained in acute and chronic ecotoxicity tests on several aromatic extracts samples. The samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter, Daphnia magna and the algae, Selenastrum capricornutum using water accommodated fractions. These results assist in determining the environmental hazard posed by aromatic extracts.

Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

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Pushkor Mukerji

2015-01-01

Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

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Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

2016-12-01

Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

Science.gov (United States)

Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2015-10-01

During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

Science.gov (United States)

Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

2010-03-01

As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

International Nuclear Information System (INIS)

Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan; Yan Guangyan; Cen Xiaobo; Deng Pengchi; Peng Feng; Xue Aiqin; Wang Yanli

2010-01-01

As titanium dioxide nanoparticles (TiO 2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO 2 NPs (dosed at 0.16, 0.4 and 1 g kg -1 , respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1 H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO 2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO 2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO 2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO 2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Maternal chronic oral infection with periodontitis and pericoronitis as a possible risk factor for preeclampsia in Egyptian pregnant women (microbiological and serological study

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Lobna A. Aly

2015-12-01

Conclusion: There was a relationship between chronic oral infection and preeclampsia, so treatment of oral infection during pregnancy may represent a novel approach and preventive strategy that reduce oral bacterial load which would decrease the incidence of preeclampsia.

Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

Science.gov (United States)

Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

2012-11-01

The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

Can the oral microflora affect oral ulcerative mucositis?

NARCIS (Netherlands)

Laheij, A.M.G.A.; de Soet, J.J.

2014-01-01

Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

Acute and chronic toxicity of uranium compounds to Ceriodaphnia-Daphnia dubia

International Nuclear Information System (INIS)

Pickett, J.B.; Specht, W.L.; Keyes, J.L.

1993-01-01

A study to determine the acute and chronic toxicity of uranyl nitrate, hydrogen uranyl phosphate, and uranium dioxide to the organism Ceriodaphnia dubia was conducted. The toxicity tests were conducted by two independent environmental consulting laboratories. Part of the emphasis for this determination was based on concerns expressed by SCDHEC, which was concerned that a safety factor of 100 must be applied to the previous 1986 acute toxicity result of 0.22 mg/L for Daphnia pulex, This would have resulted in the LETF release limits being based on an instream concentration of 0.0022 mg/L uranium. The NPDES Permit renewal application to SCDHEC utilized the results of this study and recommended that the LETF release limit for uranium be based an instream concentration of 0.004 mg/L uranium. This is based on the fact that the uranium releases from the M-Area LETF will be in the hydrogen uranyl phosphate form, or a uranyl phosphate complex at the pH (6--10) of the Liquid Effluent Treatment Facility effluent stream, and at the pH of the receiving stream (5.5 to 7.0). Based on the chronic toxicity of hydrogen uranyl phosphate, a lower uranium concentration limit for the Liquid Effluent Treatment Facility outfall vs. the existing NPDES permit was recommended: The current NPDES permit ''Guideline'' for uranium at outfall M-004 is 0.500 mg/L average and 1.0 mg/L maximum, at a design flowrate of 60 gpm. It was recommended that the uranium concentration at the M-004 outfall be reduced to 0.28 mg/L average, and 0.56 mg/L, maximum, and to reduce the design flowrate to 30 gpm. The 0.28 mg/L concentration will provide an instream concentration of 0.004 mg/L uranium. The 0.28 mg/L concentration at M-004 is based on the combined flows from A-014, A-015, and A-011 outfalls (since 1985) of 1840 gpm (2.65 MGD) and was the flow rate which was utilized in the 1988 NPDES permit renewal application

Elevated CO{sub 2} levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem

Energy Technology Data Exchange (ETDEWEB)

Yin, Ying; Hu, Zhengxue [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Du, Wenchao, E-mail: du@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Ai, Fuxun; Ji, Rong [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Gardea-Torresdey, Jorge L. [Department of Chemistry, The University of Texas at El Paso, El Paso, TX 79968 (United States); Environmental Science and Engineering PhD program, The University of Texas at El Paso, El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso, El Paso, TX 79968 (United States); Guo, Hongyan, E-mail: hyguo@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China)

2017-04-05

Highlights: • Elevated CO{sub 2} increased the Zn content in suspension by reducing pH value. • Elevated CO{sub 2} led to higher Zn accumulation in fish tissues. • Elevated CO{sub 2} also intensified the oxidative damage to fish induced by nZnO. - Abstract: Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO{sub 2} levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO{sub 2} to the ecosystem. Here we studied the toxicity of nZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400 ± 10 μL/L) or elevated (600 ± 10 μL/L) CO{sub 2} for 30 days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO{sub 2} increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of nZnO. Elevated CO{sub 2} led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO{sub 2} also intensified the oxidative damage to fish induced by nZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO{sub 2} levels.

Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock. A review.

Science.gov (United States)

López, T A; Cid, M S; Bianchini, M L

1999-06-01

The literature on Conium maculatum biochemistry and toxicology, dispersed in a large number of scientific publications, has been put together in this review. C. maculatum is a weed known almost worldwide by its toxicity to many domestic animals and to human beings. It is an Umbelliferae, characterized by long, hollow stems, reaching up to 2 m height at maturity, producing a large amount of lush foliage during its vegetative growth. Its flowers are white, grouped in umbels formed by numerous umbellules. It produces a large number of seeds that allow the plant to form thick stands in modified soils, sometimes encroaching on cultivated fields, to the extent of impeding the growth of any other vegetation inside the C. maculatum area of growth. Eight piperidinic alkaloids have been identified in this species. Two of them, gamma-coniceine and coniine are generally the most abundant and they account for most of the plant acute and chronic toxicity. These alkaloids are synthesized by the plant from eight acetate units from the metabolic pool, forming a polyketoacid which cyclises through an aminotransferase and forms gamma-coniceine as the parent alkaloid via reduction by a NADPH-dependent reductase. The acute toxicity is observed when animals ingest C. maculatum vegetative and flowering plants and seeds. In a short time the alkaloids produce a neuromuscular blockage conducive to death when the respiratory muscles are affected. The chronic toxicity affects only pregnant animals. When they are poisoned by C. maculatum during the fetuses organ formation period, the offspring is born with malformations, mainly palatoschisis and multiple congenital contractures (MCC; frequently described as arthrogryposis). Acute toxicity, if not lethal, may resolve in the spontaneous recovery of the affected animals provided further exposure to C. maculatum is avoided. It has been observed that poisoned animals tend to return to feed on this plant. Chronic toxicity is irreversible and

Toxicological evaluation of ethanolic extract of Anacyclus pyrethrum in albino wistar rats

Directory of Open Access Journals (Sweden)

Kuttan Sujith

2017-12-01

Full Text Available Objective: To evaluate the sub chronic toxicity of ethanolic extract of Anacyclus pyrethrum (A. pyrethrum in albino wistar rats. Methods: In sub chronic toxicity study ethanolic extract of A. pyrethrum prepared in 2%v/v tween 80 was administered to rats at the dose of 1 000 mg/kg per day for 90 days by oral gavage. A control group received only 2%v/v tween 80. During study period the rats were observed for changes body weight. At the end of dosing period rats relative organ weight of the liver, kidney, brain, lungs and spleen in rats treated with A. pyrethrum extract and control group were examined and also rats were subjected to haematological, biochemical and histopathological examination. Results: The administration of ethanolic extract of A. pyrethrum had no effect on body weight, growth and survival. There was no significant difference in the relative organ weight of the liver, kidney, brain, lungs and spleen in rats treated with A. pyrethrum extract and control group. In the present study, all the haematological and biochemical parameters at the end of dosing and observation period did not reveal difference between drug treated and control groups. Studies on histopathological examination of vital organs showed normal architecture suggesting no evidence of pathological lesions. Conclusions: The studies on sub chronic toxicity reveals that no mortalities or evidence of adverse effects on oral administration of extract. The findngs of the study indicate that ethanolic extract of A. pyrethrum had no treatment related toxicological abnormalities and can be considerd as safe for long-term treatment.

Secondary Hemochromatosis due to Chronic Oral Iron Supplementation

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Ronald Lands

2017-01-01

Full Text Available Iron may accumulate in excess due to a mutation in the HFE gene that upregulates absorption or when it is ingested or infused at levels that exceed the body’s ability to clear it. Excess iron deposition in parenchymal tissue causes injury and ultimately organ dysfunction. Diabetes mellitus and hepatic cirrhosis due to pancreas and liver damage are just two examples of diseases that result from iron overload. Despite the rapid growth of information regarding iron metabolism and iron overload states, the most effective treatment is still serial phlebotomies. We present a patient who developed iron overload due to chronic ingestion of oral ferrous sulfate. This case illustrates the importance of querying geriatric patients regarding their use of nonprescription iron products without a medical indication.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

Science.gov (United States)

Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

2014-03-26

Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease

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Mays, Jacqueline W.; Ambatipudi, Kiran S.; Bassim, Carol W.; Melvin, James E.

2013-05-01

Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

Science.gov (United States)

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats.

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Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

2017-01-01

A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

TOXICITY OF SOME PLANTS IMPLICATED AS POISONS IN ...

African Journals Online (AJOL)

Different parts of eight plants implicated in Akwa Ibom ethnomedicinal literature as toxic were examined for toxicity in rats after oral and intraperitoneal administration. Only the ethanolic extract of S. indica leaves was toxic by both oral and intraperitoneal routes. The extract of C. edulis roots, E. kamerunica leaves, ...

Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

Science.gov (United States)

Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

2014-08-01

Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

Science.gov (United States)

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

Science.gov (United States)

Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

2015-07-01

The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

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.

Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

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Hsiao-Wen Lin

2009-03-01

Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

Moving into advanced nanomaterials. Toxicity of rutile TiO{sub 2} nanoparticles immobilized in nanokaolin nanocomposites on HepG2 cell line

Energy Technology Data Exchange (ETDEWEB)

Bessa, Maria João, E-mail: mjbessa8@gmail.com [Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto (Portugal); Costa, Carla, E-mail: cstcosta@gmail.com [Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto (Portugal); EPIUnit - Institute of Public Health, University of Porto, Rua das Taipas 135, 4050-600, Porto (Portugal); Reinosa, Julian, E-mail: jjreinosa@icv.csic.es [Electroceramic Department, Instituto de Cerámica y Vidrio, CSIC, Campus de Cantoblanco, Calle de Kelson, 5, 28049 Madrid (Spain); Pereira, Cristiana, E-mail: cristianacostapereira@gmail.com [Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto (Portugal); EPIUnit - Institute of Public Health, University of Porto, Rua das Taipas 135, 4050-600, Porto (Portugal); Fraga, Sónia, E-mail: teixeirafraga@hotmail.com [Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto (Portugal); EPIUnit - Institute of Public Health, University of Porto, Rua das Taipas 135, 4050-600, Porto (Portugal); Fernández, José, E-mail: jfernandez@icv.csic.es [Electroceramic Department, Instituto de Cerámica y Vidrio, CSIC, Campus de Cantoblanco, Calle de Kelson, 5, 28049 Madrid (Spain); Bañares, Miguel A., E-mail: miguel.banares@csic.es [Catalytic Spectroscopy Laboratory, Instituto de Catálisis y Petroleoquímica, ICP-CSIC, Madrid (Spain); and others

2017-02-01

Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO{sub 2} NPs), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocomposites. The present work intended to evaluate the hepatic toxicity of nanocomposites (C-TiO{sub 2}), constituted by rutile TiO{sub 2} NPs immobilized in nanokaolin (NK) clay, and its individual components. These nanomaterials were analysed by means of FE-SEM and DLS analysis for physicochemical characterization. HepG2 cells were exposed to rutile TiO{sub 2} NPs, NK clay and C-TiO{sub 2} nanocomposite, in the presence and absence of serum for different exposure periods. Possible interferences with the methodological procedures were determined for MTT, neutral red uptake, alamar blue (AB), LDH, and comet assays, for all studied nanomaterials. Results showed that MTT, AB and alkaline comet assay were suitable for toxicity analysis of the present materials after slight modifications to the protocol. Significant decreases in cell viability were observed after exposure to all studied nanomaterials. Furthermore, an increase in HepG2 DNA damage was observed after shorter periods of exposure in the absence of serum proteins and longer periods of exposure in their presence. Although the immobilization of nanoparticles in micron-sized supports could, in theory, decrease the toxicity of single nanoparticles, the selection of a suitable support is essential. The present results suggest that NK clay is not the appropriate substrate to decrease TiO{sub 2} NPs toxicity. Therefore, for future studies, it is critical to select a more appropriate substrate for the immobilization of TiO{sub 2} NPs. - Highlights: • Only the MTT and AB assays were found to be suitable for cytotoxicity assessment. • Alkaline comet assay was also appropriate for genotoxicity evaluation

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish. Volume 1

Energy Technology Data Exchange (ETDEWEB)

Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

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Jinhee Kim

2015-09-01

Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Oral cadmium chloride intoxication in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B; Svendsen, P

1988-01-01

Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect...

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

Energy Technology Data Exchange (ETDEWEB)

Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

2015-11-15

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

Science.gov (United States)

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

Energy Technology Data Exchange (ETDEWEB)

Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

2012-06-15

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

Directory of Open Access Journals (Sweden)

Roberts Norman B

2011-10-01

Full Text Available Abstract Background Aluminium (Al toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. Methods HD patients only treated with Reverse Osmosis(RO treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. Results 39 patients (34 anuric were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration and the total amount of Al ingested. No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Conclusions Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07 and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.

Oral health in diabetic and nondiabetic patients with chronic kidney disease

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Lingam Amara Swapna

2017-01-01

Full Text Available The objective of our study is to assess the subjective and objective oral manifestations and salivary pH in diabetic and nondiabetic uremic patients at a nephrology clinic. A total of 194 diabetic and nondiabetic patients with chronic kidney disease (CKD, who were divided into four groups, Group A, B, C, D, and who were attending a nephrology clinic were included in the study. Predialytic unstimulated whole salivary pH was recorded using pH- measuring strips. Subjective and objective findings were evaluated and recorded in the specially designed pro forma. Dental health assessment consisted of decayed, missing, and filled teeth index and community periodontal index (CPI. Dysgeusia was found to be significantly more prevalent in nondiabetic patients on dialysis. Uremic odor showed high significance (P <0.05 with 75% patients being positive in diabetic dialysis. There was no significant difference in the incidence of tongue coating between the four groups. A statistically high significance was observed with the objective oral manifestation of mucosal petechiae, with P = 0.01. There was an increased periodontal pocket depth among diabetic CKD patients as compared to that in nondiabetic patients. A moderate significance was found, with a CPI score showing P <0.05. Increased prevalence of caries was noticed among the diabetic CKD patients (Groups A, B. Recorded salivary pH showed no significant difference among diabetic and nondiabetic CKD patients. Findings suggest that these patients are at risk of developing complications, related to systemic health causing morbidity and mortality. Hence, these patients are to be motivated for comprehensive professional oral care and self oral hygiene instructions. Additional research is necessary to elucidate and correlate the combined influence of diabetes, CKD, and dialysis on oral health.

Phytochemistry, Brine shrimp lethality and mice acute oral toxicity studies on seed extracts of Vernonia anthelmintica.

Science.gov (United States)

Jamil, Subia; Khan, Rafeeq Alam; Afroz, Syeda; Ahmed, Shadab

2016-11-01

Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)μg/ml and 216.11μg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46μg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

DEFF Research Database (Denmark)

Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E

2015-01-01

BACKGROUND: The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited. OBJECTIVE: The objective of this study was to assess the clinical app...

Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

Energy Technology Data Exchange (ETDEWEB)

Nutter, Thomas J., E-mail: tnutter@dental.ufl.edu; Cooper, Brian Y., E-mail: bcooper@dental.ufl.edu

2014-06-15

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were

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.

Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

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M. D. Jegoda

2013-06-01

Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

KAUST Repository

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; van den Heuvel, Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, Antó nio

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60% (monkfish). Arsenic (>64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73%) and iodine (71%) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according to species. For example, methylmercury bioaccessibility decreased significantly after steaming in all species, while zinc bioaccessibility increased in fish (tuna and plaice) but decreased in molluscs (mussel and octopus).Together with human exposure assessment and risk characterization, this study could contribute to the establishment of new maximum permissible concentrations for toxic elements in seafood by the European food safety authorities, as well as recommended intakes for essential elements.

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

KAUST Repository

Alves, Ricardo N.

2017-11-17

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60% (monkfish). Arsenic (>64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73%) and iodine (71%) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according to species. For example, methylmercury bioaccessibility decreased significantly after steaming in all species, while zinc bioaccessibility increased in fish (tuna and plaice) but decreased in molluscs (mussel and octopus).Together with human exposure assessment and risk characterization, this study could contribute to the establishment of new maximum permissible concentrations for toxic elements in seafood by the European food safety authorities, as well as recommended intakes for essential elements.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

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Glauco Morales

2014-01-01

Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti

Bosutinib in the management of chronic myelogenous leukemia

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Keller-von Amsberg G

2013-05-01

Full Text Available Gunhild Keller-von Amsberg, Philippe SchafhausenDepartment of Hematology and Oncology and, Stem Cell Transplantation and Pulmonology Division, Oncological Center, University Hospital Hamburg-Eppendorf, Hamburg, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily dual Src and Abl kinase inhibitor, approved by the US Food and Drug Administration for the treatment of adults with chronic, accelerated, or blast-phase Philadelphia chromosome-positive chronic myelogenous leukemia who are intolerant of or resistant to first- or second-generation tyrosine kinase inhibitors. Bosutinib effectively overcomes the majority of imatinib-resistance-conferring BCR-ABL mutations except V299L and T315I. In the Bosutinib Efficacy and Safety in chronic myeloid LeukemiA (BELA trial, bosutinib attained a faster and deeper molecular response than imatinib in newly diagnosed chronic-phase chronic myelogenous leukemia patients. Treatment-emergent adverse events are usually very manageable. Low grade, mostly self-limiting diarrhea represents the most frequently observed toxicity of bosutinib. Anti-diarrheal drugs, antiemetic agents, and/or fluid replacement should be used to treat these patients. The improved hematological toxicity of bosutinib compared with other tyrosine kinase inhibitors has been ascribed to its minimal activity against platelet-derived growth factor receptor and KIT. In this review, we give an overview on the profile of bosutinib, the clinical potential and treatment-emergent adverse events.Keywords: CML, BCR-ABL, SRC/ABL kinase inhibitor, resistance-conferring mutation

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

Energy Technology Data Exchange (ETDEWEB)

Sala, Miquel [Centre Tecnològic Forestal de Catalunya - CTFC, Solsona, Catalunya (Spain); Faria, Melissa [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Sarasúa, Ignacio [Technische Universität München, Munich, Bayern (Germany); Barata, Carlos [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona (Spain); Bonada, Núria [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona - UB, Diagonal 643, 08028 Barcelona, Catalonia (Spain); Brucet, Sandra [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Catalan Institution for Research and Advanced Studies, ICREA, Barcelona 08010 (Spain); Llenas, Laia; Ponsá, Sergio [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Prat, Narcís [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Soares, Amadeu M.V.M. [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); and others

2016-10-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl{sup −} and SO{sub 4}{sup 2−}) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm{sup −1}) with Cl{sup −}:SO{sub 4}{sup 2−} ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators

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

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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

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

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Parayath NN

2016-08-01

Full Text Available Neha N Parayath,1 Hayley Nehoff,1 Samuel E Norton,2 Andrew J Highton,2 Sebastien Taurin,1,3 Roslyn A Kemp,2 Khaled Greish1,4 1Department of Pharmacology and Toxicology, 2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 3Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA; 4Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Oral administration of paclitaxel (PTX, a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid (SMA. Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg compared to the commercially available PTX formulation (PTX [Ebewe]. In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe. In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. Keywords: oral delivery, anticancer nanomedicine, CT-26, enhanced permeability and retention (EPR effect, HUVEC, antiangiogenic

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

Comparative toxicity assessment of CeO{sub 2} and ZnO nanoparticles towards Sinorhizobium meliloti, a symbiotic alfalfa associated bacterium: Use of advanced microscopic and spectroscopic techniques

Energy Technology Data Exchange (ETDEWEB)

Bandyopadhyay, Susmita [Environmental Science and Engineering PhD Program, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso (United States); Peralta-Videa, Jose R. [Department of Chemistry, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968 (United States); Plascencia-Villa, German; Jose-Yacaman, Miguel [Department of Physics and Astronomy, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249 (United States); Gardea-Torresdey, Jorge L., E-mail: jgardea@utep.edu [Environmental Science and Engineering PhD Program, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968 (United States); Department of Chemistry, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso (United States)

2012-11-30

Highlights: Black-Right-Pointing-Pointer First cytotoxicity study of CeO{sub 2} and ZnO nanoparticles to Sinorhizobium meliloti. Black-Right-Pointing-Pointer First report upon the mechanisms of CeO{sub 2} and ZnO NPs toxicity to S. meliloti. Black-Right-Pointing-Pointer ZnO NPs were found to be bactericidal in lower concentration. Black-Right-Pointing-Pointer CeO{sub 2} NPs had bacteriostatic effect on S. meliloti. - Abstract: Cerium oxide (CeO{sub 2}) and zinc oxide (ZnO) nanoparticles (NPs) are extensively used in a variety of instruments and consumer goods. These NPs are of great concern because of potential toxicity towards human health and the environment. The present work aimed to assess the toxic effects of 10 nm CeO{sub 2} and ZnO NPs towards the nitrogen fixing bacterium Sinorhizobium meliloti. Toxicological parameters evaluated included UV/Vis measurement of minimum inhibitory concentration, disk diffusion tests, and dynamic growth. Ultra high-resolution scanning transmission electron microscopy (STEM) and infrared spectroscopy (FTIR) were utilized to determine the spatial distribution of NPs and macromolecule changes in bacterial cells, respectively. Results indicate that ZnO NPs were more toxic than CeO{sub 2} NPs in terms of inhibition of dynamic growth and viable cells counts. STEM images revealed that CeO{sub 2} and ZnO NPs were found on bacterial cell surfaces and ZnO NPs were internalized into the periplasmic space of the cells. FTIR spectra showed changes in protein and polysaccharide structures of extra cellular polymeric substances present in bacterial cell walls treated with both NPs. The growth data showed that CeO{sub 2} NPs have a bacteriostatic effect, whereas ZnO NPs is bactericidal to S. meliloti. Overall, ZnO NPs were found to be more toxic than CeO{sub 2} NPs.

Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam. Merr. in BALB/c mice

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Muhammad Kifayatullah

2015-10-01

Conclusions: The result indicates that the oral administration of Pericampylus glaucus (Lam. Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

Energy Technology Data Exchange (ETDEWEB)

Halton, D M

1995-09-01

In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC{sub LO}, LC{sub 10} and LC{sub 50} levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs.

A 27-years-old Man with Abdominal Pain; Lead Toxicity

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Maryam Kia

2017-12-01

Full Text Available Case presentation: A 27-year-old man came to our emergency department with chief complaints of abdominal pain, nausea and vomiting, colicky pain in all area of abdomen without any radiation and generalized myalgia. In his background, he had no previous medical problem. In his social history he had worked in an automobile battery-reclaiming factory for 5 years. During his physical examination, his appearance was pale with perioral priority, ill and agitated but not toxic with a blood pressure of 127/85 mmHg and a pulse of 80 beats/min, respiratory rate of 14 breaths/min and oral temperature of 37.3 °C, mild generalized abdominal tenderness without rebound. No obvious signs of sensory and motor neuropathy were found. In the head and neck examination, we found lead-lined teeth. Learning points: The most common cause of chronic metal poisoning is lead. Exposure occurs through inhalation or ingestion. Both inorganic and organic forms of lead that exist naturally produce clinical toxicity. Gastrointestinal manifestations occur more frequently with acute rather than with chronic poisoning, and concurrent hemolysis may cause the colicky abdominal pains. Patients may have complained of a metallic taste and, with long-term exposure, have bluish-gray gingival lead lines. In addition, constitutional symptoms, including arthralgia, generalized weakness, and weight loss raises the possibility of lead toxicity.

Lead elimination by ICRF 158 in rats after chronic lead exposure

Energy Technology Data Exchange (ETDEWEB)

Witting, U; Hultsch, E

1981-02-01

Lead elimination by ICRF 158, a lipophilic derivative of ethylene-diaminetetra-acetate (EDTA), was investigated in rats after chronic lead exposure. The animals had received a lead concentration of 550 ppm in their drinking water for 140 days. Subsequent treatment with ICRF 158 for 30 days led to increased mobilization and elimination of incorporated lead, and the lead-induced inhibition of hemosynthesis was removed. ICR 158 produced no renal damage in excess to lead-induced tubular nephrosis. Separate toxicity tests in mice demonstrated that is less toxic than CaNa/sub 2/EDTA. ICRF 158 does not form stable complexes with lead ions in vitro. The mechanism of action of this lipophilic EDTA derivative is compared to that of its hydrophilic correspondent, the chelating agent CaNa/sub 2/EDTA.

Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

Science.gov (United States)

Ismahil, Mohamed Ameen; Hamid, Tariq; Haberzettl, Petra; Gu, Yan; Chandrasekar, Bysani; Srivastava, Sanjay; Bhatnagar, Aruni

2011-01-01

Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with vehicle-fed mice, acrolein-fed mice exhibited significant (P acrolein adduct formation indicative of physical translocation of ingested acrolein to the heart. Acrolein also induced myocyte hypertrophy (∼2.2-fold increased myocyte area, P acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Human exposure to acrolein may have analogous effects and raise consideration of an environmental, aldehyde-mediated basis for heart failure. PMID:21908791

TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

Directory of Open Access Journals (Sweden)

Yun Wang

2017-01-01

Full Text Available Methamphetamine (MA leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS. The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA, and MA plus TBHQ-treated group (MA + TBHQ. Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

DEFF Research Database (Denmark)

Kermanizadeh, Ali; Jacobsen, Nicklas R.; Roursgaard, Martin

2017-01-01

or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation......, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models...... is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked....

FLUORIDE TOXICITY – A HARSH REALITY

OpenAIRE

Bandlapalli Pavani; Mandava Ragini; David Banji; Otilia J F Banji; N Gouri Pratusha

2011-01-01

There are many incidents of fluoride toxicity whether it is acute or chronic. Fluoride toxicity is an environmental hazard which arises from the upper layers of geological crust and is dissolved in water. Prolonged drinking of such water causes chronic fluoride toxicity. Use of fluoride containing compounds for various purposes such as dental products, metal, glass, refrigerator and chemical industries act as a source of fluoride poisoning and increase the risk of toxicity. This review reflec...

A Clinical Study on {sup 125}IT{sub 3} Resin Uptake Rate and Serum Thyroxin(T{sub 4}) in Hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

MooN, Ern Soo; Park, Yoh Han; Cho, Chang Ho; Park, In Soo; Lee, Chong Suk; Lee, Hak Choong [National Medical Center, Seoul (Korea, Republic of)

1978-09-15

Hyperthyroidism may be defined as those clinical conditions which result from an increase in the circulating levels of one or both thyroid hormones. Hyperthyroidism in broad sense could be classified with toxic diffuse goiter, toxic adenomatous goiter, and toxic multinodular goiter on the basis of the circulating thyroid hormone levels. For this study, the subject included 94 cases with hyperthyroidism were presented in 77 with toxic diffuse goiter, 8 with toxic adenomatous goiter, and 9 with toxic multinodular goiter on the levels of {sup 125}IT{sub 3} resin uptake rate and serum thyroxine (T{sub 4}). The observed results were as follows: 1) In the cases of hyperthyroidism including toxic diffuse goiter, toxic adenomatous goiter, and toxic multinodular goiter, 20.21% of the patients were male and 79.79% female. The majority of the patients were in 2nd to 4th decades of their lives. 2) There were objective signs clearly manifested in hyperthyroidism including toxic diffuse goiter and toxic adenomatous goiter which were rare in the multinodular goiter. The clinical signs in toxic diffuse and toxic adenomatous goiter included wide pulse pressure, tachycardia, systolic murmur, exophthalmos, tremor and warm skin etc. 3) The most frequent complaints of the patients with hyperthyroidism were palpitation, weight loss, increased appetite, perspiration, heat intolerance, nervousness, exertional dyspnea, and menstrual disturbance etc. There was no clear difference in the incidence of symptoms between toxic diffuse goiter and toxic adenomatous goiter, but there was clear difference between toxic multinodular goiter. 4) Considering of results of {sup 125}IT{sub 3} resin uptake rate and serum T{sub 4} level in toxic diffuse goiter, toxic adenomatous goiter and toxic multinodular goiter, {sup 125}IT{sub 3} resin uptake rate was 49.15+-9.94% (mean) and serum T{sub 4} 21.29+-7.04 ug/dl (mean) in toxic diffuse goiter. In toxic multinodular goiter, {sup 125}I T{sub 3} resin uptake

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.

Influences of the coating on silver nanoparticle toxicity in a chronic test with Daphnia magna

DEFF Research Database (Denmark)

Sakka, Y.; Mackevica, Aiga; Skjolding, Lars Michael

2015-01-01

coated AgNP in a chronic Daphnia test. One type of AgNP was coated with citrate (cAgNP), the other AgNP were generally uncoated (pAgNP; p= pure), but sterically stabilized by an organic dispersant. Particles with a similar shape and diameter were chosen. The focus of the study was to relate observed......Sources for differences in silver nanoparticle toxicity at standardized conditions can be numerous. They range from particle properties and their actual concentrations to differences in uptake or depuration by the test organisms. In the present study we compared the toxicity of two differently...... differences in toxicity to characteristics of the AgNP, like size or surface potential, or to their corresponding behaviour during the test, like dissolution or uptake. The characteristics and the behaviour of the AgNP were investigated for changes in stability and especially the release of silver ions...

The chronic toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters

Science.gov (United States)

Farag, Aïda M.; Harper, David D.

2014-01-01

Sodium bicarbonate (NaHCO3) is the principal salt in coal bed natural gas produced water from the Powder River Structural Basin, Wyoming, USA, and concentrations of up to 3000 mg NaHCO3/L have been documented at some locations. No adequate studies have been performed to assess the chronic effects of NaHCO3 exposure. The present study was initiated to investigate the chronic toxicity and define sublethal effects at the individual organism level to explain the mechanisms of NaHCO3 toxicity. Three chronic experiments were completed with fathead minnows (Pimephales promelas), 1 with white suckers (Catostomus commersoni), 1 with Ceriodaphnia dubia, and 1 with a freshwater mussel, (Lampsilis siliquoidea). The data demonstrated that approximately 500 mg NaHCO3/L to 1000 mg NaHCO3/L affected all species of experimental aquatic animals in chronic exposure conditions. Freshwater mussels were the least sensitive to NaHCO3 exposure, with a 10-d inhibition concentration that affects 20% of the sample population (IC20) of 952 mg NaHCO3/L. The IC20 for C. dubia was the smallest, at 359 mg NaHCO3/L. A significant decrease in sodium–potassium adenosine triphosphatase (Na+/K+ ATPase) together with the lack of growth effects suggests that Na+/K+ ATPase activity was shut down before the onset of death. Several histological anomalies, including increased incidence of necrotic cells, suggested that fish were adversely affected as a result of exposure to >450 mg NaHCO3/L.

Evaluation of the threat of marine CO{sub 2} leakage-associated acidification on the toxicity of sediment metals to juvenile bivalves

Energy Technology Data Exchange (ETDEWEB)

Basallote, M. Dolores, E-mail: dolores.basallote@uca.es [Cátedra UNESCO/UNITWIN WiCop, Departamento de Química-Física, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, Polígono Río San Pedro s/n, 11510 Puerto Real, Cádiz (Spain); Rodríguez-Romero, Araceli [Departamento de Ecología y Gestión Costera, Instituto de Ciencias Marinas de Andalucía (CSIC), Campus Río San Pedro, 11510 Puerto Real, Cádiz (Spain); De Orte, Manoela R.; Del Valls, T. Ángel; Riba, Inmaculada [Cátedra UNESCO/UNITWIN WiCop, Departamento de Química-Física, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, Polígono Río San Pedro s/n, 11510 Puerto Real, Cádiz (Spain)

2015-09-15

Highlights: • Short-term tests using juveniles of bivalves to study the effects of CO{sub 2} dissolved. • CO{sub 2} causes effects if the threshold concentration of the organism is overlapped. • Flows of escaped CO{sub 2} would affect the geochemical composition of sediment–seawater. • CO{sub 2}-induced acidification would affect differently to marine sediment toxicity. - Abstract: The effects of the acidification associated with CO{sub 2} leakage from sub-seabed geological storage was studied by the evaluation of the short-term effects of CO{sub 2}-induced acidification on juveniles of the bivalve Ruditapes philippinarum. Laboratory scale experiments were performed using a CO{sub 2}-bubbling system designed to conduct ecotoxicological assays. The organisms were exposed for 10 days to elutriates of sediments collected in different littoral areas that were subjected to various pH treatments (pH 7.1, 6.6, 6.1). The acute pH-associated effects on the bivalves were observed, and the dissolved metals in the elutriates were measured. The median toxic effect pH was calculated, which ranged from 6.33 to 6.45. The amount of dissolved Zn in the sediment elutriates increased in parallel with the pH reductions and was correlated with the proton concentrations. The pH, the pCO{sub 2} and the dissolved metal concentrations (Zn and Fe) were linked with the mortality of the exposed bivalves.

Association between oral manifestations and inhaler use in asthmatic and chronic obstructive pulmonary disease patients

Directory of Open Access Journals (Sweden)

Bhargavi Krishna Ayinampudi

2016-01-01

Full Text Available Objectives: To examine the association between oral manifestations and type, frequency and duration of inhaler usage, also type and dosage of medication used in asthmatic and chronic obstructive pulmonary disease (COPD patients. Materials and Methods: A cross-sectional study was conducted on 250 patients of both sexes suffering from asthma and COPD who were using inhalers. Frequency of oral manifestation seen on the tongue, buccal mucosa, teeth, periodontium, palate, floor of the mouth, lips, and xerostomia in inhaler users depending on the type of inhaler, type and dosage of medication, frequency and duration of use of inhaler were examined. Chi-square test was used for statistical analysis and P 0.05. Gingivitis/gingival enlargement (53.6% and 51.5% was almost similar but periodontitis was higher in those using >500 μg. Significant association (P < 0.05 was observed with duration <1 year; oral manifestations seen were taste alterations (53.2% in tongue, ulcerations (63.6% in the buccal mucosa, teeth affected (87%, gingivitis/gingival enlargement (66.2%, and xerostomia (89.6%. Conclusions: As asthmatics and COPD patients are at a higher risk of developing oral diseases during inhalation therapy, it is necessary to educate patients on proper oral health care and maintenance.

Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?

Directory of Open Access Journals (Sweden)

Pamela eMaher

2015-12-01

Full Text Available Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors and a class of G-protein coupled receptors (metabotropic glutamate receptors. Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

Science.gov (United States)

Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

2017-06-01

The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, poral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Association between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan

Science.gov (United States)

DeBeer, Bryann B.; Davidson, Dena; Meyer, Eric C.; Kimbrel, Nathan A.; Gulliver, Suzy B.; Morissette, Sandra B.

2017-01-01

Objective The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of Chronic Multisymptom Illness (CMI). Methods Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Results Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. Conclusions These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans’ health is needed. PMID:28045798

Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico-in-vitro-in-vivo approach.

Science.gov (United States)

Magotra, Asmita; Sharma, Anjna; Singh, Samsher; Ojha, Probir Kumar; Kumar, Sunil; Bokolia, Naveen; Wazir, Priya; Sharma, Shweta; Khan, Inshad Ali; Singh, Parvinder Pal; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

2018-02-01

Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) assay model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal

The nano-TiO{sub 2} exposure can induce hepatic inflammation involving in a JAK–STAT signalling pathway

Energy Technology Data Exchange (ETDEWEB)

Hong, Jie [Soochow University, Department of Applied Biology, School of Basic Medical and Biological Sciences (China); Hong, Fashui, E-mail: hongfsh-cn@sina.com [Huaiyin Normal University, Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection (China); Ze, Yuguan; Zhang, Yu-Qing, E-mail: sericult@suda.edu.cn [Soochow University, Department of Applied Biology, School of Basic Medical and Biological Sciences (China)

2016-06-15

TiO{sub 2} nanoparticles (TiO{sub 2} NPs) have unique physiochemical properties and thus are widely used in daily life. However, these nanoparticles also have potential toxic effects in humans and animals, and the issue of the security TiO{sub 2} NPs has also gained prominence. In this article, mice were administered a gavage instillation of 2.5, 5, or 10 mg/kg body weight TiO{sub 2} NPs (5–6 nm) for 90 days. We investigated whether TiO{sub 2} NPs activate the JAK–STAT signalling pathway, causing nano-TiO{sub 2}-induced hepatic toxicity. The results demonstrated that with increasing doses of TiO{sub 2} NPs the body weights of the mice body decreased, and the liver index, liver dysfunction, infiltration of inflammatory cells, and hepatocyte apoptosis and necrosis increased. Moreover, liver inflammation was accompanied by increased expression of Janus kinase 2, the signal transducers and activators of transcription 3, interleukin-6, cyclooxygenase-2, neutrophil gelatinase-associated lipocalin, purinergic receptor-7, and epithelial neutrophil-activating protein-78 and decreased expression of suppressors of cytokine signalling-1, peroxisome proliferator-activated receptor-γ, and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. In summary, the activation of the JAK–STAT pathway may be involved in the hepatic inflammation induced by chronic nano-TiO{sub 2} toxicity.

The effects of chronic pain on oral health related quality of life in patients with anterior disc displacement with reduction.

Science.gov (United States)

Karacayli, U; Mumcu, G; Cimilli, H; Sisman, N; Sur, H; Gunaydin, Y

2011-09-01

The aim of this study was to evaluate the effects of chronic pain on oral health related quality of life (oral QoL) in patients with anterior disc displacement with reduction (DDwR). Thirty-seven patients who had disc displacement with reduction (DDwR, F/M: 23/14, median age: 29, range: 23-49) were selected. These patients had chronic pain and had not been undergoing any treatment protocols for the previous six months. Age- and gender-matched healthy subjects healthy control, F/M: 23/14, mean age: 33.0 +/- 15.7 years) were used as a control group. Data were collected by means of a clinical examination and a questionnaire about pain status which included a jaw disability checklist RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders). Pain status was scored between 0 (no pain) and 10 (poor pain status) by the patients. Oral health related quality of life (oral QoL) over the previous six months was evaluated by an oral health impact profile-14 (OHIP-14) questionnaire. OHIP-14 score was significantly higher in patients with DDwR (median:17, min-max:6-39) than healthy controls (9, 0-18) (p = 0.000). The median duration of orofacial pain was 12 (range 7-120) months. Statistically significant correlations were observed between OHIP-14 score and the worst pain intensity in the past six months (7, 0-10) (r = 0.5 p = 0.007) and average pain intensity in the past six months (5.5, 1-10) (r = 0.4 p = 0.018). In addition, an increase in OHIP-14 score was observed in patients experiencing difficulty in smiling/laughing, cleaning their teeth or face, swallowing or talking, according to the jaw disability checklist (p = 0.042, p = 0.001, p = 0.023 and p = 0.007, respectively). Poor oral QoL was related to chronic pain and limitations in jaw function in patients with DDwR.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

Toxic waste liquor disposal

International Nuclear Information System (INIS)

Burton, W.R.

1985-01-01

Toxic waste liquors, especially radio active liquors, are disposed in a sub-zone by feeding down a bore hole a first liquid, then a buffer liquid (e.g. water), then the toxic liquors. Pressure variations are applied to the sub-zone to mix the first liquid and liquors to form gels or solids which inhibit further mixing and form a barrier between the sub-zone and the natural waters in the environment of the sub-zone. In another example the location of the sub-zone is selected so that the environement reacts with the liquors to produce a barrier around the zone. Blind bore holes are used to monitor the sub-zone profile. Materials may be added to the liquor to enhance barrier formation. (author)

Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

Directory of Open Access Journals (Sweden)

Ochiba Mohammed Lukandu

2015-01-01

Full Text Available Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

The influence of zinc hydroxystannate on reducing toxic gases (CO, NO{sub x} and HCN) generation and fire hazards of thermoplastic polyurethane composites

Energy Technology Data Exchange (ETDEWEB)

Wang, Bibo; Sheng, Haibo [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Shi, Yongqian [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Song, Lei [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Zhang, Yan [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Hu, Yuan, E-mail: yuanhu@ustc.edu.cn [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Hu, Weizhao, E-mail: hwz1988@ustc.edu.cn [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China)

2016-08-15

Highlights: • The ZnHS could significantly enhance the mechanical properties of the TPU composites. • ZnHS has excellent smoke suppression and reduction the HRR for TPU composites. • ZnHS shows significant decrease in CO, HCN, NO{sub x} for TPU composites. • These improvements are due to charring and catalytic degradation the toxic gases. - Abstract: A uniform zinc hydroxystannate (ZnHS) microcube was synthesized to reduce toxicity and fire hazards of thermoplastic polyurethane (TPU) composites using ammonium polyphosphate as a flame retardant agent. The structure, morphology and thermal properties of ZnHS were characterized by X-ray diffraction, transmission electron microscopy and thermogravimetric analysis, respectively. Smoke suppression properties and synergistic flame retardant effect of ZnHS on flame retardant TPU composites were intensively investigated by smoke density test, cone calorimeter test, and thermalgravimetric analysis. Thermogravimetric analysis/infrared spectrometry and tube furnace were employed to evaluate the toxic gases (CO, NO{sub x} and HCN) of TPU composites. The incorporation of ZnHS into TPU matrix effectively improved the fire safety and restrained the smoke density, which is attributed to that the char residue catalyzed by ZnHS enhanced barrier effect that reduced peak heat release rate, total heat release, smoke particles and organic volatiles during combustion. Furthermore, the ZnHS synergist demonstrated high efficiency in catalytic degradation of the toxic gases, which obviously decreased total volatiled product and toxic volatiles evolved, such as the CO, HCN and NO{sub x}, indicating suppressed toxicity of the TPU composites.

Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological Manual for Oral Clinicians.

Science.gov (United States)

Chidambaram, Ramasamy

2015-01-01

Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

Acute and chronic toxicity of Roundup Weathermax and Ignite 280 SL to larval Spea multiplicata and S. bombifrons from the Southern High Plains, USA

International Nuclear Information System (INIS)

Dinehart, Simon K.; Smith, Loren M.; McMurry, Scott T.; Smith, Philip N.; Anderson, Todd A.; Haukos, David A.

2010-01-01

Pesticides have been implicated in widespread amphibian declines. We assessed acute and chronic toxicity of two widely used herbicides to larval New Mexico (Spea multiplicata) and Plains (S. bombifrons) spadefoots from cropland and native grassland playas. Roundup WeatherMAX (WM) toxicity estimates (48- and 216-h LC 50 ; 48-h LC 1 ) for both species were similar to environmental concentrations expected from accidental overspray. Chronic (30-day) exposure to WM at predicted environmental concentrations (2.0 and 2.8 mg glyphosate acid equivalents/L) reduced survival of both species. Ignite 280 SL (IG) toxicity estimates (48-h LC 50 and LC 1 ) for both species were above predicted environmental concentrations of 1.0 mg glufosinate/L. Chronic exposure to predicted environmental concentrations of IG did not reduce survival of either species. Toxicity test results suggest that at predicted environmental concentrations IG would not cause extensive mortalities among larval New Mexico and Plains spadefoots. However, WM may cause extensive mortality among larvae of these species. - Roundup WeatherMAX may cause extensive mortality among larval New Mexico and Plains spadefoots; it is unlikely that exposure to Ignite 280 SL would result in extensive mortalities.

Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats

DEFF Research Database (Denmark)

Hadrup, Niels; Löschner, Katrin; Bergström, Anders

2012-01-01

Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 $, 6 #); Ag-NP at doses: 2.......25 (8 $), 4.5 (8 $) or 9 mg/kg bw/day (10 $, 6 #); or Ag-acetate 9 mg silver/kg bw/day (8 $) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were...... quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4–7, 11–14, 14–16, P\\0.05; overall, day 1–28, P\\0.01), increased plasma alkaline phosphatase (P\\0.05), decreased plasma urea (P\\0.05) and lower absolute (P\\0.01) and relative (P\\0.05) thymus...

Oral complementary medicine and alternative practitioner use varies across chronic conditions and attitudes to risk.

Science.gov (United States)

Adams, Robert J; Appleton, Sarah L; Cole, Antonia; Gill, Tiffany K; Taylor, Anne W; Hill, Catherine L

2010-11-08

To determine whether chronic conditions and patient factors, such as risk perception and decision-making preferences, are associated with complementary medicine and alternative practitioner use in a representative longitudinal population cohort. Analysis of data from Stage 2 of the North West Adelaide Health Study of 3161 adults who attended a study clinic visit in 2004-2006. The main outcome measures were the medications brought by participants to the study clinic visit, chronic health conditions, attitudes to risk, levels of satisfaction with conventional medicine, and preferred decision-making style. At least one oral complementary medicine was used by 27.9% of participants, and 7.3% were visiting alternative practitioners (naturopath, osteopath). Oral complementary medicine use was significantly associated with arthritis, osteoporosis, and mental health conditions, but not with other chronic conditions. Any pattern of complementary medicine use was generally significantly associated with female gender, age at least 45 years, patient-driven decision-making preferences (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.08-1.77), and frequent general practitioner visits (>five per year; OR 3.62, 95% CI: 2.13-6.17). Alternative practitioner visitors were younger, with higher levels of education (diploma/trade [OR 1.88, 95% CI: 1.28-2.76], bachelor's degree [OR 1.77, 95% CI: 1.11-2.82], income >$80,000 (OR 2.28, 95% CI: 1.26-4.11), female gender (OR 3.15, 95% CI: 2.19-4.52), joint pain not diagnosed as arthritis (OR 1.68, 95% CI: 1.17-2.41), moderate to severe depressive symptoms (OR 2.15, 95% CI: 1.04-4.46), and risk-taking behavior (3.26, 1.80-5.92), or low-to-moderate risk aversion (OR 2.08, 95% CI: 1.26-4.11). Although there is widespread use of complementary medicines in the Australian community, there are differing patterns of use between those using oral complementary medicines and those using alternative practitioners.

Making sense of nickel accumulation and sub-lethal toxic effects in saline waters: Fate and effects of nickel in the green crab, Carcinus maenas.

Science.gov (United States)

Blewett, Tamzin A; Glover, Chris N; Fehsenfeld, Sandra; Lawrence, Michael J; Niyogi, Som; Goss, Greg G; Wood, Chris M

2015-07-01

In freshwater, invertebrates nickel (Ni) is considered an ionoregulatory toxicant, but its mechanism of toxicity in marine settings, and how this varies with salinity, is poorly understood. This study investigated Ni accumulation and physiological mechanisms of sub-lethal Ni toxicity in the euryhaline green crab Carcinus maenas. Male crabs were exposed to 8.2μg/L (the US EPA chronic criterion concentration for salt waters) of waterborne Ni (radiolabelled with (63)Ni) at three different salinities, 20%, 60% and 100% SW for 24h. Whole body Ni accumulation in 20% SW was 3-5 fold greater than in 60% or 100% SW, and >80% of accumulated Ni was in the carapace at all salinities. Ni also accumulated in posterior gill 8, which showed a higher accumulation in 20% SW than in other salinities, a pattern also seen at higher exposure concentrations of Ni (500 and 3000μg/L). Gill perfusion experiments revealed that Ni was taken up by both anterior and posterior gills, but in 20% SW the posterior gill 8, which performs ionoregulatory functions, accumulated more Ni than the anterior gill 5, which primarily has a respiratory function. The sub-lethal consequences of Ni exposure were investigated by placing crabs in Ni concentrations of 8.2, 500, and 3000μg/L at 20, 60 or 100% SW for 24h. In 20% SW, haemolymph Ca levels were significantly decreased by exposure to Ni concentrations of 8.2μg/L or higher, whereas Na concentrations were depressed only at 3000μg/L. Na(+)/K(+)-ATPase activity was inhibited at both 500 and 3000μg/L in gill 8, but only in 20% SW. Haemolymph K, Mg, and osmolality were unaffected throughout, though all varied with salinity in the expected fashion. These data suggest that Ni impacts ionoregulatory function in the green crab, in a gill- and salinity-dependent manner. Copyright © 2015 Elsevier B.V. All rights reserved.

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

Science.gov (United States)

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback and Produced Waters

Science.gov (United States)

as part of EPA's Hydraulic Fracturing Drinking Water Assessment, EPA is summarizing existing toxicity data for chemicals reported to be used in hydraulic fracturing fluids and/or found in flowback or produced waters from hydraulically fractured wells

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.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

Directory of Open Access Journals (Sweden)

Paula Abal

2017-02-01

Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

Science.gov (United States)

Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

Directory of Open Access Journals (Sweden)

Ziyad Binkhathlan

2017-09-01

Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Oral complementary medicine and alternative practitioner use varies across chronic conditions and attitudes to risk

Directory of Open Access Journals (Sweden)

Robert J Adams

2010-11-01

Full Text Available Robert J Adams1, Sarah L Appleton1, Antonia Cole2, Tiffany K Gill3, Anne W Taylor3, Catherine L Hill11The Health Observatory, 2Rheumatology Unit, 3Population Research and Outcomes Unit, SA Health, The University of Adelaide Discipline of Medicine, Queen Elizabeth Hospital, Woodville, AustraliaObjectives: To determine whether chronic conditions and patient factors, such as risk perception and decision-making preferences, are associated with complementary medicine and alternative practitioner use in a representative longitudinal population cohort.Participants and setting: Analysis of data from Stage 2 of the North West Adelaide Health Study of 3161 adults who attended a study clinic visit in 2004–2006. The main outcome measures were the medications brought by participants to the study clinic visit, chronic health conditions, attitudes to risk, levels of satisfaction with conventional medicine, and preferred decision-making style.Results: At least one oral complementary medicine was used by 27.9% of participants, and 7.3% were visiting alternative practitioners (naturopath, osteopath. Oral complementary medicine use was significantly associated with arthritis, osteoporosis, and mental health conditions, but not with other chronic conditions. Any pattern of complementary medicine use was generally significantly associated with female gender, age at least 45 years, patient-driven decision-making preferences (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.08–1.77, and frequent general practitioner visits (>five per year; OR 3.62, 95% CI: 2.13–6.17. Alternative practitioner visitors were younger, with higher levels of education (diploma/trade [OR 1.88, 95% CI: 1.28–2.76], bachelor’s degree [OR 1.77, 95% CI: 1.11–2.82], income > $80,000 (OR 2.28, 95% CI: 1.26–4.11, female gender (OR 3.15, 95% CI: 2.19–4.52, joint pain not diagnosed as arthritis (OR 1.68, 95% CI: 1.17–2.41, moderate to severe depressive symptoms (OR 2.15, 95% CI

Two patients with ciguatera toxicity: a seafood poisoning in travellers to (sub) tropical areas.

Science.gov (United States)

Slobbe, L; van Genderen, P J J; Wismans, P J

2008-10-01

Ciguatera toxicity is a type of seafood poisoning caused by the consumption of ciguatoxic reef fish. We describe two patients with characteristic gastrointestinal and neurological symptoms, both of whom had eaten local seafood. Although mortality is low, morbidity can be considerable due to debilitating symptoms. Most cases originate in the (sub)tropics but due to expanding tourism and fish exportation, it may be encountered in more temperate regions. Treatment is supportive, but some benefit from intravenous mannitol has been reported.

Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease.

Science.gov (United States)

Landzberg, M; Doering, H; Aboodi, G M; Tenenbaum, H C; Glogauer, M

2015-06-01

Neutrophils are the primary white blood cells that are recruited to fight the initial phases of microbial infections. While healthy norms have been determined for circulating blood neutrophil counts in order to identify patients with suspected systemic infections, the levels of oral neutrophils (oPMNs) in oral health and in the presence of periodontal diseases have not been described. It is important to address this deficiency in our knowledge as neutrophils are the primary immune cell present in the crevicular fluid and oral environment and previous work has suggested that they may be good indicators of overall oral inflammation and periodontal disease severity. The objective of this study was to measure oPMN counts obtained in a standardized oral rinse from healthy patients and from those with chronic periodontal disease in order to determine if oPMN levels have clinical relevance as markers of periodontal inflammation. A parallel goal of this investigation was to introduce the concept of 'oral inflammatory load', which constitutes the inflammatory burden experienced by the body as a consequence of oral inflammatory disease. Periodontal examinations of patients with a healthy periodontium and chronic periodontal disease were performed (n = 124). Two standardized consecutive saline rinses of 30 s each were collected before patient examination and instrumentation. Neutrophils were quantified in the rinse samples and correlated with the clinical parameters and periodontal diagnosis. Average oPMN counts were determined for healthy patients and for those with mild, moderate and severe chronic periodontal diseases. A statistically significant correlation was found between oPMN counts and deep periodontal probing, sites with bleeding on probing and overall severity of periodontal disease. oPMN counts obtained through a 30-s oral rinse are a good marker of oral inflammatory load and correlate with measures of periodontal disease severity. © 2014 John Wiley & Sons A

Late toxicity in breast cancer radiotherapy

International Nuclear Information System (INIS)

Gonzalez Coletti, F.; Rafailovici, L.; Filomia, M.L.; Chiozza, J.; Dosoretz, B.

2008-01-01

Full text: The aim of this study is to describe and classify chronic complications due to radiotherapy in breast cancer. Also the impact of radiotherapy on the quality of life of patients is evaluated. Materials and methods: 50 patients with breast cancer at early stages (78% in situ, 22% I and II) treated with radiotherapy in breast volume plus boost (45/50 Gy + 18/20 Gy) with a follow up over 5 years. Acute toxicities were found retrospectively and chronic toxicities were assessed though physical examination and review of complementary studies. To facilitate data collection, pre printed forms were used. Bibliographic searches were made. Results: 10% received chemotherapy and 64% tamoxifen. The predominant chronic toxicity were found in skin (66%), although grade I and II (hyperpigmentation 26%, dryness 22%, telangiectasia 10% fibrosis, 4%, other 4%). A 50% of the patients showed hypoesthesia in ipsilateral upper limb. The other toxicities were presented in low rate and magnitude: mastodynia 16%; actinic pneumonitis 4%, pyrosis 4%, Tachycardia 2%, among others. Of the patients with acute toxicity, only 30% were grade III. The 70% of the patients had a positive impact of radiotherapy on quality of life. Conclusions: We found low rates and degrees of late toxicity. It was noticed a relationship between acute and chronic toxicity, because those who presented adverse effects during treatment developed late effects. It reflects the importance of integrating monitoring as part of radiation treatment. It should be adopted a single score of late toxicity measurement to unify data from different series. (authors) [es

90-Day oral toxicity study of D-tagatose in rats.

Science.gov (United States)

Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

1999-04-01

D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

Retrospective examination of the healthcare 'journey' of chronic orofacial pain patients referred to oral and maxillofacial surgery.

Science.gov (United States)

Beecroft, E V; Durham, J; Thomson, P

2013-03-01

To gain a deeper understanding of the clinical journey taken by orofacial pain patients from initial presentation in primary care to treatment by oral and maxillofacial surgery. Retrospective audit. Data were collected from 101 consecutive patients suffering from chronic orofacial pain, attending oral and maxillofacial surgery clinics between 2009 and 2010. Once the patients were identified, information was drawn from their hospital records and referral letters, and a predesigned proforma was completed by a single examiner (EVB). Basic descriptive statistics and non-parametric inferential statistical techniques (Krushal-Wallis) were used to analyse the data. DATA AND DISCUSSION: Six definitive orofacial pain conditions were represented in the data set, 75% of which were temporomandibular disorders (TMD). Individuals within our study were treated in nine different hospital settings and were referred to 15 distinct specialties. The mean number of consultations received by the patients in our study across all care settings is seven (SD 5). The mean number of specialities that the subjects were assessed by was three (SD 1). The sample set had a total of 341 treatment attempts to manage their chronic orofacial pain conditions, of which only 83 (24%) of all the treatments attempted yielded a successful outcome. Improved education and remuneration for primary care practitioners as well as clear care pathways for patients with chronic orofacial pain should be established to reduce multiple re-referrals and improve efficiency of care. The creation of specialist regional centres for chronic orofacial pain may be considered to manage severe cases and drive evidence-based practice.

Metal and pharmaceutical mixtures: Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?

Energy Technology Data Exchange (ETDEWEB)

Alsop, Derek, E-mail: alsopde@mcmaster.ca; Wood, Chris M.

2013-09-15

Highlights: •Zebrafish larvae were used to test the acute toxicity of contaminant mixtures. •Interactions were observed between metals, ammonia and pharmaceuticals. •Larval Na{sup +} loss was observed with exposure to all acutely toxic contaminants tested. •Water quality criteria should recognize the toxic interactions between contaminants. -- Abstract: The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4–8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC{sub 50}, one third of the LC{sub 01}) to all copper treatments decreased the copper 96 h LC{sub 50} by 58%, while sublethal copper exposure (6% of the copper LC{sub 50}, 13% of the LC{sub 01}) decreased the cadmium 96 h LC{sub 50} by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na{sup +} followed by K{sup +} (as high as 19% and 9%, respectively, in 24 h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na{sup +} and K{sup +}. Overall, whole body Na{sup +} loss showed the greatest correlation with mortality across a

Acute and chronic toxicity of copper to the euryhaline rotifer, Brachionus plicatilis ("L" strain).

Science.gov (United States)

Arnold, W R; Diamond, R L; Smith, D S

2011-02-01

This article presents data from original research, intended for the use in the development of copper (Cu) criteria for the protection of estuarine and marine organisms and their uses in the United States. Two 48-h static-acute toxicity tests-one with and one without added food-and a 96-h static multigeneration life-cycle test (P1-F2 generations) were performed concurrently using the euryhaline rotifer Brachionus plicatilis ("L" strain) to develop a Cu acute-to-chronic ratio (ACR) for this species. Tests were performed at 15 g/L salinity, at 25°C, and the exposure concentrations of dissolved Cu were verified. Supplemental chemical analyses were performed and reported for the development of a Cu-saltwater biotic ligand model (BLM). Supplemental analyses included alkalinity, calcium, chloride, dissolved organic carbon (DOC), hardness, magnesium, potassium, sodium, and temperature. The acute toxicity test measurement end points were the dissolved Cu median lethal concentration (LC₅₀) values based on rotifer survival. The chronic measurement end points were the dissolved Cu no-observed-effect concentration (NOEC), lowest-observed-effect concentration (LOEC), EC₂₅, EC₂₀, and EC₁₀ based on the intrinsic rate of rotifer population increase (r). The 48-h LC₅₀(Fed), 48-h LC₅₀(Unfed), 96-h NOEC, 96-h LOEC, EC₂₅, EC₂₀, and EC₁₀ were 20.8, 13.4, 6.1, 10.3, 11.7, 10.9, and 8.8 μg Cu/L, respectively. The ACRs were calculated as ratios of each 48-h LC₅₀ value [fed and unfed) and each of the 96-h chronic values (ChV; geometric mean of NOEC and LOEC)], EC₁₀, EC₂₀, and EC₂₅. The ACRs ranged from 1.15 to 2.63.

Endoscope-assisted, minimally invasive evacuation of sub-acute/chronic epidural hematoma: Novelty or paradox of Theseus?

Science.gov (United States)

Ansari, Ishtyaque; Futane, Sameer; Ansari, Ashfaque

2016-08-01

Sub-acute/chronic epidural hematoma (EDH) may present with nagging symptoms of headache, nausea, vomiting, lethargy, etc. We attempted to offer a minimally invasive, single burr hole, endoscope-assisted evacuation of EDHs instead of a conventional craniotomy. Seven patients with sub-acute/chronic EDH (six supratentorial and one infratentorial) presented to us 3 to 7 days after low-velocity road traffic accidents with complaints of headache and lethargy. The EDH volumes measured between 20 to 50 ml, and the patients were operated on using a single burr hole made through a small incision. We used 0-, 30- and 70-degree, angulated, rigid, high-definition endoscopes to identify and evacuate the organized clots in the extradural space. Flexible catheters were used for suction and irrigation. After achieving hemostasis, the dura was hitched back to the burr hole site. The wound was closed over a negative suction drain. All patients had prompt recovery from symptoms. Postoperative CT scans showed complete or near complete evacuation of the hematomas. The hospital stay and analgesic requirements were minimal. There was no infective complication or conversion to conventional open surgery. The average time for surgery was 77.8 min, and average blood loss was 328.5 ml. Endoscope-assisted evacuation of sub-acute/chronic EDH is a novel concept, which offers quick relief from symptoms in a minimally invasive fashion and a cosmetically acceptable way. None of the standard principles of surgery are hampered. It avoids extensive dissection of the temporalis or sub-occipital muscles. However, achieving hemostasis can be difficult. Further study and better equipment will validate the procedure.

Oral sodium bicarbonate on the nutritional status of patients on chronic dialysis program: A randomized placebo controlled clinical trial

Directory of Open Access Journals (Sweden)

Jaime Enríquez-Zarama

2013-06-01

Full Text Available Objective: To evaluate the therapeutic effect of oral sodium bicarbonate in improving the nutritional status of patients with chronic renal failure on chronic dialysis therapy (hemodialysis and peritoneal dialysis. Design: Randomized double blind placebo clinical trial. Setting: RTS Renal Units of Popayan, Colombia. Patients and Methods: 162 patients on chronic dialysis (hemodialysis and peritoneal dialysis were randomized to either placebo or bicarbonate. Patients received oral sodium bicarbonate, 1.0 g three times daily or placebo. Both groups received treatment for a 4-month period. Results: The study groups were comparable at the beginning of the study (study baseline and no significant differences were observed in any baseline parameters. At 4 months, the levels of albumin and Subjective Global Assessment (SGA improved with bicarbonate (p = 0.000, the malnutrition inflammation score and the score of malnutrition in dialysis with bicarbonate decreased significantly (p = 0.000. The PCR remained unchanged in both groups (p = 0,306. An increase of 20% or more from baseline serum albumin was observed in 6 (7.41% patients who received bicarbonate and 1 (1.23% of those receiving placebo (p = 0.02. At baseline albumin levels

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.

The responses of endothelial cells to Zr{sub 61}Ti{sub 2}Cu{sub 25}Al{sub 12} metallic glass in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Li, Jing, E-mail: monkeys0109@sina.com; Ai, Hong-jun

2014-07-01

The goal of this study was to evaluate the biocompatibility of newly developed Zr{sub 61}Ti{sub 2}Cu{sub 25}Al{sub 12} metallic glass (denoted ZT1) and its parallel material, commercially pure titanium (CP-Ti), as dental implants. To this end, we evaluated their cytotoxicity in vitro using human umbilical vein endothelial cells (HUVECs) and in vivo by performing an oral mucosa irritation test in hamsters. Specifically, cytotoxicity was determined in HUVECs by evaluating their cell morphology using scanning electron microscopy (SEM) and their cell viability using CCK-8 assays. Moreover, we examined the mRNA levels of vascular endothelial growth factor and von Willebrand factor by quantitative PCR (qPCR). In the early stages of proliferation and differentiation, no differences were observed between HUVECs inoculated on ZT1 compared to those on CP-Ti. However, in the later stages of proliferation and differentiation, the HUVECs inoculated on ZT1 were significantly better than the cells cultured on CP-Ti. In the oral mucosa irritation test, we sutured sample discs into the cheek pouch of hamsters. After 2, 3, and 4 weeks, we harvested the corresponding mucosal tissues, stained them with hematoxylin and eosin, obtained blood samples for biochemical analysis, and finally, observed the topography of the sample discs by SEM. Immunohistochemistry and hematology analyses showed no differences in the biocompatibility of ZT1 and CP-Ti, and neither of these compounds caused irritation of the mucosa. In addition, SEM images showed that no pitting occurred on the sample discs. Together, these data indicate that ZT1 may be a good candidate for dental implants and should be further studied. - Graphical abstract: The results of blood analysis. (a) WBC, (b) Mon %, (c) Neu %, and (d) Eos %. - Highlights: • We used HUVECs to evaluate the cytotoxicity of Zr{sub 61}Ti{sub 2}Cu{sub 25}Al{sub 12} BMG. • We are the first to evaluate Zr{sub 61}Ti{sub 2}Cu{sub 25}Al{sub 12} BMG using an

Spatial analysis of toxic emissions in LCA: a sub-continental nested USEtox model with freshwater archetypes.

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Kounina, Anna; Margni, Manuele; Shaked, Shanna; Bulle, Cécile; Jolliet, Olivier

2014-08-01

This paper develops continent-specific factors for the USEtox model and analyses the accuracy of different model architectures, spatial scales and archetypes in evaluating toxic impacts, with a focus on freshwater pathways. Inter-continental variation is analysed by comparing chemical fate and intake fractions between sub-continental zones of two life cycle impact assessment models: (1) the nested USEtox model parameterized with sub-continental zones and (2) the spatially differentiated IMPACTWorld model with 17 interconnected sub-continental regions. Substance residence time in water varies by up to two orders of magnitude among the 17 zones assessed with IMPACTWorld and USEtox, and intake fraction varies by up to three orders of magnitude. Despite this variation, the nested USEtox model succeeds in mimicking the results of the spatially differentiated model, with the exception of very persistent volatile pollutants that can be transported to polar regions. Intra-continental variation is analysed by comparing fate and intake fractions modelled with the a-spatial (one box) IMPACT Europe continental model vs. the spatially differentiated version of the same model. Results show that the one box model might overestimate chemical fate and characterisation factors for freshwater eco-toxicity of persistent pollutants by up to three orders of magnitude for point source emissions. Subdividing Europe into three archetypes, based on freshwater residence time (how long it takes water to reach the sea), improves the prediction of fate and intake fractions for point source emissions, bringing them within a factor five compared to the spatial model. We demonstrated that a sub-continental nested model such as USEtox, with continent-specific parameterization complemented with freshwater archetypes, can thus represent inter- and intra-continental spatial variations, whilst minimizing model complexity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chronic TiO2 nanoparticle exposure to a benthic organism, Hyalella azteca: Impact of solar UV radiation and material surface coatings on toxicity

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The present study examined the chronic toxicity of TiO2 nanoparticles (nano-TiO2) to a representative benthic species, Hyalella azteca, using an industry standard, P25, and a coated nano-TiO2 used in commercial products. There is limited information on the chronic effects of nano...

Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

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Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

2015-07-01

After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic Graft versus Host Disease

OpenAIRE

Elsaadany, Basma Abdelaleem; Ahmed, Eman Magdy; Aghbary, Sana Maher Hasan

2017-01-01

Background. Oral chronic graft versus host disease (cGVHD) is a major complication in transplantation community, a problem that can be addressed with topical intervention. Topical corticosteroids are the first line of treatment although the choice remains challenging as none of the available treatments is supported by strong clinical evidence. Objective. This systematic review aims to determine the clinical efficacy and safety of topical corticosteroids for the management of the mucosal alter...

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

Energy Technology Data Exchange (ETDEWEB)

Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States)

2012-01-01

Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints

Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

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Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

2015-02-01

Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

Energy Technology Data Exchange (ETDEWEB)

Yoshiura, Yukiko, E-mail: y-yoshiura@med.uoeh-u.ac.jp; Izumi, Hiroto [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Oyabu, Takako [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Hashiba, Masayoshi; Kambara, Tatsunori [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Tomonaga, Taisuke [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Myojo, Toshihiko [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Horie, Masanori [National Institute of Advanced Industrial Science and Technology (AIST), Health Research Institute (HRI) (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Morimoto, Yasuo [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan)

2015-06-15

In order to investigate the pulmonary toxicity of titanium dioxide (TiO{sub 2}) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO{sub 2} may not lead to chronic, irreversible legions in the lung, and that TiO{sub 2} nanoparticles may not have a high potential for lung disorder.

Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid.

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Al-Salem, Huda S; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf

2016-04-23

It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.

Chronic toxicity of fumonisins in turkeys.

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Tardieu, D; Bailly, J-D; Skiba, F; Métayer, J-P; Grosjean, F; Guerre, P

2007-09-01

Fumonisins are mycotoxins that are found worldwide. They are mainly produced by Fusarium verticillioides during its development on corn. The main toxic effects of these molecules have been well characterized in poultry in the case of acute exposure, but the subclinical and economic effects of chronic exposure are less known. Whereas the latest European recommendations suggest that maximal levels of fumonisins in corn could reach 60 mg/kg and the maximal contamination of poultry feeds could reach 20 mg/kg, no study is available at this level in turkeys. The aim of the present work was thus to characterize the effects of exposure to fumonisins (concentrations of 0, 5, 10, and 20 mg of fumonisin B1 + fumonisin B2/kg of feed) on feed consumption and growth in turkeys over a period of 9 wk. Main biochemical parameters of the liver and alteration of sphingolipid metabolism were investigated in plasma, liver, and kidney. The main results showed no effect on feed consumption and growth in exposed turkeys. Moreover, no effect was observed on the weight of tissues and markers of liver injury. By contrast, a disruption of sphingolipid metabolism was clear at a level of exposure of 10 and 20 mg of fumonisin B1 + fumonisin B2 mg/kg of feed. Both hepatic and kidney concentrations of sphinganine increased gradually throughout the exposure period. These results reveal that disruption of sphingolipid metabolism is an early and sensitive biomarker of fumonisins exposure in turkeys; the consequences on these alterations remain to be established.

Intravenous voriconazole after toxic oral administration

NARCIS (Netherlands)

Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

Oral Exposure and Absorption of Toxicants

Science.gov (United States)

This chapter provides an overview of the toxicokinetics of orally absorbed xenobiotics. This includes a description of the basic anatomy and physiology of the digestive tract most relevant to the absorption process. In addition, differences in anatomy and physiology between human...

Development of Alternatives to Chronic Ecotoxicity Tests: Predicting Early-life Stage and Endocrine-mediated Toxicity in Aquatic Vertebrate Species

Science.gov (United States)

In June 2010, the ILSI Health and Environmental Sciences Institute (HESI) with support from sanofi-aventis, NC3Rs, the Humane Society, L’Oreal, and ECVAM, held a workshop aimed at examining critical science needs related to the development of alternatives to chronic fish toxicity...

Chronic periodontitis can affect the levels of potential oral cancer salivary mRNA biomarkers.

Science.gov (United States)

Cheng, Y-S L; Jordan, L; Chen, H-S; Kang, D; Oxford, L; Plemons, J; Parks, H; Rees, T

2017-06-01

More than 100 salivary constituents have been found to show levels significantly different in patients with oral squamous cell carcinoma (OSCC) from those found in healthy controls, and therefore have been suggested to be potential salivary biomarkers for OSCC detection. However, many of these potential OSCC salivary biomarkers are also involved in chronic inflammation, and whether the levels of these biomarkers could be affected by the presence of chronic periodontitis was not known. The objective of this pilot study was therefore to measure the levels of seven previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and compare them to levels found in patients with OSCC and healthy controls. The seven salivary mRNAs were interleukin (IL)-8, IL-1β, dual specificity phosphatase 1, H3 histone family 3A, ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and spermidine/spermine N1-acetyltransferase 1. Unstimulated whole saliva samples were collected from a total of 105 human subjects from the following four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree, non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and healthy controls. Levels of each mRNA in patient groups (OSCC or chronic periodontitis) relative to the healthy controls were determined by a pre-amplification reverse transcription-quantitative polymerase chain reaction approach with nested gene-specific primers. Results were recorded and analyzed by the Bio-Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs. control groups were analyzed by the Mann-Whitney U-test with Bonferroni corrections. Only S100P showed significantly higher levels in patients with OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The difference in S100P levels between patients with OSCC and healthy controls was also marginally significant (p = 0.009). There was no

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

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