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Sample records for subchronic 90-day toxicity

  1. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    Science.gov (United States)

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Subchronic toxicity (90 days of StemEnhance™ in Wistar rats

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    Levent Dirikolu

    2011-02-01

    Full Text Available Levent Dirikolu1, Thushara Chakkath1, Susan Ball-Kell2, Christy Elamma2, David J Schaeffer11Department of Comparative Biosciences, 2Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USAAbstract: This study evaluated the subchronic toxicity of StemEnhance™, an extract of the blue-green alga Aphanizomenon flos-aquae that is used as a health supplement. Groups of 12 rats of each sex were given either 5% glycerin in water (control or 200 mg/kg of StemEnhance prepared in 5% glycerin in water for 90 days by oral gavage. The administration of StemEnhance had no effect on behavior, food and water intake, growth, or survival. Values at the end of dosing and observation periods did not reveal differences between treated and control groups for hematology and clinical chemistry. There were no significant differences in the gross and histopathology of the reproductive organs in either males or females. Sperm motility parameters were similar for control and treated males. Our results show that StemEnhance at doses ~7 times the maximum label-recommended daily dose did not produce adverse effects in Wistar rats after subchronic treatment.Keywords: algal toxicology, blue-green algae, cyanobacteria, Aphanizomenon flos-aquae

  3. A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

    Science.gov (United States)

    Llana-Ruiz-Cabello, M; Maisanaba, S; Puerto, M; Pichardo, S; Jos, A; Moyano, R; Cameán, A M

    2017-03-01

    Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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.

  5. A 90-day subchronic gavage toxicity study in Fischer 344 rats with 3-methylfuran.

    Science.gov (United States)

    Gill, S; Kavanagh, M; Cherry, W; Bourque, C; Caldwell, D; Wang, G; Bondy, G

    2017-11-24

    A 90-day gavage study was conducted with 0.0, 0.02, 0.075, 0.25, 1.0 and 4.0 mg/kg bw/day dose groups of 3-methylfuran to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including changes in gross anatomy, histopathology, clinical biochemistry and hematology. There were significant changes in the serum clinical biochemistry markers related to liver injury where males were more affected than the females for most parameters analysed. The serum liver injury marker γ-glutamyltransferase, alanine and aspartate aminotransferases were significantly increased in males in the 4.0 mg/kg dose group. Alkaline phosphatase was increased in females and males. There were increases in both gross and histological lesions in the liver of both sexes in addition to statistical differences in female liver weights at the 4.0 mg/kg bw/day dose. Significant increases in spleen weights were found in both genders. This was accompanied by a dose-dependent atrophy of both B- and T-cell regions in which the males were more affected. There were no significant changes in male kidney weights but there was microscopically decreased protein in the proximal tubules and crowding of their nuclei in the 4.0 mg/kg bw/day dose group. There were also significant changes in the kidney serum biomarkers including various electrolytes, blood urea nitrogen, creatinine and uric acid. A small, but significant increase in female kidney weights was observed and which increase was accompanied by changes in electrolytes, kidney specific markers and a dose-dependent increase in mineralization. In both genders, amylase decreased whereas lipase increased but these were not accompanied by any histological changes in the pancreas. Histopathological changes in the liver were observed consistently in male and female rats in the 0.25 mg/kg dose group and higher. Hence, a lowest observed adverse effect level (LOAEL) of 0.25 mg/kg bw/d and a no observed

  6. 90-day subchronic toxicity study in rats and mice fed N-methylpyrrolidone (NMP) including neurotoxicity evaluation in rats.

    Science.gov (United States)

    Malley, L A; Kennedy, G L; Elliott, G S; Slone, T W; Mellert, W; Deckardt, K; Gembardt, C; Hildebrand, B; Parod, R J; McCarthy, T J; Griffiths, J C

    1999-08-01

    In mice, there were no effects on body weight or food consumption. As observed in rats, mice fed 2,500 or 7,500 ppm exhibited a change in urine coloration which was not associated with morphological changes in cholesterol, triglycerides, calcium, and alkaline phosphatase occurred at 28 days but not 90 days. These changes are thus assessed as being of minor toxicological relevance. Liver weights were elevated in males fed 2,500 or 7,500 ppm and centrilobular hypertrophy was seen in both sexes fed 7,500 ppm. These changes may be regarded as an adaptation process but are clearly related to NMP exposure. Other toxicological endpoints examined were unaffected by NMP. The NOAEL was 3,000 ppm for both sexes of rats based on body weight effects and changes in 3 neurobehavioral parameters (males only) at higher feeding levels. In mice, the NOAEL was 1,000 ppm based on liver responses to higher concentrations.

  7. Bitter orange (Citrus aurantium L.) extract subchronic 90-day safety study in rats

    OpenAIRE

    Deshmukh, N.S.; Stohs, S.J.; Magar, C.C.; Kale, A.; Sowmya, B.

    2017-01-01

    Bitter orange (Citrus aurantium L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. p-Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% p-synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect...

  8. Bitter orange (Citrus aurantium L. extract subchronic 90-day safety study in rats

    Directory of Open Access Journals (Sweden)

    N.S. Deshmukh

    Full Text Available Bitter orange (Citrus aurantium L. extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. p-Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% p-synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect to any of the observed parameters of clinical signs, functional observations of sensory reactivity, grip strength and motor activity, ophthalmology, body weights, hematology, food consumption, urinalysis, organ weights, as well as gross and microscopic pathology at termination at any of the doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract resulted in non-adverse effects including fully reversible signs of repetitive head burrowing in the bedding material and piloerection for short periods of time in both sexes immediately after administration, which gradually disappeared by treatment day-81. A slight and reversible elevation of BUN and urea levels in male rats, and slight to mild increase in the relative but not absolute heart weights of male and female rats was observed. Based on these results, the no-observed-effect-level (NOEL for this bitter orange extract standardized to 50% p-synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL was 1000 mg/kg. The results indicate a high degree of safety for this bitter orange extract. Keywords: Citrus aurantium, Bitter orange, p-Synephrine, Subchronic toxicity, No-observed-adverse-effect-level (NOAEL, No-observed-effect-level (NOEL

  9. Bitter orange (Citrus aurantiumL.) extract subchronic 90-day safety study in rats.

    Science.gov (United States)

    Deshmukh, N S; Stohs, S J; Magar, C C; Kale, A; Sowmya, B

    2017-01-01

    Bitter orange ( Citrus aurantium L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. p -Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% p -synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect to any of the observed parameters of clinical signs, functional observations of sensory reactivity, grip strength and motor activity, ophthalmology, body weights, hematology, food consumption, urinalysis, organ weights, as well as gross and microscopic pathology at termination at any of the doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract resulted in non-adverse effects including fully reversible signs of repetitive head burrowing in the bedding material and piloerection for short periods of time in both sexes immediately after administration, which gradually disappeared by treatment day-81. A slight and reversible elevation of BUN and urea levels in male rats, and slight to mild increase in the relative but not absolute heart weights of male and female rats was observed. Based on these results, the no-observed-effect-level (NOEL) for this bitter orange extract standardized to 50% p -synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg. The results indicate a high degree of safety for this bitter orange extract.

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

    Science.gov (United States)

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

    2000-12-01

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

  11. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Science.gov (United States)

    2010-07-01

    ... in the control and treatment groups must be sacrificed. (10) Clinical pathology. Hematology and..., prostate, testes, epididymides, seminal vesicle(s), uterus, ovaries, female mammary gland. (G) Other—all...) Weingand K, Brown G, Hall R et al. (1996). Harmonization of Animal Clinical Pathology Testing in Toxicity...

  12. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

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    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  13. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

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    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice.

  14. Toxicity of coenzyme Q(10): a report of 90-day repeated dose toxicity study in rats.

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    Zhipeng, Wang; Mingkai, Li; Shuyu, Cui; Min, Jia; Jingru, Meng; Xue, Ma; Yumei, Wu; Xiaoxing, Luo

    2007-12-01

    Potential toxicity of CoQ(10) was studied in rats by oral gavage for 90 days at 500, 1500, and 3000 mg/kg.day. A 15-day recovery period after the administration period was investigated. Body weight and food consumption were measured throughout the study. Meanwhile, clinical observations were recorded. Hematological and blood chemistry parameters were evaluated at both the end of the dosing period and the end of the recovery period. Gross-pathologic and histopathologic examination was performed on select tissues from all animals. No adverse changes in mortality and clinical signs occurred. The body weights of males in the 1500 mg/kg dosage group were slightly reducted; likewise, the food consumption in 3000 mg/kg female rats decreased, but this is not a dose-dependent behavior. Significant change of liver function (TRIGL) and CHOL did not show a dose-dependent effect. Weight of ovary and ovary-to-body weight ratio decreased in the 1500 mg/kg dosage groups. Meanwhile, the uterus -to-body weight ratio increased the in 3000 mg/kg dosage groups. However, there were no significant histopathological changes observed in ovary and uterus: so they were not considered to be adverse. It suggested that CoQ(10) is relatively safe on the test dosage administration. Nevertheless, appetite the body weight, blood lipid and liver function should be observed during long-term clinical administration of this drug with high dosage. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 3000 mg/kg.day.

  15. A 90-day oral toxicity study of purple corn color, a natural food colorant, in F344 rats.

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    Nabae, Kyoko; Hayashi, Shim-Mo; Kawabe, Mayumi; Ichihara, Toshio; Hagiwara, Akihiro; Tamano, Seiko; Tsushima, Yoko; Uchida, Koji; Koda, Takatoshi; Nakamura, Mikio; Ogawa, Kumiko; Shirai, Tomoyuki

    2008-02-01

    A subchronic oral toxicity study of purple corn color (PCC), a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.5%, 1.5% and 5.0% for 90 days. No mortalities occurred during the treatment period. No treatment-related changes in the body weight, food and water consumption, ophthalmology, hematology, organ weight data and histopathology were observed. Regarding general conditions and gross pathology, staining of fur and black feces were noted in rats of the 1.5% and 5.0% diet groups. Moreover, brown urine and black material in the stomach, small and large intestine were evident in rats receiving 5.0%. These changes were considered due to the anthocyanin content. On clinical chemistry analysis, total cholesterol, phospholipid and triglyceride were significantly lowered in both sexes of the 5.0% group, but these were not considered to be toxicologically significant. Thus, the No-observed-adverse-effect-level (NOAEL) was judged to be 5.0% in diet for both sexes (male: 3542 mg/kg/day, female: 3849 mg/kg/day) for PCC under the present experimental conditions.

  16. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days.

    Science.gov (United States)

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats.

  17. Evaluation of 90-day oral rat toxicity studies on the food additive, gum ghatti.

    Science.gov (United States)

    Maronpot, Robert R; Davis, Jeffrey; Moser, Glenda; Giri, Dipak K; Hayashi, Shim-Mo

    2013-01-01

    Gum ghatti, a polysaccharide of natural origin, is used in foods as a thickening, gelling, emulsifying and stabilizing agent. In a 90-day toxicity study following Organization for Economic Co-operation and Development (OECD) Guideline #408, male and female Sprague-Dawley rats were exposed to 0 (control), 0.5, 1.5 and 5% gum ghatti in AIN-93M basal diet. Expected changes included increased full and empty cecal weights in 5% groups. Incidentally 2/10 females from the 5% gum ghatti group had a single colon ulcer with associated acute inflammation. In a second 90-day study increased cecal weights were present in Sprague-Dawley females exposed to 5% gum ghatti in AIN-93M and NIH-07 basal diets. A single colon ulcer with associated acute inflammation occurred in 1/20 control females given AIN-93M basal diet. The colon ulcers were considered a sporadic change possibly attributable to AIN-93M basal diet. In the second study a few statistically significant alterations in clinical chemistry were considered sporadic and unrelated to treatment. Feed consumption among treated and control groups was similar for each sex. Gum ghatti intake at the 5% dietary level ranged from 3044 to 3825mg/kg body weight/day. The 5% dietary administration was a NOAEL in both studies. NOAELs for males and females in the first study were 3044 and 3309mg/kg/day, respectively. NOAELs for females in the second study were 3670 and 3825mg/kg/day for AIN-93M and NIH-07 diets, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. A 90 days oral toxicity of imidacloprid in female rats: morphological, biochemical and histopathological evaluations.

    Science.gov (United States)

    Bhardwaj, Shipra; Srivastava, M K; Kapoor, Upasana; Srivastava, L P

    2010-05-01

    A 90 days oral toxicity study of imidacloprid was conducted in female rats with doses of 0, 5, 10, 20mg/kg/day. Decrease in the body weight gain was observed at 20mg/kg/day and at necropsy the relative body weights of liver, kidney and adrenal was also significantly increased at this dose level. No mortality occurred during treatment period while food intake was reduced at high dose level. In clinical chemistry parameters high dose of imidacloprid has caused significant elevation of serum GOT, GPT, glucose and BUN and decreased the activity of AChE in serum and brain. The spontaneous locomotor activity was also decreased at highest dose exposure where as there were no significant changes in hematological and urine parameters. The brain, liver and kidney of rats exposed with high dose of imidacloprid had showed mild pathological changes. Based on the morphological, biochemical, hematological and neuropathological studies it is evident that imidacloprid has not produced any significant effects at 5 and 10mg/kg/day doses but induced toxicological effects at 20mg/kg/day to female rats. Hence, 10mg/kg/day dose may be considered as no observed effect level (NOEL) for female rats. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  19. Safety of PVAP and PVAP-T including a 90-day dietary toxicity study in rats and genotoxicity tests with polyvinyl acetate phthalate (PVAP).

    Science.gov (United States)

    DeMerlis, C C; Schoneker, D R; Borzelleca, J F

    2014-08-01

    The safety of PVAP was evaluated in a 90-day subchronic toxicity study in rats. Sprague Dawley Crl:CD(SD) rats were administered a dietary concentration of 0.75%, 1.5% and 5.0% PVAP for a minimum of 90days. There were no adverse effects reported. The no-observed-adverse-effect level (NOAEL) in the 90-day sub chronic study was the 5% dietary concentration, which corresponds to a dose of 3120mg/kg/day for males and 3640mg/kg/day for females, the highest level tested. PVAP is co-processed with titanium dioxide to produce polyvinyl acetate phthalate and titanium dioxide (PVAP-T). The chemical composition, physiochemical properties and specifications of PVAP-T are unchanged during manufacturing process based on various analytical studies. Therefore, the toxicological data that support the safety of PVAP can be used to support the use of PVAP-T as a pharmaceutical excipient. An independent expert panel evaluated the safety of PVAP and PVAP-T. Based on the toxicology study results, safety assessment and the estimated exposure assessment for PVAP and PVAP-T, the expert panel concluded that PVAP and PVAP-T could safely be used in drug products up to 829mg per day which was the estimated exposure provided to the expert panel for current applications of PVAP and PVAP-T. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. A 90-day subchronic study of rats fed lean pork from genetically modified pigs with muscle-specific expression of recombinant follistatin.

    Science.gov (United States)

    Zou, Shiying; Tang, Min; He, Xiaoyun; Cao, Yuan; Zhao, Jie; Xu, Wentao; Liang, Zhihong; Huang, Kunlun

    2015-11-01

    Because cardiovascular disease incidence has rapidly increased in recent years, people are choosing relatively healthier diets with low animal fat. A transgenic pig with low fat and a high percentage of lean meat was created in 2011; this pig overexpresses the follistatin (FST) gene. To evaluate the safety of lean pork derived from genetically modified (GM) pigs, a subchronic oral toxicity study was conducted using Sprague-Dawley rats. GM pork and non-GM pork were incorporated into the diet at levels of 3.75%, 7.5%, and 15% (w/w), and the main nutrients of the various diets were subsequently balanced. The safety of GM pork was assessed by comparison of the toxicology response variables in Sprague-Dawley rats consuming diets containing GM pork with those consuming non-GM pork. No treatment-related adverse or toxic effects were observed based on an examination of the daily clinical signs, body weight, food consumption, hematology, serum biochemistry, and organ weight or based on gross and histopathological examination. The results demonstrate that GM pork is as safe for consumption as conventional pork. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2010-07-01

    ...) Clinical pathology. Hematology and clinical chemistry examinations must be made on all animals, including..., ovaries, female mammary gland. (G) Others—all gross lesions and masses, skin. (12) Histopathology. (i) The... Pathology Testing in Toxicity and Safety Studies. Fundam. & Appl. Toxicol. 29:198-201. (1996) ...

  2. Physicochemical analysis and repeated-dose 90-days oral toxicity study of nanocalcium carbonate in Sprague-Dawley rats.

    Science.gov (United States)

    Sung, Jae Hyuck; Park, Soo Jin; Jeong, Min Sook; Song, Kyung Seuk; Ahn, Kyu Sup; Ryu, Hyun Ryol; Lee, Han; Song, Mi Ryoung; Cho, Myung-Haing; Kim, Jun Sung

    2015-01-01

    In our previous studies of nanocalcium carbonate, in which we performed physicochemical analysis, genotoxicity, acute single-dose and repeated-dose 14-day oral toxicity testings in Sprague-Dawley (SD) rats, nanocalcium carbonate did not show a difference in toxicity compared to vehicle control. Here, we provide the first report of a repeated-dose 90-day oral toxicity test of nanocalcium carbonate in Sprague-Dawley rats, with physicochemical comparison of micro and nanocalcium carbonate. We find that the two particles differ in size, hydrodynamic size, and specific surface area, with no differences in components, crystalline structure and radical production. In terms of ionization ability, nanocalcium carbonate was slightly more ionized within 1% than microcalcium carbonate at pH 5 and pH 7. In the repeated-dose 90-day oral toxicity test of nanocalcium carbonate, there was no significant toxicity, and similar blood concentrations of Ca(2+) compared to the vehicle control group. Based on our results, although nanocalcium carbonate has different physicochemical properties, nanocalcium carbonate does not differ from microcalcium carbonate in terms of toxicity. Based on the results, we suggest that the no-observed-adverse-effect level (NOAEL) of nanocalcium carbonate is 1000 mg kg(-1) day(-1) in SD rats according to the maximum dose (OECD guideline 408). However, the NOAEL might be higher than 1000 mg kg(-1) day(-1) because there were no adverse effects revealed by consistent pathological findings or biochemical parameter changes. To justify a safe concentration of nanocalcium carbonate, which is a low toxicity chemical, more data is required on dose levels above 1000 mg kg(-1). Our findings may be useful for creating safety guidelines for the use nanocalcium carbonate.

  3. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    Science.gov (United States)

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

    Science.gov (United States)

    Nabae, K; Ichihara, T; Hagiwara, A; Hirota, T; Toda, Y; Tamano, S; Nishino, M; Ogasawara, T; Sasaki, Y; Nakamura, M; Shirai, T

    2005-07-01

    A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

  5. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 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. Copyright © 2010 Elsevier GmbH. All rights reserved.

  7. Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats.

    Science.gov (United States)

    Schwotzer, Daniela; Ernst, Heinrich; Schaudien, Dirk; Kock, Heiko; Pohlmann, Gerhard; Dasenbrock, Clemens; Creutzenberg, Otto

    2017-07-12

    Nanomaterials like cerium oxide and barium sulfate are frequently processed in industrial and consumer products and exposure of humans and other organisms is likely. Generally less information is given on health effects and toxicity, especially regarding long-term exposure to low nanoparticle doses. Since inhalation is still the major route of uptake the present study focused on pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m(3)) and BaSO4NM-220 nanoparticles (50.0 mg/m(3)) in a 90-day exposure setup. To define particle-related effects and potential mechanisms of action, observations in histopathology, bronchoalveolar lavage and immunohistochemistry were linked to pulmonary deposition and clearance rates. This further allows evaluation of potential overload related effects. Lung burden values increased with increasing nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance was impaired, suggesting lung overload. Barium elimination was extremely rapid and without any signs of overload. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation with increasing severity and post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell proliferation were significantly increased. BaSO4 showed less inflammation or persistency of effects and particularly affected the nasal cavity. CeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract after inhalation mainly in terms of inflammation. Effects at low dose levels and post-exposure persistency suggest potential long-term effects and a notable relevance for human health. The generated data might be useful to improve nanoparticle risk assessment and threshold value generation. Mechanistic investigations at conditions of non-overload and absent inflammation should be further investigated in future studies.

  8. Acute and subchronic toxicity study of the water extract from Harrisonia perforata Merr. in rats.

    Directory of Open Access Journals (Sweden)

    Seewaboon Sireeratawong

    2009-01-01

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

  9. [Acute and subchronic monensin toxicity for lambs].

    Science.gov (United States)

    Donev, B; Stoianov, K; Dzhurov, A; Dilov, P

    1980-01-01

    The acute and subchronic toxicity of monenzine (preparation Elancoban -- 100 of Elanco Co., USA) to male lambs for fattening aged 3-4 months and weighing 16-28.5 kg was studied. It was established that the single per oral dose of 5 mg/kg weight of the natrium monoenzine salt causes a temporary lack of appetitie but no changes in the behavior and the general state of the animals. The use of a 10 and 30 mg/kg weight dose of the preparation led to death of the lambs on the 72nd-120th hour. The toxicity was clinically manifested by anurexia, arumination, ataxia, paresis, and paralysis of the limbs, tachicardia, taxipnea, hypothermia and showed down and weakened rumen movements. Erosive rumitis and abomasis, catharrhalhemorrhagis duodenitis, hemorrhages on the epicardis, hyperremia and parenchymal organ oedema, 3-4 times increased gall-bladder with numerous nodes having a sunken center on its walls were observed pathologo-anatomically, while microscopically blood vessel disturbances (hyperremia, hemorrhages and oedema) of the lungs, heart, spleen, endocrinal glands (thyroid, adrenal and hypophysis), the brain, and the leptomeninges, liver distrophy, distrophic nephrosis and necrotic holecystitis were obvious. Following a long term (30 days) application to the fodder in 10 and 50 g/t doses, monenzine-natrium does not have a negative effect on the behaviour, general condition, clinical and biochemical blood composition and the structural build up of the inner organs, but in the first 5-10 days of the treatment it causes loss of appetite. Additional specific investigations are needed to elucidate the effect of the preparation on body gain.

  10. Scientific evaluation of the acute toxicity and 13-week subchronic toxicity of Rheum emodi rhizome extracts in Sprague Dawley rats.

    Science.gov (United States)

    Ye, Ben-Gui; Feng, Yong; Wang, Shu

    2014-04-01

    Rheum emodi has been used as an edible and medicinal plant in Tibet and Kashmir for a long period of time, while safety evaluation of this plant has not yet been investigated. In this study, acute and subchronic oral toxicity studies of aqueous extract of R. emodi (AERE) rhizome were conducted in SD rats. Animals were treated with a single dose of 1000, 2000, 4000 or 10,000 mg/kg of AERE in the acute toxicity. In subchronic oral toxicity, animals were randomly divided into four groups (10 rats/sex/group) and received doses of 0, 1000, 2000, and 4000 mg/kg/d of AERE for 90 days. Daily clinical observations, weekly measurement of body weight and food consumption were conducted. Blood and urine were collected on days 91 to measure changes. At necropsy, selected organs were weighed and recorded, and histological examination was performed. During the subchronic oral toxicity study, no mortality, obvious treatment-related clinical signs and urinalysis parameters were observed. Differences in weight gain, food consumption, hematology, biochemistry, relative organ weight and histopathology examinations between the treated group and the control group were not considered treatment-related. Our results indicated that the no-observed-adverse-effect level (NOAEL) for AERE was 4000 mg/kg/d in both genders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A subchronic toxicity study of ethanol root extract of baked Aconitum flavum in rats

    Directory of Open Access Journals (Sweden)

    Yuanbin Zhang

    Full Text Available ABSTRACT The genus Aconitum has strong toxicity, but the acute toxicity of baked Aconitum flavum Hand.-Mazz., Ranunculaceae, was reduced significantly on the premise of keeping anti-inflammatory and anti-nociceptive activities. However, the risk associated with long-term use is unknown. In a sub-chronic toxicity study, rats were orally administered A. flavum at doses of 0.76–3.03 g/kg for 90 days and further recovered for 14 days. Our results showed that oral treatment with A. flavum for 90 days caused significant changes in some hematological indicators at doses of 3.03 and 1.52 g/kg, such as red blood cell, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These results indicated that the A. flavum affects the structure and function of red blood cell. Furthermore, significant changes were observed in the white blood cell at dose of 3.03 g/kg in male rats, which confirmed tissue damage or toxicity. The liver function tests exhibited non-significant alterations in aspertate aminotransferase, alanine aminotransferase and avenin-like storage proteinsgene. But other parameters, such as total protein and albumin were obviously decreased at all doses. A. flavum also caused a significant decrease in glucose, cholesterol and triacylglyceride at all doses. For kidney function, there were significant elevations in urea and creatinine at doses of 3.03 and 1.52 g/kg. The levels of certain electrolytes (Na+, K+ and Cl- were significantly different after 90 days of treatment with A. flavum (3.03 and 1.52 g/kg. Organs were observed by light microscopy after hematoxylin-eosin staining. Hemosiderin depositions in the spleen were observed in the A. flavum group. These data demonstrated that the subtoxicity of A. flavum was reduced considerably by baked, but the subchronic toxicity effects on the liver, kidney and spleen should not be ignored.

  12. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

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

  13. Subchronic toxicity and mutagenicity/genotoxicity studies of Irvingia gabonensis extract (IGOB131).

    Science.gov (United States)

    Kothari, Shil C; Shivarudraiah, Prasad; Venkataramaiah, Suresh Babu; Gavara, Swapna; Soni, Madhu G

    2012-05-01

    African Bush Mango from Irvingia gabonensis is a West African culinary fruit and the mucilage from this fruit seed is used to make traditional soups and sauces. Extract from the kernel (IGOB131) has been claimed for its health benefits. In the present investigations, potential adverse effects, if any, of IGOB131 were investigated in dose-response 90-day study and genotoxicity studies. In the subchronic study, Sprague Dawley rats (20/sex/group) were gavaged with I. gabonensis extract (IGOB131) at dose levels of 0, 100, 1000 and 2500 mg/kg body weight (bw)/day for 90-days. No treatment-related changes in clinical signs, functional observations, mortality, ophthalmologic observations, body weights, body weight gain or feed consumption were noted. Similarly, hematological, clinical chemistry, urine analysis parameters, and organ weights did not reveal any toxicologically significant treatment-related changes. No treatment-related macroscopic and microscopic abnormalities were noted at the end of treatment period. The mutagenicity as evaluated by Ames assay, in vitro and in vivo chromosomal aberration test and in vivo micronucleus assay did not reveal any genotoxicity of IGOB131. The results of subchronic toxicity study suggest the no-observed-adverse-effect level (NOAEL) for I. gabonensis extract (IGOB131) as ≥ 2500 mg/kg bw/day, the highest dose tested. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    African Journals Online (AJOL)

    Purpose: To investigate the toxicological profile of the ethanol extract of Oncoba spinosa (EEOS) after acute and sub-chronic administration to rodents. Methods: In the acute toxicity study, a single administration of the extract at doses of 2000 and 5000 mg/kg, respectively, was given to the mice. Mice were observed for ...

  15. Evaluation of the safety of a genetically modified DAS-444Ø6-6 soybean meal and hulls in a 90-day dietary toxicity study in rats.

    Science.gov (United States)

    Papineni, Sabitha; Murray, Jennifer A; Ricardo, Ekmay; Dunville, Christina M; Sura, Radha Krishna; Thomas, Johnson

    2017-11-01

    A 90-day sub chronic toxicity study was conducted in rats to evaluate the safety of genetically modified DAS-444Ø6-6 soybeans expressing herbicide tolerant proteins when compared with its conventional comparators (non-transgenic near isoline control soybean and three commercially available non-transgenic line control soybeans). Rats were given diets formulated with either 10% or 20% w/w of soybean meal and 1% or 2% hulls of DAS-444Ø6-6 soybean with an equivalent amount of hulls from an isoline non-transgenic control soybean for at least 90 days. In addition, three separate 20% w/w non-transgenic commercially available soybean varieties were also given to groups of rats to serve as reference controls. Animals were evaluated by cage-side and hand-held detailed clinical observations, ophthalmic examinations, body weights/body weight gains, feed consumption, hematology, prothrombin time, urinalysis, clinical chemistry, selected organ weights, and gross and histopathologic examinations. Under the conditions of this study, the genetically modified DAS-444Ø6-6 diets did not cause any treatment-related effects in rats following 90 days of dietary administration as compared with rats fed diets with soybean of isoline control or commercial reference controls and are considered equivalent to the diets prepared from conventional comparators. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Safety assessment of lutein and zeaxanthin (Lutemax 2020): subchronic toxicity and mutagenicity studies.

    Science.gov (United States)

    Ravikrishnan, R; Rusia, Shraddha; Ilamurugan, G; Salunkhe, Ulhas; Deshpande, Jayant; Shankaranarayanan, J; Shankaranarayana, M L; Soni, Madhu G

    2011-11-01

    Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration. Lutemax 2020 is a lutein and zeaxanthin (including meso-isomer) enriched product obtained from Marigold flowers (Tagetes erecta L). The objective of the present study was to investigate adverse effects, if any, of Lutemax 2020 in acute and subchronic toxicity, and mutagenicity studies. In acute toxicity study in rats no lethality was noted at 2000 mg Lutemax 2020/kg body weight (bw). In the subchronic study, Wistar rats (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose levels of 0, 4, 40 and 400mg/kg bw/day for 90-days. Compared with the control group, administration of lutein/zeaxanthin concentrate did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No toxicologically relevant findings were noted in urinalysis, hematology or clinical biochemistry parameters at the end of the treatment or recovery period. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. The results of mutagenicity testing in Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for lutein/zeaxanthin concentrate was determined as 400mg/kg bw/day, the highest dose tested. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Acute and subchronic toxicity of metal complex azo acid dye and anionic surfactant oil on fish Oreochromis niloticus.

    Science.gov (United States)

    Amwele, Hilma Rantilla; Papirom, Pittaya; Chukanhom, Kanit; Beamish, Fredrick Henry William; Petkam, Rakpong

    2015-01-01

    The acute toxicity study of metal complex dark green azo acid dye, anionic surfactant oil and their mixture determined the 96 hr LC50, and fish behaviours. Subchronic toxicity determined haematology parameters and concentrations of copper and chromium in blood. The 96 hr LC50 was determined by probit analysis and subchronic toxicity was conducted in 90 days. No mortalities were observed in control and anionic surfactant oil treatments. The 96 hr LC50 value of mixture was 26.7 mg I(-1) (95% CL = 20.7 - 46.8) and that of metal complex dark green azo acid dye was not met as the percentage of dead was below 50% of tested organisms. In a treatment of anionic surfactant oil and that of mixture observed behaviours were respiration response, uncoordinated movement, loss of equilibrium, erratic posture and loss of responsiveness. Subchronic toxicity indicated fluctuations in number of erythrocytes, leukocytes and thrombocytes in all chemical treatments. Erythrocyte morphology such as anisocytosis, erythrocytes hypertrophy, karyolysis, cytoplasm vacuolation, ghost cell were observed in fish blood in all chemical treatments. An inverse relation was observed between total copper and chromium concentration in blood. However, the toxicity effect was chemical dose dependent and length of exposure.

  18. 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.

  19. 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.

  20. Subchronic toxicity study of the total flavonoids from Rosa laevigata Michx fruit in rats.

    Science.gov (United States)

    Zhang, Shuai; Zheng, Lingli; Xu, Lina; Sun, Huijun; Li, Hua; Yao, Jihong; Liu, Kexin; Peng, Jinyong

    2012-03-01

    The total flavonoids (TFs) from Rosa laevigata Michx fruit showed hepatoprotective and antioxidant activities. However, the safety of this natural product has not been investigated. In the present paper, a 90-day subchronic toxicity study was conducted, and the tested TFs was orally administered to rats at the doses of 500, 1000 and 2000mg/kg/day. The toxicity of the TFs was evaluated on base of ophthalmic examination, body weight, feed/water consumption, urinalysis, hematology, clinical biochemistry and pathology. No toxic signs of the TFs at the doses of 500 and 1000mg/kg/day were observed. However, decreased PLT was found in the 2000mg/kg/day groups and increased intercellular space of myocardial cells was observed in the male 2000mg/kg/day group compared with control. A significant increase in the relative cardiac weight was observed in the male 1000 and 2000mg/kg/day groups. And the significant decrease in the absolute and relative weight of adrenals in the female 1000 and 2000mg/kg groups was happened. The TFs could cause mild side effects at the dose of 1000mg/kg/day in males and females. Thus, the dose of 500mg/kg/day for male and female were selected as the no-observed-adverse-effect level (NOAEL). The present study provides useful data for subsequent researches and new drug exploration of the TFs from R. laevigata Michx fruit. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-01

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

  2. Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies

    Directory of Open Access Journals (Sweden)

    Liju Vijayasteltar

    2016-01-01

    Full Text Available Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol, as assessed by oral acute (5 g/kg b.wt. for 14 days and subchronic (0.25, 0.5 and 1 g/kg b.wt. for 90 days toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of Clovinol did not result in any toxicologically significant changes in clinical/behavioural observations, ophthalmic examinations, body weights, organ weights, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals, indicating the no observed-adverse-effect level (NOAEL as 1000 mg/kg b.wt./day; the highest dose tested. Terminal necropsy did not reveal any treatment-related histopathology changes. Clovinol did not show genotoxicity when tested on TA-98, TA-100 and TA-102 with or without metabolic activation; rather exhibited significant antimutagenic potential against the known mutagens, sodium azide, NPD and tobacco as well as against 2-acetamidoflourene, which needed metabolic activation for mutagenicity.

  3. Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies.

    Science.gov (United States)

    Vijayasteltar, Liju; Nair, Gopakumar Gopinathan; Maliakel, Balu; Kuttan, Ramadasan; I M, Krishnakumar

    2016-01-01

    Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol), as assessed by oral acute (5 g/kg b.wt. for 14 days) and subchronic (0.25, 0.5 and 1 g/kg b.wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of Clovinol did not result in any toxicologically significant changes in clinical/behavioural observations, ophthalmic examinations, body weights, organ weights, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals, indicating the no observed-adverse-effect level (NOAEL) as 1000 mg/kg b.wt./day; the highest dose tested. Terminal necropsy did not reveal any treatment-related histopathology changes. Clovinol did not show genotoxicity when tested on TA-98, TA-100 and TA-102 with or without metabolic activation; rather exhibited significant antimutagenic potential against the known mutagens, sodium azide, NPD and tobacco as well as against 2-acetamidoflourene, which needed metabolic activation for mutagenicity.

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

    OpenAIRE

    Gupta Reena; Duggal Sanjiv; Kapoor Bhupinder

    2012-01-01

    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 ...

  5. Impact of lead sub-chronic toxicity on recognition memory and motor activity of Wistar rat.

    Science.gov (United States)

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2009-01-15

    The aim of this research was to investigate the impact of lead nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain lead accumulation and especially on recognition memory of Wistar rats. Two groups of young female Wistar rats were used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking water, while control rats received drinking water only, for 3 months. An evolution of body weight, motor activity, object recognition memory and measure of brain lead levels has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the Open Field (OF) test and to the Novel Object Recognizing (NOR) memory test. The results have shown a non significant effect in gain of body weight. However, a high significance was shown for horizontal activity (pmemory term (p<0.01), at the end of testing period and for brain lead levels (p<0.05) between studied groups.

  6. Toxicological Evaluation of β-Caryophyllene Oil: Subchronic Toxicity in Rats.

    Science.gov (United States)

    Schmitt, D; Levy, R; Carroll, B

    2016-09-01

    In a subchronic toxicity study, administration of β-caryophyllene (BCP) oil by oral gavage to Wistar rats at dosages of 0, 150, 450, or 700 mg/kg/d for 90 days, including a 21-day recovery period, did not produce any significant toxicologic manifestations. The study design also included a 28-day interim sacrifice in the control and high-dose groups. The BCP oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral end points, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, and necropsy findings. The no observed adverse effect level was the highest dosage level administered of 700 mg/kg body weight/d for both male and female rats. The study was conducted as part of an investigation to examine the safety of BCP oil for its proposed use in medical food products. © The Author(s) 2016.

  7. Acute and subchronic toxicity of pyraclostrobin in zebrafish (Danio rerio).

    Science.gov (United States)

    Zhang, Cheng; Wang, Jun; Zhang, Shuai; Zhu, Lusheng; Du, Zhongkun; Wang, Jinhua

    2017-12-01

    The aim of the present study was to assess the toxic effects of pyraclostrobin on DNA damage and antioxidant enzymatic activities in the zebrafish (Danio rerio) liver. Based on the 96-h median lethal concentration (96 h LC50, 0.056 mg/L) of this chemical, fish were exposed to three doses (0.001, 0.01, and 0.02 mg/L) and sampled on days 7, 14, 21 and 28 after the initiation of a subchronic toxicity test. The levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione S-transferase (GST), reactive oxygen species (ROS) and DNA damage were determined. The amount of pyraclostrobin residue in the water was also measured. The concentrations in the three treatment groups varied no more than 5% during the exposure periods, indicating that pyraclostrobin is relatively stable during this time in an aquatic environment. ROS and MDA levels significantly changed in a dose dependent manner during the experiment. Enzymatic activities were inhibited to a certain extent. DNA damage was significantly enhanced. These results collectively indicate that pyraclostrobin induces oxidative stress and DNA damage in zebrafish. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 90-Day Inhalation Toxicity Study of Bio-Derived Gevo Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) in Rats with Neurotoxicity Testing and Genotoxicity Assay

    Science.gov (United States)

    2015-05-31

    turned and briefly held on its back,  hind leg splay: response to being dropped approximately 30 cm (12 inches). Hind legs were painted to mark the...approximately 30 cm (12 inches). Hind legs are painted to mark the location of the hind legs upon landing. This test is not done if the animal is judged...2007. Assessing toxicity of fine and nanoparticles : Comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol. Sci. 97:163– 180

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-01

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

  11. Subchronic toxicity experiment with rats fed a diet containing ergotamine-tartrate

    NARCIS (Netherlands)

    Speijers GJA; Wester PW; van Leeuwen FXR; de la Fonteyne-Blankestijn LJJ; Post W; van Egmond HP; Sizoo EA; Janssen GB

    1993-01-01

    In a subchronic toxicity study 4 groups of 10 Sprague-Dawley rats/group/sex received 0, 5, 20 and 80 mg ergotamine tartrate (EAT)/kg diet respectively during 13 weeks. Food intake and water intake were measured twice a week. Body weight gain was recorded weekly. After 7 weeks and 12 weeks urine

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

    African Journals Online (AJOL)

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

  13. Evaluation of the acute and subchronic toxicity of Aster tataricus L.F. ...

    African Journals Online (AJOL)

    ... on the liver; much less on the heart. The LD50 was 15.74 g/kg BW in mice, and the subchronic toxicity study, used a dosage of 0.34 g/kg/d.BW, showed that the toxic components of Aster tataricus L. f. were mainly concentrated in the petroleum ether fraction, followed by the ethyl acetate fraction, the n-butyl alcohol fraction, ...

  14. Safety assessment of ocimum basilicum hydroalcoholic extract in wistar rats: acute and subchronic toxicity studies.

    Science.gov (United States)

    Rasekh, Hamid Reza; Hosseinzadeh, Leila; Mehri, Soghra; Kamli-Nejad, Mohammad; Aslani, Majid; Tanbakoosazan, Farahnaz

    2012-01-01

    Ocimum basilicum L. is widely used in folk medicine of many countries including . Both O. basilicum and its oil extract have received considerable attention for their potential medicinal properties, but there are a few reports about possible toxicity of this plant. Therefore, in the present study, acute and subchronic toxicity of O. basilicum hydroalcohlic extract have been evaluated in Wistar rats. For the acute toxicity assessment, five groups of 10 animals (5 male, 5 female) received four different single dose of extract orally, the animals were, then, kept under observation for 14 days. For subchronic toxicity, the animals were divided into four groups (5 male, 5 female) and were gavaged daily by 50, 200 and 500 mg/kg of extract. Mortality, clinical signs, body weight changes, food and water consumption, and hematological and biochemical parameters were monitored during the study period. On the 45th day, animals were sacrificed and gross findings, weight of liver and left kidney and liver histological markers were assessed. The results of acute study indicated that LD50 of O. basilicum is higher than 5 mg/kg. In subchronic study, no adverse effects were observed on serum parameters in male and female rats. The hematological results showed a reduction in the hematocrit, platelets and RBC in both sexes. No abnormalities were observed in other parameters. Based on the results of this study, present data suggest that hematologic system could serve as a target organ in oral toxicity of this plant.

  15. Bioassay-guided evaluation of Dioscorea villosa - an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach

    National Research Council Canada - National Science Library

    Lima, Claudio Moreira; Lima, Adriana Karla; Melo, Marcelia G Dória; Serafini, Mairim Russo; Oliveira, Dênisson Lima; de Almeida, Enrik Barbosa; Barreto, Rosana Souza Siqueira; Nogueira, Paulo Cesar de Lima; Moraes, Valéria Regina de Souza; Oliveira, Edica Ramone Andrade; de Albuquerque, Jr, Ricardo Luiz Cavalcanti; Quintans-Júnior, Lucindo J; Araújo, Adriano Antunes Souza

    2013-01-01

    .... In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days...

  16. Chemical characterization, anti-benign prostatic hyperplasia effect and subchronic toxicity study of total flavonoid extract of Pteris multifida.

    Science.gov (United States)

    Dai, Guang-Cheng; Hu, Bin; Zhang, Wen-Fang; Peng, Fang; Wang, Rong; Liu, Zhi-Yuan; Xue, Bo-Xin; Liu, Jiang-Yun; Shan, Yu-Xi

    2017-10-01

    The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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.

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

    Science.gov (United States)

    Li, Min; Piao, Jianhua; Yang, Xiaoguang

    2010-07-01

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

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

    OpenAIRE

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

    2014-01-01

    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 rat...

  20. Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats

    OpenAIRE

    Robertson, Bruce; Burri, Lena; Berge, Kjetil

    2014-01-01

    The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute an...

  1. Acute and Subchronic Inhalation Toxicity of n-Octane in Rats.

    Science.gov (United States)

    Sung, Jae Hyuck; Choi, Byung-Gil; Kim, Hyeon Yeong; Baek, Min-Won; Ryu, Hyun Youl; Kim, Yong Soon; Choi, Young Kuk; Yu, Il Je; Song, Kyung Seuk

    2010-12-01

    We have investigated the toxic effects of the inhalation of subchronic and acute levels of n-octane. The rats were exposed to n-octane of 0, 2.34, 11.68 and 23.36 mg/L (n = 5 rats/group/gender) in an acute inhalation test (Organization for Economic Co-operation and Development (OECD) TG 403), or to 0, 0.93, 2.62 and 7.48 mg/L (n = 10 rats/group/gender) for a subchronic inhalation test (OECE TG 413), to establish a national chemical management system consistent with the Globally Harmonized Classification System (GHS). Acutely-exposed rats became lethargic but recovered following discontinuation of inhalation. Other clinical symptoms such as change of body weight and autopsy finds were absent. The LC50 for the acute inhalation toxicity of n-octane was determined to exceed 23.36 mg/L and the GHS category was 'not grouping'. Subchronically-treated rats displayed no significant clinical and histopathological differences from untreated controls; also, target organs were affected hematologically, biochemically and pathologically. Therefore, the no observable adverse effect level was indicated as exceeding 7.48 mg/L and the GHS category was 'not grouping' for the specific target organ toxicity upon repeated exposure. However, n-octane exposure should be controlled to be below the American Conference of Industrial Hygienists recommendation (300 ppm) to prevent inhalation-related adverse health effects of workers.

  2. 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

  3. Subchronic and developmental toxicity studies in rats with Ac-Di-Sol croscarmellose sodium.

    Science.gov (United States)

    Freeman, Christine; Weiner, Myra L; Kotkoskie, Lois A; Borzelleca, Joseph; Butt, Mark

    2003-01-01

    Studies were conducted to evaluate the subchronic and developmental toxicity of Ac-Di-Sol (croscarmellose sodium). In the subchronic study, groups of Sprague-Dawley rats (20/sex/group) received 0 (control), 10000, or 50000 ppm Ac-Di-Sol in the diet for 90 consecutive days (equivalent to 757 and 893 mg/kg/day for males and females fed 10000 ppm, respectively, and to 3922 and 4721 mg/kg/day for males and females fed 50000 ppm, respectively). No mortality, clinical signs of toxicity, or adverse toxicological effects on hematology or serum chemistry parameters, feed consumption, or ophthalmologic examinations were noted in any treatment group. Body weight gain was depressed in high-dose males during the final 3 weeks. The only treatment-related histological lesion noted was moderate renal mineralization at the corticomedullary junction in one high-dose female. This lesion was not considered a specific effect of Ac-Di-Sol, but rather a secondary effect resulting from a potential increase in urinary pH and renal excretion of sodium due to the high intake of sodium associated with Ac-Di-Sol. In the developmental toxicity study, groups of pregnant Sprague-Dawley rats (25/group) received 0 (control), 10000, or 50000 ppm Ac-Di-Sol in the diet on gestational days 6 to 15. No evidence of maternal, fetal, or embryo toxicity was noted. The no-observed-adverse-effect level (NOAEL) for Ac-Di-Sol in both studies exceeds 50000 ppm in the diet, which represents doses of 3922 and 4712 mg/kg/day, for males and females, respectively. The results of these studies demonstrate the low subchronic oral toxicity and developmental toxicity of Ac-Di-Sol, and support the safe use of Ac-Di-Sol in oral applications such as pharmaceuticals, dietary supplements, and sweetener tablets.

  4. Cytotoxicity, acute and subchronic toxicity of ionic liquid, didecyldimethylammonium saccharinate, in rats.

    Science.gov (United States)

    Jodynis-Liebert, Jadwiga; Nowicki, Michal; Murias, Marek; Adamska, Teresa; Ewertowska, Małgorzata; Kujawska, Małgorzata; Piotrowska, Hanna; Konwerska, Aneta; Ostalska-Nowicka, Danuta; Pernak, Juliusz

    2010-01-01

    The aim of this study was to investigate cytotoxicity, acute and subchronic oral toxicity of an ionic liquid didecyldimethylammonium saccharinate [DDA][Sac] in rat. IC(50) values tested on six human cell lines varied from 1.44 microM to 5.47 microM. The compound tested was classified to the 4th toxicity class with a fixed LD(50) cut-off value 500 mg/kg. Organ pathology induced by [DDA][Sac] in an acute experiment included exfoliation of the surface layer of the colon and alveolar septa in lung parenchyma. In a subchronic experiment rats were administered 10, 30 and 100 mg/kg/day [DDA][Sac] for 28 days. Reduced body weight gain and slightly reduced food consumption was observed particularly in high-dose rats. Slight hematology changes were found only in mid-dose females. Statistically significant changes in clinical chemistry parameters included: increases in the ALT, SDH, ALP and GGT activities, and in glucose, blood urea nitrogen and creatinine concentrations. However, these changes did not occur in both sexes and were not dose-related with the exception of ALP in females. No treatment-related microscopic changes were observed in a subchronic experiment. Under the condition of this study the lowest-observed-adverse-effect level of [DDA][Sac] was considered to be 10 mg/kg/day. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Subchronic oral toxicity studies with α-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The toxicity of α-cyclodextrin (α-CD), a cyclic polymer of six α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week

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

    Science.gov (United States)

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

    2014-10-01

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

  7. Evaluation of the subacute and subchronic toxicity of inhaled EDS hydrotreated naphtha in the rat.

    Science.gov (United States)

    McKee, R H; Hinz, J P

    1987-07-01

    Inhalation studies were conducted to assess the subacute and subchronic toxicity of EDS hydrotreated naphtha (HN). In the subacute toxicity study, male and female Sprague-Dawley rats were exposed to various concentrations of HN vapor (0.2, 1.0, and 5.0 g/m3) 6 hr/day for 5 consecutive days. Following 2 recovery days, the animals were exposed for 4 additional days and then sacrificed on the 12th study day. In the subchronic toxicity study, a similar protocol was utilized; however, the animals were exposed 5 days/week for 13 weeks. Following a 2-week recovery period, the animals were sacrificed. Parameters examined in both studies included survival, growth, clinical observations, urinalysis, blood chemistry at necropsy, and microscopic examination of selected tissues. There was some evidence of systemic effects associated with repeated inhalation exposure to HN, although these effects were mild and were primarily confined to the high-exposure groups. The major systemic effect appeared to be renal toxicity in male rats as evidenced by increased urinary excretion of renal epithelial cells, creatinine, glucose, and protein and decreased urine osmolality. However, the absence of consistent pathologic changes in the kidneys of these animals suggested that the lesions were either slight or reversible during the 2-week recovery period.

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

    African Journals Online (AJOL)

    oil from turmeric (Curcuma longa L.). Food Chem. Toxicol 2013; 53: 52–61. 20. Saravanan N, Nalini N. Hemidesmus indicus protects against ethanol-induced liver toxicity. Cell Mol Biol. Lett 2008; 13: 20–37. 21. Ramaiah SK. Preclinical safety assessment: Current gaps, challenges, and approaches in identifying translatable ...

  9. Acute and Subchronic Toxicity Study of the Median Septum of Juglans regia in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Asma Ravanbakhsh

    2016-12-01

    Full Text Available Purpose: Median septum of Juglans regia L. (Juglandaceae with anti - diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600 , 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME, and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morpholo gical and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a signific ant reduction of serum urea level (p<0.05, kidney’s xanthine dehydrogenase (XDH activity (p<0.001 and elevation of aldehyde oxidase (AO activity (p<0.05 in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epitheliu m stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administratio n of JRSME may improve kidney structure and function and help in treatment of some chronic diseases.

  10. Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies

    OpenAIRE

    Vijayasteltar, Liju; Nair, Gopakumar Gopinathan; Maliakel, Balu; Kuttan, Ramadasan; I.M., Krishnakumar

    2016-01-01

    Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol), as assessed by oral acute (5 g/kg b.wt. for 14 days) and subchronic (0.25, 0.5 and...

  11. 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

  12. A 12-week subchronic intramuscular toxicity study of risperidone-loaded microspheres in rats.

    Science.gov (United States)

    Zhang, J; Ye, L; Wang, W; Du, G; Yu, X; Zhu, X; Dong, Q; Cen, X; Guan, X; Fu, F; Tian, J

    2015-02-01

    Long-acting injectable formulations of antipsychotics have been an important treatment option to increase the compliance of the patient with schizophrenia by monitoring drug administration and identifying medication noncompliance and to improve the long-term management of schizophrenia. Risperidone, a serotoninergic 5-HT2 and dopaminergic D2 receptor antagonist, was developed to be a long-acting sustained-release formulation for the treatment of schizophrenia. In this study, 12-week subchronic toxicity study of risperidone-loaded microspheres (RMs) in rats by intramuscular injection with an 8-week recovery phase was carried out to investigate the potential subchronic toxicity of a novel long-acting sustained-release formulation. The results indicated that the dosage of 10-90 mg/kg of RM for 2 weeks did not cause treatment-related mortality. The main drug-related findings were contributed to the dopamine D2 receptor and α1-adrenoceptor antagonism of risperidone such as elevation of serum and pituitary prolactin levels and ptosis and changes in reproductive system (uterus, ovary, vagina, mammary gland, testis, seminal vesicle, epididymis, and prostate). In addition, foreign body granuloma in muscle at injection sites caused by poly-lactide-co-glycolide was observed. At the end of the recovery phase, these changes mostly returned to normal. The results indicated that RM had a good safety profile in rats. © The Author(s) 2015.

  13. Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

    Science.gov (United States)

    Dalbey, W E; Feuston, M H; Yang, J J; Kommineni, C V; Roy, T A

    1996-01-01

    Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

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

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    Kjetil Berge

    2015-01-01

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

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

    Science.gov (United States)

    Berge, Kjetil; Robertson, Bruce; Burri, Lena

    2015-01-01

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

  16. Enzymatic extract from Ecklonia cava: Acute and subchronic oral toxicity and genotoxicity studies.

    Science.gov (United States)

    Yun, Jun-Won; Kim, Seung-Hyun; Kim, Yun-Soon; You, Ji-Ran; Cho, Eun-Young; Yoon, Jung-Hee; Kwon, Euna; Yun, In-Jue; Oh, Je-Hun; Jang, Ja-June; Park, Jin-Sung; Che, Jeong-Hwan; Kang, Byeong-Cheol

    2018-02-01

    Ecklonia cava (EC) is known to have antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. Despite its wide use and beneficial properties, comprehensive toxicological information regarding EC extract is currently limited. Therefore, the purpose of this study was to investigate acute toxicity, subchronic toxicity, and genotoxicity of enzymatic EC extract according to test guidelines published by Organization for Economic Cooperation and Development. The acute oral LD50 values of this EC extract administered to rats and dogs were estimated to be more than 3000 mg/kg BW. In an oral 13-week toxicity study, changes in body weights of rats exposed to the EC extract up to 3000 mg/kg BW were found to be normal. In addition, repeated doses of EC extract failed to influence any systematic parameters of treatment-related toxic symptoms such as food/water consumption, mortality, urinalysis, hematology, serum biochemistry, organ weight, or histopathology. These results indicated that the no-observed-adverse-effect level for the EC extract was 3000 mg/kg/day for male and female rats. Data obtained from Ames test, chromosome aberration assay, and micronucleus assay indicated that EC extract was not mutagenic or clastogenic. Taken together, these results support the safety of enzymatic EC extract as a potential therapeutic for human consumption against various diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats.

    Science.gov (United States)

    Robertson, Bruce; Burri, Lena; Berge, Kjetil

    2014-01-01

    The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.

  18. Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats

    Directory of Open Access Journals (Sweden)

    Bruce Robertson

    2014-01-01

    Full Text Available The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.

  19. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Lapadula, E; Breglia, R; Bui, Q; Burnett, D; Koschier, F; Podhasky, P; White, R; Mandella, R; Hoffman, G

    1998-10-23

    A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

  20. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

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    Phool Chandra

    2012-01-01

    Full Text Available Sooktyn (SKN, mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD 50 may be greater than 2 000 mg/kg (orally for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  1. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals.

    Science.gov (United States)

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-04-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD(50) may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  2. Evaluation of the sub-chronic toxicity of a standardized flavonoid extract of safflower in rats.

    Science.gov (United States)

    Zhang, Zhilin; Liu, Runzhe; Pu, Xiaoping; Sun, Yi; Zhao, Xin

    2017-04-01

    Carthamus tinctorius L., or safflower, is an annual herbaceous crop belonging to the family Asteraceae, which is cultivated throughout China and used as a traditional Chinese medicine. Our previous study revealed anti-Parkinson's disease effects of an isolated standardized safflower flavonoid extract (SAFE). The purpose of this study is to evaluate the potential sub-chronic toxicity of SAFE. Male and female Sprague Dawley rats received three doses of SAFE (100, 300, and 500 mg/kg) q.d. by gavage for four weeks. Body weights were measured during the experiment, and blood samples were collected once per week for hematological and serum biochemical parameters. Major organs were examined after execution and histopathological analyses were performed. Body weight gain in the administration groups showed no decline compared to the control group. However, there were changes in values of aspartate transaminase (p < 0.05), alanine transaminase (p < 0.05), and blood glucose (p < 0.05) between treatments. SAFE influenced parameters related to platelets in rats receiving SAFE for both sexes under different dosages (p < 0.05). No histopathological changes were observed. SAFE might have influence on conglomeration of platelets, transaminases, and blood glucose. SAFE caused no significant toxicity and further studies may be needed to ensure safety of SAFE. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-07-01

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

  4. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    Science.gov (United States)

    Research interested in oxidative stress markers following exposure to VOCsThis dataset is associated with the following publication:Kodavanti , P., J. Royland , D.A. Moore-Smith, J. Beas, J. Richards , T. Beasley , P. Evansky , and P.J. Bushnell. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, 51: 10-19, (2015).

  5. Acute and subchronic toxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.

    Science.gov (United States)

    Griffiths, James C; Matulka, Ray A; Power, Ronan

    2006-01-01

    Selenium has been recognized as an essential nutrient for human health; however, its bioavailability is primarily dependent upon the type of selenium, elemental versus organic. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). The present studies were conducted to investigate potential oral toxicity of a unique selenized yeast preparation (Sel-Plex) when administered to (1) adult female CHS Swiss mice ICo:OFI (IOPS Caw); (2) adult female CHS Sprague-Dawley rats; and (3) adult male and female Sprague-Dawley CD rats. For the 28- and 90-day toxicity studies, (1) adult male and female Sprague-Dawley CRL:CD(R)(SD) IGS BR strain rats and (2) adult male and female 6- to 7-month-old Beagle dogs were used. The LD50 for mice was >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg) and for rats, was greater than >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg). In the two 28-day studies, for rats, the no observed adverse effects level (NOAEL) was 50 mg Sel-Plex/kg/day (0.1 mg Se/kg/day), and for the dogs, the NOAEL was 22.5 mg Sel-Plex/kg/day (0.045 mg Se/kg/day). For the two 90-day studies, for rats the NOAEL for Sel-Plex was 114 mg/kg/day (0.23 mg Se/kg/day), and for dogs, the NOAEL was 30 mg Sel-Plex/kg/day (0.06 mg Se/kg/day): the latter being the NOAEL in the most sensitive species.

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

    Science.gov (United States)

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

    2013-03-01

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

  7. 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.

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

    Science.gov (United States)

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

    2014-06-01

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

  9. Evaluation of subchronic toxicity of pet food contaminated with melamine and cyanuric acid in rats.

    Science.gov (United States)

    Chen, Kun-Chao; Liao, Chen-Wei; Cheng, Fen-Pang; Chou, Chi-Chung; Chang, Shih-Chien; Wu, Jhaol-Huei; Zen, Jyh-Myng; Chen, Yng-Tay; Liao, Jiunn-Wang

    2009-12-01

    Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%-100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%-100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%-100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.

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

    Science.gov (United States)

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

    2016-10-01

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

  11. Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys.

    Science.gov (United States)

    Tian, Jingwei; Du, Guangying; Ye, Liang; Yu, Xin; Zhang, Jianzhao; Wang, Hongbo; Yu, Pengfei; Fu, Fenghua; Liu, Wanhui; Li, Youxin; Cen, Xiaobo; Guan, Xiaolin

    2013-02-01

    Continuous dopaminergic stimulation (CDS) is an important drug development strategy in the treatment of Parkinson's disease (PD). Rotigotine is a non-ergoline D(3)/D(2)/D(1) dopamine receptor agonist for treating PD. As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), long-acting sustained-release microspheres with poly(lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial. In the present study, the subchronic toxicity in Cynomolgus monkeys has been characterized via intramuscular administration with RoMS at 0, 10, 40 and 160 mg/kg, weekly for 3 months with a 1-month recovery period. The NOAEL was 10 mg/kg/week. One male at 160 mg/kg died from an extensive pulmonary embolism. The major toxicological effects were associated with dopamine agonist-related pharmacodynamic properties of rotigotine (e.g., hyperactivity and stereotype, decreased serum prolactin level) and foreign body removal reaction induced by poly(lactide-co-glycolide) and carboxymethycellulose sodium (e.g., increased mononuclear cells and neutrophils, thymus atrophy and vacuolar degeneration of adrenal cortex, foreign body granuloma with foam cells accumulation at injection sites and foam cells accumulation in spleen and multiple lymph sinuses). At the end of recovery period, above findings recovered to a normal level or to a certain degree except vacuolar degeneration of adrenal gland. RoMS has exhibited high safety on monkeys. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in SD rats.

    Science.gov (United States)

    Ye, Liang; Guan, Xiaolin; Tian, Jingwei; Zhang, Jianzhao; Du, Guangying; Yu, Xin; Yu, Pengfei; Cen, Xiaobo; Liu, Wanhui; Li, Youxin

    2013-06-01

    Continuous dopaminergic stimulation (CDS) has been an important strategy of drug development for the treatment of Parkinson's disease (PD). Rotigotine is a non-ergoline D3/D2/D1 dopamine agonist for treating PD. As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), a long-acting sustained-release microspheres for injection with poly(lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial. In this study, subchronic toxicity of RoMS in SD rats has been characterized via intramuscular administration with RoMS (0-240 mg/kg/week) on a consecutive weekly dosing schedule for 3 months followed by 1-month recovery period. The No Observed Adverse Effect Level (NOAEL) was 45 mg/kg/week. One male at 240 mg/kg died from an extensive pulmonary embolism. The major toxicological effects were associated with the dopamine agonist-related pharmacodynamic properties of rotigotine (e.g. hyperactivity and stereotype, enlarged ovary, sporadic gastric mucous membrane lesions, decreased body weight, food consumption and prolactin, and increased mononuclear cell, neutrophil granulocyte, aspartate aminotransferase and alanine aminotransferase) and foreign body removal reaction induced by poly(lactide-co-glycolide) and carboxymethycellulose sodium. At the end of recovery period, all findings had recovered to a normal level or to a certain degree except foreign body reaction at injection sites. RoMS has exhibited high safety on SD rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. [Study on sub-chronic toxicity of powered milk containing transgenic human alpha-lactalbumin].

    Science.gov (United States)

    Zhi, Yuan; Liu, Haibo; Geng, Guiying; Wang, Huiling; Yang, Hua; Feng, Xiaolian; Gao, Peng; Yu, Qiang; Feng, Yongquan; Xu, Haibin

    2011-07-01

    To investigate the potential toxic or adverse effect of transgenic human alpha-lactalbumin powered milk on rats. Weanling Wistar rats were randomly divided into seven groups according the weight: three transgenic milk powder (T) groups, three non-transgenic milk powder (N) groups and the control (C) group. The diets of T groups contain 15%, 30% and 60% transgenic human alpha-lactalbumin milk powder. The diets of N groups contain 15%, 30% and 60% non-transgenic human alpha-lactalbumin milk powder for 90 days. The diet of C group contains only basic feed. Haematological and biochemical parameters was measured during the study (at 45th and 90th of the experiment). At the end of the 90th day, organ tissues analysis was performed. There were no transgenic human alpha-lactalbumin related adverse effects on the body weight, food intake, food consumption, hematology,serum biochemistry, as well as histopathology. There were no signs of toxic and adverse effects for transgenic human alpha-lactalbumin powdered milk on rats.

  14. Subchronic inhalation toxicity of p-nitroaniline and p-nitrochlorobenzene in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nair, R.S.; Johannsen, F.R.; Levinskas, G.J.; Terrill, J.B.

    1986-05-01

    For evaluation of subchronic toxicity of the two single-ring nitroaromatics, p-nitroaniline (PNA) and p-nitrochlorobenzene (PNCB), groups of 10 male and 10 female Sprague-Dawley rats were exposed to an aerosol/vapor of PNA in isopropanol at target concentrations of 0, 10, 30, or 90 mg/m3 or to PNCB vaporized from a solution in ethylene glycol monoethyl ether at target concentrations of 0, 5, 15, or 45 mg/m3 for 6 hr/day, 5 days/week for 4 weeks. Clinical signs of toxicity, body weights, results of ophthalmoscopic exam, hematology and clinical chemistry tests, organ weights, gross and histopathological changes were recorded. Exposure to PNA or PNCB resulted in a dose-related increase in blood methemoglobin levels. Mean red blood cell counts, hematocrit, and hemoglobin were significantly decreased in mid and high level animals exposed to PNCB. Mean spleen weights (absolute and relative to body weight) were significantly increased at the high dose levels in the two studies. A slight increase in spleen weights was also observed at the low concentration level in the PNA study. Absolute and relative liver weights also were increased among animals exposed to 45 mg/m3 PNCB. Microscopic changes were observed mainly in the spleen and included an increase in intensity of extramedullary hematopoiesis and hemosiderosis with both compounds. Spleens of animals exposed to PNCB also exhibited congestion. Neither PNA nor PNCB exhibited significant toxicological effects other than those of methemoglobinemia, anemia, and splenic changes classically associated with nitroaromatics at levels significantly above presently accepted occupational standard. Our data suggest that the current TLV for PNA which is 3 mg/m3 will provide adequate protection to the workers. OSHA's PEL of 1 mg/m3 for PNCB is to be preferred over the current TLV of 3 mg/m3 to provide a comparable margin of safety.

  15. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    Science.gov (United States)

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  16. Acute and subchronic oral toxicities of Pu-erh black tea extract in Sprague-Dawley rats.

    Science.gov (United States)

    Wang, Di; Xu, Kunlong; Zhong, Ying; Luo, Xiao; Xiao, Rong; Hou, Yan; Bao, Wei; Yang, Wei; Yan, Hong; Yao, Ping; Liu, Liegang

    2011-03-08

    Pu-erh black tea, which is obtained by first parching crude green tea leaves and then undergoes secondary fermentation with microorganisms, has been believed to be beneficial beverages for health for nearly 2000 years in China, Japan and Taiwan area. But its potential toxicity when administered at a high dose as concentrated extracts has not been completely investigated. The present study was aimed at evaluating potential toxicity of Pu-erh black tea extracts (BTE) from acute and sub-chronic administration to male and female Sprague-Dawley (SD) rats. A single BTE dose of 10,000 mg/kg of body weight was administered by oral gavage for acute toxicity in SD rats. Four groups (10 males and 10 females per group) of dose levels of 1250, 2500, and 5,000 mg/kg/day of the test article, as well as controls (distilled water) were tested as the subchronic toxicity study. No deaths and signs of toxicity occurred during the 14 days of the study. There were no test article related mortalities, body weight gain, feed consumption, clinical observation, organ weight changes, gross finding, clinical or histopathological alterations during the 91-day administration. The LD(50) of BTE can be defined as more than 10,000 mg/kg, and a dose of 5,000 mg/kg/day was identified as the no-observed-adverse-effect-level (NOAEL) in this study. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Dietary safety of a dual-enzyme preparation for animal feed: Acute and subchronic oral toxicity and genotoxicity studies.

    Science.gov (United States)

    Dillon, G P; Gaffney, M A; Curran, C M; Moran, C A

    2017-08-01

    Animal feed is routinely supplemented with exogenous enzymes to improve nutrient utilization, such as proteases to enhance protein hydrolysis in vivo and xylanases to alleviate feed related anti-nutritional factors. The present studies were conducted to evaluate the potential oral toxicity and genotoxicity of a dual-enzyme preparation, Vegpro® concentrate (VPr-C). Acute oral toxicity studies were conducted in adult male and female Sprague-Dawley Crl CD rats and CHS Swiss ICO:OFI (IOPS Caw) mice. Thirteen week preliminary and final subchronic oral toxicity studies were conducted in male and female rats. Genotoxicity was evaluated through a bacterial reverse mutation test (Ames test), an in-vitro mammalian chromosomal aberration test, and a mammalian micronucleus test. The LD50 was >2000 mg/kg of BW in mice and rats. In the 13-week oral toxicity study, the No Observed Adverse Effects Level (NOAEL) was 1000 mg/kg BW per day for females and 300 mg/kg BW per day for males. VPr-C showed no mutagenic activity in Salmonella typhimurium, did not induce significant chromosomal aberrations in cultured human lymphocytes, and did not increase the frequency or proportion of micronucleated immature erythrocytes in mice. There was no evidence of acute or subchronic toxicity or genotoxicity associated with the test article at these test dosages. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Hippocratic screening and subchronic oral toxicity assessments of the methanol extract of Vatairea macrocarpa heartwood in rodents

    Directory of Open Access Journals (Sweden)

    Neyres Z. T. Jesus

    2012-07-01

    Full Text Available Vatairea macrocarpa (Benth. Ducke, Fabaceae, is popularly known as 'angelim'. Its heartwood macerate is used to treat inflammation, gastric ulcer, diabetes and infections. The oral acute and subchronic toxicity of the methanol extract of V. macrocarpa heartwood (MEVm was evaluated. In the Hippocratic screening, a single administration of MEVm was given orally to mice at doses ranging from 100 to 5000 mg/kg. In the subchronic study, MEVm was given orally as a daily administration for thirty days to Wistar rats at doses of 20, 100 and 500 mg/kg. In Hippocrtaic screening, doses of MEVm up to 5000 mg/kg did not cause any relevant behavioral changes or deaths thus making it impossible to establish the LD50. In subchronic assay, body weight gains and food intake were significantly reduced at the last week of treatment with 20 and 500 mg/kg dose. Serum triacylglycerides, total proteins and γ-glutamyltransferase activity were significantly reduced, while alkaline phosphatase activity was elevated. In hematological parameters, MEVm increased the percentage of segmented neutrophils cells at the highest dose. All alterations observed were minor in nature and were not accompanied by any relevant clinical signs or any histopathological changes. In conclusion, the results demonstrate relative safety profile of MEVm in the experimental animals.

  19. Toxicological evaluation of the flavonoid-rich extract from Maydis stigma: Subchronic toxicity and genotoxicity studies in mice.

    Science.gov (United States)

    Peng, Ke-Zheng; Zhang, Song-Yan; Zhou, Hong-Li

    2016-11-04

    Maydis stigma (corn silk) has a long history of use as a traditional herbal medicine or functional food in China and many other countries and has been listed in the Chinese Pharmacopea. However, little data about its potential toxicity is available. In this study, we evaluated the subchronic toxicity and genotoxicity of the flavonoid-rich extract from Maydis stigma (FMS) in mice. In the subchronic toxicity study, the FMS was administered orally to mice at doses of 2.50, 5.00 and 10.00g/kg/day for 28 consecutive days. At the end of experiment, general clinical signs, mortality, haematological, biochemical and histopathological parameters were examined. The genotoxicity of FMS was also evaluated by the micronucleus assay and the sperm malformation assay. All animals survived until the scheduled necropsy, and no statistically significant or toxicologically relevant differences were observed in any of the FMS-treatment groups, compared with the control group. The no-observed-adverse-effect level (NOAEL) was determined as 10.00g/kg/day. Based on the results of the micronucleus assay and the sperm malformation assay, no evidence of genotoxicity was found either in somatic cells or germ cells even at an experimental upper limit dose (10.00g/kg/day). The results of the present studies might support the safe use of FMS as a functional food, food additive and natural remedy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation.

    Science.gov (United States)

    Chen, Rui; Zhang, Lili; Ge, Cuicui; Tseng, Michael T; Bai, Ru; Qu, Ying; Beer, Christiane; Autrup, Herman; Chen, Chunying

    2015-03-16

    The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly.

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

    Science.gov (United States)

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

  2. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    Science.gov (United States)

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period.

  3. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... termination, all survivors in the treatment groups shall be sacrificed. (12) Clinical pathology. Hematology... pathology. (i) All animals shall be subjected to a full gross necropsy which includes examination of the...) Epididymides. (6) Seminal vesicle(s). (7) Uterus. (8) Ovaries. (G) Other. (1) Lacrimal gland. (2) Mammary gland...

  4. 90-Day Inhalation Toxicity Study of FT Fuel

    Science.gov (United States)

    2011-08-01

    the low concentration, one animal had an epididymal mass determined to be a sperm granuloma. One male in the control group had a cyst on the right...release; distribution unlimited. Public Affairs Case File No. TSRL-PA-12-0004. INTRODUCTION Sperm motility, epididymal cauda sperm concentration...production and epididymal sperm reserves of pubertal and adult rats. J. Reprod. Fertil 54, 103-107. Royall, R.M . (1986). Model robust confidence intervals

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

  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. 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.

  8. Evaluation of genotoxicity and subchronic toxicity of the standardized leaves infusion extract of Copaifera malmei Harms in experimental models.

    Science.gov (United States)

    Pavan, Eduarda; Damazo, Amilcar Sabino; Lemos, Larissa Maria Scalon; Adzu, Bulus; Balogun, Sikiru Olaitan; Arunachalam, Karuppusamy; Martins, Domingos Tabajara de Oliveira

    2018-01-30

    Copaifera malmei Harms (Fabaceae), known mainly as óleo-mirim, is a native and endemic plant found in the states of Mato Grosso and Goiás of Brazil. The plant's leaves infusion is popularly used by riverine communities of the northern Araguaia microregion, Mato Grosso, Brazil, for the treatment of gastric ulcers and inflammatory diseases of the respiratory tract. The gastric antiulcer activity of the standardized leaves infusion extract of Copaifera malmei (SIECm) in rodents has been reported. The objective of this study was to advance the investigation of the safety profile of SIECm by evaluating the genotoxicity and subchronic toxicity using in vitro and in vivo experimental models. SIECm was prepared by infusion, by incubating the powdered dried leaves material in boiled water for 15min. In vitro genotoxicity of SIECm (10, 30 or 100μg/mL) was assessed by micronucleus and comet tests using Chinese hamster ovary (CHO-k1) epithelial cells. The evaluation of subchronic toxicity profile was performed by daily oral administration of SIECm (100, 400 or 1000mg/kg) to Wistar rats for 30 days. Clinical observations of toxicological related parameters were done every 6 days. After the treatment period, blood was collected for hematological and biochemical analysis, and some organs were removed for macroscopic and histopathological analysis. In the micronucleus assay, SIECm demonstrated anti-mutagenic activity. In the comet assay, SIECm presented anti-genotoxic effect preventing DNA damage at all the three concentrations tested with pre-treatment, while the same effect was only observed in the co-treatment at the lowest concentration. Post-treatment with SIECm increased the genetic damage induced by hydrogen peroxide (H2O2) at the highest concentration. In the subchronic toxicity test, few changes were observed, such as increase in feed consumption in the group of animals treated with 100mg/kg of the SIECm, which reversed after 6 days. There were no macroscopic

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

    Science.gov (United States)

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

    2006-12-01

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

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

    Science.gov (United States)

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

    2016-12-24

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

  11. 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

  12. Safety assessment of heated diacylglycerol oil: subchronic toxicity study in rats.

    Science.gov (United States)

    Morita, Osamu; Tamaki, Yasushi; Kirkpatrick, Jeannie B; Chengelis, Christopher P

    2008-08-01

    Diacylglycerol oil is an edible oil with similar taste and usability characteristics as conventional edible oil rich in triacylglycerol oil. The objective of the present study was to evaluate potential adverse effects of heated diacylglycerol and triacylglycerol oil in rats following subchronic administration. The heated diacylglycerol and triacylglycerol oils were prepared separately following deep frying potato slices at 180 degrees C for 8h per day for three days. Sprague Dawley rats were fed diets containing different ratios (concentrations) of heated to unheated diacylglycerol oil. The ratio of heated to unheated diacylglycerol was as follows: 0%/5.5% (control-1; Group 1), 1.0%/4.5% (Group 2), 2.75%/2.75% (Group 3), and 5.5%/0% (Group 4). Two additional groups received the feed containing 5.5% of unheated or 5.5% of heated triacylglycerol oil. Compared to the unheated oils, feeding of heated diacylglycerol or triacylglycerol oil did not reveal any toxicologically significant changes in clinical observation, body weights, body weight gains, feed consumption, ophthalmic examinations, functional observational battery and motor activity, clinical pathology evaluations and organ weights. Similarly, terminal necropsy did not reveal treatment-related gross or histopathology findings. Based on the results of this subchronic study, the no-observed-effect levels (NOELs) of heated diacylglycerol or triacylglycerol oil were 5.5%, the highest levels tested. The mean dietary exposure levels at the highest dose for the heated diacylglycerol and triacylglycerol oil for male and female rats ranged from 3,178 to 4,120 mg/kg/day.

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

    Directory of Open Access Journals (Sweden)

    Pongri Adarki

    2017-09-01

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

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

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    H. M. R. Abdel-Latif

    2017-08-01

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

  15. Pulmonary toxicity and global gene expression changes in response to sub-chronic inhalation exposure to crystalline silica in rats.

    Science.gov (United States)

    Umbright, Christina; Sellamuthu, Rajendran; Roberts, Jenny R; Young, Shih-Houng; Richardson, Diana; Schwegler-Berry, Diane; McKinney, Walter; Chen, Bean; Gu, Ja Kook; Kashon, Michael; Joseph, Pius

    2017-01-01

    Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m3, 6 hr/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression profiles were determined in lungs at the end of each exposure period. Crystalline silica was visible in lungs of rats especially in the 12-week group. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase (LDH) activity and albumin content and accumulation of macrophages and neutrophils in the bronchoalveolar lavage (BAL), was seen in animals depending upon silica exposure duration. The most severe histological changes, noted in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. Microarray analysis of lung gene expression profiles detected significant differential expression of 38, 77, and 99 genes in rats exposed to silica for 3-, 6-, or 12-weeks, respectively, compared to time-matched controls. Among the significantly differentially expressed genes (SDEG), 32 genes were common in all exposure groups. Bioinformatics analysis of the SDEG identified enrichment of functions, networks and canonical pathways related to inflammation, cancer, oxidative stress, fibrosis, and tissue remodeling in response to silica exposure. Collectively, these results provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic inhalation exposure to crystalline silica in rats.

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

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    Abidemi J. Akindele

    2018-01-01

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

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

    Science.gov (United States)

    Akindele, Abidemi J; Oladimeji-Salami, Joy A; Oyetola, Ramon A; Osiagwu, Daniel D

    2018-01-06

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

  18. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    Science.gov (United States)

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.

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

    Directory of Open Access Journals (Sweden)

    Toyohisa Katsumata

    2014-01-01

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

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

    Science.gov (United States)

    Katsumata, Toyohisa; Ishibashi, Takashi; Kyle, David

    2014-01-01

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

  1. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic cracked naphtha distillate in rats.

    Science.gov (United States)

    Lapin, C; Bui, Q; Breglia, R; Koschier, F; Podhasky, P; Lapadula, E; Roth, R; Schreiner, C; White, R; Clark, C; Mandella, R; Hoffman, G

    2001-01-01

    A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

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

    African Journals Online (AJOL)

    The variables included were body weights; feed consumption, organ weights, hematology and blood clinical chemistry, and histopathology were performed. Acute toxicity test revealed that, the limit dose of 2,000 mg/kg did not cause any mortality or symptoms of toxicity in all rats during the observation period. In the ...

  3. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Lapadula, E; Podhasky, P; White, R

    2000-08-11

    A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on

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

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    Mildred García-González

    2006-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-02-01

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

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

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    Farzamfar B

    2008-04-01

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

  7. Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation

    OpenAIRE

    Shrivastava, Kalpana; Bansal, Anju; Singh, Bhagwat; Sairam, Mustoori; Ilavazhagan, Govindaswamy

    2010-01-01

    Abstract The present study evaluates the toxicity from sub-chronic administration of CoCl2 (12.5 mg cobalt kg-1 BW for seven days) to male Sprague-Dawley rats in view of the beneficial effects of CoCl2 in animals and for developing efficacious therapeutic regimen in humans. 32 rats weighing 200?25g were used for all experiments. Blood was collected for hematological and biochemical analysis and various organs were dissected after perfusion of animals under anesthesia for other anal...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-30

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

  9. 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

  10. A 13-week subchronic toxicity study of madder color in F344 rats.

    Science.gov (United States)

    Inoue, Kaoru; Shibutani, Makoto; Masutomi, Naoya; Toyoda, Kazuhiro; Takagi, Hironori; Uneyama, Chikako; Nishikawa, Akiyoshi; Hirose, Masao

    2008-01-01

    A 13-week repeated oral dose toxicity study of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., was performed using F344 rats. Five groups of animals, each consisting of 10 males and 10 females, were fed diet containing 0, 0.6, 1.2, 2.5 or 5.0% MC for 13 weeks. During the experiment, lower body weight was evident from the 2.5% dose. Hematologically, fluctuation in red blood cell (RBC) parameters suggestive of weak anemia (females), and slight increases of platelet counts (both sexes) and white blood cell (WBC) counts (males) were observed at higher doses. Serum biochemically, slight fluctuations were observed in many parameters, including increased total protein (TP), conjugated bilirubin, Ca, and inorganic phosphate, and decrease of the albumin/globulin (A/G) ratio in both sexes, with dose-dependence for TP and A/G from 0.6% in females. Histopathological changes were mainly observed in the renal proximal tubules, such as microvesicular vacuolar degeneration in the cortex and karyomegaly in the outer medulla involving both sexes, lesions being evident even with 0.6%. In the outer medulla, elevation of cell proliferation activity as assessed with proliferating cell nuclear antigen was observed in males from 2.5%. Severity of focal necrosis of hepatocytes was increased only in females at 5.0%, while the increased relative liver weight as with the increased conjugated bilirubin was evident in both sexes from 1.2%. The results thus suggest that MC exerts mild toxicity, targeting liver, kidneys, and possibly RBCs and WBCs, some renal changes being evident from 0.6% in diet, that is attributable to be the lowest-observed adverse effect level (305.8-309.2mg/kg body weight/day).

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  13. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    Science.gov (United States)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (pmore in women than in men.

  14. Evidence of Tropospheric 90 Day Oscillations in the Thermosphere

    Science.gov (United States)

    Gasperini, F.; Hagan, M. E.; Zhao, Y.

    2017-10-01

    In the last decade evidence demonstrated that terrestrial weather greatly impacts the dynamics and mean state of the thermosphere via small-scale gravity waves and global-scale solar tidal propagation and dissipation effects. While observations have shown significant intraseasonal variability in the upper mesospheric mean winds, relatively little is known about this variability at satellite altitudes (˜250-400 km). Using cross-track wind measurements from the Challenging Minisatellite Payload and Gravity field and steady-state Ocean Circulation Explorer satellites, winds from a Modern-Era Retrospective Analysis for Research and Applications/Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model simulation, and outgoing longwave radiation data, we demonstrate the existence of a prominent and global-scale 90 day oscillation in the thermospheric zonal mean winds and in the diurnal eastward propagating tide with zonal wave number 3 (DE3) during 2009-2010 and present evidence of its connection to variability in tropospheric convective activity. This study suggests that strong coupling between the troposphere and the thermosphere occurs on intraseasonal timescales.

  15. Toxicological evaluation of subchronic use of pioglitazone in mice

    Directory of Open Access Journals (Sweden)

    Said Said Elshama

    2016-07-01

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

  16. Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

    Science.gov (United States)

    Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

    2014-03-01

    Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA's Alternative Framework for the Rat 90-day Feeding Study.

    Science.gov (United States)

    Hong, Bonnie; Du, Yingzhou; Mukerji, Pushkor; Roper, Jason M; Appenzeller, Laura M

    2017-07-12

    Regulatory-compliant rodent subchronic feeding studies are compulsory regardless of a hypothesis to test, according to recent EU legislation for the safety assessment of whole food/feed produced from genetically modified (GM) crops containing a single genetic transformation event (European Union Commission Implementing Regulation No. 503/2013). The Implementing Regulation refers to guidelines set forth by the European Food Safety Authority (EFSA) for the design, conduct, and analysis of rodent subchronic feeding studies. The set of EFSA recommendations was rigorously applied to a 90-day feeding study in Sprague-Dawley rats. After study completion, the appropriateness and applicability of these recommendations were assessed using a battery of statistical analysis approaches including both retrospective and prospective statistical power analyses as well as variance-covariance decomposition. In the interest of animal welfare considerations, alternative experimental designs were investigated and evaluated in the context of informing the health risk assessment of food/feed from GM crops.

  18. COMPACT and molecular structure in toxicity assessment: a prospective evaluation of 30 chemicals currently being tested for rodent carcinogenicity by the NCI/NTP.

    OpenAIRE

    Lewis, D F; Ioannides, C; Parke, D V

    1996-01-01

    A new series of 30 miscellaneous National Toxicology Program chemicals has been evaluated prospectively for carcinogenicity and overt toxicity by COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity. CYP1A and CYP2E1). Evaluations were also made by Hazardexpert, and for metal ion redox potentials; and these, together with COMPACT, were compared with results from the Ames test for mutagenicity in Salmonella, the micronucleus test, and 90-day subchronic rodent patholo...

  19. Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae in rodents

    Directory of Open Access Journals (Sweden)

    Abidemi James Akindele

    2014-04-01

    Full Text Available Flabellaria paniculata Cav. (Malpighiaceae is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of Flabellaria paniculata (HLE-FP. HLE-FP was administered p.o. (20, 100 and 500 mg/kg for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p0.05 differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p< 0.05 increases in Hb, PCV and RBC on day 30 and significant (p< 0.05 increases in MCV and MCH indices on day 60 compared to control. There were significant (p< 0.05 elevations in serum K+, urea and creatinine compared to control. The liver function tests showed slightly but non-significant alterations when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioural manifestations like restlessness, generalized body tremor, feed and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution should be exercised with i

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

    Directory of Open Access Journals (Sweden)

    Narendra S. Deshmukh

    2016-01-01

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

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

    Science.gov (United States)

    Deshmukh, Narendra S

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-06-30

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

  3. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a mobile...

  4. 30-Day, 90-day and 1-year mortality after emergency colonic surgery

    DEFF Research Database (Denmark)

    Pedersen, T; Watt, S K; Tolstrup, M-B

    2017-01-01

    PURPOSE: Emergency surgery is an independent risk factor in colonic surgery resulting in high 30-day mortality. The primary aim of this study was to report 30-day, 90-day and 1-year mortality rates after emergency colonic surgery, and to report factors associated with 30-day, 90-day and 1-year mo...

  5. Safety evaluation of Chlorella sorokiniana strain CK-22 based on an in vitro cytotoxicity assay and a 13-week subchronic toxicity trial in rats.

    Science.gov (United States)

    Himuro, Sayaka; Ueno, Sugi; Noguchi, Naoto; Uchikawa, Takuya; Kanno, Toshihiro; Yasutake, Akira

    2017-08-01

    The genus Chlorella contains unicellular green algae that have been used as food supplements. The purpose of this work was to evaluate the safety of the Chlorella sorokiniana strain CK-22 using powdered preparation (CK-22P) both by in vitro and in vivo assays. These included an experiment for cytotoxicity using Chinese hamster lung fibroblasts (V79 cells) and a 13-week repeated-dose oral toxicity trial using Wistar rats. The cytotoxicity was evaluated by MTT assay of a hot water extract (Hw-Ex) and 80% ethanol extract (Et-Ex) of CK-22P, and no effect on cell viability was observed. The 50% viability inhibitory effect (IC50) value for Hw-Ex and Et-Ex were estimated as greater than 73 and 17 μg/ml, respectively. In the subchronic toxicity test, pelleted rodent diet containing 0%, 2.5%, 5% or 10% CK-22P was given to Wistar rats (ten animals/sex/groups) for 13 weeks. During the experimental period, no CK-22P treatment-induced differences in general condition, body weight gain, food and water consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, histopathology, or animal death were observed. The no-observed-adverse-effect levels (NOAEL) were estimated to be 5.94 g/kg body-weight/day for males and 6.41 g/kg body-weight/day for females. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    National Research Council Canada - National Science Library

    Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

    2014-01-01

    Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation...

  7. Adverse effects of herbicide MCPA on dogs in a 90 day toxicological study.

    Science.gov (United States)

    Sadlonová, Irina; Hózová, Ruzena; Flaskárová, Eva

    2006-12-01

    This study was performed to investigate the toxicity of the herbicide MCPA after repeated treatment according to OECD No 409. The herbicide MCPA was administrated to dogs of both sexes in daily doses: 0, 1, 5 and 15 mg/kg per os during 90 days. Clinical observations were recorded, opthalmoscopic, haematological, clinical chemistry parameters were investigated. The morphological changes were examined using pathological and histological techniques. An increase in the activity of the enzyme ALT and of urea concentration was observed in the middle- and high-dose groups. ALP and creatinine were decreased in dogs of all dose groups. After 60 days of MCPA administration, the concentration of glucose decreased in the high-dose group. The relative weight of both testes was decreased in the males from the high-dose group in comparison to controls. The decrease in testes weight was associated with focal testicular atrophy and loss of spermatogenic cells in the lobuli of testes. Focal hepatocellular necrosis, inflammatory changes and mononuclear nodules were observed in the liver, predominantly in males of the high-dose group. Administration of MCPA did not cause mortality and had no adverse effects on hematological parameters of animals. The results of the study showed that MCPA treatment caused inflammatory lesions in the liver, moderate damage of the kidney, and had focal adverse effect on the development of spermiogenesis. The changes were reversible.

  8. A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats.

    Science.gov (United States)

    Singh, Pooja; Chacko, K Mathai; Aggarwal, M L; Bhat, Binu; Khandal, R K; Sultana, Sarwat; Kuruvilla, Binu T

    2012-09-01

    The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt.

  9. Distribution and Determinants of 90-Day Payments for Multilevel Posterior Lumbar Fusion: A Medicare Analysis.

    Science.gov (United States)

    Jain, Nikhil; Phillips, Frank M; Khan, Safdar N

    2018-01-23

    A retrospective, economic analysis. The objective of this article is to analyze the distribution of 90-day payments, sources of variation, and reimbursement for complications and readmissions for primary ≥3-level posterior lumbar fusion (PLF) from Medicare data. A secondary objective was to identify risk factors for complications. Bundled payments represent a single payment system to cover all costs associated with a single episode of care, typically over 90 days. The dollar amount spent on different health service providers and the variation in payments for ≥3-level PLF have not been analyzed from a bundled perspective. Administrative claims data were used to study 90-day Medicare (2005-2012) reimbursements for primary ≥3-level PLF for deformity and degenerative conditions of the lumbar spine. Distribution of payments, sources of variation, and reimbursements for managing complications were studied using linear regression models. Risk factors for complications were studied by stepwise multiple-variable logistic regression analysis. Hospital payments comprised 73.8% share of total 90-day payment. Adjusted analysis identified several factors for variation in index hospital payments. The average 90-day Medicare payment for all multilevel PLFs without complications was $35,878 per patient. The additional average cost of treating complications with/without revision surgery within 90 days period ranged from $17,284 to $68,963. A 90-day bundle for ≥3-level PLF with readmission ranges from $88,648 (3 levels) to $117,215 (8+ levels). Rates and risk factors for complications were also identified. The average 90-day payment per patient from Medicare was $35,878 with several factors such as levels of surgery, comorbidities, and development of complications influencing the cost. The study also identifies the risks and costs associated with complications and readmissions and emphasize the significant effect these would have on bundled payments (additional burden of up

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

    Directory of Open Access Journals (Sweden)

    Xiaofang Zhang

    2016-11-01

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

  11. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats

    DEFF Research Database (Denmark)

    Schrøder, Malene; Poulsen, Morten; Wilcks, Andrea

    2007-01-01

    An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15......, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design...

  12. Climate Prediction Center (CPC)Ensemble Canonical Correlation Analysis 90-Day Seasonal Forecast of Precipitation

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Ensemble Canonical Correlation Analysis (ECCA) precipitation forecast is a 90-day (seasonal) outlook of US surface precipitation anomalies. The ECCA uses...

  13. Evaluation of the 90-Day Inhalation Toxicity of Petroleum and Oil Shale JP-5 Jet Fuel

    Science.gov (United States)

    1985-04-01

    7) Reproductive & Endocrine Ovaries - cyst 11/63 (17) 13/57 (23) 7/57 (12) 17/94 (18) 17/93 (18) 13/96 (14) Uterus - endometrial cyst 8/66 (12) 8/68...oncornavirus infection was probably responsible. Tumors of the kidney were not seen in any of the JP-5 exposed mice. Ovarian and uterine cystic changes...were present with high frequency and variable distribution among all groups. Pituitary and thyroid follicular adenomas were also common in all groups

  14. Some patterns of metallic nanoparticles' combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles.

    Science.gov (United States)

    Katsnelson, Boris A; Minigaliyeva, Ilzira A; Panov, Vladimir G; Privalova, Larisa I; Varaksin, Anatoly N; Gurvich, Vladimir B; Sutunkova, Marina P; Shur, Vladimir Ya; Shishkina, Ekaterina V; Valamina, Irene E; Makeyev, Oleg H

    2015-12-01

    Stable suspensions of NiO and/or Mn3O4 nanoparticles with a mean diameter of 16.7 ± 8.2 nm and 18.4 ± 5.4 nm, respectively, prepared by laser ablation of 99.99% pure metals in de-ionized water were repeatedly injected IP to rats at a dose of 0.50 mg or 0.25 mg 3 times a week up to 18 injections, either separately or in different combinations. Many functional indices as well as histological features of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The accumulation of Ni and Mn in these organs was measured with the help of AES and EPR methods. Both metallic nanoparticles proved adversely bio-active, but those of Mn3O4 were found to be more noxious in most of the non-specific toxicity manifestations. Moreover, they induced a more marked damaging effect in the neurons of the caudate nucleus and hippocampus which may be considered an experimental correlate of manganese-induced parkinsonism. Mathematical analysis based on the Response Surface Methodology (RSM) revealed a diversity of combined toxicity types depending not only on particular effects these types are assessed for but on their level as well. The prognostic power of the RSM model proved satisfactory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Acute and subchronic toxicity evaluation of methanol stem-bark extract of Ximenia americana Linn (Olacaceae in Wistar rats

    Directory of Open Access Journals (Sweden)

    Isaac A. Agyigra

    2017-12-01

    Full Text Available Ximenia americana is used in African ethno-medicine for spasmodic bowel diseases with stem bark particularly used for ulcers. This study evaluated the toxicity-profile of methanol stem-bark extract. Extract doses were selected from estimated oral median lethal dose (LD50 of acute toxicity test. Ten male Wistar rats in 4-groups, weekly weighed and daily treated orally per body-weight for 28 days with normal-saline and extract-doses (250, 500, 1000 mg/kg respectively were euthanized. Blood for biochemical and haematological analyses were collected into plain and anticoagulated (EDTA sample-bottles respectively from each group. Vital-organs were isolated, weighed and fixed in buffered-formalin fixatives for histo-analyses. Mean ± standard-error of mean and statistical-significance at (p ≤ 0.05 of obtained-data were evaluated. The extract at up to 5000 mg/kg caused no mortality or behavioural toxic-signs and thus, oral LD50 was estimated to be greater than 5000 mg/kg. No changes in organ-sizes, body-weights or anatomy of brain, heart, liver and stomach occurred, but at 1000 mg/kg, kidney showed vascular-congestion with polymorphonuclear cells, lungs had consolidated areas of polymorphs infiltration, while spleen had distorted germinal-centres. Liver enzymes and urea levels were not altered significantly, but a dose dependent significant increase in total-protein only at 1000 mg/kg; and significant reduction in albumin level at 500 and 1000 mg/kg were observed. The observed dose-dependent reduction in creatinine was not significant. Total-calcium and chloride ion concentrations increased significantly only at 250 mg/kg. In conclusion, acute oral administration of methanol stem-bark extract of Ximenia americana was relatively non-toxic in mice, but minimal anatomical changes in kidney, lungs and spleen occurred when used for few weeks in rats. Keywords: Ximenia americana, Stem-bark, Methanol extract

  16. Experimental model of microcystin accumulation in the liver of Oreochromis niloticus exposed subchronically to a toxic bloom of Microcystis sp.

    Science.gov (United States)

    Deblois, Charles P; Giani, Alessandra; Bird, David F

    2011-05-01

    Although accumulation of the liver toxin microcystin in phytoplanktivorous fish has been demonstrated in captive fish and in natural ecosystems, the relation between microcystin in ingested algae and the pattern of buildup of microcystin in fish is poorly known. In this month-long study performed at a Brazilian fish farm, 45 mature Oreochromis niloticus were fed daily with fresh seston periodically dominated by toxic Microcystis sp. Microcystin was measured daily in the food and every 5 days in liver and muscle samples. Control fish received a diet of seston that was low in toxic cyanobacteria. Initially, in treatment ponds, microcystin available for fish increased from 6.5 to 66.9 ng microcystin fish(-1)day(-1), which was accompanied by an increase from 5.5 to 35.4 ng microcysting liver(-1). Microcystin in muscle was below our detection limit of 4 ng g tissue(-1) for the entire study. In the bloom phase, available microcystin reached its highest concentration (4450 ng MC fish(-1)day(-1)) then decreased to 910 ng microcystin fish(-1)day(-1) on day 31. During this period, microcystin reached its highest concentration of 81.6 ng MC g liver(-1) and stayed high until the end of the experiment. A model based on rapid uptake, saturation, and exponential loss was built with these experimental results, and verified with data from the literature. Our model showed that accumulation was up to 50% of ingestion at low doses, but at intermediate doses, the onset of elimination led to a decline of liver burden. Although the accumulation rate confirms the high contamination potential of microcystin, it was balanced by a high depuration rate and this efficient systemic elimination may explain the tolerance of these fish to toxic blooms in the wild. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  18. Effects of antimony on rats following 90-day exposure via drinking water.

    Science.gov (United States)

    Poon, R; Chu, I; Lecavalier, P; Valli, V E; Foster, W; Gupta, S; Thomas, B

    1998-01-01

    The subchronic toxicity of antimony in drinking water was studied in the rat. Male and female Sprague-Dawley rats (127-135 g body weight, 15 animals per group) were exposed to a soluble trivalent antimony salt, potassium antimony tartrate, in drinking water at concentrations of 0.5, 5, 50 and 500 ppm for 13 wk. Control rats received tap water as drinking water. An additional 10 male and 10 female rats were included in each of the control and 500 ppm groups and were given tap water for a further 4-wk recovery period after the 13-week treatment period. During treatment, the highest dose animals of both sexes consumed significantly less water and showed suppressed body weight gain. During recovery, water intake was quickly restored to that of the control groups and body weight gain was accelerated. At termination, one highest dose male had a cirrhotic liver, and three highest dose males exhibited gross haematuria. Female rats showed a dose-related decrease in serum glucose starting at 5 ppm, and rats of both sexes in the highest dose group had slightly decreased alkaline phosphatase activity and creatinine. The highest dose males had decreased red blood cell and platelet counts and increased mean corpuscular volume. Hepatic glutathione S-transferase activity was increased in the highest dose males and females and ethoxyresorufin-O-deethylase activity was increased in the highest dose males. In the highest dose groups, mild adaptive histological changes were observed in the thyroid, liver and pituitary gland of both sexes, and in the spleen of male rats and thymus of female rats. After a 4-wk recovery period, the pituitary gland of both sexes appeared normal and the changes in the liver and thyroid of both sexes became less severe. On the other hand, minimal changes persisted in the spleen of both sexes and in the thymus of males. Tissue antimony levels were dose-related and follow the order: red blood cells > > spleen, liver > kidney > brain, fat > serum. After the

  19. Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

    Directory of Open Access Journals (Sweden)

    Larisa I. Privalova

    2014-07-01

    Full Text Available In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its

  20. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

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    Qian-ying Guo

    2015-12-01

    Full Text Available BT799 is a genetically modified (GM maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt. The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58 at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control.

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

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    Narges El Golli

    2016-04-01

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

  2. Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

    Science.gov (United States)

    Privalova, Larisa I.; Katsnelson, Boris A.; Loginova, Nadezhda V.; Gurvich, Vladimir B.; Shur, Vladimir Y.; Valamina, Irene E.; Makeyev, Oleg H.; Sutunkova, Marina P.; Minigalieva, Ilzira A.; Kireyeva, Ekaterina P.; Rusakov, Vadim O.; Tyurnina, Anastasia E.; Kozin, Roman V.; Meshtcheryakova, Ekaterina Y.; Korotkov, Artem V.; Shuman, Eugene A.; Zvereva, Anastasia E.; Kostykova, Svetlana V.

    2014-01-01

    In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified. PMID:25026171

  3. Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

    DEFF Research Database (Denmark)

    Eck, Lasse Karlsen; Jensen, Thomas Bo; Mastrogiannis, Dimitrios

    2017-01-01

    OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997...... group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available...... data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly....

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

    Science.gov (United States)

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

    2016-02-03

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

  5. Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke.

    Science.gov (United States)

    Wong, Ee Tsin; Kogel, Ulrike; Veljkovic, Emilija; Martin, Florian; Xiang, Yang; Boue, Stephanie; Vuillaume, Gregory; Leroy, Patrice; Guedj, Emmanuel; Rodrigo, Gregory; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2.2-exposed groups compared with 3R4F-exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent differential gene expression following 3R4F exposure that was less pronounced in the THS2.2-exposed groups. Molecular network analysis showed that inflammatory processes were the most affected by 3R4F, while the extent of THS2.2 impact was much lower. Most other toxicological endpoints evaluated did not show exposure-related effects. Where findings were observed, the effects were similar in 3R4F- and THS2.2-exposed animals. In summary, toxicological changes observed in the respiratory tract organs of THS2.2 aerosol-exposed rats were much less pronounced than in 3R4F-exposed rats while other toxicological endpoints either showed no exposure-related effects or were comparable to what was observed in the 3R4F-exposed rats. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Diabetes Is Not Associated With Increased 90-Day Mortality Risk in Critically Ill Patients With Sepsis

    NARCIS (Netherlands)

    van Vught, Lonneke A.; Holman, Rebecca; de Jonge, Evert; de Keizer, Nicolette F.; van der Poll, Tom

    2017-01-01

    Objectives: To determine the association of pre-existing diabetes, hyperglycemia, and hypoglycemia during the first 24 hours of ICU admissions with 90-day mortality in patients with sepsis admitted to the ICU. Design: We used mixed effects logistic regression to analyze the association of diabetes,

  7. [Clinical profile and 90-day mortality in centenarian patients attended in emergency departments].

    Science.gov (United States)

    Martín-Sánchez, Francisco Javier; Fernández-Alonso, Cesáreo; Hormigo, Ana Isabel; Jiménez-Díaz, Gregorio; Roiz, Honan; Bermejo-Boixareu, Cristina; Rodríguez-Salazar, Jaime; Fernández Pérez, Cristina; Gil-Gregorio, Pedro

    2016-01-01

    To determine the clinical profile and to develop a model to predict 90-day mortality in centenarian patients attended in emergency departments (ED). This was an observational, retrospective, multicentre cohort study including patients >99years attended in 5 ED in the Community of Madrid from January to December 2012. Demographic variables were recorded, as well as, comorbidities, cognitive, functional, social basal status, geriatric syndromes, acute episode, and hospital and social resources use, and 90-day mortality. The study included 209patients aged 101years (SD 1.7) of whom 161 (77.0%) were female. Sixty four (32.5%) had severe comorbidity (Charlson index≥3), 101 (49.8%) on multiple medication, 100 (52.6%) had cognitive impairment, 82 (42.3%) had severe functional dependence, 85 (40.7%) were institutionalised, and 190 (94.5%) had a geriatric syndrome. Dyspnoea (26.8%), followed by falls (12.4%) were the most common causes of attendance. One hundred and eighteen (56.5%) were admitted, and 58 out of 174 (33.3%) died in the first 90days. The model to predict 90-day overall mortality included male sex (OR 2.42 95% CI=0.97-6.04; P=.059), emergency care in the previous 3months (OR 4.08 95% CI=1.26-13.16; P=.019) and the hospitalization by index event (OR 8.63 95% CI=3.25-22.9; P<.001) and this model had an area under ROC curve of 0.776 (95% CI=0.70-0.85; P<.001). Centenarian patients attended in ED had a significant frailty and one in three cases died in the first 90days after being attended, and this was associated with male sex, emergency care in the previous 3months, and hospitalisation. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. The involvement of sirtuin 1 and heme oxygenase 1 in the hepatoprotective effects of quercetin against carbon tetrachloride-induced sub-chronic liver toxicity in rats.

    Science.gov (United States)

    Kemelo, Mighty Kgalalelo; Pierzynová, Aneta; Kutinová Canová, Nikolina; Kučera, Tomáš; Farghali, Hassan

    2017-05-01

    The present study was designed to evaluate the therapeutic potential of quercetin in a sub-chronic model of hepatotoxicity. The roles of putative antioxidant enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1), in hepatoprotection were also addressed. Sub-chronic liver injury was induced in rats by intraperitoneal administration of 0.5 ml/kg carbon tetrachloride (CTC), once every 3 days, for 2 weeks. Some CTC rats were concurrently treated with 100 mg/kg quercetin, intragastrically, once every day, for 2 weeks. The effects of these drugs in the liver were evaluated by biochemical, histological, immunohistochemical and molecular biological studies. CTC triggered oxidative damage to the liver as unanimously shown by altered biochemical parameters and liver morphology. Furthermore, CTC highly upregulated HO-1 and SIRT1 expression levels. Concomitant treatment of rats with quercetin downregulated SIRT1 expression and ameliorated the hepatotoxic effects of CTC. However, quercetin did not have any significant effect on HO-1 expression and bilirubin levels. Collectively, these results suggest that the antioxidant and cytoprotective effects of quercetin in CTC treated rats were SIRT1 mediated and less dependent on HO-1. Thus, pharmacologic modulation of SIRT1 could provide a logic therapeutic approach in sub-chronic hepatotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Community pharmacy and mail order cost and utilization for 90-day maintenance medication prescriptions.

    Science.gov (United States)

    Khandelwal, Nikhil; Duncan, Ian; Rubinstein, Elan; Ahmed, Tamim; Pegus, Cheryl

    2012-04-01

    Pharmacy benefit management (PBM) companies promote mail order programs that typically dispense 90-day quantities of maintenance medications, marketing this feature as a key cost containment strategy to address plan sponsors' rising prescription drug expenditures. In recent years, community pharmacies have introduced 90-day programs that provide similar cost advantages, while allowing these prescriptions to be dispensed at the same pharmacies that patients frequent for 30-day quantities. To compare utilization rates and corresponding costs associated with obtaining 90-day prescriptions at community and mail order pharmacies for payers that offer equivalent benefits in different 90-day dispensing channels. We performed a retrospective, cross-sectional investigation using pharmacy claims and eligibility data from employer group clients of a large PBM between January 2008 and September 2010. We excluded the following client types: government, third-party administrators, schools, hospitals, 340B (federal drug pricing), employers in Puerto Rico, and miscellaneous clients for which the PBM provided billing services (e.g., the pharmacy's loyalty card program members). All employer groups in the sample offered 90-day community pharmacy and mail order dispensing and received benefits management services, such as formulary management and mail order pharmacy, from the PBM. We further limited the sample to employer groups that offered equivalent benefits for community pharmacy and mail order, defined as groups in which the mean and median copayments per claim for community and mail order pharmacy, by tier, differed by no more than 5%. Enrollees in the sample were required to have a minimum of 6 months of eligibility in each calendar year but were not required to have filled a prescription in any year. We evaluated pharmacy costs and utilization for a market basket of 14 frequently dispensed therapeutic classes of maintenance medications. The proportional share of claims for

  10. Clinical profile of bronchiolitis in infants younger than 90 days in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Syed Amir Ahmad

    2014-01-01

    Full Text Available Background: Bronchiolitis is a self-limiting disease of children caused by viral infections of the small airways with a wide spectrum of illness severity. Search of the literature reveals a need for refinement of criteria for testing for concomitant severe bacterial infections as well as appropriate therapeutic interventions for patients <90-day-old diagnosed with clinical bronchiolitis. We believe that a better understanding of the disease spectrum will help optimize health-care delivery to these patients. Aims: The aim of this study was to determine the clinical profile at presentation, disease course and outcome of bronchiolitis in <3-month-old infants who presented to our Pediatric Emergency Department (PED during one disease season. Settings: Retrospective chart review during one bronchiolitis season, from November 1, 2011 to April 20, 2012. Subjects: All <90-day-old infants presenting with clinical bronchiolitis presenting to Urban PED of a tertiary care university hospital during one bronchiolitis season. Materials and Methods: A retrospective chart review based on computer records of all emergency department visits of infants less than 90 days with a clinical diagnosis of bronchiolitis, covering the period between November 1, 2011 and April 30, 2012. Results: Out of the total of 1895 infants <90 days of age, 141 had a clinical diagnosis of bronchiolitis and 35 needed admission to hospital. Blood for culture was obtained from 47 infants, urine for culture was obtained from 46 infants and cerebrospinal fluid for culture was obtained from eight infants. One case of bacteremia was documented, but this was found to be a contaminant. No cases of meningitis occurred among these infants. However, one infant had a positive urine culture consistent with infection (Escherichia coli . Conclusion: Based on the results, it can be conclude that the risk of bacteremia or meningitis among infants <90 days of age with fever and bronchiolitis is low. The

  11. Are Barbed Sutures Associated With 90-day Reoperation Rates After Primary TKA?

    Science.gov (United States)

    Austin, Daniel C; Keeney, Benjamin J; Dempsey, Brendan E; Koenig, Karl M

    2017-11-01

    Studies have suggested that barbed sutures for wound closure in TKAs are an acceptable alternative to standard methods. However others have observed a higher risk of wound-related complications with barbed sutures. (1) Do 90-day TKA reoperation rates differ between patients undergoing a barbed suture arthrotomy closure compared with a traditional interrupted closure? (2) Do the 90-day reoperation rates of wound-related, deep infection, and arthrotomy failure complications differ between barbed suture and traditional closures? A retrospective analysis of a longitudinally maintained institutional primary TKA database was conducted on all TKAs performed between April 2011 and September 2015. We compared 884 primary TKAs, where the arthrotomy was closed with a barbed suture, with 1598 primary TKAs closed with the standard interrupted suture. After barbed sutures were introduced at our institution in 2012, the majority of surgeons gradually switched to barbed suture closures, with many using them exclusively by the end of the data collection period. We confirmed in-person followups and available data past 90 days for 97.4% (1556 of 1598) of the knees in patients with standard sutures and 94.8% (838 of 884) of the knees in patients with barbed sutures. Our primary endpoint was all-cause 90-day reoperation; our secondary endpoints considered: wound-related reoperation, as defined by previous studies; deep infection per Musculoskeletal Infection Society guidelines; and arthrotomy failure, defined intraoperatively as an opening or dehiscence through the previous arthrotomy closure. T tests and chi-square analyses were used to determine differences between the suture cohorts, and bivariate logistic regression was used to determine associations with our 90-day reoperation outcomes. With the numbers available, there was no association between suture type and 90-day all-cause reoperation (odds ratio [OR], 1.70; 95% CI, 0.82-3.53; p = 0.156). Suture type was not associated with

  12. Safety assessment of the aqueous extract of the flowers of Nymphaea lotus Linn (Nymphaeaceae): Acute, neuro- and subchronic oral toxicity studies in albinos Wistar rats.

    Science.gov (United States)

    Kameni Poumeni, Mireille; Bilanda, Danielle Claude; Dzeufiet Djomeni, Paul Désiré; Mengue Ngadena, Yolande Sandrine; Mballa, Marguerite Francine; Ngoungoure, Madeleine Chantal; Ouafo, Agnès Carolle; Dimo, Théophile; Kamtchouing, Pierre

    2017-03-24

    Background Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system. Methods Aqueous extract of N. lotus at doses of 200, 400 and 600 mg/kg body weight (BW) was evaluated for nitrites contents and orally administered to rats daily for 28 days (5 male, 5 female per group). The control group received distilled water (10 mL/kg) and a satellite group was used to observe reversal effects. Neurotoxicity of the plant was determined using open field test for motor coordination, ataxia and gait analysis. Clinical signs and state of livelihood were recorded during the 24 h, then for 28 days of treatments. At the end of 28-day period, animals were anesthetized and decapitated. The whole brain was homogenized for neurobiochemical analysis. Blood samples were collected with or without anticoagulant for hematological examinations and serum analysis. Specimens of liver, kidney, testis, ovaries, and brain were fixed in 10 % formalin and processed for histopathological examinations. Results Our findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract of N. lotus. Acute toxicity study revealed no signs of toxicity neither at the dose 2,000 mg/kg nor at 5,000 mg/kg. Thus the LD50 value of aqueous extract of N. lotus flowers is superior to 5,000 mg/kg. The repeated administration of N. lotus during 28 days, induced no signs of neurobehavioral changes in male, but female rats exhibited dose-dependent response in the open field test, suggesting sex and dose-relative psychotropic effects of N. lotus. The evaluation of

  13. Subchronic oral toxicity study on the three flavouring substances: octan-3-ol, 2-methylcrotonic acid and oct-3-yl 2-methylcrotonate in Wistar rats

    DEFF Research Database (Denmark)

    Lindecrona, R. H.; Mølck, A. M.; Poulsen, Morten

    2003-01-01

    Groups of 10 male and 10 female rats were administered 0, 25, 100 or 400 mg octan-3-ol/kg body weight per day, 77 mg 2-methylcrotonic acid/kg body weight per day or 163 mg oct-3-yl 2-methylcrotonate/kg body weight per day by gavage for 90 days. Relative liver weights of high-dose octan-3-ol males...

  14. Human exploration of space: A review of NASA's 90-day study and alternatives

    Science.gov (United States)

    Stever, H. Guyford; Cannon, Robert H., Jr.; Gavin, Joseph G.; Kerrebrock, Jack L.; Lanzerotti, Louis J.; Levinthal, Elliott C.; Mar, James W.; Mcelroy, John H.; Mcruer, Duane T.; Merrell, William J., Jr.

    1990-01-01

    The National Research Council (NRC) examines the NASA Report of the 90-Day Study on Human Exploration of the Moon and Mars, and alternative concepts. Included in this paper, prepared for the National Space Council, are the answers to a challenging set of questions posed by the Vice President. Concerns addressed include: the appropriate pace, the scope of human exploration, the level of long-term support required, the technology development available and needed, the feasibility of long-duration human spaceflight in a low-gravity environment, scientific objectives, and other considerations such as costs and risks.

  15. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    OpenAIRE

    Clewell, Amy; Hirka, G?bor; Gl?vits, R?bert; Palmer, Philip A.; Endres, John R.; Murbach, Timothy S.; Marx, Tennille; Pasics Szakonyin?, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular h...

  16. Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

    Directory of Open Access Journals (Sweden)

    Kajal Chakraborty

    2014-01-01

    Full Text Available The short-term (acute and long-term (subchronic toxicity profile, mean lethal dose 50 (LD50, and no-observed-adverse-effect level (NOAEL of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 g/kg body weight for 90 days in subchronic toxicity study. The LD50, variations in clinical signs, changes in body weight, body weight, food/water consumption, organ weight (liver, kidney, spleen, and brain, hematology, serum chemistry, and histopathological changes were evaluated. The LD50 of the formulation was 5,000 mg/kg BW. No test article related mortalities as well as change in body weight, and food and water consumption were observed. No toxicity related significant changes were noted in renal/hepatic function, hematological indices, and serum biochemical parameters between the control and treated groups. Histopathological alterations were not observed in the vital organs of rats. The subchronic NOAEL for the formulation in rats is greater than 2000 mg/kg. This study demonstrated that the green mussel formulation is safe to consume without any adverse effects in the body.

  17. Experimental adhesives with different hydrophilicity: microshear test in after 1, 7, and 90 days' storage.

    Science.gov (United States)

    Hori, Frederico Seidi; de Carvalho, Rubens Côrte

    2012-04-01

    To assess the microshear bond strength of 3 experimental adhesives with different degrees of hydrophilicity after 1, 7 and 90 days of storage. The bonding effectiveness of three experimental two-step etch-and-rinse adhesives (bis- GMA, bis-EMA/bis-GMA, polybutadiene [C6H12]) and one commercial adhesive (Single Bond) to sound hydrated dentin was determined using the microshear test with delimitation of the adhesive area after 1, 7, and 90 days of storage in water at 37°C. Two-way ANOVA was performed at the 0.05 probability level. The fractures were classified as adhesive, cohesive in dentin, cohesive in resin, and mixed. The experimental adhesives showed values in the range of 11.31 to 12.96 MPa, with polybutadiene (PBH) showing the lowest bond strengths, bis-GMA the highest, and bis-EMA/bis-GMA intermediary values. Single Bond yielded bond strengths of approximately 24 MPa. Water storage decreased the bond strength in all adhesives. Adhesive fractures were predominant in experimental adhesives, while mixed fractures were the most frequent type in the Single Bond group. The experimental dentin adhesives of this study were able to form resin tags, but they could not penetrate into the collagen fibers and form hybrid layers. The resulting low bond strength decreased with increasing length of storage.

  18. Oral subchronic exposure to silver nanoparticles in rats

    OpenAIRE

    Tania Garcia; Daisy Lafuente; Jordi Blanco; Domenec J. Sanchez; Juan J. Sirvent; Jose L. Domingo; Mercedes Gomez

    2016-01-01

    Oral subchronic exposure to silver nanoparticles in rats DOI: 10.1016/j.fct.2016.04.010 Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic ex...

  19. The effects of firocoxib (Previcox™ in geriatric dogs over a period of 90 days

    Directory of Open Access Journals (Sweden)

    K.E. Joubert

    2009-05-01

    Full Text Available The long-term use of non-steroidal anti-inflammatory agents in geriatric dogs with osteoarthritis has not been well studied in veterinary medicine. This study evaluated the effects of firocoxib administered to dogs over 7 years of age for 90 days. Pain and lameness scores were evaluated by the owner weekly for the 1st month and then biweekly through to the end of the study, the veterinarian evaluated the dogs monthly. Serum chemistry, including urea, creatinine, alanine transferase, aspartate transaminase, bile acids and bilirubin, urine specific gravity and a urine dipstick, were performed at monthly intervals. Forty-five dogs were enrolled into the treatment group and 9 into the control group. A total of 33 dogs completed the trial in the treatment group and 8 in the control group. Lameness and pain scores were found to be significantly lower in the treated group from day 30 for most parameters evaluated. Bile acids (although not comparable to controls, with higher mean value and a high standard deviation in the control group; in addition the control group had increased bile acids at day 0 and urea (within normal reference range provided (WNL were significantly different in the treatment group between days 0 and 90. Urea (WNL on days 30 and 90 and creatinine (WNL on day 90 were significantly different between the control group and the treatment group. The most common adverse events reported were diarrhoea, vomition, dark faeces and anorexia. This study showed that firocoxib was effective in managing pain associated with osteoarthritis for 90 days. Despite the geriatric high-risk population used for this study, minimal biochemical changes were seen and adverse drug events seen were in agreement with those previously reported.

  20. Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

    Science.gov (United States)

    Liu, Hong

    A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

  1. Effects of furan on male rat reproduction parameters in a 90-day gavage study.

    Science.gov (United States)

    Cooke, Gerard M; Taylor, Marnie; Bourque, Christine; Curran, Ivan; Gurofsky, Susan; Gill, Santokh

    2014-07-01

    Furan is produced in foods during processing and preservation techniques that involve heat treatment. Previously, we reported that furan-exposed rats exhibited dose-dependent gross and histological changes in liver which correlated with changes in liver serum enzymes ALT, AST and ALP. Here we report the effects of furan on the male reproductive system. There were no histological or weight changes in the reproductive organs. Serum testosterone levels were increased in a dose-dependent manner whereas serum LH was decreased. There were no changes in 17-OHase, 3β-HSD and 17β-HSD activities or serum FSH. Furan did not alter mRNA expression levels for the LH receptor or Tspo but in contrast, mRNA levels of StAR were increased in all doses of furan. The mRNA for the cholesterol side-chain cleavage enzyme (Cyp11a1) was increased by furan at the high dose, as was the level of intratesticular testosterone. We conclude that subchronic furan exposure affects testicular steroidogenesis. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  2. [Study on food safety of genetically modified rice which expressed cowpea trypsin inhibitor by 90 day feeding test on rats].

    Science.gov (United States)

    Zhuo, Qin; Chen, Xiaoping; Piao, Jianhua; Gu, Lüzhen

    2004-03-01

    Rats were fed by transgenic rice which expressed insecticidal protein CPTI (cowpea trypsin inhibitor) to study if the transgenic rice possessed potential toxic or adverse effects. Weanling Wistar rats were randomly divided into three groups: T, N and C group. The diet of T group contained 78.3% transgenic rice. The diet of N group contained 74.7% non transgenic rice which was the parent line of the transgenic one. The diet formula of C group was AIN93G. The macro- and micronutrient content were equal in three diets. The rats were fed for 90 days. Food intakes were weight every day, body-weight were weight and body-length were measured every week. In the middle and at the end of feeding period, haematological value and clinical chemistry parameters were measured, at the end of the 90th day, post-mortem organ coefficient were measured, organ tissues analysis was performed and bone density was measured. In most situation, there were no significant differences among the three groups(P > 0.05) and no histopathological damage were detected. At the end of the 1st month, the male rats' body length of the T group was longer than the other two groups and at the end of the test period, the male rats' blood glucose and ALT were lower than the other two groups. In the middle of the test period, the female rats' red blood cell number and hemoglobin were higher than the other two groups and at the end of the test period, the female rats' monocyte number was higher than the other two groups (P transgenic rice on rats there did not reveal any signs of toxic and adverse effects.

  3. A 90-day safety study of genetically modified rice expressing rhIGF-1 protein in C57BL/6J rats.

    Science.gov (United States)

    Tang, Maoxue; Xie, Tingting; Cheng, Wenke; Qian, Lili; Yang, Shulin; Yang, Daichang; Cui, Wentao; Li, Kui

    2012-06-01

    Genetically modified plants expressing disease resistance traits offer new treatment strategies for human diseases, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of transgenic rice expressing the recombinant human insulin-like growth factor-1 (rhIGF-1) compared to its parental wild rice. Male and female C57BL/6J rats were given a nutritionally balanced purified diet with 20% transgenic rhIGF-1 rice or 20% parental rice for 90 days. This corresponds to a mean daily rhIGF-1 protein intake of approximately 217.6 mg/kg body weight based on the average feed consumption. In the animal study a range of biological, biochemical, clinical, microbiological and pathological parameters were examined and several significant differences were observed between groups, but none of the effects were considered to be adverse. In conclusion, no adverse or toxic effects on C57BL/6J rats were observed in the design used in this 90-day study. These results will provide valuable information for the safety assessment of genetically modified food crops.

  4. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    Directory of Open Access Journals (Sweden)

    Amy Clewell

    2016-01-01

    Full Text Available A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group were administered theacrine by gavage doses of 0 (vehicle only, 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  5. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.

    Science.gov (United States)

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  6. 75 FR 41436 - Endangered and Threatened Wildlife; Notice of 90-Day Finding on a Petition to Revise Critical...

    Science.gov (United States)

    2010-07-16

    ... turtles while they are in the marine environment, feeding and migrating for example, the Federal agency... designated in the marine environment, the consultation would be with NMFS. This 90-day finding is responsive...

  7. Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data.

    Science.gov (United States)

    Donoho, Daniel A; Wen, Timothy; Babadjouni, Robin M; Schwartzman, William; Buchanan, Ian A; Cen, Steven Y; Zada, Gabriel; Mack, William J; Attenello, Frank J

    2018-01-01

    Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90-days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013-2014, with 3343 (13.2%) 30-day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90-day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery.

  8. Sub-chronic toxicological studies of transition metal complexes of ...

    African Journals Online (AJOL)

    Md. Sharif Hasan

    2017-01-18

    Jan 18, 2017 ... Objective: The purpose of this research was to investigate sub-chronic toxicity in animal model. Methods: A detailed study was done on the physical, hematological, biochemical and hormonal parame- ters of both male and female Sprague-Dawley rats after 28 days administration of naproxen and its metal.

  9. Sub-chronic toxicological studies of transition metal complexes of ...

    African Journals Online (AJOL)

    Objective: The purpose of this research was to investigate sub-chronic toxicity in animal model. Methods: A detailed study was done on the physical, hematological, biochemical and hormonal parameters of both male and female Sprague-Dawley rats after 28 days administration of naproxen and its metal complexes.

  10. Intra- and Inter-Patient Symptom Variability in Fibromyalgia: Results of a 90-Day Assessment.

    Science.gov (United States)

    Toussaint, Loren; Vincent, Ann; McAllister, Samantha J; Whipple, Mary

    2015-06-01

    Symptoms of fibromyalgia (FM)--chronic widespread pain, fatigue, unrefreshing sleep, dyscognition etcetera--present with varying degrees of severity in different individuals; however, studies reporting daily estimates of variability of symptoms are sparse. Given the limited literature on the stability and variability of FM symptoms, the purpose of the present study was to determine the feasibility of daily visual analogue, self-report measures to assess daily variability and time trends in core FM symptoms. Ten female patients completed daily assessments of common FM symptoms (pain, fatigue, anxiety, depression, stress, cognitive dysfunction, unrefreshing sleep and lightheadedness) for approximately 90 days. The completion rate was excellent (89.6%). The results demonstrated that average symptom intensity differs markedly across the different symptoms that were measured. Unrefreshing sleep, fatigue and pain are clearly higher in intensity than other symptoms and are followed by memory problems, stress, anxiety and depression. There is also notable average intra-individual change across time (10-15 points on a 100-point scale). Average symptom intensity does not appear to be related to the amount of symptom change within individuals. The results of the present study confirm that intensive longitudinal study, using comprehensive symptom assessment in patients with FM, is both possible and informative, in the sense that a rich description of the daily experience of living with FM can be obtained. Future work, utilizing larger samples, will offer the opportunity to investigate better the causes, consequences and correlates of the daily ups and downs of key symptoms that compromise quality of life in patients with FM. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Distribution and elimination of palladium in rats after 90-day oral administration.

    Science.gov (United States)

    Iavicoli, Ivo; Bocca, Beatrice; Fontana, Luca; Caimi, Stefano; Bergamaschi, Antonio; Alimonti, Alessandro

    2010-04-01

    This study determined the distribution in internal organs and the elimination routes in rats after oral administration of potassium hexachloro-palladate. Forty male Wistar rats were exposed for 90 days to 0, 10, 100 and 250 ng/mL of the palladium (Pd) salt in drinking water. Samples of urine and feces were collected on days 1, 30, 60 and 90, while organs (kidney, liver, lung, spleen and bones) and blood were collected at the end of the experiment. Quantification method was based on the sector-field inductively coupled plasma mass spectrometry. Results indicated that Pd ions were rapidly eliminated from the body. The principal excretion was through the feces (650 +/- 72.7 ng/g dry weight, at the Pd dose of 250 ng/mL), but at the higher dosing Pd was also eliminated through the urine (6.16 +/- 1.91 ng/mL for the Pd intake of 250 ng/mL). A clear relationship between the Pd ingested dose and the Pd excretion amount was observed mainly in the feces. Absorbed Pd was mostly found in the kidney of rats (124.4 +/- 23.0 ng/g dry weight, following the highest dose), while liver, lung, spleen and bones did not accumulate the metal. At the higher dosing, Pd content in the kidney raised proportionally with the Pd dose. Our findings may be useful to help in the understanding of the health impact of Pd dispersed in the environment as well as in identifying appropriate biological indices of Pd exposure.

  12. Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

    Science.gov (United States)

    Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

    2011-01-01

    INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

  13. Recent trends in the dispensing of 90-day-supply prescriptions at retail pharmacies: implications for improved convenience and access.

    Science.gov (United States)

    Liberman, Joshua N; Girdish, Charmaine

    2011-03-01

    Mail-service pharmacies offer consumers the convenience of prescriptions filled with a 90-day supply of medication. Unlike mail-service pharmacies, retail pharmacies traditionally dispensed maintenance medication prescriptions with a 30-day supply. However, the retail landscape changed in May 2008 with Walmart's announcement of an extension of its $4 Prescription Program to include 90-day-supply prescriptions. To evaluate recent changes in access to and use of 90-day-supply maintenance medications dispensed via retail pharmacy. As of the first quarter of 2007, the proportion of retail-dispensed maintenance medications with a 90-day supply (compared with all maintenance prescriptions dispensed) among Medicare Part D plans, self-insured employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for commercial health plans; the ratio among employers had risen more modestly to 6.1%. Of particular interest and importance, the proportion increased similarly for brand and for generic medications. There has been substantial growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is likely to continue as more insurance providers adopt compatible benefit designs. It is important to continue monitoring these trends and to identify opportunities to rigorously evaluate their impact on medication adherence and healthcare costs.

  14. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event

    DEFF Research Database (Denmark)

    Knudsen, Ib; Poulsen, Morten

    2007-01-01

    This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schroder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A...... study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel...... high dose level and a dietary design based upon compositional data on the GM food and toxicity data on the gene product is sensitive and specific enough to verify the presence/absence of the biological/nutritional/toxicological effects of the novel gene insert and further by the use of spiking able...

  15. Low concentration toxic metal mixture interactions: Effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure.

    Science.gov (United States)

    Cobbina, Samuel J; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Mao, Guanghua; Xu, Hai; Zhang, Zhen; Wu, Xiangyang; Yang, Liuqing

    2015-08-01

    The deleterious effects of long term exposure to individual toxic metals in low doses are well documented. There is however, a paucity of information on interaction of low dose toxic metal mixtures with toxic and essential metals. This study reports on interactions between low dose mixtures of lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd) and toxic and essential metals. For 120d, six groups of forty mice each were exposed to metal mixtures, however, the control group was given distilled water. Exposure to Pb+Cd increased brain Pb by 479% in 30d, whiles Pb+Hg+As+Cd reduced liver Hg by 46.5%, but increased kidney As by 130% in 30d. Brain Cu, increased by 221% on Pb+Hg+As+Cd exposure, however, liver Ca reduced by 36.1% on Pb+Hg exposure in 60-d. Interactions within metal mixtures were largely synergistic. Principal component analysis (PCA) showed that low dose metal exposures influenced greatly levels of Hg (in brain and liver) and As (brain). The influence exerted on essential metals was highest in liver (PC1) followed by kidney (PC2) and brain (PC3). Exposure to low dose metal mixtures affected homeostasis of toxic and essential metals in tissues of mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Combination of 24-Hour and 7-Day Relative Neurological Improvement Strongly Predicts 90-Day Functional Outcome of Endovascular Stroke Therapy.

    Science.gov (United States)

    Pu, Jie; Wang, Huaiming; Tu, Mingyi; Zi, Wenjie; Hao, Yonggang; Yang, Dong; Liu, Wenhua; Wan, Yue; Geng, Yu; Lin, Min; Jin, Ping; Xiong, Yunyun; Xu, Gelin; Yin, Qin; Liu, Xinfeng

    2018-01-03

    Early judgment of long-term prognosis is the key to making medical decisions in acute anterior circulation large-vessel occlusion stroke (LVOS) after endovascular treatment (EVT). We aimed to investigate the relationship between the combination of 24-hour and 7-day relative neurological improvement (RNI) and 90-day functional outcome. We selected the target population from a multicenter ischemic stroke registry. The National Institutes of Health Stroke Scale (NIHSS) scores at baseline, 24 hours, and 7 days were collected. RNI was calculated by the following equation: (baseline NIHSS - 24-hour/7-day NIHSS)/baseline NIHSS × 100%. A modified Rankin Scale score of 0-2 at 90 days was defined as a favorable outcome. Multivariable logistic regression analysis was used to evaluate the relationship between RNI and 90-day outcome. Receiver operator characteristic curve analysis was performed to identify the predictive power and cutoff point of RNI for functional outcome. A total of 568 patients were enrolled. Both 24-hour and 7-day RNI were independent predictors of 90-day outcome. The best cutoff points of 24-hour and 7-day RNI were 28% and 42%, respectively. Compared with those with 24-hour RNI of less than 28% and 7-day RNI of less than 42%, patients with 24-hour RNI of 28% or greater and 7-day RNI of 42% or greater had a 39.595-fold (95% confidence interval 22.388-70.026) increased probability of achieving 90-day favorable outcome. The combination of 24-hour and 7-day RNI very strongly predicts 90-day functional outcome in patients with acute anterior circulation LVOS who received EVT, and it can be used as an early accurate surrogate of long-term outcome. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

    Science.gov (United States)

    Knudsen, Ib; Poulsen, Morten

    2007-10-01

    This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the

  18. 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

  19. 77 FR 39666 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Maytenus cymosa

    Science.gov (United States)

    2012-07-05

    ... the species may meet the definition of threatened or endangered under the Act. In making this 90-day... access to Pi[ntilde]eros Island while protecting the ecology of the island by disturbing only a small... information regarding the ecology or reproductive biology of M. cymosa (e.g., lack of pollinators and/or fruit...

  20. 75 FR 13717 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Southern...

    Science.gov (United States)

    2010-03-23

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... Endangered and Threatened Wildlife and Plants. A species may be determined to be an endangered or threatened... references on impacts of sand and gravel mining to freshwater mussels and other invertebrates (e.g., Wild...

  1. Patient journey after admission for acute heart failure : length of stay, 30-day readmission and 90-day mortality

    NARCIS (Netherlands)

    Davison, Beth A.; Metra, Marco; Senger, Stefanie; Edwards, Christopher; Milo, Olga; Bloomfield, Daniel M.; Cleland, John G.; Dittrich, Howard C.; Givertz, Michael M.; O'Connor, Christopher M.; Massie, Barry M.; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; Cotter, Gad

    AimsThe course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled

  2. 76 FR 55638 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Snowy...

    Science.gov (United States)

    2011-09-08

    ... on a Petition To List the Snowy Plover and Reclassify the Wintering Population of Piping Plover... U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the snowy... becomes available concerning the status of, or threats to, the snowy plover or the piping plover or their...

  3. 75 FR 13441 - Hours of Service; Limited 90-Day Waiver for the Distribution of Anhydrous Ammonia in Agricultural...

    Science.gov (United States)

    2010-03-22

    ... Federal Motor Carrier Safety Administration 49 CFR Part 395 Hours of Service; Limited 90-Day Waiver for... Federal hours- of-service (HOS) regulations for the transportation of anhydrous ammonia from any... ultimate consumer, as long as the transportation takes place within a 100 air- mile radius of the retail or...

  4. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study

    DEFF Research Database (Denmark)

    Varis, Elina; Pettilä, Ville; Poukkanen, Meri

    2017-01-01

    Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock...... surrogate endpoints for mortality in septic shock patients....

  5. Risk of Subsequent Sepsis within 90 Days of a Previous Hospital Stay by Type of Antibiotic Exposure.

    Science.gov (United States)

    Baggs, James; Jernigan, Johm A; Halpin, Alison Laufer; Epstein, Lauren H; Hatfield, Kelly M; McDonald, L Clifford

    2017-11-09

    We examined the risk of sepsis within 90 days after discharge from a previous hospital stay by type of antibiotic received during the previous stay. We retrospectively identified a cohort of hospitalized patients from the Truven Health MarketScan Hospital Drug Database. We examined the association between the use of certain antibiotics, determined a priori, during the initial hospital stay and risk of post-discharge sepsis controlling for potential confounding factors in a multivariable logistic regression model. Our primary exposure was receipt of antibiotics more strongly associated with clinically important microbiome disruption. Our primary outcome was a hospital stay within 90 days of the index stay that included an ICD-9-CM discharge diagnosis of severe sepsis (995.92) or septic shock (785.52). Among 516 hospitals, we randomly selected a single stay for eligible patients. Of those, 0.17% developed severe sepsis/septic shock within 90 days after discharge. The risk of sepsis associated with exposure to our high risk antibiotics was 65% higher compared to those without antibiotic exposure. Our study identified an increased risk of sepsis within 90 days of discharge among patients with exposure to high risk or increased quantities of antibiotics during hospitalization. Given a significant proportion of inpatient antimicrobial use may be unnecessary, this study builds on previous evidence suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, CDI and other adverse effects, but also reduce unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

  6. 78 FR 29100 - Endangered and Threatened Wildlife; 90-Day Finding on Petitions To List the Dusky Shark as...

    Science.gov (United States)

    2013-05-17

    ... Threatened Wildlife; 90-Day Finding on Petitions To List the Dusky Shark as Threatened or Endangered Under... shark (Carcharhinus obscurus) range-wide or, in the alternative, the Northwest Atlantic and Gulf of Mexico population of the dusky shark as a threatened or endangered distinct population segment (DPS...

  7. 75 FR 22063 - Endangered and Threatened Wildlife and Plants; 90-day Finding on a Petition to List the Mohave...

    Science.gov (United States)

    2010-04-27

    ... squirrel was found to consume leaves of annual and perennial plants, their fruits and seeds, fungi, and... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-day Finding... squirrels must mate, gather enough nutrition to produce and sustain a litter, and ensure nutritional...

  8. 75 FR 52928 - Endangered and Threatened Wildlife and Plants; Notice of 90-Day Finding for a Petition to List...

    Science.gov (United States)

    2010-08-30

    ...; Notice of 90-Day Finding for a Petition to List Georgia Basin Populations of China Rockfish and Tiger Rockfish as Endangered or Threatened AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...) received a petition to list Georgia Basin populations of China rockfish (Sebastes nebulosus) and tiger...

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Arquimedes Fernandes Monteiro de Melo

    2006-01-01

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

  12. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    Science.gov (United States)

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.

  13. Safety evaluation of AB-LIFE(®) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats.

    Science.gov (United States)

    Mukerji, Pushkor; Roper, Jason M; Stahl, Buffy; Smith, Amy B; Burns, Frank; Rae, Jessica Caverly; Yeung, Nicolas; Lyra, Anna; Svärd, Laura; Saarinen, Markku T; Alhoniemi, Esa; Ibarra, Alvin; Ouwehand, Arthur C

    2016-06-01

    AB-LIFE(®) is a probiotic product consisting of equal parts of three strains of Lactobacillus plantarum (CECT 7527, 7528, and 7529) blended with inert excipients. Whole genome sequencing was performed on each of the three strains. Antibiotic resistance was evaluated by genomic mining for resistance genes, and assessment for transferability. No risk of transfer potential was identified for any antibiotic resistance genes in the three strains. AB-LIFE(®) was evaluated for potential subchronic oral toxicity in rats, with dosages of 300 and 1000 mg/kg BW/day (equivalent to 5.55 × 10(10) and 1.85 × 10(11) CFU/kg BW/day). Survival of the three test strains through the gastrointestinal tract was supported by fecal analysis. No adverse effects were identified with respect to in-life parameters, clinical or anatomic pathology, translocation, or fecal chemical analyses. The no-observed-adverse-effect level (NOAEL) for AB-LIFE(®) in male and female rats was 1000 mg/kg BW/day (1.85 × 10(11) CFU of AB-LIFE(®)/kg BW/day), the highest dose level evaluated. These results, in conjunction with a previous acute toxicity study in rats, support the conclusion that AB-LIFE(®) is safe for human consumption. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2006-07-01

    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 physiological saline and the three test groups received daily doses of 200, 600 and 2000 mg of rhLF per kg body weight. Clinical observations, growth, food consumption, food conversion efficiency, water consumption, neurobehavioural testing, ophthalmoscopy, haematology, clinical chemistry, renal concentration test, urinalysis, organ weights and gross examination at necropsy and microscopic examination of various organs and tissues were used as criteria for detecting the effects of treatment. Overall, no treatment-related, toxicologically significant changes were observed. The few findings that may be related to the treatment (lower cholesterol in high-dose females, lower urinary pH in high-dose males and females and very slightly higher kidney weight in high-dose females) were considered of no toxicological significance. Based on the absence of treatment-related, toxicologically relevant changes, the no-observed-adverse-effect level (NOAEL) was considered to be at least 2000 mg/kg body weight/day.

  15. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content--a 90-day feeding study in the Syrian Golden hamster.

    Science.gov (United States)

    Langkilde, Søren; Schrøder, Malene; Frank, Thomas; Shepherd, Louise V T; Conner, Sean; Davies, Howard V; Meyer, Otto; Danier, Jürgen; Rychlik, Michael; Belknap, William R; McCue, Kent F; Engel, Karl-Heinz; Stewart, Derek; Knudsen, Ib; Poulsen, Morten

    2012-10-01

    Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore depend on their ratio in the potato. To determine the influence of α-solanine: α-chaconine ratio in potatoes on toxicity, a GM potato line (SGT 9-2) with reduced α-solanine content, and the parental control line (Desirée wild-type) having a traditional α-solanine: α-chaconine ratio were (1) studied for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional differences between the GM line and its wildtype control these did not raise concerns related to nutritional value or safety. Results of the feeding trials showed a low number of significant differences between potato lines with different α-solanine: α-chaconine ratio but none were considered to raise safety concerns with regard to human (or animal) consumption. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Toxicological evaluation of subchronic use of pioglitazone in mice

    OpenAIRE

    Said Said Elshama; Ayman El-Meghawry El-Kenawy; Hosam-Eldin Hussein Osman

    2016-01-01

    Objective(s): Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects. This study investigates sub-chronic use of pioglitazone induced toxicity in mice by the...

  17. The Effects of Subchronic Exposure to Metribuzin on Danio rerio

    OpenAIRE

    Lucie Plhalova; Stanislava Stepanova; Eva Praskova; Lucie Chromcova; Lenka Zelnickova; Lenka Divisova; Misa Skoric; Vladimira Pistekova; Iveta Bedanova; Zdenka Svobodova

    2012-01-01

    The aim of this study was to assess the impact of metribuzin in surface waters on fish under experimental conditions. The effects of subchronic exposure to metribuzin on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver) and on activity of some biochemical markers (CYP450, EROD) in Danio rerio were investigated during a 28-day toxicity test. Juvenile growth tests were performed on D. rerio according to OECD method number 215. Fish at an initi...

  18. First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

    Science.gov (United States)

    Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

    2015-01-01

    Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

  19. The impact of hepatitis C virus infection on 90-day outcomes following major orthopaedic surgery: a propensity-matched analysis.

    Science.gov (United States)

    Chowdhury, Ritam; Chaudhary, Muhammad Ali; Sturgeon, Daniel J; Jiang, Wei; Yau, Allan L; Koehlmoos, Tracey P; Haider, Adil H; Schoenfeld, Andrew J

    2017-09-01

    The impact of hepatitis C virus (HCV) infection on outcomes following major orthopaedic interventions, such as joint arthroplasty or spine surgery, has not been effectively studied in the past. Most prior studies are impaired by small samples, limited surveillance for adverse events, or the potential for selection bias to confound results. In this context, we sought to evaluate the impact of HCV infection on 90-day outcomes following joint arthroplasty or spine surgery using propensity-matched techniques. This study utilized 2006-2014 claims from TRICARE insurance. Adults who received spine surgical procedures, total knee and hip arthroplasty were identified. Covariates included demographic factors, a diagnosis of HCV and medical co-morbidities defined by International Classification of Disease-9th revision (ICD-9) code. Outcomes consisted of 30- and 90-day mortality, complications and readmission. A propensity score was used to balance the cohorts with logistic regression techniques employed to determine the influence of HCV infection on post-operative outcomes. The propensity-matched cohort consisted of 2262 patients (1131 with and without HCV). Following logistic regression, patients with HCV were found to have increased odds of 30-day complications (OR 1.87; 95% CI 1.33, 2.64; p < 0.001), 90-day complications (OR 1.55; 95% CI 1.16, 2.08; p = 0.003) and 30-day readmission (OR 1.46; 95% CI 1.04, 2.05; p = 0.03). HCV infection was found to increase the risk of complication and readmission following spine surgery and total joint arthroplasty. Patients should be counseled on their increased risk prior to surgery. Health systems that treat a higher percentage of patients with HCV need to consider the increased risk of complications and readmission when negotiating with insurance carriers.

  20. Patient journey after admission for acute heart failure: length of stay, 30-day readmission and 90-day mortality

    OpenAIRE

    Davison, Beth A.; Metra, Marco; Senger, Stefanie; Edwards, Christopher; Milo, Olga; Bloomfield, Daniel M.; Cleland, John G. F.; Dittrich, Howard C.; Givertz, Michael M.; O'Connor, Christopher M.; Massie, Barry M.; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; Cotter, Gad

    2016-01-01

    Aims: \\ud \\ud The course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled in the PROTECT study.\\ud Methods and results: \\ud \\ud PROTECT was a randomized study that examined the effect of the adenosine blocker rolofylline in patients within 24 h of admission for ...

  1. Prediction of 90 Day and Overall Survival after Chemoradiotherapy for Lung Cancer: Role of Performance Status and Body Composition.

    Science.gov (United States)

    Bowden, J C S; Williams, L J; Simms, A; Price, A; Campbell, S; Fallon, M T; Fearon, K C H

    2017-09-01

    If appropriate patients are to be selected for lung cancer treatment, an understanding of who is most at risk of adverse outcomes after treatment is needed. The aim of the present study was to identify predictive factors for 30 and 90 day mortality after chemoradiotherapy (CRT), and factors that were prognostic for overall survival. A retrospective cohort study of 194 patients with lung cancer who had undergone CRT in South East Scotland from 2008 to 2010 was undertaken. Gender, age, cancer characteristics, weight loss, body mass index (BMI), performance status (Eastern Cooperative Oncology Group; ECOG) and computed tomography-derived body composition variables were examined for prognostic significance using Cox's proportional hazards model and logistic regression. The median overall survival was 19 months (95% confidence interval 16.3, 21.7). Four of 194 patients died within 30 days of treatment completion, for which there were no independent predictive variables; 22/194 (11%) died within 90 days of treatment completion. BMI performance status ≥2 were independent predictors of death within 90 days of treatment completion (P = 0.001 and P = 0.004, respectively). Patients with either BMI performance status ≥ 2 had an odds ratio of death within 90 days of 5.97 (95% confidence interval 2.20, 16.19), rising to an odds ratio of 13.27 (1.70, 103.47) for patients with both BMI performance status ≥ 2. Patients with low muscle attenuation had significantly reduced overall survival (P = 0.004); individuals with low muscle attenuation had a median survival of 15.2 months (95% confidence interval 12.7, 17.7) compared with 23.0 months (95% confidence interval 18.3, 27.8) for those with high muscle attenuation, equating to a hazard ratio of death of 1.62 (95% confidence interval 1.17, 2.23, P = 0.003). Poor performance status, low BMI and low muscle attenuation identify patients at increased risk of premature death after CRT. Risk factors for adverse outcomes

  2. Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system in male rats.

    Science.gov (United States)

    Wang, Er Hui; Yu, Zhou; Hu, Jing; Xu, Hai Bin

    2013-12-01

    Rice is a staple food crop; however, the threat of pests leads to a serious decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice MingHui63 to produce insect-resistant rice TT51. This study was undertaken to investigate potential unintended effects of TT51 on the reproductive system in male rats. Male rats were treated with diets containing 60% of either TT51 or MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An additional negative control group of rats were fed with a rice-based AIN93G diet. Body weights, food intake, hematology, serum chemistry, serum hormone levels, sperm parameters and relative organ/body weights were measured, and gross as well as microscopic pathology were examined. No diet-related significant differences in the values of response variables were observed between rats that were fed with diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding study. In addition, necropsy and histopathology examination indicated no treatment-related changes. The results from the present study indicated that TT51 does not appear to exert any effect on the reproductive system in male rats compared with MingHui63 or the control. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The development and succession of microbial communities in 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    Science.gov (United States)

    Sun, Yi; Liu, Hong; Fu, Yuming; Liu, Bojie; Su, Qiang; Xie, Beizhen; Qin, Youcai; Dong, Chen; Liu, Guanghui

    Lunar Palace 1, as an integrative experiment facility for permanent astrobase life-support artificial closed ecosystem, is an artificial ecosystem which consists of plant cultivation, animal breeding and waste treatment units. It has been used to carry out a 90-day bioregenerative life support experiment with three crew members. Apparently, it’s hard to prevent the growth of microorganisms in such closed ecosystem for their strong adaptive capacity. Original microorganisms in the cabin, microbes in the course of loads delivery and the autologous microorganism by crew members and animals themselves are all the main source of the interior microorganisms, which may grow and regenerate in air, water and plants. Therefore, if these microorganisms could not be effectively monitored and controlled, it may cause microbial contamination and even lead to the unsteadiness of the whole closed ecosystem. In this study, the development and succession of the microbial communities of air, water system, plant system, and key facilities surfaces in Lunar Palace 1 were continuously monitored and analyzed by using plate counting method and molecular biological method during the 90-day experiment. The results were quite useful for the controlling of internal microorganisms and the safe operation of the whole system, and could also reveal the succession rules of microorganisms in an artificial closed ecosystem.

  4. Relationship between Activities of Daily Living and Readmission within 90 Days in Hospitalized Elderly Patients with Heart Failure

    Directory of Open Access Journals (Sweden)

    Masahiro Kitamura

    2017-01-01

    Full Text Available Aims. To examine the relationship between activities of daily living (ADL and readmission within 90 days and assess the cutoff value of ADL to predict readmission in hospitalized elderly patients with heart failure (HF. Methods. This cohort study comprised 589 consecutive patients with HF aged ≥65 years, who underwent cardiac rehabilitation from May 2012 to May 2016 and were discharged home. We investigated patients’ characteristics, basic attributes, and ADL (motor and cognitive Functional Independence Measure [FIM]. We analyzed the data using the unpaired t-test, χ2 test, Cox proportional hazard model, receiver operating characteristic (ROC curve, and Kaplan-Meier method. Results. Of 589 patients, 113 met the criteria, and they were divided into the nonreadmission (n=90 and readmission groups (n=23. Age, body mass index, New York Heart Association class, hemoglobin level, and motor FIM score were significantly different between the two groups (p<0.05. The body mass index (hazard ratio [HR]: 0.87; p<0.05 and motor FIM score (HR: 0.94; p<0.01 remained statistically significant. The cutoff value for the motor FIM score determined by ROC curve analysis was 74.5 points (area under the curve = 0.78; p<0.001. Conclusion. The motor FIM score in elderly patients with HF was an independent predictor of rehospitalization within 90 days.

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

    African Journals Online (AJOL)

    Administrator

    contained 3.31% dry weight (DW) crude protein and 90.35% DW available carbohydrate (Hassan, et al., 2010). ... such as cardiovascular disease and cancer, they also contain other compounds that may lead to ... was expressed as LD50 and calculated using the limit test dose, up and down procedure of Organization for ...

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

    African Journals Online (AJOL)

    Administrator

    1Department of Pure and Applied Chemistry,. 2Department of ... Therefore, this paper reports the evaluation of the safety of seed kernel extract of the .... signs of renal failure (Hassan et al., 2005). ... Medical laboratory manual for tropical countries. ... February, 2011 from www.oecd.org/dataoecd/17/51/1948378.pdf. Ojewole ...

  7. Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    Science.gov (United States)

    Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

    A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

  8. A 90-day safety study in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA)

    DEFF Research Database (Denmark)

    Poulsen, Morten; Kroghsbo, Stine; Schrøder, Malene

    2007-01-01

    Genetically modified plants expressing insecticidal traits offer a new strategy for crop protection, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of a rice variety expressing the snowdrop Galanthus...... nivalis lectin (GNA lectin), and forms part of a EU-funded project where the objective has been to develop and validate sensitive and specific methods to assess the safety of genetically modified foods. Mate and female Wistar rats were given a purified diet containing either 60% genetically modified...... diets, but none of them were considered to be adverse. In conclusion, the design of the present animal study did not enable us to conclude on the safety of the GM food. Additional group(s) where the expressed gene products have been spiked to the diet should be included in order to be able...

  9. Patient journey after admission for acute heart failure: length of stay, 30-day readmission and 90-day mortality.

    Science.gov (United States)

    Davison, Beth A; Metra, Marco; Senger, Stefanie; Edwards, Christopher; Milo, Olga; Bloomfield, Daniel M; Cleland, John G; Dittrich, Howard C; Givertz, Michael M; O'Connor, Christopher M; Massie, Barry M; Ponikowski, Piotr; Teerlink, John R; Voors, Adriaan A; Cotter, Gad

    2016-08-01

    The course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled in the PROTECT study. PROTECT was a randomized study that examined the effect of the adenosine blocker rolofylline in patients within 24 h of admission for AHF with mild to moderate renal impairment. Geographic-region-adjusted multivariable models showed that LOS was only partly explained by the severity of heart failure (HF), comorbidities (diabetes mellitus, renal impairment, ischaemic heart disease) and degree of metabolic dysfunction (cholesterol and albumin) at baseline (adjusted R(2) 0.27). Addition of in-hospital worsening heart failure (WHF) and changes in metabolic markers contributed significantly to prediction of LOS [R(2) difference 0.050, 95% confidence interval (CI) 0.0282-0.072]. Thirty-day HF readmission was associated with more severe HF and previous HF admission but not with LOS (odds ratios 1.00, 95% CI 0.97-1.04). Death within 90 days after discharge was associated with older age, more severe HF, worse renal function, and lower sodium and bicarbonate at admission; LOS was a strong predictor of 90-day post-discharge mortality. In patients admitted for AHF, LOS is not well-predicted by traditional markers of disease severity, but strongly associated with the occurrence of in-hospital WHF. Longer LOS is a strong predictor of early mortality after discharge but not of readmission. These findings may help focus efforts to reduce LOS and post-discharge outcomes on patients' subgroups at increased risk. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  10. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Hai Bai

    Full Text Available Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1 were confirmed using the polymerase chain reaction (PCR and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt of GM sheep meat, WT sheep meat or a commercial diet (CD. Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals.

  11. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    Science.gov (United States)

    Bai, Hai; Wang, Zhixian; Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals.

  12. A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

    Science.gov (United States)

    Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

  13. The safety of PolyGlycopleX® (PGX® as shown in a 90-day rodent feeding study

    Directory of Open Access Journals (Sweden)

    Ann Marone Palma

    2009-01-01

    Full Text Available Abstract Background This study was designed to evaluate the safety of PolyGlycopleX® (PGX®, a novel viscous dietary polysaccharide (fiber, when administered to Sprague Dawley® rats in the diet for 90 days. Methods Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology. Results Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females and protein concentration (females. These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse. Conclusion The results indicate a no observed adverse effect level (NOAEL for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.

  14. Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: a biochemical and histopathological study in male rats.

    Science.gov (United States)

    Jadhav, S H; Sarkar, S N; Patil, R D; Tripathi, H C

    2007-11-01

    In the current study, we examined whether subchronic exposure via drinking water to low doses of a mixture of metals (arsenic, cadmium, lead, mercury, chromium, manganese, iron, and nickel), found as contaminants in various water sources of India, and to concentrations equivalent to WHO maximum permissible limits (MPL) in drinking water for individual metals, can alter systemic physiology of male rats. Data on water contamination with metals in India were collected from the literature and metals were selected on the basis of their frequency of occurrence and contamination level above MPL. Male Wistar rats were exposed to the mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals via drinking water for 90 days. One more group of rats was exposed to the mixture at a concentration equivalent to the MPL (WHO) in drinking water for individual metals. Toxic potential of the mixture was evaluated by assessing general toxicological end points, serum chemistry and histopathology of vital organs. The mixture decreased body weight and water consumption and increased weights of brain, liver, and kidneys with 10x and 100x doses. After 30 days of exposure, no appreciable changes were found in any blood clinical markers. After 60 days, only the 100x dose, while after 90 days both 10x and 100x doses increased activities of aspartate aminotransferase and alkaline phosphatase and levels of urea nitrogen and creatinine and decreased total protein and albumin levels, but alanine aminotransferase activity and glucose level were not affected. At 10x and 100x exposure levels, qualitatively similar, but dose-dependent vascular, degenerative, and necrotic changes were observed in brain, liver, and kidney. The results indicate that subchronic exposure to the metal mixture affected general health of male rats by altering the functional and structural integrity of kidney, liver, and brain at 10 and 100 times the mode

  15. Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863).

    Science.gov (United States)

    Doull, J; Gaylor, D; Greim, H A; Lovell, D P; Lynch, B; Munro, I C

    2007-11-01

    MON 863, a genetically engineered corn variety that contains the gene for modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm, was tested in a 90-day toxicity study as part of the process to gain regulatory approval. This study was reanalyzed by Séralini et al. who contended that the study showed possible hepatorenal effects of MON 863. An Expert Panel was convened to assess the original study results as analyzed by the Monsanto Company and the reanalysis conducted by Séralini et al. The Expert Panel concludes that the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was associated with adverse effects in the 90-day rat study. In each case, statistical findings reported by both Monsanto and Séralini et al. were considered to be unrelated to treatment or of no biological or clinical importance because they failed to demonstrate a dose-response relationship, reproducibility over time, association with other relevant changes (e.g., histopathology), occurrence in both sexes, difference outside the normal range of variation, or biological plausibility with respect to cause-and-effect. The Séralini et al. reanalysis does not advance any new scientific data to indicate that MON 863 caused adverse effects in the 90-day rat study.

  16. 76 FR 46238 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Straight...

    Science.gov (United States)

    2011-08-02

    ... documented to be toxic to other aquatic insects (Kegley et al. in litt. 2009a, pp. 2-3). Trifluralin, an... state that diazinon and carbaryl are highly toxic to stoneflies (Petition, p. 13; Kegley et al. in litt... can lead to excess algae growth, can cause oxygen depletion due to the growth and decomposition cycle...

  17. Seventeen Ketogenic steroids excretion in crewmen in a 90-day manned test of an advanced regenerative life support system

    Science.gov (United States)

    Myers, D. J.; Wamsley, J. R.

    1972-01-01

    Seventeen KGS (17-Ketogenic steroids) and Na/K were determined in 19 urine specimens collected by each of 4 crewmen during the 90-day test. The specimens represented 10% aliquots of 24-hour collections stored frozen onboard the simulator until passthrough. Electrolytes were analyzed immediately after sample passthrough while the steroids were determined post-test on aliquots of the original sample held at 203 K. Steroid data was corrected for body weight and also for analytical variation in the laboratory urine pool control. Long-term nonspecific responses to low-level stress appear to be reflected by the individual and group mean 17-KGS excretion patterns. The first 39 and the last 20 days of the test were significantly different--and presumably more stressful to the crew--than the period from days 39 to 67. Reduction of adrenocortical function during the mid-test phase is attributed to either an adaptation to chronic or intermittent stress or was the result of an actual reduction in the operational demands of the test during this time. Most remarkable of the metabolic findings is the prevalance of high Na/K ratios and an abrupt peak on day 74 for all 4 crewmen.

  18. A 90-day dietary study of a (2R,4R)-monatin salt in Beagle dogs.

    Science.gov (United States)

    Crincoli, Christine M; Brathwaite, Witty A; Rihner, Marisa O; Nikiforov, Andrey I; Harris, Stephen B; Greeley, Melanie A; Eapen, Alex K

    2016-05-01

    (2R,4R)-Monatin salt (Na/K) [sodium/potassium (2R,4R)-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate, hereafter "R,R-monatin"] was administered in the diets of groups of Beagle dogs (4/sex/group) at concentrations of 0 (basal diet), 5000, 20,000, or 35,000 ppm for 13 weeks. There were no effects on survival, clinical observations, body weight and body weight gain, feed consumption and feed efficiency, functional observational battery, ophthalmic examination, and electrocardiographic evaluation. No adverse effects on hematology, serum chemistry, and urinalysis parameters were reported. A statistically significant decrease in testicular weights associated with germ cell hypocellularity and reduced luminal sperm in the epididymides was reported in all treated male groups. Based on these findings, the dietary no-observed-adverse-effect level (NOAEL) of R,R-monatin for 90 days was considered 35,000 ppm for female dogs (approximately 1101 mg/kg bw/day) and <5000 ppm for male dogs (approximately <151 mg/kg bw/day). Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Quality Assurance Audit of Technique Failure and 90-Day Mortality after Program Discharge in a Canadian Home Hemodialysis Program.

    Science.gov (United States)

    Shah, Nikhil; Reintjes, Frances; Courtney, Mark; Klarenbach, Scott W; Ye, Feng; Schick-Makaroff, Kara; Jindal, Kailash; Pauly, Robert P

    2017-07-24

    Little is known about patients exiting home hemodialysis. We sought to characterize the reasons, clinical characteristics, and pre-exit health care team interactions of patients on home hemodialysis who died or underwent modality conversion (negative disposition) compared with prevalent patients and those who were transplanted (positive disposition). We conducted an audit of all consecutive patients incident to home hemodialysis from January of 2010 to December of 2014 as part of ongoing quality assurance. Records were reviewed for the 6 months before exit, and vital statistics were assessed up to 90 days postexit. Ninety-four patients completed training; 25 (27%) received a transplant, 11 (12%) died, and 23 (25%) were transferred to in-center hemodialysis. Compared with the positive disposition group, patients in the negative disposition group had a longer mean dialysis vintage (3.15 [SD=4.98] versus 1.06 [SD=1.16] years; P=0.003) and were performing conventional versus a more intensive hemodialysis prescription (23 of 34 versus 23 of 60; Pday mortality among patients undergoing modality conversion was 26%. Over a 6-year period, approximately one third of patients exited the program due to death or modality conversion. Patients who die or transfer to another modality have significantly higher health care resource utilization (e.g., hospitalization, respite treatments, nursing time, etc.). Copyright © 2017 by the American Society of Nephrology.

  20. A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley rats.

    Science.gov (United States)

    Zhou, Xing Hua; Dong, Ying; Xiao, Xiang; Wang, Yun; Xu, Yong; Xu, Bin; Shi, Wei Dong; Zhang, Yi; Zhu, Li Jia; Liu, Qiao Quan

    2011-12-01

    A transgenic rice line (TRS) with high amylose level has been developed by antisense RNA inhibition of starch branching enzymes. Compositional analysis of TRS demonstrated that the content of resistant starch (RS) was significantly higher compared to conventional non-transgenic rice. High level of RS is an important raw material in food industry and has various physiological effects for human health. In order to provide the reliable theory basis for field release of TRS rice, we evaluated the potential health effects of long-term consumption of the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley rats fed with diets containing 70% of either TRS rice flour, its near-isogenic rice flour or the control diet. The clinical performance variables (body weight, body weight gain and food consumption) were measured and pathological responses (hematological parameters and serum chemistry at the midterm and the completion of the experiment, urinalysis profile and serum sex hormone response at the completion of the experiment) were performed. Besides, clinical signs, relative organ weights and microscopic observations were also compared between TRS group and its near-isogenic rice group. The combined data indicates that high-amylose TRS grain is as safe as the conventional non-transgenic rice for rat consumption. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  1. High-intensity flywheel exercise and recovery of atrophy after 90 days bed-­rest­

    Science.gov (United States)

    Ohshima, Hiroshi; Rittweger, Jörn; Felsenberg, Dieter

    2017-01-01

    Aims To investigate differential muscle atrophy during bed-rest, the impact of a high-intensity concentric-eccentric (flywheel) resistance exercise countermeasure and muscle recovery after bed-rest. Methods Twenty-five healthy male subjects underwent 90 dayshead-down tilt bed-rest. Volume of individual lower-limb muscles was measured via MRI before, twice during and four times up to 1 year after bed-rest. Subjects were either inactive (n=16) or performed flywheel exercise every third day of bed-rest (n=9). Functional performance was assessed via countermovement jump. Results On ‘intent-to-treat’ analysis, flywheel prevented atrophy in the vasti (pFlywheel exercise was not effective for the hamstrings, gracilis, sartorius, peroneals and anterior tibial muscles. Muscle atrophy in vasti, soleus, gastrocnemius medialis, gastrocnemius lateralis and adductor magnus correlated with losses in countermovement jump performance. Muscle volume recovered within 90 days after bed-rest, however long-term after bed-rest, the inactive subjects only showed significantly increased muscle volume versus prebed-rest in a number of muscles including soleus (+4.3%), gastrocnemius medialis (+3.9%) and semimembranosus (+4.3%). This was not associated with greater countermovement jump performance. Conclusion The exercise countermeasure was effective in preventing or reducing atrophy in the vasti, adductor magnus and ankle dorsiflexors/toe flexors but not the hamstrings, medial thigh muscles or peroneals and dorsiflexor muscles. Trial registration number NCT00311571; results. PMID:28761699

  2. Safety assessment of genetically modified milk containing human beta-defensin-3 on rats by a 90-day feeding study.

    Science.gov (United States)

    Chen, Xin; Gao, Ming-Qing; Liang, Dong; Yin, Songna; Yao, Kezhen; Zhang, Yong

    2017-02-01

    In recent years, transgenic technology has been widely applied in many fields. There is concern about the safety of genetically modified (GM) products with the increased prevalence of GM products. In order to prevent mastitis in dairy cows, our group produced transgenic cattle expressing human beta-defensin-3 (HBD3) in their mammary glands, which confers resistance to the bacteria that cause mastitis. The milk derived from these transgenic cattle thus contained HBD3. The objective of the present study was to analyze the nutritional composition of HBD3 milk and conduct a 90-day feeding study on rats. Rats were divided into 5 groups which consumed either an AIN93G diet (growth purified diet for rodents recommended by the American Institute of Nutrition) with the addition of 10% or 30% HBD3 milk, an AIN93G diet with the addition of 10% or 30% conventional milk, or an AIN93G diet alone. The results showed that there was no difference in the nutritional composition of HBD3 and conventional milk. Furthermore, body weight, food consumption, blood biochemistry, relative organ weight, and histopathology were normal in those rats that consumed diets containing HBD3. No adverse effects were observed between groups that could be attributed to varying diets or gender. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Ninety day toxicity study of chloroacetic acids in rats.

    Science.gov (United States)

    Bhat, H K; Kanz, M F; Campbell, G A; Ansari, G A

    1991-08-01

    Chloroacetic acids are produced in drinking water as a result of disinfection processes. Chloroacetic acids are also metabolites of widely used and toxic halogenated hydrocarbons. Thus, chronic human exposure to these chemicals is likely to occur. The objective of the present study was to examine the toxic effects of monochloroacetic acid (MCA), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) in a 90-day subchronic study in rats via oral exposure by drinking water. Chloroacetic acid solutions were prepared at concentrations which provided an approximate intake of 1/4 the LD50 dose per day: MCA, 1.9 mM; DCA, 80.5 mM; TCA, 45.8 mM. Control rats received distilled water only. After 90 days, major organs were removed, fixed, paraffin embedded, and stained. Light microscopic examination of the major organs revealed variable degrees of alterations in the lung and liver of all three treated groups. In the liver, morphological changes were predominantly localized to the portal triads, which were mildly to moderately enlarged with random bile duct proliferation, extension of portal veins, fibrosis, edema, and occasional foci of inflammation. In the lungs, minimal alterations were observed as foci of perivascular inflammation on small pulmonary veins. Morphological changes in the testes and brain were seen only in the DCA treated group. Testes were atrophic with few spermatocytes and no mature spermatozoa. Focal vacuolation and gliosis were present in the forebrain and brainstem. The results of these studies indicate that, relative to their respective LD50 values, DCA given at 80.5 mM is more toxic than TCA given at 45.8 mM and MCA at 1.9 mM is least toxic.

  4. Assessment of acute and subchronic oral toxicity of ethanolic extract of Pothomorphe umbellata L. Miq (Pariparoba Avaliação da toxidade oral aguda e subcrônica de extrato etanólico de Pothomorphe umbellata L. Miq. (Parapiroba

    Directory of Open Access Journals (Sweden)

    Sonia Barros

    2005-03-01

    Full Text Available There is a high degree of concern regarding the secure use of plant extracts and, for this very reason, preclinical and clinic toxicological evaluation of these extracts are needed. With the aim to assure the quality and the safety of the extract and due to the scarcity of literature information about Pariparoba extract toxicity, our purpose was to investigate the acute and subchronic toxicity of the standardized ethanolic dried root extract of Pothomorphe umbellata L. Miq. This extract was administered orally to adult swiss mice and wistar rats and the mutagenic potencial of the extract was also evaluated. The extract showed to be non toxic.Existe uma grande preocupação quanto ao uso seguro de extratos vegetais e, por esta razão, a necessidade de estudos toxicológicos pré-clínicos e clínicos destes extratos. O objetivo deste trabalho foi o de avaliar a toxicidade aguda e subcrônica do extrato hidroalcoólico liofilizado de Pothomorphe umbellata L. Miq., administrado por via oral para animais de laboratório. O potencial mutagênico do extrato foi também avaliado pelo teste do micronúcleo. Os resultados dos estudos a curto e médio prazo demonstraram que o extrato não apresenta propriedades tóxicas.

  5. First report of 90-day support of 2 calves with a continuous-flow total artificial heart.

    Science.gov (United States)

    Karimov, Jamshid H; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A R; Fukamachi, Kiyotaka

    2015-09-01

    The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. CFTAH pumps have been implanted in 17 calves total. Hemodynamic parameters, pump performance, and device-related adverse events were evaluated during studies and at necropsy. In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure, 16 ± 3 mm Hg; right atrial pressure, 17 ± 3 mm Hg; right atrial pressure-left atrial pressure difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; and pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three animals with recent CFTAH implantation recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last 2 were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to human surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  6. Processes of 30-90 days sea surface temperature variability in the northern Indian Ocean during boreal summer

    Energy Technology Data Exchange (ETDEWEB)

    Vialard, J. [Univerite P. et M. Curie, Laboratoire d' Oceanographie Experimentation et Approches Numeriques (LOCEAN), Case 100, CNRS, IRD, Paris Cedex 05 (France); Jayakumar, A.; Gnanaseelan, C.; Goswami, B.N. [Indian Institute of Tropical Meteorology, Pune (India); Lengaigne, M. [Univerite P. et M. Curie, Laboratoire d' Oceanographie Experimentation et Approches Numeriques (LOCEAN), Case 100, CNRS, IRD, Paris Cedex 05 (France); CSIR, National Institute of Oceanography, Goa (India); Sengupta, D. [Indian Institute of Sciences, Centre of Atmospheric and Oceanic Sciences, Bangalore (India)

    2012-05-15

    During summer, the northern Indian Ocean exhibits significant atmospheric intraseasonal variability associated with active and break phases of the monsoon in the 30-90 days band. In this paper, we investigate mechanisms of the Sea Surface Temperature (SST) signature of this atmospheric variability, using a combination of observational datasets and Ocean General Circulation Model sensitivity experiments. In addition to the previously-reported intraseasonal SST signature in the Bay of Bengal, observations show clear SST signals in the Arabian Sea related to the active/break cycle of the monsoon. As the atmospheric intraseasonal oscillation moves northward, SST variations appear first at the southern tip of India (day 0), then in the Somali upwelling region (day 10), northern Bay of Bengal (day 19) and finally in the Oman upwelling region (day 23). The Bay of Bengal and Oman signals are most clearly associated with the monsoon active/break index, whereas the relationship with signals near Somali upwelling and the southern tip of India is weaker. In agreement with previous studies, we find that heat flux variations drive most of the intraseasonal SST variability in the Bay of Bengal, both in our model (regression coefficient, 0.9, against {proportional_to}0.25 for wind stress) and in observations (0.8 regression coefficient); {proportional_to}60% of the heat flux variation is due do shortwave radiation and {proportional_to}40% due to latent heat flux. On the other hand, both observations and model results indicate a prominent role of dynamical oceanic processes in the Arabian Sea. Wind-stress variations force about 70-100% of SST intraseasonal variations in the Arabian Sea, through modulation of oceanic processes (entrainment, mixing, Ekman pumping, lateral advection). Our {proportional_to}100 km resolution model suggests that internal oceanic variability (i.e. eddies) contributes substantially to intraseasonal variability at small-scale in the Somali upwelling region

  7. 77 FR 43799 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Gila...

    Science.gov (United States)

    2012-07-26

    ... collectors or scrapers feeding on a variety of water particles and algae, as well as some large plants and... larger individuals frequently feed on algae (Edmunds and Waltz 1996, p. 126). Adult mayflies have... 2010, p. 2). The petition states that aluminum is toxic to aquatic insects and cite several papers in...

  8. Evaluation of acute toxicity in mice and subchronic toxicity of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-04

    May 4, 2009 ... 2Department of Pharmacology, School of Basic Medical Sciences, College of Medicine Campus, University of Lagos, Idi-. Araba, Lagos ... plasma glucose and low density lipoprotein (LDL)-cholesterol levels, but increased high density lipoprotein ... Traditional use of plant drugs popularly known as herbal.

  9. Evaluation of acute toxicity in mice and subchronic toxicity of ...

    African Journals Online (AJOL)

    disease conditions. ... biochemical parameters, body weight and liver, heart and renal organs following oral ... The extract reduced plasma glucose and low density lipoprotein (LDL)-cholesterol levels, but ... effects on the cardiovascular risk factors but indicated that high dose of the extract on a long term use can cause

  10. Risk rtPA: An iOS mobile application based on TURN for predicting 90-day outcome after IV thrombolysis.

    Science.gov (United States)

    Asuzu, David; Nystrӧm, Karin; Schindler, Joseph; Wira, Charles; Greer, David; Halliday, Janet; Sheth, Kevin N

    2016-03-01

    We recently developed Thrombolysis risk Using mRS and NIHSS (TURN), a simple score using only prestroke mRS scores and admission NIHSS scores to predict 90-day outcome after IV thrombolysis in ischemic stroke patients. Our purpose was to develop and test a mobile application for utilization of TURN at the bedside. We developed Risk rtPA, an iOS mobile application based on TURN for prediction of 90-day excellent and severe outcome after IV thrombolysis. Excellent outcome was defined as 90-day mRS≤1. Severe outcome was defined as 90-day mRS≥5. Predictors for excellent and severe outcome were calculated using the inverse logit of -TURN and TURN respectively. We retrospectively validated our mobile application using data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Sensitivity and specificity analyses were performed using receiver operating characteristic (ROC) curves. Prediction of excellent and severe outcome using Risk rtPA followed an S-shaped curve as expected. We confirmed this finding using data from the NINDS trial. Cutoffs selected after ROC analysis predicted severe outcome with sensitivity of 94.4% and specificity of 52.2%, and excellent outcome with specificity of 83.9% and sensitivity of 61.2%. The Risk rtPA mobile application predicted 90-day excellent and severe outcome in most clinically relevant cases. This mobile application brings the TURN score to the bedside for prediction of 90-day outcome in ischemic stroke patients being evaluated for IV thrombolysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats.

    Science.gov (United States)

    Okonkwo, T J N; Okorie, O; Okonta, J M; Okonkwo, C J

    2010-05-01

    The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD(50)of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats.

  12. [Removal of retrievable inferior vena cava filters 90 days after implantation in an ovine model: is there a time limit for removal?].

    Science.gov (United States)

    de Gregorio, Miguel Angel; Laborda, Alicia; Higuera, María Teresa; Lostale, Fernando; Gómez-Arrue, Javier; Serrano, Carolina; Martínez, Miguel Angel; Viloria, Américo

    2008-11-01

    To study the feasibility and safety of removing retrievable Günther-Tulip vena cava filters (GTFs) 90 days after their implantation in an ovine model. Thirty GTFs were implanted in 30 ewes and retrieval was attempted at 90 days. Conventional cavography was performed in all cases before and after retrieval in order to evaluate inferior vena cava patency and record dimensions. The presence of complications related to placement and retrieval of the filter from the inferior vena cava was also recorded. The force required to remove the filters was measured using a modified commercial dynamometer adapted to the GTF retrieval set. Histologic study focused on the inferior vena cava wall. Implantation was performed successfully in all cases (100%). One ewe developed a small focus of thrombosis around 1 of the legs of the filter and another presented a small thrombus within the filter. Retrieval of the filter was attempted in all 30 sheep at 90 days and the result was satisfactory in all but 1 case (96.6%). None of the GTFs required a force greater than 12 N to disengage the hooks of the filter from the wall. No complications were detected on venacavography or at autopsy. Variable degrees of fibrosis were observed in the histologic study. Retrieval of GTFs 90 days after implantation in an ovine model was feasible, safe, and easy, and required little force (median, 4.2 N).

  13. Meat yield and quality of Tanzania Shorthorn Zebu cattle finished on molasses/maize grain with agro-processing by-products in 90 days feedlot period

    DEFF Research Database (Denmark)

    Asimwe, Lovince; Kimambo, Abiliza; Laswai, Germana

    2016-01-01

    treatments namely hominy feed with molasses (HFMO), rice polishing with molasses (RPMO), hominy feed with maize meal (HFMM), rice polishing with maize meal (RPMM) and maize meal with molasses (MMMO). Ad libitum amount of each dietary treatment and hay were offered to nine steers for 90 days. Cooking loss (CL...

  14. Results of post-test psychological examinations of the crewmen from the 90-day manned test of an advanced regenerative life support system

    Science.gov (United States)

    Seeman, J. S.; Macfarlane, T. G.

    1972-01-01

    The following material presents the results of two temporally remote administrations of an identical projective personality assessment device (Rorschach Inkblot) using crew members aboard the 90-day test. The first administration took place during preselection crew psychodiagnostic testing in the period extending from mid-December 1969 through mid-January 1970. Second administration took place in late May and early June, 1971, approximately one year after termination of the test. During the 90-day program duration, the subjects participated in the crew training program, were selected and served as onboard crew during the 90-day test. The testing was undertaken in order to determine the character and extent of change (if any) in basic personality dynamics accompanying or caused by participation in the 90-day test program. Results indicate that significant personality changes occurred in three of the four onboard crew members. A detailed discussion of the results is provided. Objective scores which served as the basis for the discussion are presented in the Appendix.

  15. 90-Day Inhalation Toxicity Study of Swedish Biofuel Alcohol-to-Jet (ATJ) Synthetic Kerosene with Aromatics (SPA) in Rats with Neurotoxicity Testing and Genotoxicity Assay

    Science.gov (United States)

    2015-09-01

    placed at ground level to detect horizontal movement and in an elevated frame to detect vertical rears, as well as differentiate small (stereotypic...surface and all orifices; the organs and tissues of the cranial, thoracic, abdominal and pelvic cavities and neck; and the remainder of the carcass

  16. 90-Day Inhalation Toxicity Study of Hydroprocessed Esters and Fatty Acids (HEFA) Bio-Based Jet Fuel in Rats (Rattus norvegicus) with Neurotoxicity Testing and Genotoxicity Assay

    Science.gov (United States)

    2013-06-01

    Testicular spermatid head counts and epididymal sperm counts were evaluated from the frozen right testes and frozen right epididymis (IVOS, Hamilton Thorne...through the epididymal corpus to the cauda. Sperm entering the caput are incomplete or immature, but mature as they progress to the cauda, where...Alpha 2-Microglobulin Protein ..............................................................7 3.12 Sperm Motility and Concentration

  17. Sutureless replacement of aortic valves with St Jude Medical mechanical valve prostheses and Nitinol attachment rings: feasibility in long-term (90-day) pig experiments.

    Science.gov (United States)

    Berreklouw, Eric; Koene, Bart; De Somer, Filip; Bouchez, Stefaan; Chiers, Koen; Taeymans, Yves; Van Nooten, Guido J

    2011-05-01

    Nitinol attachment rings (devices) used to attach mechanical aortic valve prostheses suturelessly were studied in long-term (90 days) pig experiments. The aortic valve was removed and replaced by a device around a St Jude Medical mechanical valve prosthesis in 10 surviving pigs. Supravalvular angiography was done at the end of the operation. No coumarin derivates were given. No or minimal aortic regurgitation was confirmed in all surviving pigs at the end of the operation. Total follow-up was 846 days. In 4 pigs, follow-up was shorter than 90 days (28-75 days); the other 6 pigs did reach 90 days' survival or more. Repeat angiography in 4 pigs at the end of follow-up confirmed the unchanged position of the device at the aortic annulus, without aortic regurgitation. At autopsy, in all pigs the devices proved to be well grown in at the annulus, covered with endothelium, and sometimes tissue overgrowth related to not using coumarin derivates. There was no case of para-device leakage, migration, or embolization. No damage to surrounding anatomic structures or prosthetic valves was found. Nitinol attachment rings can be used to replace the aortic valve suturelessly with St Jude Medical mechanical aortic valve prostheses, without para-device leakage, migration, or damage to the surrounding tissues, in long-term pig experiments during a follow-up of 90 days or more. Refraining from anticoagulation in pigs with mechanical valve prostheses can lead to tissue overgrowth of the valve prosthesis. Further studies are needed to determine long-term feasibility of this method in human beings. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  18. Safety assessment of transgenic canola RF3 with bar and barstar gene on Sprague-Dawley (SD) rats by 90-day feeding test.

    Science.gov (United States)

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

    2017-12-01

    Canola is one of the most important plant oilseed crops. To avoid the threat of herbicides, the RF3 line with bar gene and barstar gene was developed, which can act as glufosinate resistance resources and restore fertility in hybrid lines. To assess the food safety of transgenic canola RF3, 2.5%, 5% and 10% GM canola RF3 and its non-GM isogenic line Drakkar were formulated into diet to feed Spragure-Dawley (SD) rats for 90 days. The effects on the general growth and toxicological parameters, as well as gut microbiota of rats, were evaluated. Several significant differences on body weight, feed consumption, relative organ weight, hematology and serum biochemistry were observed among rats in the 90-day feeding test. However, these statistical differences were randomly observed among different groups and were not dose-related, which were not considered to be biologically significant. Furthermore, the results of bacterial 16S rRNA sequencing of fecal samples showed that the diets containing GM canola did not disturb the balance of gut microbiota. In conclusion, the canola RF3 is considered as safe and wholesome as the non-GM canola based on this 90-day feeding test and gut microbiota analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    African Journals Online (AJOL)

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

  20. Subchronic Immunotoxicity Assessment of Genetically Modified Virus-Resistant Papaya in Rats.

    Science.gov (United States)

    Lin, Hsin-Tang; Lee, Wei-Cheng; Tsai, Yi-Ting; Wu, Jhaol-Huei; Yen, Gow-Chin; Yeh, Shyi-Dong; Cheng, Ying-Huey; Chang, Shih-Chieh; Liao, Jiunn-Wang

    2016-07-27

    Papaya is an important fruit that provides a variety of vitamins with nutritional value and also holds some pharmacological properties, including immunomodulation. Genetically modified (GM) papaya plants resistant to Papaya ringspot virus (PRSV) infection have been generated by cloning the coat protein gene of the PRSV which can be used as a valuable strategy to fight PRSV infection and to increase papaya production. In order to assess the safety of GM papaya as a food, this subchronic study was conducted to assess the immunomodulatory responses of the GM papaya line 823-2210, when compared with its parent plant of non-GM papaya, Tainung-2 (TN-2), in Sprague-Dawley (SD) rats. Both non-GM and GM 823-2210 papaya fruits at low (1 g/kg bw) and high (2 g/kg bw) dosages were administered via daily oral gavage to male and female rats consecutively for 90 days. Immunophenotyping, mitogen-induced splenic cell proliferation, antigen-specific antibody response, and histopathology of the spleen and thymus were evaluated at the end of the experiment. Results of immunotoxicity assays revealed no consistent difference between rats fed for 90 days with GM 823-2210 papaya fruits, as opposed to those fed non-GM TN-2 papaya fruits, suggesting that with regard to immunomodulatory responses, GM 823-2210 papaya fruits maintain substantial equivalence to fruits of their non-GM TN-2 parent.

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

    Directory of Open Access Journals (Sweden)

    Isabely de Souza Vera Cruz

    2006-03-01

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

  2. 90-day mortality after 409,096 total hip replacements for osteoarthritis, from the National Joint Registry for England and Wales: a retrospective analysis.

    Science.gov (United States)

    Hunt, Linda P; Ben-Shlomo, Yoav; Clark, Emma M; Dieppe, Paul; Judge, Andrew; MacGregor, Alex J; Tobias, Jon H; Vernon, Kelly; Blom, Ashley W

    2013-09-28

    Death within 90 days after total hip replacement is rare but might be avoidable dependent on patient and treatment factors. We assessed whether a secular decrease in death caused by hip replacement has occurred in England and Wales and whether modifiable perioperative factors exist that could reduce deaths. We took data about hip replacements done in England and Wales between April, 2003, and December, 2011, from the National Joint Registry for England and Wales. Patient identifiers were used to link these data to the national mortality database and the Hospital Episode Statistics database to obtain details of death, sociodemographics, and comorbidity. We assessed mortality within 90 days of operation by Kaplan-Meier analysis and assessed the role of patient and treatment factors by Cox proportional hazards model. 409,096 primary hip replacements were done to treat osteoarthritis. 1743 patients died within 90 days of surgery during 8 years, with a substantial secular decrease in mortality, from 0·56% in 2003 to 0·29% in 2011, even after adjustment for age, sex, and comorbidity. Several modifiable clinical factors were associated with decreased mortality according to an adjusted model: posterior surgical approach (hazard ratio [HR] 0·82, 95% CI 0·73-0·92; p=0·001), mechanical thromboprophylaxis (0·85, 0·74-0·99; p=0·036), chemical thromboprophylaxis with heparin with or without aspirin (0·79, 0·66-0·93; p=0·005), and spinal versus general anaesthetic (0·85, 0·74-0·97; p=0·019). Type of prosthesis was unrelated to mortality. Being overweight was associated with lower mortality (0·76, 0·62-0·92; p=0·006). Postoperative mortality after hip joint replacement has fallen substantially. Widespread adoption of four simple clinical management strategies (posterior surgical approach, mechanical and chemical prophylaxis, and spinal anaesthesia) could, if causally related, reduce mortality further. National Joint Registry for England and Wales. Copyright

  3. Changes in medication regimen complexity and the risk for 90-day hospital readmission and/or emergency department visits in U.S. Veterans with heart failure.

    Science.gov (United States)

    Yam, Felix K; Lew, Tiffany; Eraly, Satish A; Lin, Hsiang-Wen; Hirsch, Jan D; Devor, Michelle

    2016-01-01

    Heart failure (HF) hospitalization is associated with multiple medication modifications. These modifications often increase medication regimen complexity and may increase the risk of readmission and/or emergency department (ED) visit. To determine the association between changes in medication regimen complexity (MRC) during hospitalization of patients with heart failure and the risk of readmission or ED visit at 90 days. Secondary objectives include examining the association between changes in MRC and time to readmission as well as the relationship between number of medications and MRC. This was a retrospective cohort study that included U.S. Veterans hospitalized with heart failure. MRC was quantified using the medication regimen complexity index (MRCI). The change in MRCI was the difference between admission MRCI and discharge MRCI recorded during the index hospitalization. Demographic and clinical data were collected to characterize the study population. Patient data for up to one year after discharge was recorded to identify hospital readmissions and ED visits. A total of 174 patients were included in the analysis. Sixty-two patients (36%) were readmitted or had an ED visit at 90 days from the index hospitalization. The mean change (SD) in MRCI during the index hospitalization among the cohort was 4.7 (8.3). After multivariate logistic regression analysis, each unit increase in MRCI score was associated with a 4% lower odds of readmission or ED visit at 90 days but this finding was not statistically significant (OR 0.955; 95% CI 0.911-1.001). In the cox proportional hazard model, the median time to hospital readmission or ED visit was 214 days. Each unit increase in MRCI score was associated with a modest but non-significant increase in probability of survival from readmission or ED visit (HR 0.978; 95% CI 0.955, 1.001). Changes in medication regimen complexity that occur during hospitalization may also be associated with optimization of medical therapy and do

  4. Factors related to high levels of ostrich chick mortality from hatching to 90 days of age in an intensive rearing system

    Directory of Open Access Journals (Sweden)

    S.W.P. Cloete

    2001-07-01

    Full Text Available Ostrich chick mortality was studied in 2522 chicks that were hatched artificially during the 1999/2000 breeding season. High levels of mortality were observed, with 1978 (78.4 % of these chicks dying before 90 days after hatching. Atotal of 46.7 %(1177 of these chicks died before 28 days of age, and a further 30.7 %(801 died between 28 and 90 days post-hatching. Chick mortality to 28 days of age could not be conclusively related to sex, day of external pipping or breeder diet. Mortality rates were higher (P < 0.05 at the beginning and end of the breeding season than in the middle months. Differences in mortality levels of chicks incubated in different incubators could be related to the time of the breeding season during which the incubator was mostly used. The regression of chick mortality to 28 days of age on day-old chick mass followed a 2nd-degree polynomial. Chicks with day-old masses below 762.5 g were particularly at risk of dying before 28 days after hatching. Chicks hatching from eggs where excessive water loss to 35 days of incubation (>18 % was recorded were also at risk of succumbing before 28 days of age. Chick mortality percentages for the period from 28 to 90 days of age exceeded 80 %in chicks weighing an average of 1050 g at 28 days. Mortaliy percentages declined sharply at higher live masses, to between 20 and 30 % in chicks weighing ?1950 g. This 'core' level of mortality remained throughout, even in the heaviest chicks. It was concluded that the high levels of chick mortality could be related to stress in chicks, resulting from an inability to adapt to the rearing environment. The high subsequent mortality percentages of low live mass chicks that survived to 28 days after hatching could probably be attributed to residual setbacks suffered earlier. Abetter understanding of the underlying principles involved in ostrich chick mortality in intensive rearing environments is required for progress in this field, resulting in more

  5. Meat yield and quality of Tanzania Shorthorn Zebu cattle finished on molasses/maize grain with agro-processing by-products in 90 days feedlot period

    DEFF Research Database (Denmark)

    Asimwe, L.; Kimambo, A E; Laswai, G

    2016-01-01

    treatments namely hominy feed with molasses (HFMO), rice polishing with molasses (RPMO), hominy feed with maize meal (HFMM), rice polishing with maize meal (RPMM) and maize meal with molasses (MMMO). Ad libitum amount of each dietary treatment and hay were offered to nine steers for 90 days. Cooking loss (CL......) and Warner Bratzler shear force (WBSF) values were determined on M. longissimus thoracis et lumborum aged for 3, 6, 9 and 12 days. Steers fed on HFMO diet had higher (P .... Meat of steers from all diets was tender with average WBSF values of 47.9 Ncm^(−2). The CL (22.0 +/- 0.61%) and WBSF (53.4 +/- 0.70 N cm^(−2)) were highest in meat aged for 3 days followed by 6, 9 and 12 days. WBSF values for meat aged for 9 and 12 days from steers fed HFMO and RPMM diets were similar...

  6. Percutaneous reduction of mitral valve regurgitation using the MitraClip system – immediate and 90-day follow-up of 3 cases

    Science.gov (United States)

    Kustrzycka-Kratochwil, Dorota; Telichowski, Artur; Witkowski, Tomasz; Banasiak, Waldemar; Jankowska, Ewa A.; Ponikowski, Piotr; Reczuch, Krzysztof

    2013-01-01

    Treatment of hemodynamically significant valvular heart diseases has been the domain of cardiac surgery for decades. However, a promising novel method is the MitraClip system, involving percutaneous connection of insufficient valve leaflets with special cobalt-chrome clips. Our study presents clinical characteristics, course of treatment with the MitraClip system, and immediate and 90-day clinical and echocardiographic follow-up of the first 3 patients treated in our institution. Subsequently, based on data from the literature and our own experience, the current position around the world, and the target group of patients who are most likely to benefit from treatment using the MitraClip system, are discussed. PMID:24570704

  7. Lack of nephrotoxicity and renal cell proliferation following subchronic dermal application of a hydroquinone cream.

    Science.gov (United States)

    David, R M; English, J C; Totman, L C; Moyer, C; O'Donoghue, J L

    1998-07-01

    Hydroquinone (HQ) is used in over-the-counter formulations of skin-lightening creams sold in the United States and European Union. HQ was introduced into these formulations to provide a safe and effective alternative to mercury and other less effective ingredients. Recent studies involving subchronic oral exposure of male F344 rats to HQ have shown nephrotoxicity and renal tubule cell proliferation (English et al., 1994), while chronic exposures of male F344 rats were reported to cause renal cell adenomas (NTP, 1989). Previous subchronic dermal toxicity studies (CTFA, 1986; NTP, 1989) with HQ failed to detect nephrotoxicity; however, these studies were not specifically designed to assess renal structure and function. More sensitive endpoints were used in the present subchronic study to address concerns over potential toxicity from repeated dermal exposure to HQ. Male and female F344 rats were given topical applications with 0, 2.0, 3.5, or 5.0% HQ in an oil-in-water emulsion cream for 13 wk (5 days/wk). Body weights, feed consumption and water consumption were monitored, and animals were observed for clinical signs of toxicity and dermal irritation. Blood taken at termination was analysed for haematological and clinical chemistry effects. Erythema, which abated when exposure stopped, was the only dermatological effect seen at the HQ-cream application sites. Cell proliferation in the kidneys was evaluated after 3, 6 and 13 wk of treatment using bromodeoxyuridine (BrdU) labelling, but no changes indicative of sustained cell proliferation were seen. The renal histopathological lesions noted after oral exposure to HQ were not present after dermal exposure. Thus, topical exposure to HQ does not result in the renal toxicity observed in previous studies with F344 rats given HQ orally.

  8. Secondary prevention lifestyle interventions initiated within 90 days after TIA or 'minor' stroke: a systematic review and meta-analysis of rehabilitation programmes.

    Science.gov (United States)

    Heron, Neil; Kee, Frank; Cardwell, Christopher; Tully, Mark A; Donnelly, Michael; Cupples, Margaret E

    2017-01-01

    Strokes are often preceded by a transient ischaemic attack (TIA) or 'minor' stroke. The immediate period after a TIA/minor stroke is a crucial time to initiate secondary prevention. However, the optimal approach to prevention, including non-pharmacological measures, after TIA is not clear. To systematically review evidence about the effectiveness of delivering secondary prevention, with lifestyle interventions, in comprehensive rehabilitation programmes, initiated within 90 days of a TIA/minor stroke. Also, to categorise the specific behaviour change techniques used. The review identified randomised controlled trials by searching the Cochrane Library, Ovid MEDLINE, Ovid EMBASE, Web of Science, EBSCO CINAHL and Ovid PsycINFO. Two review authors independently screened titles and abstracts for eligibility (programmes initiated within 90 days of event; outcomes reported for TIA/minor stroke) and extracted relevant data from appraised studies; a meta-analysis was used to synthesise the results. A total of 31 potentially eligible papers were identified and four studies, comprising 774 patients post-TIA or minor stroke, met the inclusion criteria; two had poor methodological quality. Individual studies reported increased aerobic capacity but meta-analysis found no significant change in resting and peak systolic blood pressure, resting heart rate, aerobic capacity, falls, or mortality. The main behaviour change techniques were goal setting and instructions about how to perform given behaviours. There is limited evidence of the effectiveness of early post-TIA rehabilitation programmes with preventive lifestyle interventions. Further robust randomised controlled trials of comprehensive rehabilitation programmes that promote secondary prevention and lifestyle modification immediately after a TIA are needed. © British Journal of General Practice 2017.

  9. HISTOLOGICAL STRUCTURE OF FEMORAL BONE TISSUE IN ADULT MALE RATS AFTER SUBCHRONIC PERORAL ADMINISTRATIONS OF CADMIUM AND SELENIUM

    Directory of Open Access Journals (Sweden)

    Ivana Boboňová

    2012-08-01

    Full Text Available The aim of this study was to examine effects of subchronic peroral administrations of cadmium and selenium on femoral bone microscopic structure in adult male rats. 1-month-old male Wistar rats were randomly divided into three groups, each containing 10 males. In the first group (EG1, rats were administered by cadmium at the dose of 30 mg of CdCl2/L in drinking water for 90 days. In the second group (EG2, animals received a drinking water containing 5 mg of Na2SeO3/L for the same treatment period. The third group of rats without cadmium and selenium applications, served as a control group (CG. At the end of the experiment (90 days, all animals were killed and their right femora were collected for microscopic evaluation. We found that the qualitative histological characteristics of the compact bone tissue were different in the middle part of compact bone in medial and lateral views between experimental (EG1, EG2 and control groups (CG. In Cd- and Se-treated rats, a smaller number of primary and secondary osteons was identified. Moreover, a few resorption lacunae were observed in rats perorally exposed to Cd (EG1. Histomorphometric evaluation showed a significant decrease (P<0.05 in all variables (area, perimeter, maximum and minimum diameter of the primary osteons' vascular canals in the Cd-exposed rats (EG1 as compared to the control group. In comparison with the group CG, they were significantly increased (P<0.05 in the Se-exposed rats (EG2. Values of the Haversian canals and secondary osteons were significantly decreased (P<0.05 for all variables in rats from both experimental groups (EG1, EG2 as compared to the control (CG. The results allow for the conclusion that subchronic exposure to Cd and Se at the levels used in this study significantly influenced microscopic structure of femoral bone tissue in adult male rats.

  10. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke.

    Science.gov (United States)

    Oviedo, Alberto; Lebrun, Stefan; Kogel, Ulrike; Ho, Jenny; Tan, Wei Teck; Titz, Bjoern; Leroy, Patrice; Vuillaume, Gregory; Bera, Monali; Martin, Florian; Rodrigo, Gregory; Esposito, Marco; Dempsey, Ruth; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Frailty is a predictive factor of readmission within 90 days of hospitalization for acute exacerbations of chronic obstructive pulmonary disease: a longitudinal study.

    Science.gov (United States)

    Bernabeu-Mora, Roberto; García-Guillamón, Gloria; Valera-Novella, Elisa; Giménez-Giménez, Luz M; Escolar-Reina, Pilar; Medina-Mirapeix, Francesc

    2017-10-01

    Readmission after hospital discharge is common in patients with acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD). Although frailty predicts hospital readmission in patients with chronic nonpulmonary diseases, no multidimensional frailty measures have been validated to stratify the risk for patients with COPD. The aim of this study was to explore multidimensional frailty as a potential risk factor for readmission due to a new exacerbation episode during the 90 days after hospitalization for AE-COPD and to test whether frailty could improve the identification of patients at high risk of readmission. We hypothesized that patients with moderate-to-severe frailty would be at greater risk for readmission within that period of follow up. A secondary aim was to test whether frailty could improve the accuracy with which to discriminate patients with a high risk of readmission. Our investigation was part of a wider study protocol with additional aims on the same study population. Frailty, demographics, and disease-related factors were measured prospectively in 102 patients during hospitalization for AE-COPD. Some of the baseline data reported were collected as part of a previously study. Readmission data were obtained on the basis of the discharge summary from patients' electronic files by a researcher blinded to the measurements made in the previous hospitalization. The association between frailty and readmission was assessed using bivariate analyses and multivariate logistic regression models. Whether frailty better identifies patients at high risk for readmission was evaluated by area under the receiver operator curve (AUC). Severely frail patients were much more likely to be readmitted than nonfrail patients (45% versus 18%). After adjusting for age and relevant disease-related factors in a final multivariate model, severe frailty remained an independent risk factor for 90-day readmission (odds ratio = 5.19; 95% confidence interval: 1

  12. Consequences of subchronic exposure to ethanolic extract from fruits and leaves of Schinus molle var. areira L. in mice.

    Science.gov (United States)

    Bras, Cristina; Domínguez, Sergio; Codón, Stella; Minetti, Alejandra; Ferrero, Adriana

    2010-10-28

    Several extracts of Schinus molle var. areira L. plant proved to be useful for the treatment of different pathologies and for the control of insect pest. Due to these potential uses, it is necessary to study their safety. In this work, we evaluated the effects of subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira in mice. The plant extract was added to the diet at 1 g/kg body weight/day for 90 days. At the end of the exposure, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, several biochemical and histopathological studies were realized. The exposure to extract from leaves produced an increase in the number of rearings in the open field and of urine pools in the functional observational battery. On the other hand, the exposure to extract from fruits produced an increase in the neutrophil count and a decrease in the lymphocyte count and in the total cholesterol levels. None of the exposures affected the different organs evaluated. Our results suggest that subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira should be potentially useful in the treatment of lipid pathologies and safe to use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Calf tissue liquid stowage and muscular and deep vein distension in orthostatic tests after a 90-day head down bed rest

    Science.gov (United States)

    Arbeille, P.A.; Kerbeci, P.; Audebert, P.; Capri, A.; Pascaud, L.

    2005-08-01

    The objectives were to assess the contribution of (1) the calf veins distension and(2) the tissue liquid stowage during standtest, to orthostatic intolerance "OI" after a head down bed rest (HDBR) of 90days. Method: The population consisted of a control group (Co-gr, n=9) and an exercise Fly wheel counter-measure group (CM-gr, n=9). Calf vein cross sectional area (CSA) and surrounding tissue liquid content (tissue image darkness) were assessed by echography during pre and post HDBR stand-tests. Results: From supine to standing (post HDBR), the Tibial and muscular vein CSA increased significantly in non tolerant subjects whereas in tolerant subjects the vein CSA did not change. Post HDBR the tissue image darkness (proportional to tissue liquid content) increased more from supine to standing in non tolerant than in tolerant subjects. No significant difference were found between Co and exercise CM groups. Conclusion: High calf vein CSA and tissue liquid content increase at post-HDBR stand-test were significantly correlated with occurrence of OI but not with CM.

  14. Transgenic and conventional Brazilian soybeans don't cause or prevent preneoplastic colon lesions or oxidative stress in a 90-day in vivo study

    Directory of Open Access Journals (Sweden)

    Felipe Augusto Sbruzzi

    2013-08-01

    Full Text Available OBJECTIVE: The study presents the results of a 90-day safety assessment of rats fed with four varieties of soybeans, BRS 245 RR and BRS Valiosa RR (transgenic, BRS 133 and MG BR46 Conquista (non-transgenic. METHODS: Diets were prepared by incorporating toasted soybean flour to a commercial diet at 1%, 10% or 20% weight In the in vivo experimental the rats' body weight, body weight gain, food consumption, number of aberrant crypt foci, oxidative stress biomarkers, urea and creatinine levels were analyzed and compared between experimental groups, as well as histopathological observations (digestive tract, liver, kidneys. RESULTS: The results indicate that glyphosate-tolerant soy varieties neither induce nor prevent aberrant crypt foci induction, nor do their conventional counterparts. Similarly, none of the four soybean varieties tested induced changes in the digestive tract, liver or kidney. Serum biochemical parameters were also unchanged. CONCLUSION: The consumption of both, conventional and transgenic soybeans, were insufficient to ameliorate dimethylhydrazine-induced oxidative stress.

  15. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    Science.gov (United States)

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.

  16. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.

    Science.gov (United States)

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis(®)). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist's armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome.

  17. Meropenem vs standard of care for treatment of late onset sepsis in children of less than 90 days of age: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    de Cabre Vincent

    2011-09-01

    Full Text Available Abstract Background Late onset neonatal sepsis (LOS with the mortality of 17 to 27% is still a serious disease. Meropenem is an antibiotic with wide antibacterial coverage. The advantage of it over standard of care could be its wider antibacterial coverage and thus the use of mono-instead of combination therapy. Methods NeoMero-1, an open label, randomised, comparator controlled, superiority trial aims to compare the efficacy of meropenem with a predefined standard of care (ampicillin + gentamicin or cefotaxime + gentamicin in the treatment of LOS in neonates and infants aged less than 90 days admitted to a neonatal intensive care unit. A total of 550 subjects will be recruited following a 1:1 randomisation scheme. The trial includes patients with culture confirmed (at least one positive culture from normally sterile site except coagulase negative staphylococci in addition to one clinical or laboratory criterion or clinical sepsis (at least two laboratory and two clinical criteria suggestive of LOS in subjects with postmenstrual age The study will start recruitment in September 2011; the total duration is of 24 months. Trial registration EudraCT 2011-001515-31

  18. The Effects of Subchronic Exposure to Metribuzin on Danio rerio

    Directory of Open Access Journals (Sweden)

    Lucie Plhalova

    2012-01-01

    Full Text Available The aim of this study was to assess the impact of metribuzin in surface waters on fish under experimental conditions. The effects of subchronic exposure to metribuzin on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver and on activity of some biochemical markers (CYP450, EROD in Danio rerio were investigated during a 28-day toxicity test. Juvenile growth tests were performed on D. rerio according to OECD method number 215. Fish at an initial age of 30 days were exposed to a range of metribuzin concentrations (1.5, 5, 16, 33, and 53 mg L−1. Exposure to metribuzin at 53 mg L−1 was associated with increased mortality. Negative effects with regard to total body weight, length, and the inhibition of specific growth rate were induced at concentrations of 33 and 53 mg L−1. Histopathological examination revealed pathological lesions in the liver in pesticide-exposed fish only at the highest concentration of 53 mg L−1 of metribuzin. Based on the results of growth rate, biochemical markers (CYP450, EROD, and histopathological examination, the lowest observed effect concentration (LOEC value was 33 mg L−1 and the no observed effect concentration (NOEC value was 16 mg L−1.

  19. The effects of subchronic exposure to metribuzin on Danio rerio.

    Science.gov (United States)

    Plhalova, Lucie; Stepanova, Stanislava; Praskova, Eva; Chromcova, Lucie; Zelnickova, Lenka; Divisova, Lenka; Skoric, Misa; Pistekova, Vladimira; Bedanova, Iveta; Svobodova, Zdenka

    2012-01-01

    The aim of this study was to assess the impact of metribuzin in surface waters on fish under experimental conditions. The effects of subchronic exposure to metribuzin on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver) and on activity of some biochemical markers (CYP450, EROD) in Danio rerio were investigated during a 28-day toxicity test. Juvenile growth tests were performed on D. rerio according to OECD method number 215. Fish at an initial age of 30 days were exposed to a range of metribuzin concentrations (1.5, 5, 16, 33, and 53 mg L⁻¹). Exposure to metribuzin at 53 mg L⁻¹ was associated with increased mortality. Negative effects with regard to total body weight, length, and the inhibition of specific growth rate were induced at concentrations of 33 and 53 mg L⁻¹. Histopathological examination revealed pathological lesions in the liver in pesticide-exposed fish only at the highest concentration of 53 mg L⁻¹ of metribuzin. Based on the results of growth rate, biochemical markers (CYP450, EROD), and histopathological examination, the lowest observed effect concentration (LOEC) value was 33 mg L⁻¹ and the no observed effect concentration (NOEC) value was 16 mg L⁻¹.

  20. Costs for Childhood and Adolescent Cancer, 90 Days Prediagnosis and 1 Year Postdiagnosis: A Population-Based Study in Ontario, Canada.

    Science.gov (United States)

    de Oliveira, Claire; Bremner, Karen E; Liu, Ning; Greenberg, Mark L; Nathan, Paul C; McBride, Mary L; Krahn, Murray D

    2017-03-01

    Childhood and adolescent cancers are uncommon, but they have important economic and health impacts on patients, families, and health care systems. Few studies have measured the economic burden of care for childhood and adolescent cancers. To estimate costs of cancer care in population-based cohorts of children and adolescents from the public payer perspective. We identified patients with cancer, aged 91 days to 19 years, diagnosed from 1995 to 2009 using cancer registry data, and matched each to three noncancer controls. Using linked administrative health care records, we estimated total and net resource-specific costs (in 2012 Canadian dollars) during 90 days prediagnosis and 1 year postdiagnosis. Children (≤14 years old) numbered 4,396: 36% had leukemia, 21% central nervous system tumors, 10% lymphoma, and 33% other cancers. Adolescents (15-19 years old) numbered 2,329: 28.9% had lymphoma. Bone and soft tissue sarcoma, germ cell tumor, and thyroid carcinoma each comprised 12% to 13%. Mean net prediagnosis costs were $5,810 and $1,127 and mean net postdiagnosis costs were $136,413 and $62,326 for children and adolescents, respectively; the highest were for leukemia ($157,764 for children and $172,034 for adolescents). In both cohorts, costs were much higher for patients who died within 1 year of diagnosis. Inpatient hospitalization represented 69% to 74% of postdiagnosis costs. Treating children with cancer is costly, more costly than treating adolescents or adults. Substantial survival gains in children mean that treatment may still be very cost-effective. Comprehensive age-specific population-based cost estimates are essential to reliably assess the cost-effectiveness of cancer care for children and adolescents, and measure health system performance. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

    African Journals Online (AJOL)

    La plante entière, les feuilles et plus rarement les racines de Ageratum conyzoides (Astéracées) ont une valeur en médecine traditionnelle partout où elle croît et est peu ... Les études phytochimiques de l'extrait aqueux ont révélées la présence des alcaloïdes pyrrolizidiniques, des tanins, des saponines, flavonoïdes et des ...

  2. Subchronic toxicity of propyl paraben in adult male rats | Salem ...

    African Journals Online (AJOL)

    hydroxybenzoate) to adult male rats for four consecutive weeks induced severe hepatotoxicity as revealed by the significant elevation in serum marker enzymes along with a significant decrease in serum protein and its fractions. Furthermore ...

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

    African Journals Online (AJOL)

    DR. AMINU

    , 3, 4, and 5g/kg for 28 days. The control group was given equivalent volume of water ad libitum. The animals were allowed free access to the drinking water and food (Wheat bran,Crown flower Mills, Nig. Ltd) during the four weeks period of ...

  4. 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

  5. Evaluation of acute and subchronic toxicity of Stachytarpheta ...

    African Journals Online (AJOL)

    cholesterol) levels but raised high density lipoprotein (HDL-cholesterol) level. The protein, creatinine, and phosphorous levels were significantly affected only by the highest dose of the extract while calcium level was not affected by all the doses ...

  6. Subchronic toxicity evaluation of potassium bromate in Fischer 344 rats.

    Science.gov (United States)

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

    2013-11-01

    Male F344 rats were exposed to potassium bromate (KBrO₃) in drinking water at concentrations of 0, 5, 20, 100, 200, or 400 mg/L for 2 or 13 weeks. Endpoints evaluated included clinical observations, body weights, serum chemistry, gross pathology, organ weights, and select tissue histopathology (kidney, lung, liver, thyroid, and tunica vaginalis). Weekly body weight and water consumption means were similar between KBrO₃ and control groups throughout the study. Increases in kidney weights were observed in rats of the 400 mg/L group following 2- or 13-weeks exposure. Hyaline droplets were observed in renal tubules of rats of the 200 and 400 mg/L groups following 2 weeks exposure and in rats of the 400 mg/L group at 13 weeks. There were no KBrO₃-related microscopic findings in the lung, liver, thyroid, and tunica vaginalis at the 2- and 13-week time points. A no observed effect level of 100 mg/L KBrO₃ (8.1 mg/kg/day) was selected based on the absence of microscopic alterations in the kidney. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    Groups B to F were administered orally with the aqueous extract at 1, 2, 3, 4 and 5g /kg body weight respectively and the treatment period was 28 days. A decreased in weights of the animals were observed at all dose levels. The activities of liver maker enzymes (alanine aminotransferase, aspartate aminotransferase and ...

  8. Subchronic Toxicity Study on 1,4-Dithiane.

    Science.gov (United States)

    1987-08-01

    respectively. The left-ear clipped control male in cage 14 had malocclusion (a bite defect) and was excluded from all statistical analyses. An ANOVA on the...to test an oronasal species, e.g., a rabbit . 5.) Studying other compounds (e.g., 1,4-thioxane or other mustard metabolites or 1,3-dithiane) for

  9. Acute and subchronic toxicity studies of ethanol extract of Terminalia ...

    African Journals Online (AJOL)

    If you would like more information about how to print, save, and work with PDFs, Highwire Press provides a helpful Frequently Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download link ...

  10. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Wong Brian A

    2005-10-01

    Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

  11. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content – A 90-day feeding study in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Schrøder, Malene; Frank, Thomas

    2012-01-01

    Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore...

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

    Science.gov (United States)

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

    2012-07-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Investigation of neurotoxic and immunotoxic effects of some plant growth regulators at subacute and subchronic applications on rats.

    Science.gov (United States)

    Isik, Ismail; Celik, Ismail

    2015-12-01

    The present study was aimed to investigate the effects of subacute and subchronic treatment of some plant growth regulators (PGRs), such as abscisic acid (ABA) and gibberellic acid (GA3), on neurological and immunological biomarkers in various tissues of rats. The activities of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) were selected as biomarkers for neurotoxic biomarkers. Adenosine deaminase (ADA) and myeloperoxidase (MPO) were measured as indicators for immunotoxic investigation purpose. Wistar albino rats were orally administered with 25 and 50 ppm of PGRs ad libitum for 25-50 days continuously with drinking water. The treatment of PGRs caused different effects on the activities of enzymes. Results showed that the administrations of ABA and GA3 increased AChE and BChE activities in some tissues of rats treated with both the dosages and periods of ABA and GA3. With regard to the immunotoxic effects, ADA activity fluctuated, while MPO activity increased after subacute and subchronic exposure of treated rat tissues to both dosages when compared with the controls. The observations presented led us to conclude that the administrations of PGRs at subacute and subchronic exposure increased AChE, BChE, and MPO activities, while fluctuating the ADA activity in various tissues of rats. This may reflect the potential role of these parameters as useful biomarkers for toxicity of PGRs. © The Author(s) 2013.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2009-06-17

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

  16. Comparative evaluation of copeptin and NT-proBNP in patients with severe acute decompensated heart failure, and prediction of adverse events in a 90-day follow-up period: A prospective clinical observation trial.

    Science.gov (United States)

    Jia, Jun; Chang, Guang-Lei; Qin, Shu; Chen, Jia; He, Wen-Yan; Lu, Kai; Li, Yong; Zhang, Dong-Ying

    2017-04-01

    The present study compared the prognostic value of a marker, the C-terminal section of the arginine vasopressin prohormone (copeptin), with N-terminal B-type natriuretic peptide (NT-proBNP) in patients with severe acute decompensated heart failure. A prospective, observational cohort study was conducted in a tertiary care hospital and enrolled 129 patients with severe acute decompensated heart failure. Clinicians were blinded to investigational markers except NT-proBNP, and the study participants were followed up for 90 days. The end-point was a composite of cardiovascular death or re-hospitalization due to decompensated heart failure. Of the 129 patients enrolled, 47 reached the end-point and 82 were in a stable condition during follow-up. Receiver operating characteristic curve analysis revealed that the areas under curve for the prediction of adverse events within 90 days were similar for copeptin [0.602±0.052; 95% confidence interval (CI), 0.499-0.705], NT-proBNP (0.659±0.048; 95% CI, 0.565-0.753) and their combination (0.670±0.050; 95% CI, 0.573-0.767). Kaplan-Meier survival analysis showed that the predictive value of NT-proBNP regarding the probability of survival was superior compared with that of copeptin (log-rank test for trend, P=0.001 vs. 0.040). Furthermore, multivariate Cox proportional-hazards regression analysis revealed that increased NT-proBNP and copeptin plasma concentrations were significant independent predictors of adverse events. The present study provided evidence that copeptin has similar predictive properties compared with NT-proBNP regarding adverse events within 90-days in patients with severe acute decompensated heart failure, but that copeptin may not provide superior 90-day prediction compared to NT-proBNP.

  17. Oral Toxicity Studies of Hydroalcohol Leaf Extract of Ageratum ...

    African Journals Online (AJOL)

    Erah

    Bordeaux, France. Abstract. Purpose: Ageratum conyzoides is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. The objective of this study was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats.

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Marjan Razavi

    2013-01-01

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

  20. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

    Pashov, D; Simeonov, S P; Drumev, D; Peĭnikova, Ts; Dzhurov, A

    1980-01-01

    We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

  1. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R. [Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Proctor, Deborah M. [ToxStrategies, Inc., Rancho Santa Margarita, CA 92688 (United States); Harris, Mark A. [ToxStrategies, Inc., Katy, TX 77494 (United States); Haws, Laurie C. [ToxStrategies, Inc., Austin, TX 78759 (United States); Thompson, Chad M., E-mail: cthompson@toxstrategies.com [ToxStrategies, Inc., Katy, TX 77494 (United States)

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

  2. Prediction of carcinogenic potential of chemicals using repeated-dose (13-week) toxicity data.

    Science.gov (United States)

    Woutersen, Ruud A; Soffers, Ans E M F; Kroese, E Dinant; Krul, Cyrille A M; van der Laan, Jan Willem; van Benthem, Jan; Luijten, Mirjam

    2016-11-01

    Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Toxicity test of a dental commercial composite

    OpenAIRE

    Ponce Bravo, Santa; Ledesma Montes, Constantino; Martínez Rivera, José Luis; Garcés Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite?) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 ...

  4. [Toxicity study of realgar].

    Science.gov (United States)

    Liang, Aihua; Li, Chunying; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bing; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg

    2011-07-01

    To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic. Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated. With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.

  5. Subchronic and genetic safety evaluation of a calcium fructoborate in rats.

    Science.gov (United States)

    Marone, Palma Ann; Heimbach, James T; Nemzer, Boris; Hunter, John M

    2016-09-01

    A branded calcium fructoborate product, a nature-identical calcium salt of bis (fructose) ester of boric acid found in plants and a natural source of boron in the human diet and sold under the trade name FruiteX-B(®) Brand Calcium Fructoborate ("FrxB"), was evaluated in a 90-day dietary toxicity study and two genotoxicity studies. In the 90-day study, four groups of 10 male and 10 female Crl:SD CD(®) IGS rats were fed diets with FrxB admixtures of 0.56, 1.12, and 1.68% dietary concentration, providing mean overall daily intakes of FrxB in male rats of 385.8, 774.9, and 1161.3 mg/kg bw/day, and 392.1, 784.4, and 1171.1 mg/kg bw/day in female rats. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption, food efficiency, Functional Observational Battery (FOB), or Motor Activity (MA) findings associated with the administration of FrxB. There were no adverse changes in hematology, coagulation, clinical chemistry, or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study, based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for FrxB in the diet was 1161.3 and 1171.1 mg/kg bw/day in male and female rats, respectively. Bacterial mutagenicity studies and a micronucleus test using Chinese hamster V79 cells demonstrated no mutagenic or genotoxic potential of the tested brand of calcium fructoborate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

    Directory of Open Access Journals (Sweden)

    Elena Bassi

    2012-01-01

    Full Text Available In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week of 2′-O-methyl-phosphorothioate antisense oligoribonucleotides (AONs adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage. In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules.

  7. Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats.

    Science.gov (United States)

    Golfakhrabadi, Fereshteh; Abdollahi, Mohammad; Ardakani, Mohammad Reza Shams; Saeidnia, Soodabeh; Akbarzadeh, Tahmineh; Ahmadabadi, Amir Nili; Ebrahimi, Azin; Yousefbeyk, Fatemeh; Hassanzadeh, Alireza; Khanavi, Mahnaz

    2014-10-01

    Ferulago carduchorum Boiss. & Hausskn. (Apiaceae) is known as Chavil in Persian which grows in west of Iran. Local people add Chavil to dairy and oil ghee as a natural preservative to extend the expiration date. The goal of this survey is the safety evaluation of the total extract of F. carduchorum in rats by determining both oral acute and subchronic toxicities; furthermore, the anticoagulant activity of isolated coumarins was evaluated. The aerial parts of F. carduchorum were extracted by the percolation method. The anticoagulant activity of isolated coumarins was evaluated and the total extract was used to investigate acute and subchronic toxicity in rats. In the subchronic toxicity model, doses of 250, 500, and 1000 mg/kg of the extract were administered to treated groups for 30 consecutive days by gavage. According to the results of acute toxicity, the LD50 of Chavil extract was more than 2000 mg/kg. The subchronic study showed no significant difference (p > 0.05) between the groups treated with extract and control groups in hematological (erythrocyte, total and differential leukocyte, hematocrit, hemoglobin, platelet count) and biochemical parameter (glucose, albumin, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) evaluations. The isolated coumarins (suberosin and suberenol) prolonged the prothrombin time (PT) at doses of 3 and 6 mg/kg compared with control (p coumarins showed anticoagulant effect in rats.

  8. Disruption of medial prefrontal synchrony in the subchronic phencyclidine model of schizophrenia in rats.

    Science.gov (United States)

    Young, A M J; Stubbendorff, C; Valencia, M; Gerdjikov, T V

    2015-02-26

    Subchronic treatment with the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) produces behavioral abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2mg/kg twice daily for 7 days) under urethane anesthesia. We found that this regimen reduced theta oscillations in the medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks. Copyright © 2015. Published by Elsevier Ltd.

  9. Subchronic Sleep Restriction Causes Tissue-Specific Insulin Resistance

    Science.gov (United States)

    Neylan, Thomas C.; Grunfeld, Carl; Mulligan, Kathleen; Schambelan, Morris; Schwarz, Jean-Marc

    2015-01-01

    Context: Short sleep duration is associated with an increased risk of type 2 diabetes. Subchronic sleep restriction (SR) causes insulin resistance, but the mechanisms and roles of specific tissues are unclear. Objective: The purpose of this article was to determine whether subchronic SR altered (1) hepatic insulin sensitivity, (2) peripheral insulin sensitivity, and (3) substrate utilization. Design: This was a randomized crossover study in which 14 subjects underwent 2 admissions separated by a washout period. Each admission had 2 acclimatization nights followed by 5 nights of either SR (4 hours time in bed) or normal sleep (8 hours time in bed). Main Outcome Measure/Methods: Insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp) and hepatic insulin sensitivity (measured by stable isotope techniques) were measured. In addition, we assayed stress hormone (24-hour urine free cortisol, metanephrine, and normetanephrine), nonesterified fatty acid (NEFA), and β-hydroxybutyrate (β-OH butyrate) levels. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured by indirect calorimetry. Results: Compared to normal sleep, whole-body insulin sensitivity decreased by 25% (P = .008) with SR and peripheral insulin sensitivity decreased by 29% (P = .003). Whereas hepatic insulin sensitivity (endogenous glucose production) did not change significantly, percent gluconeogenesis increased (P = .03). Stress hormones increased modestly (cortisol by 21%, P = .04; metanephrine by 8%, P = .014; normetanephrine by 18%, P = .002). Fasting NEFA and β-OH butyrate levels increased substantially (62% and 55%, respectively). REE did not change (P = 0.98), but RQ decreased (0.81±.02 vs 0.75±0.02, P = .045). Conclusion: Subchronic SR causes unique metabolic disturbances characterized by peripheral, but not hepatic, insulin resistance; this was associated with a robust increase in fasting NEFA levels (indicative of increased lipolysis), decreased RQ, and

  10. Effects of subchronic metribuzin exposure on common carp (Cyprinus carpio).

    Science.gov (United States)

    Modra, Helena; Haluzova, Ivana; Blahova, Jana; Havelkova, Marcela; Kruzikova, Kamila; Mikula, Premysl; Svobodova, Zdenka

    2008-10-01

    Effects of metribuzin on biochemical and haematological indices, induction of specific biomarkers and impacts on biometric parameters of Cyprinus carpio were investigated for subchronic conditions. Juvenile fish were exposed to 0.175 mg.L-1 or 1.75 mg.L-1 metribuzin for 28 days. Haematological indices were assessed using unified methods of haematological examination in fish. Biochemical indices were determined by biochemical analyzer, hepatic vitellogenin content was estimated by direct sandwich ELISA. Cytochrome P450 concentration and ethoxyresorufin O-deethylase activity were measured in liver spectrophotometrically and spectrofluorimetrically, respectively. Increased haematocrit and RBC count were found in fish exposed to 1.75 mg.L-1 metribuzin compared to control fish (pmetribuzin. Sublethal metribuzin pollution may have adverse impacts on haematological parameters in common carp.

  11. Derivation of an inhalation reference concentration based upon olfactory neuronal loss in male rats following subchronic acetaldehyde inhalation.

    Science.gov (United States)

    Dorman, David C; Struve, Melanie F; Wong, Brian A; Gross, Elizabeth A; Parkinson, Carl; Willson, Gabrielle A; Tan, Yu-Mei; Campbell, Jerry L; Teeguarden, Justin G; Clewell, Harvey J; Andersen, Melvin E

    2008-02-01

    Acetaldehyde inhalation induces neoplastic and nonneoplastic responses in the rodent nasal cavity. This experiment further characterizes the dose-response relationship for nasal pathology, nasal epithelial cell proliferation, and DNA-protein cross-link formation in F-344 rats exposed subchronically to acetaldehyde. Animals underwent whole-body exposure to 0, 50, 150, 500, or 1500 ppm acetaldehyde for 6 h/day, 5 days/wk for up to 65 exposure days. Respiratory tract histopathology was evaluated after 4, 9, 14, 30, and 65 exposure days. Acetaldehyde exposure was not associated with reduced body weight gain or other evidence of systemic toxicity. Histologic evaluation of the nasal cavity showed an increased incidence of olfactory neuronal loss (ONL) following acute to subchronic exposure to > or = 150 ppm acetaldehyde and increased olfactory epithelial cell proliferation following exposure to 1500 ppm acetaldehyde. The severity of the ONL demonstrated dose- and temporal-dependent behaviors, with minimal effects noted at 150-500 ppm acetaldehyde and moderately severe lesions seen in the highest exposure group, with increased lesion severity and extent as the exposure duration increased. Acetaldehyde exposure was also associated with inflammation, hyperplasia, and squamous metaplasia of the respiratory epithelium. These responses were seen in animals exposed to > or = 500 ppm acetaldehyde. Acetaldehyde exposure was not associated with increased DNA-protein cross-link formation in the respiratory or olfactory epithelium. A model of acetaldehyde pharmacokinetics in the nose was used to derive an inhalation reference concentration (RfC) of 0.4 ppm, based on the no-observed-adverse-effect level (NOAEL) of 50 ppm for the nasal pathology seen in this study.

  12. Post hoc analyses of data from a 90-day clinical trial evaluating the tolerability and efficacy of tapentadol immediate release and oxycodone immediate release for the relief of moderate to severe pain in elderly and nonelderly patients

    Science.gov (United States)

    Vorsanger, Gary; Xiang, Jim; Biondi, David; Upmalis, David; Delfgaauw, Jacqueline; Allard, René; Moskovitz, Bruce

    2011-01-01

    OBJECTIVE: To evaluate the tolerability and efficacy of tapentadol immediate release (IR) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients. METHODS: Post hoc data analyses were conducted on a 90-day randomized, phase 3, double-blind, flexible-dose study (ClinicalTrials.gov: NCT00364546) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg, or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief. Treatment-emergent adverse events and study discontinuations were recorded. RESULTS: Data from 849 patients randomly assigned (4:1 ratio) to treatment with a study drug (tapentadol IR [n=679] or oxycodone IR [n=170]) were analyzed according to age (younger than 65 years of age [nonelderly], or 65 years of age or older [elderly]) and treatment group. Among elderly patients, incidences of constipation (19.0% versus 35.6%) and nausea or vomiting (30.4% versus 51.1%) were significantly lower with tapentadol IR versus oxycodone IR (all Ptapentadol IR versus oxycodone IR (both P≤0.031). Tapentadol IR-treated elderly patients had a lower percentage of days with constipation than oxycodone IR-treated patients (P=0.020). For tapentadol IR- and oxycodone IR-treated elderly patients, respectively, incidences of study discontinuation due to gastrointestinal treatment-emergent adverse events were 15.8% and 24.4% (P=0.190). Tapentadol IR and oxycodone IR provided similar pain relief, with no overall age-dependent efficacy differences (mean pain scores [11-point numerical rating scale] decreased from 7.0 and 7.2 at baseline, to 4.9 and 5.2 at end point, respectively). CONCLUSIONS: Tapentadol IR was safe and effective for the relief of lower back pain and osteoarthritis pain in elderly patients, and was associated with a better gastrointestinal tolerability profile than oxycodone IR. PMID:22059194

  13. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

    Directory of Open Access Journals (Sweden)

    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  14. Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Dhouib, Ines Bini; Bouzid, Kahna; Lamine, Aicha Jrad; Annabi, Alya; Belhadjhmida, Nadia; Ahmed, Malika Ben; Fazaa, Saloua El; Abdelmoula, Jaouida; Gharbi, Najoua

    2014-09-01

    Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-β indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Enantioselective bioaccumulation and toxic effects of fipronil in the earthworm Eisenia foetida following soil exposure.

    Science.gov (United States)

    Qin, Fang; Gao, Yongxin; Xu, Peng; Guo, Baoyuan; Li, Jianzhong; Wang, Huili

    2015-04-01

    Enantiomers of chiral pesticides often have different bioactivity, toxicity and environmental behaviours. Fipronil has been used in racemate for agricultural purposes against soil insects, leading to increased inputs into soil environments and complex biota exposures. To understand the potential risk associated with fipronil enantiomer exposure, subchronic toxicity and bioaccumulation tests with earthworms (Eisenia foetida) in fipronil-spiked soils were evaluated under laboratory conditions. Enantioselective toxicity was measured in E. foetida biomass after 28 days of subchronic exposure, with increased toxicity from racemate and S-fipronil compared with R-fipronil. The bioaccumulation of fipronil in earthworm tissues was also enantioselective, with a preferential accumulation of S-fipronil, and the enantiomer fraction was approximately 0.56-0.60. During soil exposure, fipronil was transformed primarily into fipronil sulfide, sulfone and amide, and E. foetida rapidly accumulated fipronil and sulfone. This work demonstrates the enantioselective subchronic toxicity and bioaccumulation of enantiomers of fipronil in E. foetida. The earthworm tissues exhibited a relative enrichment of fipronil and fipronil sulfone, and these compounds might biomagnify (with a biota-to-soil accumulation factor of ≥1.0 kgOCkglip-1), allowing for the possible trophic transfer and/or bioaccumulation of all these chemicals if earthworms were consumed by predator organisms. © 2014 Society of Chemical Industry.

  16. The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

    DEFF Research Database (Denmark)

    Jørgensen, Bettina Merete Pyndt; Redrobe, Paul; Brønnum Pedersen, Tina

    The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gut microbiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gut microbiota on behavior in this model, and therefore it might be relavant to include the information...

  17. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats

    Science.gov (United States)

    1989-07-31

    buffered formalin (NBF). To standardize the degree of distension of pulmonary alveoli with fixative, the lungs were fixed by inserting a blunted needle into...the thickness of the mucosa, submucosa and muscular layers of the stomach and involved the serosa. Epithelial hyperplasia and hyperkeratosis of the

  18. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Science.gov (United States)

    2010-07-01

    ... neurotoxicity has been obtained by acute testing or by the demonstration of inhibition and aging of neurotoxic... sacrificed. (ii) Pathology—(A) Gross necropsy. In the presence of clinical signs of delayed neurotoxicity...

  19. Acute and sub-chronic toxicity study of the extract and powder of ...

    African Journals Online (AJOL)

    Major endpoints included alterations in the central and autonomic nervous system, water and food intake, body weight, hematological and biochemical parameters. Phytochemical screening identified compounds: Alkaloids, flavonoids, xanthones, leucoanthocyanidins and tannins condensate. In the acute study, mortality ...

  20. The Subchronic Oral Toxicity of 2,4-Dinitroanisole (DNAN) in Rats

    Science.gov (United States)

    2012-06-01

    Fibroadipose tissue larynx, pharynx, trachea and thyroid gland: Cellulitis , fibrinous and pyogranulomatous, diffuse, severe with edema, hemorrhage...with minimal hemorrhage. 9. Fibroadipose tissue, submandibular salivary gland: Cellulitis , fibrinosuppurative, diffuse with edema. 10. Lymph node

  1. Acute and Subchronic Toxicity Evaluations of the Halon Replacement Candidate Phosphorus Tribromide

    National Research Council Canada - National Science Library

    Wolfe, Robin

    1997-01-01

    ... on flight lines or where maintenance commonly occurs. Application of 10 or 50 microliters neat PBr3 to intact skin of an anesthetized NZW rabbit caused edema and necrosis of the treated skin within 10 minutes of dosing...

  2. Acute, sub-chronic and chronic toxicity of Solanum incanum L in ...

    African Journals Online (AJOL)

    ... was taken weekly for haematological and biochemical analysis. Clinical signs started on day two with bloat. All sheep groups showed bloat and coughing. Signs of cerebellar hyperplasia were manifested in 25%, 75% and 25% of sheep in groups 2, 3, and 4 respectively, manifested by staggering gait, lateral recumbency, ...

  3. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Science.gov (United States)

    2010-07-01

    ... experimental and control group. (6) Gross pathology. With the exception of the whole body perfusion-fixed test..., thoracic, and abdominal cavities and their contents. Gross pathology shall be performed on the following...; representative lymph node; (mammary gland); (thigh musculature); peripheral nerve/tissue; (eyes); (femur...

  4. Subchronic toxicity of propyl paraben IL-28B rs12979860 gene ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Hepatitis C virus (HCV) is largely responsible for the increase in incidence of HCC. There are few and controversial data available on the association between IL-28B single nucleotide polymorphisms (SNPs) and severity of liver fibrosis, presence of ...

  5. WITHDRAWN: Subchronic 26-week oral (gavage) toxicity study of Xylo-oligosaccharide in beagle dogs.

    Science.gov (United States)

    Zhang, Shumin; Liu, Ying; Fu, Chengyu; Ning, Jun; Lin, Xiao; Xu, Guohui

    2012-07-31

    This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  6. The Subchronic Toxicity of Diethylene Glycol Monobutyl Ether Administered Orally to Rats.

    Science.gov (United States)

    1987-08-01

    fetuses, or neonates , except a slight reduction in mean pup weight during the latter stages of lactation. In the same study, rabbits demonstrated no...the powerful surfactant properties of DGBE may 12 WMi have contributed to the development of pulmonary congestion and edema by a mechanism not yet

  7. Acute and Subchronic Inhalation Toxicity of n-Octane in Rats

    Directory of Open Access Journals (Sweden)

    Jae Hyuck Sung

    2010-12-01

    Conclusion: However, n-octane exposure should be controlled to be below the American Conference of Industrial Hygienists recommendation (300 ppm to prevent inhalation-related adverse health effects of workers.

  8. Acute and Subchronic Toxicity Study of Tud-Rak-Ka-Sai-Puu Recipe ...

    African Journals Online (AJOL)

    No defects of animal behavior were observed in the test groups. Both test and control groups (on the 90th day) as well as 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 microanatomy.

  9. Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants

    Science.gov (United States)

    1997-08-01

    place the 35 number on the dorsal surface. Five groups of 5 males were assigned to treatment groups, randomized by block design using body weights as...extracts frogs or embryos. Methods of ^^"^^t the soil for 60 to 90 days. Methods (SCFE) via earthworms or other food and^recrexposur contaminated and of...Spills 4 2. The Need for Reproductive Toxicity Testing 3. Reproductive Toxicity Assay Design 4. The Need for Developmental Toxicity Testing 5

  10. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS

    Science.gov (United States)

    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  11. Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats

    Directory of Open Access Journals (Sweden)

    Archana Vyas

    2016-01-01

    Full Text Available Aspirin (acetylsalicylic acid is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry.

  12. Analysis of sociability and preference for social novelty in the acute and subchronic phencyclidine rat.

    Science.gov (United States)

    McKibben, Claire E; Reynolds, Gavin P; Jenkins, Trisha A

    2014-10-01

    Both acute and sub-chronic phencyclidine administration produce behavioural and pathophysiological changes that resemble some features of schizophrenia. The present study aimed to determine if acute and sub-chronic phencyclidine treatment in male rats produces deficits in sociability and social novelty preference, which may reflect aspects of the negative symptomatology observed in schizophrenia. Rats were treated with phencyclidine acutely (2 or 5 mg/kg) or subchronically (2 or 5 mg/kg bi-daily for one week followed by a one week wash-out period) or vehicle. Social affiliative behaviour was assessed using the sociability and preference for social novelty paradigm where social interaction time was measured in (a) a chamber containing an unfamiliar conspecific vs an empty chamber (sociability), or (b) a chamber containing an unfamiliar conspecific vs a chamber containing a familiar conspecific (preference for social novelty). Results showed that acute administration of phencyclidine produced a reduction in measures of sociability but had no effect on preference for social novelty while sub-chronic administration of phencyclidine had no effect on sociability or social novelty. This study provides further evidence for the usefulness of phencyclidine models in modelling the symptomatology of schizophrenia. © The Author(s) 2014.

  13. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreases lung elastance

    Directory of Open Access Journals (Sweden)

    John M. Hartney

    2012-07-01

    Full Text Available Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6 mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1–/– that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  14. In vitro characterization and in vivo toxicity, antioxidant and immunomodulatory effect of fermented foods; Xeniji™.

    Science.gov (United States)

    Zulkawi, Noraisyah; Ng, Kam Heng; Zamberi, Rizi; Yeap, Swee Keong; Satharasinghe, Dilan; Jaganath, Indu Bala; Jamaluddin, Anisah Binti; Tan, Sheau Wei; Ho, Wan Yong; Alitheen, Noorjahan Banu; Long, Kamariah

    2017-06-30

    Xeniji, produced by fermenting various types of foods with lactic acid bacteria and yeast, has been commonly consumed as functional food. However, nutrition value, bioactivities and safety of different fermented products maybe varies. Organic acid and antioxidant profiles of Xeniji fermented foods were evaluated. Moreover, oral acute (5 g/kg body weight) and subchronic toxicity (0.1, 1 and 2 g/kg body weight) of Xeniji were tested on mice for 14 days and 30 days, respectively. Mortality, changes of body weight, organ weight and serum liver enzyme level were measured. Liver and spleen of mice from subchronic toxicity study were subjected to antioxidant and immunomodulation quantification. Xeniji was rich in β-carotene, phytonadione, polyphenol, citric acid and essential amino acids. No mortality and significant changes of body weight and serum liver enzyme level were recorded for both oral acute and subchronic toxicity studies. Antioxidant level in the liver and immunity of Xeniji treated mice were significantly upregulated in dosage dependent manner. Xeniji is a fermented functional food that rich in nutrients that enhanced antioxidant and immunity of mice. Xeniji that rich in β-carotene, phytonadione, polyphenol, citric acid and essential amino acids promote antioxidant and immunity in mice without causing toxic effect.

  15. Association between subchronic and chronic lead exposure and levels of antioxidants and chemokines.

    Science.gov (United States)

    Dobrakowski, Michał; Kasperczyk, Aleksandra; Pawlas, Natalia; Birkner, Ewa; Hudziec, Edyta; Chwalińska, Ewa; Kasperczyk, Sławomir

    2016-10-01

    This study aimed to compare the influence of lead on the non-enzymatic antioxidant defenses and the levels of chemokines in workers subchronically and chronically exposed to lead. The study population was divided into three groups. The first group consisted of male workers subchronically exposed to lead for 40 ± 3.2 days, while the second group included male workers chronically exposed to lead. The third group was a control group. The levels of uric acid and bilirubin were significantly higher after a subchronic exposure to lead compared to the baseline by 22 and 35 %, respectively. Similarly, the values of total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) increased by 15, 50, and 33 %, respectively. At the same time, the levels of thiol groups and albumin decreased by 5 and 8 %, respectively. Additionally, the levels of interleukin-8 (IL-8) and macrophage inflammatory protein-1β (MIP-1β) were significantly higher after a subchronic exposure to lead compared to the baseline by 34 and 20 %, respectively. Moreover, IL-8 level was significantly higher by 40 % in the group of workers chronically exposed to lead than in the control group, while the level of interferon gamma-induced protein-10 (IP-10) was significantly lower by 28 %. Similar to chronic lead exposure, subchronic exposure to lead is associated with elevated blood levels of uric acid and bilirubin in humans. This probably results in increased TAC value despite thiol depletion. However, the compensatory activation of non-enzymatic antioxidant defenses seems to be insufficient to protect against lead-induced oxidative stress, which may be additively enhanced by the pro-inflammatory action of chemokines, especially IL-8.

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

    Energy Technology Data Exchange (ETDEWEB)

    Joe Mauderly

    2009-01-07

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

  17. Dualistic immunomodulation of sub-chronic microcystin-LR exposure on the innate-immune defense system in male zebrafish.

    Science.gov (United States)

    Lin, Wang; Hou, Jie; Guo, Honghui; Qiu, Yuming; Li, Li; Li, Dapeng; Tang, Rong

    2017-09-01

    Microcystins (MCs), produced by toxic cyanobacterial blooms that appeared world wildly in eutrophication waters, have often caused fish illness and even massive death cases. Among at least 90 structural variants, microcystin-LR (MC-LR) is the most common and toxic variant. In order to better understand innate immune responses in fish disrupted by environmental concentrations of MC-LR, male zebrafish (Danio rerio) were exposed to 0, 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d, and the changes in splenic pathology and immunological gene expression as well as serum immune parameters were studied. In the low concentration groups (0.3, 1 and 3 μg/L), zebrafish displayed splenic inflammatory changes including the formation of melano-macrophage centers and the increase of macrophage pseudopodia, remarkable elevation of serum C3 levels, and significantly upregulated expression of innate immune-related genes (c3b, lyz, il1β, tnfα and ifnγ). In contrast, high concentrations of MC-LR (10 and 30 μg/L) resulted in the degeneration of splenic lymphocytes and macrophages, and down-regulation of immune-related genes as well as significant decreases in the level of serum C3. Furthermore, significant increases in the activity of serum ACP and ALP suggested that high concentrations of MC-LR increased permeability of macrophage plasma membrane or cellular necrosis, and subsequently decreased innate immune function. Our findings illustrated that sub-chronic exposure of MC-LR has dualistic influences on fish innate immune system with inflammatory activation at low exposure concentrations but turned to immune inhibition with the increases of exposure concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Imbalanced immune responses involving inflammatory molecules and immune-related pathways in the lung of acute and subchronic arsenic-exposed mice.

    Science.gov (United States)

    Li, Jinlong; Zhao, Lu; Zhang, Yang; Li, Wei; Duan, Xiaoxu; Chen, Jinli; Guo, Yuanyuan; Yang, Shan; Sun, Guifan; Li, Bing

    2017-11-01

    Inorganic arsenic has been claimed to increase the risk of pulmonary diseases through ingestion, as opposed to inhalation, which makes it a unique and intriguing environmental toxicant. However, the immunotoxic effects of lung, one of the targets of arsenic exposure, have not been extensively investigated in vivo. In the present study, we first confirmed that 2.5, 5 and 10mg/kg NaAsO2 orally for 24h dose-dependently triggered the infiltration of neutrophils, lymphocytes and macrophages in BALF. Not only the transcription activity, but also the secretion of proinflammatory cytokines IL-1β, IL-6 and TNF-α were consistently raised in the lung and BALF of acute arsenic-exposed mice. Acute oral administration of NaAsO2 also raised pulmonary MPO activity and mRNA levels of chemokine Mip-2 and Mcp-1. Meanwhile, obvious histopathological damages with inflammatory cells infiltration and erythrocyte aggregation around the capillaries were verified in the lung of mice drank arsenic-rich water freely for 3 months. Furthermore, we affirmed notable disturbance of CD4+ T-cell differentiation in the lung of acute arsenic-exposed mice, as demonstrated by up-regulated mRNA levels of regulator Gata3 and cytokine Il-4 of Th2, enhanced Foxp3 and Il-10 of Treg, down-regulated T-bet and Ifn-γ of Th1, as well as lessened Ror-γt and Il-23 of Th17. However, impressive elevation of cytokine Ifn-γ and Il-23, as well as moderate enhancement of Il-4 and Il-10 were found in the lung by subchronic arsenic administration. Finally, our present study demonstrated that both a single and sustained arsenic exposure prominently increased the expression of immune-related p38, JNK, ERK1/2 and NF-κB proteins in the lung tissue. While disrupting the pulmonary redox homeostasis by increasing MDA levels, exhausting GSH and impaired enzyme activities of CAT and GSH-Px, antioxidant regulator NRF2 and its downstream targets HO-1 and GSTO1/2 were also up-regulated by both acute and subchronic arsenic

  19. Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

    NARCIS (Netherlands)

    Verschuuren, H.G.; Kroes, R.; Vink, H.H.; Esch, G.J. van

    1966-01-01

    Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm. The lowest dietary levels found to retard growth in rats and

  20. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    Energy Technology Data Exchange (ETDEWEB)

    Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  1. Damascenine induced hepatotoxicity and nephrotoxicity in mice and in vitro assessed human erythrocyte toxicity

    Directory of Open Access Journals (Sweden)

    Bouguezza Yacine

    2015-09-01

    Full Text Available Nigella damascena seed is characterized by the presence of the major alkaloid, damascenine and its related metabolites. To our knowledge, no detailed subchronic toxicological assessment of damascenine (DA has been reported. The present study evaluated the potential toxicity of DA in vivo after sub-chronic intraperitoneal (i.p administration in mice and in vitro following human erythrocyte hemolysis. In vivo, a total of 48 adult male and female Swiss albino mice were used in a sub-chronic toxicity study. The mice received intraperitoneally two doses of DA (20 and 100 mg/kg for 28 days. Food intake, body weight and central body temperature were measured during the experiment. After completion of drug treatment, biochemical and histological analyses were performed. No mortality was observed in any of the treatment groups of mice, showing no toxic effects during the study. Neither were biochemical parameters altered; no significant differences were observed concerning glucose, bilirubin, aspartate transaminase (AST, alanine aminotransferase (ALT, urea, and creatinine parameters. No histopathological alterations were found in kidney and liver structures. In vitro, we focused on the human erythrocyte hemolytic process in the presence of several concentrations of DA. High level concentration of 1 000 μg/ml of DA revealed normal cell shapes and absence of hemolysis and deformation.

  2. Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

    Science.gov (United States)

    Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

    2012-01-01

    Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

  3. Systemic Metabolic Derangement, Pulmonary Effects, and Insulin Insufficiency Following Subchronic Ozone Exposure in Rats

    Science.gov (United States)

    This data set includes individual animal data collected for various biological endpoints that are included in the manuscript.Miller DB, Snow SJ, Henriquez A, Schladweiler MC, Ledbetter AD, Richards JE, Andrews DL, Kodavanti UP. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats. Toxicol Appl Pharmacol. 2016 Jun 28;306:47-57. The primary author Desinia Miller, an UNC-EPA co-opp Student has since completed her PhD and is no longer in EPA database.This dataset is associated with the following publication:Miller, D., S. Snow, A. Henriquez, M. Schladweiler, A. Ledbetter, J. Richards, D. Andrews, and U. Kodavanti. Systemic Metabolic Derangement, Pulmonary Effects, and Insulin Insufficiency following subchronic ozone exposure in rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, USA, 306: 47-57, (2016).

  4. Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats.

    Science.gov (United States)

    Gąsińska, Emilia; Bujalska-Zadrożny, Magdalena; Sar, Monika; Makulska-Nowak, Helena

    2012-01-01

    Dehydroepiandrosterone (DHEA), a neurosteroid, is known to be the most abundant hormone in the human body. Its role in the central nervous system has not been well defined. Previous studies indicate that DHEA is synthesized in the spinal cord and plays an important role in pain modulation. In the present study, we investigated the effect of DHEA on pain threshold in rats after both acute and subchronic treatment. Rats were orally administered with DHEA at a dose of 10 mg/kg once daily and the pain threshold was measured with mechanical and thermal stimuli. After acute treatment, DHEA exhibited pronociceptive effects which lasted up to 150 min. After subchronic administration, DHEA showed an opposite effect by elevating the pain threshold. The results suggest that DHEA could be indicated as a drug to improve treatment of chronic pain disorders.

  5. Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice

    Czech Academy of Sciences Publication Activity Database

    Lebedová, J.; Nováková, Z.; Večeřa, Zbyněk; Buchtová, Marcela; Dumková, J.; Dočekal, Bohumil; Bláhová, L.; Mikuška, Pavel; Míšek, Ivan; Hampl, A.; Hilscherová, K.

    (2018), s. 1-17 ISSN 1743-5390 R&D Projects: GA ČR(CZ) GBP503/12/G147; GA ČR(CZ) GAP503/11/2315 Institutional support: RVO:68081715 ; RVO:67985904 Keywords : nanoparticles * oxidative stress * subchronic * tissue damage Subject RIV: CB - Analytical Chemistry, Separation; DN - Health Impact of the Environment Quality (UZFG-Y) OBOR OECD: Analytical chemistry Impact factor: 6.428, year: 2016

  6. Endothelial nitric oxide synthase in rat brain is downregulated by sub-chronic antidepressant treatment.

    Science.gov (United States)

    Yoshino, Yuta; Ochi, Shinichiro; Yamazaki, Kiyohiro; Nakata, Shunsuke; Iga, Jun-Ichi; Ueno, Shu-Ichi

    2017-06-01

    Nitric oxide (NO) is a neurotransmitter that may be related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces a dose-dependent antidepressant-like effect. NO modulates major neurotransmitters involved in the neurobiology of MDD, such as norepinephrine, serotonin, dopamine, and glutamate. In this study, we investigated the effects of antidepressants as NO modulators in acute and sub-chronic treatments. Rats were injected with the SSRI paroxetine (PAR, 10 mg/kg), the SNRI milnacipran (MIL, 30 mg/kg), or the NaSSA mirtazapine (MIR, 10 mg/kg) for acute (1 h) or sub-chronic (3 weeks) treatment prior to analysis of nine brain regions (frontal cortex, temporal cortex, striatum, thalamus, hippocampus, midbrain, pons, cerebellum, and olfactory bulb). The mRNA expression levels of three NOS subtypes (neuronal: nNOS, inducible: iNOS, and endothelial: eNOS) were analyzed using real-time PCR with Taqman probes. Acute MIR treatment significantly increased nNOS mRNA expression in the hippocampus, midbrain, cerebellum and olfactory bulb, and iNOS mRNA expression in the frontal cortex and midbrain. Acute PAR and MIR treatments significantly increased eNOS mRNA expression in most brain regions. Conversely, sub-chronic treatment with all types of antidepressants resulted in significant decreases of eNOS mRNA expression in most brain regions. Sub-chronic treatment with the three types of antidepressants consistently decreased eNOS mRNA expression levels in the rat brain. These effects may be associated with the involvement of the NO system in the mechanism of action of antidepressants.

  7. GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice.

    Science.gov (United States)

    Rajagopal, Lakshmi; Burgdorf, Jeffrey S; Moskal, Joseph R; Meltzer, Herbert Y

    2016-02-15

    GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-D-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg.i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications. Copyright © 2015. Published by Elsevier B.V.

  8. Effect of artemether on rat hepatocytes during acute damage

    African Journals Online (AJOL)

    Chief OGBUZULU F

    2011-10-10

    Oct 10, 2011 ... Gassó M, Rubio M, Varela G (1996). Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride- induced cirrhosis. J. Hepatol. 25: 200-205. Hayes J, Condie L, Borzelleca J (1986). Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of carbon ...

  9. Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

    OpenAIRE

    Kajal Chakraborty; Deepu Joseph; Selsa J. Chakkalakal

    2014-01-01

    The short-term (acute) and long-term (subchronic) toxicity profile, mean lethal dose 50 (LD50), and no-observed-adverse-effect level (NOAEL) of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight) for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 ...

  10. Subchronic feeding study in beagle dogs of N-methylpyrrolidone.

    Science.gov (United States)

    Becci, P J; Gephart, L A; Koschier, F J; Johnson, W D; Burnette, L W

    1983-04-01

    The potential toxicity of N-methylpyrrolidone was evaluated following dietary administration for 13 weeks to male and female beagle dogs at dosage levels of 25, 79 and 250 mg per kg body weight per day. Body weight gain and food consumption, hematological and clinical chemical data, and ophthalmic, gross and histopathological examinations were used to study possible toxicological or pathological effects. No statistically significant treatment-related effects that were judged to be biologically meaningful were seen in any parameters of either male or female animals exposed to N-methylpyrrolidone at any dose level. However, a dose-dependent decrease in body weight and increase in platelet count that correlated with increased megakaryocytes was observed. Serum cholesterol in males decreased with increasing doses.

  11. Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice.

    Science.gov (United States)

    Ait Bali, Yassine; Ba-Mhamed, Saadia; Bennis, Mohamed

    2017-01-01

    Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH) exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks) and chronic (12 weeks) exposure (250 or 500 mg/kg/day) in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF), the elevated plus maze, the tail suspension and Splash tests (STs). Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and serotonin (5-HT) in the dorsal raphe nucleus (DRN), the basolateral amygdala (BLA) and the ventral medial prefrontal cortex (mPFC) was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes.

  12. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia.

    Science.gov (United States)

    Santini, Martin A; Ratner, Cecilia; Aznar, Susana; Klein, Anders B; Knudsen, Gitte M; Mikkelsen, Jens D

    2013-05-01

    Prefrontal serotonin 2A receptors (5-HT2A Rs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5-HT2A R at clinical relevant doses, and activation of 5-HT2A receptors by lysergic acid diethylamide (LSD) and LSD-like drugs induces a schizophrenia-like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well-established model for schizophrenia-like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5-HT2A Rs. As a measure of 5-HT2A R functionality, we used the 5-HT2A R agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch response (HTR) and mRNA expression of the immediate-early genes (IEGs) activity-related cytoskeletal associated-protein (Arc), c-fos, and early growth response protein 2 (egr-2) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5-day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated with changes in 5-HT2A R binding. Also, binding of the 5-HT1A R and the 5-HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration produces changes in the brain that result in an increase in the absolute effect of DOI. Therefore, neurotransmission involving the 5-HT2A R could contribute to the behavioral deficits observed after PCP treatment. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

  13. The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats

    Directory of Open Access Journals (Sweden)

    D. Mahmood

    2015-01-01

    Full Text Available The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment dosing of histamine H 3 receptor antagonists, ciproxifan (CPX (3 mg/kg, i.p., and clobenpropit (CBP (15 mg/kg, i.p, including clozapine (CLZ (3.0 mg/kg, i.p. and chlorpromazine (CPZ (3.0 mg/kg, i.p., the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H 3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H 3 receptor agonist, R-OC methylhistamine (10 mg/kg, i.p. counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

  14. Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice

    Directory of Open Access Journals (Sweden)

    Yassine Ait Bali

    2017-08-01

    Full Text Available Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks and chronic (12 weeks exposure (250 or 500 mg/kg/day in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF, the elevated plus maze, the tail suspension and Splash tests (STs. Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH in the substantia nigra pars compacta (SNc and serotonin (5-HT in the dorsal raphe nucleus (DRN, the basolateral amygdala (BLA and the ventral medial prefrontal cortex (mPFC was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes.

  15. Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice

    Science.gov (United States)

    Ait Bali, Yassine; Ba-Mhamed, Saadia; Bennis, Mohamed

    2017-01-01

    Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH) exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks) and chronic (12 weeks) exposure (250 or 500 mg/kg/day) in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF), the elevated plus maze, the tail suspension and Splash tests (STs). Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and serotonin (5-HT) in the dorsal raphe nucleus (DRN), the basolateral amygdala (BLA) and the ventral medial prefrontal cortex (mPFC) was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes. PMID:28848410

  16. Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon

    OpenAIRE

    Saša R. Ivanović; Dimitrijević, Blagoje; Ćupić, Vitomir; Jezdimirović, Milanka; Borozan, Sunčica; Savić, Mila; Savić, Djordje

    2016-01-01

    Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetylcholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the...

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

    Directory of Open Access Journals (Sweden)

    Micovic Zarko

    2016-09-01

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

  18. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors...... to human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  19. Concurrent Risperidone Administration Attenuates the Development of Locomotor Sensitization Following Sub-Chronic Phencyclidine in Rats.

    Science.gov (United States)

    McKibben, C E; Reynolds, G P; Jenkins, T A

    2016-03-01

    In schizophrenia early treatment may prevent disorder onset, or at least minimize its impact, suggesting possible neuroprotective properties of antipsychotics. The present study investigates the effects of chronic treatment with the atypical antipsychotic, risperidone, on locomotor sensitization in the subchronic phencyclidine-treated rat. Rats were treated with phencyclidine sub-chronically (2 mg/kg bi-daily for one week followed by a one-week wash-out period) or vehicle. Half of the phencyclidine group was concurrently treated with risperidone (0.5 mg/kg IP) twice daily for 15 days, beginning 3 days before the start of phencyclidine administration. 6 weeks after treatment all rats were injected with a phencyclidine-challenge (3.2 mg/kg) and immediately after their locomotor activity measured for 20 min. Co-administration of risperidone at the time of phencyclidine administration significantly reduced the phencyclidine-challenge locomotor effect administered 6 weeks later. These results demonstrate that concurrent risperidone is neuroprotective, and clearly suggests its functionality can be translated to a clinical setting for treating the so-called prodrome. © Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

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

    2013-10-01

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

  1. Cobb Mountain Subchron recorded at IODP Site U1306 (Eirik Drift, off SE Greenland)

    Science.gov (United States)

    Channell, J. E. T.

    2017-06-01

    The Cobb Mountain Subchron (CMS) is recorded over ∼5 m of core at ∼180 metres composite depth in the sediment sequence recovered at IODP Site U1306, in an interval where sedimentation rates are estimated at ∼15 cm kyr-1. The relatively high-resolution record of the CMS was acquired from u-channel samples from multiple core sections from four holes drilled at the site. Large-scale swings in magnetization directions at the onset of the subchron lead to virtual geomagnetic poles (VGPs) looping over the Indian Ocean, followed by a looping transit northward through the central Pacific Ocean, a ∼10 kyr (∼1.7 m) interval of VGPs at high northern latitudes particularly in the North Atlantic and NW Pacific Oceans, followed by an abrupt normal to reverse transition as VGPs track southward through Africa. Although the VGP paths are intricate and complex, they can be compared with other CMS VGP paths from Pacific and Atlantic sites, including ODP Sites 983 and 984. The age model for Site U1306 places the CMS in the 1178-1215 ka interval (∼37 kyr duration) which bridges marine isotope stages 35-36.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  4. Sub-chronic exposure to fipronil induced oxidative stress, biochemical and histopathological changes in the liver and kidney of male albino rats

    Directory of Open Access Journals (Sweden)

    Abdel-Tawab H. Mossa

    2015-01-01

    Full Text Available Fipronil (FPN is a broad-spectrum N-phenylpyrazole insecticide and has been used in agriculture and public health since the mid-1990s. The present study was designed to investigate the adverse effects of sub-chronic exposure to the FPN on the liver and kidney of male rats at three concentrations 0.1, 1 and 10 mg/L in drinking water for 45 days. Serum aspartate aminotransferases (AST, alanine aminotransferases (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity and levels of uric acid, creatinine and total protein were significantly increased in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and glutathione reduced (GSH were significantly decreased, while lipid peroxidation (LPO was significantly increased in treating rats in a concentration dependent manner. FPN caused histopathological alterations in liver and kidney of male rats. From our results, it can be concluded that FPN induced lipid peroxidation, oxidative stress, liver, and kidney injury in rats. These pathophysiological changes in liver and kidney tissues could be due to the toxic effect of FPN that associated with a generation of free radicals.

  5. Effects of subchronic exposure to waterborne cadmium on H-P-I axis hormones and related genes in rare minnows (Gobiocypris rarus).

    Science.gov (United States)

    Liu, Xiao-Hong; Wang, Zhi-Jian; Jin, Li; Huang, Jing; Pu, De-Yong; Wang, De-Shou; Zhang, Yao-Guang

    2017-11-01

    The H (hypothalamic)-P (pituitary)-I (interrenal) axis is critical in the stress response and other activities of fish. To further investigate cadmium (Cd) toxicity on the H-P-I axis and to identify its potential regulatory genes in fish, the adult female rare minnows (Gobiocypris rarus) were exposed to subchronic (5weeks) levels of waterborne Cd in the present study. This kind of treatment caused dose-dependent decline in fish growth, with significance in the high dose group (100μg/L). Correspondingly, low dose (5-50μg/L) waterborne Cd disrupted the endocrine system of H-P-I axis just at the secretion level, while high dose Cd disrupted both the secretion and synthesis of cortisol and its downstream signals in rare minnows, revealed by the significantly upregulation and positive correlation of corticosteroidogenic genes including MC2R, StAR, CYP11A1, and CYP11B1 in the kidney (including the interrenal tissue) (PPP-I axis in fish. The expression of FKBP5 in the intestine was positively and significantly correlated with that of Hsp90AA (PP<0.05), which indicated that Hsp90AA and Hsp90AB were more likely to serve as cofactors of GR and FKBP5 in response to Cd exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC

    National Research Council Canada - National Science Library

    Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

    2012-01-01

    ... 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing...

  7. Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain

    National Research Council Canada - National Science Library

    Raafat, K; El-Lakany, A

    2015-01-01

    ...) and Sambucus nigra L. aqueous (Elder) extracts, and their potential active isolates; for acute (6 h) and subchronic (8 days) glucose homeostasis, in vivo antioxidant potential and DN amelioration in alloxan-induced DM mice model...

  8. Antimony toxicity

    National Research Council Canada - National Science Library

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms...

  9. In vivo evaluation of the sealing ability of two endodontic sealers in root canals exposed to the oral environment for 45 and 90 days Avaliação, in vivo, da capacidade de selamento de dois cimentos endodônticos em canais radiculares expostos ao meio bucal por 45 e 90 dias

    Directory of Open Access Journals (Sweden)

    Patrícia Maria Poli Kopper

    2006-01-01

    Full Text Available This in vivo study evaluated the sealing ability of a resin-based sealer (AH Plus and a zinc oxide-eugenol sealer (Endofill in dogs' teeth, exposed to the oral environment for 45 and 90 days. Forty eight lower incisors from 8 dogs were endodonticaly treated. A stratified randomization determined the sealer use in each root canal. All canals were filled using the lateral condensation technique. The excess filling material at the cervical portion of the root canal was sectioned, leaving a 10-mm obturation length inside the canal. Teeth were provisionally sealed with glass ionomer cement for 24 h and the canals were exposed to the oral environment for either 45 or 90 days. Therefore, the experimental groups were as follows: A45- AH Plus for 45 days; A90- AH Plus for 90 days; E45- Endofill for 45 days; and E90- Endofill for 90 days (n=12. After the experimental period, the dogs were killed and the lower jaw was removed. The incisors were extracted and the roots were covered with two coats of nail varnish. The teeth were immersed in India ink for 96 h and submitted to diaphanization. Dye leakage (in mm was measured using stereomicroscopy (10x magnification. The results were statistically analyzed using two-way ANOVA and Tukey test for multiple comparisons (á = 0.05. Group E90 (2.03±0.94 showed significantly higher mean leakage value than all other groups (pEste estudo in vivo avaliou a capacidade de selamento de um cimento endodôntico resinoso (AH Plus e um a base de óxido de zinco eugenol (Endofill, em dentes de cães, expostos ao meio bucal, por 45 e 90 dias. Foi realizado o tratamento endodôntico de 48 incisivos inferiores de 8 cães. Uma randomização estratificada determinou o tipo de cimento a ser usado em cada canal que foram tratados pela técnica de condensação lateral. Após a obturação, o excesso de material obturador, na porção cervical do canal radicular foi seccionado, restando o comprimento de 10 mm no interior do canal

  10. Subchronic Toxicity Studies on 1,3,5-Trinitrobenzene, 1,3- Dinitrobenzene, and Tetryl in Rats. Subchronic Toxicity Evaluation of 1,3,5- Trinitrobenzene in Fischer 344 Rats

    Science.gov (United States)

    1994-05-01

    has been in use, largely for military purposes, since 1906. Wastewaters and soil at the original production sites and other plants devoted to munitions...readily absorbed through the skin (Von Burg, 1989). Tetryl was observed to be a powerful skin sensitizer in ammunition plant workers. Dermatitis, liver...MtSENTZAIC LYMPH WODI N N 9 N N x 0 N TtSItS N N W N N N N N UPIDIDYMIS N N x N N x N N S~grA6LVESICLES w N N N N N N p x x SKIN N N N N v 0 N N 9

  11. Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats.

    Science.gov (United States)

    Waghe, Prashantkumar; Sarkar, Souvendra Nath; Sarath, Thengumpallil Sasindran; Kandasamy, Kannan; Choudhury, Soumen; Gupta, Priyanka; Harikumar, Sankarankutty; Mishra, Santosh Kumar

    2017-04-01

    Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.

  12. Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain.

    Science.gov (United States)

    Fachim, Helene A; Srisawat, Umarat; Dalton, Caroline F; Harte, Michael K; Marsh, Samuel; Neill, Joanna C; Reynolds, Gavin P

    2016-09-01

    A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis.

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

    DEFF Research Database (Denmark)

    Sass, Amdi; Wörtwein, Gitta

    2012-01-01

    of subchronic treatment with the selective serotonin re-uptake inhibitor, fluoxetine (10mg/kg/day, i.p.) throughout adolescence (postnatal day 28-60) on learning and memory in the rat. Learning and memory were assessed at two time points: during adolescence, while the animals were being treated with fluoxetine...... and in young adulthood, 40 days after the termination of fluoxetine treatment. Fluoxetine treated rats were compared to a saline injected control group with respect to spatial navigation in the water maze, object recognition and object-in-place recognition memory. Additionally open field behaviour was examined....... In adolescent rats fluoxetine treatment impaired water-maze probe trial performance and object recognition at intertrial intervals of 15 and 60min, while leaving object-in-place recognition memory unaffected. In the open field the fluoxetine treated animals displayed reduced exploratory activity and higher...

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

    Science.gov (United States)

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

    2017-07-01

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

  15. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    Data.gov (United States)

    U.S. Environmental Protection Agency — Research interested in oxidative stress markers following exposure to VOCs. This dataset is associated with the following publication: Kodavanti , P., J. Royland ,...

  16. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    Science.gov (United States)

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  17. Human diets cooked by microwave or conventionally : comparative sub-chronic (13-wk) toxicity study in rats

    NARCIS (Netherlands)

    Jonker, D.; Til, H.P.

    1995-01-01

    To compare the possible effects of microwave and conventional cooking on a range of common dietary components, mixed human diets containing beef, potatoes and vegetables were fed to groups of 10 male and 10 female Wistar rats for 13 wk. The diet ingredients were cooked by either of the methods in a

  18. The Subchronic Inhalation Toxicity of DF2 (Diesel Fuel) Used in Vehicle Engine Exhaust Smoke Systems (VEESS).

    Science.gov (United States)

    1986-03-01

    times greater mortality than that experienced by the con- trol insects (Table J-2). Table J-3 shows that concentrations of 10%, 1%, and 0.1% of DF2...CO2 stimulation indicated that the chemoreceptors of the aortic and carotid bodies and the respiratory centers were functioning normally. In addition

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

    OpenAIRE

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

    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 parameter...

  20. The toxicity of beta-carotene.

    Science.gov (United States)

    Heywood, R; Palmer, A K; Gregson, R L; Hummler, H

    1985-08-01

    The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.

  1. Subchronic feeding study of high-free-lysine transgenic rice in Sprague-Dawley rats.

    Science.gov (United States)

    Yang, Qing-Qing; He, Xiao-Yun; Wu, Hong-Yu; Zhang, Chang-Quan; Zou, Shi-Ying; Lang, Tian-Qi; Sun, Samuel Sai-Ming; Liu, Qiao-Quan

    2017-07-01

    Lysine is considered to be the first essential amino acid in rice. An elite High-Free-Lysine transgenic line HFL1 was previously produced by metabolic engineering to regulate lysine metabolism. In this study, a 90-day toxicology experiment was undertaken to investigate the potential health effect of feeding different doses of HFL1 rice to Sprague-Dawley rats. During the trial, body weight gain, food consumption and food efficiency were recorded, and no adverse effect was observed in rats fed transgenic (T) rice diets compared with non-transgenic (N) or control diets. At both midterm and final assessments, hematological parameters and serum chemistry were measured, and organ weights and histopathology were examined at the end of the trial. There was no diet-related difference in most hematological or serum chemistry parameters or organ weights between rats fed the T diets and those fed the N or control diets. Some parameters were found to differ between T groups and their corresponding N and/or control groups, but no adverse histological effect was observed. Taken together, the data from the current trial demonstrates that high lysine transgenic rice led to no adverse effect in Sprague-Dawley rats given a diet containing up to 70% HFL1 rice in 90 days. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Antimony Toxicity

    Science.gov (United States)

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Improved understanding of key elements governing the toxicity of energy ash eluates.

    Science.gov (United States)

    Stiernström, S; Lindé, M; Hemström, K; Wik, O; Ytreberg, E; Bengtsson, B-E; Breitholtz, M

    2013-04-01

    Ash from incinerated waste consists mainly of a complex mixture of metals and other inorganic elements and should be classified based on its inherent hazardous effects according to EUs Waste Framework Directive. In a previous study, we classified eight eluates from ash materials from Swedish incineration plants, both chemically and ecotoxicologically (using bacteria, algae, crustacean and fish). Based on measured concentrations in the eluates together with literature acute toxicity data on the crustacean Nitocra spinipes we identified six elements (i.e. Zn, Cu, Pb, Al, K and Ca) potentially responsible for the observed ecotoxicity. However, comparing the used test methods with N. spinipes, the acute test was relatively insensitive to the eluates, whereas the (sub)chronic test (i.e. a partial life cycle test, investigating larval development ratio) was very sensitive. The overall aim of this follow-up study was to verify if the pinpointed elements could be responsible for the observed (sub)chronic toxicity of the eluates. Individual effect levels (i.e. NOEC values) for these six elements were therefore generated using the (sub)chronic test. Our results show that for six of the eight eluates, the observed ecotoxicity can be explained by individual elements not classified as ecotoxic (Al, K and Ca) according to chemical legislation. These elements will not be considered using summation models on elements classified as ecotoxic in solid material for the classification of H-14, but will have significant implications using ecotoxicological test methods for this purpose. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Differential deposition of manganese in the rat brain following subchronic exposure to manganese: a T1-weighted magnetic resonance imaging study.

    Science.gov (United States)

    Finkelstein, Yoram; Zhang, Na; Fitsanakis, Vanessa A; Avison, Malcolm J; Gore, John C; Aschner, Michael

    2008-11-01

    Manganism is a central nervous system disorder caused by toxic exposure to manganese. Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition, and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure. To characterize the regional distribution of Mn in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism before chronic exposure to Mn exerts its irreversible effects. Sprague-Dawley rats were intravenously injected with MnCl2 weekly, for a total of 14 weeks - approximately 1/10 of the lifetime of the rat. T1-weighted magnetic resonance imaging was used to detect the distribution of Mn deposition in brain tissues, as evidenced by areas of T1-weighted hyperintense signals. A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn-treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres. Prominent Mn depositions, evidenced by T1-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages, and may explain its pathophysiology.

  6. In vitro toxicity of trichothecenes on rat haematopoietic progenitors.

    Science.gov (United States)

    Parent-Massin, D; Thouvenot, D

    1995-01-01

    The fusarial toxicosis induced by trichothecenes is characterized by common syndromes such as vomiting, inflammation, haemorrhages, diarrhoea and haematological changes. Subchronic ingestion of trichothecenes causes a decrease in circulating white cells. This leukopenic change of animals is reported as a characteristic feature in the best known human disorder: Alimentary Toxic Aleukia (ATA). The aim of the present study was to evaluate whether the haematologic disorders imputed to trichothecenes were a result of myelotoxicity by investigating in an in vitro model. Rat haematopoietic progenitors, Colony Forming Units-Granulocytes and Macrophages (CFU-GM), were cultured in the presence of several concentrations of four trichothecenes; T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON). All these trichothecenes were cytotoxic to rat haematopoietic progenitor cells. It is concluded that haematological disorders observed during trichothecene intoxication of animals are caused by the destruction of haematopoietic progenitors such as CFU-GM cells.

  7. [Toxic megacolon].

    Science.gov (United States)

    Leppkes, M; Ganslmayer, M; Strauß, R; Neurath, M F

    2015-10-01

    Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.

  8. Antagonistic Effect of Laver, Pyropia yezonensis and P. haitanensis, on Subchronic Lead Poisoning in Rats.

    Science.gov (United States)

    Guo, Yingying; Gu, Xiaohui; Jiang, Yanhua; Zhu, Wenjia; Yao, Lin; Liu, Zhantao; Gao, Hua; Wang, Lianzhu

    2017-06-03

    Lead, one of the most harmful heavy metals, can cause various hazardous effects on living organisms. This study was undertaken to evaluate the antagonistic and protective effects of two economically important laver species, Pyropia yezoensis and P. haitanensis, against subchronic lead poisoning in rats by a 30-day feeding test. Sixty-four healthy Wistar rats were randomly divided into eight groups with eight rats (4♂ + 4♀) per group, among which, one group was served as the control, the others were respectively treated with lead acetate (5 mg/kg b w), and a combination of lead acetate and P. yezoensis or P. haitanensis at different dosages. Weight gain of rats was observed and recorded. Changes in antioxidant indexes, and liver and renal function markers were determined to evaluate the antagonistic effect. Lead content in rats was determined to investigate lead excretion effect of laver. The results showed that exposure to lead caused lead accumulation in kidney and liver, thus leading to significant oxidative damage and impaired liver and renal function compared to the control group. The co-treatment of laver slightly increased body weight compared to the lead-treated group. The co-administration of laver restored liver and renal function of rats by preventing the increment in the activities of alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST), and the levels of blood urea nitrogen (BUN) and creatinine (Cr). The increasing of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and lowering of the enhanced malondialdehyde (MDA) contents of rats were observed in the laver co-treated groups, which indicated that laver enhanced the antioxidative capacity of rats. The laver also enhanced lead content in feces and reduced it in liver and kidney. The results indicated that P. yezoensis and P. haitanensis could maintain or promote the normal physiological and biochemical function of lead

  9. Acute selenium toxicity associated with a dietary supplement.

    Science.gov (United States)

    MacFarquhar, Jennifer K; Broussard, Danielle L; Melstrom, Paul; Hutchinson, Richard; Wolkin, Amy; Martin, Colleen; Burk, Raymond F; Dunn, John R; Green, Alice L; Hammond, Roberta; Schaffner, William; Jones, Timothy F

    2010-02-08

    Selenium is an element necessary for normal cellular function, but it can have toxic effects at high doses. We investigated an outbreak of acute selenium poisoning. A case was defined as the onset of symptoms of selenium toxicity in a person within 2 weeks after ingesting a dietary supplement manufactured by "Company A," purchased after January 1, 2008. We conducted case finding, administered initial and 90-day follow-up questionnaires to affected persons, and obtained laboratory data where available. The source of the outbreak was identified as a liquid dietary supplement that contained 200 times the labeled concentration of selenium. Of 201 cases identified in 10 states, 1 person was hospitalized. The median estimated dose of selenium consumed was 41 749 microg/d (recommended dietary allowance is 55 microg/d). Frequently reported symptoms included diarrhea (78%), fatigue (75%), hair loss (72%), joint pain (70%), nail discoloration or brittleness (61%), and nausea (58%). Symptoms persisting 90 days or longer included fingernail discoloration and loss (52%), fatigue (35%), and hair loss (29%). The mean initial serum selenium concentration of 8 patients was 751 microg/L (reference range, selenium concentration of 7 patients was 166 microg/24 h (reference range, selenium in a liquid dietary supplement resulted in a widespread outbreak. Had the manufacturers been held to standards used in the pharmaceutical industry, it may have been prevented.

  10. 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.

  11. Toxicity of nickel ores to marine organisms.

    Science.gov (United States)

    Florence, T M; Stauber, J L; Ahsanullah, M

    1994-06-06

    Queensland Nickel proposes to import New Caledonian (Ballande) and Indonesian (Gebe) nickel ores, one option being ship-to-barge transfer in Halifax Bay, North Queensland. Because small amounts of ore may be split during the unloading and transfer operations, it was important to investigate the potential impact of the spilt ore on the ecological health of the Bay. Long-term leaching of the ores with seawater showed that only nickel and chromium (VI) were released from the ores in sufficient concentrations to cause toxicity to a range of marine organisms. The soluble fractions of nickel and chromium (VI) were released from the ores within a few days. Nickel, chromium (VI) and the ore leachates showed similar toxicity to the juvenile banana prawn Penaeus merguiensis, the amphipod Allorchestes compressa and both temperature (22 degrees C) and tropical (27 degrees C) strains of the unicellular marine alga Nitzschia closterium. In a series of 30-day sub-chronic microcosm experiments, juvenile leader prawns Penaeus monodon, polychaete worms Galeolaria caespitosa and the tropical gastropod Nerita chamaeleon were all very resistant to the nickel ores, with mortality unaffected by 700 g ore per 50 l seawater. The growth rate of the leader prawns was, however, lower than that of the controls. From these data, a conservative maximum safe concentration of the nickel ores in seawater is 0.1 g l-1. The nickel ore was not highly toxic and if spilt in the quantities predicted, would not have a significant impact on the ecological health of the Bay.

  12. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.

    Science.gov (United States)

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B; Remmers, Christine L; Xu, Jian; Meltzer, Herbert Y; Contractor, Anis

    2016-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Health and nutritional status of Wistar rats following subchronic exposure to CV127 soybeans.

    Science.gov (United States)

    Chukwudebe, Amechi; Privalle, Laura; Reed, Andrew; Wandelt, Christine; Contri, Daniela; Dammann, Martina; Groeters, Sibylle; Kaspers, Uwe; Strauss, Volker; van Ravenzwaay, Bennard

    2012-03-01

    This subchronic duration feeding study evaluated the nutritional and health status of rats fed diets containing CV127 at incorporation levels of 11% and 33%. For control comparisons, rats were also exposed to similar incorporation levels of the near isogenic conventional soybean variety (Conquista) and two other conventional soybean varieties (Monsoy, Coodetec). In spite of phenotypic differences among these four soybean varieties, there were no quantitative differences in their respective proximate and other compositional properties, including proteins, amino acids, antinutrients and nutritional cofactors. All diets were prepared by blending the respective processed soybean meal with ground Kliba maintenance meal at high (33%) and low (11%) incorporation levels, and the blended diets were fed to Wistar rats for about 91 days. Although there were some isolated parameters indicating statistically significant changes, these lacked consistency and a plausible mechanism and were thus assessed to be incidental. The totality of results demonstrate that CV127 soybeans are similar with respect to their nutritional value and systemic effects as its near isogenic conventional counterpart, as well as other conventional soybean varieties. Hence, introduction of AHAS gene into soybeans does not substantially alter its compositional properties, nor adversely affect its nutritional or safety status to mammals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The effects of subchronic lithium administration in male Wistar mice on some biochemical parameters.

    Science.gov (United States)

    Nciri, R; Allagui, Ms; Vincent, C; Murat, J C; Croute, F; El Feki, A

    2009-10-01

    Lithium salts are efficiently used for treatment of psychiatric disorders. However, prolonged treatment frequently involves adverse side effects. In this study, effects of lithium carbonate administration on some biochemical parameters were studied in male mice. Lithium carbonate (20, 40, or 80 mg/kg body weight corresponding to 3.77, 7.54, or 15.08 mg Li element/kg body weight, respectively) was injected daily for 14 or 28 days. The following parameters were recorded: drinking water consumption, body weight, lithium and testosterone serum concentrations, activities of catalase (CAT), superoxide-dismutase (SOD), and glutathione-peroxidase (GPX), and level of lipid peroxidation (expressed as TBARS) in liver was performed. Lithium treatment, especially at the highest dose for 28 days, was found to induce weight gain and polydipsia and a significant decrease of plasma testosterone level. Lipid peroxidation level and activities of SOD and GPX were increased in liver, which suggests a perturbation of the antioxidative status. Our results indicate that subchronic exposure to lithium, which induces weight gain and polydipsia under our experimental conditions, also damages the male reproductive system and triggers an oxidative stress in the liver.

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

    Directory of Open Access Journals (Sweden)

    Jonathan L Brigman

    2009-02-01

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

  16. The Air Toxics Health Effects Database (ATHED).

    Science.gov (United States)

    Woodall, George M; Smith, Roy L

    2008-11-15

    The Air Toxics Health Effects Database (ATHED) is currently used by the EPA's Office of Air Quality Planning and Standards (OAQPS) to support risk assessments for the Residual Risk Program. An assessment of the residual risk is required to be performed at a specified time (typically 8 years) following the promulgation of a technology-based Maximum Achievable Control Technologies (MACT) standard. The goal of the Residual Risk Program is to assure that the risk that remains after MACT standards are implemented (i.e., the "residual risk") is acceptable, and if not, to propose additional regulations to mitigate those risks. ATHED maintains all available reference values for each chemical as separate data records, and includes values for all exposure durations (acute, short-term, subchronic and chronic). These values are used as benchmarks to determine acceptable exposure levels to the hazardous air pollutants (HAPs) listed in Section 112 of the Clean Air Act. ATHED also provides useful background information on the uncertainty and/or modifying factors that were applied in the derivation of each reference value, as well as the point of departure and the critical study/studies. To facilitate comparisons across durations for a specific chemical, ATHED data can be graphically presented.

  17. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  18. Studying toxicity

    Science.gov (United States)

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  19. Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

    DEFF Research Database (Denmark)

    Nielsen, Brian S.; Larsen, Erik Huusfeldt; Ladefoged, Ole

    2017-01-01

    Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example......Cl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter...

  20. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  1. Subchronic exposure to diisocyanates increases guinea pig tracheal smooth muscle responses to acetylcholine.

    Science.gov (United States)

    Marek, W; Potthast, J; Marczynski, B; Mensing, T; Baur, X

    1999-01-01

    In order to study the threshold concentrations of isocyanates (IC) for induction of lung disorders, constrictive responses of tracheal smooth muscles to acetylcholine (ACH) in guinea pigs with and without diisocyanate [toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI) and diphenylmethane diisocyanate (MDI)] exposure were investigated. An IC-induced increase in smooth muscle responsiveness was studied by measuring cumulative ACH dose responses (10(-10) to 10(-4) M ACH). Basal ACH dose-response curves, measured twice in intervals of 1 h using tracheal preparations of 11 guinea pigs previously not exposed to IC, were reproducible. Subchronic in vivo exposures to TDI, HDI, and MDI atmospheres of 10 and 20 parts per billion (ppb) on 5 consecutive days led to significantly (p < 0.05) increased ACH responsiveness of tracheal smooth muscle, whereas concentrations of 2.5 and 5 ppb were not effective. Exposure to HDI atmospheres of 10 ppb for 1, 2, 4, or 8 weeks resulted in a time-dependent increase in ACH responses (p < 0.05) of guinea pig tracheal smooth muscle. Increased tracheal muscle responses to ACH were transient since tracheal preparations from animals exposed to 10 and 20 ppb MDI for 4 weeks and with an exposure-free interval of 8 weeks before preparation did not show enlarged ACH responses, which were present in preparations at the end of the exposure period (p < 0.05). Exposure to low IC concentrations as present in workplaces cause increased ACH responsiveness of guinea pig tracheal smooth muscle. The increased responsiveness of the airways seems to be largely reversible, since normal responses were found after 8 weeks of IC avoidance. Reversibility of IC-induced airway hyperresponsiveness is of great occupational and preventive medical importance. Workers with acquired airway hyperresponsiveness might escape lung damage if the changes are detected in an early stage before alterations in lung function are in a chronic stage.

  2. Subchronic exposure to acrylamide affects colon mucin secretion in juvenile wistar rats

    Directory of Open Access Journals (Sweden)

    Koledin Ivana

    2016-01-01

    Full Text Available Acrylamide (AA is an important industrial chemical worldwide. AA also forms naturally in many high-carbohydrate foods (bread, French fries, coffee, etc. when they are heated. Since AA is ubiquitous in the human diet, and more than one-third of the calories we take in each day come from foods with detectable levels of acrylamide, the aim of this study was to determine the effect of subchronic AA treatment on colon goblet cell mucin secretion. Male Wistar rats were gavaged with AA for 5 days a week for 21 days. The animals were divided into three groups that were gavaged with different AA concentrations (0, 25, 50 mg/kg/day. Colon samples were processed for histochemical (PAS-AB, HID-AB and immunohistochemical (anti-rat MUC2 antibody staining to visualize mucins in the goblet cells. AA treatment showed an alteration in mucin production and secretion in that the amount of all investigated mucin types dropped. More prominent changes were detected in the upper crypt part where a decreased number of goblet cell was observed. AA treatment elicited a significant reduction in neutral mucins, while acidic mucins showed linearly decreasing trend with respect to AA doses. Also, a linear reduction of MUC2 mucins was noticed. Sulfomucins were absent in the colon lower crypt in all experimental groups, while in the upper crypt both sulfo- and sialomucins were significantly decreased. The results of our study point to changes in the synthesis, differentiation and distribution of mucins after AA treatment, which can have adverse effect on colorectal health. [Projekat Ministarstva nauke Republike Srbije, br. III46001

  3. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.

    Science.gov (United States)

    Dudek, Magdalena; Kuder, Kamil; Kołaczkowski, Marcin; Olczyk, Adrian; Żmudzka, Elżbieta; Rak, Aleksandra; Bednarski, Marek; Pytka, Karolina; Sapa, Jacek; Kieć-Kononowicz, Katarzyna

    2016-10-01

    The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence of pitolisant - H3 histamine antagonist - on subchronic olanzapine-induced depresion-like symptoms, sedation and hypertriglicerydemia. Forced swim test was conducted to determinate depressive-like effect of olanzapine and antidepressive-like activity during the co-administered pitolisant. The test was performed after the first and fifteenth day of the treatment of the mice. The spontaneous activity of the mice was measured on the fourteenth day of the treatment with a special, innovative RFID-system (Radio-frequency identification system) - TraffiCage (TSE-Systems, Germany). Triglyceride levels were determined on the sixteenth day of the experiment after 15 cycles of drug administration. Daily olanzapine treatment (4 mg/kg b.w., i.p., d.p.d) for 15 days significantly induces sedation (p < 0.05) and prolongs immobility time in forced swim tests (FST) in mice (p < 0.05); and also elevates the level of triglycerides (p < 0.05). Administration of pitolisant (10 mg/kg b.w., i.p.) subsequentto olanzapine normalizes these adverse effects. This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs.

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

    Science.gov (United States)

    Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi

    2016-09-01

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

  5. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis Extract Affects Rat Liver Function and Antioxidant Status

    Directory of Open Access Journals (Sweden)

    Johanna Debora van der Merwe

    2015-12-01

    Full Text Available An aspalathin-enriched green rooibos (Aspalathus linearis extract (GRE was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP intake was 756 and 627 mg Gallic acid equivalents (GAE/kg body weight (bw/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study. Consumption of GRE increased feed intake significantly (p < 0.05 compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05 reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05 increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05 increased after 28 days, while glutathione (GSH content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction.

  6. Pubertal Development and Thyroid Function in Intact Juvenile Rats Exposed to 3-Nitro-1,2,4-Trazol-5-One (NTO), February-June 2012

    Science.gov (United States)

    2014-02-01

    tested, 1000 mg/kg-day of NTO. The most pronounced effects of NTO following subchronic oral exposure were testicular and epididymal toxicity and...at or above 1000 mg/kg-day. The 90-day study on NTO revealed significant reductions in testes and epididymides weights and sperm counts at dosages of...caput, corpus, and cauda, was examined in order to identify such lesions as sperm granulomas, leukocytic infiltration (inflammation), aberrant cell types

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Olakunle James Onaolapo

    2013-01-01

    Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  9. Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making.

    Science.gov (United States)

    Broos, Nienke; Loonstra, Rhianne; van Mourik, Yvar; Schetters, Dustin; Schoffelmeer, Anton N M; Pattij, Tommy; De Vries, Taco J

    2015-07-01

    Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occurred independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects. © 2014 Society for the Study of Addiction.

  10. Toxicity of malathion to mammals, aquatic organisms and tissue culture cells.

    Science.gov (United States)

    Dési, I; Dura, G; Gönczi, L; Kneffel, Z; Strohmayer, A; Szabó, Z

    The effect of malathion on rats (75 and 38 mg/kg bwt), aquatic organisms (100 to 0.001 mg/L), and cells in tissue culture (1000 to 1 ppm) was studied. The conventional toxicological tests conducted for 90 days on rats yielded negative results. ChE activity was determined in plasma, liver, brain and erythrocyte samples. It was significantly reduced in the erythrocytes of animals treated with the larger dose for 21 days and in the cerebral cortex of rats fed either of the doses. ChE activity of rats consuming malathion for 90 days did not differ significantly from that of the controls. In contrast, the psychophysiological examinations utilized in the experiments indicated abnormalities within 21 days. Alterations were observed in the EEG and EMG records after 90 days of feeding. Malathion had a definitely harmful effect on phylogenetically and ontogenetically young aquatic organisms, as well as on the cells of monkey kidney culture. The latter finding suggests that the preparation has a direct destructive effect on cells. Although it is not suggested that malathion should be regarded a toxic agent thus requiring limitation of application, attention is directed to the fact that inconsiderate use of the preparation may involve potential dangers for man and his environment.

  11. 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.

  12. [Toxic methemoglobinemia].

    Science.gov (United States)

    Bender, P; Neuhaus, H

    2011-04-01

    A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats.

    Science.gov (United States)

    Horiguchi, Masakuni; Huang, Mei; Meltzer, Herbert Y

    2011-09-01

    Subchronic administration to rodents of the N-methyl-D-aspartate non-competitive antagonist, phencyclidine (PCP), impairs novel object recognition (NOR). Atypical antipsychotic drugs (APDs) reverse the effects of subchronic PCP on NOR. The effect of metabotropic glutamate₂/₃ receptor (mGlu₂/₃) agonists upon NOR is unknown. We tested the hypotheses that the mGlu₂/₃ agonist, LY379268, by itself, or in combination with APDs or pimavanserin, a 5-HT(2A) inverse agonist, would reverse the deficit in NOR induced by subchronic treatment with PCP (2 mg/kg, b.i.d., for 7 days). The mGlu₂/₃ agonist LY379268 (1 or 3 mg/kg) did not attenuate the PCP-induced NOR deficit. However, together with sub-effective dose of the atypical APDs, clozapine (0.1 mg/kg) or lurasidone (0.03 mg/kg), but not the typical APD, haloperidol (0.1 mg/kg), or pimavanserin (3 mg/kg), LY379268, 1 mg/kg, significantly reversed the PCP-induced NOR deficit. Moreover, the effect of clozapine was blocked by the mGlu₂/₃ antagonist, LY341495 (1 mg/kg). These results indicate that mGlu₂/₃ agonism can potentiate the ability of atypical, but not typical APDs, to ameliorate the effect of subchronic PCP on NOR, that mGlu₂/₃ agonism may contribute to the ability of atypical APDs to acutely reverse the effect of subchronic PCP on NOR, but that by itself, mGlu₂/₃ agonism, is ineffective in this model of cognitive impairment in schizophrenia. These results suggest that mGlu₂/₃ receptor agonism should be investigated as an adjunctive treatment of cognitive impairment in schizophrenia rather than as monotherapy, which may be effective for control of psychosis, but not for cognitive impairment.

  14. Effects of sub-chronic Cd exposure on levels of copper, selenium, zinc, iron and other essential metals in rat renal cortex

    Directory of Open Access Journals (Sweden)

    Walter C. Prozialeck

    2016-01-01

    Full Text Available Cd (Cd is a nephrotoxic environmental pollutant that causes generalized proximal tubule dysfunction. Even though the specific mechanisms by which Cd damages the kidney have yet to be fully elucidated, there is evidence to suggest that some of these nephrotoxic effects may result from the ability of Cd to alter the levels and function of metals such as Cu, Se, Zn and Fe within the kidney. In order to further explore this issue, we examined the effects of subchronic Cd exposure on tissue levels of a panel of metals (Ca, Cu, Fe, K, Mg, Na, Se and Zn in the rat renal cortex. Adult male Sprague-Dawley rats were treated with CdCl2 (0.6 mg Cd/kg body weight in isotonic saline by subcutaneous injection, 5 days per week for 6, 9 or 12 weeks. At each time point, 24 h urine samples were collected and assayed for levels of protein, creatinine, β2 microglobulin and cystatin C. Samples of renal cortex were removed and assayed for levels of the metals of interest by inductively-coupled mass spectrometry at Michigan State University. Results showed that at 9 and 12 weeks, Cd caused significant increases in urine volume and urinary protein with no change in creatinine excretion. Increases in the excretion of the urinary biomarkers β2 microglobulin and cystatin C were evident after 6 weeks of Cd exposure. Results of the metal analyses showed that Cd caused significant increases in tissue levels of Cu and Se at all of the time points examined. Tissue levels of Zn were transiently elevated at 6 weeks but declined to control levels at 9 and 12 weeks. Cd caused a significant decrease in levels of Fe at 9 and 12 weeks. Cd had no effects on any of the other metals. Tissue levels of Cd were 530 ± 52, 863 ± 23, 837 ± 23 ppm dry weight at 6, 9 and 12 weeks, respectively. These results indicate that the early stages of Cd nephrotoxicity are associated with alterations in renal tissue levels of Cu, Se, Zn and Fe. The fact that the changes in levels of the

  15. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    Directory of Open Access Journals (Sweden)

    Barfod Kenneth K

    2010-09-01

    exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.

  16. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  17. Maintenance of filtering molluscs in aquaria for sub-chronic studies

    Directory of Open Access Journals (Sweden)

    Mara Mercedes de Andréa

    2009-02-01

    Full Text Available This work determined the best survival conditions for the clam Mytella guyanensis and the mussel Perna perna in the estuary and sea aquaria respectively over at least 12 days, which could enable their use in the ecotoxicological studies. The aquaria were set up with the appropriate water and sedimen, and allowed to establish for a minimum of one month before adding the organisms. The best survival conditions for M. guyanensis required more time for the aquarium stabilization, addition of inocula and more frequent water changes than for P. perna. The organisms' lipid contents increased and their condition index was maintained indicating the good conditions of the aquaria, hence, their possible use in the sub-chronic studies.Estudos sobre a dinâmica de contaminação de organismos marinhos devem ser feitos sob condições controladas pelo tempo necessário para que os organismos possam responder à presença do agente contaminante. No entanto, a manutenção de organismos em aquários por determinado período pode ser difícil porque todas as outras variáveis do ambiente precisam ser próximas às condições naturais. Este trabalho determinou as melhores condições de sobrevivência do marisco Mytella guyanensis e do mexilhão Perna perna, respectivamente em aquários de estuário e de mar, por período de até 12 dias. Os aquários foram montados com água e sedimento de estuário ou de mar e estabilizados por, no mínimo, um mês antes da colocação dos respectivos organismos. As melhores condições de sobrevivência de M. guyanensis requisitaram mais tempo de estabilização do aquário, adição de inóculos e trocas de água mais freqüentes do que para os P. perna. Os conteúdos de lipídios aumentaram com o tempo e o índice de condição dos organismos foi mantido, indicando as boas condições dos aquários e, conseqüentemente, a possibilidade de uso em pesquisas ecotoxicológicas.

  18. Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress.

    Science.gov (United States)

    Hodes, Georgia E; Pfau, Madeline L; Purushothaman, Immanuel; Ahn, H Francisca; Golden, Sam A; Christoffel, Daniel J; Magida, Jane; Brancato, Anna; Takahashi, Aki; Flanigan, Meghan E; Ménard, Caroline; Aleyasin, Hossein; Koo, Ja Wook; Lorsch, Zachary S; Feng, Jian; Heshmati, Mitra; Wang, Minghui; Turecki, Gustavo; Neve, Rachel; Zhang, Bin; Shen, Li; Nestler, Eric J; Russo, Scott J

    2015-12-16

    Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. Women have a higher incidence of depression than men. However, preclinical models, the first step in developing new diagnostics and therapeutics, have been performed mainly on male subjects. Using a stress-based animal model of depression that causes behavioral effects in females but not males, we demonstrate a sex-specific transcriptional profile in brain reward circuitry. This transcriptional profile can be altered by removal of an epigenetic mechanism, which

  19. Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline

    Science.gov (United States)

    Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif Z.; Boor, Paul J.; Khan, M. Firoze

    2008-01-01

    The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Splenotoxicity of aniline is associated with iron overload and generation of reactive oxygen species (ROS) which can cause oxidative damage to DNA, proteins and lipids (oxidative stress). 8-Hydroxy-2’-deoxyguanosine (8-OHdG) is one of the most abundant oxidative DNA lesions resulting from ROS, and 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase/lyase enzyme, plays a key role in the removal of 8-OHdG adducts. This study focused on examining DNA damage (8-OHdG) and repair (OGG1) in the spleen in an experimental condition preceding a tumorigenic response. To achieve that, male Sprague-Dawley rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. Aniline treatment led to a significant increase in splenic oxidative DNA damage, manifested as a 2.8-fold increase in 8-OHdG levels. DNA repair activity, measured as OGG1 base excision repair (BER) activity, increased by ~1.3 fold in the nuclear protein extracts (NE) and ~1.2 fold in the mitochondrial protein extracts (ME) of spleens from aniline-treated rats as compared to the controls. Real-time PCR analysis for OGG1 mRNA expression in the spleen revealed a 2-fold increase in expression in aniline-treated rats than the controls. Likewise, OGG1 protein expression in the NEs of spleens from aniline-treated rats was ~1.5 fold higher, whereas in the MEs it was ~1.3 fold higher than the controls. Aniline treatment also led to stronger immunostaining for both 8-OHdG and OGG1 in the spleens, confined to the red pulp areas. It is thus evident from our studies that aniline-induced oxidative stress is associated with increased oxidative DNA damage. The BER pathway was also activated, but not enough to prevent the accumulation of oxidative DNA damage (8-OHdG). Accumulation of mutagenic oxidative DNA lesions

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  1. Changes in Gut Microbiota May Be Early Signs of Liver Toxicity Induced by Epoxiconazole in Rats.

    Science.gov (United States)

    Xu, Cheng; Liu, Qian; Huan, Fei; Qu, Jianhua; Liu, Wei; Gu, Aihua; Wang, Yubang; Jiang, Zhaoyan

    2014-01-01

    The gut microbiome is essential for human health due to its effects on disease development, drug metabolism and the immune system. It may also play a role in the interaction with environmental toxicants. However, the effect of epoxiconazole, a fungicide active ingredient from the class of azoles developed to protect crops, on the abundance and composition of the gut microbiome has never been studied. We put forward the hypothesis that changes in gut microbiota may be early signs of toxicity induced by epoxiconazole. In this study, female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100 mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene sequencing. Body and organ weight, and blood biochemistry were also measured after 90 days of oral epoxiconazole exposure. Interestingly, the abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria increased. At family level, Lachnospiraceae and Enterobacteriaceae were selectively enriched following epoxiconazole exposure. Our results indicate that epoxiconazole exposure may induce changes in the gut microbiome and potential liver toxicity. Changes in the gut microbiome may be used as early indicators for monitoring the health risk of the host. © 2015 S. Karger AG, Basel

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

    Science.gov (United States)

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

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

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

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  4. Potential testicular toxicity of sodium nitrate in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Abo-Salem, Osama M; Abd-Ellah, Hala F; Abdel-Naim, Ashraf B

    2010-02-01

    Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress. Copyright 2009. Published by Elsevier Ltd.

  5. Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

    Energy Technology Data Exchange (ETDEWEB)

    Poorvu, Philip D. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Sadow, Cheryl A. [Department of Radiology, Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts (United States); Townamchai, Kanokpis; Damato, Antonio L. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

    2013-04-01

    Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.

  6. Influence of Cord Blood Fraction (below 5 kDa on Reparative Processes during Subchronic Ulcerative Gastropathy

    Directory of Open Access Journals (Sweden)

    Alexander Kirillovich Gulevsky

    2011-01-01

    Full Text Available The low molecular fraction (below 5 kDa was extracted from cord blood by ultrafiltration. It has been shown that the cord blood fraction possesses antiulcer activity on the model subchronic stomach ulcer. The cord blood fraction injections caused a significant reduction in the area of ulcer lesions and promoted recovery of microcirculation, thickness, and structure of gland layer, which was accompanied by a decrease in leucocytes infiltration and an increase in glycosaminoglycans synthesis. That resulted in a faster recovery of mucus membrane of stomach as compared with Actovegin. Application of the cord blood fraction in animals with stomach ulcer normalized the alkaline phosphatase activity and thiobarbituric acid-active product content. Gel-penetrating chromatography showed that the patterns of the low molecular substances from cord blood and Actovegin differed both qualitatively and quantitatively.

  7. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  8. Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain.

    Science.gov (United States)

    Giatti, Silvia; Foglio, Benedetta; Romano, Simone; Pesaresi, Marzia; Panzica, Giancarlo; Garcia-Segura, Luis Miguel; Caruso, Donatella; Melcangi, Roberto Cosimo

    2016-01-01

    The enzymatic conversion of progesterone and testosterone by the enzyme 5alpha-reductase exerts a crucial role in the control of nervous function. The effects of finasteride in the brain, an inhibitor of this enzyme used for the treatment of human benign prostatic hyperplasia and androgenic alopecia, have been poorly explored. Therefore, the effects of a subchronic treatment with finasteride at low doses (3 mg/kg/day) and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions as well as on the expression of classical and non-classical steroid receptors have been evaluated in male rats. After subchronic treatment (i.e., for 20 days) the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) an upregulation of the androgen receptor in the cerebral cortex and beta3 subunit of the GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex, an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma). Moreover, other changes in neuroactive steroid levels, steroid receptors (i.e., an upregulation of the estrogen receptor alpha and a downregulation of the estrogen receptor beta in the cerebral cortex) and GABA-A receptor subunits (i.e., a decrease of alpha 4 and beta 3 mRNA levels in the cerebral cortex) were detected. These findings suggest that finasteride treatment may have broad consequences for brain function. © 2015 S. Karger AG, Basel.

  9. Chronic liver disease and subchronic nephritis in a male warty chameleon (Furcifer verrucosus with transient hyperglycaemia – case report

    Directory of Open Access Journals (Sweden)

    Zdeněk Knotek

    2011-01-01

    Full Text Available A two-year old male warty chameleon (Furcifer verrucosus weighing 160 g was presented for veterinary examination following 4 weeks of decreased ability to catch insects with the tongue and difficulty in swallowing the prey. Non-invasive endoscopy did not reveal any macroscopic changes of the oral cavity mucosa or the cranial part of the esophagus. Dorsoventral and laterolateral plain and contrast radiographs revealed enlargement of the medial part of the liver without any visible abnormalities in the regions of the esophagus, stomach or small intestine. Abnormalities in the plasma chemistry profile included transient hyperglycaemia (52.68–57.18 mmol/l and hyperuricaemia (452.70–622.20 μmol/l. The chameleon was examined at 7, 20 and 22 weeks after initial examination. Its body weight decreased to 120 g. A blood profile revealed normoglycaemia (16.37–10.22 mmol/l and hyperphosphataemia (2.92–3.06 mmol/l at the last three examinations. The chameleon died suddenly 33 days after the final examination. Necropsy revealed the presence of a large liver cyst, filled with fluid. The liver had lost all of its normal structure. The kidneys showed a large area with fibrosis and multiple uric acid tophi. The post mortem findings were defined as liver with fatty degeneration and moderate fibrotic changes with large cyst, subchronic nephritis with uric acid tophi, and mineralization in the myocardium. This paper describes the first documented case of transient hyperglycaemia in a warty chameleon (Furcifer verrucosus associated with chronic liver disease and subchronic nephritis.

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

    Directory of Open Access Journals (Sweden)

    Cheng-Zhang Wang

    2015-12-01

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

  11. Asenapine Effects on Cognitive and Monoamine Dysfunction Elicited by Subchronic Phencyclidine Administration

    Science.gov (United States)

    Elsworth, John D.; Groman, Stephanie; Jentsch, J. David; Valles, Rodrigo; Shahid, Mohammed; Wong, Erik; Marston, Hugh; Roth, Robert H.

    2013-01-01

    of administration and reaching significance after 2–4 weeks of dosing. In week 4, the improvement with asenapine 150 μg/kg (p=0.01) rendered the performance of PCP-exposed monkeys indistinguishable from that of normal monkeys without compromising fine motor function. Asenapine administration (150 μg/kg twice daily) produced an increase in dopamine and serotonin turnover in most brain regions of control monkeys and asenapine (50–150 μg/kg) increased dopamine and serotonin turnover in several brain regions of subchronic PCP-treated monkeys. No significant changes in the steady-state levels of dopamine or serotonin were observed in any brain region except for the central amygdala, in which a significant depletion of dopamine was observed in PCP-treated control monkeys; asenapine treatment reversed this dopamine depletion. A significant decrease in serotonin utilization was observed in the orbitofrontal cortex and nucleus accumbens in PCP monkeys, which may underlie poor reversal learning. In the same brain regions, dopamine utilization was not affected. Asenapine ameliorated this serotonin deficit in a dose-related manner that matched its efficacy for reversing the cognitive deficit. Conclusions In this model of cognitive dysfunction, asenapine produced substantial gains in executive functions that were maintained with long-term administration. The cognition-enhancing effects of asenapine and the neurochemical changes in serotonin and dopamine turnover seen in this study are hypothesized to be primarily related to its potent serotonergic and noradrenergic receptor binding properties, and support the potential for asenapine to reduce cognitive dysfunction in patients with schizophrenia and bipolar disorder. PMID:21875607

  12. Effects of acute and sub-chronic ammonium nitrate exposure on rat ...

    African Journals Online (AJOL)

    Use of fertilizers like ammonium nitrate (NH4NO3) for agricultural purposes has increasingly contaminated the ecosystem with nitrate and/or nitrites. Nitrite is a toxic substance that can cause multiple physiological effects if allowed to build up to high concentrations in animals such as methemoglobinemia. This work is ...

  13. Acute and sub-chronic pre-clinical toxicological study of Averrhoa ...

    African Journals Online (AJOL)

    The objective of this work was to accomplish a preclinical toxicological study of the hydroalcoholic extract (HE) from A. carambola leaves. Wistar rats and Swiss mice, both male and female, were used in these experiments. The rats were used in the acute toxicity assessment, with the extract administered at doses of 0.1 to ...

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Single fiber electromyography. A method for the evaluation of motor axonopathy during toxicity studies in dogs.

    Science.gov (United States)

    Schaeppi, U; Teste, M; Siegenthaler, U

    1981-11-01

    In man, single fiber electromyography is used as a very sensitive indicator for the assessment of functional changes in motor nerves. The purpose of the present study was to adapt the above testing procedure to allow repeated investigations of dogs used in subchronic toxicity tests. Experiments were performed on anesthetized pure-bred beagle dogs. Action potentials from single muscle fibers in response to electrical stimulation of motor nerves were recorded with Medelec microelectrodes, amplified with a Medelec system and monitored on a Tektronic oscilloscope. Repeated electrical stimulation with pulses of 0.03 msec and 1 p.p.s. produced characteristic action potentials of single muscle fibers consisting of a positive, followed by a negative, deflection having a duration of from 500 to 800 microseconds altogether. Successive potentials occurred with a variable latency (the jitter) ranging from +/- 5 to 15 microseconds. Quantitative evaluation of the jitter will allow the clinical evaluation of motor axonopathies in dogs.

  16. Pathological modifications following sub-chronic exposure of medaka fish (Oryzias latipes) to microcystin-LR.

    Science.gov (United States)

    Trinchet, Isabelle; Djediat, Chakib; Huet, Hélène; Dao, Simone Puiseux; Edery, Marc

    2011-11-01

    Microcystins (MCs) are toxic monocyclic heptapeptides produced by many cyanobacteria. MCs, especially MC-LR, cause toxic effects in animals and are a recognized potent cause of environmental stress and health hazard in aquatic ecosystems when heavy blooms of cyanobacteria appear. Consequently, one of the major problems is the chronic exposure of fish to cyanotoxins in their natural environment. The present experiment involving chronic exposure confirmed initial findings on acute exposure to MC contamination: exacerbated physiological stress and tissue damage in several tissues of exposed medaka fish. The gonads were affected specifically. In female gonads the modifications included reduction of the vitellus storage, lysis of the gonadosomatic tissue and disruption of the relationships between the follicular cells and the oocytes. In the males, spermatogenesis appeared to be disrupted. This is the first report showing that a cyanotoxin can affect reproductive function, and so can impact on fish reproduction and thus fish stocks. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta).

    Science.gov (United States)

    Harikumar, Kuzhuvelil Bhaskarannair; Nimita, Chittikappil Venugopal; Preethi, Korengath Chandran; Kuttan, Ramadasan; Shankaranarayana, Madapura Lingappiah; Deshpande, Jayant

    2008-01-01

    Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form.

  18. Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium.

    Science.gov (United States)

    Li, Jin-Long; Gao, Rui; Li, Shu; Wang, Jin-Tao; Tang, Zhao-Xin; Xu, Shi-Wen

    2010-08-01

    Cadmium (Cd) is an ubiquitous environmental pollutant that has been associated with male reproductive toxicity in animal models. However, little is known about the reproductive toxicity of Cd in birds. To investigate the toxicity of Cd on male reproduction in birds and the protective effects of selenium (Se) against subchronic exposure to dietary Cd, 100-day-old cocks received either Se (as 10 mg Na(2)SeO(3) per kg of diet), Cd (as 150 mg CdCl(2) per kg of diet) or Cd + Se in their diets for 60 days. Histological and ultrastructural changes in the testis, the concentrations of Cd and Se, amount of lipid peroxidation (LPO), the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx), and apoptosis and serum testosterone levels were determined. Exposure to Cd significantly lowered SOD and GPx activity, Se content in the testicular tissue, and serum testosterone levels. It increased the amount of LPO, the numbers of apoptotic cells and Cd concentration and caused obvious histopathological changes in the testes. Concurrent treatment with Se reduced the Cd-induced histopathological changes in the testis, oxidative stress, endocrine disorder and apoptosis, suggesting that the toxic effects of cadmium on the testes is ameliorated by Se. Se supplementation also modified the distribution of Cd in the testis.

  19. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties.

    Science.gov (United States)

    van der Laan, Jan Willem; Buitenhuis, Wenny H W; Wagenaar, Laura; Soffers, Ans E M F; van Someren, Eugene P; Krul, Cyrille A M; Woutersen, Ruud A

    2016-01-01

    In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred forty-three of the 239 compounds not inducing putative preneoplastic lesions in the subchronic study did not induce tumors in the carcinogenicity study [true negatives (TNs)], whereas 96 compounds were categorized as false negatives (FNs) because tumors were observed in the carcinogenicity study. Of the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumors in the carcinogenicity study [true positives (TPs)], and 19 only showed preneoplastic lesions in subchronic studies but no tumors in the carcinogenicity study [false positives (FPs)]. In addition, we then re-assessed the prediction of the tumor outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN). For 67 compounds, the presence of cellular hyperplasia as evidence for proliferative action could be found (TP). Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92% and the ability to detect carcinogens at 98%. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorized as FN and 1 as FP), thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological properties of compounds in

  20. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    Full Text Available In an exercise designed to reduce animal use, we analysed the results of rat sub-chronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumour outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred and forty-three of the 239 compounds not inducing putative preneoplastic lesions in the sub-chronic study did not induce tumours in the carcinogenicity study (True Negatives - TN, whereas 96 compounds were categorised as False Negatives (FN, because tumours were observed in the carcinogenicity study. For the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumours in the carcinogenicity study (True positives - TP, and 19 only showed preneoplastic lesions in subchronic studies but no tumours in the carcinogenicity study (False positives - FP. In addition, we then re-assessed the prediction of the tumour outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN. For 67 compounds the presence of cellular hyperplasia as evidence for proliferative action could be found (TP. Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92 % and the ability to detect carcinogens at 98 %. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorised as FN. 1 as FP, thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological

  1. Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

    Science.gov (United States)

    Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

    2017-09-01

    Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

  2. Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy.

    Science.gov (United States)

    Masuda, Akane; Masuda, Miyabi; Kawano, Takuya; Kitsunai, Yoko; Nakayama, Haruka; Nakajima, Hiroyuki; Kojima, Hiroyuki; Kitamura, Shigeyuki; Uramaru, Naoto; Hosaka, Takuomi; Sasaki, Takamitsu; Yoshinari, Kouichi

    2017-01-01

    Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.

  3. Toxicity of OTC to Ipomoea aquatica Forsk. and to microorganisms in a long-term sewage-irrigated farmland soil.

    Science.gov (United States)

    Ma, Tingting; Chen, Li'ke; Wu, Longhua; Christie, Peter; Luo, Yongming

    2016-08-01

    Water spinach (Ipomoea aquatic Forsk.) was selected to investigate the effects of oxytetracycline (OTC) on the toxicity of soil contaminated by long-term sewage irrigation. After acute toxicity test in petri dish at nine different OTC-spiked levels for 48 h, the germination rate was found to be generally inhibited in all treatments treated with OTC but the root elongation and activities of several antioxidant enzymes, superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were either forward or backward stimulated to varying extent. During a 60-day sub-chronic toxicity test by means of a pot experiment, activities of SOD, POD and CAT in both the leaf and root tissue at 25 mg OTC per kg soil (dry weight) and in root tissue at 1 mg OTC per kg soil (dry weight) were significantly different than those in other treatments, which also indicated the higher sensitivity of the root. The foliar photosynthetic rate, stomatal conductance and transpiration rate were all gradually inhibited in spite of elevated water use efficiency under the pressure of the different OTC concentrations, which were highly significant different at 10 mg OTC per kg soil (dry weight). Indices of soil microbial diversity at 4 mg OTC kg(-1) soil were significantly different from those of the control, indicating the potential adverse effects of OTC to soil microorganisms. The results suggest that the introduction of OTC could damage both plants and soil microorganisms, and during sub-chronic incubation, the sensitivity of different indices generally followed the order of root tissue antioxidant enzyme activities, soil microbial diversity indices, leaf photosynthesis-related index and leaf tissue enzyme antioxidant activities. In addition, the application of livestock and poultry manure containing pollutants like OTC in farmland soil, especially if the soil has been contaminated before, should be taken more seriously in the context of the current pursuit of increased agricultural

  4. Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

    Science.gov (United States)

    Lohiya, Nirmal K; Manivannan, Boomi; Garg, Shipra

    2006-10-01

    Pre-clinical acute and sub-chronic toxicity studies of the methanol sub-fraction (MSF) of the seeds of Carica papaya, a putative male contraceptive, have been investigated in rats to evaluate safety of the test substance. A single oral dose of MSF at 2000 mg/kg body weight was studied over 14 days for acute toxicity, and daily oral doses of 50, 100, 250 and 500 mg/kg body weight were studied for 28- and 90-day periods for sub-chronic toxicity. Body weight, food and water intake and phenotypical toxicological symptoms were recorded daily. Sperm analysis, hematology, serum clinical biochemistry, libido and pathological examination of vital organs were recorded at the termination of the experimental periods. We observed no overt general toxicity in exposed animals. Food and water intake showed daily fluctuations within control limits. Sperm density showed a significant decrease in all 28- and 90-day repeated dose treated animals whereas total sperm motility inhibition was observed at 250 and 500 mg/kg dose levels at the 28-day time interval but in all dose groups at the 90-day interval. The preliminary results suggest the test substance may be a safe approach to male anti-fertility.

  5. Zika Phase 1 Clinical Trial Material—From Research to Release in 90 Days | FNLCR

    Science.gov (United States)

    Over the past 12 months, we’ve grown accustomed to seeing Zika in the news. The virus has been linked to thousands of cases of microcephaly in Brazilian babies. Numerous countries, including the United States, have reported Zika-related deaths. And

  6. Zika Phase I Clinical Trial Material—From Research to Release in 90 Days | Poster

    Science.gov (United States)

    Over the past 12 months, we’ve grown accustomed to seeing Zika in the news. The virus has been linked to thousands of cases of microcephaly in Brazilian babies. Numerous countries, including the United States, have reported Zika-related deaths. And there is no vaccine available at this time. In the face of what has become a global health crisis, the Vaccine Research Center (VRC) at the NIH/National Institute of Allergy and Infectious Diseases (NIAID) responded to a call from Anthony Fauci, Ph.D., head, NIAID, to get a candidate vaccine into human trials by the summer of 2016.

  7. Zika Phase 1 Clinical Trial Material—From Research to Release in 90 Days | FNLCR Staging

    Science.gov (United States)

    Over the past 12 months, we’ve grown accustomed to seeing Zika in the news. The virus has been linked to thousands of cases of microcephaly in Brazilian babies. Numerous countries, including the United States, have reported Zika-related deaths. And

  8. 546 Meat quality of Suffolk and Bergamasca lambs slaughtered at 90 days of age

    Directory of Open Access Journals (Sweden)

    Riccardo Bozzi

    2010-01-01

    Full Text Available Twenty lambs, 10 Suffolk (S e 10 Bergamasca (B born from single (SI and twin type of birth (TW, were employed. Lambs fed the same diet. Chemical-physical analysis were performed on raw Longissimus lumborum (LL. B showed the lowest cooked loss on cooked LL, the highest value of a* and b* on raw meat. As regard fatty acid composition, LL of B showed the highest saturated fatty acids and the lowest value of polyunsaturated acids. Twin subjects showed raw meat with the lowest value of ether extract and with a healthy fatty acid composition.

  9. Time course and reasons for 90-day mortality in fast-track hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Jørgensen, C C; Kehlet, H

    2017-01-01

    was pulmonary (6/28) and gastrointestinal (6/28), while the most common reported cause of death were pulmonary (9/28) and cardiac events (6/28). In five of the seven unlikely related deaths mortality was attributed to underlying cancer. CONCLUSION: Ninety-days mortality was 0.3% in THA and TKA, but only 28...

  10. Toxic hemolytic anemias.

    OpenAIRE

    ZEMANOVÁ, Vendula

    2014-01-01

    This thesis deals with toxic hemolytic anemias which are often unheeded. There are described laboratory signs of hemolytic anemias, their dividing into the various groups and it focuses mainly to toxic and drug-related hemolytic anemias and their causations.

  11. Impact of thiamine supplementation in the reversal of ethanol induced toxicity in rats.

    Science.gov (United States)

    Vidhya, A; Renjugopal, V; Indira, M

    2013-01-01

    One of the molecular mechanisms of alcohol induced toxicities is mediated by oxidative stress. Hence our studies were focused on the effect of thiamine (antioxidant) in the reversal of alcohol induced toxicity and comparison of the reversal with abstinence. Administration of ethanol at a dose of 4 g/kg body wt/day for 90 days to Sprague Dawley rats manifested chronic alcohol induced toxicity evidenced by decreased body weight, an increase in liver-body weight ratio, increase in activities of serum and liver aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT); decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver and brain. The levels of inflammatory markers, fibrosis markers and DNA fragmentation were also elevated in the serum, liver and brain. After ethanol administration for 90 days, the reversal of the alcohol induced toxicity was studied by supplementing thiamine at a dose of 25 mg/100 g body wt/day. Duration of the reversal study was 30 days. The activities of AST, ALT, GGT, scavenging enzymes as well as markers of inflammation and fibrosis in serum, liver and brain were reversed to a certain extent by thiamine. Changes in neurotransmitter levels in brain were also reversed by thiamine supplementation. DNA damage was decreased and DNA content increased in thiamine supplemented group compared to abstinence group showing a faster regeneration. In short, histopathological and biochemical evaluations indicate that thiamine supplemented abstinent rats made a faster recovery of hepatic and neuronal damage than in the abstinence group.

  12. Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication.

    Science.gov (United States)

    Todorovic, Tatjana; Vujanovic, Dragana; Dozic, Ivan; Petkovic-Curcin, Aleksandra

    2008-03-01

    Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.

  13. Exposure to sub-chronic unpredictable stress accounts for antidepressant-like effects in hamsters treated with BDNF and CNQX.

    Science.gov (United States)

    Alò, Raffaella; Mele, Maria; Fazzari, Gilda; Avolio, Ennio; Canonaco, Marcello

    2015-09-01

    Recent evidences indicate that cerebral neurotrophic factors like vascular endothelial growth factor plus signaling pathways of the glutamatergic neuroreceptor system (L-Glu) are determinant modulators of depression-like states. In the present study, the type of interaction(s) exerted by the AMPAergic antagonist, 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) and the brain derived neurotrophic factor (BDNF) on depression-like behaviors in hamsters (Mesocricetus auratus) were investigated. Sub-chronic administration of BDNF in the hippocampal dentate gyrus (DG) of stressed hamsters was responsible for very evident (phamsters treated with BDNF. Similarly, this treatment caused moderate increases of the major stress protein (Hsp70) in DG and Or-Py. Conversely, while CNQX induced similar TrkB expression levels, it instead accounted for a moderate reduction of Hsp70 mRNAs in the same brain areas. Overall these results support crucial roles played by BDNF and AMPAergic neurosignaling mechanisms during distinct adaptive responses of depression- and anxiety-like states in hamsters. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Sub-chronic exposure to noise affects locomotor activity and produces anxiogenic and depressive like behavior in rats.

    Science.gov (United States)

    Naqvi, Fizza; Haider, Saida; Batool, Zehra; Perveen, Tahira; Haleem, Darakhshan J

    2012-01-01

    Noise is defined as a displeasing and unwanted sound. It is one of the most encountered stressor to which mankind is exposed. Frustration, poor reading, impaired hearing and difficulty in problem solving activities are the common consequences of noise stress. It has been reported to produce atrophy of dendrites and alterations in neurotransmitter levels. Long term exposure to inescapable noise stress induces exhaustion, defeat, annoyance followed by decreased muscle movement, social contacts and mood changes. The present study was aimed to investigate the detrimental effects of noise exposure on behavior of rats and its association with altered neurochemistry. Changes in neurotransmitter levels in different brain regions including hippocampus have been reported following noise exposure and these changes in neurotransmitters levels have also been associated with altered behavior. In the present study, locomotor activity in rats was assessed by open field test (OFT) while anxiety and depressive behavior was monitored by elevated plus maze (EPM) and tail suspension (TST) tests. The results showed that 15 days sub-chronic exposure to noise stress induced anxiety and depression like behavior in male rats. These behavioral deficits observed in the present study suggest that an altered brain serotonergic and dopaminergic activity may be involved in the various psychological disorders following exposure to noise stress.

  15. Cadmium accumulation and elimination in tissues of juvenile olive flounder, Paralichthys olivaceus after sub-chronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Gil; Jee, Jung-Hoon; Kang, Ju-Chan

    2004-01-01

    Cd accumulation and elimination in tissue of olive flounder. - Experiments were carried out to investigate the accumulation and elimination of cadmium (Cd) in tissues (gill, intestine, kidney, liver and muscle) of juvenile olive flounder, Paralichthys olivaceus, exposed to sub-chronic concentrations (0, 10, 50, 100 {mu}g l{sup -1}) of Cd. Cd exposure resulted in an increased Cd accumulation in tissues of flounder with exposure periods and concentration, and Cd accumulation in gill and liver increased linearly with the exposure time. At 20 days of Cd exposure, the order of Cd accumulation in organs was gill > intestine > liver > kidney > muscle and after 30 days of exposure, those were intestine > gill > liver > kidney > muscle. An inverse relationship was observed between the accumulation factor (AF) and the exposure level, but AF showed an increase with exposure time. During the depuration periods, Cd concentration in the gill, intestine and liver decreased immediately following the end of the exposure periods. No significant difference was found Cd in concentration in the kidney and muscle during depuration periods. The order of Cd elimination rate in organs were decreased intestine > liver > gill during depuration periods.

  16. The duration of a Yellowstone super-eruption cycle and implications for the age of the Olduvai subchron

    Science.gov (United States)

    Rivera, Tiffany A.; Darata, Rachel; Lippert, Peter C.; Jicha, Brian R.; Schmitz, Mark D.

    2017-12-01

    Small-volume rhyolitic eruptions preceding and following a caldera-forming eruption can provide insights into the tempo of eruption cycles and timing of magmatic recharge. In this contribution, high-precision 40Ar/39Ar eruption ages were obtained on the three effusive eruptions bracketing the Huckleberry Ridge Tuff, which comprise Yellowstone's first volcanic cycle. These dates are supplemented with detailed paleomagnetic and rock magnetic analyses to resolve discrepancies with previous reported stratigraphy. The Huckleberry Ridge Tuff (2.08 Ma) was preceded by an eruption at 2.14 Ma, and followed by eruptions at 1.98 and 1.95 Ma, all of which occurred during four distinct periods of geomagnetic instability within the Matuyama chron. The first volcanic cycle of Yellowstone has now been constrained to within a 200 kyr timespan, or half of the previously proposed duration, and similar to the duration of volcanic activity for caldera-forming systems in the Jemez Volcanic Field. The maximum duration for magmatic recharge for the first Yellowstone volcanic cycle is no greater than 100 kyr, and likely closer to 40 kyr. Furthermore, the combined 40Ar/39Ar eruption ages and paleomagnetic results provide polarity anchors for the Pre-Olduvai excursion and Olduvai subchron, which are often used as tie-points in studies of early Pleistocene hominin evolution.

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

    Directory of Open Access Journals (Sweden)

    Andrea Slaninova

    2014-01-01

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

  18. Oxidative stress parameters in early developmental stages of common carp (Cyprinus carpio L.) after subchronic exposure to terbuthylazine and metribuzin.

    Science.gov (United States)

    Hostovsky, Martin; Blahova, Jana; Plhalova, Lucie; Stepanova, Stanislava; Praskova, Eva; Marsalek, Petr; Svobodova, Zdenka

    2012-01-01

    This work assessed the subchronic effects of the triazine compounds terbuthylazine and metribuzin on embryo-larval stages of common carp (Cyprinus carpio L.) using biotransformation enzyme and selected oxidative stress parameters. Early developmental stages of fish, from embryo to larvae, were exposed to terbuthylazine at concentrations of 0.9, 160, 520, and 820 μg/L, and metribuzin at concentrations of 0.9, 4, 14, and 32 mg/L for 30 days and compared to the non-treated control group. For assessment of free radical defence the activities of glutathione S-transferase (GST) and glutathione reductase (GR) were measured; the lipid peroxidation (TBARS) level was determined as a marker of free radical damage. Terbuthylazine had no significant effect (p>0.05) at any tested concentrations on GST activity. Terbuthylazine caused an increase (p0.05) effect of terbuthylazine exposure on TBARS level. In metribuzin treated groups, the activity of GST was increased (pmetribuzin induced oxidative stress in embryo-larval stages of common carp. Increased activities of biotransformation enzymes or antioxidant defence enzymes were markers of free radical attack. There was low lipid peroxidation in early developed fish after triazine exposure.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Contribution of pharmaceuticals and personal care products (PPCPs) to whole toxicity of water samples collected in effluent-dominated urban streams.

    Science.gov (United States)

    Tamura, Ikumi; Yasuda, Yusuke; Kagota, Kei-Ichiro; Yoneda, Saori; Nakada, Norihide; Kumar, Vimal; Kameda, Yutaka; Kimura, Kumiko; Tatarazako, Norihisa; Yamamoto, Hiroshi

    2017-10-01

    Water samples were collected from effluent-dominated urban streams in Tokushima, Kyoto, and Saitama in Japan to roughly determine the contribution of pharmaceuticals and personal care products (PPCPs) and surfactants to whole toxicity of the water. Approximately 100 PPCPs including anionic surfactants such as linear alkylbenzene sulfonate (LAS), were chemically analyzed. Using 14 water samples, chronic or sub-chronic toxicity tests were conducted on three aquatic species, the green alga Raphidocelis subcapitata, the cladoceran Ceriodaphnia dubia, and the zebrafish Danio rerio. Bioassays for the selected individual PPCPs were conducted using the three species. Assuming the concentration addition (CA) model, the contribution of each PPCP to the whole toxicity of the riverwater was estimated based on toxicity unit (TU). The contribution of PPCPs, which primarily consists of a few antibiotic agents such as triclosan and clarithromycin, ranged from 0.9% to 69% of the whole toxicity of the water samples for algae, whereas the selected LAS congeners accounted for at most 5.3%. In contrast, the contribution of LAS ranged from 0.067% to 86% and from 0.021% to 27% of the whole toxicity for cladoceran and zebrafish, respectively, whereas that of PPCPs for these species was at most 2.1% at all sampling points. Our results suggest a limited contribution of PPCPs except for antimicrobial agents and the possible substantial contribution of LAS to toxicity in cladocerans and zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão in Rodents

    Directory of Open Access Journals (Sweden)

    Marco Antonio Costa

    2013-01-01

    Full Text Available Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2 from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg·kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg·kg−1. In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

  2. Hemato-immunologic impact of subchronic exposure to melamine and/or formaldehyde in mice.

    Science.gov (United States)

    Abd-Elhakim, Yasmina M; Mohamed, Amany Abdel-Rahman; Mohamed, Wafaa A

    2016-09-01

    The aim of the present study was to explore the potential hematotoxic and immunotoxic effects of melamine (MA) in the absence and presence of formaldehyde (FA) in mice. Forty adult Swiss mice were equally allocated into four groups and daily treated with water, MA (50 mg/kg), FA (25 mg/kg), and MA + FA respectively via feeding needle for 60 consecutive days. Hematological status was evaluated using erythrogram and leukogram profiling. Innate immune functions were assessed by measuring white blood cells lysozyme and phagocytic activities. Serum immunoglobulin levels were evaluated as indicators of humoral immunity. In addition, histologic and immunohistochemical evaluations of splenic tissues were performed. The results indicated that either MA or FA treatment resulted in significant decreases in RBCs, Hb, MCHC, total WBC, lymphocyte, and basophile levels as well as in WBCs phagocytosis and lysozyme activity. In contrast, MCV, PCV%, and reticulocyte levels were significantly increased in these hosts. The total IgM level was significantly reduced in the MA-only-exposed mice but markedly increased in the FA-only-treated ones. A significant decrease in serum IgG levels was detected following either MA or FA treatment. The combined exposure to MA and FA, compared to levels of either toxicant alone, was revealed to evoke a significant improvement in Hb, PCV%, MCV, MCHC, neutrophil, eosinophil, total IgM level, and lysozyme activity; however these values did not reach that of the controls. Furthermore, compared to control mice, both MA-only- and FA-only-treated mice showed a strong distribution of CD4(+) and CD8(+) cells in their spleens, while a moderate presence of the former cells was obvious at their co-exposure. Taken together, these findings revealed that exposure to MA or FA resulted in significant alterations in hemato-immune parameters at variable degrees while a co-exposure resulted in the mitigation of most effects of either toxicant alone.

  3. Assessing the Toxicity and Bioavailability of 2,4-Dinitroanisole in Acute and Sub-Chronic Exposures Using the Earthworm, Eisenia fetida

    Science.gov (United States)

    2010-06-01

    Cellular Stress/NRRT  NRRT is a biomarker of cellular stress; viable cells stain red with dye  Coelomic fluid extracted and analyzed in two...minutes for 1 hour to determine neutral red retention time Two Methods of Measurement Extract 50 ul from clitellum Coelomic cells NRRT analysis Expose

  4. Determination of the Chronic Mammalian Toxicological Effects of TNT. Twenty-Six Week Subchronic Oral Toxicity Study of Trinitrotoluene (TNT) in the Beagle Dog.

    Science.gov (United States)

    1983-06-01

    Hemosiderosis In histocytes or Kupffer cells of the liver was seen for one female at 2 mg/kg/day (trace) and for all animals at 8 or 32 mg/kg/day, except for... hemosiderosis appeared to be related to the administration of 2, 8 or 32 mg/kg/day; the results at 0.5 mg/kg/day were equivocal. Five of ten dogs In the high...0 0 0 1 0 6 1 SPLEEN: Congestion 2 0 0 0 1 2 6 5 6 2 Hemosiderosis 1 0 2 3 2 3 6 4 5 5 Erythropoiesis 0 0 0 0 0 1 0 1 4 1 SMALL INTESTINE: Membranous

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

    NARCIS (Netherlands)

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

    2006-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Kingsley C. Patrick-Iwuanyanwu

    2015-11-01

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

  7. Effect of silver nanoparticle surface coating on bioaccumulation and reproductive toxicity in earthworms (Eisenia fetida).

    Science.gov (United States)

    Shoults-Wilson, William A; Reinsch, Brian C; Tsyusko, Olga V; Bertsch, Paul M; Lowry, Gregory V; Unrine, Jason M

    2011-09-01

    The purpose of this study was to investigate the effect of surface coating on the toxicity of silver nanoparticles (Ag NPs) soil. Earthworms (Eisenia fetida) were exposed to AgNO(3) and Ag NPs with similar size ranges coated with either polyvinylpyrrolidone (hydrophilic) or oleic acid (amphiphilic) during a standard sub-chronic reproduction toxicity test. No significant effects on growth or mortality were observed within any of the test treatments. Significant decreases in reproduction were seen in earthworms exposed to AgNO3, (94.21 mg kg(-1)) as well as earthworms exposed to Ag NPs with either coating (727.6 mg kg(-1) for oleic acid and 773.3 mg kg(-1) for polyvinylpyrrolidone). The concentrations of Ag NPs at which effects were observed are much higher than predicted concentrations of Ag NPs in sewage sludge amended soils; however, the concentrations at which adverse effects of AgNO(3) were observed are similar to the highest concentrations of Ag presently observed in sewage sludge in the United States. Earthworms accumulated Ag in a concentration-dependent manner from all Ag sources, with more Ag accumulating in tissues from AgNO(3) compared to earthorms exposed to equivalent concentrations of Ag NPs. No differences were observed in Ag accumulation or toxicity between earthworms exposed to Ag NPs with polyvinylpyrrolidone or oleic acid coatings.

  8. Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine

    DEFF Research Database (Denmark)

    Larsen, Marianne Hald; Rosenbrock, Holger; Sams-Dodd, Frank

    2007-01-01

    D-immunoreactivity. We find that chronic, but not sub-chronic treatment with Tesofensine increases BDNF mRNA in the CA3 region of the hippocampus (35%), and Arc mRNA in the CA1 of the hippocampus (65%). Furthermore, the number of Ki-67- and neuroD-positive cells increased after chronic, but not sub-chronic treatment....... This study shows that Tesofensine enhances hippocampal gene expression and new cell formation indicative for an antidepressant potential of this novel drug substance....

  9. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on xylanase from a genetically modified strain of Aspergillus oryzae (strain NZYM-FB)

    DEFF Research Database (Denmark)

    Poulsen, Morten; Binderup, Mona-Lise; Hallas-Møller, Torben

    . The xylanase is intended to be used in a number of food manufacturing processes, such as starch processing, beverage alcohol (distilling), brewing, baking and other cereal based processes. The dietary exposure was assessed according to the Budget method. The food enzyme did not induce gene mutations...... in bacteria nor chromosome aberrations in human peripheral blood lymphocytes. Therefore, there is no concern with respect to genotoxicity. The systemic toxicity was assessed by means of a 90-day subchronic oral toxicity study in rodents. A No Observed Adverse Effect Level was derived, which compared...

  10. Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lypopolysaccharide in the hippocampus and striatum of male mice

    Energy Technology Data Exchange (ETDEWEB)

    Astiz, Mariana, E-mail: marianaastiz@gmail.com; Diz-Chaves, Yolanda, E-mail: ydiz@cajal.csic.es; Garcia-Segura, Luis M., E-mail: lmgs@cajal.csic.es

    2013-10-15

    Dimethoate is an organophosphorus insecticide extensively used in horticulture. Previous studies have shown that the administration of dimethoate to male rats, at a very low dose and during a sub-chronic period, increases the oxidation of lipids and proteins, reduces the levels of antioxidants and impairs mitochondrial function in various brain regions. In this study, we have assessed in C57Bl/6 adult male mice, whether sub-chronic (5 weeks) intoxication with a low dose of dimethoate (1.4 mg/kg) affects the expression of inflammatory molecules and the reactivity of microglia in the hippocampus and striatum under basal conditions and after an immune challenge caused by the systemic administration of lipopolysaccharide. Dimethoate increased mRNA levels of tumor necrosis factor α (TNFα) and interleukin (IL) 6 in the hippocampus, and increased the proportion of Iba1 immunoreactive cells with reactive phenotype in dentate gyrus and striatum. Lipopolysaccharide caused a significant increase in the mRNA levels of IL1β, TNFα, IL6 and interferon-γ-inducible protein 10, and a significant increase in the proportion of microglia with reactive phenotype in the hippocampus and the striatum. Some of the effects of lipopolysaccharide (proportion of Iba1 immunoreactive cells with reactive phenotype and IL6 mRNA levels) were amplified in the animals treated with dimethoate, but only in the striatum. These findings indicate that a sub-chronic period of administration of a low dose of dimethoate, comparable to the levels of the pesticide present as residues in food, causes a proinflammatory status in the brain and enhances the neuroinflammatory response to the lipopolysaccharide challenge with regional specificity. - Highlights: • The dose of pesticide used was comparable to the levels of residues found in food. • Dimethoate administration increased cytokine expression and microglia reactivity. • Hippocampus and striatum were differentially affected by the treatment.

  11. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  12. The top of the Olduvai subchron in a high-resolution magnetostratigraphy from the West Turkana core WTK13, Hominin Sites and Paleolakes Drilling Project (HSPDP)

    Science.gov (United States)

    Sier, Mark; Langereis, Cor; Dupont-Nivet, Guillaume; Feibel, Craig; Jordeens, Jose; van der Lubbe, Jeroen; Beck, Catherine; Olago, Daniel; Cohen, Andrew

    2017-04-01

    One of the major challenges in understanding the evolution of our own species is identifying the role climate change has played in the evolution of earlier hominin species. To clarify the influence of climate, we need long and continuous high-resolution paleoclimate records, preferably obtained from hominin-bearing sediments, that are well-dated by tephro- and magnetostratigraphy and other methods. This is hindered, however, by the fact that fossil-bearing sediments are often discontinuous, and subject to weathering, which may lead to oxidation and remagnetization. To obtain fresh, unweathered sediments, the Hominin Sites and Paleolakes Drilling Project (HSPDP) collected a 216- meter core (WTK13) in 2013 from deposits of Early Pleistocene paleolake Lorenyang in the western Turkana Basin (Kenya). Here, we present the magnetostratigraphy of the core. Rock magnetic analyses reveal the presence of iron sulphides carrying the remanent magnetizations. To recover polarity orientation from the near-equatorial WTK13 core drilled at 5°N, we developed and successfully applied two independent drill-core reorientation methods taking advantage of (1) the sedimentary fabric as expressed in the Anisotropy of Magnetic Susceptibility (AMS) and (2) the occurrence of a viscous component oriented in the present day field. The reoriented directions reveal a normal to reversed polarity reversal identified as the top of the Olduvai subchron. From this excellent record, we find no evidence for the 'Vrica subchron' previously reported in the area. We suggest that outcrop-based interpretations supporting the presence of the Vrica subchron have been affected by the oxidation of iron sulphides initially present in the sediments as evident in the core record, and by subsequent remagnetization. Based on our new high-resolution magnetostratigraphy and stratigraphic markers, we provide constraints for an initial age model of the WTK13 core. We discuss the implications of the observed geomagnetic

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

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    M Emamghoreishi

    2012-02-01

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

  14. Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

    Science.gov (United States)

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

    2017-01-01

    To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek ( Trigonella foenum-graecum L) seed extract in laboratory rats. The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without

  15. GDNF-induced cerebellar toxicity: A brief review.

    Science.gov (United States)

    Luz, Matthias; Mohr, Erich; Fibiger, H Christian

    2016-01-01

    Recombinant-methionyl human glial cell line-derived neurotrophic factor (GDNF) is known for its neurorestorative and neuroprotective effects in rodent and primate models of Parkinson's disease (PD). When administered locally into the putamen of Parkinsonian subjects, early clinical studies showed its potential promise as a disease-modifying agent. However, the development of GDNF for the treatment of PD has been significantly clouded by findings of cerebellar toxicity after continuous intraputamenal high-dose administration in a 6-month treatment/3-month recovery toxicology study in rhesus monkeys. Specifically, multifocal cerebellar Purkinje cell loss affecting 1-21% of the cerebellar cortex was observed in 4 of 15 (26.7%; 95% confidence interval [CI]: 10.5-52.4%) animals treated at the highest dose level tested (3000μg/month). No cerebellar toxicity was observed at lower doses (450 and 900μg/month) in the same study, or at similar or higher doses (up to 10,000μg/month) in subchronic or chronic toxicology studies testing intermittent intracerebroventricular administration. While seemingly associated with the use of GDNF, the pathogenesis of the cerebellar lesions has not been fully understood to date. This review integrates available information to evaluate potential pathogenic mechanisms and provide a consolidated assessment of the findings. While other explanations are considered, the existing evidence is most consistent with the hypothesis that leakage of GDNF into cerebrospinal fluid during chronic infusions into the putamen down-regulates GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF generates the observed lesions. The implications of these findings for clinical studies with GDNF are discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Raspberry ketone in food supplements – High intake, few toxicity data – A cause for safety concern?

    DEFF Research Database (Denmark)

    Bredsdorff, Lea; Wedebye, Eva Bay; Nikolov, Nikolai Georgiev

    2015-01-01

    Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies...... on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 μg/day for Class 1 substances. The margin of safety (MOS...... effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry...

  17. Sub-chronic copper pretreatment reduces oxidative damage in an experimental Huntington's disease model.

    Science.gov (United States)

    Martínez-Lazcano, Juan Carlos; Montes, Sergio; Sánchez-Mendoza, María Alicia; Rodríguez-Páez, Lorena; Pérez-Neri, Iván; Boll, Marie Catherine; Campos-Arroyo, Hortensia Denise; Ríos, Camilo; Pérez-Severiano, Francisca

    2014-12-01

    Quinolinic acid (QUIN) striatal injection in rat reproduces the main neurochemical features of Huntington's disease (HD), including oxidative damage. In this study, we evaluated the effect of a copper (Cu) supplement in drinking water (90 ppm Cu, 28 days) on the QUIN-induced HD model in the rat. Copper exposure caused no signs of liver toxicity; however, it produced significant Cu accumulation in striatum. It is noteworthy that QUIN also caused increased striatal Cu content; when the supplement was administered to animals with QUIN-injury, an even higher metal striatal accumulation was observed. Cu pre-treatment preserved striatal gamma-aminobutyric acid (GABA) content, which was reduced by QUIN intrastriatal injection. Similarly, apomorphine-induced circling behavior was reduced in Cu-pretreated QUIN-damaged rats. Metal supplement in drinking water prevented both lipid peroxidation and reactive oxygen species (ROS) formation caused by QUIN in striatum. In Cu-treated groups, superoxide dismutase-1 (SOD1) activity showed a significant increase, while SOD2 activity was slightly enhanced. Although the pathophysiological role for higher Cu levels in patients with HD and in experimental models of the disease is not fully understood, results in the present study suggest that Cu oral intake stimulates anti-oxidant defenses, an effect that may be a potential factor for reducing the progression of HD.

  18. The immunotoxicological pattern of subchronic and chronic benzene exposure in rats.

    Science.gov (United States)

    Karaulov, Alexander V; Mikhaylova, Irina V; Smolyagin, Alexander I; Boev, Viktor M; Kalogeraki, Alexandra; Tsatsakis, Aristides M; Engin, Ayse Basak

    2017-06-05

    Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which were subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment. The percentage of CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer. Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The decrease in the total lymphocyte and T cell counts were associated with increased benzene exposure duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4+T cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive correlation between benzene toxicity and indicated increased immune responses, 45-day exposure to benzene appeared to be the most sensitive time point for evaluating benzene cytotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium.

    Science.gov (United States)

    Begic, Aida; Djuric, Ana; Ninkovic, Milica; Stevanovic, Ivana; Djurdjevic, Dragan; Pavlovic, Milos; Jelic, Katarina; Pantelic, Ana; Zebic, Goran; Dejanovic, Bratislav; Stanojevic, Ivan; Vojvodic, Danilo; Milosavljevic, Petar; Djukic, Mirjana; Saso, Luciano

    2017-12-01

    Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2(·-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.

  20. Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption.

    Science.gov (United States)

    Nardi, Jessica; Moras, Patricia Bonamigo; Koeppe, Carina; Dallegrave, Eliane; Leal, Mirna Bainy; Rossato-Grando, Luciana Grazziotin

    2017-02-01

    Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    than uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt...uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt.”5...FEMALES AND TOXIC LEADERSHIP A thesis presented to the Faculty of the U.S. Army Command and General Staff College in

  2. CHEMICAL TOXICITY OF URANIUM

    Directory of Open Access Journals (Sweden)

    Sermin Cam

    2007-06-01

    Full Text Available Uranium, occurs naturally in the earth’s crust, is an alpha emitter radioactive element from the actinide group. For this reason, U-235 and U-238, are uranium isotopes with long half lives, have got radiological toxicity. But, for natural-isotopic-composition uranium (NatU, there is greater risk from chemical toxicity than radiological toxicity. When uranium is get into the body with anyway, also its chemical toxicity must be thought. [TAF Prev Med Bull 2007; 6(3.000: 215-220

  3. Altered resistance to Trichinella spiralis infection following subchronic exposure of adult mice to chemicals of environmental concern

    Energy Technology Data Exchange (ETDEWEB)

    Luebke, R.W.

    1981-01-01

    The effects of subchronic chemical exposure on expulsion of adult Trichinella spiralis from the small intestine of mice and encystment of newborn larvae in the host's musculature were investigated. Exposure to diethylstilbestrol, benzo(a)pyrene, tris-(1,3-dichloro-2-propyl) phosphate, cyclophosphamide, phorbol myristate acetate, and dimethylvinylchloride prior to infection of mice with 200 infective larvae resulted in larger worm burdens in treated animals than in controls 14 days after infection. Worm expulsion was not affected by exposure to tris-(2,3-dibromopropyl)phosphate, orthophenylphenol, and indomethacin. Increased burdens of muscle-phase larvae were found in animals that maintained significant numbers of adult worms in the gut at 14 days, except in mice administered diethylstilbestrol and dimethylvinylchloride. Exposure to diethylstilbestrol and cyclophosphamide resulted in decreased inflammatory reactions in the tissues of the small intestine and development of bone marrow eosinophilia in infected mice. Marrow eosinophilia was likewise decreased in mice given tris-(1,3-dichloro-2-propyl)phosphate before infection. Additional studies with diethylstilbestrol administered either before, at the time of, or after infection showed inhibition of worm expulsion. Drug exposure during a primary infection inhibited the expulsion of a second T. spiralis infection, but did not affect worm elimination when given during a second infection. Treatment with diethylstilbestrol after artificial sensitization of mice with Trichinella antigens decreased delayed hypersensitivity responses to the sensitizing antigen. Immune functions, assessed by lymphoproliferative responses to mitogens and antibody responses to sheep red blood cells, generally correlated with altered host resistance to T. spiralis infection.

  4. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

    Directory of Open Access Journals (Sweden)

    Ji-Woon Kim

    Full Text Available Autism spectrum disorder (ASD is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model. We found that prenatal exposure of valproic acid (VPA induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.

  5. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

    Science.gov (United States)

    Kim, Ji-Woon; Seung, Hana; Kwon, Kyung Ja; Ko, Mee Jung; Lee, Eun Joo; Oh, Hyun Ah; Choi, Chang Soon; Kim, Ki Chan; Gonzales, Edson Luck; You, Jueng Soo; Choi, Dong-Hee; Lee, Jongmin; Han, Seol-Heui; Yang, Sung Min; Cheong, Jae Hoon; Shin, Chan Young; Bahn, Geon Ho

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.

  6. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum

    Directory of Open Access Journals (Sweden)

    Huai Guan

    2016-01-01

    Full Text Available We previously reported that arsenic (As impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR/retinoid X receptor (RXR heterodimer and thyroid hormone (TH may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3’-triiodothyronine (T3 and thyroxin (T4 levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  7. Modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration.

    Science.gov (United States)

    Chauhan, Shailender Singh; Ojha, Sudarshan; Mahmood, Akhtar

    2011-11-01

    Excessive consumption of fluoride and ethanol has been identified as injurious to human health. Fluoride and ethanol co-exposures are commonly seen among the alcoholics residing in endemic fluoride areas worldwide. This study was undertaken to examine the modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration. Female Sprague-Dawley rats were divided into four groups: group I (control), group II (fluoride was given orally at a dose of 25 mg/kg body weight), group III (30% ethanol was given orally at a dose of 1 mL/kg body weight), and group IV (a combination of fluoride and ethanol was administered orally at the dose described for groups II and III). Lipid peroxidation was elevated (Pethanol treatments for 20 or 40 days. However, glutathione content was reduced by fluoride (32 and 44%) and ethanol (21 and 40%) treatments after 20 and 40 days, respectively. Fluoride-exposed animals showed reduction (Pglutathione peroxidase (22 and 35%), glutathione reductase (32 and 34%), and glutathione-S-transferase (24 and 30%) after 20 and 40 days. A similar decrease (Pethanol for 20 or 40 days. The observed changes in lipid peroxidation, reduced glutathione levels, and enzyme systems were further augmented in intestine of rats exposed to fluoride and ethanol together. Intestinal histology showed large reactive lymphoid follicles along with mild excess of lymphocytes in lamina propria of villi, villous edema, focal ileitis, and necrosis of villi in animals exposed to fluoride and ethanol for 40 days. These findings suggest that fluoride and ethanol exposure induces considerable changes in lipid peroxidation, antioxidant defense, and morphology of rat intestine, which may affect its functions. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Subchronic exposure to ellagic acid impairs cytotoxic T-cell function and suppresses humoral immunity in mice.

    Science.gov (United States)

    Allen, C T; Peden-Adams, M M; EuDaly, J; Keil, D E

    2003-08-01

    Ellagic acid (EA) is present in a variety of foods such as grapes, strawberries, raspberries, and nuts. It is a dietary plant phenol that has been shown to inhibit oxidative stress and chemical carcinogenesis. Although several studies have examined the protective mechanisms of dietary EA including the induction of detoxifying enzymes, regulation of cell cycle, chelation of nickel, and prevention of DNA methylation, none have addressed the role of EA in immunological surveillance. This study investigates the status of immune function in B6C3F1 mice exposed continuously to EA in drinking water at 0.5, 1.0, or 2.0 mg/kg/day for 28 days. Although this range of exposure is above the estimated human daily intake (approximately 940 microg/day for 70 kg person or 13.4 microg/kg/day), these levels would not be unreasonable if EA were used as a dietary supplement or as a chemotherapeutic agent. Previous reports have demonstrated the anticarcinogenic effects of EA at levels 10- to 250-fold greater than those applied in this study. Immunological parameters assessed included natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity, IgM antibody plaque forming cell (PFC) response, thymus, spleen, kidney, and liver mass, and total cellularity for the thymus and spleen. Subchronic exposure to EA for 28 days in drinking water caused significant suppression of specific IgM antibody responses in the 2.0 mg/kg EA treatment group and suppressed cytotoxic T-cell function in the 0.5 and 1.0 mg/kg EA treatment groups. All other immunological parameters were within normal ranges. Kidney and liver mass were not altered after treatment with EA. The results from this study indicate that EA suppressed both IgM antibody responses and CTLs. These observations suggest important implications on human health should EA be prescribed as a chemotherapeutic agent or a preventative dietary supplement for cancer.

  9. Social isolation rearing in rats alters plasma tryptophan metabolism and is reversed by sub-chronic clozapine treatment.

    Science.gov (United States)

    Möller, Marisa; Du Preez, Jan L; Emsley, Robin; Harvey, Brian H

    2012-06-01

    Schizophrenia is associated with increased oxidative stress, although the source of this redox disequilibrium requires further study. Altered tryptophan metabolism has been described in schizophrenia, possibly linked to inflammation and glutamate-directed excitotoxicity. Social isolation rearing (SIR) in rats induces various behavioural manifestations akin to schizophrenia, as well as altered frontal cortical glutamate N-methyl-d-aspartate (NMDA) receptor binding and increased oxidative stress, all reversed by antipsychotic treatment. Tryptophan is catabolized via the kynurenine pathway to kynurenine, 3-hydroxykynurenine, quinolinic acid (QA), kynurenic acid (KYNA), anthranilic acid and 3-hydroxyanthranilic acid (3-OHAA), ultimately contributing to neuronal integrity and redox balance in the brain. We studied tryptophan metabolism and neuroprotective-neurodegenerative balance in post-natal SIR rats, and its response to clozapine treatment. Male Sprague-Dawley (SD) rats (10 rats/group) were exposed to SIR or social rearing for 8 weeks, whereupon they received either sub-chronic vehicle or clozapine (5 mg/kg i.p) treatment. Plasma tryptophan metabolites were analysed by liquid-chromatography electrospray ionization tandem mass spectrometry.