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Sample records for oral toxicity study

  1. Subchronic oral toxicity studies with y-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    1998-01-01

    The toxicity of γ-cyclodextrin (γ-CD), a cyclic polymer of eight α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered

  2. Subacute (90 Days) Oral Toxicity Studies of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    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.

  3. Subacute(90Days) Oral Toxicity Studies of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    R.VIJAYARAGHAVAN; MANINDERSINGH; 等

    2000-01-01

    Kombucha tes(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 coutries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments,viz.,intestinal disorders,arthritis,ageing and stiumulation of immunological system.Though KT is used in several parts of the world its eneficial 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 goups of rats were maintained:(a) control group given tap water orally,(b) KT given 2ml/kg orally,(c)plain tea(PT) given 2ml/kg orally,(d)KT given in drinking water,1%(v/v)and (e)PT given indrinking 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 progrssive body weight change.The organ to body weight ration and histologuical 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 day showed no toxic effects.

  4. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

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    Xiu Wen P'ng, Gabriel Akyirem Akowuah and Jin Han Chin*

    2012-11-01

    Full Text Available Clinacanthus nutans Lindau (Family: Acanthaceae has attracted public interest recently due to its high medicinal values for the treatment of cancer, inflammation and various skin problems. This study was aimed to determine the oral LD50 value of the methanol leaves extract of C. nutans and identify the targeted organs in mice. This acute oral toxicity study was conducted in accordance to OECD 423 guidelines by using male Swiss albino mice weighing 25-35 g. First group was served as control group which received distilled water (vehicle while second and third group were orally treated with single daily dose of 0.9 g/kg and 1.8 g/kg of methanol leaves extract of C. nutans, respectively. All the animals were closely observed for 14 days. Body weight for each mouse was recorded at day-0, day-3, day-7 and day-14. Relative organ weights for liver, kidney, spleen, lung and heart were also determined. All the results were presented as mean ± standard deviation and analyzed using Dunnett’s Test after ANOVA test. From the results obtained, no mortality was observed in both treatment groups either post 24 hours or 14 days of oral administration of C. nutans. Body weight for each mouse and relative organ weight showed insignificant difference when compared to the control group. In conclusion, acute exposure of 1.8 g/kg of C. nutans was safe in male mice without causing any adverse effects or mortality. The oral LD50 of methanol leaves extract of C. nutans was suggested to be greater than 1.8 g/kg bw in male mice.

  5. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  6. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  7. Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 1

    Science.gov (United States)

    1996-02-02

    collection and fixation of the following tissues/organs in 10% neutral buffered formalin (NBF). The subcutaneously implanted microchip was also...10 10 10 10 10 10 10 10 10 ivf r.\\< •-Significant Difference from Control P < .05 Page 58 Table 8.2 SIX MONTH ORAL TOXICITY STUDY OF WR23

  8. 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 mortalit

  9. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA Repeated dose 28-day oral toxicity study in rodents. 799.9305 Section 799.9305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  10. 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 a

  11. PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ACUTE ORAL TOXICITY STUDY OF CLITORIA TERNATEA LINN. ROOTS IN ALBINO MICE

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    Deka Manalisha

    2011-12-01

    Full Text Available Clitoria ternatea has been using since the ancient times for its medicinal values. Almost all the parts of the plant have medicinal property. The root of the plant is reported to have anti diarrheal, Anti histamic, cholinergic activity etc. Traditionally the root has been using for the treatment of many diseases like leucorrhoea, diarrhea, urinary problems, diuretic, impotency, stomach trouble etc. The present study was designed to investigate the preliminary phytochemical analysis and acute oral toxicity of the root of the plant. The shed dried materials were grinded and used in the study. The preliminary phytochemical analysis was done by following standard protocols. For acute oral toxicity study, methanolic extract of the root was used. The extract was prepared by standard protocol. The preliminary phytochemical analysis showed the presence of proteins, carbohydrates, glycosides, resins, saponin, flavonoid, alkaloids, steroids and phenol. The acute oral toxicity study showed no mortality up to a dose of 3000 mg per kg body weight. The presence of plant chemicals revealed the medicinal values and the non toxic property of the plant indicated the value of the plant as medicine. Thus we can conclude that, the root of the plant can be used as a safe drug against many diseases.

  12. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    Science.gov (United States)

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

  13. PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ACUTE ORAL TOXICITY STUDY OF MUCUNA PRURIENS LINN. IN ALBINO MICE

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    Deka Manalisha

    2012-02-01

    Full Text Available Mucuna Pruriens Linn. is an annual, climbing shrub which has an important place among aphrodisiac herbs in India since the ancient times. The plant has been using traditionally for many medicinal purposes such as Infertility, Parkinson’s disease, Loss of libido, Antioxidant, Anti venom, Anti microbial etc. The present study was carried out to investigate the preliminary phytochemical analysis and acute oral toxicity of the seeds of M.pruriens on albino mice. Matured seeds of M.pruriens were dried in shed and grinded in a mechanical grinder. The preliminary phytochemical analysis was done by following standard protocols. For acute oral toxicity study, methanolic extract of the seeds were used. The extract was prepared in a Soxlet apparatus. The preliminary phytochemical analysis showed the presence of protein, carbohydrates, glycosides, alkaloids, steroids, flavonoids, phenols and tannins. The acute oral toxicity study showed no mortality up to a dose of 4000 mg per kg body weight. The presence of plant chemicals revealed the medicinal values and the non toxic property of the plant indicated the value of the plant as medicine. Thus, we can conclude that, the seed of the plant can be used as a safe drug against many diseases.

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

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    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

  15. Acute oral toxicity and histopathological study of combination of endosulfan and cypermethrin in wistar rats.

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    Raj, Jaya; Mohineesh; Ray, Ruma; Dogra, T D; Raina, Anupuma

    2013-01-01

    Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations. The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage. When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control. Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats.

  16. Cytotoxicity and Oral Acute Toxicity Studies of Lantana camara Leaf Extract

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    Badakhshan Mahdi Pour

    2011-05-01

    Full Text Available Background: The objective of this study was to investigate the toxicity of Lantana camara methanol extract. Methods: In order to evaluate the toxicity of Lantana camara, the acute toxicity of the methanolic extract on adult mice and cytotoxicity test on Vero cell line were investigated. A fixed large dose of 2 g/kg body weight of L. camara leaf extract was administrated by a single oral gavage according to the OECD procedure. Results: In 2 weeks, L. camara leaf extract showed no obvious acute toxicity. While female mice lost body weight after being treated with single dose of leaf extract in acute toxicity test, male ones lost organ mass, particularly for heart and kidney. The biochemical liver function tests showed significantly elevated TBIL and ALT in the L. camara leaf extract treated female mice group compared with the control group. Cytotoxicity effect of leaf extract of L. camara was estimated through a MTT assay. Cytotoxicity tests on Vero cell line disclosed that leaf extract at concentrations up to 500 µg/mL inhibited the growth of cells 2.5 times less than did Triton 100× 1%. More interestingly, the cytotoxicity initiated to decline at elevated concentrations of this extract. Conclusions: The results of both tests confirm that L. camara shows a pro toxic effect.

  17. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats

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    Zakiah Ismail

    2014-01-01

    Full Text Available The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group at 0 (control, 0.01, 0.14, and 2 g/kg body weight (BW for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect.

  18. Subchronic oral toxicity study of Vegeta in Sprague-Dawley rats

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    Hedi R. Dewoto

    2006-12-01

    Full Text Available The objective of this study was to determine the safety and toxic effect of Vegeta giving orally for a period of 90 days in rats. Eighty rats of Sprague-Dawley strain were randomly devided into 4 groups. Each group consists of 20 rats, 10 male and 10 female rats. Each group received 0.25 g/ kgBW; 0.50 g / kgBW; 1.00 g / kgBW Vegeta (in aquadest solution respectively, and the control group received 5 mL /kgBW aquadest , given orally by gastric tube for 90 days. The rat’s body weight and behavior were daily evaluated. On the 90th day, the rats were decapitated and the blood samples were withdrawn for evaluation of Hemoglobin, leucocyte, SGPT, SGOT, creatinine, and ureum concentration. Visceral organs were also removed, being weighted and were examined microscopically. The results showed that Vegeta with dose of 0.25 g / kgBW; 0.50 g / kgBW, and 1.00 g / kgBW did not affect body weight, liver and renal function compared to control group. There was no significant difference for hemoglobin value compared to control group, but the number of leucocyte increased in 1.00 g / kgBW Vegeta dose group, which was possibly caused by infection. In Vegeta group, there was different spleen and brain weight in male rats, and different lung and heart weight in female rats compared to the control group. However, since it was not dose-related and there was no specific abnormality in microscopic examination compared to the control group, it was not indicated as Vegeta toxic effect. The No observed effect level (NOEL value of Vegeta for 90 day oral administration in male and female rats of Sprague-Dawley strain was 1.00 g / kgBW. (Med J Indones 2006; 15:223-8Keywords: Vegeta, subchronic toxicity, oral, rats

  19. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts

    Science.gov (United States)

    Safinar Ismail, Intan; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  20. Acute Oral Toxicity Study of GAL-57 (Bentazon + Dicamba Herbicide in Rats

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    Dragica Brkić

    2009-01-01

    Full Text Available An acute oral toxicity study of the herbicide GAL-57 (Avalon, a mixture of bentazon and dicamba as active ingredients, was conducted to assess its acute oral toxicity to rats, using a new method that has been used in the past several years (2001. Clinical observations were performed for all animals after different time intervals, and gross necropsy was performed at termination of examination. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone and dyspnoea from mild to marked degree were noted after administration of 2000 mg/kg. Animals were found dead 30 minutes to one hour after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behaviour of animals were normal during the 14-day observation period. The acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats and was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System and Category III of the EPA classification.

  1. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

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    Madhu Katyayani Balijepalli

    2015-01-01

    Full Text Available Background: Swietenia macrophylla King. (Meliaceae seeds (SMS; commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS at a single-dose oral administration of 2 g/kg body weight (bw in sprague dawley (SD rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats′ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach; the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats.

  2. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

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    Kura, Aminu Umar; Cheah, Pike-See; Hussein, Mohd Zobir; Hassan, Zurina; Tengku Azmi, Tengku Ibrahim; Hussein, Nor Fuzina; Fakurazi, Sharida

    2014-05-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant ( p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant ( p brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

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

    Institute of Scientific and Technical Information of China (English)

    Feroz Ahmad; Nahida Tabassum

    2013-01-01

    Objective: To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods: 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. Result: Phytochemical screening revealed that the roots ofP. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2000 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. Conclusions: The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

  4. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

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    Diego A. Fernández

    2014-01-01

    Full Text Available Okadaic acid (OA and its analogues, dinophysistoxin 1 (DTX1 and dinophysistoxin 2 (DTX2, are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p. lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  5. Experimental basis for the high oral toxicity of dinophysistoxin 1: a comparative study of DSP.

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    Fernández, Diego A; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2014-01-03

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2-10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  6. Oral 4-week and 13-week toxicity studies of polyvinyl acetate vinyl laurate copolymer in rats.

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    Messinger, Horst; Bär, Albert

    2014-10-01

    Polyvinyl acetate vinyl laurate copolymer (PVAcVL) is a useful component of gum base for chewing gum production. The safety of PVAcVL was examined in a 4-week and a 13-week oral toxicity study in rats. Finely powdered PVAcVL was administered with the diet at levels of 1.25%, 2.0% and 5% in the 4-week study and 1.25%, 2.5% and 5% in the 13-week study. There were no treatment related effects on mortality, bodyweight gains feed efficiency, ophthalmoscopic findings, hematological and clinical chemical parameters, neurobehavioral observations as well as gross and histopathological changes of standard organs and tissues. The highest dose tested in the 13-week study (3783 and 4396mg/kgbw/d for males and females, respectively) proved to be a NOAEL.

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

    Institute of Scientific and Technical Information of China (English)

    Feroz; Ahmad; Nahida; Tabassum

    2013-01-01

    Objective:To carry out a preliminary phytochemical,acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis(P.officinalis)L.Methods: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.Result: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 2000 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.Conclusions:The aqueous extract of P.officinalis is safe and possesses antihepatotoxic potential.

  8. Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.

    Science.gov (United States)

    Bakhtiar, Ray; Ramos, Luis; Tse, Francis L S

    2004-01-01

    Ritalin or methylphenidate (MPH) is often prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The therapeutic activity of MPH is principally due to D-threo-[2R,2'R]-MPH. Hence, in order to establish a kinetic relationship between doses and exposure levels in a non-rodent species, a 13-week oral (capsule) toxicity study of D-threo-[2R,2'R]-MPH was performed in beagle dogs. A previously reported chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) with a limit of quantification (LLOQ) of 1.09 ng/ml was utilized. The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration. The peak concentration was reached within 1-2 h. Based on the area under the curve (AUC) values, the plasma exposure of D-MPH was over-proportional to the dose. With the exception of two groups of animals (male/female, 7.5 mg/kg/day on day 1 and male/female, 3.0 mg/kg/day on week 7), the data showed no difference in MPH concentrations between the male and female dogs. Taking the statistical variations into account, concentrations of D-MPH that were observed after 7.5 mg/kg/day doses of D-MPH and 15 mg/kg/day doses of the racemate were similar. Following the racemate doses, the concentrations of L-MPH were consistently higher than those of the D-isomer. No accumulation of MPH was observed after 13 weeks of repeated daily administration.

  9. Acute Oral Toxicity Studies of Ethanol Leaf Extracts Of Derris Scandens & Pulicaria Wightiana In Albino Rats

    Directory of Open Access Journals (Sweden)

    Vidya Sabbani

    2015-02-01

    Full Text Available Objective: The present study was designed to find out LD50 and to ascertain the safety of ethanol extracts of leaves of Derris scan dens and Pulicaria wightiana by acute oral toxicity study in female rats as per OECD guideline 425.Methods: Rats were sequentially administered with ethanol leaf extracts of Derris scandens (Ds & Pulicaria wightiana(Pw  in single dosages of 175, 550, and 2000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters and body weight for 14 days.Results: No mortality and no significant changes were observed in body weight and wellness parameters at 175, 550 and 2000 mg/kg body wt. doses of both Derris scandens and Pulicaria wightiana , which reveal the safety of these plants  in the doses up to 2000 mg/kg body weight.Conclusion: Conclusively, LD50 value of ethanol extracts of leaves of Derris scandens and Pulicaria wightiana were found to be more than 2000 mg/kg body weight.

  10. PRELIMINARY PHYTOCHEMICAL SCREENING AND ACUTE ORAL TOXICITY STUDY OF THE FLOWER OF PHLOGACANTHUS THYRSIFLORUS NEES IN ALBINO MICE

    Directory of Open Access Journals (Sweden)

    Chakravarty Sharmistha

    2012-04-01

    Full Text Available Medicinal plants contains a variety of chemical substances with important therapeutic properties that can be utilised in the treatment of human diseases. Phlogacanthus thyrsiflorus Nees of family Acanthaceae is used in folklore remedies for treatment of Cough, Bronchitis, Fever, Asthama, Cancer and many other ailments. The present investigation was carried out to assess the qualitative phytochemical analysis of aqueous extract of the flower of Phlogacanthus thyrsiflorus Nees. The phytochemical screening reveals the presence of Tannin, Saponin, Flavonoid, Steroid, Triterpenoid, Phenol. For Acute Oral Toxicity study aqueous extract of the flower was used. The Acute Oral Toxicity test showed no mortality upto 1000 mg/kg body weight. The presence of these phytochemicals reveals its medicinal properties and non toxic nature of the plant indicated the value of the plant as medicine. This result suggests that the flower of Phlogacanthus thyrsiflorus can be used to cure various ailments.

  11. Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

    Institute of Scientific and Technical Information of China (English)

    Kean Tatt Lim; Vuanghao Lim; Jin Han Chin

    2012-01-01

    Objective:To examine the oral toxicity of repeated dosing of Strobilanthes crispus (S. crispus) ethanol leaves extract on the liver and kidney functions in Sprague Dawley rats. Methods:Young female rats aged between 8 and 12 week-old were randomly assigned into four groups with five animals each group (n=5). The first group served as control, while the second, third and fourth groups were orally treated with a single dose daily with 150 mg/kg, 300 mg/kg, and 600 mg/kg of S. crispus ethanol leaves extract for 14 d consecutively. Cage-side observation was conducted for first 4 h after each dosing. The body weight changes, food consumptions and water intake were also recorded. Serum biochemical parameters, i.e., aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea were determined at Day 15. All results were expressed as mean±SD and analysed using Dunnett's test. Results: It was obtained that 14-day oral administration of S. crispus ethanol leaves extract did not cause any adverse effects or lethality to the female Sprague Dawley rats. No significant changes in serum biochemical parameters, relative organs weights, body weights, food intake and water consumptions were observed between the treatment groups and control. Conclusions:In conclusion, 14-day oral administration of S. crispus ethanol leaves extract was safe to be consumed in female rats without affecting the liver and kidney functions.

  12. Subchronic oral toxicity study with regular and enzymatically depolymerized sodium carboxymethylcellulose in rats.

    Science.gov (United States)

    Bär, A; Til, H P; Timonen, M

    1995-11-01

    Enzymatically depolymerized sodium carboxymethylcellulose (CMC-ENZ) is a new functional food ingredient which has a lower molecular weight and viscosity than regular sodium carboxymethylcellulose (CMC). Both compounds are known not to be absorbed to a significant extent, and the human safety of CMC as a thickening agent and stabilizer in food is well established. In the present study, the subchronic oral toxicity of CMC-ENZ was examined and compared with that of CMC in Wistar rats. Seven groups of 20 rats/sex were fed diets with 0 (controls), 2.5, 5 and 10% CMC and 2.5, 5 and 10% CMC-ENZ for a 3-month period. There was only one death that was unrelated to the treatment. Water intake, urine production and urinary sodium excretion increased with increasing doses of CMC and CMC-ENZ due to their sodium content of about 7-8%. The treatment-related occurrence of diarrhoea and caecal enlargement in the mid- and high-dose groups, a slight increase of plasma alkaline phosphatase, and increased urinary calcium and citrate excretions were considered to be generic effects that typically are observed in rodent studies with low digestible carbohydrates. The increased occurrence of nephrocalcinosis and hyperplasia of the urothelial epithelium in some of the treated groups was interpreted as an indirect consequence of a more alkaline urine coupled with an increased calcium excretion. As the frequency and severity of all these changes did not differ between corresponding CMC and CMC-ENZ dose groups, it is concluded that the two products have a similar toxicological profile.

  13. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    Science.gov (United States)

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while testing of cosmetic ingredients.

  14. Pyridostigmine Synergistic Toxicity Study.

    Science.gov (United States)

    1995-05-31

    AND DEET IN THE LABORATORY RAT 1. Executive Sum m ary .............................................................................................. 2 2...TOXICOLOGICAL STUDY 75-48-2665 ACUTE ORAL TOXICITY STUDY OF PYRIDOSTIGMINE BROMIDE. PERMETHRIN. AND DEET IN THE LABORATORY RAT 1. REFERENCES: See Appendix A... LABORATORY RAT 1. PURPOSE: The purpose of this study was to determine potential toxic interactions when pyridostigmine bromide. permethrin. and DEET are given

  15. Sub-acute oral toxicity study of methanol leaves extract of Catharanthus roseus in rats

    Institute of Scientific and Technical Information of China (English)

    LYW Kevin; AH Hussin; I Zhari; JH Chin

    2012-01-01

    Objective: To examine the sub-acute (14 d) oral toxic effects of methanol leaves extract ofCatharanthus roseus (C. roseus) (Family: Apocynaceae) on liver and kidney functions in Sprague Dawley (SD) rats. Methods: Twenty four female SD rats were used throughout the experiment. The first group was orally treated with distilled water and served as control, whereas the remaining three groups were orally treated with single dose daily of 0.1 g/kg, 0.5 g/kg, 1 g/kg of C. roseus extract, respectively for 14 d. Cage-side observations were done daily. Any animal died during the experiment was dissected for gross organ examination. Body weight changed, food consumption and water intake were recorded weekly. Blood was collected via cardiac puncture on day-15 and used for determination of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. The relative organ weights were also measured. All results were expressed as mean ± S.E.M and analysed using Dunnett’s test. The level of significance was set at P<0.05 when compared to the control group. Results: Repeated oral administration of 0.5 g/kg and 1 g/kg of methanol leaves extract of C. roseus caused mortality and diarrhoea in rats after few days of treatment. There were no significant changes observed in serum biochemical markers, body weight changed, water and food intake and relative organ weight in rats treated with a single dose daily of 0.1 g/kg of C. roseus extract treatment for 14 d when compared to control group. Conclusionds: Fourteen days repeated oral administration of 0.1 g/kg of methanol leaves extract of C. roseus was safe in female SD rats without causing any significant damages to liver and kidney.

  16. Thirteen-week oral dose toxicity study of Oligonol containing oligomerized polyphenols extracted from lychee and green tea.

    Science.gov (United States)

    Kitadate, Kentaro; Homma, Kohei; Roberts, Ashley; Maeda, Takahiro

    2014-02-01

    Oligonol is a functional food containing catechin-type monomers and proanthocyanidin oligomer converted from polymer forms via a novel manufacturing process. The catechin component of green tea extract has been associated with nasal toxicity in rats following subchronic exposure. To assess the potential for Oligonol to induce nasal toxicity a 13-week repeated oral dose toxicity study was conducted in rats using doses of 100, 300, and 1000 mg/kg/d. Clinical signs and mortality were not affected by Oligonol treatment. Compound-colored stools and an increase in food consumption were observed in some treated groups; however, there were no treatment-related differences in terminal body weights or with respect to the results of the gross postmortem examinations. Histopathological evaluation of the nasal cavity tissues revealed no treatment-related lesions. The results from this toxicity study indicate that Oligonol does not induce nasal toxicity and further supports the results of previous studies demonstrating the safety of Oligonol for human consumption.

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

    NARCIS (Netherlands)

    Jonker, D.; Kuper, C.F.; Fraile, N.; Estrella, A.; Rodríguez Otero, C.

    2003-01-01

    Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal biomas

  18. Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

    NARCIS (Netherlands)

    Wolterbeek, A.; Oosterwijk, T.; Schneider, S.; Landsiedel, R.; Groot, D. de; Ee, R. van; Wouters, M.; Sandt, H. van de

    2015-01-01

    Synthetic amorphous silica (SAS) like NM-200 is used in a wide variety of technological applications and consumer products. Although SAS has been widely investigated the available reproductive toxicity studies are old and do not cover all requirements of current OECD Guidelines. As part of a CEFIC-L

  19. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows

    NARCIS (Netherlands)

    Appel, M.J.; Veen, H.A. van; Vietsch, H.; Salaheddine, M.; Nuijens, J.H.; Ziere, B.; Loos, F. de

    2006-01-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received physiologica

  20. Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 2

    Science.gov (United States)

    1996-02-02

    STUDY MO: 1!>2 ABBR: HCV SEX: FEMALE UNITS: fL Animal ID Week U Week 13 Week 26 GROUP: 1-F:0 mg base/kg/day 426 57.8 55.4 57.9 427 58.8 55.5 57.5...Microscopic (Micro) Findings (Section V). The codes used as entries in these tables are explained in the Report Codes Table. The results of the bone...TOXICITY STUDY OF WR23 8605 SUCCINATE IN RATS SUMMARY OF CLINICAL CHEMISTRY TESTS TEST: Creatine Kinase [uj Ul STUDY ID: UIC-15B STUDY NO

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

    Directory of Open Access Journals (Sweden)

    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.

  2. A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats.

    Science.gov (United States)

    Nikiforov, Andrey I; Eapen, Alex K

    2008-01-01

    Rebaudioside A is one of several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) stevia that has been identified as a potential sweetener. The present study (initiated in April 2006 and completed in October 2006) evaluated the safety of this sweetener when administered as a dietary admix at target exposure levels of 500, 1000, and 2000 mg/kg/day to Sprague-Dawley rats for 90 days. There were no treatment-related effects on the general condition and behavior of the animals as determined by clinical observations, functional observational battery, and locomotor activity assessments. Evaluation of clinical pathology parameters revealed no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Lower mean body weight gains were noted in males in the 2000 mg/kg/day group throughout the study, which was considered to be test article related; however, given the small magnitude of the difference as compared to controls, this effect was not considered to be adverse. Results of this study clearly demonstrate that dietary administration of high concentrations of rebaudioside A for 90 consecutive days to Sprague-Dawley rats was not associated with any signs of toxicity.

  3. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    Science.gov (United States)

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    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.

  4. Preclinical toxicity profile of oral bilastine.

    Science.gov (United States)

    Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

    2012-06-01

    As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

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

    NARCIS (Netherlands)

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

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,

  8. Acute and sub-chronic oral toxicity studies of an aqueous stem bark extract of Pterocarpus soyauxii Taub (Papilionaceae) in rodents.

    Science.gov (United States)

    Tchamadeu, M C; Dzeufiet, P D D; Nana, P; Kouambou Nouga, C C; Ngueguim Tsofack, F; Allard, J; Blaes, N; Siagat, R; Zapfack, L; Girolami, J P; Tack, I; Kamtchouing, P; Dimo, T

    2011-01-27

    Pterocarpus soyauxii Taub (Papilionaceae) is used in Cameroonian traditional medicine and pharmacopoeia to treat hypertension, diabetes, gastrointestinal parasitizes and cutaneous diseases. The present investigation was carried out to evaluate the safety of an aqueous stem bark extract of Pterocarpus soyauxii by determining toxicity after acute and sub-chronic oral administration in male and female rodents. The acute toxicity test was conducted in mice. An aqueous extract of barks was administrated by gavage in single doses of 2.5-12.5 g/kg. General behaviour and mortality were examined for up to 7 days. The sub-chronic toxicity test was performed in rats. The plant extract was administered by daily gavage of 150-600 mg/kg for 42 days. Body weight, food and water intakes were followed weekly. Haematological, biochemical and organ parameters were determined at the end of the 42-day administration. In the acute study in mice, oral administration of the aqueous extract of Pterocarpus soyauxii caused dose-dependent general behaviour adverse effects and mortality. The no-observed adverse effect level (NOAEL) of the extract was 5.0 g/kg. The lowest-observed adverse effect level (LOAEL) was 7.5 mg/kg. Mortality increased with the dose, LD(50) was>10.75 g/kg for the mouse. In the sub-chronic study in rats, daily oral administration of the aqueous extract of Pterocarpus soyauxii did not result in death or significant changes in haematological or biochemical parameters, excepted increased hepatic catalase activity (PPterocarpus soyauxii Taub had very low toxicity in oral acute high dose administration and no toxicity in oral sub-chronic low dose administration and indicate that the plant could be considered safe for oral medication. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-03-01

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

  10. Acute oral toxicity study of ethanol extract of Ceiba pentandra leaves as a glucose lowering agent in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Hadiza Lami Muhammad; Adamu Yusuf Kabiru; Musa Bola Busari; Abdullah Mann; Abubakar Siddique Abdullah; Abdulrazaq Taye Usman; Usman Adamu

    2016-01-01

    Objective: To evaluate the use of Ceiba pentandra (C. pentandra) as a glucose lowering agent and the attendant physiological changes in albino rats. Methods: Acute oral toxicity study of the extract was carried out by the administration of 10, 100, 1 000, 1 600, 2 900, and 5 000 mg/kg body weight of C. pentandra to rats in their respective groups. Twenty healthy albino rats weighing between 140 and 150 g were randomly allotted to five groups of four rats each. 100 mg/kg body weight of alloxan monohydrate was i.p. administered to rats and rats with blood glucose ? 200 mg/dL were considered diabetic. 5 mg/kg body weight of standard drug, 200 and 400 mg/kg body weight of ethanol extract of C. pentandra were orally administered to diabetic rats in their respective groups once daily for 12 days while the control groups received 0.1 mL of normal saline for the same period. The blood glucose was checked after every 4 days and the experiment was terminated on the 17th day. Results: The safe dose (LD50) of the extract was greater than 5 000 mg/kg body weight. The extract treated groups exhibited a remarkable reduction in blood glucose [(87.72 ± 7.67) mg/dL for 200 mg/kg body weight dose and (86.33 ± 4.54) mg/dL for 400 mg/kg body weight dose] competitively with the normoglycemic group [(88.71 ± 4.56) mg/dL]. The body weight of the extract and standard drug treated groups appreciated significantly (P Conclusions: Ethanol extract of C. pentandra has glucose lowering effect and can ameliorate the biochemical abnormalities associated with diabetes mellitus.

  11. Ninety-Day Subchronic Oral Toxicity Study of Pyridostigmine Bromide in Rats. Volume 1

    Science.gov (United States)

    1990-05-01

    near the termination of the study: 1. specific gravity (osmolarity) 2. pH 3. protein 4. ketones 5. glucose 6. bilirubin 7. urobilinogen 8. occult blood...HHHW o’~cn4 HHC’ JHHH HH~r IH4 HI) (t - -x -jx 0 H ko m HCV ) N k w r) r HI H 4N- O OC AC)( H)1 )4 ICL OV O )L O% Iw - 7- - Morgan et al--117 O CO

  12. Thirteen Week Oral Toxicity Study of WR242511 in Rats. Volume 2

    Science.gov (United States)

    1994-01-14

    production of a direct methemoglobin-forming metabolite. Hemosiderosis in the spleen of high dose females was probably secondary to mild hemolytic...anemia. Significant methemoglobin production was also observed in mid and high dose animals. Thymic lymphocyte depletion in high dose males was...this study. 11. Page 5 Section 8.5 Change Test Article Vehicle from Ŕ.5% Na* carboxymethylcellulose /0.3% Tween 80" to ŕ% Methylcellulose/0.2

  13. One Hundred Eighty Day Subchronic Oral Toxicity Study of Pyridostigmine Bromide in Rats. Volume 1

    Science.gov (United States)

    1990-06-01

    Portage, MI) were used in this study. Tail tattoos were used to identify each animal individually. Four animals were used for necropsy quality controls...and brown pigment , probably hemosiderin, within splenic macrophages (Group 7A). However, the microscopic lesions were also observed in the controls...start of dosing: 141 - 272 g Identification procedures: Tail tattoo (SOP OP-ARG-1) Pretest conditioning: Quarantine/acclimation from 21 October - 3

  14. 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.

  15. 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.

  16. 40 CFR 798.2650 - Oral toxicity.

    Science.gov (United States)

    2010-07-01

    ... an adequate toxicological evaluation include: Analyses of lipids, hormones, acid/base balance....2650 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... considered appropriate to all studies: Electrolyte balance, carbohydrate metabolism, and liver and kidney...

  17. A chronic oral toxicity study of marine collagen peptides preparation from chum salmon (Oncorhynchus keta) skin using Sprague-Dawley rat.

    Science.gov (United States)

    Liang, Jiang; Pei, Xin-Rong; Zhang, Zhao-Feng; Wang, Nan; Wang, Jun-Bo; Li, Yong

    2012-01-01

    Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet.

  18. Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma.

    Science.gov (United States)

    Vail, D M; Husbands, B D; Kamerling, S G; Simpson, H; Kurzman, I D; McDonnell, A

    2012-01-01

    Idarubicin, a PO bioavailable anthracycline antibiotic-class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery. The primary objective of this study was to determine the maximally tolerated dose (MTD), dose-limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD. Client-owned dogs with measurable lymphoma. Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines. The MTD in dogs > 15 kg body weight was 22 mg/m(2) . Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol. PO administered idarubicin was generally well-tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated-dose, randomized clinical trials. Copyright © 2012 by the American College of Veterinary Internal Medicine.

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

    Science.gov (United States)

    1982-09-01

    Lewis-- 14 a ~1 A Lewis--15 TEST SUBSTANCE 1. Chemical name: 4-Nitrophenyl Methyl (Phenyl) Phosphinate Chemical Abstract Service Registry No.: None...11.25 2. Chemical name: Polysorbate 80 (Tween 80) Chemical Abstract Service Registry No.: 9005-65-6 Molecular structure: HO(C 2 40) ( C 2 H 4 )XOH...particularly in chronic toxicity studies in experimental data. APPENDIX A (Cant) Lewis--17 3. Chemical name: Citric Acid, monohydrate Chemical Abstract Service

  20. Polymer coated liposomes for use in the oral cavity - A study of the in vitro toxicity, effect on cell permeability and interaction with mucin

    DEFF Research Database (Denmark)

    Klemetsrud, Therese; Kjøniksen, Anna-Lena; Hiorth, Marianne

    2016-01-01

    (NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations...... formulations promising for oromucosal administration. Although the chitosan coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.......In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions.

    Science.gov (United States)

    Mukaratirwa, Sydney; Garcia, Begonya; Isobe, Kaori; Petterino, Claudio; Bradley, Alys

    2016-10-01

    This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.

  3. 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

    2017-03-10

    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 (Cmax), 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.

  4. Acute Oral Toxicity and Kinetic Behaviors of Inorganic Layered Nanoparticles

    Directory of Open Access Journals (Sweden)

    Jin Yu

    2013-01-01

    Full Text Available Layered double hydroxide (LDH nanoparticles, also known as anionic clays, have attracted a great deal of interest for their potential as delivery carriers. Recent studies showed that LDH nanoparticles can efficiently deliver drugs or bioactive molecules into cells, which are highly related to their endocytic pathway. However, the efficient cell permeation capacity of LDH may also raise concern about their toxicity potential. In this study, the acute oral toxicity of LDH nanoparticles was assessed, and their kinetic behaviors, such as plasma concentration-time curve, tissue distribution, and excretion, were also evaluated in mice. No significant effects of oral LDH nanoparticles on behaviors, body weight gain, survival rate, and organosomatic index were observed up to the dose of 2000 mg/kg for 14 days. Serum biochemical parameters did not significantly increase, indicating that LDH nanoparticles did not cause acute liver or kidney injury. Plasma concentration of LDH nanoparticles rapidly decreased within 30 min depending on exposure doses, but they did not accumulate in any specific organ. Their excretion via urine and feces was observed within 24 h. These findings suggest that LDH nanoparticles do not exhibit acute oral toxicity and favorable kinetic behaviors in mice and, therefore, will be promising candidates for biological and pharmaceutical applications.

  5. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    Science.gov (United States)

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  6. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  7. A 56-Day Oral Toxicity Study of the Aqueous Extract of Rapanea melanophloeos (L.) Mez in Rats

    Science.gov (United States)

    Mbaria, James M.; Thaiyah, Andrew G.; Thoithi, Grace N.; Gathumbi, Peter K.

    2016-01-01

    Rapanea melanophloeos is a tropical tree that is extensively utilized in African traditional medicine to treat helminthiases, tuberculosis, and heart-water. As with many other medicinal plants, there is insufficient information regarding the safety of therapeutic R. melanophloeos extracts. An aqueous extract of R. melanophloeos stem bark was administered to Sprague Dawley rats at doses of 100 mg/kg, 300 mg/kg, and 1000 mg/kg for 56 days to characterize its potential toxicity after prolonged dosing. Blood samples were obtained fortnightly for serum chemistry and hematology, while organs were collected at the end of the study. The extract caused an increase in organ weight indices of the kidneys and testis at 300 mg/kg and 1000 mg/kg. Hematological and biochemical examination revealed a drop in leukocyte counts and the hematocrit at 1000 mg/kg dose level, while there was a general but nondose-related elevation in alkaline phosphatase activity. There were time-associated variations in the hematological and clinical chemistry parameters at days 28, 42, and 56 in all dose levels, but most values remained within physiological limits. No pathological lesions were evident at histopathology after treatment with the extract. Our data shows that the aqueous extract of R. melanophloeos is not likely to be toxic at the doses tested and provides support to its medicinal use. PMID:28105062

  8. A 90-day oral (dietary) toxicity and mass balance study of corn starch fiber in Sprague Dawley rats.

    Science.gov (United States)

    Crincoli, Christine M; Nikiforov, Andrey I; Rihner, Marisa O; Lambert, Elizabeth A; Greeley, Melanie A; Godsey, Justin; Eapen, Alex K; van de Ligt, Jennifer L G

    2016-11-01

    The potential toxicity of corn starch fiber was assessed and compared to polydextrose, a commonly used bulking agent with a long history of safe use in the food supply. Groups of male and female Crl:CD(SD) rats were fed 0 (control), 1,000, 3,000, or 10,000 mg/kg-bw/day corn starch fiber in the diet for 90 days. The polydextrose reference article was offered on a comparable regimen at 10,000 mg/kg-bw/day. Following a single gavage dose of [(14)C]-corn starch fiber on study day 13 or 90, the mass balance of the test article was assessed by analysis of excreta samples collected from 0 to 168 h post-dose. There were no toxicologically or biologically relevant findings in any of the test article-treated groups. The few minor differences observed between the corn starch fiber and polydextrose exposed groups were considered to be due to normal biological variation. Following [(14)C]-corn starch fiber dosing, nearly complete excretion of the administered dose occurred over 168 h post-dosing, with the majority excreted in the feces. The dietary no-observed-adverse-effect level of corn starch fiber after 90 days was 10,000 mg/kg-bw/day. Similar toxicity profiles for corn starch fiber and polydextrose were observed due to the structural and compositional similarities of these materials.

  9. Neutral red uptake cytotoxicity tests for estimating starting doses for acute oral toxicity tests.

    Science.gov (United States)

    Stokes, William S; Casati, Silvia; Strickland, Judy; Paris, Michael

    2008-05-01

    In vitro cytotoxicity assays can be used as alternative toxicity tests to reduce the total number of animals needed for acute oral toxicity tests. This unit describes two methods for determining the in vitro cytotoxicity of test substances using neutral red uptake (NRU) and using the in vitro data to determine starting doses for in vivo acute oral systemic toxicity tests, e.g., the up-and-down procedure or the acute toxic class method. The use of the NRU methods to determine starting doses for acute oral toxicity tests may reduce the number of animals required, and for relatively toxic substances, this approach may also reduce the number of animals that die or require humane euthanasia due to severe toxicity. An interlaboratory validation study has demonstrated that the methods are useful and reproducible for these purposes. Two standardized protocols provide details for performing NRU tests with rodent and human cells.

  10. A subchronic (180-day) oral toxicity study of ethyl tertiary-butyl ether, a bioethanol, in rats.

    Science.gov (United States)

    Miyata, Katsumi; Koga, Takayuki; Aso, Sunao; Hoshuyama, Satsuki; Ajimi, Syozo; Furukawa, Kotaro

    2014-07-01

    A subchronic (180-day) toxicity study was conducted to evaluate the effects of ethyl tertiary-butyl ether (ETBE), a biomass fuel, in male and female rats. ETBE was administered at dose levels of 0, 5, 25, 100 and 400 mg/kg/body weight (b.w.)/day by gavage. No treatment-related adverse effects were observed at 5, 25 or 100 mg/kg. Centrilobular hypertrophy of hepatocytes was observed in males and females and their relative liver weights were increased, suggesting enhanced metabolic activity. From these results, we concluded that the no observed adverse effect level of ETBE was 100 mg/kg b.w./day under the conditions tested.

  11. Oral toxicity of bacterial toxins against thrips species

    NARCIS (Netherlands)

    Gerritsen, L.J.M.; Visser, J.H.; Jongsma, M.A.

    2004-01-01

    The oral toxicity of excretion products of several Photorhabdus and Xenorhabdus strains was tested on two thrips species: Frankliniella occidentalis and Thrips tabaci. Out of 46 Photorhabdus isolates and 6 Xenorhabdus isolates only 6 North American P. temperata isolates were toxic to the thrips spec

  12. Oral toxicity of bacterial toxins against thrips species

    NARCIS (Netherlands)

    Gerritsen, L.J.M.; Visser, J.H.; Jongsma, M.A.

    2004-01-01

    The oral toxicity of excretion products of several Photorhabdus and Xenorhabdus strains was tested on two thrips species: Frankliniella occidentalis and Thrips tabaci. Out of 46 Photorhabdus isolates and 6 Xenorhabdus isolates only 6 North American P. temperata isolates were toxic to the thrips

  13. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute oral toxicity. 799.9110 Section 799.9110 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... Part 792—Good Laboratory Practice Standards. (3) Test procedures—(i) Preparations. Healthy young...

  14. First-in-Human study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics and Pharmacodynamics, in Patients with Metastatic Cancer

    Science.gov (United States)

    Blagden, Sarah; Olmin, Aurelius; Josephs, Debra; Stavraka, Chara; Zivi, Andrea; Pinato, David J.; Anthoney, Alan; Decordova, Shaun; Swales, Karen; Riisnaes, Ruth; Pope, Lorna; Noguchi, Kohei; Shiokawa, Rie; Inatani, Michiyasu; Prince, Jenny; Jones, Keith; Twelves, Chris; Spicer, James; Banerji, Udai

    2014-01-01

    Purpose This Phase I dose-escalation study investigated the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary clinical activity of CH5132799. Patients and Methods Patients with metastatic solid tumors were eligible for the study. CH5132799 was administered orally once daily (QD) or twice daily (BID) in 28-day cycles. Results Thirty-eight patients with solid tumors received CH5132799 at 2-96 mg QD or 48-72 mg BID. The MTD was 48 mg on the BID schedule but was not reached on the QD schedule. DLTs were grade 3 elevated liver function tests (LFT), grade 3 fatigue, grade 3 encephalopathy, grade 3 diarrhea and grade 3 diarrhea with grade 3 stomatitis; all DLTs were reversible. Most drug-related adverse events were grade 1/2. Diarrhea (34%) and nausea (32%) were the most common events. Mean Cmax and AUC0-24 in steady state at MTD were 175 ng/ml and 1,550 ng·hr/ml respectively, consistent with efficacious exposure based on preclinical modelling. Reduction in SUVmax with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) was observed in five of seven patients at MTD. A patient with PIK3CA-mutated clear cell carcinoma of the ovary achieved a partial response by GCIG CA125 criteria and further, a heavily pre-treated patient with triple negative breast cancer had marked improvement in her cutaneous skin lesions lasting 6 cycles. Conclusion CH5132799 is well tolerated at the MTD dose 48 mg BID. At this dose the drug had a favorable PK and PD profile and preliminary evidence of clinical activity. PMID:25231405

  15. Acute and subacute oral toxicity of periodate salts in rats.

    Science.gov (United States)

    Lent, Emily May; Crouse, Lee C B; Eck, William S

    2017-02-01

    Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD50 up to LD50) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL10s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

  16. Aqueous extract of Senecio candicans DC induce liver and kidney damage in a sub-chronic oral toxicity study in Wistar rats.

    Science.gov (United States)

    Lakshmanan, Hariprasath; Raman, Jegadeesh; Pandian, Arjun; Kuppamuthu, Kumaresan; Nanjian, Raaman; Sabaratam, Vikineswary; Naidu, Murali

    2016-08-01

    Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P < 0.05) in serum uric acid, creatinine, aspartate transaminase (AST) and alanine transaminase (ALP) levels. Histological examination of liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use

  17. Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

    Science.gov (United States)

    Warheit, D B; Boatman, R; Brown, S C

    2015-12-01

    Six different commercial forms and sizes of titanium dioxide particles were tested in separate developmental toxicity assays. The three pigment-grade (pg) or 3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2) particle-types were evaluated for potential maternal and developmental toxicity in pregnant rats by two different laboratories. All studies were conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In addition, all test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively (see Table 1). The test substances were formulated in sterile water. In all of the studies, the formulations were administered by oral gavage to time-mated rats daily beginning around the time of implantation and continuing until the day prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD) 6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles), the formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats). The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal

  18. Oral and Topical Toxicity of Fipronil to Melon Fly and Oriental Fruit Fly (Diptera: Tephritidae)

    Science.gov (United States)

    BACKGROUND: The objective of this study was to develop basic oral and topical toxicity data for Fipronil in Solulys protein bait to wild melon fly, Bactrocera cucurbitae (Coquillett) and the oriental fruit fly, Bactrocera dorsalis (Hendel). RESULTS: For the oral study, both females and males were ...

  19. Oral toxicity of elephant foot yam (Amorphophallus paeoniifolius tuber in mice

    Directory of Open Access Journals (Sweden)

    Yadu Nandan Dey

    2017-02-01

    Full Text Available Context: Amorphophallus paeoniifolius tuber is an important constituent of Ayurvedic system of medicine. The tuber of this plant has high medicinal value and is consumed as a food. It is associated with acridity (itchy sensation in mouth and throat upon oral consumption and presence of high oxalates raphides. Aims: To evaluate the acute and subacute oral toxicity studies of methanolic (APME and aqueous (APAE extracts of Amorphophallus paeoniifolius tuber in Swiss albino mice according to OECD guidelines. Methods: In acute oral toxicity study, the mice were orally administered a single dose of APME or APAE (2000 mg/kg and clinical signs and mortality were observed for 14 days. In subacute (repeated dose oral toxicity study, the mice were administered once daily, orally with APME or APAE (1000 mg/kg up to 28 days. The parameters assessed were behavior, clinical signs, body weight, feed and water consumption, urinary, biochemical, hematological and major organ weights and histology. Results: In acute toxicity study, there was no treatment related mortality and morbidity in any of the group. In subacute toxicity study, there were no significant changes in behavior, body weight, feed and water consumption, urinary, biochemical, hematological and organ weight and histological parameters compared to vehicle treated group. There was no treatment related mortality or morbidity. Conclusions: Administration of methanolic and aqueous extracts of Amorphophallus paeoniifolius tuber, individually in acute and 28 days repeated dose in mice, did not exhibit any toxicity or adverse effect at the doses used.

  20. Oral Toxicity of 2,4-Dinitroanisole in Rats.

    Science.gov (United States)

    Lent, Emily May; Crouse, Lee C B; Wallace, Shannon M

    2016-11-01

    Subacute and subchronic studies were conducted to assess the toxicity of 2,4-dinitroanisole (DNAN) and to provide information important for protecting the health of military and civilian personnel. In the subchronic study, male and female Sprague-Dawley rats were dosed with DNAN via oral gavage at 0, 1.25, 5, 20, and 80 mg/kg/d. Likely owing to its conversion to 2,4-dinitrophenol, an inhibitor of energy homeostasis, DNAN caused an apparent increase in metabolism, leading to reduced feed efficiency ratios and body mass gains in males. Anemia, splenic enlargement, hemosiderosis, and extramedullary hematopoiesis indicated blood as a target organ, with females more sensitive than males. The DNAN was a testicular toxicant, causing decreased mass of testes and epididymides, as well as degeneration and atrophy of testicular seminiferous tubules and epididymal aspermia. Stereotypical behavior in males, gait irregularities, and cerebellar lesions indicated that DNAN is neurotoxic. Splenic enlargement, anemia, testicular toxicity, and neurotoxicity occurred only at or near lethal doses in the subchronic study. © The Author(s) 2016.

  1. Randomized study of nutritional status and treatment toxicities of oral arginine, glutamine, and Omega-3 fatty acids during concurrent chemoradiotherapy for head and neck cancer patients

    Directory of Open Access Journals (Sweden)

    Imjai Chitapanarux

    2016-03-01

    Full Text Available Background: Patients with head and neck cancer (HNC undergoing concurrent chemoradiotherapy (CCRT are at high risk of dysphagia, malnutrition, and immunosuppression. Arginine, glutamine, and Omega-3 fatty acidsare immune-enhanced nutrition that can promote cellular immunity.We aimed to examine the impact of immunonutrition diet on nutritional status, and CCRT toxicities, in this group of patients. Methods: Forty patients with HNC who treated with curative CCRT were randomized to: group A (n = 20, patients who received a regular diet and dietary counselingby a protocol dietician; group B (n = 20, patients who received a regular diet plus immune-enhanced nutrition supplements and dietary counseling by the same protocol dietician. Outcome measures were weight loss, protein and energy intake, serum pre-albumin and albumin, and toxicities of CCRT were evaluated at baseline, weekly and at the end of treatment. Results:Both groups were well balanced at baseline.One patient from group A (1/20 withdrew consent. Seven patients from group B (7/20 withdrew from the study; 1 patient could not tolerate the side effect of chemotherapy and 6 patients could not tolerate the taste of oral immune-enhanced nutrition.A significant loss in total body weight was observed in group A patients (p<0.001, whereas not significant loss in group B (p=0.109. Median percentage change from baseline of energy intake was 19.6%, and 22.9% at the end of treatment for group A, and B, respectively. The circulating levels of nutritional markers, pre-albumin and albumin decreased after CCRT in both groups. There was a significantly decreased level of albumin in group A more than group B, at the end of treatment. During CCRT; 4 patients (20% in group A and 1 patient(5% in group B developed grade 3 mucositis, respectively. One patient (5% in group A had grade 3 radiation dermatitis. Grade 3 – 4 hematologic toxicities, mainly in absolute neutrophil count (ANC were significant higher in

  2. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    Science.gov (United States)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  5. Subacute (28-day) toxicity of furfural in Fischer 344 rats: A comparison of the oral and inhalation route

    NARCIS (Netherlands)

    Arts, J.H.E.; Muijser, H.; Appel, M.J.; Kuper, C.F.; Bessems, J.G.M.; Woutersen, R.A.

    2004-01-01

    The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 d

  6. 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.

  7. Experimental oral lead toxicity in young dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stowe, H.D.; Goyer, R.A.; Krigman, M.M.; Wilson, M.; Cates, M.

    1973-02-01

    Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia, and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.

  8. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  9. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    OpenAIRE

    Sim, K. S.; A M Sri Nurestri; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereski...

  10. ACUTE AND SUB-CHORONIC ORAL TOXICITY OF ASIATICOSIDE TO MICE

    Directory of Open Access Journals (Sweden)

    Uvarajan Sampath

    2012-09-01

    Full Text Available The components in Centellaasiatica (gotukala, vallarai was reported to possess different biological activities in various in vitro and in vivo test models including gastric ulcer healing, wound healing, memory enhancing, immunomodulating effects along with cytotoxic, neuroprotective, antioxidant potential. Asiaticoside is one of the major triterpenoid saponin isolated from Centellaasiatica. Currently, there is no evidence for safety details of asiaticoside in experimental mice. The purpose of this study is to explore the acute and sub-chronic oral toxicities of asiaticoside. Acute oral toxicity study was conducted by giving 300-5000 mgkg-1 bodyweight of asiaticoside and the animals were observed after 1 h administration of the drug and also examined after 14 days of administration for mortality and morbidity.The lethal dose (LD50 was found to greater than 2000 mgkg⁻¹ bodyweight. In sub-chronic oral toxicity studies, the selected oral doses were 200, 500, 1000 mgkg⁻¹and the evaluation was carried out after 90 days of oral administration of asiaticoside. Biochemical, histopathological and hematological changes along with body and relative organ weights of the mice were analysed and significant changes were observed in the mice treated with 1000 mgkg-1 of asiaticoside.. The observed results were statistically analyzed using one way ANOVA which suggested that Asiaticoside does not possess any toxic effect up to 500mg/kg bodyweight and it is best suited for any kind of future application related to its efficacy.

  11. Activity, toxicity and analysis of resistance of essential oil from Chenopodium ambrosioides after intraperitoneal, oral and intralesional administration in BALB/c mice infected with Leishmania amazonensis: a preliminary study.

    Science.gov (United States)

    Monzote, Lianet; Montalvo, Ana M; Scull, Ramón; Miranda, Migdalia; Abreu, Juan

    2007-01-01

    The World Health Organization has classified the leishmaniasis as a major tropical disease. Current therapy is toxic, expensive and cause several adverse effects. The majority of people in endemic areas of leishmaniasis depend of natural and traditional medicine. This study was developed to examine the activity of the essential oil from Chenopodium ambrosioides in BALB/c mice infected with Leishmania amazonensis. The infected animals received two cycle of treatment by different routes (intraperitoneal, oral or intralesional route). The intraperitoneal administration of the essential oil at dose of 30 mg/Kg prevented lesion development and decrease the parasite burden. Oral administration retarded the infection in the experimental model compared with untreated mice, although it was less effective that the intraperitoneal route. The administration by intralesional route did not show activity. Intraperitoneal and oral treatment at 30 mg/Kg with the essential oil had better antileishmanial effect that treatment with the reference drug, amphotericin B at 1 mg/Kg. Preliminarily, we examined the toxicity and the resistance after treatment. Signs of toxicity were evident only in the animals treated by intraperitoneal route. No resistance was detected in L. amazonensis isolates obtained from treated mice. These data clearly demonstrated that this natural product could be an alternative for the development of a new drug against cutaneous leishmaniasis based in the ethnomedical information.

  12. Acute Oral Toxicity of Nitroguanidine in Mice

    Science.gov (United States)

    1988-04-01

    microscopic examination. These areas did not respond t o special bacterial stains and may have been due to mouse hepa t i tis virus . Mic r oscopic...Observation Study i Animal Receipt Dosinq Teri od Termination J 4 84C00440 22 24 Dead 84C00445 20 2 b Dead 84C00446 22 28...iiisfil ’iy noin«’ Iwp.ititio virus . An mal ID*! 84C003<»7 P.it.holooy Af-ci’ssion »•■ 30)17. Slide 19A! Eye

  13. Acute oral toxicities of wildland fire control chemicals to birds

    Science.gov (United States)

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  14. Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents

    Institute of Scientific and Technical Information of China (English)

    Arunachalam Muthuraman; Nirmal Singh

    2012-01-01

    Objective: To determine the acute and sub-acute oral toxicity profile of the hydroalcoholic extract of Acorus calamus (HAE-AC) in mice and rats respectively. Methods: In acute toxicity study, mice were assessed to any alteration of general behavior and mortality rate within 24 h. Further, in sub-acute toxicity study, rats were used for assessment of mortality, body weight, hematological, biochemical and histopathological changes. Results: Single oral administrations of the HAE-AC 2500-10000 mg/kg induced increase in general behavioral abnormalities in mice. The mortality rate also increased with increasing dosage (median lethal dose; LD50 = 5 070.59 mg/kg). Daily single oral doses of HAE-AC 200, 500 and 1 000 mg/kg were observed to be well tolerated behaviorally after 28 days of dosing and induced no significant changes in body and organs weights of rats. Further, a mild rise in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and histopatholological changes in liver tissue was noted at 1000 mg/kg dose of HAE-AC. Conclusions: Overall, the findings of this study indicate that, HAE-AC is non-toxic and has at high dose, a mild but acceptable toxicity potential.

  15. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    Directory of Open Access Journals (Sweden)

    K S Sim

    2010-01-01

    Full Text Available Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia.

  16. In vitro examination of oral tissue conditioners potential toxicity

    Directory of Open Access Journals (Sweden)

    Krunić Nebojša

    2011-01-01

    Full Text Available The oral tissue conditioners are applied temporarily to the gingival surface of a denture for the purpose of reconditioning the abused denture supporting tissues, allowing them to return to a normal, healthy state. According to chemical composition they can be classified into methacrylic and silicon conditioners. The objective of this research was to examine the potential toxicity of one, seven and thirty day extracts of different concentrations. Different effective concentrations (5, 12.5, 25 and 50% of two silicone and four methacrylic conditioners extracts were used after extraction period of one, seven and thirty days. Amount of toxic substances and dynamics of their release were monitored by high-pressure liquid chromatography (HPLC. HPLC analysis could not be applied to the silicone conditioners because they consist of polymeric and inorganic 19 substances. Evaluation of cell proliferation, as cytotoxic parameters, was done by Mosmann’s MTT assay based on reduction of yellow tetrazole (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide - MTT to purple formazan by mitochondrial succinate dehydrogenase of metabolic active cells. With increasing of extraction period, the amount of released potential toxic substances increased. The cytotoxicity of tested materials significantly increased with extract concentration increase and duration of extraction period. To improve the biological characteristics of mobile dentures relined by soft materials, soaking in water the day before insertion into patient’s mouth was recommended. Silicone conditioners showed less cytotoxicity compared to the methacrylic conditioners, so they are more appropriate for daily dental practice.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. 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.

  19. Acute and sub-acute oral toxicity of Brazilian red propolis in rats.

    Science.gov (United States)

    da Silva, Rafaela Oliveira; Andrade, Valléria Matos; Bullé Rêgo, Ester Seixas; Azevedo Dória, Grace Anne; Santos Lima, Bruno Dos; da Silva, Francilene Amaral; de Souza Araújo, Adriano Antunes; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cordeiro Cardoso, Juliana; Zanardo Gomes, Margarete

    2015-07-21

    Propolis is a bee product widely used in folk medicine due to its numerous pharmacological properties. However, samples from different regions can differ in chemical composition, effectiveness, and side effects. Despite the widespread use of Brazilian red propolis, which is an isoflavone-rich variety, its toxicity has not been carefully studied. To assess the acute and sub-acute toxicity of the hydroethanolic extract of red propolis (HERP) administered orally to rats. HERP for the acute (300mg/kg) and sub-acute (10, 100 and 200mg/kg) toxicity studies was administered orally to rats according to OECD Guidelines 420 and 407, respectively. Clinical signs were identified, and hematological and biochemical analyses were performed. Water and food uptake as well as body and organ weights of animals were recorded. The acute study revealed no lethal effects at 300mg/kg of HERP, but toxic signs were observed, as HERP had an LD50 of more than 300mg/kg, indicating a warning. The most toxic signals in sub-acute studies were observed in males at a dose of 200mg/kg HERP. These results suggest estrogen-like activity, possibly from the isoflavones in HERP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    Science.gov (United States)

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  1. Toxicity Studies on "840 Biologic Pesticide"

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    [Objective] "840 Biologic Pesticide" is a very effective biologic pesticide. It consists of Abamectin and celastrus angulatus. Toxicity study was aimed to provide scientific toxicological basis. [Methods] The acute toxicity test,Ames test,micronucleus test and testicle chromosome aberration test were done. [Results] The acute toxicity of single dose of "840 Biologic Pesticide" showed that acute oral LD50 for female and male rats are 4 300 and 4 280 mg/kg,and for female and male mice are 2 330 and 5 110 mg/kg,respectively. The dermal LD50 was >2 000 mg/kg for female and male rats. The mutagenesis studies indicated that Ames test,micronucleus test and testicle chromosome aberration test were negative. [Conclusion] Tested pesticidc belongs to low toticity grade.

  2. Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract from Croton stellatopilosus Ohba

    Directory of Open Access Journals (Sweden)

    Chatchai Chaotham

    2013-01-01

    Full Text Available Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50=10.25 g/kg. The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day. These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

  3. Reduced Glutathione Mediates Resistance to H2S Toxicity in Oral Streptococci.

    Science.gov (United States)

    Ooi, Xi Jia; Tan, Kai Soo

    2016-01-22

    Periodontal disease is associated with changes in the composition of the oral microflora, where health-associated oral streptococci decrease while Gram-negative anaerobes predominate in disease. A key feature of periodontal disease-associated anaerobes is their ability to produce hydrogen sulfide (H2S) abundantly as a by-product of anaerobic metabolism. So far, H2S has been reported to be either cytoprotective or cytotoxic by modulating bacterial antioxidant defense systems. Although oral anaerobes produce large amounts of H2S, the potential effects of H2S on oral streptococci are currently unknown. The aim of this study was to determine the effects of H2S on the survival and biofilm formation of oral streptococci. The growth and biofilm formation of Streptococcus mitis and Streptococcus oralis were inhibited by H2S. However, H2S did not significantly affect the growth of Streptococcus gordonii or Streptococcus sanguinis. The differential susceptibility of oral streptococci to H2S was attributed to differences in the intracellular concentrations of reduced glutathione (GSH). In the absence of GSH, H2S elicited its toxicity through an iron-dependent mechanism. Collectively, our results showed that H2S exerts antimicrobial effects on certain oral streptococci, potentially contributing to the decrease in health-associated plaque microflora. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. 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.

  5. Strain differences in toxicity of oral cadmium intake in rats.

    Science.gov (United States)

    Ninkov, Marina; Popov Aleksandrov, Aleksandra; Mirkov, Ivana; Demenesku, Jelena; Mileusnic, Dina; Jovanovic Stojanov, Sofija; Golic, Natasa; Tolinacki, Maja; Zolotarevski, Lidija; Kataranovski, Dragan; Brceski, Ilija; Kataranovski, Milena

    2016-10-01

    Influence of genetic background on toxicity of oral cadmium (Cd) administration (30 days, in drinking water; 5 ppm and 50 ppm of cadmium) was examined in Albino Oxford (AO) and Dark Agouti (DA) rats. Similar cadmium deposition was noted in gut and draining mesenteric lymph nodes (MLN) of both strains but intensity and/or the pattern of responses to cadmium in these tissues differ. Less intense intestinal damage and leukocyte infiltration was observed in gut of cadmium-exposed AO rats. While gut-associated lymph node cells of DA rats responded to cadmium with an increase of cell proliferation, oxidative activity, IFN-γ, IL-17 production and expression, no changes of these activities of MLN cells of cadmium-treated AO rats were observed. Spleen, which accumulated cadmium comparable to MLN, responded to metal by drop in cell viability and by reduced responsiveness of proliferation and cytokine production to stimulation in DA rats solely, which suggest tissue dependence of cadmium effects. More pronounced cadmium effects on MLN and spleen cells of DA rats (which accumulated similar cadmium doses as AO rats), showed greater susceptibility of this strain to cadmium. The results presented, for the first time, depict the influence of genetic background to effects of oral cadmium administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail

    Science.gov (United States)

    Hill, E.F.; Soares, J.H.

    1987-01-01

    The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

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

    OpenAIRE

    Chandrasekaran Chinampudur Velusami; Srinivasa Rao Boddapati; Srikanth Hongasandra Srinivasa; Edwin Jothie Richard; Joshua Allan Joseph; Murali Balasubramanian; Amit Agarwal

    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 m...

  8. Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

    Science.gov (United States)

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Vega, Yamile; Torres, Leonid

    2011-05-01

    We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low.

  9. Studies on the subchronic oral toxicity of neem oil in mice%印楝油对小鼠的亚慢性经口毒性研究

    Institute of Scientific and Technical Information of China (English)

    石东霞; 蒋忠荣; 殷中琼; 龙兴发; 李太强; 贾仁勇; 徐娇; 张玉群; 杨帆

    2011-01-01

    To determine the subchronic oral toxicity of neem oil in mice,eighty mice were divided into three experiment groups and one control group at random. The mice in the 3 experiment groups were orally administrated with neem oil(mixed with 10 g/L CMC) at the doses of 177,533 and 1 600 mg/kg for 90 days respectively,and the mice in the control group were orally administrated with 10 g/L CMC at the dose of 533 mg/kg, then continued to observe for 30 days post-the last administration with neem oil. On day 90 and 120 post-beginning of administration, the general clinical manifestations, serum biochemistry, organ coefficients of the heart, liver, spleen,lung, and kidney were determined,and the histopathological changes of the heart, liver, spleen, lung, kidney and testicle were observed. The serum biochemistry and the organ coefficients of heart, liver, spleen, lung and kidney in the 3 experiment groups were not statistically different from those in the control group. On day 90 post-beginning of administration,the pathological examinations showed that 177 and 533 mg/kg doses of neem oil had low damage on each organ,such as slight vascular congestion,while 1 600 mg/kg dose of neem oil had damage on each organ to some extent,mainly degeneration on cells. After recovery for 30 days,the degree of injury to the tissues was lessened or even to be the restored. The level at which no adverse effects was 177 mg/kg for mice and the target organs of neem oil were determined to be the testicle,liver and kidneys.%为研究印楝油对小鼠的亚慢性经口毒性作用,确定印楝油的最大无作用剂量和毒作用靶器官,取健康小鼠80只,随机分成3个试验组和1个对照组,每日9点对各试验组小鼠经口给予177、533和1600mg/kg的印楝油混悬液(用10 g/L羧甲基纤维素钠与其混悬),对照组则给予533 mg/kg的10 g/L羧甲基纤维素钠溶液,连续90 d,停药后继续观察30 d.试验90 d和120 d后分别观察记录各组小鼠的一般临床

  10. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    Science.gov (United States)

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  11. Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice.

    Science.gov (United States)

    Mehta, Amit Kumar; Arora, Naveen; Gaur, Shailendra Nath; Singh, Bhanu Pratap

    2009-08-01

    Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined.

  12. Acute Oral Toxicity of Methanolic Seed Extract of Cassia fistula in Mice

    Directory of Open Access Journals (Sweden)

    Sreenivasan Sasidharan

    2011-06-01

    Full Text Available Background and objective: Cassia fistula is widely used in traditional medicine to treat various types of ailments. The evaluation of toxic properties of C. fistula is crucial when considering public health protection because exposure to plant extracts can result in undesirable effects on consumers. Hence, in this study the acute oral toxicity of C. fistula seeds extract was investigated in mice. Results: Oral administration of crude extract at the highest dose of 5000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that C. fistula in nontoxic. Throughout 14 days of the treatment no changes in behavioural pattern, clinical sign and body weight of mice in both control and treatment groups. Also there were no any significant elevations observed in the biochemical analysis of the blood serum. Further, histopathological examination revealed normal architecture and no significant adverse effects observed on the kidney, heart, liver, lung and spleen. Conclusions: Overall, the results suggest that, the oral administration of C. fistula methanolic seeds extract did not produce any significant toxic effect in mice. Hence, the extract can be utilized for pharmaceutical formulations.

  13. In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy adult mice.

    Science.gov (United States)

    Hassankhani, Ramin; Esmaeillou, Mohammad; Tehrani, Ali Asghar; Nasirzadeh, Keyvan; Khadir, Fatemeh; Maadi, Hamid

    2015-01-01

    The increasing use of silica nanoparticles (SiNPs) in various applications including industrial, agriculture, and medicine has raised concerns about their potential risks to human health. Various nanotoxicity researches have been done on the assessment of SiNPs' toxic effects; however, a few in vivo investigations exist. In this investigation, an in vivo study was done in order to evaluate the oral toxicity of SiNPs. The biochemical levels of 19 different serum parameters were assessed. Moreover, the histopathological changes have been examined as well. We showed that SiNPs with diameters of 10-15 nm in size can cause significant changes in albumin, cholesterol, triglyceride, total protein, urea, HDL, and LDL as well as in alkaline phosphatase and aspartate aminotransferase activity. In addition, histopathological examinations demonstrated that SiNPs have toxic effects on various tissues including liver, kidney, lung, and testis.

  14. Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.

    Science.gov (United States)

    Schauss, A G; Somfai-Relle, S; Financsek, I; Glavits, R; Parent, S C; Endres, J R; Varga, T; Szücs, Z; Clewell, A

    2009-01-01

    The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

  15. Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

    Science.gov (United States)

    Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

    2016-01-01

    Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

  16. 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.

  17. Toxicidad aguda oral de la o-vainillina Acute oral toxicity of o-vanillin

    Directory of Open Access Journals (Sweden)

    Yamisleydi Alonso Moreno

    2008-04-01

    Full Text Available El 2-hidroxi-3-metoxibenzaldehído (o-vainillina posee una probada actividad anti sickling y una baja actividad hemolítica sobre hematíes SS y normales, por lo que puede ser eficaz en el tratamiento de la anemia drepanocítica, enfermedad genética de alta prevalencia a nivel global. En este sentido se desarrolló un estudio de toxicidad aguda oral, con el objetivo de determinar sus efectos adversos. Se administró una dosis de 2 000 mg/kg de peso corporal a un grupo de ratas (3 hembras y 3 machos y el vehículo a otro grupo utilizado como control. Los animales se mantuvieron en observación durante 14 días, se determinaron las variaciones de peso, la presencia o no de síntomas y signos clínicos, y la necropsia al finalizar el estudio. Como resultado no se observó disminución del peso corporal en ninguno de los grupos experimentales, presentaron síntomas como: piloerección, respiración acelerada, actividad disminuida, acicalamiento, aislamiento a la esquina de la caja y la muerte de un animal. El análisis macroscópico de los órganos no detectó variación alguna. La DL50 de la o-vainillina se encuentra por encima de 2 000 mg/kg de peso corporal, según el sistema global armonizado2-hydroxy-3-methoxybenzaldehyde (o-vanillin has a proven anitsickling activity and a low haemolytic activity on SS and normal red corpuscles, so it may be efficient in the treatment of drepanocytic anemia, a genetic disease of high prevalence at the world level. In this sense, an acute oral toxicity study was conducted aimed at determining its adverse effects. A dose of 2 000 mg/kg of body weight was administered to a group of rats (3 females and 3 males, where the vehicle was given to the control group. The animals were observed for 14 days. The variations of weight, the presence or not of symptoms and clinical signs, and the necropsy at the end of the study were determined. Body weight reduction was not observed in any of the experimental groups. They

  18. Investigation of repeated dose (90 day oral toxicity, reproductive/developmental toxicity and mutagenic potential of ‘Calebin A’

    Directory of Open Access Journals (Sweden)

    Muhammed Majeed

    2015-01-01

    Full Text Available The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as “No Observed Adverse Effect Level (NOAEL” under the test conditions.

  19. Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism.

    Science.gov (United States)

    Hsu, Chih-Hsiang; Lin, Ching-Lung; Wang, Sheue-Er; Sheu, Shuenn-Jyi; Chien, Chiang-Ting; Wu, Chung-Hsin

    2015-01-01

    The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males.

  20. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    Science.gov (United States)

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

  1. Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats.

    Science.gov (United States)

    Prabu, P C; Panchapakesan, S; Raj, C David

    2013-08-01

    Withania somnifera is a widely used medicinal plant for several disorders. Toxicity studies on Withania somnifera are not available. Acute and sub-acute oral toxicities of Withania somnifera root extract in Wistar rats were evaluated in the present study. In the acute toxicity study, WSR extract was administered to five rats at 2000 mg/kg, once orally and were observed for 14 days. No toxic signs/mortality were observed. In the sub-acute study, WSR extract was administered once daily for 28 days to rats at 500, 1000 and 2000 mg/kg, orally. No toxic signs/mortality were observed. There were no significant changes (P < 0.05) in the body weights, organ weights and haemato-biochemical parameters in any of the dose levels. No treatment related gross/histopathological lesions were observed. The present investigation demonstrated that the no observed adverse effect level was 2000 mg/kg body weight per day of hydroalcoholic extract of W. somnifera in rats and hence may be considered as non-toxic.

  2. Can TiC nanoparticles produce toxicity in oral administration to rats?

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    Julie Laloy

    2014-01-01

    Conclusion: No sign of toxicity was found after oral administration. TiC was excreted mostly in feces producing mineral absorption alterations. Low traces were retrieved in urine, indicating that TiC can cross the intestinal barrier.

  3. Acute Oral Toxicity Potential of 4-Nitrophenyl Methkyl Phenyl Phosphinate.

    Science.gov (United States)

    1982-09-01

    methyl phenyl phosphinate Chemical Abstract Service Registry No.: None Molecular structure: C Ii NO P 13 12 4 .0 0~ NO., CH3 o o...C 56.33 56.17 H 4.36 4.28 N 5.05 5.14 P 11.17 11.25 2. Chemical Name: Polysorbate 80 (Tween 80) Chemical Abstract Service Registry No.: 9005-65-6...administration particularly in chronic toxicity studies in experimental data. 3. Chemical Name: Citric Acid, monohydrate Chemical Abstract Service

  4. Modelling acute oral mammalian toxicity. 1. Definition of a quantifiable baseline effect.

    Science.gov (United States)

    Koleva, Yana K; Cronin, Mark T D; Madden, Judith C; Schwöbel, Johannes A H

    2011-10-01

    Quantitative structure-activity relationships (QSARs) provide a useful tool to define a relationship between chemical structure and toxicity and allow for the prediction of the toxicity of untested chemicals. QSAR models based upon an anaesthetic or narcosis mechanism represent a baseline, or minimum, toxicity, i.e. unless a chemical acts by another, more specific, mechanism, its toxicity will be predicted by such models. The aim of this investigation was to develop baseline models for the acute toxicity of chemicals to mammals (rat and mouse) following the oral route of administration. The availability of such baseline toxicity models for mammalian species can provide a probe for testing new chemicals with respect to their molecular mechanism of toxicity. Multiple-regression type structure-toxicity relationships were derived . (i.e., from oral log LD(50)(-1) data for mammalian species (rat and mouse) and the 1-octanol/water partition coefficient (log P) of classic non-polar narcotics). Subsequently, these models were used to distinguish between reactive chemicals of different mechanistic domains and baseline toxic chemicals. Comparison of measured toxicity data for oral rat and mouse LD(50) with predictions from baseline QSAR provides a means of identifying mechanistic categories and for categorising more specific acute mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil

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    Ghader Jalilzadeh-Amin

    2015-02-01

    Full Text Available Objectives: Mentha longifolia L. (Lamiaceae is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acute toxicity evaluation, rats were orally administrated with single dose of EOML at doses ranging from 10 to 1000 mg/kg. Results: EOML caused a significant (p

  6. Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism

    OpenAIRE

    Hsu CH; Lin CL; Wang SE; Sheu SJ; Chien CT; Wu CH

    2015-01-01

    Chih-Hsiang Hsu,1 Ching-Lung Lin,1 Sheue-Er Wang,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the ...

  7. Relationship between lethal toxicity in oral administration and injection to mice: effect of exposure routes.

    Science.gov (United States)

    Wang, Yu; Ning, Zhong H; Tai, Hong W; Long, Shuang; Qin, Wei C; Su, Li M; Zhao, Yuan H

    2015-03-01

    The lethal toxicity (LD₅₀) in oral administration, intravenous, intraperitoneal, intramuscular and subcutaneous injections were used to investigate relationships of log 1/LD₅₀ from different exposure routes. Regression analysis showed that log 1/LD₅₀ in oral route was related to the toxicity in injection route. This relationship in lethality between the two routes is apparently due to the same mechanisms of the compounds to the same species. However, the scatter in the correlation curve indicates that exposure route is an important factor that influences the relationship. Some compounds with low intestinal absorption exhibit much less toxicity in oral administration than that in the injection route. A systemic bias of log 1/LD₅₀ between oral and injection routes indicates that tissue distribution of compounds between blood and target site is a very rapid process, leading to log 1/LD₅₀ in injection greater than those in oral administration. Although compounds can be metabolized in the body both from oral and injection routes, first-pass metabolism occurs in oral route but not in injection route. This will result in decrease of toxicity in oral route for most compounds as compared with injection route. In addition, experimental uncertainty, differences in gender, and species can also affect relationships of log1/LD₅₀ between exposure routes.

  8. Acute and chronic oral toxicity of standardized water extract from the fruit of Phyllanthus emblica Linn.

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    K Jaijoy

    2010-03-01

    Full Text Available Summary: Phyllanthus emblica Linn. (Euphorbiaceae is an herbal plant commonly used in Asian traditional medicine systems for treatment of many disorders. In the present study, we investigated for the first time acute and chronic toxicity of the standardized water extract of P. emblica fruit. The water extract of P. emblica was prepared according to the Thai Herbal Pharmacopoeia and standardized to 20% gallic acid. For studying acute toxicity study, single oral dose of 5000 mg water extract /kg body weight was administered to Sprague Dawley rats (five females, five males. The results showed no toxicity in terms of general behavior change, mortality, or change in gross appearance of internal organs (LD50 > 5,000 mg/kg. Chronic toxicity was studied by daily oral dose (ten females, ten males of 300, 600 and 1,200 mg/kg for 270 days. The results showed slightly significant differences in the body and organ weights between the control and treatment groups. In addition, the rats were analyzed for final body and organ weights, necropsy, and hematological, blood chemical and histopathological parameters. Hematological analysis and clinical blood chemistry revealed slightly changes, but were within the normal limits. No gross or histopathology findings were observed in the treatment groups. Altogether, the standardized water extract from the fruit of P. emblica did not produce acute and chronic toxicity in its traditional uses. Industrial relevance: Traditional medicine is still stronghold of more than 50% of the world population, especially in developing countries. Nowadays, a number of medicinal plants (such as Phyllanthus emblica Linn. are commercially available on local markets as a tonic, food and/or dietary supplement product commonly used for clinical management of several conditions. Despite the widespread use of this plant, there is still little literature on the scientific evaluation of their toxicity. Results of the current study provide

  9. Epidemiological studies of oral cancer.

    Science.gov (United States)

    Pindborg, J J

    1977-06-01

    The FDI has shown considerable interest in the oral cancer and has in recent years arranged three symposia on the subject. The incidence of oral cancer shows marked geographic differences mostly depending upon environmental factors. In the present paper the epidemiology of oral cancer is illustrated by the relative frequency to total number of cancers and incidence rates from a number of countries. Canada has the highest rate of cancer of the vermilion border, which is extremely rare among dark-skinned people. Even within one country differences may be found, a fact which is illustrated by findings from Czechoslovakia and India. In most of the studies dealing with the etiology of oral cancer tobacco usage in its various forms is shown to be the outstanding factor.

  10. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

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    Jumpei Washio

    2016-06-01

    Full Text Available Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  11. Assessment of thirteen-week subchronic oral toxicity of cyadox in Beagle dogs.

    Science.gov (United States)

    Wang, Xu; Zhou, Wen; Ihsan, Awais; Chen, Dongmei; Cheng, Guyue; Hao, Haihong; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-11-01

    Cyadox (2-formylquinoxaline-N(1),N(4)-dioxide cyanocetylhydrazone) is a new antimicrobial agent and growth-promoter to be used in food-producing animals. Although its toxicity has been clearly documented in rodents, no study is available in non-rodent animals. Therefore, we studied the subchronic effects of cyadox in Beagle dogs to provide additional information with which to establish safety criteria for human exposure. For this purpose, 36 Beagle dogs, 18 males and 18 females, were divided into four groups and fed diets containing 0, 100, 450 and 2500 mg/kg of cyadox, respectively, for 13 weeks. It was found that there were no significant changes among the examined parameters, except for an increase in the level of serum potassium (K(+)) in 2500 mg/kg cyadox group in males at week 13 of the study. However, the K(+) level returned to normal during the recovery period. In conclusion, cyadox showed slight effects in Beagle dogs in the subchronic oral toxicity study. The no-observed-adverse-effect level of cyadox was considered to be 450 mg/kg diet, which equates to approximately 15.3-15.4 mg/kg b.w./day. The study provided subchronic effects of cyadox in Beagle dogs, suggesting that cyadox might present mild toxicity in non-rodents.

  12. Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone.

    Science.gov (United States)

    Xiao, Yingying; Zhu, Yewei; Yu, Suhong; Yan, Cuicui; Ho, Rodney J Y; Liu, Jian; Li, Tao; Wang, Jie; Wan, Liyuan; Yang, Xingtian; Xu, Huo; Wang, Jichuang; Tu, Xiaohuang; Jia, Lee

    2016-01-01

    Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs. The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses. Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight. The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses.

  13. 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; Joseph, Joshua Allan; Balasubramanian, Murali; Agarwal, Amit

    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.

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

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    Chandrasekaran Chinampudur Velusami

    2013-01-01

    Full Text Available 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.

  15. Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats

    Institute of Scientific and Technical Information of China (English)

    Siti Balkis BUDIN; Seri Masran SITINOR AIN; Baharuddin OMAR; Izatus Shima TAIB; Othman HIDAYATULFATHI

    2012-01-01

    Litsea elliptica Blume has been traditionally used to treat headache,fever,and stomach ulcer,and has also been used as an insect repellent.The acute and subacute toxicities of L.el/iptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats.For the acute toxicity study,L.e//iptica essential oil was administered in doses from 500 to 4000 mg/kg (single dose),and in the subacute toxicity test,the following doses were used:125,250,and 500 mg/kg,for 28 consecutive days.In the acute toxicity study,L.elliptica essential oil caused dose-dependent adverse behaviours and mortality.The median lethal dose value was 3488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg.The subacute toxicity study of L.elliptica essential oil did not reveal alterations in body weight,and food and water consumptions.The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined,except for the hemoglobin,mean cell hemoglobin concentration,mean cell volume,mean cell hemoglobin,serum albumin,and serum sodium.However,these differences were still within the normal range.No abnormalities or histopathological changes were observed in the liver,pancreatic islet of Langerhans,and renal glomerulous and tubular cells of all treated groups.In conclusion,L.el/iptica essential oil can be classified in the U group,which is defined as a group unlikely to present an acute hazard according to World Health Organization (WHO) classification.

  16. 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.

  17. Drinking water toxicity study of the environmental contaminant--Bromate.

    Science.gov (United States)

    Dongmei, Liu; Zhiwei, Wang; Qi, Zhu; Fuyi, Cui; Yujuan, Shan; Xiaodong, Liu

    2015-12-01

    Bromate is a byproduct of water disinfection that is produced when waters contain bromide treated with ozone. To investigate the level of the toxicity of bromate and find the most sensitive indicators in a short time, a series of toxicological assessments were conducted including the acute toxicity, cumulative toxicity, genetic toxicity and subacute toxicity of bromate (using Potassium Bromate to represent bromate). The LD50 of orally administered Potassium Bromate was 215 mg/kg in Wistar rats and 464 mg/kg in ICR mice. The cumulative toxicity of Potassium Bromate was not obvious. The Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test did not indicate mutagenicity. The results of the subacute study did not exhibit significant differences in most of the parameters, except the white blood cell count, which was significantly decreased in male rats. In addition, Potassium Bromate influenced the albumin, creatinine, total cholesterol, triglycerides and glucose levels in male rats to various extents. A thorough analysis of the above tests clearly demonstrates that bromate has toxicity, not obvious cumulative toxicity and the white blood cell count can be used as an indicator to reflect the toxicity of bromate and investigate bromate's toxic mechanism.

  18. Acute oral toxicity of the herbicide BUREX EKO in pheasants.

    Science.gov (United States)

    Legáth, J; Mlynarcíková, H; Svický, E; Lenhardt, L; Kacmár, P; Benová, K; Kovác, G

    1996-12-01

    The aim of this study was to determine the acute LD50, clinical symptoms and pathological changes of acute BUREX EKO intoxication in pheasants according to OECD No 205. Medium lethal dose (LD50) of BUREX EKO in pheasant is 3.84 ml/kg body weight with the upper level of reliability 4.50 ml and lower level of reliability 3.27 ml/kg body weight. As far as the calculation to the effective substance is concerned it is 1077 mg of chloridazone per kg body weight with the interval of reliability from 919 to 1263 mg/kg body weight. Calculated the effective substance of chloridazone (3.84 ml is LD50 of BUREX EKO which contains 1077 mg of chloridazone) BUREX EKO can be classified as the moderately toxic substance to pheasants. There were following clinical symptoms of the BUREX EKO intoxication in pheasants: apathy, drowsiness, incapability to move, ruffled feathers, slight diarrhoea, strenuous respiration, tonico-clonical cramps before death, decease with the head expressively bent rearwards. There was a relatively fast beginning of rigor mortis in dead pheasants. Pathologico-anatomical dissection of the pheasants obtained under conditions of acute intoxication did not reveal any changes on the organs of both experimental and control pheasants which would be immediately connected with the effect of the administered substance. Hyperaemia was recorded by histologico-pathological investigation of the liver and kidneys. No changes on the brain and intestine wall were recorded.

  19. Subchronic (13-week) oral toxicity of neohesperidin dihydrochalcone in rats.

    Science.gov (United States)

    Lina, B A; Dreef-van der Meulen, H C; Leegwater, D C

    1990-07-01

    Neohesperidin dihydrochalcone was administered to groups of 20 male and 20 female Wistar rats at dietary levels of 0, 0.2, 1.0 and 5.0% for 91 days. No treatment-related ophthalmoscopical, haematological or histopathological effects were observed. In the high-dose group, a marked caecal enlargement occurred in both sexes, accompanied by soft stools in the early stages of the study, somewhat lower plasma urea concentrations and increased plasma alkaline phosphatase activity and a decreased urinary pH. This group also showed slight growth depression accompanied by transient reduction in food intake; in males the body weights remained relatively low throughout the experimental period. Furthermore, bilirubin level was increased in females and total protein level was decreased in males of the high-dose group. The above changes were considered adaptive responses or chance effects rather than manifestations of clear toxicity. The low-and intermediate- dose groups did not show any compound-related untoward effect. It was concluded that the intermediate dose, providing an overall intake of about 750 mg neohesperidin dihydrochalcone per kg body weight per day, was the no-effect level.

  20. 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

  1. Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism

    Directory of Open Access Journals (Sweden)

    Hsu CH

    2015-05-01

    Full Text Available Chih-Hsiang Hsu,1 Ching-Lung Lin,1 Sheue-Er Wang,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group and the B401 (50 mg/kg group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO production, levels of neuronal nitric oxide synthase (nNOS and endothelial nitric oxide synthase (eNOS, expression levels of factors governing angiogenesis (vascular endothelial growth factor, oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal, inflammation (tumor necrosis factor alpha, apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3 were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in

  2. One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

    Science.gov (United States)

    Zeljenková, Dagmar; Aláčová, Radka; Ondrejková, Júlia; Ambrušová, Katarína; Bartušová, Mária; Kebis, Anton; Kovrižnych, Jevgenij; Rollerová, Eva; Szabová, Elena; Wimmerová, Soňa; Černák, Martin; Krivošíková, Zora; Kuricová, Miroslava; Líšková, Aurélia; Spustová, Viera; Tulinská, Jana; Levkut, Mikuláš; Révajová, Viera; Ševčíková, Zuzana; Schmidt, Kerstin; Schmidtke, Jörg; Schmidt, Paul; La Paz, Jose Luis; Corujo, Maria; Pla, Maria; Kleter, Gijs A; Kok, Esther J; Sharbati, Jutta; Bohmer, Marc; Bohmer, Nils; Einspanier, Ralf; Adel-Patient, Karine; Spök, Armin; Pöting, Annette; Kohl, Christian; Wilhelm, Ralf; Schiemann, Joachim; Steinberg, Pablo

    2016-10-01

    The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.

  3. One‑year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

    NARCIS (Netherlands)

    Kleter, G.A.; Kok, E.J.

    2016-01-01

    The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in

  4. Preliminary Assessment of the Oral Toxicity of 1-5-Diazido-3-Nitrazapentane, 2- and 6-Week Feeding Study, Male and Female Rats

    Science.gov (United States)

    1993-02-01

    TAB Unanounced Just1ficato 0, Distribution/ •-• ~~Avallabillty Codoegl IL Dfat f dpeelar - -- I. l Y ma DEPARTMENT OF THE ARMY U. S. ARMY...May 91 Sep 92 TABLE 3. HEMATOLOGY Hematocrit Hemoglobin Erythrocyte Count Total and Differential Leukocyte Counts Mean Cell Volume Mean Cell ...Hemoglobin Mean Cell Hemoglobin Ccncentration TABLE 4. PREDICTED VERSES ACTUAL DAILY DOSE (MG/ML/DAY) (2-WEEK FEEDING STUDY) DANPE SOLUTIONS (MALE RATS

  5. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats.

    Science.gov (United States)

    Lina, B A R; Wolterbeek, A P M; Suwa, Y; Fujikawa, S; Ishikura, Y; Tsuda, S; Dohnalek, M

    2006-03-01

    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA or DHA. In this study the safety of SUNTGA40S as source of ARA, not only for use in infant formulas but also for nutritional products or food supplements, was evaluated in a subchronic study in Wistar rats, preceded by a 4-week pretreatment period of parental (F(0)) rats and exposure of the F(0) dams throughout mating, gestation and lactation. SUNTGA40S was administered at dietary levels of 0.5%, 1.5% and 5% (wt/wt) adjusted with corn oil to 5.76% added fat. An additional group received 3.65% (wt/wt) SUNTGA40S in conjunction with 2.11% (wt/wt) high DHA Tuna oil, providing an ARA:DHA ratio of 2.7:1. High-fat and low-fat controls received basal diet with or without 5.76% corn-oil supplement. The content, stability and homogeneous distribution of the test substances in the diet were confirmed under study conditions. The administration of SUNTGA40S, with or without DHA oil, did not affect health, growth, fertility or reproductive performance of the parental rats, nor pup characteristics (condition, weight gain, viability, number per litter or sex ratio). In the subchronic study with the offspring (F(1)) rats, no significant differences were found in condition, neurobehavioural observations, ophthalmoscopy, growth, urinalysis or macroscopic and microscopic findings between the test groups and the low-fat or the high-fat controls. In males of the 5% SUNTGA40S and the SUNTGA40S/DHA group, red blood cell counts, haemoglobin concentration and packed cell volume were lower and reticulocytes were slightly higher than in the high-fat and low-fat control groups. Cholesterol, triglycerides and phospholipids in plasma were lower than in the high-fat controls in both sexes in the 5

  6. Oral toxicity of isotretinoin, misoprostol, methotrexate, mifepristone and levonorgestrel as pregnancy category X medications in female mice

    OpenAIRE

    KIM, SEONG-KWAN; Shin, Soo-Jeong; YOO, YOHAN; KIM, NA-HYUN; KIM, DONG-SOON; Zhang, Dan; PARK, JIN-A; Yi, Hee; Kim, Jin-Suk; Shin, Ho-Chul

    2015-01-01

    An oral toxicity study of several pregnancy category X drugs was performed in female ICR mice. The drugs were administered orally once daily for 3 days at doses of 1, 10 and 100 ?g/kg for isotretinoin; 6.7, 67 and 670 ?g/kg for misoprostol; 83, 830 and 8,300 ?g/kg for methotrexate; 3.3, 33 and 330 ?g/kg for mifepristone; and 25, 250 and 2,500 ?g/kg for levonorgestrel. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry and necropsy findings were exam...

  7. 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.

  8. Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Moon, Changjong; Kim, Je-Hein; Kim, Hyoung-Chin; Kim, Jong-Choon

    2016-10-28

    Copper nanoparticles (Cu NPs) have great potential in electronics and biomedical fields because of their efficient thermodynamic and anti-microbial properties. However, their potential toxic effects and kinetic data following repeated exposure are still unclear. We evaluated the physicochemical properties of Cu NPs (25 nm) and copper microparticles (Cu MPs, 14-25 μm). Comparative in vivo toxicity of Cu NPs and Cu MPs was evaluated by conducting a 28-day repeated oral dose study at equivalent dose levels of 0, 100, 200, and 400 mg/kg/day (vehicle, 1 % hydroxypropyl methylcellulose). We determined Cu levels in the blood, tissues, urine, and feces by using inductively coupled plasma mass spectrometry. The solubility of Cu NPs and Cu MPs was 84.5 and 17.2 %, respectively, in an acidic milieu; however, they scarcely dissolved in vehicle or intestinal milieus. The specific surface area of Cu NPs and Cu MPs was determined to be 14.7 and 0.16 m(2)/g, respectively. Cu NPs exhibited a dose-dependent increase of Cu content in the blood and tested organs, with particularly high levels of Cu in the liver, kidney, and spleen. Only for liver and kidney increased Cu levels were found in Cu MPs-treated rats. Cu NPs caused a dose-related increase in Cu levels in urine, whereas Cu MPs did not affect the urine Cu levels. Extremely high levels of Cu were detected in the feces of Cu MPs-treated rats, whereas much lower levels were detected in the feces of Cu NPs-treated rats. A comparative in vivo toxicity study showed that Cu NPs caused damages to red blood cells, thymus, spleen, liver, and kidney at ≥200 mg/kg/days, but Cu MPs did not cause any adverse effects even at the highest dose. Overall, the in vivo repeated dose toxicity study of Cu NPs and Cu MPs demonstrated that large surface area and high solubility in physiological milieus could directly influence the toxicological responses and biodistribution of Cu particles when administered orally. Under these experimental

  9. 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...

  10. Chronic oral DDT toxicity in juvenile coho and chinook salmon

    Science.gov (United States)

    Buhler, Donald R.; Rasmusson, Mary E.; Shanks, W.E.

    1969-01-01

    Technical and p,p′-DDT was incorporated into test diets and fed to juvenile chinook and coho salmon for periods as long as 95 days. Pure p,p′-DDT was slightly more toxic to young salmon than was the technical DDT mixture. Chinook salmon appeared to be 2–3 times more sensitive to a given concentration of DDT in the diet than were coho salmon. The size of the fish greatly influenced toxicity, smaller younger fish being more susceptible to a given diet than larger older fish. The dose of DDT accumulated within the median survival time ranged from 27–73 mg/kg for chinook salmon and from 56–72 mg/kg for coho salmon. The extrapolated 90-dose LD50 (Hayes, 1967) for young chinook and coho salmon were 0.0275 and 0.064 mg/kg/day, respectively. Liver size decreased on prolonged feeding with DDT, and carcass lipid content was increased. A severe surface ulceration of the nose region appeared in coho salmon fed DDT over long periods. In addition, an interesting localized degeneration of the distal convoluted tubule was observed in the kidney of coho salmon receiving DDT.

  11. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    Science.gov (United States)

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  12. 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.

  13. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    Directory of Open Access Journals (Sweden)

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P<0.05 and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  14. Developmental toxicity of N-methylaniline following prenatal oral administration in rats

    Directory of Open Access Journals (Sweden)

    Krystyna Sitarek

    2016-06-01

    Full Text Available Objectives: The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA administered by gavage to pregnant female rats. Material and Methods: Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w., 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating to the day prior to the scheduled caesarean section (the 20th day of pregnancy. General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results: All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3 and free triiodothyronine (FT4 thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions: Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL for the progeny.

  15. Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb.

    Science.gov (United States)

    Devaraj, Sutha; Esfahani, Azadeh Sabetghadam; Ismail, Sabariah; Ramanathan, Surash; Yam, Mun Fei

    2010-04-22

    Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

  16. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Ramgopal Mopuri; Balaji Meriga

    2014-01-01

    Objective: To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T.paniculata) ethanolic extract in Sprague Dawley rats. Methods: The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results:Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions:Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

  17. Study on General Reproductive Toxicity of Oral Administration of Pineapple Leaves Extract in Mice%新药用资源菠萝叶小鼠一般生殖毒性的研究

    Institute of Scientific and Technical Information of China (English)

    袁梽漪; 邢东明; 杜力军; 卢希; 雷帆; 柴玉爽; 冯天师; 姜敬非; 赵爽; 王欣佩; 李慧玉

    2014-01-01

    目的:对菠萝叶小鼠的一般生殖毒性进行研究,有助于更好的评价该植物的药用价值。方法:分别灌胃给予成年雄性和雌性小鼠菠萝叶,然后合笼进行交配。对于交配成功的雌鼠继续饲养。分别对孕鼠的妊娠、胎鼠的发育及生产的子代小鼠的情况进行实验观察。结果:菠萝叶除了大剂量(4 g·kg-1)对亲本雄性鼠体重有一定降低外,对其它各项指标均无明显影响。对孕鼠及其子代小鼠均未见有明显影响。结论:提示菠萝叶对小鼠一般生殖功能无明显毒性。%This article was aimed to study the general reproductive toxicity in mice in order to give a better evalua-tion of the medicinal plant of pineapple leaves (A nanas comasus L). Adult male and female mice were orally admin-istered with pineapple leaves. And then, each of the male and female mice was put together in one cage for mating. The mating success females were fed continuously. The experimental observation was conducted in pregnancy, fetal development, as well as the offspring of mice. The results showed that in addition to a large dose of pineapple leaves (4 g·kg-1) of the parental male rats having a lower body weight, pineapple leaves did not significantly affect on other parameters. There were no significant effects on pregnant mice and their offspring of mice. It was concluded that the pineapple leaves did not influence the general reproductive function of mice apparently.

  18. Review of Ammonium Dinitramide Toxicity Studies

    Science.gov (United States)

    2011-01-01

    reproductive toxicant in rats, causing implantation failure in early gestation; follow-on studies implied that ADN is embryotoxic . EPR studies indicated that...mutagenic. 15. SUBJECT TERMS Ammonium dinitramide, ADN, toxicity, reproductive, embryotoxic , genotoxicity 16. SECURITY CLASSIFICATION OF: U 17...reproductive studies, reproduction and fertility, pre-implantation and post-implantation studies, implied that ADN is embryotoxic . A mouse embryo

  19. Chronic toxicity study of Hyptis suaveolens (L. Poit in rats

    Directory of Open Access Journals (Sweden)

    Bunjong Chaorai

    2005-09-01

    Full Text Available The effect of water extract of Hyptis suaveolens (H. suaveolens was evaluated for 6-month chronic toxicity in Wistar rats. Control group received distilled water orally 10 ml/kg/day. The extract was orally given to five treatment groups at the doses of 5, 50, 250, 500 and 500 mg/kg/day for 6 months. The last group was served as the recovery group. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. The results of hematological, biochemical parameters and histopathological lesions showed that the extract did not produce any significant doserelated changes. Therefore, it may be concluded that the extract of H. suaveolens at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment.

  20. Safety evaluation of Morinda citrifolia (noni leaves extract: assessment of genotoxicity, oral short term and subchronic toxicity

    Directory of Open Access Journals (Sweden)

    Alicia Lagarto

    2013-02-01

    Full Text Available Morinda citrifolia L (noni is an evergreen or small tree that grows in many tropical regions of the world. The use of the noni leaves has not been so studied however; there are reports of its pharmacological benefits. Aims: The objective of this investigation was to assess the genotoxicity, short-term, and subchronic oral toxicity of Morinda citrifolia L leaves aqueous extract. Methods: The genotoxicity of the M. citrifolia extract was investigated by measuring the frequency of micronuclei in mice bone marrow cells. The animals were treated with three doses of the extract (500, 1000, and 2000 mg/kg. For short-term toxicity, both sexes Wistar rats received 1000 mg/kg/day for 28 days. Animals were sacrificed for hematological and biochemical evaluation. For the subchronic study, Wistar rats were administered with three doses of M. citrifolia extract (100, 300, and 1000 mg/kg by oral route for 90 days. Mortalities, clinical signs, body weight changes, food and water consumption, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. Results: Genotoxicity and short-term toxicity test resulted in absence of toxicity at doses between 500 and 2000 mg/kg. Significant differences were observed in hemoglobin, and differential leukocyte count after subchronic dosing of the extract. Histology evaluation did not reveal treatment-related abnormalities. Variations observed were within to normal range and reversible. Conclusions: In summary, 1000 mg/kg orally was the NOAEL for M. citrifolia extract for effects other than transient variations in some hematological parameters within normal range. [J Intercult Ethnopharmacol 2013; 2(1.000: 15-22

  1. Review of reproductive and developmental toxicity studies with isopropanol.

    Science.gov (United States)

    Faber, Willem D; Pavkov, Kenneth L; Gingell, Ralph

    2008-10-01

    Published studies for reproductive and developmental toxicity conducted with isopropanol have been conducted by the inhalation and oral gavage routes of administration. Interpretation of the data from these studies has resulted in discussions regarding NOAELs and additional benchmark dose modeling publications. Unpublished reproductive and developmental toxicity studies administered in the drinking water were also conducted by BIBRA, and the results of those studies are presented here. In addition, all of the reproductive and developmental toxicity studies conducted with isopropanol are summarized and evaluated for concordance of effects and NOAELs. Endpoints of concern for regulatory agencies were decreases in male mating index and reductions in postnatal pup survival. Original study reports were evaluated and data collated to address these two endpoints, and the data summarized. Data are presented suggesting that there were technical problems in the study that implied a decrease in male mating index, and based on the results from the drinking water studies, the weight of evidence suggests that isopropanol does not affect male mating or fertility at dose levels of up to 1000 mg/kg/day. The weight of evidence suggests that isopropanol can cause decreases in postnatal pup survival following oral gavage administration of 1000-1200 mg/kg/day to the dams. The NOAEL for this endpoint with oral gavage administration was 700 mg/kg/day. Indications of maternal toxicity were also an important predictor for decreased postnatal survival. Decreased postnatal pup survival was also noted in the drinking water studies with isopropanol with a LOAEL of 2278 mg/kg/day and a NOAEL of 1947 mg/kg/day.

  2. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    OpenAIRE

    2010-01-01

    In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme) of the Federal University of São Paulo (UNIFESP): 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995), 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for...

  3. Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

    OpenAIRE

    Vandenberg, Laura N; Welshons, Wade V.; Frederick S vom Saal; Toutain, Pierre-Louis

    2014-01-01

    For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of ‘oral’ exposures. It is now widely used – and in some cases required – by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, ga...

  4. Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate.

    Science.gov (United States)

    Bhattacharya, R; Satpute, R M; Hariharakrishnan, J; Tripathi, H; Saxena, P B

    2009-09-01

    Oral toxicity of several cyanogens and their reversal by alpha-ketoglutarate (A-KG; oral) were studied in rats. LD(50) of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), and succinonitrile (SCN) was 4891, 143.3, 69.8, 122.9, 69.8 and 488.7 mg/kg, respectively while the protection index of A-KG (ratio of LD(50) of cyanogens in the presence or absence of A-KG) was>2.0 against MCN (7.6), PCN (2.7) and SNP (3.6) only. We further studied the efficacy of A-KG against acute toxicity of these three cyanogens (0.75 LD(50)) on various hematological and biochemical variables in blood and soft tissues 24h post-exposure. We observed increase in white blood cells (SNP), plasma alanine (PCN, SNP) and aspartate (PCN) aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), Na(+) (MCN, PCN) and cyanide (PCN), and decrease in K(+) (MCN, SNP) accompanied by an increase in brain, kidney and liver malondialdehyde (PCN), decrease in brain glutathione peroxidase, glutathione reductase (PCN, SNP), reduced glutathione (MCN, PCN, SNP) and cytochrome oxidase (PCN), liver rhodanese (PCN, SNP), and kidney cytochrome oxidase (PCN). The study indicates that (i) PCN was most toxic among all the cyanogens and (ii) beside cyanide, A-KG could be considered as an effective antidote for cyanogens.

  5. Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma.

    Science.gov (United States)

    Poirier, Valérie J; Kaser-Hotz, Barbara; Vail, David M; Straw, Rodney C

    2013-01-01

    Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5-5.5 months (45-165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty-one cats with histologically confirmed oral SCC and T1-3N0M0 were treated with 10 once-daily fractions (Monday-Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow-up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression-free survival (PFS) was 105 days (1 year PFS of 23%), median local progression-free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.

  6. Copper pellets simulating oral exposure to copper ammunition: Absence of toxicity in American kestrels (Falco sparverius)

    Science.gov (United States)

    Franson, J. Christian; Lahner, Lesanna L.; Meteyer, Carol U.; Rattner, Barnett A.

    2012-01-01

    To evaluate the potential toxicity of copper (Cu) in raptors that may consume Cu bullets, shotgun pellets containing Cu, or Cu fragments as they feed on wildlife carcasses, we studied the effects of metallic Cu exposure in a surrogate, the American kestrel (Falco sparverius). Sixteen kestrels were orally administered 5 mg Cu/g body mass in the form of Cu pellets (1.18–2.00 mm in diameter) nine times during 38 days and 10 controls were sham gavaged on the same schedule. With one exception, all birds retained the pellets for at least 1 h, but most (69%) regurgitated pellets during a 12-h monitoring period. Hepatic Cu concentrations were greater in kestrels administered Cu than in controls, but there was no difference in Cu concentrations in the blood between treated and control birds. Concentration of the metal-binding protein metallothionein was greater in male birds that received Cu than in controls, whereas concentrations in female birds that received Cu were similar to control female birds. Hepatic Cu and metallothionein concentrations in kestrels were significantly correlated. Histopathologic alterations were noted in the pancreas of four treated kestrels and two controls, but these changes were not associated with hepatic or renal Cu concentrations, and no lesions were seen in other tissues. No clinical signs were observed, and there was no treatment effect on body mass; concentrations of Cu, hemoglobin, or methemoglobin in the blood; or Cu concentrations in kidney, plasma biochemistries, or hematocrit. Based on the parameters we measured, ingested Cu pellets pose little threat to American kestrels (and presumably phylogenetically related species), although the retention time of pellets in the stomach was of relatively short duration. Birds expected to regurgitate Cu fragments with a frequency similar to kestrels are not likely to be adversely affected by Cu ingestion, but the results of our study do not completely rule out the potential for toxicity in

  7. 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.

  8. Ethylbenzene: 4- and 13-week rat oral toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mellert, Werner; Deckardt, Klaus; Kaufmann, Wolfgang; Ravenzwaay, Bennard van [BASF Aktiengesellschaft, Department of Product Safety, Ludwigshafen (Germany)

    2007-05-15

    Ethylbenzene was administered to groups of male and female Wistar rats by gavage for 4 (n = 5/dose/sex) and 13 weeks (n = 10/dose/sex) (OECD 408) at doses of 0 (vehicle control), 75, 250, and 750 mg/kg bodyweight/day (mg/kg bw/day), administered am/pm as half doses. In the 4-week study, {>=}250 mg/kg increased serum alanine aminotransferase, total bilirubin and cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and kidney weights; males also had post-dose salivation, increased urinary epithelial cell casts and cells, and hyaline droplet nephropathy. In the 13-week study, {>=}250 mg/kg increased water consumption and produced post-dose salivation. Liver-related effects: increased serum alanine aminotransferase, gamma-glutamyltransferase, bilirubin, total protein, albumin and globulins, cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and reduced prothrombin times. Kidney-related effects: increased serum potassium, calcium, magnesium, kidney weights, and (males only) urea and hyaline droplets in renal tubular epithelium, and reduced sodium (females only); creatinine was reduced in 750 mg/kg males. The NOAEL of ethylbenzene in these studies, based on hepatocyte hypertrophy and liver- and kidney-related clinical chemistry changes, was 75 mg/kg bw/day. (orig.)

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Acute Oral Toxicity and Brine Shrimp Lethality of Elaeis guineensis Jacq., (Oil Palm Leaf Methanol Extract

    Directory of Open Access Journals (Sweden)

    Yeng Chen

    2010-11-01

    Full Text Available Elaeis guineensis (Arecaceae is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC50 values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively, confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

  11. Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil palm leaf) methanol extract.

    Science.gov (United States)

    Syahmi, Abdul Rani Muhamad; Vijayarathna, Soundararajan; Sasidharan, Sreenivasan; Latha, Lachimanan Yoga; Kwan, Yuet Ping; Lau, Yee Ling; Shin, Lai Ngit; Chen, Yeng

    2010-11-10

    Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

  12. Evaluation of the subchronic toxicity of oral treatment with Chenopodium ambrosioides in mice.

    Science.gov (United States)

    Pereira, Wanderson S; Ribeiro, Bruno P; Sousa, Anildes I P; Serra, Izabel C P B; Mattar, Nadia S; Fortes, Thiare S; Reis, Aramys S; Silva, Lucilene A; Barroqueiro, Elizabeth S B; Guerra, Rosane N M; Nascimento, Flávia R F

    2010-02-17

    The leaves of Chenopodium ambrosioides L. (Chenopodiaceae) have been used by native people to treat many diseases. Recently, we showed that the treatment with small dose (5mg/kg) of hydroalcoholic extract (HE) from Chenopodium ambrosioides' leaves has immunestimulatory effects. The aim of this study was to investigate the subchronic toxicity of the oral treatment with this HE in preclinical assays. Swiss mice were divided into 4 groups (n=10/group). They received the HE daily at the doses of 5, 50 and 500 mg/kg by gavage during 15 days. The control group received only water. They were observed each hour for 24h and each day for 15 days, when the blood was collected. The serum was used to perform the biochemical analysis. The mice were then killed and the vital and lymphoid organs were collected and evaluated. There was neither death nor alterations in the body weight in the HE-treated groups, but there were alterations in the weight of some organs. There was an increase in the lymph node cells number in the highest two doses. The number of cells in the bone marrow was high in the HE-treated groups, but the number of peritoneal cells was smaller in the HE-treated groups when compared to the control. There was no alteration in the AST, but there was a reduction in the albumin levels in the HE500 group and in the triglycerides and VLDL in the highest doses. The subchronic treatment with HE induced punctual alterations in the groups treated with the highest doses. However, the HE treatment was not lethal and did not induce toxic alterations using the therapeutic dose, suggesting that it is safe to use this product in the adequate dose. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  13. Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid.

    Science.gov (United States)

    Sun, Jiarui; Zhang, Xinchen; Cao, Yinan; Zhao, Qiling; Bao, Endong; Lv, Yingjun

    2016-01-01

    Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.

  14. Distribution, Metabolism and Toxic Effects of Beta-Cypermethrin in Lizards (Eremias argus) Following Oral Administration.

    Science.gov (United States)

    Chen, Li; Xu, Peng; Diao, Jinling; Di, Shanshan; Li, Ruiting; Zhou, Zhiqiang

    2016-04-01

    Beta-cypermethrin (BCYP), a synthetic pyrethriod (PYR) pesticide which is a mixture of the alpha- and theta- cypermethrin, have been reported various toxicological profiles to non-target organisms. But little is known about assimilation, accumulation and toxic effects of BCYP in reptiles. The present study firstly elucidated absorption, tissue distribution, excretion of BCYP in Eremias argus . Treated group were administered orally with BCYP 20mg/kg body weight (bw) dissolved in corn oil. Neurotoxicity was observed at 24h after gavage, and the poisoning symptom ameliorated at 72h. The changes of BCYP concentration depended on degradation time and tissues. Lizards had a strong capacity to eliminate BCYP with different tissue distribution. The tissues concentration of BCYP from high to low were intestine, stomach, heart, kidney, blood, lung, liver and brain. Bimodal phenomena were observed in lung, liver and kidney. These results may be due to the activities of enzymes, circadian rhythm, and enterohepatic circulation in lizards. Based on the results of organ coefficient and histopathology analysis in liver, the liver was confirmed as the main target organ.

  15. Preliminary acute toxicity study on imidacloprid in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Preeti Bagri

    2013-12-01

    Full Text Available Aim: To ascertain the maximum tolerated dose (MTD and to investigate the acute oral toxic effects of imidacloprid towards Swiss albino male mice.Materials and Methods: The MTD of imidacloprid was determined in pilot dose range finding study following the standard method. Animals were observed for toxic signs and symptoms after oral administration of MTD of imidacloprid in single dose. The body weights of animals were recorded on alternate day. Animals were sacrificed on 14th day and changes in hematological parameters (Hb, TEC, TLC and DLC and morphometric measurements (length, breadth, thickness and weight of various body organs (heart, liver, spleen, kidney, testis and epididymis were examined. The student's t-test was applied to statistically analyze the results.Results: The MTD of imidacloprid was determined to be 110 mg/kg body weight. The sign and symptoms of acute toxicity were ataxia, rigidity and fasciculation of muscles, protrusion of eye ball and tremors of head. Imidacloprid treatment resulted in decreased body weight gain as compared to the control group. The changes in hematological parameters were not significant between imidacloprid treated and control groups. Also the values of relative organ weights and morphometric measurements of various body organs did not differ significantly between the control and imidacloprid treated animals.Conclusions: MTD of imidacloprid in Swiss albino male mice through oral route was determined for the first time. Study revealed a non-toxic effect of imidacloprid on body weight, relative organs weight, hematological parameters and morphometric measurements of various body organs in mice.

  16. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

    Directory of Open Access Journals (Sweden)

    Kim YR

    2014-12-01

    either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN,20(- (20 nm or SiO2EN,100(- (100 nm was observed. The results of this study indicate that the NOAEL for SiO2EN,20(- and SiO2EN,100(- would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. Keywords: silica nanoparticles, particle size, 90-day oral dose toxicity, no observed adverse effect level

  17. Tropically stable novel oral lipid formulation of amphotericin B (iCo-010): biodistribution and toxicity in a mouse model.

    Science.gov (United States)

    Sivak, Olena; Gershkovich, Pavel; Lin, Molly; Wasan, Ellen K; Zhao, Jinying; Owen, David; Clement, John G; Wasan, Kishor M

    2011-08-08

    The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010). BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected. The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone treatment induced necrotic changes in hepatic and kidney tissues. Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.

  18. Tropically stable novel oral lipid formulation of amphotericin B (iCo-010: biodistribution and toxicity in a mouse model

    Directory of Open Access Journals (Sweden)

    Owen David

    2011-08-01

    Full Text Available Abstract Background The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010. Methods BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone® 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected. Results The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone® resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone® treatment induced necrotic changes in hepatic and kidney tissues. Conclusions Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.

  19. Subacute and Reproductive Oral Toxicity Assessment of the Hydroethanolic Extract of Jacaranda decurrens Roots in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Joyce Alencar Santos

    2013-01-01

    Full Text Available Jacaranda decurrens subsp. symmetrifoliolata Farias & Proença (Bignoniaceae is a species traditionally used for the treatment of inflammatory and infectious diseases. Previous findings from our group reported scientifically that J. decurrens has anti-inflammatory efficacy. However, more toxicological studies are needed to support and ensure its safe use. The present study was carried out to evaluate the toxic effects of a prolonged treatment with hydroethanolic root extract of J. decurrens (EJD on hematological, biochemical, and reproductive parameters in adult male rats. The animals received by oral gavage 0; 250; 500; or 1000 mg/kg body weight of EJD for 28 days. After the treatment, biochemical, hematological, histopathological, and reproductive parameters were analyzed. The EJD treatment did not cause adverse effects on body weight gain, feed and water consumption, hematological and biochemical profiles, or histopathological analysis of liver and kidney. Similarly, there were no statistically significant differences in reproductive parameters, such as sperm production, number of sperm in the epididymis, and sperm morphology. These results demonstrate the absence of subacute toxicity as a result of the oral treatment with EJD for 28 days in adult male rats. However, other studies should be performed to evaluate the total safety of this plant.

  20. 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.

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

    Science.gov (United States)

    Strupp, Christian

    2011-01-01

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

  2. Extrapolation for exposure duration in oral toxicity: A quantitative analysis of historical toxicity data

    NARCIS (Netherlands)

    Groeneveld, C.N.; Hakkert, B.C.; Bos, P.M.J.; Heer, C.de

    2004-01-01

    For human risk assessment, experimental data often have to be extrapolated for exposure duration, which is generally done by means of default values. The purpose of the present study was twofold. First, to derive a statistical distribution for differences in exposure duration that can be used in a p

  3. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    Science.gov (United States)

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides.

  4. Oral Piercing and Oral Diseases: A Short Time Retrospective Study

    Directory of Open Access Journals (Sweden)

    Francesco Inchingolo, Marco Tatullo, Fabio M. Abenavoli, Massimo Marrelli, Alessio D. Inchingolo, Antonio Palladino, Angelo M. Inchingolo, Gianna Dipalma

    2011-01-01

    Full Text Available Body piercing indicates the puncturing of a part of the body in which jewelry may be worn. In recent years, oral piercing is increasingly popular especially among young people. Body piercing has to be considered as a surgical procedure to all intents and purposes and, as such, has to be performed only by qualified personnel able to assure high standards of professionalism in facilities subject to sanitary inspections.The aim of the present work is to verify what risks patients may be exposed to and what complications may occur after a healthcare professional performs oral piercing.Our retrospective study includes 108 patients (74 males and 34 females aged between 14 and 39 years, who had oral piercing done 12±4 months earlier. All the patients underwent clinical examination to reveal the possible presence of late complications. After piercing, none of the 108 patients developed widespread complications.Although all patients said they had followed the piercers' instructions, 96% of them reported postoperative local complications such as bleeding within 12 hours of piercing (90%, perilesional edema for 3±2 days after piercing surgery (80%, and persistent mucosal atrophy (70%.

  5. 崖柏精油的急性经口毒性、皮肤刺激性和致敏性实验%Experimental Studies on Acute Oral Toxicity, Skin Irritation and Skin Allergy of Thuja Essential Oil

    Institute of Scientific and Technical Information of China (English)

    彭锦; 唐璐; 肖艳; 陈洋; 鲍美华

    2016-01-01

    目的:评价崖柏精油的急性经口毒性、皮肤刺激性和致敏性,为其临床安全用药提供依据。方法:急性经口毒性采用霍恩(Horn’s)法测定。选用昆明种小鼠40只随机分为4组,给予不同剂量崖柏精油(21.50,10.00,4.64,2.15 g· kg-1),观察14 d。记录死亡数,查表求得LD50,并记录死亡时间及中毒表现等。皮肤刺激性采用健康成年的白色家兔9只随机分为3组,分别给予崖柏精油100%浓度、50%浓度、25%浓度。采用食用植物油作为阴性对照。观察药物贴敷后1,24,48,72 h受试部位皮肤红斑、水肿的反应并评分。采用迟发型致敏反应最大剂量法进行崖柏精油致敏性测定。取健康白色豚鼠30只,随机平均分为3组:给药组,空白对照组(给予植物油基质)、阳性对照组(1%的2,4-二硝基氯苯)。经皮内诱导、局部诱导阶段后,观察崖柏精油激发24 h及48 h的皮肤变态反应情况并进行评分。结果:崖柏精油21.50 g· kg-1可使小鼠全部死亡,10.00,4.64 g· kg-1组可使动物部分死亡,2.15 g· kg-1组动物无死亡,查表求得崖柏精油对雌雄性小鼠的 LD50分别为7.94,9.26 g· kg-1。皮肤刺激性结果显示,崖柏精油(100%浓度)贴敷后1 h有强刺激性,而稀释后的药物刺激性逐渐减弱,25%浓度崖柏精油无明显刺激性。致敏性结果显示,阳性对照组可使豚鼠皮肤出现中度或重度融合性红斑及水肿,具有明显致敏性。而崖柏精油组未见明显红斑和水肿,显示无致敏性。结论:崖柏精油具有明显皮肤刺激性,急性经口毒性属实际无毒,未见致敏性。%Objective:To evaluate the acute oral toxicity , skin irritation and skin allergy of Thuja essential oil ( TEO) , and pro-vide experimental basis for the clinical use of TEO .Methods:The acute oral toxicity was measured by

  6. Acute Toxicity Prediction in Multiple Species by Leveraging Mechanistic ToxCast Mitochondrial Inhibition Data and Simulation of Oral Bioavailability.

    Science.gov (United States)

    Bhhatarai, Barun; Wilson, Daniel M; Bartels, Michael J; Chaudhuri, Shubhra; Price, Paul S; Carney, Edward W

    2015-10-01

    There is great interest in assessing the in vivo toxicity of chemicals using nonanimal alternatives. However, acute mammalian toxicity is not adequately predicted by current in silico or in vitro approaches. Mechanisms of acute toxicity are likely conserved across invertebrate, aquatic, and mammalian species, suggesting that dose-response concordance would be high and in vitro mechanistic data could predict responses in multiple species under conditions of similar bioavailability. We tested this hypothesis by comparing acute toxicity between rat, daphnia, and fish and by comparing their respective acute data to inhibition of mitochondria membrane potential (MMP) using U.S. Environmental Protection Agency ToxCast in vitro high-throughput screening data. Logarithmic scatter plots of acute toxicity data showed a clear relationship between fish, daphnia, and intravenous rat but not oral rat data. Similar plots versus MMP showed a well-delineated upper boundary for fish, daphnia, and intravenous data but were scattered without an upper boundary for rat oral data. Adjustments of acute oral rat toxicity values by simulating fractional absorption and CYP-based metabolism as well as removing compounds with hydrolyzable linkages or flagged as substrates for glucuronidation delineated an upper boundary for rat oral toxicity versus MMP. Mitochondrial inhibition at low concentrations predicted highly acutely toxic chemicals for fish and daphnia but not the rat where toxicity was often attenuated. This use of a single high-throughput screening assay to predict acute toxicity in multiple species represents a milestone and highlights the promise of such approaches but also the need for refined tools to address systemic bioavailability and the impact of limited absorption and first pass metabolism.

  7. Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.

    Science.gov (United States)

    Giovanni, Marcella; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Xie, Jianping; Ong, Choon Nam; Fan, Rongli; Yue, Junqi; Zhang, Lifeng; Leong, David Tai

    2015-12-01

    Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries.

  8. Oral hairy leukoplakia: An exfoliative cytology study.

    Science.gov (United States)

    Reginald, Ajay; Sivapathasundharam, B

    2010-01-01

    Oral hairy leukoplakia (OHL) is a white, hyperplastic, vertically corrugated lesion that occurs on the lateral border of the tongue, usually unilateral. Caused by the Epstein-Barr Virus (EBV), the lesion is said to be an early indicator of an immune deficiency status, thereby unmasking subclinical systemic conditions. OHL mimics many other white lesions of the oral cavity; therefore, it becomes imperative to identify the lesion. This study used exfoliative cytology, a noninvasive procedure, which helped in identifying the cellular changes brought about by the virus in the oral epithelium. The study revealed a subclinical phase of OHL, where the cellular changes were seen even before the appearance of the clinical lesion.

  9. Toxicity Studies of Ethyl Maltol and Iron Complexes in Mice.

    Science.gov (United States)

    Li, Zhen; Lu, Jieli; Wu, Chonghui; Pang, Quanhai; Zhu, Zhiwei; Nan, Ruipeng; Du, Ruochen; Chen, Jia

    2017-01-01

    Ethyl maltol and iron complexes are products of ethyl maltol and the iron found in the cooking pots used to prepare the Chinese dish, hot-pot. Because their safety is undocumented, the toxicity study of ethyl maltol and iron complexes was conducted in male and female Kunming (KM) mice. The animal study was designed based on the preliminary study conducted to determine the median lethal dose (LD50). The doses used in the study were 0, 1/81, 1/27, 1/9, and 1/3 of the LD50 (mg kg body weight (BW)(-1) day(-1)) dissolved in the water. The oral LD50 of the ethyl maltol and iron complexes was determined to be 743.88 mg kg BW(-1) in mice. The ethyl maltol and iron complexes targeted the endocrine organs including the liver and kidneys following the 90 D oral exposure. Based on the haematological data, the lowest-observed-adverse-effect level (LOAEL) of the ethyl maltol and iron complexes was determined to be 1/81 LD50 (9.18 mg kg BW(-1) day(-1)) in both male and female mice. Therefore, we suggest that alternative strategies for preparing the hot-pot, including the use of non-Fe-based cookware, need to be developed and encouraged to avoid the formation of the potentially toxic complexes.

  10. Quantitative structure-toxicity relationship (QSTR) studies on the organophosphate insecticides.

    Science.gov (United States)

    Can, Alper

    2014-11-04

    Organophosphate insecticides are the most commonly used pesticides in the world. In this study, quantitative structure-toxicity relationship (QSTR) models were derived for estimating the acute oral toxicity of organophosphate insecticides to male rats. The 20 chemicals of the training set and the seven compounds of the external testing set were described by means of using descriptors. Descriptors for lipophilicity, polarity and molecular geometry, as well as quantum chemical descriptors for energy were calculated. Model development to predict toxicity of organophosphate insecticides in different matrices was carried out using multiple linear regression. The model was validated internally and externally. In the present study, QSTR model was used for the first time to understand the inherent relationships between the organophosphate insecticide molecules and their toxicity behavior. Such studies provide mechanistic insight about structure-toxicity relationship and help in the design of less toxic insecticides. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. A k-NN algorithm for predicting the oral sub-chronic toxicity in the rat.

    Science.gov (United States)

    Gadaleta, Domenico; Pizzo, Fabiola; Lombardo, Anna; Carotti, Angelo; Escher, Sylvia E; Nicolotti, Orazio; Benfenati, Emilio

    2014-01-01

    Repeated dose toxicity is of the utmost importance to characterize the toxicological profile of a chemical after repeated administration. Its evaluation refers to the Lowest-Observed-(Adverse)-Effect-Level (LO(A)EL) explicitly requested in several regulatory contexts, such as REACH and EC Regulation 1223/2009 on cosmetic products. So far in vivo tests have been the sole viable option to assess repeated dose toxicity. We report a customized k-Nearest Neighbors approach for predicting sub-chronic oral toxicity in rats. A training set of 254 chemicals was used to derive models whose robustness was challenged through leave-one-out cross-validation. Their predictive power was evaluated on an external dataset comprising 179 chemicals. Despite the intrinsically heterogeneous nature of the data, our models give promising results, with q²≥0.632 and external r²≥0.543. The confidence in prediction was ensured by implementing restrictive user-adjustable rules excluding suspicious chemicals irrespective of the goodness in their prediction. Comparison with the very few LO(A)EL predictive models in the literature indicates that the results of the present analysis can be valuable in prioritizing the safety assessment of chemicals and thus making safe decisions and justifying waiving animal tests according to current regulations concerning chemical safety.

  12. Study on alternative methods for the acute oral toxicity in detection of chemicals%急性经口毒性替代方法在化学品检验中的应用研究

    Institute of Scientific and Technical Information of China (English)

    谭剑斌; 赵敏; 杨杏芬; 周轶琳; 陈壁锋; 陈瑞仪; 黄建康

    2011-01-01

    ,the concordance rates of FDP,ATC and UDP was 91.7%(11/12),75.0%(9/12) and 83.0%(10/12),respectively.The number of animals required in three alternative methods was significantly lower than that in traditional test (P<0.05),but the time required in three alternative methods was significantly higher than that in traditional test (P<0.05 ).Conclusions High consistency and correlation were found between each alternative method and LD50 test.FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.

  13. Weight-of-the-evidence review of acrylonitrile reproductive and developmental toxicity studies.

    Science.gov (United States)

    Neal, Barbara H; Collins, James J; Strother, Dale E; Lamb, James C

    2009-01-01

    Risk assessment of acrylonitrile (AN) toxicity to humans has focused on potential carcinogenicity and acute toxicity. Epidemiological studies from China reported reproductive and developmental effects in AN workers, including infertility, birth defects, and spontaneous abortions. A weight-of-the-evidence (WoE) evaluation of the AN database assessed study strength, characterized toxicity, and identified no-observed-adverse-effect levels (NOAELs). The epidemiological studies do not demonstrate causality and are not sufficiently robust to be used for risk assessment. Rodent developmental studies showed fetotoxicity and malformations at maternally toxic levels; there was no unique developmental susceptibility. NOAELs for oral and inhalation exposures were 10 mg/kg/day and 12 ppm (6 h/day), respectively. Drinking-water and inhalation reproductive toxicity studies showed no clear effects on reproductive performance or fertility. Maternally toxic concentrations caused decreased pup growth. The drinking-water reproductive NOAEL was 100 ppm (moderate confidence due to study limitations). The inhalation exposure reproductive and neonatal toxicity high confidence NOAEL was 45 ppm (first generation 90 ppm) (6 h/day). The inhalation reproductive toxicity study provides the most robust data for risk assessment. Based on the WoE evaluation, AN is not expected to be a developmental or reproductive toxicant in the absence of significant maternal toxicity.

  14. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    Directory of Open Access Journals (Sweden)

    Douglas Rossi Jesus

    2015-01-01

    Full Text Available The large consumption of biodegradable films from cassava starch acetate (FCSA as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.

  15. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    Science.gov (United States)

    Jesus, Douglas Rossi; Barbosa, Lorena Neris; Prando, Thiago Bruno Lima; Martins, Leonardo Franco; Gasparotto, Francielli; Guedes, Karla Moraes Rocha; Dragunski, Douglas Cardoso; Lourenço, Emerson Luiz Botelho; Dalsenter, Paulo Roberto; Gasparotto Junior, Arquimedes

    2015-01-01

    The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm. PMID:26451154

  16. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Donald Albert

    2013-05-01

    Full Text Available Introduction: There are few reports summarizing the effectiveness of oral and intravenous (IV acetylcysteine. We determined the proportion of acetaminophen poisoned patients who develop hepatotoxicity (serum transaminase > 1000 IU/L when treated with oral and IV acetylcysteine.Methods: Studies were double abstracted by trained researchers. We determined the proportions of patients who developed hepatotoxicity for each route using a random effects model. Studies were further stratified by early and late treatment.Results: We screened 4,416 abstracts; 16 articles, including 5,164 patients, were included in the meta-analysis. The overall rate of hepatotoxicity for the oral and IV routes were 12.6% and 13.2%, respectively. Treatment delays are associated with a higher rate of hepatotoxicity.Conclusion: Studies report similar rates of hepatotoxicity for oral and IV acetylcysteine, but direct comparisons are lacking. While it is difficult to disentangle the effects of dose and duration from route, our findings suggest that the rates of hepatotoxicity are similar for oral and IV administration. [West J Emerg Med. 2013;14(3:218–226.

  17. CDP-choline: acute toxicity study.

    Science.gov (United States)

    Grau, T; Romero, A; Sacristán, A; Ortiz, J A

    1983-01-01

    The acute toxicity of a single dose of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) by different administration routes in mice and rats has been studied. LD50 values were determined according to the cumulative method by Reed-Muench for mortality rate, and Pizzi's method for calculation of standard error.

  18. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  19. 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.

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

    Science.gov (United States)

    Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

    2017-01-01

    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. PMID:28245573

  1. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Science.gov (United States)

    2010-07-01

    ... displaying each type of lesion. (ii) When applicable, all observed results, qualitative and quantitative... obtained by acute testing. The subchronic oral study has been designed to permit the determination of the... be used throughout the duration of the study and the research sample should be stored under...

  2. Acute Toxicity Test of Kushencangshu Oral Liquid%苦参苍术口服液急性毒性研究

    Institute of Scientific and Technical Information of China (English)

    高艳艳; 周德刚; 高富红

    2014-01-01

    In order to evaluate the actue toxicity of Kushencangshu oral liquid,the experiment was conducted in accordance with acute toxicity requirements in compilation of veterinary drug registration data. The acute toxicity of Kushencangshu oral liquid was studied in mice in this experiment,the toxicity of Kushencangshu oral liquid was demonstrated by the minimal lethal dose and the LD50 of mice. The results showed that the LD50 of the Kushencangshu oral liquid was 20.51 mL/kg,equal to 68.91 g/kg of the crude drug every day,it had light poi-sonous; the minimal lethal dose ranged between 16.37 and 25.9 mL/kg,which was equivalent to from 27.3 to 43.2 times of daily dosage of poultry. Kushencangshu oral liquid was relatively safe in clinical application.%为了考察苦参苍术口服液的安全性,按《兽药注册资料汇编》的要求,选用小白鼠进行了急性毒性试验。结果显示,苦参苍术口服液灌胃给药的LD50为20.51 mL/kg,相当于生药量68.91 mL/kg,可判断苦参苍术口服液为小毒。95%可信限(可信区间)范围为16.37~25.90 mL/kg,相当于禽临床用量的27.3~43.2倍,说明苦参苍术口服液临床使用安全。

  3. Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats. Preliminary investigations.

    Science.gov (United States)

    Tryphonas, L; Truelove, J; Todd, E; Nera, E; Iverson, F

    1990-10-01

    A recent outbreak of marine food poisoning in humans was attributed to the consumption of blue mussels (Mytilus edulis L.) contaminated with domoic acid (DA) that was produced by the diatom Nitzschia pungens. The clinical and morphological effects of single oral doses of extracts of mussels contaminated with DA or of DA isolated from toxic mussels were investigated in small groups (one to six) of cynomolgus monkeys (Macaca fascicularis; 0.5-10 mg DA/kg body weight) and of Sprague-Dawley rats (60 to 80 mg DA/kg body weight). Control animals were either given saline or were not treated. To test whether monosodium glutamate, present in the food consumed by some affected humans, and dimethylsulphoxide, suspected of being present in the plankton, enhanced the response, monosodium glutamate (at 0.25% of mussel extract bolus) or dimethylsulphoxide (at 1 g per bolus) were co-administered to two (one each) of the DA-treated monkeys. DA-treated monkeys developed transient excitation characterized by vomiting. DA-treated rats showed withdrawal followed by hyperexcitation and death (in one case). Mild to moderate central nervous system lesions consistent with neuroexcitation were present in both monkeys and rats. The addition of monosodium glutamate and dimethylsulphoxide had no significant effect on the appearance and severity of central nervous system clinical signs and lesions. The wide variations in the response of test animals to orally administered DA were attributed to the protective effect of vomiting, and to suspected incomplete or slow gastro-intestinal absorption of the toxic agent. The results reinforce the view that DA is an emetic and that under appropriate conditions may also inflict excitotoxic central nervous system damage.

  4. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    Directory of Open Access Journals (Sweden)

    Kwan Yuet Ping

    2013-01-01

    Full Text Available Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P>0.05 in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity.

  5. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats.

    Science.gov (United States)

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam; Sasidharan, Sreenivasan

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5,000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5,000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1,000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity.

  6. [Study on the oral hygiene of patients with oral cavity cancer].

    Science.gov (United States)

    Bratoĭcheva, M St; Kondeva, V K

    2008-01-01

    Many authors consider oral hygiene an important factor in the etiology and pathogenesis of oral cavity cancer. The aim of the present study was to establish the role of poor oral hygiene in the development of malignant lesions in the oral cavity. One hundred and three patients were interviewed. Questions, regarding oral hygiene were included in the interview. Results showed that 53,80% of urban residents brush their teeth twice daily whereas 65,52% of rural residents brush their teeth irregularly - poral hygiene - poral cavity cancer is more frequent in men, rural residents and in the elderly. Oral hygiene is a factor in the development of oral cavity cancer.

  7. Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

    Science.gov (United States)

    Vandenberg, Laura N; Welshons, Wade V; Vom Saal, Frederick S; Toutain, Pierre-Louis; Myers, John Peterson

    2014-06-25

    For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of 'oral' exposures. It is now widely used--and in some cases required--by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, gavage exposures avoid these interactions, leading to dramatic differences in absorption, bioavailability and metabolism with implications for toxicokinetic assumptions and models. Additionally, there are well acknowledged complications associated with gavage, such as perforation of the esophagus that diminish its value in toxicological experiments. Finally, the gavage protocol itself can induce stress responses by the endocrine system and confound the assessment of EDCs. These serious flaws have not been taken into account in interpreting results of EDC research. We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic. We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful, and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs.

  8. Stevens-Johnson Syndrome and toxic epidermal necrolysis overlap due to oral temozolomide and cranial radiotherapy.

    Science.gov (United States)

    Sarma, Nilendu

    2009-01-01

    A 46-year-old man developed Stevens-Johnson syndrome and toxic epidermal necrolysis overlap, with severe localized denudation of the skin on the head and neck, following radiotherapy and oral temozolomide therapy for cranial glioblastoma multiforme. He also had a primary malignant fibrous histiocytoma of the thigh that was amputated 5 years earlier. A rash developed after 7 days of radio- and chemotherapy. It was an extensive maculopapular rash that started over the temporal area of the head and rapidly spread, sparing only the distal limbs. Radiotherapy and temozolomide were stopped on the tenth day but the rash rapidly progressed for the next 4-6 days. Following this, the spread halted and complete recovery was observed within the next 2 weeks. The peculiarity of the presentation in this case was that the brunt of the disease with severe skin denudation was localized to the surrounding areas of cranial radiotherapy. The patient was also receiving oral phenytoin, diclofenac, and parenteral dexamethasone before chemotherapy was started. These medications were continued, even after development of the skin rash, until well after full recovery from the skin lesions. After critical evaluation of disease onset, progression, and recovery, and their relationship to the introduction and withdrawal of different medicines, it appeared that either temozolomide alone or in combination with radiotherapy most probably triggered the condition.

  9. Oral toxicity of Photorhabdus luminescens and Xenorhabdus nematophila (Enterobacteriaceae) against Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    da Silva, Onilda Santos; Prado, Geronimo Rodrigues; da Silva, João Luiz Rosa; Silva, Carlos Eugenio; da Costa, Marisa; Heermann, Ralf

    2013-08-01

    Dengue fever is an important vector-borne disease, mainly transmitted by Aedes aegypti. To date, there are no vaccines or effective drugs available against this arboviral disease. As mosquito control is practically the only method available to control dengue fever, alternative and cost-effective pest control strategies need to be explored. The gram-negative enteric bacteria Xenorhabdus and Photorhabdus are symbiotically associated with nematode parasites, which themselves are highly pathogenic for insect larvae. Here, we evaluate the oral toxicity of these entomopathogenic bacteria in A. aegypti larvae. The susceptibility of larvae (third late or fourth early instars) was assessed by exposing them to suspensions containing Photorhabdus luminescens or Xenorhabdus nematophila, respectively. Two diet treatments were tested with larvae fed on pet food and unfed larvae. After 24 h, larvae began to die when exposed to the bacteria. Exposure to P. luminescens killed 73% of the fed and 83% of the unfed larvae, respectively. In comparison, X. nematophila was less pathogenic, killing 52% of the larvae in the fed and 42% in the unfed treatment. Remarkably, cannibalism was observed in all bioassays after exposing larvae to either of the bacterial species. To our knowledge, this is the first report demonstrating the efficiency of these entomopathogenic bacteria for oral A. aegypti killing. Our results provide a promising basis for using these bacteria as bioinsecticides for mosquito control in the future.

  10. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    Science.gov (United States)

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties.

  11. Evaluation of ATC as an Orally Administered Drug in Treatment of Cadmium Toxicity of Rat Organs

    Directory of Open Access Journals (Sweden)

    S. Nabilaldine Fatemi

    2009-01-01

    Full Text Available The effect of N-tetramethylene dithiocarbamate (ATC as a chelating agent on the excretion of cadmium was evaluated in cadmium-poisoned Wistar rats following administration through food and drink. The present research aimed to characterize the potential efficiency of ATC as an orally administered chelator drug after cadmium administration for 60 days. This chelator significantly enhanced the urinary and biliary excretion of cadmium and restored the altered levels of iron. Cadmium and iron concentrations in different tissues were determined by graphite furnace and flame atomic absorption spectrometry (GF AAS and F AAS methods, respectively. The chelation therapy results show that ATC is able to remove cadmium ions from different tissues while iron concentration returned to the normal level and the clinical symptoms were also reduced. In summary, we conclude that ATC is able to mobilize and promote the excretion of cadmium in rat organs and reduce the side effects and general symptoms of toxicity caused by cadmium and might be useful for preliminary testing of the efficacy of chelating agents in human body. However, these results should be confirmed in different experimental models before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in cadmium toxicity.

  12. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    OpenAIRE

    Samir Attoub; Karam, Sherif M.; Abderrahim Nemmar; Kholoud Arafat; Annie John; Wafa Al-Dhaheri; Mahmood Ahmed Al Sultan; Haider Raza

    2014-01-01

    Background: Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant ...

  13. Biodistribution and tissue toxicity of amphotericin B in mice following multiple dose administration of a novel oral lipid-based formulation (iCo-009).

    Science.gov (United States)

    Gershkovich, Pavel; Sivak, Olena; Wasan, Ellen K; Magil, Alex B; Owen, David; Clement, John G; Wasan, Kishor M

    2010-12-01

    The purpose of this study was to assess the biodistribution and toxicity of amphotericin B (AMB) following multiple dose administration of an oral lipid-based formulation (iCo-009). BALB/c female mice were used. ICo-009 was administered twice daily for 5 days at doses of 2.5-20 mg/kg. Untreated animals, oral vehicle or intravenous Fungizone® (1 or 2 mg/kg) served as control groups. The animals were sacrificed 12 h following the last administration of AMB, and blood and multiple tissues were harvested for drug analysis and histopathological evaluation. Plasma or tissue samples were analysed for concentrations of AMB or creatinine by means of HPLC-UV. A dose-dependent accumulation of AMB in liver, spleen, kidney and lung tissues was found. The concentration of the drug in all these organs exceeded the corresponding concentrations in plasma at the same dose. The concentrations of AMB in heart and brain were similar to the corresponding concentrations in plasma. Creatinine concentrations were elevated above normal concentrations in the 2 mg/kg Fungizone® group only. Histopathological analysis of kidney and liver tissues revealed a normal pattern in all treated groups, except the 2 mg/kg Fungizone® group. No gastrointestinal toxicity was found in this study. A multiple dose treatment regimen with iCo-009 in mice results in a gradual accumulation of AMB in tissues. Despite significant concentrations of AMB, no kidney or liver toxicity of orally administered AMB was detected in this study. Furthermore, multiple oral administration of iCo-009 or of vehicle control did not induce gastrointestinal toxicity.

  14. Development of methods for avian oil toxicity studies using the double crested cormorant (Phalacrocorax auritus).

    Science.gov (United States)

    Cunningham, Fred; Dean, Karen; Hanson-Dorr, Katie; Harr, Kendal; Healy, Kate; Horak, Katherine; Link, Jane; Shriner, Susan; Bursian, Steven; Dorr, Brian

    2017-07-01

    Oral and external dosing methods replicating field exposure were developed using the double crested cormorant (DCCO) to test the toxicity of artificially weathered Deepwater Horizon Mississippi Canyon 252 oil. The majority of previous oil dosing studies conducted on wild-caught birds used gavage methods to dose birds with oil and determine toxicity. However, rapid gut transit time of gavaged oil likely reduces oil absorption. In the present studies, dosing relied on injection of oil into live feeder fish for oral dosing of these piscivorous birds, or applying oil to body contour feathers resulting in transdermal oil exposure and oral exposure through preening. Both oral and external oil dosing studies identified oil-related toxicity endpoints associated with oxidative stress such as hemolytic anemia, liver and kidney damage, and immuno-modulation or compromise. External oil application allowed for controlled study of thermoregulatory stress as well. Infrared thermal images indicated significantly greater surface temperatures and heat loss in treated birds following external oil applications; however, measurements collected by coelomically implanted temperature transmitters showed that internal body temperatures were stable over the course of the study period. Birds exposed to oil externally consumed more fish than control birds, indicating metabolic compensation for thermal stress. Conversely, birds orally dosed with oil experienced hypothermia and consumed less fish compared to control birds. Published by Elsevier Inc.

  15. Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests.

    Science.gov (United States)

    Bouhifd, Mounir; Bories, Gilles; Casado, Juan; Coecke, Sandra; Norlén, Hedvig; Parissis, Nicholaos; Rodrigues, Robim M; Whelan, Maurice P

    2012-06-01

    Application of High Throughput Screening (HTS) to the regulatory safety assessment of chemicals is still in its infancy but shows great promise in terms of facilitating better understanding of toxicological modes-of-action, reducing the reliance on animal testing, and allowing more data-poor chemicals to be assessed at a reasonable cost. To promote the uptake and acceptance of HTS approaches, we describe in a stepwise manner how a well known cytotoxicity assay can be automated to increase throughput while maintaining reliability. Results generated with selected reference chemicals compared very favourably with data obtained from a previous international validation study concerning the prediction of acute systemic toxicity in rodents. The automated assay was then included in a formal ECVAM validation study to determine if the assay could be used for binary classification of chemicals with respect to their acute oral toxicity, using a threshold equivalent to a dose of 2000 mg/kg b.w. in a rodent bioassay (LD50). This involved the blind-testing of 56 reference chemicals on the HTS platform to produce concentration-response and IC50 data. Finally, the assay was adapted to a format more suited to higher throughput testing without compromising the quality of the data obtained. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Oral hairy leukoplakia: An exfoliative cytology study

    Directory of Open Access Journals (Sweden)

    Ajay Reginald

    2010-01-01

    Full Text Available Oral hairy leukoplakia (OHL is a white, hyperplastic, vertically corrugated lesion that occurs on the lateral border of the tongue, usually unilateral. Caused by the Epstein-Barr Virus (EBV, the lesion is said to be an early indicator of an immune deficiency status, thereby unmasking subclinical systemic conditions. OHL mimics many other white lesions of the oral cavity; therefore, it becomes imperative to identify the lesion. This study used exfoliative cytology, a noninvasive procedure, which helped in identifying the cellular changes brought about by the virus in the oral epithelium. The study revealed a subclinical phase of OHL, where the cellular changes were seen even before the appearance of the clinical lesion.

  17. Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors.

    NARCIS (Netherlands)

    Jonge, M.J.A. de; Punt, C.J.A.; Sparreboom, A.; Planting, A.S.T.; Peters, M.E.W.J.; Schraaf, J. van de; Jackman, A.; Smith, R.J.H.; Mulder, P.H.M. de; Verweij, J.

    2002-01-01

    PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once d

  18. Oral toxicity of isotretinoin, misoprostol, methotrexate, mifepristone and levonorgestrel as pregnancy category X medications in female mice.

    Science.gov (United States)

    Kim, Seong-Kwan; Shin, Soo-Jeong; Yoo, Yohan; Kim, Na-Hyun; Kim, Dong-Soon; Zhang, Dan; Park, Jin-A; Yi, Hee; Kim, Jin-Suk; Shin, Ho-Chul

    2015-03-01

    An oral toxicity study of several pregnancy category X drugs was performed in female ICR mice. The drugs were administered orally once daily for 3 days at doses of 1, 10 and 100 μg/kg for isotretinoin; 6.7, 67 and 670 μg/kg for misoprostol; 83, 830 and 8,300 μg/kg for methotrexate; 3.3, 33 and 330 μg/kg for mifepristone; and 25, 250 and 2,500 μg/kg for levonorgestrel. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry and necropsy findings were examined. Following administration of methotrexate at 8,300 μg/kg, a number of animals exhibited decreased spontaneous activity, and one animal died. In the hematological analysis, compared with those treated with the control, the animals treated with the drugs exhibited similar significant decreases in the number of granulocytes and granulocyte differentiation, and increases in lymphocyte differentiation. In the serum biochemical analysis, animals receiving high doses of the five drugs demonstrated significant changes in uric acid, glucose, alkaline phosphatase, total bilirubin, lipase, total cholesterol and calcium. At necropsy, intestinal redness was frequently observed in animals that received the high dose of methotrexate. Uterus enlargement and ovary dropsy were also detected in the groups receiving mifepristone and levonorgestrel. Despite the short-term exposure, these drugs exhibited significant side effects, including white blood cell toxicity, in the mouse model. Category X drugs can be traded illegally via the internet for the purpose of early pregnancy termination. Thus, illegal abuse of the drugs should be further discouraged to protect mothers.

  19. Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

    Directory of Open Access Journals (Sweden)

    Talib Hussain

    2012-04-01

    Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

  20. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    Science.gov (United States)

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Anti-Osteoporotic Effects of Angelica sinensis (Oliv. Diels Extract on Ovariectomized Rats and Its Oral Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Dong Wook Lim

    2014-10-01

    Full Text Available Angelica sinensis root is one of the herbs most commonly used in China; it is also often included in dietary supplements for menopause in Europe and North America. In the present study, we examined the anti-osteoporotic effects of A. sinensis extract in an ovariectomized (OVX rat model of osteoporosis as well as toxicity of the extract after repeated oral administration. The OVX rats were treated with 17β-estradiol (10 μg/kg i.p. once daily or A. sinensis extract (30, 100, and 300 mg/kg, p.o. once daily for four weeks. The bone (femur mineral density (BMD of rats treated with the extract (300 mg/kg was significantly higher than that of the OVX-control, reaching BMD of the estradiol group. Markers of bone turnover in osteoporosis, serum alkaline phosphatase, collagen type I C-telopeptide and osteocalcin, were significantly decreased in the extract group. The body and uterus weight and serum estradiol concentration were not affected, and no treatment-related toxicity was observed during extract administration in rats. The results obtained indicate that A. sinensis extract can prevent the OVX-induced bone loss in rats via estrogen-independent mechanism.

  2. Quantitative structure-activity relationship modelling of oral acute toxicity and cytotoxic activity of fragrance materials in rodents.

    Science.gov (United States)

    Papa, E; Luini, M; Gramatica, P

    2009-10-01

    Fragrance materials are used as ingredients in many consumer and personal care products. The wide and daily use of these substances, as well as their mainly uncontrolled discharge through domestic sewage, make fragrance materials both potential indoor and outdoor air pollutants which are also connected to possible toxic effects on humans (asthma, allergies, headaches). Unfortunately, little is known about the environmental fate and toxicity of these substances. However, the use of alternative, predictive approaches, such as quantitative structure-activity relationships (QSARs), can help in filling the data gap and in the characterization of the environmental and toxicological profile of these substances. In the proposed study, ordinary least squares regression-based QSAR models were developed for three toxicological endpoints: mouse oral LD(50), inhibition of NADH-oxidase (EC(50) NADH-Ox) and the effect on mitochondrial membrane potential (EC(50) DeltaPsim). Theoretical molecular descriptors were calculated by using DRAGON software, and the best QSAR models were developed according to the principles defined by the Organization for Economic Co-operation and Development.

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

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

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

  4. Superoxide dismutase and glutathione peroxidase in oral submucous fibrosis, oral leukoplakia, and oral cancer: A comparative study

    Directory of Open Access Journals (Sweden)

    Shubha Gurudath

    2012-01-01

    Full Text Available Objectives: Present study was undertaken to estimate and compare erythrocyte superoxide dismutase (E-SOD and glutathione peroxidase (GPx levels in oral submucous fibrosis, oral leukoplakia, oral cancer patients, and healthy subjects. Materials and Methods: E-SOD and GPx levels were estimated in OSF, oral leukoplakia, and oral cancer patients with 25 subjects in each group. The results obtained were compared with the corresponding age-/sex- matched control groups. Results: Statistically significant ( P 0.05. Oral cancer group had the lowest levels amongst the study groups. Conclusion: Imbalance in antioxidant enzyme status may be considered as one of the factors responsible for the pathogenesis of cancer and may serve as a potential biomarker and therapeutic target to reduce the malignant transformation in oral premalignant lesions/conditions.

  5. An Oral Contraceptive Drug Interaction Study

    Science.gov (United States)

    Bradstreet, Thomas E.; Panebianco, Deborah L.

    2004-01-01

    This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

  6. An Oral Contraceptive Drug Interaction Study

    Science.gov (United States)

    Bradstreet, Thomas E.; Panebianco, Deborah L.

    2004-01-01

    This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

  7. Oral coatings: a study on the formation, clearance and perception

    NARCIS (Netherlands)

    Camacho, S.

    2015-01-01

    Oral coatings are residues of food and beverages that coat the oral mucosa after consumption. Several studies have reported on the lubrication properties in mouth, and the after-feel and after-taste impact of oral coatings. Further, oral coatings have been suggested to influence subsequent taste per

  8. Acute and subchronic toxicity studies of kernel extract of Sclerocarya ...

    African Journals Online (AJOL)

    Administrator

    evaluation was done by oral feeding of the rats with the seed kernel extract daily at doses .... Significantly different from the control (P < 0.05) using one way analysis of variance. Subchronic ... acute toxicity did not produce any grossly negative behavioural changes such .... against garlic-induced oxidative stress. Journal of ...

  9. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wei

    Full Text Available A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah, to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg, medium-dose group (200 mg/kg, low-dose group (100mg/kg and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05 with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  10. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Science.gov (United States)

    Wei, Xiaojuan; Zhang, Jiyu; Niu, Jianrong; Zhou, Xuzheng; Li, Jianyong; Li, Bing

    2015-01-01

    A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  11. Comparative study of effectiveness of oral acyclovir with oral erythromycin in the treatment of Pityriasis rosea.

    Science.gov (United States)

    Amatya, A; Rajouria, E A; Karn, D K

    2012-01-01

    Pityriasis rosea is an acute, self-limiting disease, probably infective in origin, affecting mainly children and young adults, characterized by distinctive skin eruptions and minimal constitutional symptoms. Both oral Erythromycin and oral Acyclovir have been used in its management. To compare the effectiveness of oral Erythromycin and oral Acyclovir in the treatment of Pityriasis rosea. Forty two patients with clinical diagnosis of Pityriasis rosea were enrolled. They were randomized into two groups. One group was given high-dose oral Acyclovir and another group oral Erythromycin in standard dose. The participants were evaluated one, two, four, six and eight weeks and six months after commencement of the study. Forty two patients including 26 males and 16 females completed the study. After 8th week, all patients showed complete response in both the groups. The response to oral Acyclovir compared with that to oral Erythromycin was better and was statistically significant in 1st, 2nd, 4th and 6th weeks. Although it is a self-limiting disease which resolves within three weeks to three months, this study reveals that both oral Acyclovir and oral Erythromycin are helpful in decreasing the severity and duration of Pityriasis rosea. Moreover, the study also indicates that oral Acyclovir is more effective than oral Erythromycin in reducing the severity and duration of Pityriasis rosea.

  12. ACUTE AND SUB ACUTE TOXICITY STUDY ON SIDDHA DRUG VELVANGA PARPAM

    Directory of Open Access Journals (Sweden)

    K. Samraj*, K. Kanagavalli , P. Sathiya Rajeswaran and P. Parthiban

    2013-11-01

    Full Text Available Benign Prostatic Hyperplasia (BPH is a common progressive disease among men, with an incidence that is high among elderly. Velvanga parpam (VP has been employed as traditional remedy for Benign Prostatic Hyperplasia (BPH which is a herbo mineral formulation. As a mandate, steps were taken to evaluate safety profile of VP in rats and mice following OECD guidelines. Acute toxicity studies, different doses of VP were administered orally to rats once daily for one week. Sub-acute toxicity studies were carried in four different groups in which VP was administrated orally to rats once daily for 28 days in various doses ranging from 2.5, 5, 10 Mg/kg for mice respectively. Detailed hematological, biochemical, necropsy and histopathological evaluation of organs was performed for all animals. The VP was well tolerated and no toxic manifestations were seen in any animal. Histopathological analysis revealed that Spleen, Testes, Pancreas, Lung, Liver, Brain, Heart, Stomach, Intestine, Bone, Ovary, and Kidney tissues of treated groups did not show any signs of toxicity. Mortality observed in highdose. The VP was found to be safe in animals. No toxic effect was observed up to 5mg/kg of Velvanga parpam in acute and sub-acute toxicity studies.

  13. Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, E; Pedersen, H

    1987-01-01

    The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir...

  14. Avisalmvac: evaluation studies of stability and toxicity

    Directory of Open Access Journals (Sweden)

    Daniela Botus,

    2008-12-01

    Full Text Available In Pasteur Institute laboratories there was developed AVISALMVAC, a vaccine against avian Salmonella, a biological product that contains S. enteritidis and S. typhimurium bacterin, with oil adjuvant. This paper presents the results of the studies regarding the stability and toxicity evaluation of this vaccine stored under conditions recommended by the manufacturer (2-80C at the end of the period of validity. The vaccine stability was assessed by serological and histopathological analysis of samples from SPF chickens vaccinated with the product at the end of the period of validity. The study of Avisalmvac toxicity was carried out by inoculation of the product or its components on Vero cell monolayer, and the effects were microscopically recorded or by MTT test, applied at 6 days post-inoculation. Antibody titers recorded at 2 and 3 weeks post vaccination demonstrated the vaccine ability (used after an year since manufacture to induce synthesis of specific antibodies and therefore, the product stability was proven. Histopathological examinations carried out on samples taken at 18 days post vaccinationfrom the vaccination site (skeletal muscle and skin and spleen, did not show any lesions associated to vaccination with Avisalmvac. The cytotoxicity analysis made by inoculating the vaccine or its components on Vero cell monolayer and the microscopic examination did not record visible cytopathic effects for any vaccine dilutions or vaccine components. The cell metabolism evaluation by MTT assay made at 6 days after vaccine/vaccine components inoculation on Vero monolayer, shown the ability of the vaccine and oil adjuvant to stimulate cell metabolism, and a certain degree of toxicity / inhibition of dehydrogenase metabolism associated to one of emulsifier but at dilutions higher than those used in the vaccine formula.

  15. Subchronic toxicity study of GH transgenic carp.

    Science.gov (United States)

    Yong, Ling; Liu, Yu-Mei; Jia, Xu-Dong; Li, Ning; Zhang, Wen-Zhong

    2012-11-01

    A subchronic toxicity study of GH (growth hormone) transgenic carp was carried out with 60 SD rats aged 4 weeks, weight 115∼125 g. Ten male and 10 female rats were allotted into each group. Animals of the three groups (transgenic carp group (GH-TC), parental carp group (PC) and control group) were fed soy- and alfalfa-free diet (SAFD) with 10% GH transgenic carp powder, 10% parental carp powder or 10% common carp powder for 90 consecutive days, respectively. In the end of study, animals were killed by exsanguination via the carotid artery under diethyl ether anesthesia, then weights of heart, liver, kidneys, spleen, thymus, brain, ovaries and uterus/testis were measured. Pathological examination of organs was determined. Endocrine hormones of triiodothyronine (T3), thyroid hormone (T4), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone (P) and testosterone (T) levels were detected by specific ELISA kit. Parameters of blood routine and blood biochemical were measured. The weights of the body and organs of the rats, food intake, blood routine, blood biochemical test and serum hormones showed no significant differences among the GH transgenic carp-treated, parental carp-treated and control groups (P>0.05). Thus, it was concluded that at the dose level of this study, GH transgenic carp showed no subchronic toxicity and endocrine disruption to SD rats.

  16. Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center

    Directory of Open Access Journals (Sweden)

    V M Patil

    2014-01-01

    Full Text Available Background: Recent studies indicate neoadjuvant chemotherapy (NACT can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routine administration if an average relative dose intensity (ARDI of ≥0.90 or more in at least 70% of the patients. Materials and Methods: Technically unresectable oral cancers with Eastern Cooperative Oncology Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE 4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2 cycles of planned chemotherapy with ARDI of 0.85 or more, reason for delay, toxicity, and response are presented. Results: The NACT was completed by all patients. The number of subjects who completed all planned cycles of chemotherapy are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11 (91.67%. All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients (91.67%. The response rate of chemotherapy was 83.33%. There were three complete response, seven partial response, and two stable disease seen post NACT in this study. Conclusion: Docetaxel, cisplatin and 5 fluorouracil regimen can be routinely administered at our center with the supportive care methods and precautionary methods used in our study.

  17. Transcriptomic studies on liver toxicity of acetaminophen.

    Science.gov (United States)

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  18. Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

    Science.gov (United States)

    Choonara, Imti; Conroy, Sharon

    2017-01-01

    Background Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels. Methods A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included. Results One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths). Conclusions Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR. PMID:28125632

  19. Experimental Studies of Toxicity on HNIW and Its Intermediates

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; CHEN Shu-sen; JIN Shao-hua; CUI Zhao-kuan

    2006-01-01

    The polycyclic nitramine hexanitrohexaazaisowurtane(HNIW) is a compound of high energy density. HNIW can replace 1, 3, 5-trinitro-1, 3, 5-triazacyclohexane(RDX)or HMX, but its toxicity is unknown. In this paper,HNIW, hexabenzylhexaazaisowurtzitane ( HBIW ), tetraacetyldibenzulhexaazaisowurtzitane ( TADBIW ), tetraacetyldiformylhexaazaisowurtzitane(TADFIW) and tetraacetylhexaazaisowurtzitane(TAIW), which are intermediates of the synthesis of the HNIW, were selected as the tested objects in acute toxicity test, acute eye stimulation test and skin irritation test according to the standards of "chemical product testing method-401: acute oral toxicity test", "chemical product testing means-405: acute eye irritation/corrosion test" and "chemical product testing means-404: acute dermal irritation/corrosion test" of National Circumstance Protect Bureau. The results show that all of the five objects have no toxicity, no stimulation to eye and skin under the tested conditions.

  20. Epidemiological and clinicopathological study of oral leukoplakia

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    Mishra Minati

    2005-01-01

    Full Text Available BACKGROUND: Oral white lesions that cannot be clinically or pathologically characterized by any specific disease are referred to as leukoplakia. Such lesions are well known for their propensity for malignant transformation to the extent of 10-20%.Exfoliative cytology is a simple and useful screening tool for detection of malignant or dysplastic changes in such lesions. AIMS: A clinicoepidemiological and cytological study of oral leukoplakia was undertaken to detect their malignant potential and value of cytology in diagnosis. METHODS: This 2 year duration multicentre study was undertaken on all patients presenting with oral white lesions to the out patient department of the two institutions. Those cases in which a specific cause (infective, systemic disease or specific disease entity for the white lesions were elicited were excluded from the study. The group with idiopathic white lesions was included in the study and was subjected to periodic exfoliative cytological study at three monthly intervals to detect any malignant change. Patients presenting less than two times for follow up were excluded from the final analysis of the study. RESULTS: Out of total 2920 patients studied, 89.53% showed benign, 9.93% showed dysplastic and, 0.72% showed malignant cells on exfoliative cytological study. All the dysplastic and malignant lesions were subjected to histopathological study by incisional biopsy. Among the dysplastic lesions 13.79% proved benign and the rest true dysplastic. Among the cytologically malignant group 4.76% showed dysplasia and the rest true malignant lesions. CONCLUSION: Persistent leukoplakia has a potential for malignant transformation and exfoliative cytology could be a simple method for early detection of dysplastic and malignant changes.

  1. 啮齿类动物28天重复剂量经口毒性改良试验简介与进展%Introduction and progress on the enhancement of repeated dose 28-day oral toxicity study in rodents

    Institute of Scientific and Technical Information of China (English)

    王恒娟; 刘兆平

    2012-01-01

    Repeated dose 28-day oral toxicity study in rodents ( OECD Test Guidelines 407) is widely used to evaluate the general toxicity of chemicals. In 1998, the Organization for Economic Co-operation and Development (OECD) enhanced existing TG 407 to develop new Test Guidelines for screening and testing potential endocrine disruptors. This procedure has been verified by an extensive international validation program. To provide reference for developing endocrine disruptor evaluation system in China, the enhanced TG 407, its progress and its advantages and disadvantages were summarized in this paper.%经济合作与发展组织(Organization for Economic Co-operation and Development,OECD)推荐的啮齿类动物28天重复剂量经口毒性试验( OECD TG 407)是一种广泛用于评价化学物一般毒性的毒理学试验方案.OECD在1998年对其进行改良后,建立TG 407改良试验并经世界多国实验室验证,用于检测化学物的内分泌干扰作用.本文简要介绍了OECD TG 407改良试验指南,并对其进展情况以及优缺点进行综述,以期为我国的内分泌干扰物的评价体系提供参考.

  2. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Bladeren, van P.J.; Rietjens, I.M.C.M.

    2006-01-01

    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be high

  3. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Bladeren, van P.J.; Rietjens, I.M.C.M.

    2006-01-01

    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be high

  4. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    Science.gov (United States)

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety.

  5. Subchronic oral toxicity evaluation of ethanolic whole plant extract of Eleucine indica on haematological and biochemical indices in Wistar albino rats

    Institute of Scientific and Technical Information of China (English)

    Ette Okon Ettebong; PaulAlozie Nwafor

    2016-01-01

    Objective: To evaluate the effect of ingestion of ethanolic whole plant extract of Eleucine indica on haematological and biochemical parameters of Wistar albino rats. Methods: Subchronic toxicity study was carried out by oral administration of different doses (200, 400 and 600 mg/kg body weight) of the extract on alternate-day basis to different groups of rats for 28 days. The animals were subsequently sacrificed and blood samples were collected by cardiac puncture for haematological and biochemical analyses. Results: Haematological indices were preserved and the extract showed significant (P Conclusions: The results obtained indicated that ingestion of Eleucine indica whole plant extract for a long period of time reduces both bleeding and clotting times, reduces blood sugar and shows no apparent toxic effect on liver and kidneys. The results of this study may be useful as a basis for clinical trials in humans.

  6. Protocols to study the physiology of oral biofilms.

    Science.gov (United States)

    Lemos, José A; Abranches, Jacqueline; Koo, Hyun; Marquis, Robert E; Burne, Robert A

    2010-01-01

    The oral cavity harbors several hundred different bacterial species that colonize both hard (teeth) and soft tissues, forming complex populations known as microbial biofilms. It is widely accepted that the phenotypic characteristics of bacteria grown in biofilms are substantially different from those grown in suspensions. Because biofilms are the natural habitat for the great majority of oral bacteria, including those contributing to oral diseases, a better understanding of the physiology of adherent populations is clearly needed to control oral microbes in health and disease. In this chapter, we use oral streptococci as examples for studying the physiology of oral biofilms.

  7. Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity.

    Directory of Open Access Journals (Sweden)

    Kwangkook Lee

    Full Text Available Botulinum neurotoxins (BoNTs are produced by Clostridium botulinum and cause the fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released together with several auxiliary proteins as progenitor toxin complexes (PTCs to become highly potent oral poisons. Here, we report the structure of a ∼760 kDa 14-subunit large PTC of serotype A (L-PTC/A and reveal insight into its absorption mechanism. Using a combination of X-ray crystallography, electron microscopy, and functional studies, we found that L-PTC/A consists of two structurally and functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in the harsh environment of the gastrointestinal tract. BoNT absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. We identified monosaccharides that blocked oral BoNT intoxication in mice, which suggests a new strategy for the development of preventive countermeasures for BoNTs based on carbohydrate receptor mimicry.

  8. Ninety Day Toxicity and Toxicokinetics of Fluorochloridone after Oral Administration in Rats

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    Suhui Zhang

    2015-05-01

    Full Text Available The ninety day toxicity and toxicokinetics of fluorochloridone (FLC were accessed in Wistar rats. Animals were gavaged with FLC at doses of 31.25 mg/kg, 125 mg/kg and 500 mg/kg for ninety days, followed by thirty days for recovery. On the 1st, 60th, 75th and 90th days of the dosing phase, plasma of ten animals of all groups treated with FLC was collected for toxicokinetic analysis of FLC by an UPLC-MS/MS method. Numerous changes in body weight, hematology, serum chemistry, and organ weight ratios were observed by the 45th and 90th dosing day. Most changes in groups treated with FLC were absent on the last recovery day. Testis and epididymis lesions were consistently seen in histopathological observations on the 45th, 90th dosing day and the last recovery day. Repeated administration of FLC increased the level of testosterone in serum in male rats on the 90th dosing day. FLC plasma concentrations could be detected in all animal drug-treated groups during the dosing phase, and a dose proportional relationship was seen between FLC dose and AUC or Cmax. This study will support future studies on the mechanism of FLC-induced toxicity.

  9. Evaluation of the sub-acute oral toxic effect of methanol extract of Clinacanthus nutans leaves in rats

    Institute of Scientific and Technical Information of China (English)

    Xiu Wen P’ng; Gabriel Akyrem Akowuah; Jin Han Chin

    2013-01-01

    Objective: To examine the possible sub-acute toxic effect after 14 d oral administration with 0.3 g/kg, 0.6 g/kg and 0.9 g/kg of methanol leaves extract of Clinacanthus nutans (C. nutans) on liver and kidney functions in young male Sprague Dawley (SD) rats. Methods: This study was carried out according to OECD 407 guideline. A total of 24 young healthy male SD rats aged between 8-12 weeks old were used throughout the experiments. Each group consisted of six rats (n=6). All animals were observed twice daily until day-14. Body weight, food consumption and water intake were measured on day-3, 7 and day-14. Blood samples were collected and used to analyse the serum levels of AST, ALT, ALP, bilirubins, urea and creatinine in rats. Relative organ weights for liver, kidney, heart, spleen and lung were calculated. Results: From the results obtained, all the serum biochemical parameters, food and water intake, relative organs weight showed no significant changes when compared to the control group. No lethality and abnormal behavioural changes were seen in both control and treatment groups during experiment.Conclusions: For conclusion, repeatedly dosing of C. nutans extract at 0.3g/kg, 0.6g/kg and 0.9 g/kg up to 14 d was proven safe in male SD rats without causing any adverse effects and organ damages in male SD rats.

  10. Oral teratogenicity studies of methyl bromide in rats and rabbits.

    Science.gov (United States)

    Kaneda, M; Hojo, H; Teramoto, S; Maita, K

    1998-05-01

    Teratogenicity studies of methyl bromide, a widely used fumigant, were conducted in rats and rabbits. Methyl bromide was dissolved in corn oil and administered orally to groups of 24 copulated female Crj:CD (SD) rats at dose levels of 0 (corn oil), 3, 10 or 30 mg/kg/day on days 6-15 of gestation and to groups of 18 artificially inseminated female Kbl:JW rabbits at 0, 1, 3 or 10 mg/kg/day on days 6-18 of gestation. Maternal rats and rabbits were euthanized on respective days 20 and 27 of gestation. Foetuses were examined for survival, growth and teratological alterations. Maternal toxicity was evident in the high-dose groups for both species. In these groups, maternal body weight gains and food consumption were significantly decreased during the dosing and post-dosing periods. Necropsy of maternal rats also revealed erosive lesions in the stomach and the surrounding organs. However, no treatment-related adverse effects were found in foetuses of the treated groups for both rat and rabbit studies. These results led to the conclusion that methyl bromide was not foetotoxic or teratogenic to rat and rabbit foetuses up to dose levels of 30 and 10 mg/kg/day, respectively, at which maternal toxicity was evident for both species.

  11. In vivo toxicity study of Lantana camara

    Institute of Scientific and Technical Information of China (English)

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara(L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions:Methanolic extract of L. camara is relatively safe on short-term exposure.

  12. Evaluation of statistical tools used in short-term repeated dose administration toxicity studies with rodents.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Sakuratani, Yuki; Abe, Takemaru; Kamata, Eiichi; Hayashi, Makoto

    2008-02-01

    In order to know the different statistical tools used to analyze the data obtained from twenty-eight-day repeated dose oral toxicity studies with rodents and the impact of these statistical tools on interpretation of data obtained from the studies, study reports of 122 numbers of twenty-eight-day repeated dose oral toxicity studies conducted in rats were examined. It was found that both complex and easy routes of decision trees were followed for the analysis of the quantitative data. These tools include Scheffe's test, non-parametric type Dunnett's and Scheffe's tests with very low power. Few studies used the non-parametric Dunnett type test and Mann-Whitney's U test. Though Chi-square and Fisher's tests are widely used for analysis of qualitative data, their sensitivity to detect a treatment-related effect is questionable. Mann-Whitney's U test has better sensitivity to analyze qualitative data than the chi-square and Fisher's tests. We propose Dunnett's test for analysis of quantitative data obtained from twenty-eight-day repeated dose oral toxicity tests and for qualitative data, Mann-Whitney's U test. For both tests, one-sided test with p=0.05 may be applied.

  13. Biochemical and serological studies on oral ureaplasma.

    Science.gov (United States)

    Saito, Y; Ishikawa, O; Iritani, A; Yonemoto, R; Horikawa, T

    1984-09-01

    This study was conducted to study chemically and serologically the characteristics of the Ureaplasmas isolated from the human oral cavity. Two hundred and fifty-one healthy and 12 periodontitis subjects were examined for the incidence of the isolation of Ureaplasmas from their oral cavity. A total of twenty-six strains was isolated from the healthy human saliva. But no strains could be isolated from a variety of clinical specimens obtained from the patients. The serological properties of the isolates were tested by the method of metabolism inhibition test (MI test). Seven out of 26 isolates were serologically identical with either one of the ATCC standard strains. However, the serological types of the other strains could not be demonstrated by the MI test. The biological characteristics of 4 isolates and ATCC strains were tested by the usual method. The isolates did not metabolize glucose and arginine, while all strains hydrolyzed urea. On the other hand, none of the isolates lysed skimmed milk and gelatin. The proteolytic activity of the isolates could be demonstrated by using casein and horse serum proteins as substrates. Zymogram patterns from one of the isolates and Streptococcus salivarius were obtained by polyacrylamide gel electrophoresis of the cells lysed with digitonin or cell protein extracts. On the basis of the gel electrophoresis patterns, it is clear that the urease of the Ureaplasma is different from that of the Streptococcus salivarius.

  14. A review of toxicity studies of single-walled carbon nanotubes in laboratory animals.

    Science.gov (United States)

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-02-01

    We summarized the findings of in vivo toxicity studies of single-walled carbon nanotubes (SWCNTs) in laboratory animals. The large majority addressed the pulmonary toxicity of SWCNTs in rodents. Inhalation, pharyngeal aspiration, and intratracheal instillation studies revealed that SWCNTs caused acute and chronic inflammation, granuloma formation, collagen deposition, fibrosis, and genotoxic effects in the lungs. Pulmonary toxicity of well-dispersed SWCNTs was more potent than less dispersed ones. Airway exposure to SWCNTs also induced cardiovascular diseases in mice. Oxidative stress was caused by the administration of SWCNTs. Injected SWCNTs were distributed throughout most of the organs including the brain, mainly retained in the lungs, liver, and spleen, and eliminated through the kidney and bile duct. Orally administered SWCNTs are suggested to be absorbed from the gastrointestinal tract to the blood circulation in mice and rats. Although no definitive study on the carcinogenicity of SWCNTs is available at present, evidence of carcinogenicity has not been reported in toxicity studies cited in this review. Overall, the available data provides initial information on SWCNT toxicity. To further clarify their toxicity and risk assessment, studies should be conducted using well-characterized SWCNTs, standard protocols, and the relevant route and doses of human exposure.

  15. Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.

    Science.gov (United States)

    Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria

    2015-08-01

    With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates.

  16. Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

    Science.gov (United States)

    Xu, Zhi; Huang, Chun-Ming; Shao, Zhe; Zhao, Xiao-Ping; Wang, Meng; Yan, Ting-Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Liu, Ke; Shang, Zheng-Jun

    2017-01-01

    Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway. PMID:28257034

  17. 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.

  18. 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)

  19. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Kim YR

    2014-12-01

    Full Text Available Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea  *These authors contributed equally to this work Abstract: Nanoparticles (NPs are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s of 100 nm negatively (ZnOAE100[-] or positively (ZnOAE100[+] charged zinc oxide (ZnO NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s. After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg

  20. [Toxicity studies of Pharmachem's tylosin tartrate for broilers and turkeys].

    Science.gov (United States)

    Donev, B; Angelov, A K; Vitanov, S

    1978-01-01

    Studied were the acute, subchronic, and chronic toxicity of the Pharmachim tylosin tartrate as well as the tolerance of chicken broilers and turkeys. The mean lethal dose of the antibiotic at subcutaneous application to 28-32 day-old broilers was 620 mg/kg; the oral dose was 1500 mg/kg. In the case of 42-45-day-old broilers these values were 740 and 5400 mg/kg. The LD50 at i/v infusion for 75-77-day-old ones was 48 mg/kg. Beside the age and route of introduction toxicity was found to depend on the initial biologic activity of tylosin tartrate. The subcutaneous injection of tylosin tartrate at the rate of 30 mg/kg for 20 days did not lead to changes in the appetite, behaviour, growth, and structure of viscera. A 42-day treatment at the same rate, however, resulted in slightly manifested and fully reversible dystrophic changes in the liver and kidneys. Higher doses (90 and 150 mg/kg) led to transient depression, stunting of growth, and a rise of the urea level and the activity of blood transaminases as well as to moderate destructive changes in the liver and kidneys. The stimulation of growth and the improvement of feed conversion (without deviations in the clinical and biochemical indices of the blood and the structure and development of the viscera in broilers) were recorded after the application of a water-soluble formula of tylosin tartrate for a period of 98 days offered via the drinking water in amounts equal to or exceeding 2 to 4 times the ED50. Turkeys' tolerance for the preparation was evaluated as very good so far as single i/m injective applications were concerned in doses exceeding 3, 5, and 10 times the average effective rates, no differences in this respect being noted with the comparative use of tylosin tartrate produced by the Elanco firm.

  1. Oral hybrid verrucous carcinoma: a clinical study.

    Science.gov (United States)

    Gokavarapu, Sandhya; Rao S, L M Chandrasekhara; Tantravahi, Uma Sankar; Gundimeda, Sandhya Devi; Rao, T Subramaneshwar; Murthy, Sudha

    2014-12-01

    Hybrid Verrucous Carcinoma is an uncommon tumour wherein Verrucous Carcinoma (VC) is coexisting with conventional Squamous Cell Carcinoma (SCC) within same maternal field. The heterogeneous nature, infrequency of occurrence and the difficulties associated with diagnosis and management of this tumor is discussed through a retrospective study. Patients of primary hybrid VC treated from Jan 2010 to May 2013 at a tertiary institute were analyzed on multivariate cox regression model. During the above mentioned period; 37 patients of hybrid VC were reported; 18(48.6 %) were male and 19(51.3 %) were female. Age ranged between 33 years to 78 years. Median follow up period was 32 months. T stage status and Stage grouping was not statistically significant for mortality (p value: 0.338). In the multivariate cox-regression model, the presence of second primary oral cancer was significantly associated with mortality, adjusted HR; 23.10 (95 % CI: 1.73, 307.65) (p = 0.017). Tumour staging is often unreliable in predicting prognosis of hybrid VC, occurrence of second primary oral cancer and recurrence appears to be significant factors effecting prognosis.

  2. Acute Toxicity of Fengshigubi Oral Liquid%风湿骨痹口服液急性毒性研究

    Institute of Scientific and Technical Information of China (English)

    辛玲歌

    2014-01-01

    目的:观察小鼠灌胃风湿骨痹口服液的急性毒性反应,测定半数致死量( LD50)及最大给药量,为临床安全用药提供依据。方法小鼠给予风湿骨痹口服液灌胃,通过预试验测定 LD50及最大给药量。结果 LD50未测出;小鼠最大给药量为1236 g生药/kg,相当于临床人用量的1799倍,在此剂量下灌胃对小鼠无急性毒性反应。结论风湿骨痹口服液毒性较低,在临床规定用法用量下安全可靠。%Objective To observe the acute toxicity reaction of Fengshigubi Oral Liquid by gastric gavage in mice,and to determine LD50 and the maximum dosage to provide the basis for clinical safe medication. Methods The mice were given Fengshigubi Oral Liq-uid by gastric gavage. The median lethal dose( LD50) and the maximum dose were determined by the pre-experiment. Results LD50 was not detected out and the maximum dose in mice was 1 236 g crude drug/kg,which was equivalent to 1 799 times of human dosage in clinic,the gastric gavage of this dose had no acute toxicity in mice. Conclusion Fengshigubi Oral Liquid has low toxicity and it is safe under the clinical provision of usage and dosage.

  3. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    Science.gov (United States)

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

  4. Reliability of intra-oral camera using teledentistry in screening of oral diseases – Pilot study

    Directory of Open Access Journals (Sweden)

    Kalyana Chakravarthy Pentapati

    2017-04-01

    Conclusion/recommendations: Intra-oral camera was shown to be a reliable tool to identify common oral diseases. Further studies involving applications like sealant retention, pre-malignant lesions, recurrent apthae, gingival recession and dental malocclusion and effectiveness in regular screening are needed.

  5. Studies on Toxicity, Anti_stress and Hepato_protective Properties of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective The objective of the study was to evaluate toxicity, anti_stress activity and hepato_protective properties of Kombucha tea. Method Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti_stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/ blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato_toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. Results The effect of oral administration of different doses of K_tea to albino rats was examined and the results indicate that K_tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K_tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K_tea has also been found to decrease the Wrap_restraint faecal pellet output in rats. K_tea has also been found to decrease paracetamol induced hepatotoxicity significantly. Conclusion The study shows that K_tea has anti_stress and hepato_protective activities.

  6. Studies on Toxicity,Anti—stress and Hepato—Protective properties of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    PAULINE,T.; KAVIMANI,S

    2001-01-01

    Objective :The objective of the study was to evaluate toxicity,anti-stress activity and hepatoprotective properties of Kombucha tea.Method :Kombucha tea was fed orally for 15 days using three different doses i.e.normal dose,five and ten times the dose,Rats were then sacrficed and various biochemical,and histological parameters were estimated.Anti-stress activity was evaluated either by 1)by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output.Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol(1gm/kg)orally and determining the plasma levels of SGPT,SGOT and MDA.REsults:The effect of oral administration of different doses of K-tea to albion rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters.K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber.Further,K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats.K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly.Conclusion:The study shows that K-tea has anti-stress and hepato-protective activities.

  7. Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products.

    Science.gov (United States)

    Ruiz, Patricia; Begluitti, Gino; Tincher, Terry; Wheeler, John; Mumtaz, Moiz

    2012-07-27

    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 (LD₅₀) for determining relative toxicity of a number of substances. In general, the smaller the LD₅₀ value, the more toxic the chemical, and the larger the LD₅₀ value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD₅₀ 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 LD₅₀ 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 LD₅₀ 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.

  8. Reproductive toxicity in rats with crystal nephropathy following high doses of oral melamine or cyanuric acid.

    Science.gov (United States)

    Stine, Cynthia B; Reimschuessel, Renate; Keltner, Zachary; Nochetto, Cristina B; Black, Thomas; Olejnik, Nicholas; Scott, Michael; Bandele, Omari; Nemser, Sarah M; Tkachenko, Andriy; Evans, Eric R; Crosby, Tina C; Ceric, Olgica; Ferguson, Martine; Yakes, Betsy J; Sprando, Robert

    2014-06-01

    The industrial chemical melamine was used in 2007 and 2008 to raise the apparent protein content in pet feed and watered down milk, respectively. Because humans may be exposed to melamine via several different routes into the human diet as well as deliberate contamination, this study was designed to characterize the effect of high dose melamine or cyanuric acid oral exposure on the pregnant animal and developing fetus, including placental transfer. Clear rectangular crystals formed following a single triazine exposure which is a different morphology from the golden spherulites caused by combined exposure or the calculi formed when melamine combines with endogenous uric acid. Crystal nephropathy, regardless of cause, induces renal failure which in turn has reproductive sequelae. Specifically, melamine alone-treated dams had increased numbers of early and late fetal deaths compared to controls or cyanuric acid-treated dams. As melamine was found in the amniotic fluid, this study confirms transfer of melamine from mammalian mother to fetus and our study provides evidence that cyanuric acid also appears in the amniotic fluid if mothers are exposed to high doses.

  9. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    Science.gov (United States)

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  11. 13-week oral toxicity study with stanol esters in rats

    NARCIS (Netherlands)

    Turnbull, D.; Whittaker, M.H.; Frankos, V.H.; Jonker, D.

    1999-01-01

    Plant sterols and their saturated derivatives, known as stanols, reduce serum cholesterol when consumed in amounts of approximately 2 g per day. Stanol fatty acid esters have been developed as a highly fat-soluble form that may lower cholesterol more effectively than stanols. Stanol esters occur nat

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    African Journals Online (AJOL)

    aghomotsegin

    use plant extracts, parts and powders to protect stored food commodities from insect pests. The widely used plants .... fast growing hardwood tall tree, 30 to 55 m in height; with diameter at ..... aggressive advertisement by commercial pesticides.

  14. Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

    Science.gov (United States)

    Obici, Simoni; Otobone, Fernanda Jacques; da Silva Sela, Vânia Ramos; Ishida, Kelly; da Silva, José Carlos; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Audi, Elisabeth Aparecida

    2008-01-01

    Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

  15. Study on the developmental toxicity of combined artesunate and mefloquine antimalarial drugs on rats.

    Science.gov (United States)

    Boareto, Ana Cláudia; Müller, Juliane Centeno; de Araujo, Samanta Luiza; Lourenço, Ana Carolina; Lourenço, Emerson Luiz Botelho; Gomes, Caroline; Minatovicz, Bruna; Lombardi, Natália; Paumgartten, Francisco Roma; Dalsenter, Paulo Roberto

    2012-12-01

    Antimalarial drug combinations containing artemisinins (ACTs) have become first choice therapies for Plasmodium falciparum malaria. Data on safety of ACTs in pregnancy are limited and no previous study has been conducted on the developmental toxicity of artesunate-mefloquine combinations on the first trimester of gestation. To evaluate the developmental toxicity of an artesunate/mefloquine combination, pregnant rats were treated orally with artesunate (15 and 40 mg/kg bwt/day), mefloquine (30 and 80 mg/kg bwt/day) and artesunate/mefloquine (15/30 and 40/80 mg/kg bwt/day) on gestation days 9-11. Dams were C-sectioned on day 20, and their uteri and fetuses removed and examined for soft tissue and skeleton abnormalities. Artesunate increased embryolethality and the incidence of limb long bone malformations on the absence of overt maternal toxicity. Mefloquine (80 mg/kg bwt/day) was maternally toxic and enhanced fetal variations. Combination of artesunate and mefloquine did not enhance their toxicity compared to the toxicity observed after its separate administration. Embryotoxicity of artesunate was apparently attenuated when it is co-administered with mefloquine.

  16. The role of metabolic biomarkers in drug toxicity studies.

    Science.gov (United States)

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  17. Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

    Science.gov (United States)

    Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

    2013-01-01

    Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

  18. Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

    Science.gov (United States)

    Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

    2013-01-01

    Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

  19. Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Joviano-Santos, J.V.; Sá, M.A.; De Maria, M.L.A.; Almeida, T.C.S. [Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Geraldo, V.; Oliveira, S.; Ladeira, L.O. [Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2014-05-23

    It has been demonstrated that carbon nanotubes (CNTs) associated with sodium hyaluronate (HY-CNTs) accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL). Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg). The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

  20. Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

    Directory of Open Access Journals (Sweden)

    J.V. Joviano-Santos

    2014-07-01

    Full Text Available It has been demonstrated that carbon nanotubes (CNTs associated with sodium hyaluronate (HY-CNTs accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL. Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg. The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

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

    Directory of Open Access Journals (Sweden)

    Damiana Diniz Rosa

    2014-06-01

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

  2. Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

    Science.gov (United States)

    Lewis, John R; O'Brien, Thomas G; Skorupski, Katherine A; Krick, Erika L; Reiter, Alexander M; Jennings, Michael W; Jurney, Carrie H; Shofer, F S

    2013-01-01

    This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

  3. Flavorings Boost Toxicity of E-Cigarettes in Lab Study

    Science.gov (United States)

    ... news/fullstory_161111.html Flavorings Boost Toxicity of E-Cigarettes in Lab Study Increasing device's voltage, to get ... Sept. 22, 2016 (HealthDay News) -- Flavorings used in e-cigarettes can increase the toxicity of the vapor that ...

  4. Essential and Toxic Metals in Oral Fluid-a Potential Role in the Diagnosis of Periodontal Diseases.

    Science.gov (United States)

    Herman, Malgorzata; Golasik, Magdalena; Piekoszewski, Wojciech; Walas, Stanislaw; Napierala, Marta; Wyganowska-Swiatkowska, Marzena; Kurhanska-Flisykowska, Anna; Wozniak, Anna; Florek, Ewa

    2016-10-01

    Recently, many studies have investigated the relationship between the level of metals in the body and various diseases. The objective of this study was to examine any possible influence of periodontal disease upon the concentration of metals in oral fluid and blood and to explore the usability of applying cluster analysis coupled with the analysis of selected elements in oral fluid, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn), cadmium (Cd) and lead (Pb), for effectively distinguishing people affected by periodontitis from healthy individuals. The quantification of eight metals in oral fluid and blood samples was performed by two inductively coupled plasma techniques-inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Most of the examined elements were detected at elevated concentration in the oral fluid of periodontal patients. However, the differences were statistically significant in the case of three metals: Cu, Mg and Mn (p oral fluid of the periodontal patients compared to the controls. Cluster analysis confirmed the statistical significance of the differences in the level of metals in the oral fluid between the two groups in most cases, plus enabled the correct classification of the subjects into patients and controls. The relationship between concentrations of metals and periodontal disease may in the future serve to prevent the development of such disease.

  5. Toxicological evaluation of ammonium perfluorobutyrate in rats: Twenty-eight-day and ninety-day oral gavage studies

    Science.gov (United States)

    Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH4+PFBA) at doses up to 150 and 30 mg/kg/d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30 mg/kg/d in the 28-d study. Fe...

  6. The Acute Oral Toxicity of Black Garlic%黑蒜经口急性毒性试验研究

    Institute of Scientific and Technical Information of China (English)

    王月明; 刘宇峰; 马若波; 韩秋菊

    2015-01-01

    The acute oral toxicity of black garlic was tested based on "Health Food Inspection and Evaluation of Technical Specifications" by the People's Republic of China Ministry of Health. The Kunming mice was administered intragastrically with black garlic at a dose of 20 000mg/kg twice within 24 hours. Mice had no toxicity symptom and no death within 14 days, the results showed that the MTD of acute toxic test was higher than the dosage of 20 000 mg/kg. Conclusion: the black garlic is an actually nonpoisonous material.%为研究黑蒜的经口急性毒性,按中华人民共和国卫生部《保健食品检验与评价技术规范》规定的方法。将黑蒜于24h 内两次经口灌胃给予昆明种小鼠20000 mg/kg·BW,对小鼠的生存状态进行观察和记录14d。在14d 观察期内,未见小鼠有任何中毒症状,更无死亡,表明黑蒜对昆明种小鼠的经口急性毒性剂量大于20000mg/kg·BW。说明黑蒜属实际无毒物质。

  7. Intensive cisplatin/oral etoposide for epithelial ovarian cancer: the Cambridge Gynae-Oncology Centre experience: too toxic for relapse?

    Science.gov (United States)

    Gounaris, Ioannis; Iddawela, Mahesh; Parkinson, Christine; Pratt, Jennie; Hatcher, Helen; Basu, Bristi; Tan, Li Tee; Brenton, James D; Earl, Helena M

    2016-03-01

    Intensive cisplatin and oral etoposide for relapsed epithelial ovarian cancer (EOC), commonly known as the van der Burg (VDB) protocol, has been reported to improve response rates and progression-free survival. We report on all patients with relapsed EOC treated on the VDB protocol at the Cambridge Gynae-Oncology Centre. From the institutional databases, we identified all patients treated since 2001. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used Cox regression to identify predictors of survival. A total of 35 patients were treated on the VDB protocol. Toxicity was significant, with grade 3/4 fatigue, nausea and vomiting affecting 46, 46 and 29% of patients, respectively. Six patients had grade 3/4 infection and four (11%) deaths occurred on treatment. Efficacy was encouraging, with a radiological response rate of 43%, a median progression-free survival of 5.8 months and a median overall survival of 14.1 months. No significant difference in efficacy was seen between platinum-resistant and sensitive patients. We report significant activity of the VDB protocol in a routine clinical setting. However, the high rates of serious toxicity and treatment-related deaths among patients treated with palliative intent proved unacceptable. The Cambridge Gynae-Oncology Centre no longer uses this regimen in women with relapsed EOC.

  8. Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer.

    Science.gov (United States)

    Nagy, Katalin; Urban, Edit; Fazekas, Olga; Thurzo, Laszlo; Nagy, Elisabeth

    2007-09-01

    The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biotène Oral Balance gel [Lacléde Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biotène products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biotène products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer.

  9. A Study of Oral Production Tests

    Institute of Scientific and Technical Information of China (English)

    陈瑜

    2013-01-01

    Testing the ability to speak is a most important aspect of language testing. Testing of students’spoken English can bring in a positive washback for English teaching. However,it’s extremely difficult to test. This paper conducts a general analysis of oral production tests from overview,types and items of oral tests and scoring methods,which’s supposed to serve as an introduction to the issue under discussion.

  10. ACUTE AND SUBACUTE TOXICITY STUDY ON SPERMATOGENIC SIDDHA DRUG ‘ISAPPUKOL CHOORANAM’ (IC

    Directory of Open Access Journals (Sweden)

    S. Thillaivanan*, K. Kanagavalli , P. Sathiyarajeswaran and P. Parthiban

    2013-11-01

    Full Text Available Herbal medicines have been broadly used in developed countries hence they are natural and comparatively safe. They contain plant materials as their pharmacologically active components. Infertility is one of the most extremely tragic all over the world. Despite recent advances in the treatment of male infertility, the problem has not been satisfactorily tackled. The male infertility is mainly due to an inadequate number of spermatozoa in the semen, the failure of the spermatozoa to move with sufficient vigor towards their goal. Aim of the study is to evaluate the acute and sub-acute toxicity of the spermatogenic siddha drug Isappukol Chooranam (IC (siddha drug.For acute studies, different doses of IC were administered orally to rats once daily for one week. Forsub-acute studies, different doses of IC were administered orally to rats once daily for 28 days in various doses at 50,100,200 mg/kg of body weight. Detailed hematological, biochemical, necropsy and Histopathological evaluation of organs was performed for all animals. Histopathological analysis revealed that Spleen, Testes, Pancreas, Lung, Liver, Brain, Heart, Stomach, Intestine, Bone, Ovary, and Kidney tissues of treated groups did not show any signs of toxicity. No impairment in hepatic, renal, haemopoietic functions were observed throughout the study. No mortality was observed up to 200 mg/kg of body weight in acute and sub-acute toxicity studies.

  11. [Oral contraceptives: recent safety studies (author's transl)].

    Science.gov (United States)

    Edgren, R A

    1983-09-01

    Considerable research evidence now exists to suggest that the risks of oral contraceptive (OC) use were seriously overestimated in earlier work. Because experimentation in medicine is never possible in the rigorous sense in which it is employed in basic sciences, other sources of information must be substituted. Information on the dangers of OC use has come from anecdotal reports, retrospective case control studies, prospective cohort studies, and statistical analyses of deaths, each source being associated with specific problems of interpretation. Recent findings of the Royal College of General Practitioners, the Walnut Creek Study, and the Oxford Study have suggested a lowered incidence of malignant neoplasms in OC than in IUD or diaphragm users; a reduced incidence of breast cancer although the relationship did not consistently achieve statistical significance, and a reduced incidence of ovarian and endometrial cancer. The risks of cervical cancer among OC users appeared slightly higher but disappeared when sexual behavior was controlled. Despite much concern with the possibility of postpill amenorrhea and perhaps sterility among women discontinuing OC use, it now appears that after 2 years there is no difference in the fertility of women who have discontinued use of OCs, IUDs, or diaphragms. Use of OCs as a contraceptive before pregnancy does not appear to be associated with fetal malformations, spontaneous abortion, or perinatal mortality, and the inadvertent use of OCs in early pregnancy is apparently associated with only a very slight risk of anomalies. Recent studies of cardiovascular disease risks indicate that the relative risks of cardiovascular disease among OC users have been greatly exaggerated, especially when smoking is taken into account. Various studies of mortality data have failed to establish a link between OC use and excess mortality from cardiovascular disease.

  12. 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...

  13. Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study

    OpenAIRE

    Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya; Gaitán Cepeda, Luis Alberto

    2016-01-01

    Background To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. Material and Methods In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses wer...

  14. Estimation of salivary lactate dehydrogenase in oral leukoplakia and oral squamous cell carcinoma: a biochemical study.

    Science.gov (United States)

    Patel, Shrikant; Metgud, Rashmi

    2015-01-01

    Enzyme Lactate Dehydrogenase (LDH) is found in the cells of almost all body tissues. The profile of salivary total LDH enzymes is similar to that found in oral epithelium, indicating that the major source of salivary LDH is probably the oral epithelium-shedding cells. Consequently, LDH concentration in saliva, as an expression of cellular necrosis, could be a specific indicator for oral lesions that affect the integrity of the oral mucosa. Study comprised of three groups as follows: Group I: Comprised of 25 healthy individuals of comparable age. Group II: 25 otherwise healthy and consenting patients with oral leukoplakia (OL). Group III: 25 otherwise healthy and consenting oral squamous cell carcinoma (OSCC) patients. Biochemical estimation of LDH was done with the help of Semiautomatic Analyzer. Inter comparison of salivary total LDH levels between all the three groups revealed that salivary LDH levels increase from healthy control group to Oral Leukoplakia group to further increase in OSCC group. On comparisons between the histopathological grades of OSCC group the level of LDH were found to increase from well differentiated to moderately differentiated to further increase in poorly differentiated patients. The present salivary analysis for LDH enzyme reveals an overall altered salivary LDH enzyme level in OL and OSCC cases.

  15. Achieving the Advanced Oral Proficiency in Arabic: A Case Study

    Science.gov (United States)

    Samimy, Keiko K.

    2008-01-01

    This article is based on a case study of a white American graduate student, Mark, who achieved "Superior" oral proficiency in Arabic according to the ACTFIi Oral Proficiency Scale. Based on multiple data sources (e.g., interviews, observation, document analysis), the study highlights Mark's multiple identities as a language learner, language…

  16. Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study

    Institute of Scientific and Technical Information of China (English)

    Geng-Tao Liu; Yan Li; Huai-Ling Wei; Hong Lu; Hui Zhang; Yu-Gui Gao; Ling-Zhi Wang

    2005-01-01

    AIM: To study the toxicity of bicyclol to animals.METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d.Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol[150, 300, 600 mg/kg, 100-400 folds corresponding to for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2%sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6,50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

  17. Effects of SiC nanoparticles orally administered in a rat model: Biodistribution, toxicity and elemental composition changes in feces and organs

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Omar, E-mail: omar.lozanogarcia@fundp.ac.be [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Laloy, Julie; Alpan, Lütfiye [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Mejia, Jorge [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Rolin, Stéphanie [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Toussaint, Olivier [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Laboratory of Biochemistry and Cellular Biology (URBC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Dogné, Jean-Michel [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); and others

    2012-10-15

    Background: Silicon carbide (SiC) presents noteworthy properties as a material such as high hardness, thermal stability, and photoluminescent properties as a nanocrystal. However, there are very few studies in regard to the toxicological potential of SiC NPs. Objectives: To study the toxicity and biodistribution of silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24 h) and subacute (28 days) oral administrations. The acute doses were 0.5, 5, 50, 300 and 600 mg·kg{sup −1}, while the subacute doses were 0.5 and 50 mg·kg{sup −1}. Results: SiC biodistribution and elemental composition of feces and organs (liver, kidneys, and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and other elements in feces excretion increased by the end of the subacute assessment. SiC did not accumulate in organs but some elemental composition modifications were observed after the acute assessment. Histopathological sections from organs (stomach, intestines, liver, and kidneys) indicate the absence of damage at all applied doses, in both assessments. A decrease in the concentration of urea in blood was found in the 50 mg·kg{sup −1} group from the subacute assessment. No alterations in the urine parameters (sodium, potassium, osmolarity) were found. Conclusion: This is the first study that assesses the toxicity, biodistribution, and composition changes in feces and organs of SiC nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low traces were retrieved in urine, indicating that SiC can cross the intestinal barrier. No sign of toxicity was however found after oral administration. -- Highlights: ► SiC nanoparticles were orally administered to rats in acute and subacute doses. ► SiC was found in low traces in urine. It is mostly excreted in feces within 5 days. ► SiC excretion rate, feces and organ elemental composition change with time. ► No morphological alteration were found on GI tract, liver, kidneys

  18. Oral health promotion in Gauteng: a qualitative study.

    Science.gov (United States)

    Molete, Mpho Primrose; Daly, Blanaid; Hlungwani, Tintswalo Mercy

    2013-03-01

    One of the aims of the South African Oral Health Promotion Framework is to integrate oral health promotion activities into general health promotion using the Common Risk Factor Approach (CRFA). Though policies have directed that oral health should be integrated into general health promotion in South Africa, little is known about the implementation of the CRFA in daily oral health promotion practice. This study aimed to assess how health promoters in Gauteng integrate oral health into their general health promotion activities. The objectives were (i) to describe how health promoters undertake health promotion in Gauteng; (ii) to describe how health promoters incorporate oral health promotion into health promotion activities; and (iii) to describe the opportunities and challenges for health promoters in applying the CRFA. This was a qualitative study and data were collected using semi-structured interviews. A purposive sample of 10 formally trained health promoters agreed to be interviewed. Thematic analysis was used to analyse the data. Participants' work was centred mostly on healthy lifestyle campaigns and there was little integration of oral health into health promotion activities. While most health promoters had an understanding of the CRFA, this understanding was not common amongst other levels of management. Oral health literacy was low and health promoters perceived few opportunities for using a CRFA when weighed against other priorities such as poverty and HIV/AIDS. Currently there is little evidence of integration of oral health into general health promotion activities.

  19. Acute and subchronic toxicity study of the water extract from root of Citrus aurantifolia (Christm. et Panz. Swingle in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available Acute and subchronic toxicities of the water extract from the roots of Citrus aurantifolia were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 300, 600 and 1,200 mg/kg body weight for 90 days (10 male, 10 female. The examinations of signs, animal behavior and health monitoring showed no signs of abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The oral administration of 1,200 mg/kg/ day of the extract of C. aurantifolia in male and female rats caused a significant increase in the liver enzymes, which remained within the normal range, but did not produce a significant histopathological change in the internal organs. In conclusion, the extract from the roots of C. aurantifolia administered orally did not cause acute or subchronic toxicities to male and female rats.

  20. Oral mucocele: A clinical and histopathological study

    Science.gov (United States)

    More, Chandramani B; Bhavsar, Khushbu; Varma, Saurabh; Tailor, Mansi

    2014-01-01

    Background: Oral mucocele is the most common benign minor (accessory) salivary gland lesion, caused due to mechanical trauma to the excretory duct of the gland. Clinically they are characterized by single or multiple, soft, fluctuant nodule, ranging from the normal color of the oral mucosa to deep blue. It affects at any age and is equally present in both sexes with highest incidence in second decade of life. They are classified as extravasation or retention type. Objectives: To analyze the data between 2010 and 2011 of, clinically and histopathologically diagnosed 58 oral mucoceles for age, gender, type, site, color, cause, symptoms and dimension. Results: Oral mucoceles were highly prevalent in the age group of 15-24 years, were seen in 51.72% of males and 48.28% of females, with a ratio of 1.07:1. The extravasation type (84.48%) was more common than the retention type (15.52%). The most common affected site was lower lip (36.20%) followed by ventral surface of the tongue (25.86%). The lowest frequency was observed in floor of mouth, upper lip and palate. The maximum numbers of mucoceles were asymptomatic (58.62%), and the color of the overlying mucosa had color of adjacent normal mucosa (48.28%). It was also observed that most of the mucoceles had diameter ranging from 5 to 14 mm. The causative factors of the lesion were lip biting (22.41%), trauma (5.18%) and numerous lesions (72.41%). Conclusion: Oral Mucoceles are frequently seen in an oral medicine service, mainly affecting young people and lower lip, measuring around 5 to 14 mm and the extravasation type being the most common. PMID:25364184

  1. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    Science.gov (United States)

    Lam, Chiu-wing; James, John T.

    2009-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

  2. Oral bioavailability of glyphosate: studies using two intestinal cell lines.

    Science.gov (United States)

    Vasiluk, Luba; Pinto, Linda J; Moore, Margo M

    2005-01-01

    Glyphosate is a commonly used nonselective herbicide that inhibits plant growth through interference with the production of essential aromatic amino acids. In vivo studies in mammals with radiolabeled glyphosate have shown that 34% of radioactivity was associated with intestinal tissue 2 h after oral administration. The aim of our research was to investigate the transport, binding, and toxicity of glyphosate to the cultured human intestinal epithelial cell line, Caco-2, and the rat small intestinal crypt-derived cell line, ileum epithelial cells-18 (IEC-18). An in vitro analysis of the transport kinetics of [14C]-glyphosate showed that 4 h after exposure, approximately 8% of radiolabeled glyphosate moved through the Caco-2 monolayer in a dose-dependent manner. Binding of glyphosate to cells was saturable and approximately 4 x 10(11) binding sites/cell were estimated from bound [14C]. Exposure of Caco-2 cells to > or =10 mg/ml glyphosate reduced transmembrane electrical resistance (TEER) by 82 to 96% and increased permeability to [3H]-mannitol, indicating that paracellular permeability increased in glyphosate-treated cells. At 10-mg/ml glyphosate, both IEC-18 and Caco-2 cells showed disruption in the actin cytoskeleton. In Caco-2 cells, significant lactate dehydrogenase leakage was observed when cells were exposed to 15 mg/ml of glyphosate. These data indicate that at doses >10 mg/ml, glyphosate significantly disrupts the barrier properties of cultured intestinal cells.

  3. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  4. A Validation Study of the Student Oral Proficiency Assessment (SOPA).

    Science.gov (United States)

    Thompson, Lynn E.; Kenyon, Dorry M.; Rhodes, Nancy C.

    This study validated the Student Oral Proficiency Assessment (SOPA), an oral proficiency instrument designed for students in elementary foreign language programs. Elementary students who were tested with the SOPA were also administered other instruments designed to measure proficiency. These instruments included the Stanford Foreign Language Oral…

  5. Toxicity studies of Cordia salicifolia extract Estudo da toxidade do extrato de Cordia salicifolia

    Directory of Open Access Journals (Sweden)

    Roberto Kenji Nakamura Cuman

    2005-03-01

    Full Text Available Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nos parâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animaisThis study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certain biochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920 mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals

  6. Toxicity studies of Cordia salicifolia extract = Estudo da toxidade do extrato de Cordia salicifolia

    Directory of Open Access Journals (Sweden)

    Silvana Martins Caparroz-Assef

    2005-01-01

    Full Text Available This study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certainbiochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals.Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nosparâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animais.

  7. Oral mucocele: A clinical and histopathological study

    Directory of Open Access Journals (Sweden)

    Chandramani B More

    2014-01-01

    Objectives: To analyze the data between 2010 and 2011 of, clinically and histopathologically diagnosed 58 oral mucoceles for age, gender, type, site, color, cause, symptoms and dimension. Results: Oral mucoceles were highly prevalent in the age group of 15-24 years, were seen in 51.72% of males and 48.28% of females, with a ratio of 1.07:1. The extravasation type (84.48% was more common than the retention type (15.52%. The most common affected site was lower lip (36.20% followed by ventral surface of the tongue (25.86%. The lowest frequency was observed in floor of mouth, upper lip and palate. The maximum numbers of mucoceles were asymptomatic (58.62%, and the color of the overlying mucosa had color of adjacent normal mucosa (48.28%. It was also observed that most of the mucoceles had diameter ranging from 5 to 14 mm. The causative factors of the lesion were lip biting (22.41%, trauma (5.18% and numerous lesions (72.41%. Conclusion: Oral Mucoceles are frequently seen in an oral medicine service, mainly affecting young people and lower lip, measuring around 5 to 14 mm and the extravasation type being the most common.

  8. Feasibility of a porcine oral mucosa equivalent: a preclinical study.

    Science.gov (United States)

    Kinikoglu, Beste; Hemar, Julie; Hasirci, Vasif; Breton, Pierre; Damour, Odile

    2012-08-01

    Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell-based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non-keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts.

  9. Analysis of the toxicity and histopathology induced by the oral administration of Pseudanabaena galeata and Geitlerinema splendidum (cyanobacteria) extracts to mice.

    Science.gov (United States)

    Rangel, Marisa; Martins, Joyce C G; Garcia, Angélica Nunes; Conserva, Geanne A A; Costa-Neves, Adriana; Sant'Anna, Célia Leite; de Carvalho, Luciana Retz

    2014-01-22

    Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the

  10. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria Extracts to Mice

    Directory of Open Access Journals (Sweden)

    Marisa Rangel

    2014-01-01

    Full Text Available Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt of the Institute of Botany of Brazil, the acetic acid extracts (AE of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia

  11. Exposición infantil a plastificantes potencialmente tóxicos en productos de uso oral Infant exposure to potentially toxic plasticizers in products for oral use

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    Lilia Patricia Bustamante-Montes

    2004-12-01

    Full Text Available OBJETIVO: Determinar la prevalencia en el uso de productos infantiles orales entre menores de tres años de edad y medir su concentración de ftalatos, sustancias potencialmente tóxicas. MATERIAL Y MÉTODOS: Se realizó, en 1999, una entrevista domiciliaria a 199 madres de niños del área metropolitana de la ciudad de Toluca. Por cromatografía de gases se identificaron y cuantificaron diversos ftalatos de productos de uso oral empleados por los niños participantes y se estimó la contribución de estas fuentes a la ingesta diaria de ftalatos. RESULTADOS: La prevalencia de uso de estos productos fue de 13%, siendo mayor entre los niños, menores de 18 meses de edad, pertenecientes al estrato socioeconómico bajo. Las concentraciones variaron desde trazas hasta 67.0% del peso. La exposición media calculada proveniente de los productos manufacturados con policloruro de vinilo y ftalatos fue de 13.94 µg/ kg de peso/día, IC 95% (9.08, 18.89. CONCLUSIONES: La exposición a ftalatos proveniente de productos para chupar o morder se encuentra dentro de los límites reportados en otros países; sin embargo, otras fuentes pueden incrementarla. Dado que algunos ftalatos han mostrado ser tóxicos en el sistema reproductivo, y este potencial efecto es plausible en el hombre, es necesaria la investigación de otras fuentes y determinar la exposición total a través de biomarcadores.OBJECTIVE: To estimate the prevalence of oral product use in children less than three years of age, and to measure the concentration of phthalates as potentially toxic products. MATERIAL AND METHODS: In 1999, 199 mothers of children living in the city of Toluca agreed to household interviews. Samples of oral products used by the children were taken and analyzed by gas chromatography to identify and quantify phthalate concentrations, to estimate the daily intake of phthalates from this source. RESULTS: The prevalence of oral product use was 13%. Male infants less than 18

  12. Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

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    Maznah Ismail

    2013-06-01

    Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  13. 90-Day Inhalation Toxicity Study of FT Fuel

    Science.gov (United States)

    2011-08-01

    vapors of a distillate of light catalytic cracked naphtha (LCCN-D, CAS no. 64741-55-5) in Sprague-Dawley rats. Target exposure concentrations were 0...cracked naphtha distillate in rats. Int J Toxicol. (2001) 20:307-319. McDougal JN, Rogers JV. Local and systemic toxicity of JP-8 from cutaneous exposures...petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats. J Toxicol

  14. Avaliação da toxicidade oral subcrônica da bixina para ratos Oral toxicity assessment of annatto in rats

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    Ana Rita Pedreira Lapa Bautista

    2004-06-01

    determined. The health of the animals was checked. At the end of the study a biochemistry (glucose, creatinine, total cholesterol, triglyceride, asparagine transaminase and g-glutamyl transaminase and hematological examination was carried out. All the animals were subjected to a gross-pathological assessment followed by liver, kidney, adrenals, spleen and tests weight. A histopathological analysis (liver and kidney was performed. From the weight parameters clinical, clinical chemistry and haematology, necroscopy and histology viewpoints, it can be said that annatto, under the chosen test condition, was no toxic to the rat.

  15. A phase contrast cytomorphometric study of squames of normal oral mucosa and oral leukoplakia: Original study

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    Afreen Nadaf

    2014-01-01

    Full Text Available Oral leukoplakia represents the most common potentially malignant oral disorder, representing 85% of such lesions. The worldwide prevalence of leukoplakia is 1.5- 4.3%. Leukoplakia is often associated with carcinogenic exposures, such as from use of tobacco, alcohol or betel nut. The level of risk for malignant transformation of leukoplakia is associated with lesion histology. The overall malignant transformation rates for dysplastic lesions range from 11% to 36%, depending on the length of follow-up. Exfoliative cytology is a simple and minimally invasive method. Phase contrast microscope, an essential tool in the field of biology and medical research provides improved discrimination of cellular details. Aims: To study and compare the cytomorphological and cytomorphometric features of squames obtained from the mucosa of normal individuals, tobacco habituates with and without clinically evident leukoplakia. To assess the role of phase contrast microscopy as an alternative and easy method of cytological evaluation of wet and unstained smears. Materials and Methods: Fifty cases from each group were taken. Fixed, unstained smears were viewed under phase contrast microscope and were evaluated morphologically and morphometrically for nuclear and cellular diameters. Results: The study showed a significant increase in the mean nuclear diameter and decrease in the mean cellular diameter. Conclusion: Cytomorphometric changes could be the earliest indicators of cellular alterations. This indicates that there could be a cause-effect relationship between tobacco and quantitative alterations.

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

    Science.gov (United States)

    Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

  17. Importance of genomic studies for drug withdrawal with mental toxicities

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    Da Yong Lu

    2011-09-01

    Full Text Available Undesired side-effects and toxicities of drugs, especially in the area of new-drug development, are negligibleless, unpredicable and often disastrous once being encountered. The suicidal behavior caused by antidepressant treatment is a typical of clinical evidence recently being discovered. We previously hypothesized that patients’ genetic status would decide the suicidal incident rate of antidepressants - it is pharmacogenetics of antidepressants may contribute of this toxicity in patients. In this review, we discuss this problem by comparing many strings of pharmacogenomics evidence of antidepressants recently being published with many other strings of evidence such as drug withdrawal with hepatotoxicity. We argue herein that pharmacogenetics may be very useful in drug withdrawal for mental toxicity. Because this is low-incidence toxicities, which are more reliable on human’s genetic characteristics. We stress the importance of genomics studies for drug withdrawal in future.

  18. ACUTE DERMAL TOXICITY STUDIES OF TROISTM IN NEWZEALAND WHITE RABBITS

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    Anurag Payasi

    2010-06-01

    Full Text Available The study was performed to assess the acute dermal toxicity of TroisTM in Newzealand white rabbit. Test substance was applied as such to the shaven skin of group of rabbits at the dose of 2000 mg/Kg body weight. Control group of animals were similarly treated but only with base. Following dosing up to 14 days the rabbits were observed for mortality and clinical sign of toxicity. No visible signs of toxicity after treatment were observed on the animals of both control and treated animals up to 14 days. Various haematological and biochemical parameters were evaluated and found to be in the normal limit, which indicates that no sign of toxicity in NewZealand white rabbits after 14 days treatment in respect to control group, proving safety of TroisTM in topical application.

  19. Evaluating toxic endpoints of exposure to a commercial PCB mixture: an in vivo laboratory study

    OpenAIRE

    Herve Aloysius; Daniel Desaulniers; Bandiera, Stelvio M.

    2015-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that produce a wide range of toxic effects. To determine sensitive endpoints in various organ systems, the effects of Aroclor 1260 on immune, endocrine, and hepatic systems were evaluated in a dose-response study. Nine-week old male rats were treated with Aroclor 1260 by oral gavage at dosages ranging from 0.025 to 156 mg/kg/day for 10 consecutive days and killed two days after the last treatment. Eight days prior to s...

  20. Subchronic oral toxicity evaluation of ethanolic whole plant extract of Eleucine indica on haematological and biochemical indices in Wistar albino rats

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    Ette Okon Ettebong

    2016-02-01

    Full Text Available Objective: To evaluate the effect of ingestion of ethanolic whole plant extract of Eleucine indica on haematological and biochemical parameters of Wistar albino rats. Methods: Subchronic toxicity study was carried out by oral administration of different doses (200, 400 and 600 mg/kg body weight of the extract on alternate-day basis to different groups of rats for 28 days. The animals were subsequently sacrificed and blood samples were collected by cardiac puncture for haematological and biochemical analyses. Results: Haematological indices were preserved and the extract showed significant (P < 0.01–0.001 haemostatic potentials. There was significant reduction (P < 0.05–0.001 in total bilirubin, aspartate aminotransferase (P < 0.001, alanine transaminase (P < 0.05, alkaline phosphatase (P < 0.001 and blood glucose (P < 0.001 compared to control. The level of total protein increased significantly (P < 0.05–0.001. Kidney functions were, however, intact. Conclusions: The results obtained indicated that ingestion of Eleucine indica whole plant extract for a long period of time reduces both bleeding and clotting times, reduces blood sugar and shows no apparent toxic effect on liver and kidneys. The results of this study may be useful as a basis for clinical trials in humans.

  1. COMPARISON OF MAST CELL COUNT AND MAST CELL DENSITY IN NORMAL MUCOSA, ORAL LEUKOPLAKIA, ORAL LICHEN PLANUS, ORAL SUBMUCOUS FIBROSIS AND ORAL SQUAMOUS CELL CARCINOMA – A STUDY ON 50 CASES

    OpenAIRE

    Monica Kinra; Karthikeyan Ramalingam; Amitabha sarkar; Farzan Rehman; Girish KL

    2012-01-01

    The present study was carried out for quantitative analysis of the mean MCC/optical field and also MCD/sq. mm in oral submucous fibrosis (OSMF), oral lichen planus (OLP), oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and normal buccal mucosa which constituted control group. This study was carried out in the Department of Oral Pathology and Microbiology, Jaipur Dental College, Jaipur. Histologically confirmed 10 cases each of OSMF, OL, OLP and OSCC were selected. The sections were...

  2. Oral Verrucous Carcinoma: A Study of 12 Cases

    OpenAIRE

    Alkan, Alper; Bulut, Emel; Gunhan, Omer; Ozden, Bora

    2010-01-01

    Objectives: The purpose of this clinical study was to identify a clinical and histopathological relationship between verrucous hyperplasia, verrucous keratosis, and verrucous carcinoma. Methods: We evaluated 12 patients who had developed oral verrucous carcinoma in the past 10 years in a follow-up study. In this study, the diagnostic criteria included clinical and histopathological features of the lesions. Each lesion was examined by a single oral pathologist. Results: All the patients were d...

  3. A COMPARATIVE STUDY BETWEEN ORAL CLONIDINE AND ORAL MIDAZOLAM AS PREMEDICANT IN CHILDREN

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    Gurudatta

    2015-08-01

    Full Text Available Majority of Paediatric patients experience significant anxiety in the preoperative holding area and during induction of anesthesia. Such anxiety often prolongs the induction of Anesthesia, increases post - operative pain and produces negative behavioral changes in chil dren. Effective premedication is the answer, which permits less traumatic separation of child from parents and facilitates smooth induction of anesthesia. The aim of the study is to evaluate and compare the efficacy of oral clonidine v/s oral midazolam adm inistered as a pre medicant in children. METHODS: 100 patients of ASA group I/II of either sex between the age group 4 years to 12 years scheduled for elective surgery were divided into two groups. (1 Group C received tablet oral clonidine 4μg/kg mixed wi th 5 ml of water 90 minutes before the induction. (2 Group M – received oral midazolam syrup 0.5mg/kg 45 minutes before the induction. Both the groups were assessed for: (1 drug acceptance (2 sedation score (3 anxiety score (4 onset of sedation (5 ma sk acceptance (6 Cardio respiratory scoring (7 OPS scoring (8 Parental acceptance. The results were statistically analysed. CONCLUSION: Premedication with oral clonidine is a suitable alternative to oral midazolam. It has several advantages compared to oral midazolam, like better acceptance of the drug by the children, adequate sedation and anxiolysis, easy acceptance of mask and I.V. cannulation, minimal side effects, adequate analgesia, good parental satisfaction. One disadvantage of clonidine is slowe r onset of action

  4. Clinical effectiveness, toxicity, and failure patterns of helical tomotherapy for postoperative oral cavity cancer patients

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    Hsieh CH

    2014-03-01

    Full Text Available Chen-Hsi Hsieh,1–3 Pei-Wei Shueng,1,4 Li-Ying Wang,5 Li-Jen Liao,6 Yu-Chin Lin,7 Ying-Shiung Kuo,8 Wu-Chia Lo,6 Chien-Fu Tseng,8 Hui-Ju Tien,1 Hsiu-Ling Chou,9,10 Yen-Ping Hsieh,11 Le-Jung Wu,1 Yu-Jen Chen3,12–14 1Department of Radiation Oncology, Far Eastern Memorial Hospital, 2Department of Medicine, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Department of Radiation Oncology, National Defense Medical Center, 5School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, 6Department of Otolaryngology, 7Division of Medical Oncology and Hematology, Department of Internal Medicine, 8Department of Dentistry and Oral Surgery, 9Department of Nursing, Far Eastern Memorial Hospital, 10Department of Nursing, Oriental Institute of Technology, Taipei, 11Department of Senior Citizen Service Management, National Taichung University of Science and Technology, Taichung, 12Department of Radiation Oncology, 13Department of Medical Research, Mackay Memorial Hospital, 14Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan Background: The outcome of postoperative high- and intermediate-risk oral cavity cancer (OCC patients receiving helical tomotherapy (HT remains limited. Materials and methods: Between November 2006 and November 2012, 53 postoperative high- and intermediate-risk OCC patients treated with HT were enrolled. Results: The 4-year locoregional, local, and regional control rates were 66%, 76.4%, and 94.3%, respectively. The 4-year locoregional control rates of oral tongue and buccal mucosa cancer were 88.3% and 37.1%, respectively (P=0.012. Eleven (20.8% patients experienced locoregional failure. In-field failure occurred in six of 53 (11.3% in the primary area and three of 53 (5.7% in the regional lymph-node area. No marginal failure was noted. Two of 53 (3.8% experienced out-of-field failure. The rates of grade 3 dermatitis

  5. Combinations of genetic data in a study of oral cancer

    DEFF Research Database (Denmark)

    Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki

    2015-01-01

    for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...... with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome...

  6. Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats.

    Science.gov (United States)

    Vega, Katherine; Edwards, James; Beilstein, Paul

    2015-12-01

    Two studies examined the effects of dietary astaxanthin on Hanlbm Wistar (SPF) rats. Male and female rats receiving astaxanthin concentrations up to 1.52% of the feed for 13 weeks showed no evidence of toxicity; no effects were noted in the offspring of female rats exposed to astaxanthin at up to 1.39% of the feed during the period of organogenesis (GD 7-16). Discoloration of the feces and yellow pigmentation of adipose tissue was seen in the 13-week study, an intrinsic property of the substance, and not a sign of toxicity. Differences between the control and astaxanthin groups, some of which reached statistical significance, were generally sporadic (i.e., transient and/or not related to astaxanthin concentration) and not considered of biological or toxicological significance. Blood cholesterol levels, for example, were greater in animals receiving astaxanthin for 13 weeks, but remained within the normal range. The highest dietary concentration of astaxanthin in each of the studies is proposed as a no-observable-adverse-effect level (NOAEL). Specifically, 1.52% for the 13-week study, corresponding to a mean intake of 1033 mg/kg bw/day (range: 880-1240 mg/kg bw/day), and 1.39% for the developmental toxicity study, corresponding to a mean intake of approximately 830 mg/kg bw/day (range: 457-957 mg/kg bw/day).

  7. Studies of acetaminophen and metabolites in urine and their correlations with toxicity using metabolomics.

    Science.gov (United States)

    Sun, Jinchun; Schnackenberg, Laura K; Beger, Richard D

    2009-08-01

    A LC/MS-based metabolomic assay was utilized to investigate a drug's excretion kinetic profile in urine so that the drug toxicity information could be obtained. Groups of 10 male Sprague-Dawley rats per dose were orally gavaged with a single dose of 0.2% carboxymethylcellulose, 400 mg acetaminophen (APAP)/kg body weight or 1600 mg APAP/kg. UPLC/MS and NMR were used to evaluate the excretion kinetics of major drug metabolites. N-acetyl-L-cysteine acetaminophen (APAP-NAC) had statistically significant correlations with clinical chemistry data, endogenous metabolite concentrations and histopathology data. The potential toxicity of a drug can be assessed through the study of the drug's metabolite profiles.

  8. Subchronic, reproductive, and maternal toxicity studies with tertiary butyl acetate (TBAC).

    Science.gov (United States)

    Faber, Willem; Kirkpatrick, Daniel; Coder, Pragati; Li, Abby; Borghoff, Susan; Banton, Marcy

    2014-04-01

    Tertiary-butyl acetate (TBAC) was tested for subchronic toxicity in rats and mice and reproductive toxicity in rats at inhalation concentrations of 0, 100, 400 or 1600ppm. An oral maternal toxicity study was conducted in rats at dose levels of 0, 400, 800, 1000 and 1600mgkg(-1)d(-1). In the inhalation studies, hematology, clinical chemistry, urinalysis, gross pathology and the majority of body weight and feed consumption values were unaffected. Exposure to TBAC at concentrations of 400ppm and higher caused transient hyperactivity in mice and some evidence of increased motor activity counts in male rats at the 1600ppm exposure level. TBAC caused α2u-globulin accumulation in male rat kidneys from all exposure groups and increased liver weights in 1600ppm rats and mice. Levels of thyroxin were decreased in male mice exposed to 1600ppm TBAC for 4weeks but otherwise thyroid endpoints were unaffected in rats and mice at either the 4 or 13weeks time points. There was no evidence or immunotoxicity or reproductive toxicity in rats. Pregnant rats receiving 1000mgkg(-1)d(-1) TBAC exhibited severe signs of acute neurotoxicity and decreased feed consumption and body weight gain. Fetal viability and growth were unaffected.

  9. Tri-Service Center for Oral Health Studies (TSCOHS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Tri-Service Center for Oral Health Studies (TSCOHS), a service of the Postgraduate Dental College, is chartered by the Department of Defense TRICARE Management...

  10. A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.

    Science.gov (United States)

    Wilson, Richard H; Evans, Tr Jeffry; Middleton, Mark R; Molife, L Rhoda; Spicer, James; Dieras, Veronique; Roxburgh, Patricia; Giordano, Heidi; Jaw-Tsai, Sarah; Goble, Sandra; Plummer, Ruth

    2017-03-28

    This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1-14) combined with carboplatin (day 1) in 21-day cycles. Dose-limiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles. Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, and 48 other primary cancers), with a median of three prior therapies (range, 1-7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade ⩾3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg ml(-1) min(-1). Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 h), and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers. Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190).

  11. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    Directory of Open Access Journals (Sweden)

    Subramanion L. Jothy

    2013-01-01

    Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

  12. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    Science.gov (United States)

    Jothy, Subramanion L.; Chen, Yeng; Kanwar, Jagat R.; Sasidharan, Sreenivasan

    2013-01-01

    Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats. PMID:23878610

  13. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    Directory of Open Access Journals (Sweden)

    Samir Attoub

    2014-05-01

    Full Text Available Background: Pistacia lentiscus (Anacardiaceae is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10-6 - 10-3 did not affect the viability (cell death and proliferation of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. Conclusion: These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in

  14. [The study of HPV prevalence in normal oral mucosa and oral squamous cell carcinoma].

    Science.gov (United States)

    Jiang, Qian; Zhang, Zhi-yuan

    2007-10-01

    Mucosal infection with high-risk human papiloma virus(HPV) types 16 and 18 is the cause of cervical cancer and might be a subset of oral squamous cell carcinoma (OSCC), yet the prevalence and type distribution of HPV in oral SCC remained unclear. We systematically reviewed published studies of OSCC biopsies, which were employed to detect and genotype HPV through different methods. The aim of this investigation is to carry out a bibliographic review on the prevalence of HPV in OSCC and normal oral mucosa. Supported by Key Project of National Natural Science Foundation of China (Grant No.30630065), Key Lab Project of Science and Technology Committee of Shanghai Municipality (Grant No.06DZ22026) and Shanghai Leading Academic Discipline Project (Grant No. Y0203).

  15. A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives

    Science.gov (United States)

    Wang, Yanli; Yuan, Lulu; Yao, Chenjie; Ding, Lin; Li, Chenchen; Fang, Jie; Sui, Keke; Liu, Yuanfang; Wu, Minghong

    2014-11-01

    At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L-1, or to Vc at a concentration less than 300 mg L-1, there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L-1 of ZnO NPs and 300 mg L-1 of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the

  16. The use of pig hepatocytes for biotransformation and toxicity studies

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.

    1991-01-01

    The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue

  17. The use of pig hepatocytes for biotransformation and toxicity studies.

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.

    1991-01-01

    The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue toxicolo

  18. Sub-chronic toxicity and heavy metal toxicity study on Kappaphycus alvarezii in albino rats

    Institute of Scientific and Technical Information of China (English)

    AbiramiRG; KowsalyaS

    2012-01-01

    Objective: This study aimed to evaluate the toxicity of Kappaphycus alvarezii methanolic extracts in albino rats. Methods: Sub-chronic toxicity was tested with a single dose of intraperitonal administration of the extract as per the OECD guidelines in the experimental group rats and the control group rats was fed with standard diet and water ad libitum. Mortality, behaviour changes, clinical signs and symptoms, food intake, body weight and any abnormalities of the visceral organs were observed. Results: The results revealed that the algal extract resulted in neither mortality nor any abnormalities. The Most of the serum biochemical parameters and hematological values were similar in control and experimental groups, histopathological examination of the vital organs like liver, kidney, spleen, brain and heart revealed no obvious abnormality in the control group and Kappaphycus alvarezii treated group. Conclusion: It may be concluded that Kappaphycus alvarezii rich in nutrient and nutraceutial potentials and also safety food for human consumption.

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

    Directory of Open Access Journals (Sweden)

    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

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

  20. The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective study.

    NARCIS (Netherlands)

    Meij, van der E.H.; Schepman, K.P.; Waal, van der I.

    2003-01-01

    OBJECTIVES: The possible malignant transformation of oral lichen planus (OLP) is the subject of an ongoing and controversial discussion in the literature. The main criticism of studies on this subject relates to the lack of sufficient data to support the initial diagnosis of OLP in cases that finall

  1. Two-generation reproduction toxicity study in rats with methoxychlor.

    Science.gov (United States)

    Aoyama, Hiroaki; Hojo, Hitoshi; Takahashi, Ken L; Shimizu-Endo, Naoko; Araki, Masayuki; Takeuchi-Kashimoto, Yukiko; Saka, Machiko; Teramoto, Shoji

    2012-03-01

    A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

  2. Family history and oral health: findings from the Dunedin Study

    Science.gov (United States)

    Shearer, Dara M; Thomson, W. Murray; Caspi, Avshalom; Moffitt, Terrie E; Broadbent, Jonathan M; Poulton, Richie

    2011-01-01

    Context The effects of the oral health status of one generation on that of the next within families are unclear. Objective To determine whether parental oral health history is a risk factor for oral disease. Methods Oral examination and interview data were collected during the age-32 assessments in the Dunedin Study. Parental data were also collected on this occasion. The sample was divided into two familial-risk groups for caries/tooth loss (high risk and low risk) based on parents’ self-reported history of tooth loss at the age-32 assessment interview. Main outcome measures Probands’ dental caries and tooth loss status at age 32, together with lifelong dental caries trajectory (age 5–32). Results Caries/tooth-loss risk analysis was conducted for 640 proband-parents groups. Referent groups were the low-familial-risk groups. After controlling for confounding factors (sex, episodic use of dental services, socio-economic status and plaque trajectory), the prevalence ratio (PR) for having lost 1+ teeth by age 32 for the high-familial-risk group was 1.41 (95% confidence interval [CI] 1.05, 1.88) and the rate ratio for DMFS at age 32 was 1.41 (95% CI 1.24, 1.60). In the high-familial-risk group, the PR of following a high caries trajectory was 2.05 (95% CI 1.37, 3.06). Associations were strongest when information was available about both parents’ oral health. Nonetheless, when information was available for one parent only, associations were significant for some proband outcomes. Conclusions People with poor oral health tend to have parents with poor oral health. Family/parental history of oral health is a valid representation of the intricacies of the shared genetic and environmental factors that contribute to an individual’s oral health status. Associations were strongest when data from both parents can be obtained. PMID:22022823

  3. Family history and oral health: findings from the Dunedin Study.

    Science.gov (United States)

    Shearer, Dara M; Thomson, W Murray; Caspi, Avshalom; Moffitt, Terrie E; Broadbent, Jonathan M; Poulton, Richie

    2012-04-01

    The effects of the oral health status of one generation on that of the next within families are unclear.   To determine whether parental oral health history is a risk factor for oral disease. Oral examination and interview data were collected during the age-32 assessments in the Dunedin Study. Parental data were also collected on this occasion. The sample was divided into two familial-risk groups for caries/tooth loss (high risk and low risk) based on parents' self-reported history of tooth loss at the age-32 assessment interview. Probands' dental caries and tooth loss status at age 32, together with lifelong dental caries trajectory (age 5-32). Caries/tooth loss risk analysis was conducted for 640 proband-parent groups. Reference groups were the low-familial-risk groups. After controlling for confounding factors (sex, episodic use of dental services, socio-economic status and plaque trajectory), the prevalence ratio (PR) for having lost 1+ teeth by age 32 for the high-familial-risk group was 1.41 [95% confidence interval (CI) 1.05, 1.88] and the rate ratio for DMFS at age 32 was 1.41 (95% CI 1.24, 1.60). In the high-familial-risk group, the PR of following a high caries trajectory was 2.05 (95% CI 1.37, 3.06). Associations were strongest when information was available about both parents' oral health. Nonetheless, when information was available for one parent only, associations were significant for some outcomes. People with poor oral health tend to have parents with poor oral health. Family/parental history of oral health is a valid representation of the intricacies of the shared genetic and environmental factors that contribute to an individual's oral health status. Associations are strongest when data from both parents can be obtained. © 2011 John Wiley & Sons A/S.

  4. Models hosts for the study of oral candidiasis.

    Science.gov (United States)

    Junqueira, Juliana Campos

    2012-01-01

    Oral candidiasis is an opportunistic infection caused by yeast of the Candida genus, primarily Candida albicans. It is generally associated with predisposing factors such as the use of immunosuppressive agents, antibiotics, prostheses, and xerostomia. The development of research in animal models is extremely important for understanding the nature of the fungal pathogenicity, host interactions, and treatment of oral mucosal Candida infections. Many oral candidiasis models in rats and mice have been developed with antibiotic administration, induction of xerostomia, treatment with immunosuppressive agents, or the use of germ-free animals, and all these models has both benefits and limitations. Over the past decade, invertebrate model hosts, including Galleria mellonella, Caenorhabditis elegans, and Drosophila melanogaster, have been used for the study of Candida pathogenesis. These invertebrate systems offer a number of advantages over mammalian vertebrate models, predominantly because they allow the study of strain collections without the ethical considerations associated with studies in mammals. Thus, the invertebrate models may be useful to understanding of pathogenicity of Candida isolates from the oral cavity, interactions of oral microorganisms, and study of new antifungal compounds for oral candidiasis.

  5. Comparative study of number and distribution of IgG+ cells in oral lichen planus and oral lichenoid lesions

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani

    2009-01-01

    Full Text Available Background: Oral lichen planus is a common mucocutaneous disorder with unknown etiology. While current data suggest that oral lichen planus is a cell-mediated disease, differential diagnosis of this disease and oral lichenoid lesions is very problematic, both clinically and histopathologically. This study aimed to compare immunohistochemical features of these similar diseases. Methods: This was a descriptive-analytic study in which formalin-fixed and paraffin-embedded tis-sue sections of 30 oral lichen planus and 30 oral lichenoid lesions were immunohistochemically ana-lyzed for number and distribution of IgG + cells. A standard biotin-streptavidin procedure after anti-gen retrieval was used. Data were analyzed in SPSS software using Mann-Whitney U test. Results: There were some significant differences in distribution of IgG + cells among different loca-tions in oral lichen planus and also in oral lichenoid lesions separately; but the differences between distribution of IgG + cells between the two groups of oral lichen planus and oral lichenoid lesions were not significant. Conclusion: There was no significant difference in number and distribution of IgG + cells between the two groups. So, this study can suggest that location of IgG is similar in samples of oral lichen planus and oral lichenoid lesions and consequently, this marker cannot help us differentiate them from each other. Other markers can be analyzed in further studies in order to find an appropriate distinguisher between the two lesions.

  6. Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients

    OpenAIRE

    2014-01-01

    Background Low concentrations of nitric oxide (NO) are necessary for the biology and physiology of spermatozoa, but high levels of NO are toxic and have negative effects on sperm functions. Although several studies have considered the relationship between infertility and semen NO concentrations, no study on the effects of asthenospermia treatments such as oral zinc supplementation on concentrations of NO, which are important in fertility, has been reported. Studies have shown that oral zinc s...

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

    Science.gov (United States)

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

    2014-06-01

    Introducción: El kéfir es obtenido por fermentación de la leche con una población microbiana compleja presente en sus granos. Al consumo de kéfir se le atribuyen múltiples efectos beneficiosos sobre la salud. Objetivo: Evaluar la toxicidad subcrónica del kéfir en ratas Wistar, administrado por vía oral en dosis normal (normodosis) y sobredosis. Se evaluaron además, los parámetros de peso corporal, hematología, química sanguínea, translocación bacteriana e integridad de la mucosa intestinal. Métodos: Se conformaron tres grupos de seis animales de manera aleatoria: grupo control, recibió 0,7 mL de agua; grupo kéfir recibió 0,7 mL/día de kéfir (normodosis) y grupo Hkéfir recibió 3,5 mL/día de kéfir (dosis cinco veces superior). La administración se llevó a cabo mediante sonda. Los animales se alojaron individualmente, y se mantuvieron bajo las mismas condiciones de manejo y alimentación durante 4 semanas. Resultados: La administración de kéfir en dosis normal y sobredosis no afectó los parámetros evaluados en los animales, el peso corporal, indicadores hematológicos, de química sanguínea, y la patogenicidad potencial en los tejidos se encontraron dentro de límites normales, lo que demostró que el consumo de kéfir en dosis normal y sobredosis es seguro. Además, se evidenció que la administración de normodosis de kéfir redujo los niveles de colesterol y mejoró la mucosa intestinal de las ratas. Conclusión: Se demostró que el consumo de kéfir es seguro. Destacar que, la administración de sobredosis no evidenció daños, no obstante, se recomienda el consumo de normodosis, debido a los marcados efectos beneficiosos y de seguridad.

  8. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho

    2016-01-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  9. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  10. An oral bioassay for the toxicity of hydramethylnon to individual workers and queens of Argentine ants, Linepithema humile.

    Science.gov (United States)

    Hooper-Bùi, L M; Rust, M K

    2001-11-01

    We have developed an oral bioassay to determine the toxicity of hydramethylnon to individual workers and queens of the Argentine ant, Linepithema humile. We fed seven concentrations of hydramethylnon in suspension to individual workers or queens, determined the amount of hydramethylnon ingested and evaluated the individual ants for mortality 14 days later. At concentrations > or = 0.37 g liter-1, the amount of liquid the queens ingested decreased dramatically, indicating that Argentine ant queens may detect hydramethylnon. Significantly larger volumes of the two highest concentrations of the hydramethylnon suspension were ingested by the workers, compared to the lower concentrations, suggesting that hydramethylnon may act as a feeding stimulant for the workers. Worker mortality was higher than queen mortality at the highest concentrations tested. The highest worker mortality resulted when the ants ingested 1.03 micrograms of hydramethylnon per mg of ant tissue. At the highest concentration (1.0 g liter-1) tested, workers ingested almost 12 times as much active ingredient per mg of body weight as did queens, suggesting that, in order to increase mortality of queens, multiple feedings must occur.

  11. Comparative toxicity study on classical and modified version of Jawarish Jalinoos (a traditional Unani formulation in rats

    Directory of Open Access Journals (Sweden)

    Gulam Mohammed Husain

    2017-03-01

    Conclusion: The 90-day repeated dose oral toxicity study demonstrates that the no observed adverse effect level of SFJJ and JJ is greater than 2024 mg/kg bw/d and 2000 mg/kg bw/d (p.o. in rats, respectively. Both formulations were found to be safe up to the tested dose levels and experimental conditions, and therefore safe for clinical use as specified in the literature.

  12. Sub-Chronic Toxicity study of Aqueous extract of Clerodendrum Phlomidis Leaves

    Directory of Open Access Journals (Sweden)

    Gupta Reena

    2012-09-01

    Full Text Available Clerodendrum phlomidis Linn. has been traditionally used for treatment of gynecological disturbances and for agricultural uses. It has been used in many Ayurvedic polyherbal formulations as an immunomodulatory agent. Irrespective of its widespread use, no data on subchronic toxicity has been described. The present study was designed to access sub-chronic toxicity of aqueous extract of Clerodendrum phlomidis leaves. Aqueous extract of Clerodendrum phlomidis leaves was given orally at doses of 200, 400 and 800 mg/kg/day for 90 days for the evaluation of sub-chronic toxicity study. General behavior, mortality, animal body weight, food and water consumption were observed throughout the study period. Hematological, biochemical parameters and histopathological analysis were done at the end of study period. No mortality and abnormal behavior was observed in rats exposed to all the three dose levels. Highest dose produced significant decrease in the red blood cell, hemoglobin and increase in white blood cell count. Biochemical parameters like triglycerides, bilirubin, creatinine and total proteins were significantly altered at high dose. Histopathological findings revealed architectural changes in the liver and kidneys with high dose.

  13. 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

  14. Acute and subacute oral toxicity assessment of the oil extracted from Attalea phalerata Mart ex Spreng. pulp fruit in rats.

    Science.gov (United States)

    Freitas de Lima, Fernando; Traesel, Giseli Karenina; Menegati, Sara Emilia Lima Tolouei; Santos, Ariany Carvalho Dos; Souza, Roosevelt Isaias Carvalho; de Oliveira, Vinícius Soares; Sanjinez-Argandoña, Eliana Janet; Cardoso, Claudia Andrea Lima; Oesterreich, Silvia Aparecida; Vieira, Maria do Carmo

    2017-01-01

    Attalea phalerata Mart. ex Spreng., popularly known as "bacuri", is a native plant from the brazilian Cerrado and used in folk medicine as a pulmonary decongestant, an anti-inflammatory for joints and antipyretic. There is an expectation about the use in chronic disease of the Attalea phalerata oil since its composition is high in carotenoids and beneficial fatty acids. The aim of the study was to evaluate the toxicological profile of the oil extracted from Attalea phalerata Mart. ex Spreng. pulp (APO). Acute and subacute toxicity studies were performed in male and female Wistar rats according to the OECD - Guidelines 425 and 407. For the acute toxicity, one single dose of the APO (2000mg/kg) was administered by gavage to five female rats. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the APO were administered to male and female rats for 28 consecutive days. No deaths or behavioral changes were observed during both experiments as well as no changes in organ weights, hematological, histopathological parameters. The biochemical parameters showed changes in phosphatase alkaline and albumin levels, however these values are within the normal range for the species. A significant reduction in cholesterol and triglycerides was also observed in some of the animals treated with the APO. Therefore, the LD50 is higher than 2000mg/kg and the APO oil can be considered safe at the doses tested in rats. However, further assessments are required in order to proceed to clinical studies in humans.

  15. Malaria in cynomolgus monkeys used in toxicity studies in Japan.

    Science.gov (United States)

    Ohta, Etsuko; Nagayama, Yuko; Koyama, Naoki; Kakiuchi, Dai; Hosokawa, Satoru

    2016-01-01

    Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies.

  16. Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Andersen, E; Elbaek, K

    1988-01-01

    In a phase I trial 4-demethoxydaunorubicin (4-dm DNR) was administered as oral capsules once a week to 51 adults with advanced mainly gastrointestinal solid tumors. No fatal toxicity was observed at doses up to 25.0 mg/m2. Dose-limiting granulocytopenia and non-hematologic toxicity developed...

  17. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

    Science.gov (United States)

    Choi, Jonghye; Kim, Heyjin; Kim, Pilje; Jo, Eunhye; Kim, Hyun-Mi; Lee, Moo-Yeol; Jin, Seon Mi; Park, Kwangsik

    2015-01-01

    Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

  18. PUNARNAVA MANDUR: TOXICITY STUDY OF CLASSICAL AYURVEDIC FORMULATION IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    P. S. Jamadagni

    2013-06-01

    Full Text Available Punarnava Mandur is an iron containing classical Ayurvedic formulation which was studied for repeated dose oral toxicity study in Wistar rats for 90 days. Total 48 Wistar rats (24 male and 24 female were selected based on the body weight and were randomly distributed into four groups followed by administration of Punarnava Mandur at the dose of 0, 90, 450, 900 mg/kg body weight for 90 consecutive days. Body weight, Weekly Feed and Water consumption, Clinical Chemistry, Hematology, Differential leukocyte Count, Reticulocyte count and Organ weights were recorded and analyzed statistically. At termination, rats were sacrificed, examined for gross pathological changes, organs were collected, weighed and processed for histopathological evaluation. There was no effect on body weights and feed consumption, no abnormal findings in the histopathological evaluation of high dose group animals but there was significant increase in weight of liver in females of high dose group as compared to control. Hence, the dose level 450 mg/kg of Punarnava Mandur was found as NOAEL (No Observable Adverse Effect Level. However, the NOEL (No Observed Effect Level could not be established. It was suggested to carry out a toxicity study at possible higher doses so as to establish target organ of toxicity.

  19. Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study

    Directory of Open Access Journals (Sweden)

    Shweta Jaitley

    2015-01-01

    Full Text Available The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology. In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions.

  20. Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study.

    Science.gov (United States)

    Jaitley, Shweta; Agarwal, Pankaj; Upadhyay, Ramballabh

    2015-01-01

    The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF) patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC) study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology). In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions.

  1. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

    Science.gov (United States)

    Srinath, Sahana; Iyengar, Asha R; Mysorekar, Vijaya

    2016-01-01

    Background: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. Aim: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. Materials and Methods: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. Statistical Analysis: Chi-Square test was used to analyze the results. Results: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. Conclusion: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia. PMID:27721600

  2. PHYTOCHEMICAL AND TOXICITY STUDY OF EMBLICA OFFICINALIS (AMLA

    Directory of Open Access Journals (Sweden)

    Pandey Govind

    2011-03-01

    Full Text Available In the present study, phytochemistry and toxicities (acute and chronic of Emblica officinalis fruit (Amla have been determined. The hydroalcoholic extract (HAE of amla was prepared and its extractability was found to be 46.9%. Different chemical tests showed the presence of various active principles or phytoconstituents, viz., alkaloids, glycosides, reducing sugars, tannins, resins, saponins, sterols and fixed oils. For acute toxicity, including median lethal dose (LD50 of amla, its HAE was administered @ 250, 500 and 1000 mg/kg body weight to female albino rats of groups 2 to 4, respectively. Rats of group 1 were given normal saline to serve as control. There was no mortality up to 48 hr, hence this drug showed the LD50 above 1000 mg/kg. For chronic toxicity of E. officinalis HAE, similar drug dosage schedule was applied in groups 1 to 4 of rats as used for acute toxicity study; however, the drug was given for 3 weeks. During this period, E. officinalis did not cause any untoward effect.

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

    Institute of Scientific and Technical Information of China (English)

    Tesemma Sileshi; Eyasu Makonnen; Asfaw Debella; Birhanu Tesfaye

    2014-01-01

    Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract ofMoringa stenopetala(M. stenopetala) leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results:Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P Conclusions:The present study revealed that the crude ethanol extract and solvent-solvent fractions as well as chromatographic fractions have antihyperglycemic effect. Furthermore, the crude ethanol extract have some effect on liver of the mice on subchronic administration. Therefore, further study should be done to identify the active principal compound responsible for antihyperglycemic effect and to rule out the safety in other animal model.

  4. A COMPARATIVE STUDY BETWEEN MANAGEMENT OF ORAL SUBMUCOUS FIBROSIS

    Directory of Open Access Journals (Sweden)

    Nidhi

    2014-09-01

    Full Text Available : BACKGROUND: Oral Submucous Fibrosis is a potentially premalignant disorder well known for its chronic and resistant nature. Currently available treatment with local injection of corticosteroids with Hyaluronidase is effective to some extent. The aim of the study was to evaluate whether the efficacy of the current treatment modality for submucous fibrosis can be improved by adding either oral lycopene or oral anti-oxidants along with local injection of steroids. METHODS: This study was conducted from July 2012 to August 2014 A total of 38 patients were included under this study with either grade 3 or 4 submucous fibrosis they were randomly divided in to 2 groups consisting 19 patients each Group 1 were given oral lycopene of dose 16mg/day along with once weekly intralesional injection of steroids and Hyaluronidase. Group 2 were given only once weekly intralesional injection of steroids and Hyaluronidase. Mouth opening recorded from baseline to 6 weeks. Cases were followed up for 6 months thereafter. RESULTS: There was significant increase in mouth opening in both the groups. The results were statistically significant between Group 1 and Group 2. Group 1 patients responded better than the other group and P value <0.001. CONCLUSION: Lycopene in combination with intralesional steroids and Hyaluronidase, is highly efficacious in improving the mouth opening and reducing other symptoms in patients with Oral Submucous Fibrosis.

  5. Pseudoepitheliomatous hyperplasia after diode laser oral surgery. An experimental study

    Science.gov (United States)

    Seoane, Juan; González-Mosquera, Antonio; García-Martín, José-Manuel; García-Caballero, Lucía; Varela-Centelles, Pablo

    2015-01-01

    Background To examine the process of epithelial reparation in a surgical wound caused by diode laser. Material and Methods An experimental study with 27 Sprage-Dawley rats was undertaken. The animals were randomly allocated to two experimental groups, whose individuals underwent glossectomy by means of a diode laser at different wattages, and a control group treated using a number 15 scalpel blade. The animals were slaughtered at the 2nd, 7th, and 14th day after glossectomy. The specimens were independently studied by two pathologists (blinded for the specimens’ group). Results At the 7th day, re-epithelisation was slightly faster for the control group (conventional scalpel) (p=0.011). At the 14th day, complete re-epithelization was observed for all groups. The experimental groups displayed a pseudoepitheliomatous hyperplasia. Conclusions It is concluded that, considering the limitations of this kind of experimental studies, early re-epithelisation occurs slightly faster when a conventional scalpel is used for incision, although re-epithelisation is completed in two weeks no matter the instrument used. In addition, pseudoepitheliomatous hyperplasia is a potential event after oral mucosa surgery with diode laser. Knowledge about this phenomenon (not previously described) may prevent diagnostic mistakes and inadequate treatment approaches, particularly when dealing with potentially malignant oral lesions. Key words:Diode laser, animal model, oral biopsy, oral cancer, oral precancer, pseudoepitheliomatous hyperplasia. PMID:26116841

  6. Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

    Science.gov (United States)

    Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Gujar, Niranjan L; Bhattacharya, Rahul

    2013-09-01

    Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD₅₀ was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD₅₀=66.4 mg/kg) and SNP by intraperitoneal (LD₅₀=16.7 mg/kg) and subcutaneous (LD₅₀=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD₅₀ ATCN. Order of cyanogens (0.75 LD₅₀; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)PCN≈ACN (8h)toxicity of different cyanogens, suitable therapeutic windows can be designed for their management.

  7. [Studies on distribution, excretion and subacute toxicity of squalane in dogs].

    Science.gov (United States)

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H; Inoue, H; Sato, K; Ohkubo, M

    1989-05-01

    In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19,23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, which was regarded as the most important etiologic agent of yusho among PCB and PCDF congeners found in the causal rice oil. We also reported that, in rats, squalane was not essentially absorbed from the gastrointestinal tract, and did not show any appreciable side effects during the 3-month treatment. In the present paper, we have investigated the distribution, excretion and subacute toxicity of squalane in beagle dogs. The fecal excretion of squalane accounted for about 83% of dose during the initial 2 days after administration at a single oral dose of 1,200 mg/kg to male dogs. On day 3, absorbed squalane was mostly distributed to the hair and the skin, and the concentrations in these tissues were decreased on day 6. These results suggested that most of squalane administered orally was not absorbed from the gastrointestinal tract, but a part was absorbed and excreted through the hair. In addition, squalane distributed into the liver was found to be eliminated rather slowly. A long-term (13-week) treatments with squalane orally at doses of 400 mg/kg/day or 1,200 mg/kg/day in male and female dogs, resulted also in accumulation of squalane in the liver at a level of about 3% (400 mg/kg) or about 6% (1,200 mg/kg) of the daily dose. This accumulation of squalane in the liver was highest among all the tissues. Nevertheless, no appreciable toxic signs were observed in the serum biochemical tests and the hepatic functional test for squalane groups. Therefore, squalane accumulating in the liver, did not seem to disturb the hepatic physiological functions. It was suggested also in a long-term treatment that the skin and the hair played the most important role in the elimination of squalane. In conclusion, the present studies on subacute toxicity tests suggested that squalane did not give any

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Oral cavity lesions: A study of 21 cases

    Directory of Open Access Journals (Sweden)

    S Pudasaini

    2011-03-01

    Full Text Available Background: Development of lesions in the oral cavity is strongly linked with smoking and alcohol consumption. Non neoplastic lesions are mainly inflammatory conditions. It has been seen that the benign lesions are more common than malignant. Materials and methods: This was a retrospective study carried out in the Department of Histopathology of Helping Hands Community Hospital during a period of one and a half years from January 2009 to June 2010. The study included 21 cases of oral cavity lesions. Results: The most common site was lip with 9 cases (42.8% followed by buccal cavity with 5 cases (23.8%. Out of the 21 cases of oral cavity lesions, 20 cases (95.2% were benign and 1 case (4.8% was malignant. The malignant lesion was a case of squamous cell carcinoma of soft palate. Conclusion: Any oral cavity lesion should have a tissue diagnosis for rational management of the case and to avoid mutilating surgery. Keywords: Oral cavity; Fibroma; Mucocele DOI: 10.3126/jpn.v1i1.4452 Journal of Pathology of Nepal (2011 Vol.1, 49-51

  10. Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO : methodology and quality of the literature

    NARCIS (Netherlands)

    Brennan, Michael T.; Elting, Linda S.; Spijkervet, Fred K. L.

    Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate

  11. In vivo toxicity studies of europium hydroxide nanorods in mice.

    Science.gov (United States)

    Patra, Chitta Ranjan; Abdel Moneim, Soha S; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

    2009-10-01

    Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu(III)(OH)(3)] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg(-1) day(-1)) and time dependent manner (8-60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.

  12. Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil

    OpenAIRE

    Ghader Jalilzadeh-Amin; Massoud Maham

    2015-01-01

    Objectives: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acut...

  13. Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

    DEFF Research Database (Denmark)

    Ladefoged, Ole; Lam, Henrik Rye; Ostergaard, G.

    1998-01-01

    of the effects on kidney, peripheral nerves, and vision, which have previously been reported after exposure to styrene, might be induced by the styrene metabolite, PGA. If PGA has ototoxic effects in rats, the dosing in the present study is not sufficient to induce the necessary ototoxic concentration in blood....... Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA. (C) 1998 Inter Press, inc....

  14. Informing the debate on oral health care for older people: a qualitative study of older people's views on oral health and oral health care.

    Science.gov (United States)

    Borreani, E; Jones, K; Scambler, S; Gallagher, J E

    2010-03-01

    Older people represent a growing and diverse section of the population. As age increases, people are more likely to experience health and mobility problems and be at higher risk of developing oral disease. Nevertheless, few older people utilise primary oral healthcare services. It is therefore important to understand the value older people place on oral health and dental services to inform providers and planners of oral health care. This research was conducted as part of a study to identify potential ways of minimising barriers to oral health care in older people. To explore perceptions of oral health and oral healthcare services amongst older people living in a socially deprived inner city area and how these are related to service utilisation. A qualitative approach was utilised to explore the range of issues related to older people's perceptions of oral health and their views on health care. This involved a combination of focus groups and semi-structured individual interviews with older people and their carers. Data analysis was conducted using the Framework approach. * Thirty-nine older people and/or their carers participated in focus groups. * Oral health perception: Oral health was associated with the presence of natural teeth, the absence of pain, practical/social functioning, preferably supported by positive assessment by a dentist. * Oral health life-course: Older people have a long and complex dental history. Past negative experiences with oral health care, especially in childhood, strongly influenced present attitudes towards dentistry and dental personnel. * Citizenship and right to health care: There was a strong perception that, as 'British citizens', older people should have a right to free health care and that the National Health Service (NHS) should support them in this phase of their life. The oral health life-course of older people is an important influence on their perceptions of oral health and dental attendance. They consider oral health of

  15. Antibiotics and oral contraceptive failure - a case-crossover study

    NARCIS (Netherlands)

    Toh, Sengwee; Mitchell, Allen A.; Anderka, Marlene; de Jong-van den Berg, Lolkje T. W.; Hernandez-Diaz, Sonia

    2011-01-01

    Background: Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users. Study Designs: We performed a case-crossover study of 1330

  16. ORAL HYGIENE HABITS AND ORAL HEALTH STATUS OF FEMALE ADOLESCENTS UNDER STATE PROTECTION: A PILOT STUDY

    Directory of Open Access Journals (Sweden)

    Cenker Zeki Koyuncuoğlu

    2017-01-01

    Full Text Available Purpose: The aim of this study is to evaluate oral health status and oral hygiene practices of female adolescents under state protection. Subjects and Methods: Fifty-five female participants between the age of 12 and 18 who are under the care of The Child Protection Institution were included in this study. Self-administered questionnaires were used to obtain information regarding knowledge of oral health and habits. Dental caries status was scored according to the criteria of the World Health Organization (WHO, using the indices of Decayed (D, Missing (M, Filled (F, Surfaces (S (DMFS. In addition, Gingival Index (GI and Plaque Index (PI were recorded during periodontal assessment. Data were statistically analyzed by using Oneway analysis of variance, Tukey’s HSD and Student’s t tests. Results: Fourteen children had dental fear and 52.7% of them were not satisfied with their esthetic appearance. Although 78.2% of the children knew that brushing prevents dental caries, only 18 of them were brushing regularly twice per day. Mean DMFS, GI and PI scores were 13.18±5.68, 1.35±0.37 and 1.33±0.45, respectively. Only 20% of the children were using dental floss. There was statistically no significant difference between the DMFS scores of the children in terms of flossing. However, the difference between the mean GI and PI of the same group was found to be statistically significant (p<0.05. Conclusion: Children under state protection were found to have a reasonable knowledge of the causes of dental caries and gingival bleeding. Therefore, adequate management of this positive attitude can significantly improve the oral health of this population.

  17. Developmental Toxicity Studies with Atrazine and its Major Metabolites in Rats and Rabbits

    Science.gov (United States)

    Scialli, Anthony R; DeSesso, John M; Breckenridge, Charles B

    2014-01-01

    Atrazine (ATR), hydroxyatrazine (OH-ATR), and the three chloro metabolites of ATR (deethylatrazine [DEA], deisopropylatrazine [DIA], diaminochlorotriazine [DACT]) were evaluated for developmental effects in rats and rabbits. Three developmental toxicity studies were conducted on ATR in rats (two studies) and rabbits and a developmental toxicity study was conducted in rats for each of the four ATR metabolites DEA, DIA, DACT, and OH-ATZ. ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit) did not statistically significantly alter the incidence of developmental abnormalities or malformations at dose levels up to 100 (rat) or 75 (rabbit) mg/kg bw/day. There were no effects on developmental toxicity parameters for DEA, DIA, DACT, or OH-ATR at oral dose levels up to 100, 100, 150, or 125 mg/kg bw/day, respectively, with the exception of reductions in fetal body weight by DACT and OH-ATR in the presence of decreased maternal body weight gain. ATR did not adversely affect developmental end points in a two-generation study conducted in rats exposed to dose levels up to 500 ppm (38.7 mg/kg/day) in the diet. The 500-ppm dose level resulted in significantly reduced maternal body weight gain. Overall, data show that neither ATR nor its metabolites statistically significantly affected rat or rabbit embryo-fetal development even at dose levels producing maternal toxicity. PMID:24797531

  18. Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats

    Institute of Scientific and Technical Information of China (English)

    Janet Mobolaji Olaniyan; Hadiza Lami Muhammad; Hussaini Anthony Makun; Musa Bola Busari; Abubakar Siddique Abdullah

    2016-01-01

    Objective: To evaluate the acute and sub-acute toxicity of aqueous and methanol ex-tracts of Nelsonia campestris (N. campestris) in rats. Methods: Acute oral toxicity study of aqueous and methanol extracts was carried out by administration of 10, 100, 1 000, 1 600, 2 900 and 5 000 mg/kg body weight of N. campestris extracts to rats in the respective groups. Sub-acute toxicity study was conducted by oral administration of the extracts at daily doses of 100, 300 and 600 mg/kg body weight to another group of rats for 28 days, while rats in the control group received 0.5 mL of normal saline. Results: The LD50 of the N. campestris extracts in rats was determined to be greater than 5 000 mg/kg body weight. There was no significant difference (P>0.05) between the test groups administered with aqueous and methanol extracts in relation to the control group for serum electrolytes (Na+, K+, Cl−, HCO3−), serum albumin, total and conjugated bili-rubin. Similarly, mean organ-to-body weight ratio and all haematological parameters (white blood cell, red blood cell, mean cell volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, packed cell volume) evaluated were not significantly different (P > 0.05) from the control. There was a significant increase (P Conclusions: Intake of high doses of this plant extracts may exhibit mild organ toxicity.

  19. Subacute toxicity of orally applied alpha-cypermethrin in Swiss mice.

    Science.gov (United States)

    Luty, S; Latuszynska, J; Obuchowska-Przebirowska, D; Tokarska, M; Haratym-Maj, A

    2000-01-01

    The effect of a synthetic pyrethroid - alpha-cypermethrin administered per os for 28 days to Swiss mice was examined on phagocytic and bactericidal activity of neutrophils, and leukocytic image, IL-12 p70 level in blood plasma, as well as histologic and ultrastructural picture of the liver, heart, kidneys, lung and spleen. A synthetic pyrethroid alpha-cypermethrin, [(R,S)-alpha-cyano-3-phenoxybenzyl (R,S)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], produced by the Chemical Plant in Jaworzno was used in the study. The preparation for the application per os was used in doses 1/2 LD(50) (25 mg/kg body mass) and 1/5 LD(50) (10 mg/kg body mass). The results were presented as mean (x) +/- standard error (SEM) and subjected to statistical analysis by the parametric t-Student test. Subacute poisoning of mice with alpha-cypermethrin in doses 1/2 LD(50) and 1/5 LD(50) resulted in decreased bactericidal activity of neutrophils. The dose 10 mg/kg body mass had a stronger stimulatory effect on phagocytic activity than 25 mg/kg body mass. Significantly higher numbers of monocytes and lymphocytes were observed in the blood of male mice poisoned with 1/5 LD(50) alpha-cypermethrin. The administration of alpha-cypermethrin resulted for both doses in the decrease in IL-12 p70 serum secretion. The lowest IL-12 p70 level (pg/ml) was noted among female mice administered 1/2 LD(50) of the preparation. The results of the study may indicate that the pyrethroid in the study had a suppressive effect on Il-12 p70 production. In mice administered 1/5 LD(50) or 1/2 LD(50) of the preparation examined, histopathologic and ultrastructural changes were observed in the liver and kidneys.

  20. Optimal initial dose of oral cyclosporine in relation to its toxicities for graft-versus-host disease prophylaxis following reduced-intensity stem cell transplantation in Japanese patients.

    Science.gov (United States)

    Kishi, Y; Murashige, N; Kami, M; Miyakoshi, S; Shibagaki, Y; Hamaki, T; Takaue, Y; Taniguchi, S

    2005-06-01

    Since the introduction of reduced-intensity stem-cell transplantation (RIST), allogeneic stem-cell transplantation has become available for elderly patients. While pharmacokinetics of cyclosporine might differ according to age or other factors, cyclosporine is uniformly started at an oral dose of 6 mg/kg/day. We retrospectively reviewed medical records of 35 patients aged between 32 and 65 (median 52) years who had undergone RIST. Doses of cyclosporine were adjusted to the target blood trough level of 150-250 ng/ml. Cyclosporine dosages were changed in 33 patients (94%). Dose reduction was required in 32 patients because of high blood levels (n=25), renal dysfunction (n=3), hepatic dysfunction (n=2), and hypertension (n=2). Cyclosporine doses were increased in one because of the suboptimal level. The median of the achieved stable doses was 3.1 mg/kg/day (range, 1.0-7.4). Five patients sustained Grade III toxicities according to NCI-CTC version 2.0: renal dysfunction (n=4), hyperbilirubinemia (n=2), and hypertension (n=2). No patients developed grade IV toxicity. There was no statistically significant difference in the frequency and severity of cyclosporine toxicities between patients aged 50 years and above and those below 50 years. The initial oral cyclosporine dose of 6 mg/kg/day was unnecessarily high irrespective of age. The possible overdose of cyclosporine might have aggravated regimen-related toxicities.

  1. Metabolomics and its application to studying metal toxicity.

    Science.gov (United States)

    Booth, Sean C; Workentine, Matthew L; Weljie, Aalim M; Turner, Raymond J

    2011-11-01

    Here we explain the omics approach of metabolomics and how it can be applied to study a physiological response to toxic metal exposure. This review aims to educate the metallomics field to the tool of metabolomics. Metabolomics is becoming an increasingly used tool to compare natural and challenged states of various organisms, from disease states in humans to toxin exposure to environmental systems. This approach is key to understanding and identifying the cellular or biochemical targets of metals and the underlying physiological response. Metabolomics steps are described and overviews of its application to metal toxicity to organisms are given. As this approach is very new there are yet only a small number of total studies and therefore only a brief overview of some metal metabolomics studies is described. A frank critical evaluation of the approach is given to provide newcomers to the method a clear idea of the challenges and the rewards of applying metabolomics to their research.

  2. Oral toxicity, formulation effects, and field performance of flufenoxuron against the German cockroach (Dictyoptera: Blattellidae).

    Science.gov (United States)

    Reid, B L; Appel, A G; Demark, J J; Bennett, G W

    1992-08-01

    Laboratory and field studies on the benzoylphenyl urea (BPU) chitin synthetase inhibitor flufenoxuron (DPX EY-059) showed great potential for its use in suppressing infestations of German cockroach, Blattella germanica (L.). When fed continuously to fifth (last) instars, the LC50 of flufenoxuron was estimated at 0.82 ppm (95% FL, 0.76-0.87 ppm). A rating scale specific for BPU effects was developed and shown to be positively correlated with the insect's exposure to concentration of flufenoxuron. Manipulating the particle size of wettable powder formulations of flufenoxuron significantly altered their activity in contact bioassays. Larger particles (volume mean diameter, 12.2 mu; range, 10-20 mu) were more active. Field trials in multifamily housing with this wettable powder formulation at 0.033 and 0.066% (AI) achieved high level (greater than 80%) population suppression within 8 wk of treatment. The potential for the use of flufenoxuron in B. germanica management programs is discussed.

  3. Oral vs. pharyngeal dysphagia: surface electromyography randomized study.

    Science.gov (United States)

    Vaiman, Michael; Nahlieli, Oded

    2009-05-21

    A clear differential diagnosis between oral and pharyngeal dysphagia remains an unsolved problem. Disorders of the oral cavity are frequently overlooked when dysphagia/odybophagia complaints are assessed. Surface electromyographic (sEMG) studies were performed on randomly assigned patients with oral and pharyngeal pathology to evaluate their dysphagia complaints for the sake of differential diagnosis. Parameters evaluated during swallowing for patients after dental surgery (1: n = 62), oral infections (2: n = 49), acute tonsillitis (3: n = 66) and healthy controls (4: n = 50) included timing and amplitude of sEMG activity of masseter, infrahyoid and submental muscles. The duration of swallows and drinking periods was significantly increased in dental patients and was normal in patients with tonsillitis. The electric activity of masseter was significantly lower in Groups 1 and 2 in comparison with the patients with tonsillitis and controls. The submental and infrahyoid activity was normal in dental patients but infrahyoid activity in patients with tonsillitis was high. Dysphagia following dental surgery or oral infections does not affect pharynx and submental muscles and has clear sEMG signs: increased duration of a single swallow, longer drinking time, low activity of the masseter, and normal range of submental activity. Patients with tonsillitis present hyperactivity of infrahyoid muscles. These data could be used for evaluation of symptoms when differential dental/ENT diagnosis is needed.

  4. Oral vs. pharyngeal dysphagia: surface electromyography randomized study

    Directory of Open Access Journals (Sweden)

    Nahlieli Oded

    2009-05-01

    Full Text Available Abstract Background A clear differential diagnosis between oral and pharyngeal dysphagia remains an unsolved problem. Disorders of the oral cavity are frequently overlooked when dysphagia/odybophagia complaints are assessed. Surface electromyographic (sEMG studies were performed on randomly assigned patients with oral and pharyngeal pathology to evaluate their dysphagia complaints for the sake of differential diagnosis. Methods Parameters evaluated during swallowing for patients after dental surgery (1: n = 62, oral infections (2: n = 49, acute tonsillitis (3: n = 66 and healthy controls (4: n = 50 included timing and amplitude of sEMG activity of masseter, infrahyoid and submental muscles. Results The duration of swallows and drinking periods was significantly increased in dental patients and was normal in patients with tonsillitis. The electric activity of masseter was significantly lower in Groups 1 and 2 in comparison with the patients with tonsillitis and controls. The submental and infrahyoid activity was normal in dental patients but infrahyoid activity in patients with tonsillitis was high. Conclusion Dysphagia following dental surgery or oral infections does not affect pharynx and submental muscles and has clear sEMG signs: increased duration of a single swallow, longer drinking time, low activity of the masseter, and normal range of submental activity. Patients with tonsillitis present hyperactivity of infrahyoid muscles. These data could be used for evaluation of symptoms when differential dental/ENT diagnosis is needed.

  5. Acute and subchronic toxicity study of the water extract from the fruits of Piper chaba Hunter in rats

    Directory of Open Access Journals (Sweden)

    K Jaijoy

    2010-12-01

    Full Text Available Summary: The water extract from the fruits of Piper chaba Hunter was evaluated for acute and subchronic toxicity in both male and female rats. For the study of acute toxicity, a single oral dose of 5,000 mg/kg body weight was administered in rats (five females, five males. The results showed no signs of toxicity such as general behavior change, mortality, or change in gross appearance of internal organs. Subchronic toxicity was studied by daily oral doses (ten females, ten males of 300, 600 and 1,200 mg/kg body weight for consecutive 90 days. The satellite group was treated with the extract at the dose of 1,200 mg/kg/day for 90 days and kept for other 28 days after treatment. The results showed no abnormalities in treated groups as compared to the controls. Although significantly different, all of the values were within normal limits. Neither gross abnormalities nor histopathological changes were observed. The results suggest that P. chaba extract does not produce acute or subchronic toxicity in either female or male rats. Industrial relevance: Herbal medicines are popular and extensively used in the developing world. In many places, they offer a more wide available and more affordable alternative to pharmaceutical drugs and natural food supplements. The data of the acute and subchronic toxicity studies on medicinal plants or preparations derived from them should be obtained in order to increase the confidence in its safety to human, particularly for use in the development of pharmaceutical.

  6. Malnutrition in patients treated for oral or oropharyngeal cancer-prevalence and relationship with oral symptoms : an explorative study

    NARCIS (Netherlands)

    Jager-Wittenaar, Harriet; Dijkstra, Pieter U.; Vissink, Arjan; van Oort, Rob P.; van der Laan, Bernard F. A. M.; Roodenburg, Jan L. N.

    2011-01-01

    This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment. In this cross-sectional study, malnutrition (weight loss a parts per thousand yenaEuro parts per thousand 10% in 6 months or a

  7. Malnutrition in patients treated for oral or oropharyngeal cancer-prevalence and relationship with oral symptoms : an explorative study

    NARCIS (Netherlands)

    Jager-Wittenaar, Harriet; Dijkstra, Pieter U.; Vissink, Arjan; van Oort, Rob P.; van der Laan, Bernard F. A. M.; Roodenburg, Jan L. N.

    2011-01-01

    This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment. In this cross-sectional study, malnutrition (weight loss a parts per thousand yenaEuro parts per thousand 10% in 6 months or a

  8. A clinical study of oral mucous membrane pemphigoid.

    Science.gov (United States)

    Alkan, A; Günhan, O; Alkan, A; Otan, F

    2003-01-01

    We present 13 cases of oral mucous membrane pemphigoid (MMP) and review the literature. The cases were retrieved from the archives of Ondokuz Mayis University and Gülhane Military Medical Academy, Turkey, between 1997 and 2002. Inclusion criteria were clinical findings of oral MMP verified by histological and immunofluorescent examination. Thirteen patients (two males and 11 females), aged 16-72 years, were identified. Involvement was confined to the mouth in all cases except one, in which the conjunctiva was also affected. Two individuals in the study were < 20 years old, an age group rarely affected. The oral mucosa is often the initial site of MMP lesions, so it is important that dentists as well as physicians are aware of the symptoms and signs. A swift diagnosis, made in consultation with other specialists such as ophthalmologists and dermatologists, is needed in order to prevent a delay in treatment.

  9. Contribution to Study About Metastasis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fernanda Ferreira LOPES

    2006-09-01

    Full Text Available Objective: This paper is a retrospective study with aim of collecting information about neoplasm metastasis of oral squamous cell carcinoma. Method: The registry of patients with the histopathology diagnose of oral squamous cell carcinoma in Oncology Institute Aldenora Belo (IMOAB in São Luis - MA, from 1992 to 2004, was analyzed and 18 cases were selected. Results: The most common anatomical region of primary neoplasm was tongue, following by buccal floor and cheek. In related to anatomical area compromised by metastasis, the cervical ones were the most frequent, followed by tongue and buccal floor. Conclusion: It concluded that the tongue was the most common site of oral squamous cell carcinoma, where frequently, shows metastasis, and the most common loco-regional metastasis was on cervical area, especially.

  10. Subacute toxicity evaluation of KR-33493, FAF1 inhibitor for a new anti-parkinson's disease agent, after oral administration in rats and dogs.

    Science.gov (United States)

    Jeong, Jong-Woo; Yu, Changsun; Lee, Jong-Hwa; Moon, Kyoung-Sik; Kim, Eunhee; Yoo, Sung-Eun; Koo, Tae-Sung

    2016-11-01

    KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed. In rats, weight gain decreased in both sexes at 500 mg/kg/day, with no significant differences. In dogs, some significant differences compared with the control were found during the trial; however, at the end of recovery periods, these were no longer observed and there was no dose correlation. Some histopathological findings were observed, but these were considered as incidental changes. Since no other significant changes were observed, doses above 500 and 1000 mg/kg KR33493 in rat and dogs, respectively, caused no observed adverse effects. Therefore, based on these results, the Phase 1 clinical trial for KR33493 was approved by the Korean Food & Drug Administration.

  11. Comparative 28-day repeated oral toxicity of Longdan Xieganwan, Akebia trifoliate (Thunb.) koidz., Akebia quinata (Thunb.) Decne. and Caulis aristolochiae manshuriensis in mice.

    Science.gov (United States)

    Xue, Xiang; Xiao, Ying; Gong, Likun; Guan, Shuhong; Liu, Yongzhen; Lu, Henglei; Qi, Xinming; Zhang, Yunhai; Li, Yan; Wu, Xiongfei; Ren, Jin

    2008-09-02

    Longdan Xieganwan, which contains Aristolochia species, is a traditional Chinese prescription. It has been used for thousands of years to "enhance liver". However, many cases of Longdan Xieganwan induced nephropathy were reported recently. This study was designed to compare the possible toxic effects of Longdan Xieganwan and three different Aristolochia species, i.e. Akebia trifoliate (Thunb.) koid (Akebia trifoliate), Akebia quinata (Thunb.) Decne. (Akebia quinata) and Caulis aristolochiae manshuriensis (Aristolochia manshuriensis). Mice were orally administered these drugs for 28 days. Clinical signs, body weights, serum biochemistry, organ weights and histopathology were examined. Significantly decreased body weights and obvious nephropathy were noticed in the Aristolochia manshuriensis groups at doses higher than 0.24 g/kg/d. A few endothelial cell degenerations in renal glomerulus were observed in the Akebia trifoliate group at a high-dose of 2.00 g/kg/d. No significant changes were observed in the other groups. The no-observed-adverse-effect levels (NOAELs) for Aristolochia manshuriensis, Akebia trifoliate, Akebia quinata and Longdan Xieganwan in this study for mice were 0.06 g/kg/d, 0.40 g/kg/d, higher than 3.00 g/kg/d and higher than 10.00 g/kg/d, which were equivalent to 0.25 times, 5 times, 25 times and 10 times of normal human dose in clinical prescription, respectively.

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

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

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

  13. Acute Toxicity Test of Oral Administration of Artequick in KM mice%青蒿素哌喹片对昆明种小鼠灌胃给药的急性毒性试验

    Institute of Scientific and Technical Information of China (English)

    徐勤; 李晓波; 刘婵; 袁征; 宋健平; 关业枝; 王琪

    2014-01-01

    Objective To study the acute toxicity of artequick after oral administration in mice. Methods By using the Bliss method,the LD50 and its 95 % confidence of artequick in mice were determined after single oral administration for evaluation of the toxicity within 14 days. The gross anatomy and histopathological examination for the dead mice were also carried out. Results After single oral administration,the mice showed various degrees of toxic reaction, showing as less spontaneous activities,closing eyes,face lying,incoordination,tremor,terror,forced paroxysmal spasm,and opisthotonus. The LD50 of artequick in mice was 2802.38 mg·kg-1 and its 95 % confidence was 2343.51~3520.11 mg·kg-1. No abnormal alteration was shown in the organs of all the postmortem mice after the gross anatomy. Conclusion Single oral administration of Artequick has some toxic effects in mice,and the target of toxic organs may be involved the central nervous system.%目的:研究青蒿素哌喹片(ATQ)对昆明种小鼠灌胃给药的急性毒性。方法按 Bliss 法设计试验,对小鼠单次灌胃 ATQ,测定 ATQ 对小鼠半数致死量(LD50)和 LD50的95%可信限,观察14 d 内小鼠的毒性反应和死亡情况,对小鼠进行大体解剖,肉眼观察并进行组织病理学检查。结果 ATQ 单次灌胃给药可使小鼠出现不同程度的毒性反应,包括自发活动减少、闭眼、俯卧、运动失调、震颤、惊跳、强制性-阵挛性抽搐、角弓反张。小鼠 LD50为2802.38 mg·kg-1,LD50的95%可信限为2343.51~3520.11 mg·kg-1,死亡小鼠肉眼观察未发现各脏器异常。结论 ATQ 对小鼠单次灌胃给药具有一定的毒性,涉及的毒性靶器官可能是中枢神经系统。

  14. On the Importance of Cultural Factors in Oral English Studying

    Institute of Scientific and Technical Information of China (English)

    Xiong Juan

    2016-01-01

    Language communication, in some way, is cultural communication, in order to have a better ability of communicating, students have to know and understand enough culture knowledge. This paper will analyze the relationship between language and culture, emphasize the importance of cultural factors in oral English studying.

  15. Oral cancer: a retrospective study of 100 Danish cases

    DEFF Research Database (Denmark)

    Pinholt, E M; Rindum, J; Pindborg, J J

    1997-01-01

    One hundred Danes with oral cancer who were collected consecutively from 1986 to 1991 were evaluated retrospectively. The study included subjective and objective observations in 56% men and in 44% women. M:F ratio was 1.2:1. Fifty percent of the patients were non-smokers. Nine percent were women ...

  16. Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1-5 of a 3-weekly cycle in patients with advanced solid tumours

    NARCIS (Netherlands)

    M.J.A. de Jonge (Maja); S.B. Kaye (Stan); J. Verweij (Jaap); C. Brock (C.); S. Reade (Sarah); M. Scurr (M.); L. van Doorn (Leni); C. Verheij (Coleta); W.J. Loos (Walter); C. Brindley (C.); H.D. Mistry; M. Cooper (Meghan); I.R. Judson (Ian)

    2004-01-01

    textabstractXR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 w

  17. Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1-5 of a 3-weekly cycle in patients with advanced solid tumours

    NARCIS (Netherlands)

    M.J.A. de Jonge (Maja); S.B. Kaye (Stan); J. Verweij (Jaap); C. Brock (C.); S. Reade (Sarah); M. Scurr (M.); L. van Doorn (Leni); C. Verheij (Coleta); W.J. Loos (Walter); C. Brindley (C.); H.D. Mistry; M. Cooper (Meghan); I.R. Judson (Ian)

    2004-01-01

    textabstractXR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 w

  18. Oral health-related quality of life in diabetic patients: comparison of the Persian version of Geriatric Oral Health Assessment Index and Oral Health Impact Profile: A descriptive-analytic study

    OpenAIRE

    Nikbin, Ava; Bayani, Mohammadali; Jenabian, Niloofar; Khafri, Soraya; Motallebnejad, Mina

    2014-01-01

    Background Diabetes mellitus is one of the systemic disease which is show important oral manifestation and influence oral health. This study describes how diabetes mellitus affects oral health and oral health-related quality of life. The aim of this study was to evaluate the oral health and oral health-related quality of life of diabetic patients and compare the discriminative capability of Persian versions of two GOHAI and OHIP-14 questionnaires in these patients. Methods A total of 350 pati...

  19. Developmental toxicity study of pentachlorophenol in the rabbit.

    Science.gov (United States)

    Bernard, B K; Ranpuria, A K; Hoberman, A M

    2001-01-01

    The potential for developmental toxicity of pentachlorophenol (penta) was studied in New Zealand white rabbits at doses of 0 (corn oil), 7.5, 15, and 30 mg/kg/day administered by gavage on days 6 to 18 of gestation. The rabbits were sacrificed on day 29 of presumed gestation and necropsied. Measurements included number of corpora lutea, pregnancy, number and distribution of implantations, early and late resorptions, live and dead fetuses, fetal weight, gender, and gross external, soft tissue, and skeletal alterations. The mid and high doses reduced maternal body weight gain; the high dose caused transient weight loss and reduced feed consumption. There were no effects on embryofetal development at any of the doses evaluated. Based on these data, the maternal no-observable-adverse-effect level (NOAEL) is 7.5 mg/kg/day, while the developmental NOAEL is 30 mg/kg/day. Penta is not a developmental toxicant in a nonrodent animal model.

  20. Subchronic toxicity study in mice fed Spirulina maxima.

    Science.gov (United States)

    Salazar, M; Martínez, E; Madrigal, E; Ruiz, L E; Chamorro, G A

    1998-10-01

    The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue-green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w/w) for 13 weeks. The alga ingestion had no effect on behavior, food and water intake, growth or survival. Terminal values in hematology and clinical chemistry did not reveal differences between treated and control groups. However, male and female mice showed significant changes in serum cholesterol levels at 20 and 30% algal concentrations, but a toxic effect of S. maxima was excluded. Post-mortem examination revealed no differences in gross or microscopic findings. Our results show that S. maxima up to high feeding levels did not produce adverse effects in mice after subchronic treatment.

  1. Misonidazole with dexamethasone rescue: an escalating dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Tanasichuk, H.; Urtasun, R.C.; Fulton, D.S.; Raleigh, J.

    1984-09-01

    Neurotoxicity induced by misonidazole (MISO) and desmethylmisonidazole (DMM) has become the dose limiting factor in clinical work. In 1981, the authors reported a preliminary study suggestive that Dexamethasone (DEXA) does have a protective effect against peripheral neuropathies (PN) resulting from toxicity of misonidazole. The authors are presently investigating the use of DEXA, with escalating doses of MISO in an attempt to modify its neurotoxicity. To date, 16 patients have been registered to receive total doses of MISO given in 9 equally divided doses over 3 weeks. DEXA is given 3 days prior to the first dose and continues for the duration of therapy. All patients receive palliative radiation. No toxicity was seen at the total dose of 13.5 gm/M/sub 2/. One grade I PN occurred in the first four patients receiving 15.5 gm/M/sub 2/. Six additional patients were entered at this dose level and no further incidence of PN was observed.

  2. Oral pyogenic granuloma: a epidemiologic study of 191 cases

    Directory of Open Access Journals (Sweden)

    Thiago de Santana SANTOS

    2008-01-01

    Full Text Available Objectives: To evaluate the prevalence of pyogenic granuloma and compare the data obtained with those of other reports in the worldliterature. Methods: The study material was surveyed from the records of patients with diagnosis of oral pyogenic granuloma, at the Oral Pathology Laboratory of the School of Dentistry of the University of Pernambuco, in the period from January 1992 to March 2007 (15 years. The following indicators were analyzed: gender, age group, race, anatomic location, diameter of lesions and presence of symptomatology.Results: Among the 5007 records in the laboratory, 3.81% corresponded to lesions diagnosed as oral pyogenic granuloma, in which 19.9% of the patients were in the second decade of life, 40.1% were white, the gingiva was the most affected location (77.9% and lesion of smaller diameter (0.1 to 2 cm were those most observed at the initial diagnosis. Conclusion: The clinical-pathological characteristics of oral pyogenic granuloma in the studied population are similar to those of other studies in the literature

  3. Photocatalytic degradation of rosuvastatin: Analytical studies and toxicity evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Tiele Caprioli, E-mail: tiele@enq.ufrgs.br [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil); Pizzolato, Tânia Mara [Chemical Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Arenzon, Alexandre [Ecology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Segalin, Jeferson [Biotechnology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Lansarin, Marla Azário [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil)

    2015-01-01

    Photocatalytic degradation of rosuvastatin, which is a drug that has been used to reduce blood cholesterol levels, was studied in this work employing ZnO as catalyst. The experiments were carried out in a temperature-controlled batch reactor that was irradiated with UV light. Preliminary the effects of the photocatalyst loading, the initial pH and the initial rosuvastatin concentration were evaluated. The experimental results showed that rosuvastatin degradation is primarily a photocatalytic process, with pseudo-first order kinetics. The byproducts that were generated during the oxidative process were identified using nano-ultra performance liquid chromatography tandem mass spectrometry (nano-UPLC–MS/MS) and acute toxicity tests using Daphnia magna were done to evaluate the toxicity of the untreated rosuvastatin solution and the reactor effluent. - Highlights: • The photocatalytic degradation of rosuvastatin was studied under UV irradiation. • Commercial catalyst ZnO was used. • Initial rosuvastatin concentration, photocatalyst loading and pH were evaluated. • The byproducts generated during the oxidative process were detected and identified. • Acute toxicity tests using Daphnia magna were carried out.

  4. Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study

    Science.gov (United States)

    Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya

    2016-01-01

    Background To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. Material and Methods In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with ≥2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS®20.0). Results The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and ≥2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. ≥2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. Conclusions Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established. Key words:Quality of life, quality of life related to oral health

  5. Oral implications of the vegan diet: observational study.

    Science.gov (United States)

    Laffranchi, L; Zotti, F; Bonetti, S; Dalessandri, D; Fontana, P

    2010-01-01

    The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.

  6. Clinicopathological Studies on Gentamicin Toxicity in White Leghorn Commercial Layers

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    Najam Ul Islam, M. Zargham Khan1, M. Kashif Saleemi*1, Ahrar Khan1, Sheraz Ahmed Bhatti1, Muhammad Yousaf2 and Zahoor-ul-Hassan3

    2011-10-01

    Full Text Available Gentamicin is an effective and economical drug used to control infectious diseases in poultry but is highly toxic and had slow clearance from the body. This study aimed to report three cases of gentamicin toxicity in three White Leghorn (WLH layer flocks in different poultry producing areas of Pakistan. In first case, gentamicin was injected in a 9000 WLH layer flock @ 10 mg/kg body weight (BW for seven times during 9-15 weeks for age. In second case, gentamicin was injected in a flock of 7500 WLH layers @ 25 mg/kg BW for four times during 17-18 weeks of age. In third case, gentamicin was injected in flock of 16000 WLH layers @ 22.22 mg/kg BW three times in 20-21 weeks of age. Flock wise mortality was 8.69, 82.63 and 71.86%, respectively. Birds were dehydrated, emaciated and had prominent keel bone. Clinical signs included dehydration, decreased body weight leading to emaciation, decreased feed intake, increased water intake and watery diarrhea. Necropsy revealed prominent keal bone, shrunken muscles swollen kidneys bulging out from bony sockets. Petechial and echymotic hemorrhages were present on heart and skeletal muscles. Liver was enlarged with hemorrhagic streaks on its surface. Microscopically, hemorrhages and acute tubular necrosis was recorded in kidneys. Liver had hemorrhages, cellular infiltration and vacuolar (fatty degeneration of hepatocytes. From the results, it could be concluded that overdosing and repeated administration of gentamicin was highly toxic to birds.

  7. Pharmacokinetic and local toxicity studies of liposome-encapsulated and plain mepivacaine solutions in rats.

    Science.gov (United States)

    Tofoli, Giovana Radomille; Cereda, Cíntia Maria Saia; de Araujo, Daniele Ribeiro; de Paula, Eneida; Brito, Rui Barbosa; Pedrazzoli, José; Meurer, Eduardo; Barros, Fábio Alessandro Proença; Groppo, Francisco Carlos; Volpato, Maria Cristina; Ranali, José

    2010-02-01

    The pharmacokinetics and the local toxicity of commercial and liposome-encapsulated mepivacaine formulations injected intra-orally in rats were studied. Animals were divided in groups (n = 4-6) and treated with 0.1 mL of the formulations: 2% mepivacaine with 1:100,000 epinephrine (MVC(2%EPI)), 3% mepivacaine (MVC(3%)), and 2% liposome-encapsulated mepivacaine (MVC(LUV)). The results showed that the 2% liposome-encapsulated mepivacaine reduced C(max), prolonged AUC(0-infinity) and t(1/2) compared with 3% plain and 2% vasoconstritor-associated mepivacaine, after intraoral injection. In addition, it was also observed that liposomal mepivacaine might protect the tissue against local inflammation evoked by plain or vasoconstrictors-associated mepivacaine, giving supporting evidence for its safety and possible clinical use in dentistry.

  8. Sub-acute toxicity studies of acetaminophen in Sprague Dawley rats.

    Science.gov (United States)

    Venkatesan, Pachaiyappan Sampath; Deecaraman, Munuswamy; Vijayalakshmi, Melanathuru; Sakthivelan, Sigamany Masilamani

    2014-01-01

    The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.

  9. A study of complexity of oral mucosa using fractal geometry

    Directory of Open Access Journals (Sweden)

    S R Shenoi

    2017-01-01

    Full Text Available Background: The oral mucosa lining the oral cavity is composed of epithelium supported by connective tissue. The shape of the epithelial-connective tissue interface has traditionally been used to describe physiological and pathological changes in the oral mucosa. Aim: The aim is to evaluate the morphometric complexity in normal, dysplastic, well-differentiated, and moderately differentiated squamous cell carcinoma (SCC of the oral mucosa using fractal geometry. Materials and Methods: A total of 80 periodic acid–Schiff stained histological images of four groups: normal mucosa, dysplasia, well-differentiated SCC, and moderately differentiated SCC were verified by the gold standard. These images were then subjected to fractal analysis. Statistical Analysis: ANOVA and post hoc test: Bonferroni was applied. Results: Fractal dimension (FD increases as the complexity increases from normal to dysplasia and then to SCC. Normal buccal mucosa was found to be significantly different from dysplasia and the two grades of SCC (P < 0.05. ANOVA of fractal scores of four morphometrically different groups of buccal mucosa was significantly different with F (3,76 = 23.720 and P< 0.01. However, FD of dysplasia was not significantly different from well-differentiated and moderately differentiated SCC (P = 1.000 and P = 0.382, respectively. Conclusion: This study establishes FD as a newer tool in differentiating normal tissue from dysplastic and neoplastic tissue. Fractal geometry is useful in the study of both physiological and pathological changes in the oral mucosa. A new grading system based on FD may emerge as an adjuvant aid in cancer diagnosis.

  10. A retrospective study of oral lichen planus in paediatric population

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    Kabita Chatterjee

    2012-01-01

    Full Text Available Aim: Well documented cases of oral lichen planus, a cell mediated immune condition is infrequently reported in paediatric population. This study was undertaken to obtain epidemiological data retrospectively and also to explore the possibility of any association that might exist among the clinical and histopathological features in paediatric patients suffering from oral lichen planus. Subjects and Methods: A retrospective study was carried out on 22 patients, younger than 18 years with clinical and histopathological diagnosis of oral lichen planus over a period of 14 years. The clinical characteristics and histopathological features were observed. The statistical analysis of the data was performed using Statistical Analysis Software (SAS, Version 9.1. Results: Analysis of data of 22 patients revealed that the average age of patient is 15.18 years with equal male and female predilection. The most common site is buccal mucosa (50% and most frequent clinical form is erosive (63.64%. Focusing on the histopathological findings, parakeratosis was found in 86.36% of the cases, acanthosis in 63.64% of cases, moderate basal cell degeneration was identified in 63.64% of cases and dense lymphocytic infiltration at juxtaepithelial connective tissue region was found in 59.09% of cases. Conclusions: Oral lichen planus in paediatric population is rare and appeared between 8 to 18 years of age. There is no significant gender predominance. The most common clinical form is erosive, manifesting mainly in buccal mucosa. Histopathological findings characteristic of oral lichen planus in paediatric patients include parakeratosis, acanthosis, liquefaction degeneration of basal cells and lymphocytic infiltration in the subepithelial layer.

  11. Does use of oral contraceptives enhance the toxicity of carbon disulfide through interactions with pyridoxine and tryptophan metabolism?

    Science.gov (United States)

    Calabrese, E J

    1980-01-01

    It is proposed that oral contraceptive (OC) users are at increased risk to experiencing adverse psychological disorders (e.g. irritability, depression) from exposures to elevated levels of carbon disulfide (CS2). This theory is based on studies indicating that both OCs and CS2 induce either a vitamin B6 deficiency and/or enhance its requirement. Since disruptions of B6 metabolism are thought to explain, at least in part, the adverse psychological effects of OCs and CS2, it is speculated that joint exposure to these substances may result in an exaggerated disruption of B6 metabolism with the development of CS2 induced adverse psychological effects occurring at exposure levels below those normally associated with adverse effects.

  12. Role of glutamine versus placebo in prevention of acute gastrointestinal toxicity in pelvic radiotherapy: A randomized control study

    Directory of Open Access Journals (Sweden)

    Kazi Sazzad Manir

    2014-01-01

    Full Text Available Context: Nausea, vomiting, diarrhoea, abdominal cramping, ano-proctitis are common acute gastrointestinal (GI toxicities during pelvic radiotherapy (RT, having important impact on treatment outcome. Glutamine has a major role in mucosal growth and function. This phase III study is conducted to evaluate the role of prophylactic glutamine supplementation in prevention of acute GI toxicities during pelvic RT. Materials and Methods: Eighty five nonmetastatic patients with pelvic malignancy needing pelvic RT are included in this double blind randomized control trial. During RT 42 patients (Arm A received 10 g glutamine oral supplementation 1 h before every RT fraction. Forty three patients received glycine as placebo (Arm B in same schedule. Patients were assessed weekly for common acute RT induced GI toxicities. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.02. Results: Two arms were well balanced with all baseline parameters. Median age was 57. 56.47% (n = 48 patients had cervical cancer. There was no significant difference between two arms in grade wise incidence of any of the GI toxicities. Trends of diarrhoea during weekly assessments also similar in both arms. Conclusion: There is no significant beneficial effect of glutamine during pelvic RT. As per our study data and our dose schedule glutamine should not be indicated in pelvic RT.

  13. The master switch: Comparative study of mast cell in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cells carcinoma and their association with inflammation and angiogenesis

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    Neethu Telagi

    2015-01-01

    Full Text Available Background: Dental and medical practitioners encounter wide spectrum of oral lesions in their day-to-day practice. Many of the lesions such as leukoplakia, oral submucous fibrosis (OSF, etc., are associated with tobacco and betel nut chewing. Oral leukoplakia, OSF, oral lichen planus and oral squamous cell carcinoma (OSCC are the most commonly occurring oral diseases associated with characteristic clinical and histological features and are associated with chronic inflammation at some stage of the disease process. Aims: To study and compare the number, morphology and topographical distribution of mast cells in oral epithelial dysplasia (OED, OSF and OSCC and to correlate different types of mast cells with the inflammatory infiltrate and vascularity of the lesions. Materials and Methods: Total number of subjects was 120 and equally divided into four groups of 30 as controls, OED, OSF and OSCC cases. Two sections of from each tissue embedded in paraffin wax block were made which were stained with hematoxylin and eosin and toluidine blue stain. Mast cells were counted in five different zones. Results: In the present study, increased numbers of mast cells were seen in all lesions. The cases with mild, moderate and severe inflammation showed increased number of typical (TMCs, atypical (AMCs and granular mast cells (GMCs, respectively. Conclusion: The result of the present study concludes that the mast cells play a key role in mediating the cross links between external angiogenic agent and local immunologic factors.

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

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    A. V. Voronkov

    2016-01-01

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

  15. Investigation of the toxicity of some organophosphorus pesticides in a repeated dose study in rats.

    Science.gov (United States)

    Baconi, Daniela Luiza; Bârcă, Maria; Manda, Gina; Ciobanu, Anne Marie; Bălălău, C

    2013-01-01

    The study aimed to the investigation of the toxicity of organophosphorus pesticides malathion (MLT) and diazinon (DZN) in Wistar rats in a repeated dose study for 35 days. MLT and DZN in corn oil vehicle were oral administered. Body and organs weights, plasma and brain cholinesterase activities, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathological changes in liver and kidney, and some parameters of the immune function, such as leukocyte formula, spleen weight and cellularity, spleen lymphocytes proliferation in response to concanavalin A (Con A) were investigated; the potential oxidative stress (malondialdehyde in plasma and brain, and blood catalase activity) was also evaluated. No clinical toxicity signs attributed to pesticides were noted; no significant changes in the organ weights have been found. Body weight tends slightly to increase, predominantly in DZN treated rats. The results suggest that plasma cholinesterase is more susceptible than brain cholinesterase to the inhibitory effect of DZN and MLT. Other serum biochemical parameters showed no significant difference. DZN produced a marked increase of the number of spleen lymphocytes without a significant gain of the relative spleen weight. The both pesticides produced an increase of the number of mononuclear cells÷weight spleen. The splenic lymphocyte proliferation has not been influenced by MLT or DZN treatment. Histopathological observations identified some changes (vasodilatation, microvacuoles, and granular dystrophy) in the liver, with MLT, inducing macrovacuolar steatosis. The study indicates that repeated exposure, at subclinical doses, to organophosphorus MLT and DZN causes some biochemical, histopathological and immune alterations in rats.

  16. Clinicopathologic Correlation of Oral Lichen Planus and Oral Lichenoid Lesions: A Preliminary Study

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    Marinka Mravak-Stipetić

    2014-01-01

    Full Text Available Oral lichen planus (OLP and oral lichenoid lesions (OLL are clinically and histologically similar lesions but their treatment planning and prognosis are different. The review of the literature indicates numerous criteria to distinguish these two lesions; however there is a lot of inconsistency. Thus, the aim of this study was to determine the correlation of histopathology and clinical OLP and OLL diagnosis and to clarify which histopathologic criteria could best distinguish these two diagnoses. A retrospective study showed that clinically diagnosed 92 OLPs and 14 OLLs have been confirmed histopathologically in 52.2% and 42.9% of cases, respectively. In addition, histopathology showed statistically significant more eosinophils (P<0.0005, plasma cells (P<0.0005, and granulocytes (P<0.05 in OLL than OLP. To establish histopathological diagnosis of OLP and OLL it should be mandatory to define the type of cells in mononuclear infiltrate, which can be associated more accurately with clinical feature and patient history. Therefore, currently accepted diagnostic criteria for OLP and OLL should be modified and validated on a larger number of patients taking into account particular distinguishing histopathological features.

  17. Mammalian Toxicity of Munitions Compounds. Phase I. Acute Oral Toxicity, Primary Skin and Eye Irritation, Dermal Sensitization, Disposition and Metabolism and Ames Tests of Additional Compounds

    Science.gov (United States)

    1978-12-08

    Assay of 300 Chemicals, Proc. Nat. Acad. Sci., 72:5135-5139, 1975. 17. Wang, C. Y., K. Muraoka, and G. T. Bryan, Yatagenicity of Nitrofurans ...L. H. DiSalvo, and J. Ng, Toxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Microbial Metabolites , Appl. Environ. Microbiol., 31:576-580

  18. Evaluación de la toxicidad aguda oral e irritación sobre mucosa bucal de la solución CM-95 tratada magnéticamente Oral acute toxicity and irritation on buccal mucosa evaluation of the CM-95 solution magnetically treated

    Directory of Open Access Journals (Sweden)

    Jorge Díaz Bestard

    2008-12-01

    Full Text Available La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993

  19. Oral healthcare of preschool children in Trinidad: a qualitative study of parents and caregivers.

    LENUS (Irish Health Repository)

    Naidu, Rahul

    2012-01-01

    Little is known about oral health in early childhood in the West Indies or the views and experiences of caregivers about preventive oral care and dental attendance The aims of this study were to explore and understand parents and caregivers\\' experience of oral healthcare for their preschool aged children and how, within their own social context, this may have shaped their oral health attitudes and behaviours. These data can be used to inform oral health promotion strategies for this age group.

  20. Toxic influence of chronic oral administration of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice

    Institute of Scientific and Technical Information of China (English)

    REN Jin-peng; ZHAO Yu-wu; SUN Xiao-jiang

    2009-01-01

    Background Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice. Methods A total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry, mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique. Results Locomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.

  1. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  2. [Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats].

    Science.gov (United States)

    Ogawa, Yukio; Sekita, Kiyoshi; Umemura, Takashi; Saito, Minoru; Ono, Atsushi; Kawasaki, Yasushi; Uchida, Osayuki; Matsushima, Yuko; Inoue, Tohru; Kanno, Jun

    2004-02-01

    A 52-week study of oral-repeated-dose toxicity for the extraction powder of Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted in both genders of Wistar rats. The rats were administered a graded dose of GS at 0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with the basal powder diet without GS, for 52 weeks. General conditions were recorded daily. Body weights and food consumptions were recorded weekly up to 12 weeks, and thereafter at longer intervals. At 26 weeks, for an intermediate examination, and 52 weeks, for the final examination, animals were subjected to hematology, serum chemistry, and pathological examination. None of the animals died in the period up to 52 weeks. No exposure-related changes in body-weight, in the food consumption, in the hematological examinations, or in the serum biochemical examinations were recognized. No histopathological alterations were seen. Thus, it was concluded that there was no toxic effect in rats treated with GS at up to 1.00% in the diet for 52 weeks. The no-observable-effect level from this study is 1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for female as mean daily intake, for 52 weeks.

  3. [Issues of the study of patient compliance to treatment with oral anticancer chemotherapy: advantages of pharmacokinetics-pharmacodynamics modelisation].

    Science.gov (United States)

    Hénin, Emilie; You, Benoit; Tranchand, Brigitte; Freyer, Gilles; Girard, Pascal

    2007-01-01

    Nowadays, more and more oral anticancer chemotherapies are developed either for cytotoxic or new targeted drugs. But this relatively new route of administration in oncology drives to new problems in treatment management and particularly to non-compliance, i.e. the deviance of the actual way patients take their treatment with the prescription. Population PK-PD models and Monte-Carlo simulations allow to study the impact of non-compliance on toxicities. After a brief review on recent developments about oral chemotherapies, this work presents a simulation where non-compliance, modelled with a two state Markov chain defining four compliance profiles from excellent to poor, is linked to two dose-toxicity (continuous or categorical) population models. Simulated patients with the lowest compliance level were less exposed to treatment and therefore experienced less toxicity with shorter events. Nevertheless treatment efficacy is also lower, and this loss of efficacy may compromise patient's outcome. These results foresee the necessity of global simulations, combining compliance, toxicity and efficacy modelling.

  4. A recombinant fusion protein containing a spider toxin specific for the insect voltage-gated sodium ion channel shows oral toxicity towards insects of different orders.

    Science.gov (United States)

    Yang, Sheng; Pyati, Prashant; Fitches, Elaine; Gatehouse, John A

    2014-04-01

    Recombinant fusion protein technology allows specific insecticidal protein and peptide toxins to display activity in orally-delivered biopesticides. The spider venom peptide δ-amaurobitoxin-PI1a, which targets insect voltage-gated sodium channels, was fused to the "carrier" snowdrop lectin (GNA) to confer oral toxicity. The toxin itself (PI1a) and an amaurobitoxin/GNA fusion protein (PI1a/GNA) were produced using the yeast Pichia pastoris as expression host. Although both proteins caused mortality when injected into cabbage moth (Mamestra brassicae) larvae, the PI1a/GNA fusion was approximately 6 times as effective as recombinant PI1a on a molar basis. PI1a alone was not orally active against cabbage moth larvae, but a single 30 μg dose of the PI1a/GNA fusion protein caused 100% larval mortality within 6 days when fed to 3rd instar larvae, and caused significant reductions in survival, growth and feeding in 4th - 6th instar larvae. Transport of fusion protein from gut contents to the haemolymph of cabbage moth larvae, and binding to the nerve chord, was shown by Western blotting. The PI1a/GNA fusion protein also caused mortality when delivered orally to dipteran (Musca domestica; housefly) and hemipteran (Acyrthosiphon pisum; pea aphid) insects, making it a promising candidate for development as a biopesticide.

  5. Capping and in vivo toxicity studies of gold nanoparticles

    Science.gov (United States)

    Nghiem, Thi Ha Lien; Tuyen Nguyen, Thi; Fort, Emmanuel; Phuong Nguyen, Thanh; Nhung Hoang, Thi My; Quy Nguyen, Thi; Nhung Tran, Hong

    2012-03-01

    Water-dispersed colloidal gold nanoparticles (AuNPs) with high concentration were synthesized from metal precursor HAuCl4. The bovine serum albumin (BSA) and heterobiofunctionalized thiol polyethylene glycol acid (HS-PEG-COOH) were used as biofunctionalized layers for the synthesized AuNPs. The BSA and HS-PEG-COOH bound to the AuNPs were characterized qualitatively and quantitatively by transmission electron microscope and UV-VS spectrophotometer. The fabricated BSA and HS-PEG-COOH-capped AuNPs were introduced in mouse to study its toxicity and its availability in the liver.

  6. [Oral contraceptive pill and thrombotic risk: epidemiological studies].

    Science.gov (United States)

    Fruzzetti, F; Perini, D; Spirito, N; Manca, R

    2012-12-01

    The venous thromboembolism (VTE) is a rare event during childbearing age and during the assumption of combined oral contraceptive. The absolute risk of VTE in users of combined oral contraceptives is 20-30 per 100000 women years. A number of case-control studies published in recent years have shown an apparent increase in the risk of VTE among users of oral contraceptives (OCs) containing desogestrel, gestodene, drospirenone and cyproterone, relative to the use of levonorgestrel. The data derived from these recent studies is of borderline statistical significance because any important factors are not considered to evaluate the real correlation between the assumption of OCs and risk of venous thromboembolism. Among the factors that should be considered, there are: EE dose, duration of use, coexistance of other risk factors of venous thromboembolism (age, BMI, familiarity, surgical interventions) and other prescription bias. The lack of these factors is likely to contribute to the increased risk of venous thromboembolism observed in users of third-generation OCs when compared to that in users of second-generation OCs. To date, because of the inadequacy of epidemiological studies, the data about the correlation between OCs and TVE, are not conclusive and it will be necessary to carry out other studies to clarify this debating point, definitively.

  7.  A CROSS-SECTIONAL STUDY OF ORAL HEALTH AND ORAL-HEALTH-RELATED QUALITY OF LIFE AMONG FRAIL ELDERLY PERSONS ON ADMISSION TO A SPECIAL ORAL-HEALTHCARE PROGRAM IN COPENHAGEN CITY,

    DEFF Research Database (Denmark)

    Christensen, Lisa Bøge; Hede, Borge; Nielsen, Ellen

    2012-01-01

    health-care programme. Clinical data and data from interviews comprising social factors, life-style, dental visit habits, oral hygiene practices and self-perceived oral health were collected. A modified index on perceived dysfunction, discomfort and disability due to oral disorders was used. Results......A cross-sectional study of oral health and oral health-related quality of life among frail elderly persons on admission to a special oral health care programme in Copenhagen City, Denmark Aim: To describe the oral health and the oral-health-related quality of life (OHRQoL) of citizens in Copenhagen...... City on admission to a specific oral health-care programme for disabled elderly persons. Further, to analyse how various factors influence the oral health and the OHRQoL among these patients. Methods: A cross-sectional study of 189 persons (average 85 years) consecutively admitted to a special oral...

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

    Science.gov (United States)

    Kim, Jong-Kyu; Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-09-01

    This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

  9. STUDIES OF CHOSEN TOXIC ELEMENTS CONCENTRATION IN MULTIFLOWER BEE HONEY

    Directory of Open Access Journals (Sweden)

    Ewa Popiela

    2011-04-01

    Full Text Available 72 544x376 Normal 0 21 false false false  The aim of the study was to determine the bioaccumulation level of chosen toxic elements (Zn, Cu, Pb, As and Cd in multiflower honey collected from Brzeg area. Biological material (honey was mineralized using the microwave technique at an elevated pressure in the microprocessor station of pressure in the type Mars 5. Quantitative analysis of elements (As, Cd, Cu, Pb and Zn was performed by plasma spectrometry method using a Varian ICP-AES apparatus. The presence of toxic elements was determined in examined biological materials. The elements fallowed the fallowing decreasing order with respect to their content of honey: Zn>Cu>Pb>As>Cd. The average concentrations of studied elements observed in multi-flower honey were as follows: 6.24 mg.kg-1 of zinc, 2.75 mg.kg-1 of copper, 0.53, 0.071, 0.042 mg.kg-1of lead, arsenic and cadmium, respectively. Lead was the most problematic in bee honey because its average content exceeded the maximum acceptable concentration. Additionally, this metal concentration was 60% higher in studied samples than allowable standard of lead content.doi:10.5219/134 

  10. Treatment of oral leukoplakia with photodynamic therapy: A pilot study

    Directory of Open Access Journals (Sweden)

    Niranzena Panneer Selvam

    2015-01-01

    Full Text Available Aim of the Study: Oral leukoplakia (OL is the most common potentially malignant disorder that may transform into oral carcinoma. By treating leukoplakia in its incipient stage, the risk of occurrence of oral carcinoma can be prevented. In this aspect, photodynamic therapy (PDT can serve as a useful treatment modality. The aim of the study is to treat patients with OL using PDT in which 5-aminolevulinic acid (ALA is used as a photosensitizer. Materials and Methods: Five patients with OL were included in the study. They were treated with 10% ALA mediated PDT (light source: Xenon lamp, power: 0.1 W, wavelength: 630 ± 5 nm, total dose: 100 J/cm 2 per session for 6-8 sessions. Follow-up was done for a period of 1 year. Results: One month (4 weeks after ALA-PDT, the response was evaluated based on clinical examination. It was as follows: Complete response: Two patients; partial response: Two patients; and no response: One patient. There was no recurrence in any of the cases. Conclusion: There was satisfactory reduction in the size of the OL lesion without any side-effects. Thus, ALA mediated PDT seems to be a promising alternative for the treatment of OL.

  11. Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

    Science.gov (United States)

    Gupta, S; Shukla, R; Prabhu, K M; Aggrawal, S; Rusia, U; Murthy, P S

    2002-01-01

    Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

  12. Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study.

    Science.gov (United States)

    Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya; Gaitán-Cepeda, Luis-Alberto

    2016-03-01

    To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with ≥2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS®20.0). The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and ≥2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. ≥2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established.

  13. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    Science.gov (United States)

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys.

  14. E-Cigarettes May Be Less Toxic Than Tobacco, Study Suggests

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163433.html E-Cigarettes May Be Less Toxic Than Tobacco, Study ... 6, 2017 (HealthDay News) -- Smokers who switch to e-cigarettes can substantially reduce their intake of toxic ...

  15. Role of chronic toxicology studies in revealing new toxicities.

    Science.gov (United States)

    Galijatovic-Idrizbegovic, Alema; Miller, Judith E; Cornell, Wendy D; Butler, James A; Wollenberg, Gordon K; Sistare, Frank D; DeGeorge, Joseph J

    2016-12-01

    Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our review shows that majority of the findings are observed in the subchronic studies since additional target organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 studies in non rodents and 6 studies in rodents yielded new findings that were not seen in studies of 3-month or shorter duration. For 3 compounds the new safety findings did contribute to termination of clinical development plans. Although the incidence of compound termination associated with chronic toxicology study observations is low (∼10%), the observations made in these studies can be important for evaluating human safety risk.

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

    Directory of Open Access Journals (Sweden)

    Syed Mehmood Hasan

    2016-06-01

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

  17. [Epidemiological study of oral health in a young adult Mapuche population].

    Science.gov (United States)

    de la Maza, F J; Cueto, M V

    1989-04-01

    An epidemiological study on oral health was conducted on 200 mapuche natives, aged from 14 to 30 years in order to correlate their oral health level with their oral health habits, scholar level, age and sex. DMFT index and the simplified Oral Hygiene Index were evaluated in the sample of studied patients. It was found a 18.15 DMFT score, higher than the national level in our country, and the simplified Oral Hygiene Index (OHI-S) was 1.7, showing deficient oral hygiene habits. A direct relationship between a low scholar level and a high caries index and a high OHI-S index was found.

  18. Oral Hygiene Levels in Children of Tribal Population of Eastern Ghats: An Epidemiological Study

    OpenAIRE

    Raju, P. Krishnam; Vasanti, D; Kumar, J Raghavendra; Niranjani, K; Kumar, M S Saravana

    2015-01-01

    Background: Oral hygiene has been given due importance since ages. Different cultures have been using different methods for the maintenance of good oral hygiene. The study was done to find out the oral hygiene levels in children of tribal population and to correlate the brushing methods used and the oral hygiene levels. Methodology: A total of 5129 children of 5-12 years age (boys 2778, girls 2351) were checked for the simplified oral hygiene index in the study. Results: The overall oral hygi...

  19. 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

  20. Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam – a Siddha preparation on rodents

    OpenAIRE

    Marimuthu Kannadasana; Ganesan Sumathy; Palanivel Thirusangu Sangeetha; Chidambaram Saravanababu; Kathirvelu Baskar

    2016-01-01

    Objective: To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam (KAC) in Sprague Dawley rats of both sexes. Methods: Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min, 1, 2, 4 and 24 h and for up to 14 days. In repeated 28-day oral toxicity study, the KAC formulation was administered orally with 600, 900 and 1200 mg/k...

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

    Science.gov (United States)

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

    2016-05-01

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

  2. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.

    Science.gov (United States)

    Boudreau, Mary D; Imam, Mohammed S; Paredes, Angel M; Bryant, Matthew S; Cunningham, Candice K; Felton, Robert P; Jones, Margie Y; Davis, Kelly J; Olson, Greg R

    2016-03-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon.

  3. Distribution and toxicity of monosodium methanearsonate following oral administration of the herbicide to dairy sheep and goats.

    Science.gov (United States)

    Shariatpanahi, M; Anderson, A C

    1984-01-01

    Iranian fat-tailed sheep and dairy goats were administered the herbicide monosodium methanearsonate orally at a dose of 10 mg. MSMA (as arsenic) per kg. of body weight. The concentration time curves of MSMA in the blood of sheep and goats followed a first order composite exponential equation of the form: Cb(t) = Ae- alpha t + Be- beta t - C degrees be-kat. Absorption, distribution and elimination of MSMA, therefore, corresponds to an open two-compartment model. Arsenic from MSMA was readily absorbed from gastrointestinal tract and distributed in the body fluids and the various tissues. Approximately 90% of the arsenic was excreted in the urine within 120 hrs and small amounts were also recovered in feces. Arsenic accumulation in the tissues was low and urinary excretion was the most important exit route. Arsenic concentrations in milk were low when compared to the controls, which indicates that arsenic is not excreted in the milk to significant levels. The absorption, distribution and overall elimination rate constants for the two animal species studied were statistically different at the 0.95 level of confidence which indicates that there are apparently differences in MSMA metabolism by sheep and goats.

  4. Acute toxicity and gastroprotection studies with a newly synthesized steroid.

    Directory of Open Access Journals (Sweden)

    Kamal A Ketuly

    Full Text Available BACKGROUND: Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP, on ethanol-induced gastric mucosa injuries in rats. METHODOLOGY/PRINCIPAL FINDING: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg, was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg. After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2 and malondialdehyde (MDA content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. CONCLUSION/SIGNIFICANCE: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful

  5. In vitro study of natural plant products against oral bacteria

    Institute of Scientific and Technical Information of China (English)

    Siddiqui R; Siti AsmaH; Tang L; Jie CC; Rosliza AR; Roziawati Y

    2009-01-01

    Objective:To analyze the effect of selected plant product against several bacterial which commonly causes oral infection.It was hope that in future,this product will become the remedy for treatment of oral infection and with the hope that it can substitute antibiotics.Methods:A total of 5 species of oral bacteria from American Type Culture Collection (ATCC)were employed in this study(S.mutans,S.aureus,P.aeruginosa,S.sobri-nus and L.salivarius).Three types of natural plants crude extracts were used (garlic,curry leaves and cloves).Bactericidal and bacteriostatic effects of these herbs were tested.Results:It was shown garlic had an-tibacterial effects on all bacteria.The Minimal Inhibitory Concentration (MIC in g/mL)of garlic towards S. aureus,P.aeruginosa,S.mutans,S.sobrinus and L.salivarius were 0.3,1.8,1.2,0.5 and 1.8,respectively. There was significant difference among the MIC of garlic on tested bacteria.It was more potent toward S.au-reus.The curry leaf solution on the other hand,did not show any zone of inhibition in all bacteria plates but adversely showed enhanced growth of those bacteria.Clove had shown its antibacterial effects on S.aureus and P.aeruginosa.The clove was more potent toward S.aureus with the MIC of 0.45 g/mL.P.aeruginosa was more sensitive to clove compared to garlic.For S.aureus,it was more sensitive to garlic compared to clove. Conclusion:The antibacterial activity of garlic and clove crude extracts shown in our study further confirm these natural plants'potential usage in therapeutic use for oral diseases or infections.This could be the platform for the interested party to do research and development on it and to produce oral health products which are more affordable for lower economic income groups and with fewer side effects as seen in synthetic drug.

  6. 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.

  7. 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. PMID:24416121

  8. 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.

  9. Evaluation of Residual Toxic Substances in the Stomach Using Upper Gastrointestinal Endoscopy for Management of Patients With Oral Drug Overdose on Admission

    OpenAIRE

    Miyauchi, Masato; Hayashida, Makiko; Yokota, Hiroyuki

    2015-01-01

    Abstract The guidelines on the indications for gastric lavage were published in 1997, and a less-aggressive initial approach has been used for poisoned patients. Clinical studies have shown that the outcomes of retrieval of residual toxic substances in the stomach are variable and that no beneficial effect is obtained. However, the presence of residual toxic substances in the stomach before gastric lavage has not been estimated. The objective of this study was to evaluate the residual stomach...

  10. Platelet function studies in women on oral contraceptive pills.

    Science.gov (United States)

    Ishak, R; Mohamed, A B; Hassan, K

    1990-06-01

    A study was conducted on a total of 100 women attending the Family Planning Clinic in Kuala Lumpur. 50 took combined low-dose estrogen and progesterone pills for a year or more and the other 50 used different methods of birth control. Platelet aggregation, ATP release, Thromboxane B2, and 6-keto-prostaglandin F1alpha estimations were made to evaluate the effect of oral contraceptives (OCs) on platelet function and prostanoid production. The results showed no significant differences in the parameters measured in the 2 groups investigated. These findings are comparable to those reported by other studies, suggesting relatively low risk, if any, of thrombosis in OC users.

  11. Oral Submucous Fibrosis (OSMF : A study of 101 cases

    Directory of Open Access Journals (Sweden)

    J V Tupkari

    2007-01-01

    The study showed male preponderance affecting individuals in second and third decades of life. All the patients had the habit of chewing betel leaves, betel nuts, tobacco, gutkha, alone or in various combinations. The associated causative factors were high chilli intake, nutritional deficiencies, and the clinical features were varied such as burning sensation, intolerance to spicy food, restricted mouth opening and difficulty in speech and deglutition. Histopathology was the characteristic of OSMF and was consistent with clinical grades of the disease but could not be corelated to the degree of mouth opening. The study of 101 cases of oral submucous fibrosis is reported.

  12. Zilascorb(2H), a new reversible protein synthesis inhibitor: clinical study of an oral preparation.

    Science.gov (United States)

    Semb, K A; Fodstad, O; Klem, B; Bibow, K; Osmundsen, K; Aamdal, S

    1997-03-01

    The new anti-cancer drug zilascorb(2H) has shown promising activity in preclinical models. Its putative mechanism of action is reversible protein synthesis inhibition and long-term treatment is required. As a clinical treatment modality, long-term daily zilascorb(2H) infusions, as used in previous studies, are not regarded feasible. Therefore, an oral formulation of the drug was developed, and pharmacokinetic profile, toxicity and antitumor activity of zilascorb(2H) tablets were studied. Thirteen patients with advanced solid cancer not amenable to established therapy, but with adequate performance status and organ functions, were included. The treatment was given as a daily i.v. zilascorb(2H) infusion for 5 days, followed by zilascorb(2H) tablets twice daily for 3 months. Blood and urine sampling was performed when estimated plasma steady-state level was reached for each formulation, respectively. Analyses of drug concentrations in plasma and urine were performed by high performance liquid chromatography. Zilascorb(2H) in tablet formulation had a bioavailability of 32%, was quickly absorbed and slowly eliminated. Concomitant use of the H2-blocker ranitidine possibly enhanced bioavailability. Zilascorb(2H) was well tolerated. Two patients experienced drug-related fever, disturbing the treatment schedule for one of them. Moderate nausea was reported. One objective response was obtained. The bioavailability of zilascorb(2H) tablets was satisfactory. The principle of oral administration of zilascorb(2H) is feasible for long-term treatment and the side effects are acceptable. The mechanisms of action and the very low toxicity of the drug makes it a candidate for combination with other anticancer agents.

  13. Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

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    Akhil Kapoor

    2016-01-01

    Full Text Available Introduction: Acute myeloid leukemia (AML in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m 2 . The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61-86 years with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6. Males had median OS of 7 months (95% CI: 5.4-8.6 versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008. There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities.

  14. Preventive Effect of Rebamipide Gargle on Chemoradiotherpy-Induced Oral Mucositis in Patients with Oral Cancer: a Pilot Study

    Directory of Open Access Journals (Sweden)

    Takashi Yasuda

    2011-11-01

    Full Text Available Objectives: To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer.Material and Methods: Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks. The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy.Results: Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12 or placebo-gargle (n = 12 during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3 was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036. In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group.Conclusions: For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

  15. Preventive effect of rebamipide gargle on chemoradiotherpy-induced oral mucositis in patients with oral cancer: a pilot study.

    Science.gov (United States)

    Yasuda, Takashi; Chiba, Hiroshige; Satomi, Takafumi; Matsuo, Akira; Kaneko, Tadayoshi; Chikazu, Daichi; Miyamatsu, Hironobu

    2012-01-01

    To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer. Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week) were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks). The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy. Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12) or placebo-gargle (n = 12) during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3) was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036). In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group. For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

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

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

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

  17. Recent studies on biomethylation and demethylation of toxic elements.

    Science.gov (United States)

    Ridley, W P; Dizikes, L; Cheh, A; Wood, J M

    1977-08-01

    Methylcobalamin (methyl-B12) has been implicated in the biomethylation of the heavy metals (mercury, tin, platinum, gold, and thallium) as well as the metalloids (arsenic, selenium, tellurium and sulfur). In addition, methylcobalamin has been shown to react with lead, but the lead-alkyl product is unstable in water. Details of the kinetics and mechanisms for biomethylation of arsenic are presented, with special emphasis on synergistic reactions between metal and metalloids in different oxidation states. This study explains why synergistic, or antagonistic, processes can occur when one toxic element reacts in the presence of another. The relative importance of biomethylation reactions involving methylcobalamin will be compared to those reactions where S-adenosylmethionine is involved.

  18. Metabolism and toxicity studies supporting the safety of rebaudioside D.

    Science.gov (United States)

    Nikiforov, Andrey I; Rihner, Marisa O; Eapen, Alex K; Thomas, Jennifer A

    2013-07-01

    Rebaudioside D (Reb D) is one of the several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) which has been identified as a potential sweetener. The metabolism of Reb A and Reb D was evaluated in various in vitro matrices (simulated gastrointestinal fluids, rat liver microsomes, and rat cecal contents) and through analysis of plasma collected from rats in a dietary toxicity study. Reb A and Reb D showed similar stability when exposed to simulated stomach and small intestine fluids, with susceptibility to hydrolytic degradation by enteric bacteria collected from the cecum. Incubations with rat liver microsomes indicated that neither compound is expected to be metabolized by the liver enzymes. Plasma concentrations of Reb D, Reb A, and/or the final hydrolysis product of each compound, free/conjugated steviol, were consistent between animals administered either Reb D or Reb A in the diet. A repeated exposure dietary toxicity study was conducted to compare the safety of Reb D, when administered at target exposure levels of 500, 1000, and 2000 mg/kg body weight (bw)/d to Sprague-Dawley rats for 28 days, to that of Reb A administered at a target exposure level of 2000 mg/kg bw/d. There were no treatment-related effects on the general condition and behavior of the animals and no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Results were comparable between the group administered 2000 mg/kg/d Reb D and the group administered 2000 mg/kg/d Reb A.

  19. Once-daily oral administration of cyclosporine in a lung transplant patient with a history of renal toxicity of calcineurin inhibitors.

    Science.gov (United States)

    Matsuda, Yuya; Chen, Fengshi; Miyata, Hitomi; Date, Hiroshi

    2014-07-01

    Cyclosporine is usually administered orally in two divided doses every 12 h in transplant patients. However, some patients have difficulty in achieving therapeutic levels after transplantation. In fact, cyclosporine is reportedly administered once daily in renal and liver transplantation cases, but not in lung transplantation cases. We report a patient with a history of calcineurin inhibitor-induced renal toxicity who successfully underwent living-donor lobar lung transplantation (LDLLT) with the novel immunosuppressive strategy of once-daily administration of cyclosporine. An 18-year old man with progressive respiratory insufficiency after bone marrow transplantation was referred to our hospital for lung transplantation. He had a history of renal toxicity due to calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine-induced renal toxicity, we decided to initiate basiliximab as induction therapy, followed by once-daily cyclosporine administration to obtain high enough blood cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood concentrations (C0) for protection of renal function as maintenance therapy. LDLLT was successfully performed, and the postoperative course was uneventful and free of rejection episodes. Cyclosporine dosing was adjusted with intensive therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT, the patient is alive and well with no problems with daily life activities. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Matija Murko, Wilhelm Radloff, and Oral Epic Studies

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    Aaron Phillip Tate

    2011-10-01

    Full Text Available Commonly regarded as pioneers in the documentation of oral epic singing, Wilhelm Radloff and Matija Murko were personally acquainted and spent time together in St. Petersburg, Russia, during the 1880s—a fact not widely known until now. This essay excavates Murko’s (untranslated Slovenian-language memoirs and discloses a number of historical considerations from the autobiographical account, placing this acquaintance into a wider context, always with an eye toward the history of folklore studies and with special attention paid to a history of Central European research that has been at times neglected on account of its linguistic and historical complexity.

  1. Psychiatric morbidity in oral lichen planus: A preliminary study

    Directory of Open Access Journals (Sweden)

    Abhishek Ranjan Pati

    2014-01-01

    Full Text Available Objective: To study the clinical types and association of psychological factors in patients with Oral Lichen Planus (OLP. Materials and Methods: An analytical age- and sex-matched study involved 30 patients with oral lichen planus (group 1 and 30 control subjects (group 2. We applied the following psychometric tests to both groups: General Health Questionnaire (GHQ and Hospital Anxiety and Depression Scale (HADS. Results: The patients with OLP were found to exhibit statistically significant higher anxiety, insomnia, and social dysfunction with the tests that were used (GHQ 24 and HADS than the control group (P > 0.05. The study group likewise exhibited greater depression and somatic symptoms. The mean total of the GHQ and HAD scores were found to be higher in the study group than in the controls (P > 0.05. Among the various types of OLP, patients with the erosive type had higher mean scores for anxiety and insomnia, social dysfunction and depression. Conclusion: In most patients psychiatric morbidity was strongly associated with OLP, which could support its role in the etiopathogenesis of the disease. The higher scores of the General Health Questionnaire and Hospital Anxiety and Depression Scale gave an insight into the hypothesis that psychological factors are associated with the causation of OLP.

  2. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

    Science.gov (United States)

    Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

    2017-02-01

    This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl2 ). After 15 days of oral administration of CO (2 ml kg(-1) body weight) and MO (2 ml kg(-1) body weight) along with intraperitoneal (i.p.) administration of HgCl2 (5 mg kg(-1) body weight) alone or in combination, we found that CO treatment did not protect against HgCl2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl2 (2 ml kg(-1) body weight + 5 mg kg(-1) body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl2 -induced oxidative damage.

  3. Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae in Swiss Mice

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    Germana Freire Rocha Caldas

    2013-01-01

    Full Text Available Hyptis martiusii Benth. (Lamiaceae is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM. Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice.

  4. Oral verrucous carcinoma: a study of 12 cases.

    Science.gov (United States)

    Alkan, Alper; Bulut, Emel; Gunhan, Omer; Ozden, Bora

    2010-04-01

    The purpose of this clinical study was to identify a clinical and histopathological relationship between verrucous hyperplasia, verrucous keratosis, and verrucous carcinoma. We evaluated 12 patients who had developed oral verrucous carcinoma in the past 10 years in a follow-up study. In this study, the diagnostic criteria included clinical and histopathological features of the lesions. Each lesion was examined by a single oral pathologist. All the patients were diagnosed with verrucous carcinoma following excisional biopsy. One patient was diagnosed with verrucous hyperplasia and another with verrucous keratosis in their initial histological findings. Mandibular, posterior alveolar crest, and retromolar trigone were the most affected sites (41.6%), followed by the buccal mucosa (16.6%), the palate (16.6%), the floor of the mouth (16.6%), and the lip (8.3%). No patients had evidence of recurrence after treatment. Verrucous hyperplasia, verrucous keratosis, and verrucous carcinoma may not be distinguished clinically or may coexist, resulting in diagnostic difficulties. It should be kept in mind that verrucous hyperplasia may also develop from leukoplakic lesions, and it may transform into verrucous carcinoma or squamous-cell carcinoma, acting as a potential precancerous lesion.

  5. Dose finding study of oral PSC 833 combined with weekly intravenous etoposide in children with relapsed or refractory solid tumours.

    Science.gov (United States)

    Pein, F; Pinkerton, R; Berthaud, P; Pritchard-Jones, K; Dick, G; Vassal, G

    2007-09-01

    PSC 833 is an effective MDR1 reversal agent in vitro, including studies with paediatric cancer cell lines such as neuroblastoma and rhabdomyosarcoma. This study was performed to determine the safety profile, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in children with solid tumours and to determine the influence of PSC 833 on the pharmacokinetics of co-administered etoposide. Each patient received one cycle of intravenous etoposide (100 mg/m2 daily for 3 days on three consecutive weeks) to document baseline pharmacokinetics, and subsequently the same schedule using a dose of 50 mg/m2 was given combined with PSC 833 given orally every 6h at a starting dose of 4 mg/kg. Thirty two eligible patients (23 male, median age 8.3 years) were enrolled. Neuroblastoma and rhabdomyosarcoma were the common disease types. Brain tumours were excluded. DLT was defined as any non-haematological grade 3-4 toxicity (common toxicity criteria) and using a specific toxicity scale for cerebellar toxicity. The MDT was defined as the first dose below which 2 or more patients per dose level experienced DLT. Grade 1-2 ataxia occurred in cohorts 2 and 3 (4 and 5 mg/kg, respectively). Three patients developed grade 3 neurotoxicity in the 6 mg/kg cohort and this defined the MTD. Six responses were observed (2 CR, 4 PR). Pharmacokinetic studies indicated that the clearance of etoposide was reduced by approximately 50% when combined with PSC 833. It is concluded that the toxicity profile and MDT is similar in both children and adults, as is the effect on etoposide metabolism. The study demonstrated the feasibility and safety of carrying out a paediatric phase 1 trial across European boundaries and acts as a model for future cooperative studies in rare cancers among children.

  6. Methodology in Seeking Stakeholder Perceptions of Effective Technical Oral Presentations: An Exploratory Pilot Study

    Science.gov (United States)

    Bhattacharyya, Ena; Patil, Arun; Sargunan, Rajeswary Appacutty

    2010-01-01

    Engineering communication studies indicate the importance of oral presentations as an indispensable component of workplace oral communication activities; however, since there is limited literature regarding stakeholder perceptions of effective presentation skills and attributes in technical oral presentations or final year engineering project…

  7. Findings from the oral health study of the Danish Health Examination Survey 2007-2008

    DEFF Research Database (Denmark)

    Kongstad, Johanne; Ekstrand, Kim; Qvist, Vibeke

    2013-01-01

    Abstract Objective. The aims of the oral part of the Danish Health Examination Survey (DANHES 2007-2008) were (1) to establish an oral health database for adult Danes and (2) to explore the influence of general diseases and lifestyle on oral health. This paper presents the study population, exami...

  8. Oral Rinse as a Simpler Approach to Exfoliative Cytology: A Comparative Study

    OpenAIRE

    Mulki, Shaila; Shetty, Pushparaj; Pai, Prakash

    2013-01-01

    Background: Oral rinse is a novel method that can be used to detect dysplasia in potentially malignant disorders and malignant oral lesions in resource challenged areas. A study was undertaken to compare the quality of the normal smears prepared with the oral rinse and that of the wooden tongue spatula.

  9. Melatonin and oral cavity.

    Science.gov (United States)

    Cengiz, Murat İnanç; Cengiz, Seda; Wang, Hom-Lay

    2012-01-01

    While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers.

  10. Melatonin and Oral Cavity

    Directory of Open Access Journals (Sweden)

    Murat İnanç Cengiz

    2012-01-01

    Full Text Available While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers.

  11. Oral submucous fibrosis: A clinico-histopathological study in Chennai

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    Kiran Kumar K

    2007-01-01

    Full Text Available Background: Oral submucous fibrosis (OSF is a precancerous condition associated with the use of areca nut in various forms. There are very few reports to correlate the clinical stage to histopathological grading in OSF. Materials and Methods: A hospital-based study was conducted on 75 OSF cases who visited our hospital in Chennai from 2000-2003. A detailed history of each patient was recorded along with a clinical examination. Biopsy was performed for histopathological correlation. Clinical stage of the disease in terms of the ability to open one′s mouth was correlated with histopathological grading. Results: The male to female ratio of OSF cases was 6:1. All forms of areca nut products were associated with OSF. Chewing of paanmasala was associated with early presentation of OSF as compared to chewing of the betel nut. Out of 57 cases, which were in clinical stage II, 91.2% had histological grading of I and II in equal proportions and 8.8% had histological grade III. Out of 13 cases that showed a clinical stage of III, 52% showed a histological grade of II, 40% grade III and 8% grade I. Conclusion: In the present study, there was no direct correlation between clinical stages and histopathological grading. The possibility of difference in the severity and extent of fibrosis in different regions of the oral mucosa and involved muscles were considered as contributory factors for this variation.

  12. Study on the toxic effect of the mixture of organophosphorus pesticide on perinatal rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To observe the toxic effect of the mixture of organophosphorus pesticide (MOP) on maternal rats and on the growth and development of their offspring. Methods Totally 40 Sprague-Dawley pregnant rats were randomly divided into three MOP dose groups and one control to which their offspring would be assigned. The experimental dosage of MOP and distilled water were administered orally starting on gestation day 15 and continued for 35 days. The physical development indices and the learning ability of F1...

  13. Attenuation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by resveratrol: a comparative study with different routes of administration.

    Science.gov (United States)

    Ishida, Takumi; Takeda, Tomoki; Koga, Takayuki; Yahata, Masahiro; Ike, Ayako; Kuramoto, Chihiro; Taketoh, Junko; Hashiguchi, Isamu; Akamine, Akifumi; Ishii, Yuji; Yamada, Hideyuki

    2009-05-01

    The activation of aryl hydrocarbon receptor with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to be antagonized by co-treatment with resveratrol. However, such a protective effect has been suggested from studies using subcutaneous injection of this polyphenol. To evaluate the practical usefulness of resveratrol, this study examined the protective effect of oral resveratrol on the sub-acute toxic effects of TCDD in C57BL/6J mice. A TCDD-induced wasting syndrome was not alleviated by treating mice for 28 d with oral resveratrol. However, subcutaneous injection of resveratrol for 5 d significantly improved the symptoms. Neither oral nor subcutaneous administration of resveratrol alleviated TCDD-induced hepatomegaly and thymic atrophy. Steatosis produced by TCDD was markedly counteracted by co-treatment with oral resveratrol, whereas resveratrol injected subcutaneously had no effect. The reason for the lack of protective effect via the latter dosing route was assumed to be due to the minor accumulation of hepatic lipids 5 d after TCDD treatment. To clarify the mechanisms, the activity of ethoxyresorufin O-deethylase and the content of thiobarbituric acid-reactive substances in the liver were measured. Both indices increased by TCDD treatment were significantly suppressed by subcutaneous injection of resveratrol. In contrast, oral resveratrol failed to rescue them. In agreement with the greater protective effects of subcutaneously-injected resveratrol, pharmacokinetic studies indicated that the area under the curve extrapolated to infinity (AUC(infinity)) was 8.2-times greater following subcutaneous injection compared with oral administration. These data suggest that 1) oral resveratrol is attractive candidate as an agent capable of combating dioxin toxicity and 2) increasing the bioavailability of this polyphenol enhances its protective effect.

  14. Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats.

    Science.gov (United States)

    El Kabbaoui, Mohamed; Chda, Alae; El-Akhal, Jamila; Azdad, Ouarda; Mejrhit, Najlae; Aarab, Lotfi; Bencheikh, Rachid; Tazi, Abdelali

    2017-09-14

    Cistus ladaniferus L. (C.ladaniferus) (Cistaceae) is an aromatic shrub native to the Mediterranean region. The leaves are widely used in traditional medicine throughout Morocco for the treatment of various diseases including, diabetes, diarrhea, inflammation, and skin ailments. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. The study carried out evaluates the potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL extract) shrub, through the method of acute and sub-chronic oral administration in mice and rats. During the acute toxicity study, male and female mice were orally administrated with CL aqueous extract at single doses of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. During the sub-chronic toxicity study, the aqueous extract was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to Wistar rats of both sexes for 90 days. The general behavior of the rats was observed daily, and their body weight was recorded weekly. A urinalysis, biochemical analysis, hematological analysis, macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. During the acute toxicity test, when mice were administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30% mortality rate, respectively, and induced signs of toxicity. However, no mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg. In the subchronic study, the CL extract induced no mortality or treatment-related adverse effects with regard to body weight, general behavior, relative organ weights, urine, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal

  15. [Advance in study on zearalenone's toxicity and determination].

    Science.gov (United States)

    He, Qing-Hua; Xu, Yang

    2005-07-01

    The article is intended to introduce the zearalenone's toxicity, determination methods and prevention. Zearalenone is one of the most widely distributed mycotoxins produces by Fusarium Species, it is harm to animals and human. And it can induce human liver cancer,carcinoma of tesis esophagus cancer. Now we use high-performance liquid chromatography, gas chromatography, thin layer chromatography, non-toxicity determinations to detect it.

  16. Temporomandibular disorders and parafunctional oral habits: an anamnestic study

    Directory of Open Access Journals (Sweden)

    Melissa de Oliveira Melchior

    2012-04-01

    Full Text Available OBJECTIVE: To assess the frequency and severity of the signs and symptoms of temporomandibular disorders (TMD, the frequency of parafunctional oral habits and the correlation between the variables by means of the patients' perception regarding their problem. METHODS: One hundred patients diagnosed with TMD, through a clinical examination of their masticatory system, answered the questions of a previously published protocol concerning the signs and symptoms most frequently reported in the literature. RESULTS: According to the results from the non parametric statistical analysis, the frequency for the following signs and symptoms was significant: Fatigue and muscle pain, joint sounds, tinnitus, ear fullness, headache, chewing impairment and difficulty to yawn (p<0.01 and otalgia (p<0.05. As to the parafunctional oral habits, there was a significant presence of teeth clenching during the day and night (p<0.01 and teeth grinding at night (p<0.05. The variable correlation analysis showed that there was a positive correlation between symptom frequency and severity; age was correlated with the presence of otalgia, cervical pain and teeth sensitivity, besides being correlated with muscle and joint pain severity. Habit frequency was negatively correlated with age. TMD duration was also positively correlated with the symptoms of tinnitus, ear fullness, muscle and joint pain. CONCLUSION: The study results showed that the anamnestic assessment using ProDTMMulti can predict the severity of the TMD case.

  17. A 13-week subchronic toxicity study of sodium iron chlorophyllin in F344 rats.

    Science.gov (United States)

    Toyoda, Takeshi; Cho, Young-Man; Mizuta, Yasuko; Akagi, Jun-ichi; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-02-01

    Sodium iron chlorophyllin (SIC), a water-soluble chlorophyll derivative, has been used as a food additive for green coloration. In the present study, a subchronic toxicity study of SIC was performed in male and female F344 rats with oral administration in diet at concentrations of 0%, 0.2%, 1.0%, and 5.0% for 13 weeks. No mortalities, abnormal clinical signs, and hematological changes were observed in any of the groups during the experiment. Significant reduction of body weight gain was noted in 5.0% males. In serum biochemistry, serum transferrin levels were significantly increased in 5.0% males and females. Relative spleen weights of both sexes were markedly reduced with 5.0% SIC as compared to the controls, and absolute weights of spleen were also significantly decreased in males. On histopathological assessment, diffuse hypertrophy of acinar cells in the parotid gland was observed in all examined 5.0% males and females, but not in the other groups. Based on the histopathology of the parotid glands, the no-observed-adverse-effect level (NOAEL) of SIC in the present study was estimated to be 1.0% (609 mg/kg bw/day for males and 678 mg/kg bw/day for females).

  18. Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats.

    Science.gov (United States)

    Blum, René; Kiy, Thomas; Tanaka, Satohiro; Wong, Andrea W; Roberts, Ashley

    2007-12-01

    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the non-toxigenic and non-pathogenic marine protist, Ulkenia sp. The safety of DHA-algal oil was assessed in a subchronic toxicity study and in genotoxicity studies. In a 90-day study, rats were orally administered water or DHA-algal oil at concentrations of 0, 500, 1000, and 2000 mg/kg in combination with 2000, 1500, 1000 or 0 mg/kg DHA-containing fish oil, respectively. Additional animals were administered water, 2000 mg/kg DHA-algal oil, or 2000 mg/kg fish oil for 90 days, followed by a 4-week recovery phase. No treatment-related effects were observed in clinical observations, food and water consumption, mortality, gross pathology, and histopathology. Increased body weights and liver weights in oil-treated groups were attributed to the large lipid load and were not regarded as toxicologically significant. Furthermore, no treatment-related differences in the measured parameters between the DHA-algal oil and fish oil groups were detected. In genotoxicity experiments, DHA-algal oil exerted no mutagenic activity in various bacterial strains, nor did it induce chromosomal aberrations in Chinese hamster fibroblast cells. These results support the safety of DHA-algal oil as a dietary source of DHA.

  19. ROLE OF CARICINOGENS IN ORAL CANCER: A MICRONUCLEUS STUDY

    Directory of Open Access Journals (Sweden)

    Pratheepa Sivasankari. N

    2015-12-01

    Full Text Available Background: The three most common fatal cancers were oral, stomach, lung in men. Tobacco related cancers represented 42% in male and 18.3% in female cancer deaths. Poly cyclic aromatic hydrocarbons (PAH is the carcinogen present in tobacco leads to squamous cell carcinoma of oral cavity. Context and purpose of the study: To study the genotoxicity of tobacco and alcohol on the buccal mucosa of alchoholics, smokers and betel nut chewers which is indicated by increased Micro nuclei. 20 persons having the habit of consuming alcohol and smoking and betel nut chewing were compared with 20 controls. After getting the informed consent the material was collected and stained for MN Assay. Results: MN frequency in alcoholic, smokers, betel nut chewers were found to be significant with the ‘P’ value of <0.05 in our study. Conclusion: The present study has revealed that there is a correlation of significant increased frequency of micro nucleus present in users of (1 alcohol and smoking in combination (2 betel nut chewers as compared to normal counterparts, indicating strong cytogenetic damage which may lead to cancerous proliferation. Tobacco can be considered as a leading carcinogenic agent for causing DNA damage which is indicated by increased micro nucleus. Implication: The present micro nuclear study shows a feasible and economical method which could be used as a screening test in population having the habit of alcohol and smoking or betel nut chewing for identifying the effects of genomic instabilities and to introduce timely interventional strategy in order to treat and control the epidemic.

  20. Study of oral Ketoconazole on recurrent & extensive Pityriasis Versicolor