WorldWideScience

Sample records for subchronic toxicity testing

  1. 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...

  2. [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.

  3. 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.

  4. 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.

  5. [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.

  6. 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.

  7. [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.

  8. 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 ...

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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 ...

  14. 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.

  15. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

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

  20. 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.

  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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

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

  8. 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.

  9. 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.

  10. 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.

  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. 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.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  15. 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, ...

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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.

  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. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  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. 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 ...

  16. 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

  17. 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.

  18. 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...

  19. 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.

  20. 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

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Abidemi J. Akindele

    2018-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. 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).

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Zakiah Ismail

    2014-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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 ...

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Mildred García-González

    2006-12-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Farzamfar B

    2008-04-01

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

  13. 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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    H. M. R. Abdel-Latif

    2017-08-01

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

  16. 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.

  17. 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

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. [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.

  9. 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.

  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. 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.

  12. 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...

  13. 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.

  14. 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...

  15. 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.

  16. 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...

  17. The future of toxicity testing.

    Science.gov (United States)

    Andersen, Melvin E; Al-Zoughool, Mustafa; Croteau, Maxine; Westphal, Margit; Krewski, Daniel

    2010-02-01

    In 2007, the U.S. National Research Council (NRC) released a report, "Toxicity Testing in the 21st Century: A Vision and a Strategy," that proposes a paradigm shift for toxicity testing of environmental agents. The vision is based on the notion that exposure to environmental agents leads to adverse health outcomes through the perturbation of toxicity pathways that are operative in humans. Implementation of the NRC vision will involve a fundamental change in the assessment of toxicity of environmental agents, moving away from adverse health outcomes observed in experimental animals to the identification of critical perturbations of toxicity pathways. Pathway perturbations will be identified using in vitro assays and quantified for dose response using methods in computational toxicology and other recent scientific advances in basic biology. Implementation of the NRC vision will require a major research effort, not unlike that required to successfully map the human genome, extending over 10 to 20 years, involving the broad scientific community to map important toxicity pathways operative in humans. This article provides an overview of the scientific tools and technologies that will form the core of the NRC vision for toxicity testing. Of particular importance will be the development of rapidly performed in vitro screening assays using human cells and cell lines or human tissue surrogates to efficiently identify environmental agents producing critical pathway perturbations. In addition to the overview of the NRC vision, this study documents the reaction by a number of stakeholder groups since 2007, including the scientific, risk assessment, regulatory, and animal welfare communities.

  18. 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.

  19. 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.

  20. 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...

  1. A Miniscale Algal Toxicity Test

    DEFF Research Database (Denmark)

    Arensberg, Pia; Hemmingsen, Vicky H.; Nyholm, Niels

    1995-01-01

    A simple miniscale (approx. 1 - 2.5 ml) toxicity test procedure with the freshwater green algaSelenastrum capricornutum is described. The procedure fulfils the validity criteria of the ISO (International Association for Standardization) standard test protocol. Practically identical concentration...... and test volumes (down to 1 ml) could also be used. Tissue culture treated polystyrene microplates were found toxic to algae and thus unusable. pH control is achieved more easily in the minitest than in larger size shake flasks due to greater turbulence and a larger surface/volume ratio which both...... facilitates CO2 mass transfer. Uniform illumination of the individual units of a minitest setup is obtained readily due to the small area that has to be illuminated. Using the rapidly growing green alga S. capricornutum as test organism, it is proposed generally to reduce the standard test duration from 3...

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Narges El Golli

    2016-04-01

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

  4. 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

  5. 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

  6. 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

  7. 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...

  8. Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia.

    Science.gov (United States)

    McAllister, K A L; Mar, A C; Theobald, D E; Saksida, L M; Bussey, T J

    2015-11-01

    It is becoming increasingly clear that the development of treatments for cognitive symptoms of schizophrenia requires urgent attention, and that valid animal models of relevant impairments are required. With subchronic psychotomimetic agent phencyclidine (scPCP), a putative model of such impairment, the extent to which changes following scPCP do or do not resemble those following dysfunction of the prefrontal cortex is of importance. The present study carried out a comparison of the most common scPCP dosing regimen with excitotoxin-induced medial prefrontal cortex (mPFC) dysfunction in rats, across several cognitive tests relevant to schizophrenia. ScPCP subjects were dosed intraperitoneal with 5 mg/kg PCP or vehicle twice daily for 1 week followed by 1 week washout prior to behavioural testing. mPFC dysfunction was induced via fibre-sparing excitotoxin infused into the pre-limbic and infralimbic cortex. Subjects were tested on spontaneous novel object recognition, touchscreen object-location paired-associates learning and touchscreen reversal learning. A double-dissociation was observed between object-location paired-associates learning and object recognition: mPFC dysfunction impaired acquisition of the object-location task but not spontaneous novel object recognition, while scPCP impaired spontaneous novel object recognition but not object-location associative learning. Both scPCP and mPFC dysfunction resulted in a similar facilitation of reversal learning. The pattern of impairment following scPCP raises questions around its efficacy as a model of cognitive impairment in schizophrenia, particularly if importance is placed on faithfully replicating the effects of mPFC dysfunction.

  9. 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.

  10. 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.

  11. BIOEQUIVALENCE APPROACH FOR WHOLE EFFLUENT TOXICITY TESTING

    Science.gov (United States)

    Increased use of whole effluent toxicity (WET) tests in the regulatory arena has brought increased concern over the statistical analysis of WET test data and the determination of toxicity. One concern is the issue of statistical power. A number of WET tests may pass the current...

  12. Differential effects of subchronic phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests.

    Science.gov (United States)

    Enkel, Thomas; Thomas, Mara; Bartsch, Dusan

    2013-04-15

    Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents. We addressed the question whether subchronic PCP (scPCP) treatment (5 mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light-dark exploration test (LDT) and in an open field environment (OFT). The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity. Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. 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

    Full Text Available A busca de novos medicamentos tem levado ao desenvolvimento de novosfármacos que sejam eficientes e destituídos de toxicidade. Uma das fronteiras nessas pesquisas são os medicamentos fitoterápicos. No Brasil, a Agência Nacional de Vigilância Sanitária (ANVISA regulariza essas pesquisas e padroniza os procedimentos. A Resoluçãoda Diretoria Colegiada (RDC 48/2004, por exemplo, regulariza o registro de fitoterápicos. O Anacardium occidentale Linn está entre as plantas mais estudadas, devido às ações antibiótica e antiinflamatória de seus metabólitos secundários, principalmente taninos. Esta planta também possui a capacidade de impedir a formação da placa bacteriana bucal. Diante dessas ações, formas farmacêuticas acabadas (cremes e géis foram desenvolvidas a partir do extrato bruto seco (EBS das cascas do caule do A. occidentale Linn para registro de um novo fitomedicamento. Entretanto, testes pré-clínicos e clínicos devem ser feitos de acordo com a lei vigente. O presente trabalho avaliou a toxicidade subcrônica do EBS em cães sem raçadefinida (SRD. Os testes revelaram apenas hepatotoxicidade transitória demonstrada pela elevação dos níveis da alanina transaminase (ALT e aspartato transaminase (AST. Research on new medicaments has led to the development of efficient and non-toxic drugs. In Brazil, the Agência Nacional de VigilânciaSanitária (National Department of Sanitary Supervision – ANVISA regularizes and standardizes the procedure. Anacardium occidentale is amongst the most researched plants, due to the antibiotics and antinflammatory properties of its secondary metabolites, mainlytannins and flavonoids. Furthermore, it prevents the dental plaque formation. On account of these actions, finished pharmaceutical forms (creams and gels were developed from the crude dry extract (CDE of A. occidentale Linn stem rinds, in order to register a new form.However, pre-clinical and clinical assays can be made in

  14. Rats tested after a washout period from sub-chronic PCP administration exhibited impaired performance in the 5-Choice Continuous Performance Test (5C-CPT) when the attentional load was increased.

    Science.gov (United States)

    Barnes, Sam A; Young, Jared W; Neill, Jo C

    2012-03-01

    It is well documented that schizophrenia patients exhibit dysfunction in various cognitive domains, including attention/vigilance, as demonstrated by impaired performance in the myriad of Continuous Performance Tests (CPTs). NMDA receptor antagonists provide a pharmacological model in animals of the cognitive disruption presented in the disorder. We therefore examined the effects of a sub-chronic PCP treatment regimen (5.0mg/kg 7-days bi-daily) in the recently developed rodent test of vigilance, the 5-Choice Continuous Performance Test (5C-CPT). We assessed the effects of this regimen after at least a 7-day washout period on both baseline performance and when the attentional load was increased. Sub-chronic PCP treatment impaired 5C-CPT performance in a manner consistent with impaired vigilance in patients with schizophrenia, with reduced hit rate and impaired signal sensitivity. These effects were only evident when performance was challenged following parameter manipulations. These data demonstrate that attention/vigilance is sensitive to disruption following sub-chronic PCP treatment in a pre-clinical task that may demonstrate increased analogy to human vigilance tasks. Although the PCP-induced attentional deficits are not as large as those deficits observed in other domains, these data provide evidence that this pharmacological model can affect multiple cognitive domains and may be useful for assessing putative pro-cognitive therapeutics for schizophrenia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. 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.

  16. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Toussaint, M.W. [Geo-Centers, Inc., Fort Washington, MD (United States); Shedd, T.R. [Army Biomedical Research and Development Lab., Frederick, MD (United States); Schalie, W.H. van der [Environmental Protection Agency, Washington, DC (United States); Leather, G.R. [Hood Coll., Frederick, MD (United States). Dept. of Biology

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  17. 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 ...

  18. The basis of toxicity testing

    National Research Council Canada - National Science Library

    Ecobichon, Donald J

    1992-01-01

    This book discusses fundamental principles and concepts behind toxicological tests, their design and implementation, interpretation of results, and significance of individual studies in the overall...

  19. THE FUTURE OF TOXICITY TESTING AND ASSESSMENT ...

    Science.gov (United States)

    The National Research Council's Board on Environmental Studies and Toxicology is conducting a two-part study to assess and advance current approaches to toxicity testing and assessment to meet regulatory data needs. The first part of the study was completed January 2006, in which the committee prepared a report reviewing selected aspects of several relevant reports by EPA and others on this topic. In the second part of the study currently underway, the committee will prepare a final report presenting a long-range vision and strategic plan for advancing the practices of toxicity testing and human health assessment for environmental contaminants. In developing the vision and strategic plan, the committee will consider evolving regulatory data needs; current toxicity testing guidelines and standards used by EPA and other federal agencies; the use of emerging science and tools (e.g., genomics, proteomics, transgenics, bioinformatics, computational toxicology, in vitro testing, and other alternatives to animal testing); and the challenges of incorporating more complex understanding of toxicity (e.g., toxicokinetics, mechanisms of action, systems biology) into human health risk assessment. The final report is expected to be released as early as the end of January, 2007. To develop a long-range vision and strategic plan for advancing the practices of toxicity testing and human health assessment for environmental contaminants.

  20. Bioequivalence approach for whole effluent toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, R.; Wang, Q.; Fulk, F.; Deng, C.; Denton, D.

    2000-01-01

    Increased use of whole effluent toxicity (WET) tests in the regulatory arena has brought increased concern over the statistical analysis of WET test data and the determination of toxicity. One concern is the issue of statistical power. A number of WET tests may pass the current hypothesis test approach because they lack statistical power to detect relevant toxic effects because of large within-test variability. Additionally, a number of WET tests may fail the current approach because they possess excessive statistical power, as a result of small within-test variability, and detect small differences that may not be biologically relevant. The strengths and limitations of both the traditional hypothesis test approach and the bioequivalence approach for use in the National Pollutant Discharge Elimination System program were evaluated. Data from 5,213 single-concentration, short-term chronic WET tests with Ceriodaphnia dubia provided the database for analysis. Comparison of results between the current approach and the bioequivalence approach indicates that the current approach to WET testing is generally sound but that adopting the proposed bioequivalence approach resolves concerns of statistical power. Specifically, within this data set, applying the bioequivalence approach resulted in failure for tests with relatively large test variability and a pass for tests with relatively small within-test variability.

  1. The C. elegans model in toxicity testing.

    Science.gov (United States)

    Hunt, Piper Reid

    2017-01-01

    Caenorhabditis elegans is a small nematode that can be maintained at low cost and handled using standard in vitro techniques. Unlike toxicity testing using cell cultures, C. elegans toxicity assays provide data from a whole animal with intact and metabolically active digestive, reproductive, endocrine, sensory and neuromuscular systems. Toxicity ranking screens in C. elegans have repeatedly been shown to be as predictive of rat LD50 ranking as mouse LD50 ranking. Additionally, many instances of conservation of mode of toxic action have been noted between C. elegans and mammals. These consistent correlations make the case for inclusion of C. elegans assays in early safety testing and as one component in tiered or integrated toxicity testing strategies, but do not indicate that nematodes alone can replace data from mammals for hazard evaluation. As with cell cultures, good C. elegans culture practice (GCeCP) is essential for reliable results. This article reviews C. elegans use in various toxicity assays, the C. elegans model's strengths and limitations for use in predictive toxicology, and GCeCP. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons Ltd. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

  2. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

    The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much...... in anthropomorphism leads to better research/testing. Current trends in toxicity testing will result in tests involving more sophisticated techniques, better quality of laboratory animals, and eventually the use of fewer animals....

  3. 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.

  4. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  5. 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...

  6. 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.

  7. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    Directory of Open Access Journals (Sweden)

    Jing Dai

    2016-10-01

    Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

  8. 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.

  9. 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.

  10. 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.

  11. Toxicity of Uranium Adsorbent Materials using the Microtox Toxicity Test

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jiyeon [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jeters, Robert T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gill, Gary A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kuo, Li-Jung [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bonheyo, George T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-10-01

    The Marine Sciences Laboratory at the Pacific Northwest National Laboratory evaluated the toxicity of a diverse range of natural and synthetic materials used to extract uranium from seawater. The uranium adsorbent materials are being developed as part of the U. S. Department of Energy, Office of Nuclear Energy, Fuel Resources Program. The goal of this effort was to identify whether deployment of a farm of these materials into the marine environment would have any toxic effects on marine organisms.

  12. SEDIMENT TOXICITY ASSESSMENT: COMPARISON OF STANDARD AND NEW TESTING DESIGNS

    Science.gov (United States)

    Standard methods of sediment toxicity testing are fairly well accepted; however, as with all else, evolution of these methods is inevitable. We compared a standard ASTM 10-day amphipod toxicity testing method with smaller, 48- and 96-h test methods using very toxic and reference ...

  13. 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.

  14. Toxicity testing using microcosms. Chapter 13

    Energy Technology Data Exchange (ETDEWEB)

    Sheppard, S.C

    1996-07-01

    Microcosms are, literally, small worlds, and there are very nearly as many interpretations of what that means as there are researchers willing to use them. There is a lively debate on what constitutes a microcosm, and if there are any advantages to be gained over single-species ecotoxicological investigations (Cairns, 1983). As a result, few microcosm toxicity tests have any form of official sanction (van Gestel and van Straalen, 1994), and no soil microcosm tests are in widespread, routine usage. The American Society for Testing and Materials (ASTM) does list one soil microcosm methodology (E 1197-87, ASTM, 1987). As Golley (1985) comments, there are 4 or 5 million species of organisms on earth, and they each live in communities of 1000 to 2000 species with substantial ecological interconnections. We cannot build systems as complex, and yet we must study impacts on such systems. Microcosms offer an additional step on the way from studies of single species toward studies of true ecological complexity. (author)

  15. 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

  16. 78 FR 69414 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2013-11-19

    ... AGENCY Toxic Substances Control Act Chemical Testing; Receipt of Test Data AGENCY: Environmental... test rule issued by EPA under the Toxic Substances Control Act (TSCA). The purpose of this notice is to... pigments; Toxicity to Algae; Acute emulsion polymerization in Inhalation Toxicity in paper, textile, fiber...

  17. Alternative testing strategies for predicting developmental toxicity of antifungal compound

    NARCIS (Netherlands)

    Li, H.

    2016-01-01

    Determination of safe human exposure levels of chemicals in toxicological risk assessments largely relies on animal toxicity data. In these toxicity studies, the highest number of animals are used for reproductive and developmental toxicity testing. Because of economic and ethical reasons, there is

  18. An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

    Science.gov (United States)

    Hoffmann, Krista Callinan; Deanovic, Linda; Werner, Inge; Stillway, Marie; Fong, Stephanie; Teh, Swee

    2016-10-01

    A novel 2-tiered analytical approach was used to characterize and quantify interactions between type I and type II pyrethroids in Hyalella azteca using standardized water column toxicity tests. Bifenthrin, permethrin, cyfluthrin, and lambda-cyhalothrin were tested in all possible binary combinations across 6 experiments. All mixtures were analyzed for 4-d lethality, and 2 of the 6 mixtures (permethrin-bifenthrin and permethrin-cyfluthrin) were tested for subchronic 10-d lethality and sublethal effects on swimming motility and growth. Mixtures were initially analyzed for interactions using regression analyses, and subsequently compared with the additive models of concentration addition and independent action to further characterize mixture responses. Negative interactions (antagonistic) were significant in 2 of the 6 mixtures tested, including cyfluthrin-bifenthrin and cyfluthrin-permethrin, but only on the acute 4-d lethality endpoint. In both cases mixture responses fell between the additive models of concentration addition and independent action. All other mixtures were additive across 4-d lethality, and bifenthrin-permethrin and cyfluthrin-permethrin were also additive in terms of subchronic 10-d lethality and sublethal responses. Environ Toxicol Chem 2016;35:2542-2549. © 2016 SETAC. © 2016 SETAC.

  19. Bacterial and enzymatic bioassays for toxicity testing in the environment.

    Science.gov (United States)

    Bitton, G; Koopman, B

    1992-01-01

    Microbioassays using bacteria or enzymes are increasingly applied to measure chemical toxicity in the environment. Attractive features of these assays may include low cost, rapid response to toxicants, high sample throughput, modest laboratory equipment and space requirements, low sample volume, portability, and reproducible responses. Enzymatic tests rely on measurement of either enzyme activity or enzyme biosynthesis. Dehydrogenases are the enzymes most used in toxicity testing. Assay of dehydrogenase activity is conveniently carried out using oxidoreduction dyes such as tetrazolium salts. Other enzyme activity tests utilize ATPases, esterases, phosphatases, urease, luciferase, beta-galactosidase, protease, amylase, or beta-glucosidase. Recently, the inhibition of enzyme (beta-galactosidase, tryptophanase, alpha-glucosidase) biosynthesis has been explored as a basis for toxicity testing. Enzyme biosynthesis was found to be generally more sensitive to organic chemicals than enzyme activity. Bacterial toxicity tests are based on bioluminescence, motility, growth, viability, ATP, oxygen uptake, nitrification, or heat production. An important aspect of bacterial tests is the permeability of cells to environmental toxicants, particularly organic chemicals of hydrophobic nature. Physical, chemical, and genetic alterations of the outer membrane of E. coli have been found to affect test sensitivity to organic toxicants. Several microbioassays are now commercially available. The names of the assays and their basis are: Microtox (bioluminescence), Polytox (respiration), ECHA Biocide Monitor (dehydrogenase activity), Toxi-Chromotest (enzyme biosynthesis), and MetPAD (enzyme activity). An important feature common to these tests is the provision of standardized cultures of bacteria in freeze-dried form. Two of the more recent applications of microbioassays are in sediment toxicity testing and toxicity reduction evaluation. Sediment pore water may be assayed directly or

  20. Status and applications of echinoid (phylum echinodermata) toxicity test methods

    Energy Technology Data Exchange (ETDEWEB)

    Bay, S.; Burgess, R.; Nacci, D.

    1993-01-01

    The use of echinoderms for toxicity testing has focused primarily on sea urchins and sand dollars (Strongylocentrotus purpuratus, Arbacia punctulata, Lytechinus pictus, and Dendraster excentricus, for example). The status and relative sensitivity of various test methods are described. The most frequently used test methods consist of short-term exposures of sea urchin sperm or embryos; these tests can be easily conducted at all times of the year by using species with complementary spawning cycles or laboratory conditioned populations of a single species. Data from reference toxicant and effluent toxicity tests are summarized. Information on the precision and sensitivity of echinoid test methods are limited and preclude rigorous comparisons with other test methods. The available data indicate that the sensitivity and precision of these methods are comparable to short-term chronic methods for other marine invertebrates and fish. Recent application of the sperm test in toxicity identification evaluations (TIEs) and studies of effluent toxicity decay and sediment toxicity illustrate the versatility of this rapid (10 to 60 min exposure) test method. Embryo tests typically use a 48 to 96 h exposure period and measure the occurrence of embryo malformations. Most recent applications of the embryo test have been for the assessment of sediment elutriate toxicity. Adult echinoderms are not frequently used to assess effluent or receiving water toxicity. Recent studies have had success in using the adult life stage of urchins and sand dollars to assess the effects of contaminated sediment on growth, behavior, and bioaccumulation.

  1. 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.

  2. In vitro Toxicity Testing in the Twenty-First Century.

    Science.gov (United States)

    Roggen, Erwin L

    2011-01-01

    The National Research Council (NRC) article "Toxicity Testing in the 21st Century: A vision and A Strategy" (National Research Council, 2007) was written to bring attention to the application of scientific advances for use in toxicity tests so that chemicals can be tested in a more time and cost efficient manner while providing a more relevant and mechanistic insight into the toxic potential of a compound. Development of tools for in vitro toxicity testing constitutes an important activity of this vision and contributes to the provision of test systems as well as data that are essential for the development of computer modeling tools for, e.g., system biology, physiologically based modeling. This article intends to highlight some of the issues that have to be addressed in order to make in vitro toxicity testing a reality in the twenty-first century.

  3. In Vitro Toxicity testing in the 21st Century

    Directory of Open Access Journals (Sweden)

    Erwin L Roggen

    2011-02-01

    Full Text Available The National Research Council (NRC article Toxicity Testing in the 21st Century: A vision and A Strategy (National Research Council, 2007 was written to bring attention to the application of scientific advances for use in toxicity tests so that chemicals can be tested in a more time and cost efficient manner while providing a more relevant and mechanistic insight into the toxic potential of a compound.Development of tools for in vitro toxicity testing constitutes an important activity of this vision and contributes to the provision of test systems as well as data that are essential for the development of computer modelling tools for e.g. system biology, physiologically-based modelling. This article intends to highlight some of the issues that have to be addressed in order to make in vitro toxicity testing a reality in the 21st century.

  4. 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

  5. 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...

  6. Aquatic toxicity testing for hazard identification of engineered nanoparticles

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard

    been on the algal growth rate inhibition test and acute and chronic toxicity tests with crustaceans, all commonly applied in a regulatory context. The exposure timing measures included aging of ENPs in test media prior to incubation, and/or shortened exposure duration. For algae, shorter exposure...... toxicity of ENPs, the applicability of the generated data for hazard identification purposes is generally impaired by poor reproducibility and reliability of data, and limited understanding of the underlying effect mechanisms. Consequently, it has been questioned whether the standardized aquatic toxicity...... tests, developed for testing soluble compounds, are equally applicable for ENPs. The preconditions for aquatic toxicity tests include aqueous solubility of the chemical test compound and stability during incubation. These criteria are not met for ENPs, as they are suspended rather than dissolved...

  7. RESULTS OF SOLID PHASE SEDIMENT TOXICITY TESTS WITH REDUCED SEDIMENT VOLUMES FOR SEDIMENT TOXICITY

    Science.gov (United States)

    Development and standardization of sediment toxicity test methods for freshwater organisms have been underway for several years. Both EPA and ASTM have published methods for assessing the short-term (e.g., 10-d) toxicity of sediments to two benthic freshwater organisms (Hyalella ...

  8. EVALUATION OF ALTERNATIVE REFERENCE TOXICANTS FOR USE IN THE EARTHWORM TOXICITY TEST

    Science.gov (United States)

    The use of the 14-d earthworm toxicity test to aid in the evaluation of the ecological impact of contaminated soils is becoming increasingly widespread. However,the method is in need of further standardization. As part of this continuing process, the choice of reference toxicants...

  9. Screening of toxic potential of graphene family nanomaterials using and alternative toxicity testing systems

    Directory of Open Access Journals (Sweden)

    Nivedita Chatterjee

    2015-07-01

    Full Text Available Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]–pristine, carboxylate [COOH] and amide [NH2] and graphene oxides (single layer [SLGO] and few layers [FLGO]. The human bronchial epithelial cells (Beas2B cells as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs’ toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial’s physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

  10. 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

    Full Text Available A busca de novos medicamentos tem levado ao desenvolvimento de novos fármacos que sejam eficientes e destituídos de toxicidade. Uma das fronteiras nessas pesquisas são os medicamentos fitoterápicos. No Brasil, a Agência Nacional de Vigilância Sanitária (ANVISA regulariza essas pesquisas e padroniza os procedimentos. A Resolução da Diretoria Colegiada (RDC 48/2004, por exemplo, regulariza o registro de fitoterápicos. O Anacardium occidentale Linn está entre as plantas mais estudadas, devido às ações antibiótica e antiinflamatória de seus metabólitos secundários, principalmente taninos. Esta planta também possui a capacidade de impedir a formação da placa bacteriana bucal. Diante dessas ações, formas farmacêuticas acabadas (cremes e géis foram desenvolvidas a partir do extrato bruto seco (EBS das cascas do caule do A. occidentale Linn para registro de um novo fitomedicamento. Entretanto, testes pré-clínicos e clínicos devem ser feitos de acordo com a lei vigente. O presente trabalho avaliou a toxicidade subcrônica do EBS em cães sem raça definida (SRD. Os testes revelaram apenas hepatotoxicidade transitória demonstrada pela elevação dos níveis da alanina transaminase (ALT e aspartato transaminase (ASTResearch on new medicaments has led to the development of efficient and non-toxic drugs. In Brazil, the Agência Nacional de Vigilância Sanitária (National Department of Sanitary Supervision – ANVISA regularizes and standardizes the procedure. Anacardium occidentale is amongst the most researched plants, due to the antibiotics and antinflammatory properties of its secondary metabolites, mainly tannins and flavonoids. Furthermore, it prevents the dental plaque formation. On account of these actions, finished pharmaceutical forms (creams and gels were developed from the crude dry extract (CDE of A. occidentale Linn stem rinds, in order to register a new form. However, pre-clinical and clinical assays can be made in

  11. Draft Test Guideline: Whole Sediment Acute Toxicity Invertebrates, Marine

    Science.gov (United States)

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  12. 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.

  13. 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.

  14. Rice seed toxicity tests for organic and inorganic substances

    Science.gov (United States)

    Wang, W.

    1994-01-01

    Plant seed toxicity tests can be used to evaluate hazardous waste sites and to assess toxicity of complex effluents and industrial chemicals. Conventional plant seed toxicity tests are performed using culture dishes containing filter paper. Some reports indicate that filter papers might interfere with the toxicity of inorganic substances. In this study, a plastic seed tray was used. Rice was used as the test species. A comparison of results in the literature and this study revealed that variation of test species, methods, exposure duration, and other factors may affect the test results. The results of this study showed that the order of decreasing toxicity of metal ions was Cu>Ag>Ni>Cd>Cr(VI)>Pb>Zn>Mn>NaF for rice. The test results were similar to those reported in the literature for lettuce Ag>Ni>Cd,Cu>Cr (VI)>Zn>Mn, millet Cu,Ni>Cd>Cr(VI)>Zn>Mn, and ryegrass Cu>Ni>Mn>>Pb>Cd>Zn> Al>Hg>Cr>Fe. The order of decreasing toxicity of organic herbicides was paraquat, 2,4-D>>glyphosate>bromacil.

  15. 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 ...

  16. 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.

  17. Biological assays for aquatic toxicity testing

    CSIR Research Space (South Africa)

    Slabbert, JL

    1999-10-01

    Full Text Available and management purposes of effluents. If receiving water is used for drinking water purposes, the Ames Salmonella mutagenicity and toad embryo teratogenicity tests should be included in the battery of tests. Some of the rapid microbiotests, the petrozoan oxygen...

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

    Directory of Open Access Journals (Sweden)

    Čolović Mirjana B.

    2013-01-01

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

  19. The status of toxicity tests with sediment in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, R.P.A. [Companhia de Tecnologia e Saneamento Ambiental, Sao Paulo (Brazil)

    1995-12-31

    The earliest studies in Brazil aiming to evaluate sediment quality through toxicity tests started in the beginning of the 80`s. These were developed by the Environmental Sanitation Agency of Sao Paulo State (CETESB) in Cubatao River and Billings Reservoir, which are located in industrialized and populous regions. Elutriate phase sediment toxicity tests were run with Daphnia similis. In the Cubatao River Basin the combination of toxicity, chemistry data and benthic community structure provided clear indications of sites with different levels of pollution. At this time there was a consensus that the study of a complex compartment such as sediment needed improvements in sampling and analysis procedures. Only in the 90`s the investigations involving sediment toxicity assessment were resumed by CETESB, and it was clear that integrative studies were needed in order to make environmental quality assessment. This kind of studies were conducted by CETESB in some highly polluted areas of Sao Paulo State, Ceriodaphnia dubia and Photobacterium phosphoreum interstitial water tests and Hyalella sp whole sediment tests were run, and the results correlated with several sediment organic and inorganic contaminants. The Sediment Quality Triad proposed by Chapman was applied in one of these studies. This approach was extremely useful in interpreting the data. At the same time marine sediment toxicity tests were developed by CETESB in collaboration with Sao Paulo University, and tests were run with the amphipods Tiburonella viscana, Battyporeiapus bisetosus; tanaidacean Kalliapseudes shubarti and the echinoderm Lytechinus variegatus. The embryo test with L. variegatus was the most adequate in these studies. Nowadays there are other groups in some universities developing sediment toxicity tests with Hyalella and Chironomus in response to a growing concern in Brazil to establish adequate sediment quality assessment guidelines.

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

    African Journals Online (AJOL)

    Background: Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. Objective: LD and phytochemistry of four medicinal plants 50 of West Africa ...

  1. A Mini-Nitrification Test for Toxicity Screening, Minntox

    DEFF Research Database (Denmark)

    Arvin, Erik; Dyreborg, Søren; Menck, C.

    1994-01-01

    There is a high demand for a rapid, simple, and inexpensive test for screening of the toxicity of wastewater, polluted groundwater and chemicals in order to protect sewage treatment plants and aquatic and terrestrial recipients. The mini-nitrification test, MINNTOX, presented here, fulfils...

  2. Acute Toxicity Tests Of Brewery Effluent on the Ostracoda ...

    African Journals Online (AJOL)

    The acute toxicity of brewery effluent to Strandesia prava Klie (crustacean, ostracoda) was determined in 24, 48 and 96 hour static bioassay under laboratory conditions. The test was conducted in replicates of 100, 50, 25, 12.5, 6.25 and 3.125% effluent concentrations. Mortality of the test organism increased with the ...

  3. 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.

  4. Use of blue crab (Callinectes sapidus) embryos for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, R.; O`Malley, K. [Skidaway Inst. of Oceanography, Savannah, GA (United States)

    1995-12-31

    After fertilization, blue crab embryos develop in egg sacs attached to the female pleopods, often referred to as the sponge. Lipovitellin and lipid droplets in the egg sacs provide energy and nutrition for the developing embryos. Embryos were removed from the sponge and transferred to 24 well culture plates containing sea water with or without toxicants, Each well contained 10 embryos. After 7 to 10 days, embryos hatched to swimming zoea. The effects of toxicants at various concentrations on hatching were determined and the EC{sub 50} calculated. For example, the EC{sub 50} for tributyltin, fenvalerate and mercuric chloride were 50, 30 and 90 ng/liter, respectively. The hatching success of control embryos ranged from 95 to 98%. Formation of the heart, eyespot formation, appendage formation and utilization rate of lipovitellin were also effected by exposure to toxicants. At a low concentration of mercuric ion (30ng/liter) the heart formed, but there was no heart beat. Eyespot formation was abnormal in the presence of high concentrations of cadmium (2 {micro}g/liter) and zinc (5 {micro}g/liter), Crab embryos offer many advantages for toxicity testing of pure compounds or mixtures in water, including toxicity testing of sediment pore water. The crab embryos may also serve as models to understand the effect of specific toxicants on the heart and eye spots of crustaceans.

  5. Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    Science.gov (United States)

    Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

    2014-05-01

    Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver

  6. Functional toxicology: tools to advance the future of toxicity testing

    Science.gov (United States)

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  7. Functional toxicology: tools to advance the future of toxicity testing.

    Science.gov (United States)

    Gaytán, Brandon D; Vulpe, Chris D

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds-information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes.

  8. Functional toxicology: tools to advance the future of toxicity testing

    Directory of Open Access Journals (Sweden)

    Brandon David Gaytán

    2014-05-01

    Full Text Available The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds – information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1 novel insights into chemical toxicity; (2 pathways and mechanisms deserving of further study; and (3 candidate human toxicant susceptibility or resistance genes.

  9. Scanning respirometer for toxicity tests using micro-organisms

    Science.gov (United States)

    Zhang, Min-Quan; Li, Xiang-Ming; Wong, Yuk-Shan; Kwan, FolkYear

    1995-09-01

    A novel respirometer is developed for microbial toxicity tests. The respirometer is based on luminescent quenching of oxygen to measure the concentration of dissolved oxygen in cell vessels and evaluate the toxicity of chemicals by monitoring the effect of toxicants on cell respiration of micro-organisms. The oxygen sensing element is ruthenium complex absorbed on the surface of silica particles followed by immobilizing on a silicone rubber film. The oxygen sensing film is coated on the inner bottom of a transparent cell vessel. A sensing device scanning under the cell vessel is used for remote monitoring of the oxygen concentration inside the cell vessels so that a large number of samples can be handled in one batch. The sensing device includes the excitation light sources and an optical cable connected to a filter and a photomultiplier tube for detecting the luminescence in the cell vessel which can then be related to the dissolved oxygen concentration inside the cell vessel. The movement of the sensing device and data acquisition are controlled by a personal computer. The toxicity of heavy metals to activated sludge, soil bacteria and E. coli were tested using the present device. The scanning respirometer provides a new alternative for fast and large scale screening and monitoring of toxicants using micro-organisms.

  10. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Science.gov (United States)

    2010-07-01

    ... the test organisms, including the scientific name and method of verification, average length, age... concentrations, including method validations and reagent blanks. (12) The data records of the holding... apply to this guideline: (1) “Chronic toxicity test” means a method used to determine the concentration...

  11. Controlling type-1 error rates in whole effluent toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R.; Johnson, S.C. [EcoAnalysis, Inc., Ojai, CA (United States)

    1995-12-31

    A form of variability, called the dose x test interaction, has been found to affect the variability of the mean differences from control in the statistical tests used to evaluate Whole Effluent Toxicity Tests for compliance purposes. Since the dose x test interaction is not included in these statistical tests, the assumed type-1 and type-2 error rates can be incorrect. The accepted type-1 error rate for these tests is 5%. Analysis of over 100 Ceriodaphnia, fathead minnow and sea urchin fertilization tests showed that when the test x dose interaction term was not included in the calculations the type-1 error rate was inflated to as high as 20%. In a compliance setting, this problem may lead to incorrect regulatory decisions. Statistical tests are proposed that properly incorporate the dose x test interaction variance.

  12. Mollusc reproductive toxicity tests - Development and validation of test guidelines

    DEFF Research Database (Denmark)

    Ducrot, Virginie; Holbech, Henrik; Kinnberg, Karin Lund

    . Draft standard operating procedures (SOPs) have been designed based upon literature and expert knowledge from project partners. Pre-validation studies have been implemented to validate the proposed test conditions and identify issues in performing the SOPs and analyzing test results. Pre-validation work...... for P. antipodarum consisted in a comparative 28-day study between four laboratories and with two test substances: cadmium (Cd) and bisphenol A (BPA). For L. stagnalis, pre-validation consisted in a comparative 56-day study between six laboratories and with two test substances: Cd and tributyltin (TBT...... in partner laboratories and exhibited homogenous age and size at the beginning of the tests. All laboratories found a concentration-dependent decrease of fecundity in both species under Cd exposure. Values of NOECs and LOECs were generally homogenous among laboratories. Results of the pre-validation studies...

  13. In vitro Cell Culture Model for Toxic Inhaled Chemical Testing

    Science.gov (United States)

    Ahmad, Shama; Ahmad, Aftab; Neeves, Keith B.; Hendry-Hofer, Tara; Loader, Joan E.; White, Carl W.; Veress, Livia

    2014-01-01

    Cell cultures are indispensable to develop and study efficacy of therapeutic agents, prior to their use in animal models. We have the unique ability to model well differentiated human airway epithelium and heart muscle cells. This could be an invaluable tool to study the deleterious effects of toxic inhaled chemicals, such as chlorine, that can normally interact with the cell surfaces, and form various byproducts upon reacting with water, and limiting their effects in submerged cultures. Our model using well differentiated human airway epithelial cell cultures at air-liqiuid interface circumvents this limitation as well as provides an opportunity to evaluate critical mechanisms of toxicity of potential poisonous inhaled chemicals. We describe enhanced loss of membrane integrity, caspase release and death upon toxic inhaled chemical such as chlorine exposure. In this article, we propose methods to model chlorine exposure in mammalian heart and airway epithelial cells in culture and simple tests to evaluate its effect on these cell types. PMID:24837339

  14. Freshwater toxicity testing using rehydrated Philodina sp. (Rotifera) as test animals.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B

    2017-10-01

    Rotifers have become widely used in aquatic toxicology as a rapid screening test for toxicity. The commercial availability of diapausing embryos (cysts) have facilitated their popularity because test animals can be obtained without having to master the details of culturing. Other rotifer species have life stages capable of surviving desiccation and also could be used in non-culture systems for toxicity assessment. In this article, we describe a system for toxicity testing in freshwater based on rehydrating desiccated bdelloid rotifers in the genus Philodina. These animals can remain in this anhydrobiotic state for more than one year and then rehydrate within hours to provide animals for toxicity tests. We describe three endpoints: a 1.5 h ingestion test, a 24 h mortality test, and a five day reproductive test. The latter test requires feeding and a method using a dried commercial product is explained. Using desiccated rotifers and dried food in toxicity tests make this system especially attractive because of its flexibility and low threshold of biological expertise required to execute the tests. The use of the Philodina toxicity test is illustrated with four metals: copper, lead, mercury and cadmium. Reproduction generally was the most sensitive endpoint, with EC50s of 0.33, 0.44, 0.60, and 0.12 mg/L, respectively. Ingestion was a close second with EC50s of 0.13, 1.64, 0.64, and 6.26 mg/L, respectively. © 2017 Wiley Periodicals, Inc.

  15. Effects of using synthetic sea salts when measuring and modeling copper toxicity in saltwater toxicity tests.

    Science.gov (United States)

    Arnold, W Ray; Cotsifas, Jeffrey S; Winter, Anna R; Klinck, Joel S; Smith, D Scott; Playle, Richard C

    2007-05-01

    Synthetic sea salts are often used to adjust the salinity of effluent, ambient, and laboratory water samples to perform toxicity tests with marine and estuarine species. The U.S. Environmental Protection Agency (U.S. EPA) provides guidance on salinity adjustment in its saltwater test guidelines. The U.S. EPA suggests using commercial sea salt brands, such as Forty Fathoms (now named Crystal Sea Marinemix, Bioassay Grade), HW Marinemix, or equivalent salts to adjust sample salinity. Toxicity testing laboratories in Canada and the United States were surveyed to determine synthetic sea salt brand preference. The laboratories (n = 27) reported using four brands: Crystal Sea Marinemix (56%), HW Marinemix (22%), Instant Ocean (11%), and Tropic Marin (11%). Saline solutions (30 g/L) of seven synthetic sea salts were analyzed for dissolved copper and dissolved organic carbon (DOC) content. Brands included those listed above plus modified general-purpose salt (modified GP2), Kent Marine, and Red Sea Salt. The synthetic sea salts added from analysis of variance, Tukey, alpha = 0.05, p copper toxicity. However, the measured dissolved copper effective concentration 50% (EC50) for Crystal Sea Marinemix was 9.7 microg Cu/L, similar to other tested sea salts. Analysis indicates that the organic matter in Crystal Sea Marinemix differs considerably from that of natural organic matter. On the basis of consistently adding little DOC and little dissolved copper, GP2 and Kent Marine are the best salts to use.

  16. Large Dataset of Acute Oral Toxicity Data Created for Testing ...

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are being developed due to animal welfare and resource considerations. We compiled a large dataset of oral rat LD50 values to assess the predictive performance currently available in silico models. Our dataset combines LD50 values from five different sources: literature data provided by The Dow Chemical Company, REACH data from eChemportal, HSDB (Hazardous Substances Data Bank), RTECS data from Leadscope, and the training set underpinning TEST (Toxicity Estimation Software Tool). Combined these data sources yield 33848 chemical-LD50 pairs (data points), with 23475 unique data points covering 16439 compounds. The entire dataset was loaded into a chemical properties database. All of the compounds were registered in DSSTox and 59.5% have publically available structures. Compounds without a structure in DSSTox are currently having their structures registered. The structural data will be used to evaluate the predictive performance and applicable chemical domains of three QSAR models (TIMES, PROTOX, and TEST). Future work will combine the dataset with information from ToxCast assays, and using random forest modeling, assess whether ToxCast assays are useful in predicting acute oral toxicity. Pre

  17. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  18. Biological test method: Acute test for sediment toxicity using marine or estuarine amphipods

    National Research Council Canada - National Science Library

    McLeay, D. J; Sprague, John B

    1992-01-01

    Methods recommended by Environment Canada for performing 10-day tests for sediment toxicity, using one or more of the following species of marine or estuarine sediment-burrowing amphipods, are described in this report...

  19. Using single-species toxicity tests, community-level responses, and toxicity identification evaluations to investigate effluent impacts

    Energy Technology Data Exchange (ETDEWEB)

    Maltby, L.; Clayton, S.A.; Yu, H.; McLoughlin, N.; Wood, R.M.; Yin, D.

    2000-01-01

    Whole effluent toxicity (WET) tests are increasingly used to monitor compliance of consented discharges, but few studies have related toxicity measured using WET tests to receiving water impacts. Here the authors adopt a four-stage procedure to investigate the toxicity and biological impact of a point source discharge and to identify the major toxicants. In stage 1, standard WET tests were employed to determine the toxicity of the effluent. This was then followed by an assessment of receiving water toxicity using in situ deployment of indigenous (Gammarus pulex) and standard (Daphnia magna) test species. The third stage involved the use of biological survey techniques to assess the impact of the discharge on the structure and functioning of the benthic macroinvertebrate community. In stage 4, toxicity identification evaluations (TIE) were used to identify toxic components in the effluent. Receiving-water toxicity and ecological impact detected downstream of the discharge were consistent with the results of WET tests performed on the effluent. Downstream of the discharge, there was a reduction in D. magna survival, in G. pulex survival and feeding rate, in detritus processing, and in biotic indices based on macroinvertebrate community structure. The TIE studies suggested that chlorine was the principal toxicant in the effluent.

  20. Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems.

    Science.gov (United States)

    Chatterjee, Nivedita; Yang, Ji Su; Park, Kwangsik; Oh, Seung Min; Park, Jeonggue; Choi, Jinhee

    2015-01-01

    The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

  1. Toxicity testing: The search for an in vitro alternative to animal testing

    OpenAIRE

    May, J. E.; Xu, J.; Morse, R.; Avent, N; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must\\ud undergo rigorous toxicity testing to ensure their safety.\\ud Traditionally, this has been achieved using in vivo animal\\ud models. However, besides ethical reasons, there is a\\ud continual drive to reduce the number of animals used for\\ud this purpose due to concerns such as the lack of\\ud concordance seen between animal models and toxic effects\\ud in humans. Adequate testing to ensure any toxic\\ud metabolites are detected can be fu...

  2. [Modification of the Photobacterium phosphoreum toxicity test method].

    Science.gov (United States)

    Lin, Z; Yu, H; Xu, S; Wang, L

    2001-03-01

    In order to reduce the variation of Photobacterium phosphoreum luminous intensity during testing, the Photobacterium phosphoreum toxicity test was modified by a correction factor, PIacetone, in this paper. The effects of magnetic stirring time, culture time, culture generation and culture temperature on the measured results were discussed. The modified method had good laboratory repeatability and the relative standard deviation (RSD) was between 2.1% and 13.1%. Reliable data could be obtained using the modified method. It would be beneficial to the development of the quantitative structure-activity relationships on multicomponent organic compounds.

  3. 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.

  4. 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.

  5. 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

  6. Fractionating nanosilver: importance for determining toxicity to aquatic test organisms.

    Science.gov (United States)

    Kennedy, Alan J; Hull, Matthew S; Bednar, Anthony J; Goss, Jennifer D; Gunter, Jonas C; Bouldin, Jennifer L; Vikesland, Peter J; Steevens, Jeffery A

    2010-12-15

    This investigation applied novel techniques for characterizing and fractionating nanosilver particles and aggregates and relating these measurements to toxicological endpoints. The acute toxicity of eight nanosilver suspensions of varying primary particle sizes (10-80 nm) and coatings (citrate, polyvinylpyrrolidone, EDTA, proprietary) was assessed using three aquatic test organisms (Daphnia magna, Pimephales promelas, Pseudokirchneriella subcapitata). When 48-h lethal median concentrations (LC50) were expressed as total silver, both D. magna and P. promelas were significantly more sensitive to ionic silver (Ag(+)) as AgNO(3) (mean LC50 = 1.2 and 6.3 μg/L, respectively) relative to a wide range in LC50 values determined for the nanosilver suspensions (2 -126 μg/L). However, when LC50 values for nanosilver suspensions were expressed as fractionated nanosilver (Ag(+) and/or toxicity and underscores the importance of characterizing dissolved fractions in nanometal suspensions.

  7. 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.

  8. TRACKING PYRETHROID TOXICITY IN SURFACE WATER SAMPLES: EXPOSURE DYNAMICS AND TOXICITY IDENTIFICATION TOOLS FOR LABORATORY TESTS WITH HYALELLA AZTECA (AMPHIPODA).

    Science.gov (United States)

    Deanovic, Linda A; Stillway, Marie; Hammock, Bruce G; Fong, Stephanie; Werner, Inge

    2017-09-09

    Pyrethroid insecticides are commonly used in pest control and are present at toxic concentrations in surface waters of agricultural and urban areas worldwide. Monitoring is challenging due to their high hydrophobicity and low toxicity thresholds, which often fall below the detection limits of analytical methods. Standard daphnid bioassays used in surface water monitoring are not sensitive enough to protect more susceptible invertebrate species such as the amphipod, Hyalella azteca, and chemical loss during toxicity testing is of concern. In this study, we quantified toxicity loss during storage and testing, using both natural and synthetic water, and present a tool to enhance toxic signal strength for improved sensitivity of H. azteca toxicity tests. The average half-life during storage in LDPE cubitainers at 4°C of five pyrethroids (permethrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, esfenvalerate) and one organophosphate (chlorpyrifos; used as reference) was 1.4 d, and piperonyl butoxide (PBO) proved an effective tool to potentiate toxicity. We conclude that toxicity tests on ambient water samples containing these hydrophobic insecticides are likely to underestimate toxicity present in the field, and mimic short pulse rather than continuous exposures. Where these chemicals are of concern, the addition of PBO during testing can yield valuable information on their presence or absence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. A REVIEW OF SINGLE SPECIES TOXICITY TESTS: ARE THE TESTS RELIABLE PREDICTORS OF AQUATIC ECOSYSTEM COMMUNITY RESPONSES?

    Science.gov (United States)

    This document provides a comprehensive review to evaluate the reliability of indicator species toxicity test results in predicting aquatic ecosystem impacts, also called the ecological relevance of laboratory single species toxicity tests.

  10. Current and future needs for developmental toxicity testing.

    Science.gov (United States)

    Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

    2011-10-01

    A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. © 2011 Wiley Periodicals, Inc.

  11. Guanicid and PHMG Toxicity Tests on Aquatic Organisms

    Directory of Open Access Journals (Sweden)

    Eva Poštulková

    2016-01-01

    Full Text Available The emergence and development of new algicidal products is caused by the ever increasing popularity of garden ponds as well as the use of these products in the fisheries sector, especially for disposal of cyanobacteria and algae. Most frequent means of combating cyanobacteria and algae are applications of algicidal substances. Newly developed algaecides include Guanicid and polyhexamethylene guanidine hydrochloride (PHMG. The aim of the study was to identify toxic effects of Guanicid and PHMG on zebrafish (Danio rerio and green algae (Desmodesmus communis. We determined the acute toxicity in fish according to ČSN EN ISO 7346-1, and conducted the freshwater algae growth inhibition test according to ČSN ISO 8692 methodology. For inhibition tests with green algae we chose Guanicid and PHMG concentrations of 0.001, 0.005, and 0.010 ml/L. For fish short-term acute toxicity tests we chose Guanicid concentrations of 0.010, 0.050, 0.150, 0.200, 0.250, and 0.300 ml/L and PHMG concentrations of 0.010, 0.025, 0.050, 0.075, 0.100, and 0.125 ml/L. In case of zebrafish (Danio rerio, the LC50 value for Guanicid is 0.086 ml/L, while the LC50 value for PHMG is 0.043 ml/L. Effects of Guanicid on inhibition of green algae (Desmodesmus communis appear highly significant (p < 0.010 at a concentration of 0.010 ml/L. For PHMG, these effects are highly significant (p < 0.001 at concentrations of 0.005 and 0.010 ml/L in 48 hours.

  12. Organotypic liver culture models: meeting current challenges in toxicity testing.

    Science.gov (United States)

    LeCluyse, Edward L; Witek, Rafal P; Andersen, Melvin E; Powers, Mark J

    2012-07-01

    Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment.

  13. Microtox solid phase test: Effect of diluent used in toxicity test.

    Science.gov (United States)

    Volpi Ghirardini, Annamaria; Girardini, Marco; Marchetto, Davide; Pantani, Claudio

    2009-03-01

    Microtox solid phase test is an acute toxicity test for solid matrices based on inhibition of natural bioluminescence of the marine bacterium Vibrio fischeri. Protocols developed to overcome the effects of confounding factors are proposed in the literature that differs by important practical and methodological issues. This work focused on diluents used for sediment resuspension and dilution. Two artificial seawaters, one natural seawater and two phosphate buffer solutions, were compared. The results showed that toxicity data obtained using different diluents were not comparable and that test sensitivity is highest using 0.1M phosphate buffer solution. The effects of medium on test organism were also investigated, in order to verify the capacity of media to maintain bioluminescence. The results underlined the importance of pH and Eh to explain the observed differences in toxicity.

  14. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  15. Photosynthesis tests as an alternative to growth tests for hazard assessment of toxicant

    DEFF Research Database (Denmark)

    Petersen, S.; Kusk, Kresten Ole

    2000-01-01

    Acute (3- and 6-h) toxic responses toward Cu, linear alkylbenzene sulfonate (LAS), and tributyltin (TBT) of lightsaturated and unsaturated photosynthesis were investigated for Rhodomonas salina and Skeletonema costatum obtained from exponentially growing batch cultures and from chemostat cultures...... limited by either nitrogen or phosphorus. The sensitivity of the photosynthesis tests were compared to standardized growth tests applied to the same species and toxicants. For Cu and S. costatum the photosynthesis test was up to 300 times more sensitive at light saturation than at light limitation....... For the remaining photosynthesis tests no dependence on light condition were found. The photosynthesis tests with Cu and S. costatum were up to 10 times as sensitive as the growth test and most sensitive when the algae were obtained from a phosphatelimited chemostate. For the other photosynthesis tests...

  16. 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.

  17. 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.

  18. Development and validation of OECD test guidelines on mollusc reproductive toxicity tests

    DEFF Research Database (Denmark)

    Lagadic, Laurent; Holbech, Henrik; hutchinson, tom

    in L. stagnalis. Pre-validation tests were successful in both species. Indeed, both species could be successfully cultured at the lab. Toxicity tests provided consistent results among laboratories for each species (e.g. homogenous and nonsignificantly different NOECs, LOECs and EC 50 values for most......Validated guidelines in line with the OECD Conceptual Framework for the Testing and Assessment of Endocrine Disrupting Chemicals (EDTA) have been developed for rodents, amphibians, fish, aquatic insects and crustaceans. Only aquatic arthropods have been considered in this test battery although...... the comparison of endpoints relevant for reproduction in invertebrates often shows a much higher sensitivity in molluscs vs. e.g. daphnids. The OECD test guideline programme has thus been extended to cover reproduction effects of chemicals in molluscs. Existing mollusc toxicity test protocols have been reviewed...

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

    DEFF Research Database (Denmark)

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

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

  20. Role of omics techniques in the toxicity testing of nanoparticles

    Directory of Open Access Journals (Sweden)

    Eleonore Fröhlich

    2017-11-01

    Full Text Available Abstract Nanotechnology is regarded as a key technology of the twenty-first century. Despite the many advantages of nanotechnology it is also known that engineered nanoparticles (NPs may cause adverse health effects in humans. Reports on toxic effects of NPs relay mainly on conventional (phenotypic testing but studies of changes in epigenome, transcriptome, proteome, and metabolome induced by NPs have also been performed. NPs most relevant for human exposure in consumer, health and food products are metal, metal oxide and carbon-based NPs. They were also studied quite frequently with omics technologies and an overview of the study results can serve to answer the question if screening for established targets of nanotoxicity (e.g. cell death, proliferation, oxidative stress, and inflammation is sufficient or if omics techniques are needed to reveal new targets. Regulated pathways identified by omics techniques were confirmed by phenotypic assays performed in the same study and comparison of particle types and cells by the same group indicated a more cell/organ-specific than particle specific regulation pattern. Between different studies moderate overlap of the regulated pathways was observed and cell-specific regulation is less obvious. The lack of standardization in particle exposure, in omics technologies, difficulties to translate mechanistic data to phenotypes and comparison with human in vivo data currently limit the use of these technologies in the prediction of toxic effects by NPs.

  1. Custom-designed nanomaterial libraries for testing metal oxide toxicity.

    Science.gov (United States)

    Pokhrel, Suman; Nel, André E; Mädler, Lutz

    2013-03-19

    Advances in aerosol technology over the past 10 years have enabled the generation and design of ultrafine nanoscale materials for many applications. A key new method is flame spray pyrolysis (FSP), which produces particles by pyrolyzing a precursor solution in the gas phase. FSP is a highly versatile technique for fast, single-step, scalable synthesis of nanoscale materials. New innovations in particle synthesis using FSP technology, including variations in precursor chemistry, have enabled flexible, dry synthesis of loosely agglomerated, highly crystalline ultrafine powders (porosity ≥ 90%) of binary, ternary, and mixed-binary-and-ternary oxides. FSP can fulfill much of the increasing demand, especially in biological applications, for particles with specific material composition, high purity, and high crystallinity. In this Account, we describe a strategy for creating nanoparticle libraries (pure or Fedoped ZnO or TiO₂) utilizing FSP and using these libraries to test hypotheses related to the particles' toxicity. Our innovation lies in the overall integration of the knowledge we have developed in the last 5 years in (1) synthesizing nanomaterials to address specific hypotheses, (2) demonstrating the electronic properties that cause the material toxicity, (3) understanding the reaction mechanisms causing the toxicity, and (4) extracting from in vitro testing and in vivo testing in terrestrial and marine organisms the essential properties of safe nanomaterials. On the basis of this acquired knowledge, we further describe how the dissolved metal ion from these materials (Zn²⁺ in this Account) can effectively bind with different cell constituents, causing toxicity. We use Fe-S protein clusters as an example of the complex chemical reactions taking place after free metal ions migrate into the cells. As a second example, TiO₂ is an active material in the UV range that exhibits photocatalytic behavior. The induction of electron-hole (e⁻/h⁺) pairs followed by

  2. Simple diagnostic tests to detect toxic alcohol intoxications.

    Science.gov (United States)

    Shin, Jai Moo; Sachs, George; Kraut, Jeffrey A

    2008-10-01

    Methanol, ethylene glycol, and diethylene glycol intoxications can produce visual disturbances, neurologic disturbances, acute renal failure, pulmonary dysfunction, cardiac dysfunction, metabolic acidosis, and death. Metabolic acidosis and an increased serum osmolality are important clues to their diagnosis. The former reflects the organic acids produced by metabolism of the parent alcohol, whereas the latter is caused by accumulation of the offending alcohol. However, neither the clinical nor the laboratory findings are specific for toxic alcohol ingestions. The definitive diagnosis of the alcohol intoxications is commonly based on detection of the alcohol or its metabolites in blood. Early diagnosis is important, because initiation of appropriate treatment can markedly decrease their rates of morbidity and mortality. Currently, detection of the parent alcohol in body fluids is inferred from its measurement in blood. This measurement is often performed by specialty laboratories using expensive equipment, and a long delay between obtaining the specimen and getting the results is not unusual. In this report, we describe liquid-based tests that detect methanol, ethylene glycol, diethylene glycol, and ethanol in saliva. The tests are sensitive, and they have different specificity for each of the alcohols facilitating distinction among them. The relatively high sensitivity and specificity of the tests as a whole will facilitate the rapid diagnosis of each of these alcohol intoxications.

  3. Towards sensible toxicity testing for nanomaterials: proposal for the specification of test design.

    Science.gov (United States)

    Potthoff, Annegret; Weil, Mirco; Meißner, Tobias; Kühnel, Dana

    2015-12-01

    During the last decade, nanomaterials (NM) were extensively tested for potential harmful effects towards humans and environmental organisms. However, a sound hazard assessment was so far hampered by uncertainties and a low comparability of test results. The reason for the low comparability is a high variation in the (1) type of NM tested with regard to raw material, size and shape and (2) procedures before and during the toxicity testing. This calls for tailored, nanomaterial-specific protocols. Here, a structured approach is proposed, intended to lead to test protocols not only tailored to specific types of nanomaterials, but also to respective test system for toxicity testing. There are existing standards on single procedures involving nanomaterials, however, not all relevant procedures are covered by standards. Hence, our approach offers a detailed way of weighting several plausible alternatives for e.g. sample preparation, in order to decide on the procedure most meaningful for a specific nanomaterial and toxicity test. A framework of several decision trees (DT) and flow charts to support testing of NM is proposed as a basis for further refinement and in-depth elaboration. DT and flow charts were drafted for (1) general procedure-physicochemical characterisation, (2) choice of test media, (3) decision on test scenario and application of NM to liquid media, (4) application of NM to the gas phase, (5) application of NM to soil and sediments, (6) dose metrics, (S1) definition of a nanomaterial, and (S2) dissolution. The applicability of the proposed approach was surveyed by using experimental data retrieved from studies on nanoscale CuO. This survey demonstrated the DT and flow charts to be a convenient tool to systematically decide upon test procedures and processes, and hence pose an important step towards harmonisation of NM testing.

  4. Toxicity testing: the search for an in vitro alternative to animal testing.

    Science.gov (United States)

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  5. 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.

  6. 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 ...

  7. Can interpreting sediment toxicity tests a mega sites benefit from novel approaches to normalization to address batching of tests?

    Science.gov (United States)

    Sediment toxicity tests are a key tool used in Ecological Risk Assessments for contaminated sediment sites. Interpreting test results and defining toxicity is often a challenge. This is particularly true at mega sites where the testing regime is large, and by necessity performed ...

  8. Early Evolution of the Toxicity Identification Evaluation Process: Contributions from the USEPA Effluent Testing Program

    Science.gov (United States)

    As part of its whole effluent testing program, the USEPA developed an effects-directed analysis (EDA) approach to identifying the cause of toxicity in toxic effluents or ambient waters, an EDA process termed a “Toxicity Identification Evaluation” (TIE), which is the focus of this...

  9. Comparison of Weibull and Probit Analysis in Toxicity Testing of ...

    African Journals Online (AJOL)

    Purpose; Hunteria umbellata has been found to have therapeutic potentials in the treatments of diseases such as yaws, peptic ulcers, diabetes, piles and infertility in Nigeria; hence, the statistical analysis on the determination of acute toxicity of Hunteria umbellata was carried out in mice. Methods; Data on the acute toxicity ...

  10. Implementing Lecane quadridentata acute toxicity tests to assess the toxic effects of selected metals (Al, Fe and Zn).

    Science.gov (United States)

    Guzmán, Félix Torres; González, Francisco Javier Avelar; Martínez, Roberto Rico

    2010-03-01

    An environmental study revealed that three metals (Al, Fe and Zn) are common in the San Pedro River (SPR) (Aguascalientes, Mexico). Regrettably, in many samples the concentrations of these metals exceeded the maximum allowed toxicant concentrations levels as defined in by Mexican legislation. The highest concentrations of the three metals were found during the 2005 dry season, with elevated Al concentrations present along the entire river. Not surprisingly, the highest concentrations for all three metals came from locations adjacent to industrial areas. Estimates of the contribution of these metals to total toxicity revealed that these three metals are important contaminants of the river and responsible for most of the lethal toxicity found in environmental samples. To assess the importance of these reports, we conducted acute toxicity tests to determine LC50 for Al, Fe and Zn on the freshwater rotifer Lecane quadridentata. This permitted us to estimate the contribution of these metals to total toxicity during 2005-2006. Based on LC50 values, all three metals should be considered very toxic, with the zinc LC50 value (0.12 mg L(-1)) making it the most toxic metal for L. quadridentata. This approach can be applied to other sites with similar concentrations of these metals. (c) 2009 Elsevier Inc. All rights reserved.

  11. Development of a new integrative toxicity index based on an improvement of the sea urchin embryo toxicity test.

    Science.gov (United States)

    Morroni, L; Pinsino, A; Pellegrini, D; Regoli, F; Matranga, V

    2016-01-01

    The sea urchin embryo toxicity test is classically used to assess the noxious effects of contaminated marine waters and sediments. In Italian guidelines on quality of dredged sediments, the standard toxicity criteria used for this assay are based on a single endpoint at 48 hours of development, corresponding to the pluteus stage. Different typologies of abnormalities, including those which occur at earlier stages, are not categorized, thus preventing the evaluation of the actual teratogenic hazards. A new integrative toxicity index has been developed in this study based on the analysis of two developmental stages, at 24 and 48h post-fertilization, and the differentiation between development delays and germ layers impairments: the new toxicity index is calculated by integrating the frequency of abnormal embryos with the severity of such abnormalities. When tested on dredged sediments, the evaluation of increasing levels of toxicity affecting embryonic outcomes enhanced the capability to discriminate different samples, appearing particularly relevant to validate the sea urchin embryo toxicity assay, and supporting its utility in practical applications such as the sediments classification in harbor areas. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Aquatic toxicity testing of liquid hydrophobic chemicals – Passive dosing exactly at the saturation limit

    DEFF Research Database (Denmark)

    Stibany, Felix; Nørgaard Schmidt, Stine; Schäffer, Andreas

    2017-01-01

    inhibition tests with green algae Raphidocelis subcapitata. Growth rate inhibition at DDB solubility was 13 ± 5% (95% CI) in a first and 8 ± 3% (95% CI) in a repeated test, which demonstrated that improved exposure control can lead to good precision and repeatability of toxicity tests. This moderate toxicity......The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing...... at chemical activity of unity was higher than expected relative to a reported hydrophobicity cut-off in toxicity, but lower than expected relative to a reported chemical activity range for baseline toxicity. The present study introduces a new effective approach for toxicity testing of an important group...

  13. Toxicity test of xanthone from mangosteen on zebrafish embryos

    Science.gov (United States)

    Noordin, Muhammad Akram Mohd; Noor, Mahanem Mat; Kamaruddin, Wan Mohd Aizat Wan; Lazim, Azwan Mat; Fazry, Shazrul

    2016-11-01

    Xanthone is a chemical compound identified in mangosteen pericarp. A previous study showed that xanthone has anti-proliferating effect on cancer cells. In this study we investigate the toxicity level of xanthone in zebrafish embryo to for future reference on other animal model. We employed Fish Embryo Toxicity (FET) assay to determine the toxicity level of different concentrations of xanthone. Embryos were observed at 24, 48 and 72 hours post fertilization (hpf) under microscope at 4× magnification. The extract showed toxicity effect on embryo at concentrations of 250, 125 and 62.5 µg/mL. Concentrations at 15.63, 7.81 and 3.91 µg / mL of xanthone did not harm the embryos and showed 100% of survival.

  14. Pyrrolizidine Alkaloids: Testing for Toxic Constituents of Comfrey.

    Science.gov (United States)

    Vollmer, John J.; And Others

    1987-01-01

    Discusses the possibilities of toxins present in medicinal herbs. Describes an experiment in which toxic constituents can be selectively detected by thin-layer chromatography and NMR spectroscopy. (TW)

  15. 76 FR 38170 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2011-06-29

    ...: Kathy Calvo, Chemical Control Division (7405M), Office of Pollution Prevention and Toxics, Environmental... Toxicity to Fish. 9. Acute Toxicity to Aquatic Invertebrates. 10. Toxicity to Aquatic Plants, e.g., Algae... 0175 and 0184 Daphnia, Daphnia Static Acute, OECD 202. Acute Toxicity to Plants, 0176 and 0184 Algae...

  16. 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.

  17. 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

  18. Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

    Science.gov (United States)

    Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

    2017-11-01

    Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

  19. Improving toxicity assessment of pesticide mixtures: the use of polar passive sampling devices extracts in microalgae toxicity tests

    Directory of Open Access Journals (Sweden)

    Sandra KIM TIAM

    2016-09-01

    Full Text Available Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively aimed i at characterizing the toxic potential of waters using dose-response curves, and ii at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed.

  20. Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests.

    Science.gov (United States)

    Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

    2016-01-01

    Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the "toxic potential" of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed.

  1. Anodonta imbecillis copper sulfate reference toxicant test, Clinch River - Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1997-06-01

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Toxicity testing of copper sulfate reference toxicant was conducted from May 12-21, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed an LC{sub 50} value of 1.12 mg Cu/L which is lower than the value of 2.02 mg Cu/L obtained in a previous test. Too few tests have been conducted with copper as the toxicant to determine a normal range of values.

  2. Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

    Science.gov (United States)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

    Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

  3. Alternative approaches for identifying acute systemic toxicity : Moving from research to regulatory testing

    NARCIS (Netherlands)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, B|info:eu-repo/dai/nl/068359802; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for

  4. Population growth rate determinants for Arbacia: Evaluating ecological relevance of toxicity test endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Nacci, D.; Gleason, T.; Munns, W.R. Jr. [Environmental Protection Agency, Narragansett, RI (United States). Environmental Research Lab.

    1995-12-31

    A population dynamics model for the sea urchin, Arbacia punctulata, was recently developed incorporating life stage endpoints frequently measured in acute and chronic toxicity studies. Model elasticity analysis was used to demonstrate that population growth rate was influenced most by adult survival and least by early life stage success, calling into question the ecological relevance of results from standardized Arbacia fertilization and larval development toxicity tests. Two approaches were used to continue this evaluation. Actual and hypothetical dose-response curves for toxicant exposures over multiple life stages were used to evaluate contributions to population growth rate of stage-specific toxicant effects. Additionally, relationships between critical life stages were developed from laboratory data for Arbacia. The results of this analysis underscore the importance of understanding both endpoint sensitivity to toxicants and sensitivity of population growth rate to test endpoints in determining the ecological relevance of toxicity tests results.

  5. Development and application of a marine sediment porewater toxicity test using algal spores

    Energy Technology Data Exchange (ETDEWEB)

    Hooten, R. [Texas A and M Univ., Corpus Christi, TX (United States); Carr, R.S. [National Biological Service, Corpus Christi, TX (United States)

    1995-12-31

    An acute pore water toxicity test protocol using germination and growth of marine macroalgae as endpoints was developed to indicate the presence of toxic compounds in marine/estuarine and sediment porewater samples. Zoospores collected from Ulva fasciata and U. lactuca were used as test organisms. Preliminary results with sodium dodecyl sulfate (SDS, a reference toxicant) indicate that zoospores germination and growth of embryonic gametophytes are as sensitive as the sea urchin fertilization and embryological development toxicity tests. Algal germination and growth data for copper, mercury and other metals will be presented. The results of tests utilizing this algal assay with sediment pore water from contaminated sediments will be compared with more traditional sediment toxicity test methods.

  6. Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests.

    Science.gov (United States)

    Schirmer, Kristin; Tanneberger, Katrin; Kramer, Nynke I; Völker, Doris; Scholz, Stefan; Hafner, Christoph; Lee, Lucy E J; Bols, Niels C; Hermens, Joop L M

    2008-11-11

    This paper details the derivation of a list of 60 reference chemicals for the development of alternatives to animal testing in ecotoxicology with a particular focus on fish. The chemicals were selected as a prerequisite to gather mechanistic information on the performance of alternative testing systems, namely vertebrate cell lines and fish embryos, in comparison to the fish acute lethality test. To avoid the need for additional experiments with fish, the U.S. EPA fathead minnow database was consulted as reference for whole organism responses. This database was compared to the Halle Registry of Cytotoxicity and a collation of data by the German EPA (UBA) on acute toxicity data derived from zebrafish embryos. Chemicals that were present in the fathead minnow database and in at least one of the other two databases were subject to selection. Criteria included the coverage of a wide range of toxicity and physico-chemical parameters as well as the determination of outliers of the in vivo/in vitro correlations. While the reference list of chemicals now guides our research for improving cell line and fish embryo assays to make them widely applicable, the list could be of benefit to search for alternatives in ecotoxicology in general. One example would be the use of this list to validate structure-activity prediction models, which in turn would benefit from a continuous extension of this list with regard to physico-chemical and toxicological data.

  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. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

    Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

  9. A toxicity scoring system for the 10-day whole sediment test with Corophium insidiosum (Crawford).

    Science.gov (United States)

    Prato, Ermelinda; Biandolino, Francesca; Libralato, Giovanni

    2015-04-01

    This study developed a tool able to evaluate the potential contamination of marine sediments detecting the presence or absence of toxicity supporting environmental decision-making processes. When the sample is toxic, it is important to classify its level of toxicity to understand its subsequent effects and management practices. Corophium insidiosum is a widespread and frequently recorded species along the Mediterranean Sea, North Sea and western Baltic Sea with records also in the Atlantic Ocean and Pacific Ocean. This amphipod is found in high abundance in shallow brackish inshore areas and estuaries also with high turbidity. At Italian level, C. insidiosum is more frequently collectable than Corophium orientale, making routine toxicity tests easier to be performed. Moreover, according to the international scientific literature, C. insidiosum is more sensitive than C. orientale. Whole sediment toxicity data (10 days) with C. insidiosum were organised in a species-specific toxicity score on the basis of the minimum significance difference (MSD) approach. Thresholds to rank samples as non-toxic and toxic were based on sediment samples (n=84) from the Gulf of Taranto (Italy). A five-class toxicity score (absent, low, medium, high and very high toxicity) was developed, considering the distribution of the 90th percentile of the MSD normalised to the effects on the negative controls (samples from reference sites). This toxicity score could be useful for interpreting sediment potential impacts and providing quick responsive management information.

  10. Tests for bioequivalence of control media and test media in studies of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, W.P.; McDonald, L.L. [Western EcoSystems Technology, Inc., Cheyenne, WY (United States)

    1995-07-01

    Statistical tests of the classical (null) hypothesis--that there is no difference in effects of control media and tested--are commonly used to make statistical inferences toward the no-observed-adverse-effect concentration. However, failing to rejects this hypothesis is not considered as scientific proof the hypothesis is true. An effect may exist, but high variation due to inadequate replication, variation in experimental units, or imprecise measurement techniques may yield data for which the hypothesis is not rejected. An experiment may also be too precise, yielding effects that are statistically significant but not biologically important. The authors propose the use of tests of bioequivalence of control media and test media to alleviate these unsatisfactory characteristics of tests and of the classical hypotheses for regulatory decisions. They review and illustrate the test for bioequivalence using acute and chronic toxicity data. They also define a procedure for determining the level of effect at which there will be high power to refute the hypothesis that there is a lack of bioequivalence if in fact the biological response in the control media is identical to the responses in the test media.

  11. Gamma Radiation Reduced Toxicity of Azoxystrobin Tested on Artemia franciscana.

    Science.gov (United States)

    Dvorak, P; Zdarsky, M; Benova, K; Falis, M; Tomko, M

    2016-06-01

    Fungicide azoxystrobin toxicity was monitored by means of a 96-h biotest with Artemia franciscana nauplius stages after exposure to solutions with concentrations of 0.2, 0.4, 0.6 and 0.8 mg L(-1) irradiated with (60)Co gamma radiation with doses of 1, 2.5, 5 and 10 kGy. The effects of ionization radiation on azoxystrobin toxicity were mainly manifested by a statistically significant reduction of lethality after 72- and 96-h exposure. A maximum reduction of lethality of 72 % was achieved using doses of 1-5 kGy for an azoxystrobin initial concentration of 0.4 mg L(-1) and after 72 h of exposure. At a 96-h exposure, a difference of lethal effects reached up to 70 % for a dose of 10 kGy. The observed effect of gamma ionizing radiation on azoxystrobin toxicity suggest that this approach can be applied as an alternative for a reduction of azoxystrobin residua in food.

  12. Evaluation of Daphnia ambigua for Routine Aquatic Toxicity Testing at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Specht, W.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Harmon, S.M. [University of South Carolina, Columbia, SC (United States)

    1997-09-01

    Short-term whole effluent toxicity testing, which is currently a requirement of the U.S. EPA`s National Pollution Discharge Elimination System (NPDES), commonly uses the cladoceran species Ceriodaphnia dubia. Despite the advantages to using a common test species to model the toxic effects of effluents, it could be argued that toxicity test results would be more meaningful if a wider variety of test organisms were commonly used. One particular argument against C. dubia is that tests conducted with this species do not always reflect local, site-specific conditions. The careful selection and use of an indigenous test species would produce a more realistic model of local instream effects and would account for regional differences in water quality. Permitted effluent discharges from Savannah River Site (SRS), a government weapons facility operated by the U.S. Department of Energy, require toxicity testing with C. dubia. However, water quality in these receiving streams is markedly different (lower pH and hardness) from standard laboratory water used for the culturing and testing of C. dubia, and it has been shown that this receiving water presents varying degrees of toxicity to C. dubia. Based on these results, it is possible that toxic effects observed during an effluent study could be the result of test organism stress from the dilution water and not the effects of SRS effluents. Therefore, this study addressed the substitution of C. dubia with an indigenous cladoceran species, Daphnia ambigua for routine regulatory testing at SRS. Given the indigenous nature of this species, combined with the fact that it has been successfully cultured by other investigators, D. ambigua was ideal for consideration as a replacement for C. dubia, but further study of the overall success and sensitivity of laboratory-reared D. ambigua was required. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol and

  13. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles.

    NARCIS (Netherlands)

    Park, M.V.; Annema, W.; Salvati, A.; Lesniak, A.; Elsaesser, A.; Barnes, C.; McKerr, G.; Howard, C.; Lynch, I.; Dawson, K.; Piersma, A.H.; de Jong, W.H.

    2009-01-01

    While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining

  14. Development of protocols for chronic toxicity testing of Pacific marine species

    Energy Technology Data Exchange (ETDEWEB)

    Langdon, C.J.; Seim, W.K.; Hoffman, R.L.; Weber, L.

    1990-03-01

    The development of a year-round capability for conducting short-term toxicity tests for estimating chronic-effect levels of toxic materials with a native Pacific coast fish and a native Pacific coast mysid shrimp was the goal of the project. In order to achieve acceptable sensitivity as a surrogate for chronic toxicity tests, targeting the reproductive portion of the mysid life cycle and all or part of the embryonic, larval, or early post-larval portion of the fish life cycle was deemed necessary. This targeting is consistent with conclusions based upon earlier work in developing similar tests with Atlantic coast, Gulf coast, and freshwater fish and invertebrates.

  15. Toxicity Tests of Whole Sediment Samples Using the Hyallella (H. azteca) Survival and Growth Tests (ASTM E 1283-93)

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — 10-day toxicity tests using Hyalella azteca were conducted with sediment samples collected by the U.S. Fish & Wildlife Service, Bloomington, Indiana facility to...

  16. 40 CFR 795.120 - Gammarid acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... definitions also apply to this guideline: Death means the lack of reaction of a test organism to gentle... concentration, i.e., that concentration of a chemical in air or water killing 50 percent of the test batch of... dilution water through each chamber is adjusted to the rate desired. In a static test, the test substance...

  17. TPK Sarimukti, Cipatat, West Bandung compost toxicity test using Allium test

    Energy Technology Data Exchange (ETDEWEB)

    Wardini, Trimurti Hesti; Notodarmojo, Peni Astrini [Biology Study Program, School of Life Science and Technology, Bandung Institute of Technology (Indonesia)

    2015-09-30

    TPK Sarimukti, Cipatat, West Bandung produced 2 kinds of compost from traditional market waste, liquid and solid compost. The aim of this research is to evaluate toxicity of compost produced in TPK Sarimukti using shallots (Allium cepa). Tests carried out by treated shallots with liquid compost (2,5%, 5%, 10% and 12,5% (w/v)) or solid compost (25%, 50%, 75% and 100% (w/v)) for 48 hours. Results showed reduced root growth rate and mitotic index (MI) in accordance with increased concentrations of compost. Sub lethal concentrations are liquid compost 5% and 10% and solid compost 75%. Lethal concentrations are liquid compost 12,5 % and solid compost 100%. Micronuclei (MN) increased with increase in liquid compost concentration. MN found at very high frequencies in highest solid compost concentration (100%), but very low at lower concentrations. Cells with binuclei and cell necrosis increased with increasing concentrations of given compost. Nuclear anomalies (NA) found in high frequency in 75% and 100% solid compost. Based on research, we can conclude that liquid compost is more toxic because it can reduce MI and root growth rate at lower concentrations than solid compost. Both types of compost have genotoxic properties because it can induce chromosome aberration (CA), MN, binuclei and NA formation.

  18. The assessment of sewage sludge gasification by-products toxicity by ecotoxicologial test.

    Science.gov (United States)

    Werle, Sebastian; Dudziak, Mariusz

    2015-08-01

    The process of gasification of sewage sludge generates by-products, which may be contaminated with toxic and hazardous substances, both organic and inorganic. It is therefore important to assess the environmental risk associated with this type of waste. The feasibility of using an ecotoxicological tests for this purpose was determined in the presented study. The applied tests contained indicator organisms belonging to various biological groups (bacteria, crustaceans, plants). The subject of the study were solid (ash, char) and liquid (tar) by-products generated during gasification (in a fixed bed reactor) of dried sewage sludge from various wastewater treatment systems. The tested samples were classified based on their toxic effect. The sensitivity of the indicator organisms to the tested material was determined. In-house procedures for the preparation for toxicity analysis of both sewage sludge and by-products generated during the gasification were presented. The scope of work also included the determination of the effect of selected process parameters (temperature, amount of gasifying agent) on the toxicity of gasification by-products depending on the sewage sludge source. It was shown that both the type of sewage sludge and the parameters of the gasification process affects the toxicity of the by-products of gasification. However, the results of toxicity studies also depend on the type of ecotoxicological test used, which is associated with a different sensitivity of the indicator organisms. Nevertheless, it may be concluded that the by-products formed during the gasification of the low toxicity sewage sludge can be regarded as non-toxic or low toxic. However, the results analysis of the gasification of the toxic sludge were not conclusive, which leads to further research needs in this area. © The Author(s) 2015.

  19. Interlaboratory Evaluation of Hyalella Azteca and Chironomus Tentans Short-term and Long-term Sediment Toxicity Tests

    Science.gov (United States)

    This paper presents the results of interlaboratory toxicity tests on sediment toxicity methods for use in routine testing and this data has been presented in an EPA report and this is a summary of that data.

  20. Sensitivity comparison of laboratory-cultured and field-collected amphipod Corophium multisetosum in toxicity tests.

    Science.gov (United States)

    Menchaca, Iratxe; Belzunce, María Jesús; Franco, Javier; Garmendia, Joxe Mikel; Montero, Natalia; Revilla, Marta

    2010-04-01

    The feasibility of using lab-cultured amphipods Corophium multisetosum (Stock 1952) to evaluate the toxicity of contaminants present within marine sediments was studied. This was done by comparing the sensitivity of lab-cultured amphipods in a cadmium toxicity test and to toxic sediment samples, during a 10-days bioassay, with field collected individuals. Different responses were observed between field and cultured individuals. Cadmium test indicated high temporal variability in the LC(50) values of field amphipods (2.40-6.55 mg L(-1)). Sensitivity of cultured amphipods was within the seasonal range of the field individuals (5.81 mg L(-1), LC(50)). However, culture amphipods showed much lower sensitivity in toxic sediment samples. Our results indicate that sensitivity should be determined using a sediment matrix, if the assessment of toxicity is based upon bioassays performed with cultured burrower-amphipods.

  1. Tapioca-starch wastewater toxicity characterized by Microtox and duckweed tests

    Energy Technology Data Exchange (ETDEWEB)

    Bengtsson, Bengt-Erik (Stockholm University, Institute of Applied Environmental Research, Laboratory for Aquatic Ecotoxicology, Nykoeping (Sweden)); Triet, T. (University of Wisconsin, Institute for Environmental Studies, Madison, WI (United States))

    1994-12-01

    The toxicity of treated and untreated effluents from a tapioca (cassava), Manihot esculenta, starch industry in Thailand were tested on Microtox and a subtropical duckweed, Lemna aequinoctialis. Untreated samples demonstrated high toxicity in both tests, but also the treated effluent was toxic to duckweed. Aging of wastewater resulted in decreased toxicity which was partly correlated to cyanide content, but other (unidentified) components of the tapioca tubers also contribute to the toxicity. Considering the present findings and the fact that the majority of the tapioca starch industries in Southeast Asia have no effluent treatment there is a great risk for severe effects on crops (e.g. young stages of rice, vegetables, etc.) when the wastewater in traditional way is used for irrigation of farmland. Negative effects on local aquaculture and/or sensitive stages of valuable feral fish and crustacea populations in receiving water bodies can also be expected. 32 refs, 6 tabs

  2. 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...

  3. Development and application of a marine sediment pore-water toxicity test using Ulva fasciata zoospores

    Energy Technology Data Exchange (ETDEWEB)

    Hooten, R.L.; Carr, R.S. [Texas A and M Univ., Corpus Christi, TX (United States). Geological Survey

    1998-01-01

    An acute (96 h) pore-water toxicity test protocol using germination and growth of Ulva fasciata zoospores as endpoints was developed to test the toxicity of marine and estuarine sediment pore-water samples. Tests with an organic toxicant (sodium dodecyl sulfate; SDS), three metals (Cd, Cu, and Zn), and ammonia (NH{sub 3}) were conducted to determine zoospore sensitivity. Zoospore germination and gametophyte growth were as sensitive to SDS as sea urchin (Arbacia punctulata) fertilization and embryological development. Zoospore sensitivity to metals was greater than or comparable to that of adult macroalgae. Zoospores were less sensitive to NH{sub 3} than were other commonly used toxicity test organisms. Test results using this algal assay with sediment pore-water samples with high NH{sub 3} concentrations were compared with results from sea urchin fertilization and embryological development tests for the same samples. Ulva fasciata zoospore germination was not affected by samples with high NH{sub 3} concentrations that were toxic in both sea urchin tests. Zoospore tolerance of NH{sub 3} and sensitivity to other contaminants indicate that their response may be useful in toxicity identification evaluation studies with pore-water samples that contain high concentrations of unionized NH{sub 3}.

  4. Development and application of a marine sediment pore-water toxicity test using Ulva fasciata zoospores

    Science.gov (United States)

    Hooten, Russell L.; Carr, R. Scott

    1998-01-01

    An acute (96 h) pore-water toxicity test protocol using germination and growth of Ulva fasciatazoospores as endpoints was developed to test the toxicity of marine and estuarine sediment pore-water samples. Tests with an organic toxicant (sodium dodecyl sulfate; SDS), three metals (Cd, Cu, and Zn), and ammonia (NH3) were conducted to determine zoospore sensitivity. Zoospore germination and gametophyte growth were as sensitive to SDS as sea urchin (Arbacia punctulata) fertilization and embryological development. Zoospore sensitivity to metals was greater than or comparable to that of adult macroalgae. Zoospores were less sensitive to NH3than were other commonly used toxicity test organisms. Test results using this algal assay with sediment pore-water samples with high NH3 concentrations were compared with results from sea urchin fertilization and embryological development tests for the same samples. Ulva fasciatazoospore germination was not affected by samples with high NH3 concentrations that were toxic in both sea urchin tests. Zoospore tolerance of NH3 and sensitivity to other contaminants indicate that their response may be useful in toxicity identification evaluation studies with pore-water samples that contain high concentrations of unionized NH3.

  5. Modifying Foods and Feeding Regimes to Optimize the Performance of Hyalella azteca during Chronic Toxicity Tests

    Science.gov (United States)

    The amphipod Hyalella azteca is commonly used to assess the toxicity of sediments and waters. However, laboratories have reported varying success in maintaining healthy cultures and in obtaining consistent growth and reproduction (where applicable), especially during tests...

  6. Toxic Substances Control Act Test Submissions 2.0 (TSCATS 2.0)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxic Substances Control Act Test Submissions 2.0 (TSCATS 2.0) tracks the submissions of health and safety data submitted to the EPA either as required or...

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  9. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... the carapace. (iv) Feeding. A variety of foods (e.g., unicellular green algae) have been demonstrated... introduction or the test substance delivery system and the flow rate (in flow-through test) expressed as volume...

  10. Revolutionizing Toxicity Testing For Predicting Developmental Outcomes (DNT4)

    Science.gov (United States)

    Characterizing risk from environmental chemical exposure currently requires extensive animal testing; however, alternative approaches are being researched to increase throughput of chemicals screened, decrease reliance on animal testing, and improve accuracy in predicting adverse...

  11. An Evaluation of Select Test Variables Potentially Affecting Acute Oil Toxicity.

    Science.gov (United States)

    Echols, Brandi S; Smith, A; Gardinali, P; Rand, G

    2016-02-01

    In the wake of the Deepwater Horizon incident (2010) in the Gulf of Mexico, an abundance of research studies have been performed, but the methodologies used have varied making comparisons and replication difficult. In this study, acute toxicity tests with mysids and inland silversides were performed to examine the effect of different variables on test results. The toxicity test variables evaluated in this study included (1) open versus closed static test chambers, (2) natural versus artificial diluent, (3) aerated versus nonaerated test solution, and (4) low versus medium energy water-accommodated (WAF) mixing energies. The use of tests using natural or artificial diluent showed no difference in either toxicity test or analytical chemistry results. Based on median lethal concentrations (LC50) of WAFs of unweathered oil (MASS), mysid tests performed in closed chambers were approximately 41 % lower than LC50 values from open-chamber studies, possibly a result of the presence of low-molecular weight volatile aromatics (i.e., naphthalenes). This research also showed that using a medium-energy WAF (with a 20–25 % vortex) increases the number of chemical components compared with low-energy WAF, thus affecting the composition of the exposure media and increasing toxicity. The comparison of toxic units as a measure of the potential toxicity of fresh and weathered oils showed that weathered oils (e.g., Juniper, CTC) are less toxic than the unweathered MASS oil. In the event of future oil spills, these variables should be considered to ensure that data regarding the potential toxicity and environmental risk are of good quality and reproducible.

  12. Comparison of amphipods Corophium insidiosum and C. orientale (Crustacea: Amphipoda) in sediment toxicity testing.

    Science.gov (United States)

    Prato, Ermelinda; Bigongiari, Nicola; Barghigiani, Corrado; Biandolino, Francesca

    2010-09-01

    The aim of this study was to compare the sensitivity of two Corophidae: Corophium orientale a standardized species and Corophium insidiosum a species more available in the Ionian sea (Southern Italy), in order to evaluate the suitability and applicability of C. insidiosum to sediment toxicity test. The sensitivity of the 2 species was compared through simultaneous bioassays: the 96-h static water-only toxicity test and a 10-day static sediment toxicity test. Sediment samples were collected in the Livorno harbour (Ligurian Sea). Both amphipods showed high sensitivity to reference toxicant and no significant differences were found between the two Corophiidae (t test; p > 0.05). Numerical Sediment Quality Guidelines (SQGs) have been used to relate the chemical concentrations of sediment samples to biological effects. Both amphipod species indicated the same sediment samples as potentially toxic according to chemical data. The results indicate that Corophium insidiosum would be suitable as an alternative test species to the recommended species C. orientale, in the development of sediment toxicity test.

  13. On the possibility of using biological toxicity tests to monitor the work of wastewater treatment plants

    Directory of Open Access Journals (Sweden)

    Zorić Jelena

    2008-01-01

    Full Text Available The aim of this study was to ascertain the possibility of using biological toxicity tests to monitor influent and effluent wastewaters of wastewater treatment plants. The information obtained through these tests is used to prevent toxic pollutants from entering wastewater treatment plants and discharge of toxic pollutants into the recipient. Samples of wastewaters from the wastewater treatment plants of Kragujevac and Gornji Milanovac, as well as from the Lepenica and Despotovica Rivers immediately before and after the influx of wastewaters from the plants, were collected between October 2004 and June 2005. Used as the test organism in these tests was the zebrafish Brachydanio rerio Hamilton - Buchanon (Cyprinidae. The acute toxicity test of 96/h duration showed that the tested samples had a slight acutely toxic effect on B. rerio, except for the sample of influent wastewater into the Cvetojevac wastewater treatment plant, which had moderately acute toxicity, indicating that such water should be prevented from entering the system in order to eliminate its detrimental effect on the purification process.

  14. Assessment of Jatropha curcas L. biodiesel seed cake toxicity using the zebrafish (Danio rerio) embryo toxicity (ZFET) test.

    Science.gov (United States)

    Hallare, Arnold V; Ruiz, Paulo Lorenzo S; Cariño, J C Earl D

    2014-05-01

    Consequent to the growing demand for alternative sources of energy, the seeds from Jatropha curcas remain to be the favorite for biodiesel production. However, a significant volume of the residual organic mass (seed cake) is produced during the extraction process, which raises concerns on safe waste disposal. In the present study, we assessed the toxicity of J. curcas seed cake using the zebrafish (Danio rerio) embryotoxicity test. Within 1-h post-fertilization (hpf), the fertilized eggs were exposed to five mass concentrations of J. curcas seed cake and were followed through 24, 48, and 72 hpf. Toxicity was evaluated based on lethal endpoints induced on zebrafish embryos namely egg coagulation, non-formation of somites, and non-detachment of tail. The lowest concentration tested, 1 g/L, was not able to elicit toxicity on embryos whereas 100 % mortality (based also on lethal endpoints) was recorded at the highest concentration at 2.15 g/L. The computed LC50 for the J. curcas seed cake was 1.61 g/L. No further increase in mortality was observed in the succeeding time points (48 and 72 hpf) indicating that J. curcas seed cake exerted acute toxicity on zebrafish embryos. Sublethal endpoints (yolk sac and pericardial edema) were noted at 72 hpf in zebrafish embryos exposed to higher concentrations. The observed lethal endpoints induced on zebrafish embryos were discussed in relation to the active principles, notably, phorbol esters that have remained in the seed cake even after extraction.

  15. Progress Toward Replacing Animals in Toxicity Testing for Cosmetics

    OpenAIRE

    Nye, Marisa B.

    2006-01-01

    In the 1980’s, animal rights activists successfully motivated the cosmetic industry to begin researching alternatives to animal tests. The European Union has taken action to stimulate development and validation of alternatives to animal testing through the Sixth and Seventh Amendments to the Cosmetics Directive. In this paper, I will briefly describe the history of the search for alternatives to animal testing for cosmetics. I will then discuss the progress that has been ma...

  16. Field Validation of Toxicity Tests to Evaluate the Potential for Beneficial Use of Produced Water

    Energy Technology Data Exchange (ETDEWEB)

    Joseph Bidwell; Jonathan Fisher; Naomi Cooper

    2008-03-31

    This study investigated potential biological effects of produced water contamination derived from occasional surface overflow and possible subsurface intrusion at an oil production site along the shore of Skiatook Lake, Oklahoma. We monitored basic chemistry and acute toxicity to a suite of standard aquatic test species (fathead minnow-Pimephales promelas, Daphnia pulex, Daphnia magna, and Ceriodaphnia dubia) in produced water and in samples taken from shallow groundwater wells on the site. Toxicity identification evaluations and ion toxicity modeling were used to identify toxic constituents in the samples. Lake sediment at the oil production site and at a reference site were also analyzed for brine intrusion chemically and by testing sediment toxicity using the benthic invertebrates, Chironomus dilutus, and Hyallela azteca. Sediment quality was also assessed with in situ survival and growth studies with H. azteca and the Asian clam, Corbicula fluminea, and by benthic macroinvertebrate community sampling. The produced water was acutely toxic to the aquatic test organisms at concentrations ranging from 1% to 10% of the whole produced water sample. Toxicity identification evaluation and ion toxicity modeling indicated major ion salts and hydrocarbons were the primary mixture toxicants. The standardized test species used in the laboratory bioassays exhibited differences in sensitivity to these two general classes of contaminants, which underscores the importance of using multiple species when evaluating produced water toxicity. Toxicity of groundwater was greater in samples from wells near a produced water injection well and an evaporation pond. Principle component analyses (PCA) of chemical data derived from the groundwater wells indicated dilution by lake water and possible biogeochemical reactions as factors that ameliorated groundwater toxicity. Elevated concentrations of major ions were found in pore water from lake sediments, but toxicity from these ions was

  17. TOXICITY TESTING IN THE 21ST CENTURY: A VISION AND A STRATEGY

    DEFF Research Database (Denmark)

    Krewski, D.; Acosta, D.; Andersen, M.

    2010-01-01

    With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U. S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal...... on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced...... stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays...

  18. 40 CFR 797.1930 - Mysid shrimp acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... rate through each chamber and the concentration of the test substance in each chamber. The general... rate of dilution water. The loading shall not cause the dissolved oxygen concentration to fall below... guideline. (1) “Death” means the lack of reaction of a test organism to gentle prodding. (2) “Flow-through...

  19. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Science.gov (United States)

    2010-07-01

    ... young. (C) Any ephippia are produced by control animals. (v) The number of immobilized daphnids in each.... Dissolved oxygen concentration, pH, temperature, the concentration of test substance, and other water... during the test to determine any significant differences (p≤0.05) in immobilization and reproduction as...

  20. Toxicity evaluation of trap and skeet shooting targets to aquatic test species.

    Science.gov (United States)

    Baer, K N; Hutton, D G; Boeri, R L; Ward, T J; Stahl, R G

    1995-12-01

    : Large quantities of trap and skeet clay targets are used in shooting activities around the United States. For example, the number of targets used since 1970 has averaged approximately 560 million a year. A number of acute and chronic tests were performed to determine the toxicity of Remington Arms Company Blue Rock(®) trap and skeet target fragments upon selected freshwater and marine organisms. These studies were undertaken in support of an environmental impact study of trap and skeet shooting activities at a major gun club in the northeast United States. Targets were composed of approximately 67% dolomitic limestone, 32% petroleum pitch and 1% fluorescent aqueous paint (painted targets only). The majority of samples were painted, new targets obtained from the manufacturer and painted and aged targets collected around a shooting range. Additional tests were conducted using non-painted, new targets and leachates prepared from both painted, new and aged targets. Targets were crushed to small fragments and were either directly added to the test vessels at extremely high concentrations ranging from 670 to 600 000 mgl(-1) or used in leachate tests. In direct tests all target materials were essentially non-toxic to marine and freshwater organisms, except for the non-painted new targets which exhibited minimal acute toxicity to Daphnia magna (48 h EC 50=2200 mgl(-1)). In leachate tests, the leachate was not-toxic to mysid shrimp, the only organism tested. Additional samples of crushed targets were analysed for the presence of selected priority pollutants (EP toxicity test) and polycyclic aromatic hydrocarbons (PAHs). The targets did not exhibit the characteristics of toxicity as determined by the EP toxicity test but did contain substantial amounts of PAHs. However, results from new and aged targets suggest that PAH are tightly bound in the petroleum pitch and limestone matrix and are unlikely to be readily available in the environment. The potential impact of targets

  1. Assigning ethical weights to clinical signs observed during toxicity testing.

    Science.gov (United States)

    Ringblom, Joakim; Törnqvist, Elin; Hansson, Sven Ove; Rudén, Christina; Öberg, Mattias

    2017-01-01

    Reducing the number of laboratory animals used and refining experimental procedures to enhance animal welfare are fundamental questions to be considered in connection with animal experimentation. Here, we explored the use of cardinal ethical weights for clinical signs and symptoms in rodents by conducting trade-off interviews with members of Swedish Animal Ethics Committees in order to derive such weights for nine typical clinical signs of toxicity. The participants interviewed represent researchers, politically nominated political nominees and representatives of animal welfare organizations. We observed no statistically significant differences between these groups with respect to the magnitude of the ethical weights assigned, though the political nominees tended to assign lower weights. Overall, hunched posture was considered the most severe clinical sign and body weight loss the least severe. The ethical weights assigned varied considerably between individuals, from zero to infinite value, indicating discrepancies in prioritization of reduction and refinement. Cardinal ethical weights may be utilized to include both animal welfare refinement and reduction of animal use in designing as well as in retrospective assessment of animal experiments. Such weights may also be used to estimate ethical costs of animal experiments.

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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

  6. 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 ...

  7. 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.

  8. 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 ...

  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. [Pulmonary function tests at different stages of toxic oil syndrome].

    Science.gov (United States)

    Martin Escribano, P; Fernandez Sanchez Alarcos, J M; Dominguez-Lozano, M J; Diaz de Atauri, J; Barbosa-Ayucar, C; Cantalapiedra, J A; Lopez Encuentra, A

    1984-01-01

    The toxic oil syndrome is a new multisystemic disease, caused by ingestion of adulterated olive oil; this oil had a part of rapeseed oil, which was denatured with aniline for industrial use, and then re-refined. It is estimated that 20,000 people were more or less affected, the mortality being 1.7%. There is no clear pathogenetic mechanism, but the most probable is the generation of free radicals, caused by anilides. The clinical picture began with fever, acute interstitial pneumonia, pruritus, exanthems, myalgias and eosinophilia. The main pathological findings were generalized endothelial lesions, septal oedema, mild inflammatory mononuclear infiltrates and hydropic degeneration of type I and II pneumocytes with desquamation of type I. The pneumonic syndrome had a favourable evolution, except in 5% of the patients who went into acute respiratory distress and suffered an important mortality. In 10% of the patients, a moderate hypoxaemia remained with normal chest film; in these cases, a transbronchial biopsy showed more severe endothelial lesions and, in some of these patients, it was possible to find clinical signs of pulmonary hypertension, which was moderate and did not improve with oxygen or vasoactive agents. The neurological symptomatology was progressive, leading to very severe muscular atrophy and, in some cases, to alveolar hypoventilation. The neuromyopathy, as the other clinical manifestations, improved slowly during the following months. A year after the onset, a pulmonary restriction with a low transfer factor of CO remained, and some patients had residual neuromyopathy and severe scleroderma-like lesions of the skin. (ABSTRACT TRUNCATED AT 250 WORDS)

  11. Recreating the seawater mixture composition of HOCs in toxicity tests with Artemia franciscana by passive dosing

    Energy Technology Data Exchange (ETDEWEB)

    Rojo-Nieto, E., E-mail: elisa.rojo@uca.es [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Smith, K.E.C. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Perales, J.A. [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Mayer, P. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark)

    2012-09-15

    The toxicity testing of hydrophobic organic compounds (HOCs) in aquatic media is generally challenging, and this is even more problematic for mixtures. The hydrophobic properties of these compounds make them difficult to dissolve, and subsequently to maintain constant exposure concentrations. Evaporative and sorptive losses are highly compound-specific, which can alter not only total concentrations, but also the proportions between the compounds in the mixture. Therefore, the general aim of this study was to explore the potential of passive dosing for testing the toxicity of a PAH mixture that recreates the mixture composition found in seawater from a coastal area of Spain, the Bay of Algeciras. First, solvent spiking and passive dosing were compared for their suitability to determine the acute toxicity to Artemia franciscana nauplii of several PAHs at their respective solubility limits. Second, passive dosing was applied to recreate the seawater mixture composition of PAHs measured in a Spanish monitoring program, to test the toxicity of this mixture at different levels. HPLC analysis was used to confirm the reproducibility of the dissolved exposure concentrations for the individual PAHs and mixtures. This study shows that passive dosing has some important benefits in comparison with solvent spiking for testing HOCs in aquatic media. These include maintaining constant exposure concentrations, leading to higher reproducibility and a relative increase in toxicity. Passive dosing is also able to faithfully reproduce real mixtures of HOCs such as PAHs, in toxicity tests, reproducing both the levels and proportions of the different compounds. This provides a useful approach for studying the toxicity of environmental mixtures of HOCs, both with a view to investigating their toxicity but also for determining safety factors before such mixtures result in detrimental effects.

  12. Boar spermatozoa successfully predict mitochondrial modes of toxicity: implications for drug toxicity testing and the 3R principles.

    Science.gov (United States)

    Vicente-Carrillo, A; Edebert, I; Garside, H; Cotgreave, I; Rigler, R; Loitto, V; Magnusson, K E; Rodríguez-Martínez, H

    2015-04-01

    Replacement of animal testing by in vitro methods (3-R principles) requires validation of suitable cell models, preferably obtained non-invasively, defying traditional use of explants. Ejaculated spermatozoa are highly dependent on mitochondrial production and consumption of ATP for their metabolism, including motility display, thus becoming a suitable model for capturing multiple modes of action of drugs and other chemicals acting via mitochondrial disturbance. In this study, a hypothesis was tested that the boar spermatozoon is a suitable cell type for toxicity assessment, providing a protocol for 3R-replacement of animals for research and drug-testing. Boar sperm kinetics was challenged with a wide variety of known frank mito-toxic chemicals with previously shown mitochondrial effects, using a semi-automated motility analyser allied with real-time fluorescent probing of mitochondrial potential (MitoTracker & JC-1). Output of this sperm assay (obtained after 30 min) was compared to cell viability (ATP-content, data obtained after 24-48 h) of a hepatome-cell line (HepG2). Results of compound effects significantly correlated (Pbreeding boars, are confirmed as suitable biosensors for preclinical toxicology screening and ranking of lead compounds in the drug development processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Application of leaching tests for toxicity evaluation of coal fly ash

    Energy Technology Data Exchange (ETDEWEB)

    Tsiridis, V.; Samaras, P.; Kungolos, A.; Sakellaropoullos, G.P. [Technological Educational Institute for West Macedonia, Kozani (Greece). Dept. for Pollution Control Technology

    2006-08-15

    The toxic properties of coal fly ash samples obtained from various coal combustion power plants were evaluated in this work using physicochemical analyses and bioassays. Physicochemical analyses showed that heavy metals present in solid samples included Cr, Cu, Mn, Ni, Pb, and Zn. The results of the chemical analysis of eluates deduced by the application of standard leaching tests according to EN 12457-2 and Toxicity Characteristic Leaching Procedure (TCLP) methods indicated that the compounds contained in fly ashes could potentially be transferred to the liquid phase depending upon the leaching method used. Heavy metal concentrations were higher in TCLP eluates, indicating that the initial pH value of the leaching medium significantly affected the transfer of these elements to the liquid phase. Tests conducted with the photobacterium Vibrio fischeri (Microtox test), the crustacean Daphnia magna, and the rotifer Brachionus calyciflorus were used to assess toxicity of eluates obtained by both leaching tests. Daphnia magna was the most sensitive test organism. The EN 12457-2 method proved to be more reliable for toxicity evaluation of eluates. In contrast, the TCLP method showed some interference owing to acetic acid toxicity, and precipitation occurred after pH adjustment of eluates from acid to neutral range. The toxicity of both fly ashes and the corresponding solid leaching residues of EN 12457-2 and TCLP leaching tests was also measured using the Microtox Basic Solid phase Test. The results generated with this bioassay indicated that toxicity was greatly influenced by the pH status of the solid samples.

  14. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. High-Throughput Toxicity Testing: New Strategies for ...

    Science.gov (United States)

    In recent years, the food industry has made progress in improving safety testing methods focused on microbial contaminants in order to promote food safety. However, food industry toxicologists must also assess the safety of food-relevant chemicals including pesticides, direct additives, and food contact substances. With the rapidly growing use of new food additives, as well as innovation in food contact substance development, an interest in exploring the use of high-throughput chemical safety testing approaches has emerged. Currently, the field of toxicology is undergoing a paradigm shift in how chemical hazards can be evaluated. Since there are tens of thousands of chemicals in use, many of which have little to no hazard information and there are limited resources (namely time and money) for testing these chemicals, it is necessary to prioritize which chemicals require further safety testing to better protect human health. Advances in biochemistry and computational toxicology have paved the way for animal-free (in vitro) high-throughput screening which can characterize chemical interactions with highly specific biological processes. Screening approaches are not novel; in fact, quantitative high-throughput screening (qHTS) methods that incorporate dose-response evaluation have been widely used in the pharmaceutical industry. For toxicological evaluation and prioritization, it is the throughput as well as the cost- and time-efficient nature of qHTS that makes it

  16. NMSBA: Aken Technologies Final Report: Toxicity Testing of Liquidoff

    Energy Technology Data Exchange (ETDEWEB)

    Ruffing, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jensen, Travis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Strickland, Lucas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-01

    To determine the effect of Liquidoff on bacteria, three bacterial strains were tested: Escherichia coli DH5α, Synechococcus sp. PCC 7002, and Synechococcus elongatus PCC 7942. E. coli DH5α is a Gram-negative, aerobic bacterium that is often found in normal gut flora and is commonly used the laboratory due to its fast growth rate. Synechococcus sp. PCC 7002 and S. elongatus PCC 7942 are Gram-negative, aquatic, autophototrophic cyanobacteria. Synechococcus sp. PCC 7002 is a marine cyanobacterium isolated from ‘fish pens’ on Magueyes Island, Puerto Rico in 1962, while S. elongatus PCC 7942 is a freshwater cyanobacterium. It should be noted that no Gram-positive bacterium was tested in this study.

  17. 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.

  18. Development of a Chronic Toxicity Testing Method for Daphnia pulex

    Science.gov (United States)

    2015-08-01

    Protection Agency YCT yeast , cereal leaves, and trout chow (from a commercial vendor) ERDC/EL SR-15-5 1 1 Introduction The chronic...cm with Milli-Q water) • YCT ( yeast , cereal leaves, trout chow) • ALG- algae, Selenastrum capricornutum(from a commercial vendor); also known as...screened holes (10 replicate beakers for each test concentration) • One modified Zumwalt box (Figures A1-A3) with water exchange system (optional) • One

  19. Dispersed oil toxicity tests with biological species indigenous to the Gulf of Mexico. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fucik, K.W.; Carr, K.A.; Balcom, B.J.

    1994-08-01

    Static and flowthrough aquatic acute toxicity testing protocols were utilized on eggs and larvae of seven commercially important invertebrates and fishes from the Gulf of Mexico. Test organisms were exposed to Central and Western Gulf oils, dispersed oil, and Corexit 9527. Species included brown shrimp (Penaeus aztecus), white shrimp (Penaeus setiferus), blue crab (Callinectes sapidus), eastern oyster (Crassostrea virginica), red drum (Sciaenops ocellatus), inland silverside (Menidia berylina), and spot (Leiosomus xanthurus). Atlantic menhaden (Brevoortia tyrannus) was also tested because gulf menhaden were not available. Mysids (Mysidopsis bahia) were evaluated as part of a chronic toxicity assessment.

  20. 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.

  1. Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics

    NARCIS (Netherlands)

    Bosgra, S.; Westerhout, J.

    2015-01-01

    In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and

  2. Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-15

    This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

  4. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  5. Optimizing the design of a reproduction toxicity test with the pond snail Lymnaea stagnalis

    DEFF Research Database (Denmark)

    Charles, Sandrine; Ducrot, Virginie; Azam, Didier

    2016-01-01

    This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from...... nine countries participated in these ring-tests. Survival and reproduction were evaluated in L. stagnalis exposed to cadmium, tributyltin, prochloraz and trenbolone according to an OECD draft Test Guideline. In total, 49 datasets were analysed to assess the practicability of the proposed experimental...... statistical analysis, the optimal test duration was established and the most sensitive and cost-effective reproduction toxicity endpoint was identified, to be used as the core endpoint. This validation process and the resulting optimized protocol were used to consolidate the OECD Test Guideline...

  6. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Posgai, Ryan; Ahamed, Maqusood [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Hussain, Saber M. [Applied Biotechnology Branch, Human Effectiveness Directorate Air Force Research Laboratory/RHBP, Wright-Patterson Air Force Base, OH, 45433 (United States); Rowe, John J. [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Nielsen, Mark G., E-mail: Mark.Nielsen@notes.udayton.edu [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States)

    2009-12-20

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  7. Development of marine sediment bioassays and toxicity tests for monitoring and regulation in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Thain, J.; Matthiessen, P.

    1995-12-31

    There is a need in Europe and elsewhere for a broad suite of whole-sediment bioassays and toxicity tests which can be used for routine monitoring and assessment of the marine environment and for evaluating the toxic effects of chemicals which may find their way into sediments. Until recently, few European species had been incorporated into such tests but the availability of suitable methodologies is now increasing rapidly. Perhaps the most important recent activity in this area consisted of an international ring test of acute sediment toxicity test methods which was organized by the Oslo and Paris Commissions in 1993, using up to 4 offshore chemicals as test materials. It evaluated the performance of 4 acute (5--10 day) tests involving: the sea urchin Echinocardium cordatum, the bivalve mollusc Abra alba, the amphipod crustacean Corophium volutator, and the polychaete worm Arenicola marina. The ring test concluded that the C. volutator test was the most appropriate for evaluating offshore chemicals, but all these methods are now widely used in Europe, both as toxicity tests and as bioassays. For example, the A. marina procedure (which has both lethal and sublethal endpoints), in combination with the C. volutator method, is now routinely used in the UK for monitoring the toxicity of estuarine sediments. Further activities are in progress. Perhaps the most important is the development of chronic marine sediment tests and bioassays which can be used to assess the long-term effects of the many sedimentary contaminants which are able to persist in this type of habitat and possibly cause delayed effects on the growth and reproduction, etc. of benthic fauna.

  8. Consensus report on the future of animal-free systemic toxicity testing.

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  9. Sperm toxicity testing: UK best practice guideline from the Association of Biomedical Andrologists.

    Science.gov (United States)

    Long, S; Woodward, B; Tomlinson, M

    2018-02-09

    In order to ensure the quality and integrity of diagnostic semen analysis results, materials used should be tested to ensure that they do not interfere with sperm function. As a toxicity test, complex sperm function testing may be considered controversial, since the fertilizing capacity of single sperm can never be assured. In preference, sperm motility offers a unique means of assessing the toxicity of reagents and materials before they are used in routine practice. Motility is the semen parameter most likely to be influenced by the external environment. Indeed, it is the main reason that laboratories insist on supplying their own approved specimen containers and ensuring that patients, as far as possible, adhere to strict conditions for sample collection and transport prior to testing. This differs to other indirect tests of toxicity such as the mouse embryo assay, whereby the rate of mouse pre-implantation embryo development to the blastocyst stage is compared. This guideline is aimed at health care scientists who deal with andrology in both general pathology and specialised fertility laboratories, and provides a model approach to sperm toxicity testing. For assisted reproduction clinics, the same methodology can be used to test any consumables that are used for sperm processing, and as an indirect guide for any consumables that come into direct contact with oocytes and pre-implantation embryos.

  10. New animal-free concepts and test methods for developmental toxicity and peripheral neurotoxicity.

    Science.gov (United States)

    Leist, Marcel

    2017-11-01

    The complex toxicological fields of repeat dose organ toxicity (RDT) and developmental and reproductive toxicity (DART) still require new concepts and approaches to achieve a fully animal-free safety assessment of chemicals. One novel approach is the generation of relevant human cell types from pluripotent stem cells, and the use of such cells for the establishment of phenotypic test methods. Due to their broad endpoints, such tests capture multiple types of toxicants, i.e. they are a readout for the activation of many adverse outcome pathways (AOPs). The 2016 Lush Science Prize was awarded for the development of one such assay, the PeriTox test, which uses human peripheral neurons generated from stem cells. The assay endpoints measure various cell functions, and these give information on the potential neurotoxicity and developmental neurotoxicity hazard of test compounds. The PeriTox test method has a high predictivity and sensitivity for peripheral neurotoxicants, and thus addresses the inherent challenges in pesticide testing and drug development. Data from the test can be obtained quickly and at a relatively high-throughput, and thus, the assay has the potential to replace animal-based safety assessment during early product development or for screening potential environmental toxicants. 2017 FRAME.

  11. Use of standard effluent toxicity tests for protection of endangered and threatened species

    Energy Technology Data Exchange (ETDEWEB)

    Henke, C.E.; Dwyer, F.J.; Ingersoll, C.G.; Mount, D.R. [National Biological Service, Columbia, MO (United States); Mayer, F.L. [Environmental Protection Agency, Gulf Breeze, FL (United States)

    1995-12-31

    Water quality criteria and many other environmental assessment tools are based on the results of laboratory toxicity tests. For a variety of reasons, these tests are typically conducted using one of several common laboratory species; results from these tests are then extrapolated with the intention of providing protection for other species not tested directly. This surrogate species approach is particularly necessary for threatened and endangered (listed) species, for which direct toxicity testing is often impractical. However, without direct knowledge of listed species sensitivity, it is not possible to be certain whether these species are adequately protected by current environmental practices. Moreover, the level of protection intended by water quality criteria (e.g., 95% of species) may not be sufficient to meet the requirements of the Endangered Species Act. The authors conducted short-term chronic toxicity tests using Ceriodaphnia dubia and fathead minnows and two listed species, bonytail chub and Colorado squawfish. Methods for Ceriodaphnia dubia and fathead minnow tests were as described by USEPA for effluent testing under the NPDES program; tests with listed species were patterned after the fathead minnow test procedures. Tests were conducted with; (1) ammonia, (2) carbaryl, and (3) a mixture of carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin. Preliminary data analysis indicates that the two listed species respond in a similar manner as the fathead minnow. The sensitivity of listed species to contaminant exposures and implications for regulatory procedures will be discussed.

  12. A Lymnaea stagnalis Embryo Test for Toxicity Bioindication of Acidification and Ammonia Pollution in Water

    Directory of Open Access Journals (Sweden)

    Robert Mazur

    2016-07-01

    Full Text Available The paper presents a study leading to a new acute toxicity test on embryonic and juvenile organisms of the great pond snail (Lymnaea stagnalis Linnaeus. Sulfuric acid, nitric acid, and ammonium hydroxide were used as waterborne toxicants in laboratory experiments. The exposure time was 24 h. Tests were conducted in 5–10 replications for each toxicant. The toxicity of the substances was classified according to different scales and the test’s sensitivity was compared to that of the commonly used bioindicator Daphnia magna Straus. The assessment of toxicity impact was supported by microscopic observations. The probit method was used as a parametric statistical procedure to estimate LC50 and the associated 95% confidence interval. Our study showed that the early developmental stages of Lymnaea stagnalis are very sensitive bioindicators, making it possible to detect even very low levels of the above-mentioned water toxicants. The highest toxicity is shown by ammonium hydroxide with LC50/24h values, respectively, 24.27 for embryos and 24.72 for juvenile forms, and the lowest is shown by nitric acid ions with LC50/24h values, respectively, 105.19 for embryos and 170.47 for juvenile forms. It is highly cost-effective due to simple and efficient breeding and the small size of the organisms in the bioassay population. Compared with Daphnia magna, relatively low concentrations of toxicants caused a lethal effect on embryonic and juvenile organisms of the great pond snail. Owing to their common occurrence and sensitivity, early developmental forms of Lymnaea stagnalis can be a valuable new tool in biomonitoring of the freshwater environment.

  13. Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes.

    Science.gov (United States)

    Fouad, Amr A; Qutub, Hatem O; Fouad, Abo Elyazied A; Audeh, Ahmed M; Al-Melhim, Walid N

    2017-12-01

    Epigallocatechin-3-gallate (EG), the main active flavonoid in green tea, has well-known anti-inflammatory, antioxidant, and anti-apoptotic activities. The EG protection against testicular injury induced by cisplatin was studied in Sprague-Dawley rats. Cisplatin (10 mg/kg, i.p) was given as a single injection to rats. EG was given at 40 and 80 mg/kg/day, i.p., for 5 days, starting the same day of cisplatin insult. Serum testosterone, and testicular malondialdehyde, total antioxidant status, nitric oxide, interleukin-6, interleukin-1β, cytochrome C, Bax/Bcl-2 ratio, and caspase-3 were measured. In addition, testicular histopathological examination and immunohistochemical expression of testicular tumour necrosis factor-α were evaluated. Cisplatin, compared to the control, significantly decreased serum testosterone (6.48 ± 0.7 vs. 50.8 ± 4.91 ng/10 mL), and testicular tissue antioxidant status (17.3 ± 1.21 vs. 64.12 ± 5.4 μmol/g), and significantly increased interleukin-6 (85.81 ± 6.11 vs. 38.2 ± 2.79 pg/100 mg), interleukin-1β (98.09 ± 8.31 vs. 32.52 ± 2.08 pg/100 mg), malondialdehyde (74.5 ± 5.88 vs. 23.8 ± 1.91 nmol/g), nitric oxide (104.98 ± 8.5 vs. 52.68 ± 5.12 nmol/100 mg), cytochrome C (5.97 ± 0.33 vs. 1.6 ± 0.99 ng/mg protein), Bax/Bcl-2 ratio (4.01 ± 0.38 vs. 0.71 ± 0.0), and caspase-3 (3.2 ± 0.21 vs. 0.98 ± 0.08 O.D. 405 nm) in rat testes. EG (40 and 80 mg/kg, respectively) caused significant increases of serum testosterone (33.9 ± 2.89 and 47.88 ± 4.4 ng/10 mL), and testicular antioxidant status (47.1 ± 3.92 and 58.22 ± 3.58 μmol/g), and significant decreases of interleukin-6 (57.39 ± 4.2 and 48.18 ± 3.98 pg/100 mg), interleukin-1β (65.12 ± 5.88 and 41.96 ± 3.51 pg/100 mg), malondialdehyde (42.3 ± 3.9 and 28.67 ± 2.49 nmol/g), nitric oxide (70.6 ± 6.79 and 61.31

  14. Differential toxicity of Disperse Red 1 and Disperse Red 13 in the Ames test, HepG2 cytotoxicity assay, and Daphnia acute toxicity test.

    Science.gov (United States)

    Ferraz, E R A; Umbuzeiro, G A; de-Almeida, G; Caloto-Oliveira, A; Chequer, F M D; Zanoni, M V B; Dorta, D J; Oliveira, D P

    2011-10-01

    Azo dyes are of environmental concern due to their degradation products, widespread use, and low-removal rate during conventional treatment. Their toxic properties are related to the nature and position of the substituents with respect to the aromatic rings and amino nitrogen atom. The dyes Disperse Red 1 and Disperse Red 13 were tested for Salmonella mutagenicity, cell viability by annexin V, and propidium iodide in HepG2 and by aquatic toxicity assays using daphnids. Both dyes tested positive in the Salmonella assay, and the suggestion was made that these compounds induce mainly frame-shift mutations and that the enzymes nitroreductase and O-acetyltransferase play an important role in the observed effect. In addition, it was shown that the presence of the chlorine substituent in Disperse Red 13 decreased the mutagenicity about 14 times when compared with Disperse Red 1, which shows the same structure as Disperse Red 13, but without the chlorine substituent. The presence of this substituent did not cause cytotoxicity in HepG2 cells, but toxicity to the water flea Daphnia similis increased in the presence of the chlorine substituent. These data suggest that the insertion of a chlorine substituent could be an alternative in the design of dyes with low-mutagenic potency, although the ecotoxicity should be carefully evaluated. Copyright © 2010 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    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.

  17. Review of the use of Ceramium tenuicorne growth inhibition test for testing toxicity of substances, effluents, products sediment and soil

    Science.gov (United States)

    Eklund, Britta

    2017-08-01

    A growth inhibition test has been developed based on two clones of the red macroalga Ceramium tenuicorne, one originating from 7 PSU and the other from 20 PSU. The species can be adapted to different salinities and the test can be carried out between 4 and 32 PSU. This test became an ISO standard in 2010 (ISO 107 10) for testing of chemicals and water effluents. In this study new and published data has been compiled on toxicity of single substances, waste waters from pulp mills, leachates from antifouling paints, harbour sediments and soil used for maintenance of leisure boats. The results show that the alga is sensitive to both metals and organic compounds and to biocides used in antifouling paints. By testing leachates from antifouling paints these could be ranked according to their toxicity. Similarly, the toxicity of waste waters from pulp mills was determined and the efficiency of secondary treatment evaluated. Further, the test method proved useful to test the toxicity in sediment samples. Sediments from small town harbours and ship lanes were shown to be harmful and compounds originating from antifouling paints were responsible for a large part of the inhibiting effect. The alga proved to be sensitive to contaminants leaking from boat yard soil. The growth inhibition test is a robust test that has high repeatability and reproducibility and easily can be applied on water, soil and sediment samples without being too costly. The species is found worl-wide in temperate waters, which makes the results relevant for large areas. In the Baltic Sea C. tenuicorne is the most common red alga species and is thus particularly relevant for this area. The overall results show that contaminants from boat activities and the use of antifouling paints in particular pose a threat to the environment.

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

    Science.gov (United States)

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

    2014-09-01

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

  19. Development of methods for laboratory culture and toxicity testing of the endangered desert pupfish, Cyprinodon macularius, and evaluation of the acute toxicity of selenium

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — We conducted a series of studies to evaluate methods for laboratory culture and toxicity testing with the endangered desert pupfish, Cyprinodon macularius. This...

  20. Evaluation of different biological test systems to assess the toxicity of metabolites from fungal biocontrol agents.

    Science.gov (United States)

    Skrobek, Anke; Boss, Désirée; Défago, Geneviève; Butt, Tariq M; Maurhofer, Monika

    2006-02-08

    The development of fungal biocontrol agents (BCAs) as alternatives to chemical pesticides is of increasing public interest. Tools to assess the toxicity of the secondary metabolites that these BCAs produce are often not available or existing methods have not yet been evaluated for these compounds. This study compares five different test systems, which include a representative bacterium, protozoan, arthropod and insect and human cell lines, as regards their sensitivity. It also compares the cost in time and resources for conducting the tests. Pure metabolites and crude extracts from two fungal BCAs as well as two chemical pesticides (hoestar and chlorpyrifos) and the mycotoxin patulin were employed as test compounds. All tests systems proved to be suitable for toxicity studies of metabolites from fungal BCAs and showed different grades of sensitivity to the different substances. The possibility of employing an array of test systems to determine ecotoxicological properties is discussed.

  1. Development of a standard acute dietary toxicity test for the silkworm (Bombyx mori L.)

    NARCIS (Netherlands)

    Sun, X.; Valk, H.; Jiang, H.; Wang, X.; Yuan, S.; Zhang, Y.; Roessink, I.; Gao, X.

    2012-01-01

    Larvae of the silkworm (Bombyx mod L.) may be exposed to pesticide residues on the leaves of their food plant, the mulberry tree (Morus spp.), which can lead to adverse effects on silk production. A new acute dietary toxicity test method was evaluated as the basis for pesticide risk assessment. A

  2. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  3. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  4. 76 FR 38169 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2011-06-29

    ..., Chemical Control Division (7405M), Office of Pollution Prevention and Toxics, Environmental Protection... interest to those persons who are concerned about data on health and/or environmental effects and other.... metallocenes, paints and varnishes, flame retardant for plastics. Methyl isoamyl ketone Percutaneous Absorption...

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-30

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

  7. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

    OpenAIRE

    Ruhdel, Irmela; Vanparys, Philippe; Knudsen, Thomas B.; ROGGEN Erwin; Oué draogo, Gladys; Basketter, David A; Daneshian, Mardas; Eskes, Chantra; Rossi, Annamaria; Skinner, Nigel; Blaauboer, Bas; Pelkonen, Olavi; Maxwell, Gavin; Yager, James

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds esp...

  8. Dredged Material Evaluations: Review of Zooplankton Toxicity Test Methods for Marine Water Quality Evaluations

    Science.gov (United States)

    2016-09-01

    for elutriate toxicity tests are fish, invertebrates ( crustaceans ), and zooplankton. Freshwater evaluations (following CWA regulations) use standard...one species each representative of phytoplankton or zooplankton, crustacean or mollusk, and fish species chosen from ERDC TN-DOER-R24 September...Organisation for Economic Cooperation and Development (OECD) and ASTM. Much of this work has focused on full life-cycle testing of the epibenthic

  9. Toxicity of uranium, molybdenum, nickel, and arsenic to Hyalella azteca and Chironomus dilutus in water-only and spiked-sediment toxicity tests.

    Science.gov (United States)

    Liber, Karsten; Doig, Lorne E; White-Sobey, Suzanne L

    2011-07-01

    A series of laboratory spiked-sediment toxicity tests with the amphipod Hyalella azteca and the midge Chironomus dilutus were undertaken to determine acute and chronic toxicity thresholds for uranium (U), molybdenum (Mo), nickel (Ni), and arsenic (As) based on both whole-sediment (total) and pore water exposure concentrations. Water-only toxicity data were also generated from separate experiments to determine the toxicities of these metals/metalloids under our test conditions and to help evaluate the hypothesis that pore water metal concentrations are better correlated with sediment toxicity to benthic organisms than whole-sediment metal concentrations. The relative toxicity of the four elements tested differed depending on which test species was used and whether whole-sediment or pore water metal concentrations were correlated with effects. Based on measured whole-sediment concentrations, Ni and As were the two most acutely toxic elements to H. azteca with 10-d LC50s of 521 and 532 mg/kg d.w., respectively. Measured pore water concentrations indicated that U and Ni were the two most acutely toxic elements, with 10-d LC50s to H. azteca of 2.15 and 2.05 mg/L, respectively. Based on pore water metal concentrations, the no-observed-effect concentrations (NOECs) for growth were (H. azteca and C. dilutus, respectively) 0.67 and 0.21 mg/L for U, 260-fold higher, respectively, than the CNSC LELs for these metals/metalloids. Data on pore water metal concentrations in toxic sediment would be a useful addition to future Guidelines documents. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Toxicity testing with constant or decreasing concentrations of chemically dispersed oil

    Energy Technology Data Exchange (ETDEWEB)

    Kiesser, S.L.; Fleishmann, M.L.; McQuerry, D.L.; Riley, R.G.

    1982-10-01

    An exposure system and method of quantitating toxicity have been developed to provide an estimate of the effects of dispersed oil on marine organisms under a variety of exposure conditions. Results of constant concentration exposures (for hours or days) can be compared to those of diluting exposures (decreasing to zero in 8 or 24 h) on a basis of the ''toxicity index.'' This index is equal to the total exposure when time in hours or days is multiplied by the concentration at each hour (ppm h or ppm days). Tests have been conducted with shrimp (Pandalus danae), two oils (Prudhoe Bay crude and a light Arabian crude), and two dispersants. There is a seasonal pattern to the tolerance of the shrimp. Tests in the colder months (fall/winter) produce toxicity indices approximately three times higher than summer/spring values. During tests in summer, there was also little difference observed when the toxicity of the light Arabian oil was compared to that of Prudhoe Bay crude (2.3 and 3.4 ppm days, respectively). The usefulness of our methods is that in addition to the comparisons already noted, it is possible to predict the outcome of dispersant application under varying environmental conditions.

  11. Evaluation of ability of reference toxicity tests to identify stress in laboratory populations of the amphipod Hyalella azteca

    Science.gov (United States)

    McNulty, E.W.; Dwyer, F.J.; Ellersieck, Mark R.; Greer, E.I.; Ingersoll, C.G.; Rabeni, C.F.

    1999-01-01

    Standard methods for conducting toxicity tests imply that the condition of test organisms can be established using reference toxicity tests. However, only a limited number of studies have evaluated whether reference toxicity tests can actually be used to determine if organisms are in good condition at the start of a test. We evaluated the ability of reference toxicants to identify stress associated with starvation in laboratory populations of the amphipod Hyalella azteca using acute toxicity tests and four reference toxicants: KCl, CdCl2, sodium pentachlorophenate (NaPCP), and carbaryl. Stress associated with severe starvation was observed with exposure of amphipods to carbaryl or NaPCP but not with exposure to KCl or CdCl2 (i.e., lower LC50 with severe starvation). Although the LC50s for NaPCP and carbaryl were statistically different between starved and fed amphipods, this difference may not be biologically significant given the variability expected in acute lethality tests. Stress associated with sieving, heat shock, or cold shock of amphipods before the start of a test was not evident with exposure to carbaryl or KCl as reference toxicants. The chemicals evaluated in this study provided minimal information about the condition of the organisms used to start a toxicity test. Laboratories should periodically perform reference toxicity tests to assess the sensitivity of life stages or strains of test organisms. However, use of other test acceptability criteria required in standard methods such as minimum survival, growth, or reproduction of organisms in the control treatment at the end of a test, provides more useful information about the condition of organisms used to start a test compared to data generated from reference toxicity tests.

  12. Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy.

    Science.gov (United States)

    Farcal, Lucian; Torres Andón, Fernando; Di Cristo, Luisana; Rotoli, Bianca Maria; Bussolati, Ovidio; Bergamaschi, Enrico; Mech, Agnieszka; Hartmann, Nanna B; Rasmussen, Kirsten; Riego-Sintes, Juan; Ponti, Jessica; Kinsner-Ovaskainen, Agnieszka; Rossi, François; Oomen, Agnes; Bos, Peter; Chen, Rui; Bai, Ru; Chen, Chunying; Rocks, Louise; Fulton, Norma; Ross, Bryony; Hutchison, Gary; Tran, Lang; Mues, Sarah; Ossig, Rainer; Schnekenburger, Jürgen; Campagnolo, Luisa; Vecchione, Lucia; Pietroiusti, Antonio; Fadeel, Bengt

    2015-01-01

    Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry - hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO - uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques - precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2

  13. Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy.

    Directory of Open Access Journals (Sweden)

    Lucian Farcal

    Full Text Available Nanomaterials (NMs display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS. Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues. The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry - hydrophilic (NM-103 and hydrophobic (NM-104, two forms of ZnO - uncoated (NM-110 and coated with triethoxycapryl silane (NM-111 and two SiO2 NMs produced by two different manufacturing techniques - precipitated (NM-200 and pyrogenic (NM-203. Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h (ZnO>SiO2>TiO2. Longer term exposure (7 to 21 days significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103. This ranking was different in the case of embryonic tissues, for which TiO2

  14. Toxicity testing and drug screening using iPSC-derived hepatocytes, cardiomyocytes, and neural cells.

    Science.gov (United States)

    Csöbönyeiová, Mária; Polák, Štefan; Danišovič, L'uboš

    2016-07-01

    Unexpected toxicity in areas such as cardiotoxicity, hepatotoxicity, and neurotoxicity is a serious complication of clinical therapy and one of the key causes for failure of promising drug candidates in development. Animal studies have been widely used for toxicology research to provide preclinical security evaluation of various therapeutic agents under development. Species differences in drug penetration of the blood-brain barrier, drug metabolism, and related toxicity contribute to failure of drug trials from animal models to human. The existing system for drug discovery has relied on immortalized cell lines, animal models of human disease, and clinical trials in humans. Moreover, drug candidates that are passed as being safe in the preclinical stage often show toxic effects during the clinical stage. Only around 16% drugs are approved for human use. Research on induced pluripotent stem cells (iPSCs) promises to enhance drug discovery and development by providing simple, reproducible, and economically effective tools for drug toxicity screening under development and, on the other hand, for studying the disease mechanism and pathways. In this review, we provide an overview of basic information about iPSCs, and discuss efforts aimed at the use of iPSC-derived hepatocytes, cardiomyocytes, and neural cells in drug discovery and toxicity testing.

  15. Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test.

    Science.gov (United States)

    McKee, Richard H; Steup, David; Schreiner, Ceinwen; Podhasky, Paula; Malley, Linda A; Roberts, Linda

    2014-01-01

    Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4. All animals survived the treatment period. Principal effects of repeated exposure included increased liver weights in males and females, increased kidney weights in males, and histological changes in the thyroid, secondary to liver enzyme induction. These changes were not considered to be toxicologically meaningful and are not relevant to humans. There were no treatment-related effects in functional observation tests or motor activity; no significant reductions in fertility or changes in other reproductive parameters; and no evidence of developmental toxicity in offspring. The overall no observed adverse effect concentration was 3000 ppm (approximately 13, 600 mg/m(3)). In conclusion the HSRN effects on liver and kidney are consistent with the results of other studies of volatile fractions or other naphthas or formulated gasoline, and there were no HSRN effects on neurological developmental or reproductive parameters.

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

    Science.gov (United States)

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

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

  17. Influence of potentially confounding factors on sea urchin porewater toxicity tests.

    Science.gov (United States)

    Carr, R S; Biedenbach, J M; Nipper, M

    2006-11-01

    The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment.

  18. 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.

  19. 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.

  20. 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

  1. Toxicity Testing of Restorative Dental Materials Using Brine Shrimp Larvae (Artemia salina

    Directory of Open Access Journals (Sweden)

    Manar M. Milhem

    2008-08-01

    Full Text Available This study investigated the effect of extracts of different composites, glass ionomer cement (GICs and compomers on the viability of brine shrimp larvae. Ethanolic extracts of four dental composites (Z-100; Solitaire 2; Filtek P60 and Synergy, a conventional GIC (Ketac-Fil, a resin-modified glass ionomer cement (Vitremer, two compomers (F2000; Dyract AP, and a flowable compomer (Dyract Flow were prepared from each material. Following evaporation of the ethanol, the extracts were resuspended in distilled water, which was then used to test the effects on the viability of brine shrimp larvae. For the composites, the extract of Synergy was the least toxic (88% viability followed by the extracts of Solitaire 2, Z100 and P60 (75%, 67.5% and 50% viability, respectively. One-way ANOVA revealed highly significant differences between the resin composite materials (p<0.001. Follow-up comparison between the composite groups by Tukey's pairwise multiple-comparison test (α =0.05 showed that the extract of Synergy was significantly less toxic than the extracts of all the other materials except that of Solitaire 2. The compomers showed 100% lethality, while the percentage of viable larvae for the extracts of Ketac-Fil, and Vitremer were 32.3%, and 37.0%, respectively. One-way ANOVA revealed highly significant differences between the groups of materials (p<0.001. Follow-up comparison between the groups by Tukey's test (α = 0.05 showed that the toxic effect of the extracts of the compomers were significantly greater than that of Ketac-Fil, and Vitremer. The differences in the toxic effects of Vitremer and Ketac-Fil were not statistically significant. In conclusion, the toxicity of composite materials varied according to their chemical composition. Compomers were the most lethal materials to brine shrimp larvae followed by GICs and then composites.

  2. History and sensitivity comparison of the Spirodela polyrhiza microbiotest and Lemna toxicity tests

    Directory of Open Access Journals (Sweden)

    Baudo R.

    2015-01-01

    Full Text Available The history of toxicity tests with duckweeds shows that these assays with free-floating aquatic angiosperms are gaining increasing attention in ecotoxicological research and applications. Standard tests have been published by national and international organizations, mainly with the test species Lemna minor and Lemna gibba. Besides the former two test species the great duckweed Spirodela polyrhiza is to date also regularly used in duckweed testing. Under unfavorable environmental conditions, the latter species produces dormant stages (turions and this has triggered the attention of two research groups from Belgium and Greece to jointly develop a “stock culture independent” microbiotest with S. polyrhiza. A 72 h new test has been worked out which besides its independence of stock culturing and maintenance of live stocks is very simple and practical to perform, and much less demanding in space and time than the conventional duckweed tests. Extensive International Interlaboratory Comparisons on the S. polyrhiza microbiotest showed its robustness and reliability and triggered the decision to propose this new assay to the ISO for endorsement and publication as a standard toxicity test for duckweeds. Sensitivity comparison of the 72 h S. polyrhiza microbiotest with the 7d L. minor assay for 22 compounds belonging to different groups of chemicals revealed that based on growth as the effect criterion both duckweed assays have a similar sensitivity. Taking into account its multiple advantages and assets, the S. polyrhiza microbiotest is a reliable and attractive alternative to the conventional duckweed tests.

  3. Increased RO concentrate toxicity following application of antiscalants - acute toxicity tests with the amphipods Gammarus pulex and Gammarus roeseli.

    Science.gov (United States)

    Feiner, Mona; Beggel, Sebastian; Jaeger, Nadine; Geist, Juergen

    2015-02-01

    In reverse osmosis, a frequently used technology in water desalination processes, wastewater (RO concentrate) is generated containing the retained solutes as well as so-called antiscalants (AS), i.e. chemical substances that are commonly applied to prevent membrane-blocking. In this study, a risk assessment of a possible discharge of concentrate into a small stream was conducted. The acute toxicity of two concentrates containing two different ASs and of concentrate without AS to the amphipods Gammarus pulex and Gammarus roeseli was studied. Mortality of gammarids exposed to the concentrate without AS was not different to the control, whereas concentrates including ASs caused mortality rates up to 100% at the highest test concentrations after 168 h. Resulting EC50-values were 36.2-39.4% (v/v) after 96 h and 26.6-58.0% (v/v) after 168 h. These results suggest that the ecotoxicological relevance of antiscalants is greater than currently assumed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

  5. Burrowing mayfly Ephemera orientalis (Ephemeroptera: Ephemeridae) as a new test species for pesticide toxicity.

    Science.gov (United States)

    Mo, Hyoung-Ho; Kim, Yongeun; Lee, Yun-Sik; Bae, Yeon Jae; Khim, Jong Seong; Cho, Kijong

    2016-09-01

    The potential of mayfly Ephemera orientalis McLachlan eggs and first-instar larvae in ecotoxicological testing was investigated. Both stages of E. orientalis showed high tolerance to various environmental variables, such as water temperature, pH, water hardness, and dissolved organic carbon. Toxicological assays were conducted with three insecticides (emamectin benzoate, endosulfan, and cypermethrin), one fungicide (mancozeb), and one herbicide (paraquat dichloride). The two toxicity endpoints for the assay were the 14-day egg median hatching rate (EHC50) in static and renewal exposure systems and 24-h median larval mortality (LC50). Cypermethrin was the most toxic to both eggs (EHC50 in static system = 36.9 μg/L; EHC50 in renewal system < 0.15 μg/L) and larvae (LC50 = 4.5 μg/L), and paraquat dichloride was the least toxic to eggs (EHC50 in static system = 54,359.8 μg/L; EHC50 in renewal system = 49541.3 μg/L) and larvae (LC50 = 9259.5 μg/L). The results were compared to literature data of Daphnia magna Straus and Cloeon dipterum Linnaeus to determine its relative sensitivity to pesticides. These three species had different toxicities to the tested pesticides, especially according to the exposure system. E. orientalis eggs in the static system were found to be less sensitive were D. magna and C. dipterum, but eggs in the renewal system and larvae had similar or higher sensitivities to the tested pesticides. The results revealed that this species has potential for use in ecotoxicological testing of pesticides. Because of its geographic distribution, E. orientalis may be used as an alternative or complementary test species for ecotoxicological studies in Northeast Asian countries, where natural populations of the international standard species, D. magna, are rarely found.

  6. Modified whole effluent toxicity test to assess and decouple wastewater effects from environmental gradients.

    Directory of Open Access Journals (Sweden)

    Sebastián Sauco

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

  7. Test Results for a Non-toxic, Dual Thrust Reaction Control Engine

    Science.gov (United States)

    Robinson, Philip J.; Veith, Eric M.; Turpin, Alicia A.

    2005-01-01

    A non-toxic, dual thrust reaction control engine (RCE) was successfully tested over a broad range of operating conditions at the Aerojet Sacramento facility. The RCE utilized LOX/Ethanol propellants; and was tested in steady state and pulsing modes at 25-lbf thrust (vernier) and at 870-lbf thrust (primary). Steady state vernier tests vaned chamber pressure (Pc) from 0.78 to 5.96 psia, and mixture ratio (MR) from 0.73 to 1.82, while primary steady state tests vaned Pc from 103 to 179 psia and MR from 1.33 to 1.76. Pulsing tests explored EPW from 0.080 to 10 seconds and DC from 5 to 50 percent at both thrust levels. Vernier testing accumulated a total of 6,670 seconds of firing time, and 7,215 pulses, and primary testing accumulated a total of 2,060 seconds of firing time and 3,646 pulses.

  8. Marine and estuarine porewater toxicity testing -- species and end point comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Carr, R.S.; Chapman, D.C.; Biedenbach, J.M.; Robertson, L. [NBS, Corpus Christi, TX (United States). NFCR Field Research Station

    1994-12-31

    As part of their continuing development and evaluation of the porewater toxicity test approach for assessing the quality of marine and estuarine sediments, a variety of studies involving species and endpoint comparisons as well as validation studies have recently been conducted. The results from numerous extensive sediment quality assessment surveys have demonstrated that porewater toxicity tests are considerably more sensitive than the standard solid-phase tests and invariably exhibit a higher degree of concordance with sediment quality assessment guidelines than the standard tests. Species that have been evaluated for use in testing marine and estuarine pore water include a life-cycle test with the polychaete Dinophilus gyrociliatus, survival and hatching success with embryo-larval stages of red drum Sciaaenops ocellatus, survival of nauplii stages of the harpacticoid copepod Longipedia sp., and three different assays (fertilization, embryological development, and cytogenetic) with the sea urchin Arbacia punctulata. The different species and end points have been compared using sediment pore water from a variety of contaminated sites. Although the results of tests with the different species and end points were often comparable, in general, the sea urchin embryological development assay appears to be the most sensitive porewater test evaluated thus far in their laboratory.

  9. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    Science.gov (United States)

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

  10. Adjusting for mortality effects in chronic toxicity testing: Mixture model approach

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.C.D.; Smith, E.P.

    2000-01-01

    Chronic toxicity tests, such as the Ceriodaphnia dubia 7-d test are typically analyzed using standard statistical methods such as analysis of variance or regression. Recent research has emphasized the use of Poisson regression or more generalized regression for the analysis of the fecundity data from these studies. A possible problem in using standard statistical techniques is that mortality may occur from toxicant effects as well as reduced fecundity. A mixture model that accounts for fecundity and mortality is proposed for the analysis of data arising from these studies. Inferences about key parameters in the model are discussed. A joint estimate of the inhibition concentration is proposed based on the model. Confidence interval estimations via the bootstrap method is discussed. An example is given for a study involving copper and mercury.

  11. Evaluation of the toxicity of Araribá (Centrolobium tomentosum using brine Shrimp test

    Directory of Open Access Journals (Sweden)

    Roberto Carlos de Sá Silva

    2013-12-01

    Full Text Available Since the dawn of medicine, man has used natural products for the treatment of disease. There has been a recent increase in studies of the therapeutic characteristics plants in popular use in many places of the world. In this context, the species Centrolobium tomentosum, Fabaceae, known popularly as Araribá or Araruva, is used in Brazilian folk medicine as an astringent for wound treatment and bruises due to the large amount of tannins contained in the bark. This work used toxicity tests to assess the biological activity of ethanolic extracts from C. tomentosum with the specific objectives of obtaining concentrated extracts from the bark and wood of this species and determining the total phenols and tannins present in these extracts. We collected araribá samples in order to obtain ethanolic extracts through the percolation process. We then made a qualitative chemical identification of hydrolysable tannins and condensed tannins. We used the Folin-Ciocalteu method for the phenols quantification and the casein precipitation method for the tannins determination. The toxicity of extracts was evaluated using the brine shrimp bioassay (Artemia salina, in which the C. tomentosum bark extract showed moderate toxicity, with estimated LC50 = 416 μg.ml-1, whereas the leaves and wood extracts of this species showed low toxicity with LC50 = 537 μg.ml-1 and 826 μg.ml-1, respectively.

  12. Implications for toxicity tests with amphipod Gammarus aequicauda: effects of temperature and salinity on life cycle.

    Science.gov (United States)

    Prato, E; Biandolino, F; Scardicchio, C

    2008-12-01

    This study explored the effect of temperature and salinity on the life cycle of Gammarus aequicauda in order to establish temperature and salinity ranges advantageous for chronic toxicity testing. A broad range of salinity-temperature conditions (salinities of 10, 20 and 36 per thousand, and temperatures of 10, 18 and 24 degrees C combined in nine different treatments) significantly influenced various reproductive aspects of G. aequicauda reared in the laboratory, from newly released juveniles to first brood production by mature adults. There was a significant linear regression between the brood size and the body size of the female. The number of juveniles released per female was highest at 10 degrees C and lowest at 24 degrees C. The temperature and salinity variations had a significant effect on the fecundity of G. aequicauda. A high temperature led to a faster individual growth and a quicker sexual development than a lower temperature. A temperature acceptable for chronic toxicity tests can be 18 degrees C, at which an acceleration of the life cycle without a lowering of the amphipod's performance was observed. Regarding salinity, results from this study showed that salinities down to 36 per thousand may also be used in sediment toxicity tests with G. aequicauda, so providing a proper and gradual acclimation.

  13. Evaluation of the hazardous impact of landfill leachates by toxicity and biodegradability tests.

    Science.gov (United States)

    Kalcíková, G; Vávrová, M; Zagorc-Koncan, J; Gotvajn, A Zgajnar

    2011-01-01

    The aim of our research was to assess the ecotoxicity and biodegradability of leachates originating from two parts of a municipal landfill before and after biological treatment in the existing treatment plant. Biotests represent important tools for adequate environmental characterization of landfill leachates and could be helpful in reliable assessment and monitoring of the treatment plant efficiency. For ecotoxicity testing of landfill leachate before and after biological treatment, different organisms were chosen: the bacteria Vibrio fischeri, a mixed culture of activated sludge, duckweed Lemna minor, white mustard Sinapis alba, brine shrimp Artemia salina, and water flea Daphnia magna. For assessment of biodegradability, the method for determination of oxygen demand in a closed respirometer was used. The investigated leachates were heavily polluted, and in some cases, effluent limits were exceeded even after treatment. Results indicated that toxicity tests and physico-chemical parameters determined before and after treatment equivalently assess the efficiency of the existing treatment plant. However, the investigated leachates showed higher toxicity to Daphnia magna and especially to Lemna minor in contrast to Vibrio fischeri and Artemia salina (neither was sensitive to any of the leachates). No leachates were readily biodegradable. Experiments confirmed that the battery of toxicity tests should be applied for more comprehensive assessment of landfill leachate treatment and for reliable assessment of the treated leachate's subsequent environmental impact. It was confirmed that treated leachate, in spite of its better physico-chemical characteristics, still represents a potential environmental risk and thus should not be released into the environment.

  14. Toxicity minimization of pipelines hydrostatic tests fluids, stage I: laboratory essays

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, Jorge A.S.; Penna, Monica de O.; Portela, Daniele B.; Christino, Fernando P.; Silva, Joao L.B. da; Geraldo, Lucia M.L. [Petroleo do Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil); Mota, Vanessa V.C. [Fundacao Gorceix, Ouro Preto, MG (Brazil); Cravo Junior, Walter [Pontificia Univ. Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil)

    2009-07-01

    This paper presents the results of the laboratory essays stage of the project for toxicity minimization of pipelines hydrostatic tests fluids. The hydrostatic-hibernation fluid composition most used by PETROBRAS in offshore operations is seawater added with sodium bis sulfite, fluorescein, alquildimetilbenzilamonium chloride, and tetrakis-hydroxymethyl-phosphonium sulfate (THPS). In order to reduce the toxicity of the fluid used in hydrostatic tests, the use of lesser concentrations of THPS was attempted with UV radiation application as a disinfection technique prior to the adding of the fluid's components. The compositions were evaluated in different conditions of temperature use of UV radiation or not and oxygen scavenger adding (presence and absence). The fluids were kept hibernating for 120 days. All the parameters tested after hibernation were compared to fresh from preparation samples (zero time samples). The fluid's characteristics were evaluated by microbiological control and toxicity as well as the THPS residual. Results showed that the UV treatment was more effective in the absence of oxygen scavenger. The temperature acts as a microbial growth control agent, as expected. To large scale operations, a water quality monitoring must be performed previously to any field operations, in order to determinate the best treatment to be used in each case. (author)

  15. Use of solid-phase adsorbents with the Microtox test for determining the toxicity of hydrophobic chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, G.T. [CSIRO Division of Coal and Energy Technology, Sydney, New South Wales (Australia). Centre for Advanced Analytical Chemistry

    1995-12-31

    The determination of the toxicity of hydrophobic chemicals and to aquatic organisms can be a problem. Often no toxicity is found at concentrations near the solubility of the chemical in water. Solvents are used to increase the solubility of the chemical but the toxicity of the solvent may interfere with the test. Organic extracts of sediments and soil also suffer from the same solubility problems. The Solid-Phase Microtox Test protocol, which involves the incubation of Photobacterium phosphoreum with sediment particles, followed by removal of the particles by filtration, is used for the direct testing of sediment toxicity. The physical and chemical properties of the sediment, however, affect its apparent toxicity to Microtox, giving variable results between polluted and unpolluted sites. Adsorbents, designed for solid-phase extraction, were used as surrogate sediment particles. Toxicants were adsorbed to these materials and were tested for toxicity using the Solid Phase Microtox Test. The advantage of using the absorbent is that they are have a defined surface chemistry, particle size and pore size. Adsorbents containing a variety of functional groups are widely available and can be used for concentrating toxicants from solution by ion exchange, normal phase or reversed phase chromatographic processes. The toxicity of a range of adsorbents to Microtox was determined using the solid-phase protocols. The most toxic absorbent were Florisil and NH{sub 2}(amino) with EC,, values of 2.1 and 5.7 g/L, respectively. Most absorbent had EC{sub 50} values between 50 and 100 g/L and could be used in small amounts for Microtox Tests. Diol and CN(cyanopropyl) absorbent showed no toxicity at concentrations of 100 g/L, the equivalent of one solid-phase cartridge (300 mg) in 3 mL Microtox diluent.

  16. Sulfide as a confounding factor in toxicity tests with the sea urchin Paracentrotus lividus: comparisons with chemical analysis data.

    Science.gov (United States)

    Losso, Chiara; Arizzi Novelli, Alessandra; Picone, Marco; Volpi Ghirardini, Annamaria; Ghetti, Pier Francesco; Rudello, Danilo; Ugo, Paolo

    2004-02-01

    Sperm cell and embryo toxicity tests with the sea urchin Paracentrotus lividus were performed to assess the toxicity of sulfide, which is considered a confounding factor in toxicity tests. For improved information on the sensitivity of these methods to sulfide, experiments were performed in the same aerobic conditions used for testing environmental samples, with sulfide concentrations being monitored at the same time by cathodic stripping voltammetry. New toxicity data for sulfide expressed as median effective concentration (EC50) and no-observed-effect concentration (NOEC) are reported. The EC50 value for the embryo toxicity test (total sulfide at 0.43 mg/L) was three times lower than for the sperm cell test (total sulfide at 1.20 mg/L), and the NOEC values were similar (on the order of total sulfide at 10(-1) mg/L) for both tests. The decrease in sulfide concentration during the bioassay as a consequence of possible oxidation of sulfide by dissolved oxygen was determined by voltammetric analysis, indicating a half-life of about 50 min in the presence of gametes. To check the influence of sulfide concentrations on toxicity effects in real samples, toxicity (with the sperm cell toxicity test) and chemical analyses also were performed in pore-water samples collected with an in situ sampler in sediments of the Lagoon of Venice (Italy). A highly positive correlation between increased acute toxicity and increased sulfide concentration was found. Examination of data revealed that sulfide is a real confounding factor in toxicity testing in anoxic environmental samples containing concentrations above the sensitivity limit of the method.

  17. 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

  18. Rapid toxicity assessment of sediments from estuarine ecosystems: A new tandem in vitro testing approach

    Science.gov (United States)

    Johnson, B. Thomas; Long, E.R.

    1998-01-01

    Microtox?? and Mutatox?? were used to evaluate the acute toxicity and genotoxicity, respectively, of organic sediment extracts from Pensacola Bay and St. Andrew Bay, two estuaries that cover about 273 and 127 km2, respectively, along the Gulf coast of Florida, USA. The sensitivity and selectivity of these two bioluminescent toxicity assays were demonstrated in validation studies with over 50 pesticides, genotoxins, and industrial pollutants, both as single compounds and in complex mixtures. The 50% effective concentration (EC50) values of insecticides, petroleum products, and polychlorinated biphenyls determined by Microtox all tended to group around the mean EC50 value of 1.2 (0.8) mg/L. The polycyclic aromatic hydrocarbon sensitivity of Mutatox was in general similar to that reported in the Ames test. Surficial sediment samples were collected, extracted with dichloromethane, evaporated and concentrated under nitrogen, dissolved in dimethyl sulfoxide, assayed for acute toxicity and genotoxicity, and compared with reference sediments. Samples with low EC50 values, and determined to be genotoxic, were detected in Massalina Bayou, Watson Bayou, East Bay, and St. Andrew Bay-East in St. Andrew Bay as well as Bayou Grande, Bayou Chico, and Bayou Texar in Pensacola Bay. An overview of these data sets analyzed by Spearman rank correlation showed a significant correlation between acute toxicity and genotoxicity (p < 0.05). Microtox and Mutatox in tandem was a sensitive, cost-effective, and rapid (<24 h) screening tool that identified troublesome areas of pollution and assessed the potential sediment toxicity of lipophilic contaminants in aquatic ecosystems.

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

    DEFF Research Database (Denmark)

    Vergauwen, Lucia; Nørgaard Schmidt, Stine; Stinckens, Evelyn

    2015-01-01

    , our objective was to improve exposure conditions in FET tests by evaluating a passive dosing format using silicone O-rings in standard 24-well polystyrene plates. We exposed zebrafish embryos to a series of phenanthrene concentrations until 120 h post fertilization (hpf), and obtained a linear...... was not attributed to impaired swim bladder inflation, but rather to baseline toxicity. We conclude that silicone O-rings (1) produce a linear dilution series of phenanthrene in the 120 hpf FET test, (2) generate and maintain aqueous concentrations for reliable determination of effect concentrations, and allow...

  20. The role of in vitro methods as alternatives to animals in toxicity testing.

    Science.gov (United States)

    Anadón, Arturo; Martínez, María Aranzazu; Castellano, Victor; Martínez-Larrañaga, María Rosa

    2014-01-01

    It is accepted that animal testing should be reduced, refined or replaced as far as it is practicably possible. There are also a wide variety of in vitro models, which are used as screening studies and mechanistic investigations. The ability of an in vitro assay to be reliable, biomedically, is essential in pharmaceutical development. Furthermore, it is necessary that cells used in in vitro testing mimic the phenotype of cells within the human target tissue. The focus of this review article is to identify the key points of in vitro assays. In doing so, the authors take into account the chemical agents that are assessed and the integrated in vitro testing strategies. There is a transfer of toxicological data from primary in vivo animal studies to in vitro assays. The key element for designing an integrated in vitro testing strategy is summarized as follows: exposure modeling of chemical agents for in vitro testing; data gathering, sharing and read-across for testing a class of chemical; a battery of tests to assemble a broad spectrum of data on different mechanisms of action to predict toxic effects; and applicability of the test and the integrated in vitro testing strategies and flexibility to adjust the integrated in vitro testing strategies to test substance. While these methods will be invaluable if effective, more studies must be done to ensure reliability and suitability of these tests for humans.

  1. Single species aquatic toxicity testing for environmental regulation of chemicals. Proposal for a flexible testing approach

    Energy Technology Data Exchange (ETDEWEB)

    Kristensen, P.; Roghair, C.; Tyle, H.

    1995-12-31

    In a co-operation between Denmark and The Netherlands, a Detailed Review Paper on Aquatic Testing Methods for Pesticides and Industrial Chemicals has been elaborated for the consideration of the National Coordinators of the OECD Test Guideline Programme. The objective of the review is to identify the need for revision of existing OECD Test Guidelines and also to identify the need for elaboration of new guidelines. The background for the recommendations made is (1) a comprehensive review of more than 600 pelagic and benthic testing methods collected from national standardization organizations and from the scientific literature, (2) an evaluation of the methods based on a set of formalized evaluation criteria, (3) an identification of the present needs in national and international aquatic effects assessment schemes and (4) a proposed framework for future assessment of chemicals in specific types of aquatic environments. It is foreseen that future assessments (which go beyond the initial generic assessment) may be directed toward specific types of aquatic environments. The proposal for new testing methods has therefore been framed into five testing scenarios. Four testing scenarios for the benthic and pelagic compartments, respectively: cold freshwater environment, warm freshwater environment, cold marine environment and warm marine environment and a testing scenario for assessment of biological waste water treatment. The rational for the elaboration of single species testing scenarios will especially be addressed.

  2. Structure-activity relationships for chloro- and nitrophenol toxicity in the pollen tube growth test

    Energy Technology Data Exchange (ETDEWEB)

    Schueuermann, G. [UFZ Centre for Environmental Research, Leipzig (Germany). Dept. of Chemical Ecotoxicology; Somashekar, R.K. [Bangalore Univ. (India). Dept. of Botany; Kristen, U. [Univ. Hamburg (Germany). Inst. fuer Allgemeine Botanik

    1996-10-01

    Acute toxicity of 10 chlorophenols and 10 nitrophenols with identical substitution patterns is analyzed with the pollen tube growth (PTG) test. Concentration values of 50% growth inhibition (IC50) between 0.1 and 300 mg/L indicate that the absolute sensitivity of this alternative biotest is comparable to conventional aquatic test systems. Analysis of quantitative structure-activity relationships using lipophilicity (log K{sub ow}), acidity (pK{sub a}), and quantum chemical parameters to model intrinsic acidity, solvation interactions, and nucleophilicity reveals substantial differences between the intraseries trends of log IC50. With chlorophenols, a narcotic-type relationship is derived, which, however, shows marked differences in slope and intercept when compared to reference regression equations for polar narcosis. Regression analysis of nitrophenol toxicity suggests interpretation in terms of two modes of action: oxidative uncoupling activity is associated with a pK{sub a} window from 3.8 to 8.5, and more acidic congeners with diortho-substitution show a transition from uncoupling to a narcotic mode of action with decreasing pK{sub a} and log K{sub ow}. Model calculations for phenol nucleophilicity suggest that differences in the phenol readiness for glucuronic acid conjugation as a major phase-II detoxication pathway have no direct influence on acute PTG toxicity of the compounds.

  3. Comparative rice seed toxicity tests using filter paper, growth pouch-tm, and seed tray methods

    Science.gov (United States)

    Wang, W.

    1993-01-01

    Paper substrate, especially circular filter paper placed inside a Petri dish, has long been used for the plant seed toxicity test (PSTT). Although this method is simple and inexpensive, recent evidence indicates that it gives results that are significantly different from those obtained using a method that does not involve paper, especially when testing metal cations. The study compared PSTT using three methods: filter paper, Growth Pouch-TM, and seed tray. The Growth Pouch-TM is a commercially available device. The seed tray is a newly designed plastic receptacle placed inside a Petri dish. The results of the Growth Pouch-TM method showed no toxic effects on rice for Ag up to 40 mg L-1 and Cd up to 20 mg L-1. Using the seed tray method, IC50 (50% inhibitory effect concentration) values were 0.55 and 1.4 mg L-1 for Ag and Cd, respectively. Although results of filter paper and seed tray methods were nearly identical for NaF, Cr(VI), and phenol, the toxicities of cations Ag and Cd were reduced by using the filter paper method; IC50 values were 22 and 18 mg L-1, respectively. The results clearly indicate that paper substrate is not advisable for PSTT.

  4. 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.

  5. Toxicity testing of dispersed oil requires adherence to standardized protocols to assess potential real world effects.

    Science.gov (United States)

    Coelho, Gina; Clark, James; Aurand, Don

    2013-06-01

    Recently, several researchers have attempted to address Deepwater Horizon incident environmental fate and effects issues using laboratory testing and extrapolation procedures that are not fully reliable measures for environmental assessments. The 2013 Rico-Martínez et al. publication utilized laboratory testing approaches that severely limit our ability to reliably extrapolate such results to meaningful real-world assessments. The authors did not adopt key methodological elements of oil and dispersed oil toxicity standards. Further, they drew real-world conclusions from static exposure tests without reporting actual exposure concentrations. Without this information, it is not possible to compare their results to other research or real spill events that measured and reported exposure concentrations. The 1990s' Chemical Response to Oil Spills: Ecological Effects Research Forum program was established to standardize and conduct exposure characterization in oil and dispersed oil aquatic toxicity testing (Aurand and Coelho, 2005). This commentary raises awareness regarding the necessity of standardized test protocols. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Use of sublethal endpoints in sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Chris G.; Brunson, Eric L.; Dwyer, F. James; Hardesty, Douglas K.; Kemble, Nile E.

    1998-01-01

    Short-term sediment toxicity tests that only measure effects on survival can be used to identify high levels of contamination but may not be able to identify marginally contaminated sediments. The objective of the present study was to develop a method for determining the potential sublethal effects of contaminants associated with sediment on the amphipod Hyalella azteca (e.g., reproduction). Exposures to sediment were started with 7- to 8-d-old amphipods. On day 28, amphipods were isolated from the sediment and placed in water-only chambers where reproduction was measured on day 35 and 42. Typically, amphipods were first in amplexus at about day 21 to 28 with release of the first brood between day 28 to 42. Endpoints measured included survival (day 28, 35, and 42), growth (as length and weight on day 28 and 42), and reproduction (number of young/female produced from day 28 to 42). This method was used to evaluate a formulated sediment and field-collected sediments with low to moderate concentrations of contaminants. Survival of amphipods in these sediments was typically >85% after the 28-d sediment exposures and the 14-d holding period in water to measure reproduction. Reproduction was more variable than growth; hence, more replicates might be needed to establish statistical differences among treatments. Previous studies have demonstrated that growth of H. azteca in sediment tests often provides unique information that can be used to discriminate toxic effects of exposure to contaminants. Either length or weight can be measured in sediment tests with H. azteca. However, additional statistical options are available if length is measured on individual amphipods, such as nested analysis of variance that can account for variance in length within replicates. Ongoing water-only studies testing select contaminants will provide additional data on the relative sensitivity and variability of sublethal endpoints in toxicity tests with H. azteca.

  7. Acute toxicity of copper oxide nanoparticles to Daphnia magna under different test conditions

    DEFF Research Database (Denmark)

    Thit, Amalie; Huggins, Krista; Selck, Henriette

    2017-01-01

    suspensions changed in a way similar to what is known for dissolved Cu: first in ISO standard test conditions (pH 7.8), second with slight acidity (pH 6.5), third in the presence of citric acid, and fourth in the presence of humic acid. For all four exposure conditions, the toxicity of Cu employed...... in the three forms followed the same sequence, i.e., CuSO4 > monodispersed 6 nm CuO ≫ poly-dispersed CuO. The toxicity of all Cu forms decreased from pH 6.5, ≫ pH 7.8, > pH 7.8 + citric acid, to ≫ pH 7.8 + humic acid. This pattern is in agreement with concentrations of Cu2+ calculated using the equilibrium...

  8. Evaluation of Complex Toxicity of Canbon Nanotubes and Sodium Pentachlorophenol Based on Earthworm Coelomocytes Test.

    Science.gov (United States)

    Yang, Yang; Xiao, Yao; Li, Mei; Ji, Funian; Hu, Changwei; Cui, Yibin

    2017-01-01

    As a standard testing organism in soil ecosystems, the earthworm Eisenia fetida has been used widely in toxicity studies. However, tests at the individual level are time- and animal-consuming, with limited sensitivity. Earthworm coelomocytes are important for the assimilation and elimination of exogenous compounds and play a key role in the processes of phagocytosis and inflammation. In this study, we explored an optimal condition to culture coelomocytes of E. fetida in vitro and investigated the cytotoxicity of multiwalled carbon nanotubes (MWCNTs) and sodium pentachlorophenol (PCP-Na) using coelomocytes via evaluating lethal toxicity, oxidative stress, membrane damage, and DNA damage. The results showed that coelomocytes can be successfully cultured in vitro in primary under the RPMI-1640 medium with 2-4×104 cells/well (1-2×105 cells/mL) in 96-well plates at 25°C without CO2. Both MWCNTs and PCP-Na could cause oxidative damage and produce ROS, an evidence for lipid peroxidation with MDA generation and SOD and CAT activity inhibition at high stress. The two chemicals could separately damage the cell membrane structure, increasing permeability and inhibiting mitochondrial membrane potential (MMP). In addition, our results indicate that PCP-Na may be adsorbed onto MWCNTs and its toxicity on earthworm was accordingly alleviated, while a synergetic effect was revealed when PCP-Na and MWCNTs were added separately. In summary, coelomocyte toxicity in in vitro analysis is a sensitive method for detecting the adverse effects of carbon nanotubes combined with various pollutants.

  9. Standardization of a chronic sediment toxicity test with Chironomus riparius -- An EU collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, R.; Grootelaar, L.; Guchte, C. van de [WRc Medmenham, Marlow (United Kingdom)]|[RIZA, Lelystad (Netherlands)

    1995-12-31

    Because of the need for sensitive measures of low level contaminants in European sediments, a chronic sediment toxicity test method, using Chironomus riparius has been developed as part of a collaborative program for the European Commission. The protocol is a partial life cycle test exposing the animals from egg stage to pre-emergence in sediment-water systems. In 1995 the protocol was ring tested in several laboratories in Europe, the US and Canada using the moth-proofer permethrin as a model substance. This was spiked into a natural sediment using a spiking protocol also developed in this program. Results of the ring test and details of the protocols will be presented.

  10. A mechanistic redefinition of adverse effects - a key step in the toxicity testing paradigm shift.

    Science.gov (United States)

    Boekelheide, Kim; Andersen, Melvin E

    2010-01-01

    The efforts of the committee that produced the report on Toxicity Testing in the 21st Century reflected the need to look at the issue of assessing risks to humans from exposure to various chemicals through a lens of 21st century biology. The problem - determining if there is a risk of specific exposures - is as old as humanity; every generation brings its own perspective and tools for examining the problem and coming to answers and solutions. Bringing this generation's tools to bear requires us to see the problem of chemical risk assessment in a different light, both in terms of testing of toxicity pathways in vitro and in the interpretation of the tests for estimating whether exposures will be safe. One key issue will be to assess when pathway perturbations are believed to be excessive, i.e., when they are deemed adverse. Redefinition of adversity based on in vitro testing will require a new perception of dose response functions as probabilities of failures, with multiple underlying processes acting sequentially and in parallel leading to failure at a cellular and an organism level. These dose response relationships for adversity will also require a computational systems biology approach for examining toxicity pathway dynamics and stress pathway overload. While the overall approach of defining adversity for in vitro endpoints and using this definition of adversity for risk assessment can be painted in broad brush strokes, as we have done here for DNA-reactive compounds, it will take implementation with a series of prototypes to show the process in practice.

  11. Acute toxicity and inactivation tests of CO2 on invertebrates in drinking water treatment systems.

    Science.gov (United States)

    Yin, Wen-Chao; Zhang, Jin-Song; Liu, Li-Jun; Zhao, Jian-Shu; Li, Tuo

    2011-01-01

    In addition to the esthetic problem caused by invertebrates, researchers are recently starting to be more aware of their potential importance in terms of public health. However, the inactivation methods of invertebrates which could proliferate in drinking water treatment systems are not well developed. The objective of this study is to assess the acute toxicity and inactivation effects of CO2 on familiar invertebrates in water treatment processes. The results of this study revealed that CO2 has a definite toxicity to familiar invertebrates. The values of 24-h LC50 (median lethal concentration) were calculated for each test with six groups of invertebrates. The toxicity of CO2 was higher with increasing concentrations in solution but was lower with the increase in size of the invertebrates. Above the concentration of 1,000 mg/L for the CO2 solution, the 100% inactivation time of all the invertebrates was less than 5 s, and in 15 min, the inactivation ratio showed a gradient descent with a decline in concentration. As seen for Mesocyclops thermocyclopoides, by dosing with a sodium bicarbonate solution first and adding a dilute hydrochloric acid solution 5 min later, it is possible to obtain a satisfactory inactivation effect in the GAC (granular activated carbon) filters.

  12. Green Tea Protects Testes against Atrazine-induced Toxicity in Rat

    Directory of Open Access Journals (Sweden)

    Reza Kheirandish

    2017-06-01

    Full Text Available Background: Atrazine (ATZ is a common herbicide in agriculture for control of grass and broad-leaved weeds. It persists in the environment and causes reproductive problems in both human and animals. The present study was aimed at protective effect of green tea against ATZ toxicity in the reproductive system of male rats. Methods: The present study was performed in Veterinary School, Shahid Bahonar University of Kerman in 2016. ATZ and treatment groups received ATZ daily 200 mg/kg BW orally for 14 d. In addition, 0.2% methanolic green tea extract was administrated in the treatment group. Results: In histopathologic investigation, number of germinal layers reduced in the most seminiferous tubules in the ATZ group and spermatids were absence. Necrotic spermatocytes, spermatids, and spermatozoa were evident in the testicular tubules. In the morphometric measurements, tubular diameter, germinal epithelium height, and meiosis index decreased significantly. Conclusion: Green tea extract had reduced testicular toxicity of atrazine significantly. ATZ induces toxicity through oxidative damage and green tea extract can protect the testes due to antioxidant activity of its polyphenols especially flavonoids.

  13. Use of power analysis to develop detectable significance criteria for sea urchin toxicity tests

    Science.gov (United States)

    Carr, R.S.; Biedenbach, J.M.

    1999-01-01

    When sufficient data are available, the statistical power of a test can be determined using power analysis procedures. The term “detectable significance” has been coined to refer to this criterion based on power analysis and past performance of a test. This power analysis procedure has been performed with sea urchin (Arbacia punctulata) fertilization and embryological development data from sediment porewater toxicity tests. Data from 3100 and 2295 tests for the fertilization and embryological development tests, respectively, were used to calculate the criteria and regression equations describing the power curves. Using Dunnett's test, a minimum significant difference (MSD) (β = 0.05) of 15.5% and 19% for the fertilization test, and 16.4% and 20.6% for the embryological development test, for α ≤ 0.05 and α ≤ 0.01, respectively, were determined. The use of this second criterion reduces type I (false positive) errors and helps to establish a critical level of difference based on the past performance of the test.

  14. Sediment toxicity test results for the Urban Waters Study 2010, Bellingham Bay, Washington

    Science.gov (United States)

    Biedenbach, James M.

    2011-01-01

    The Washington Department of Ecology annually determines the quality of recently deposited sediments in Puget Sound as a part of Ecology's Urban Waters Initiative. The annual sediment quality studies use the Sediment Quality Triad (SQT) approach, thus relying on measures of chemical contamination, toxicity, and benthic in-faunal effects (Chapman, 1990). Since 2002, the studies followed a rotating sampling scheme, each year sampling a different region of the greater Puget Sound Basin. During the annual studies, samples are collected in locations selected with a stratified-random design, patterned after the designs previously used in baseline surveys completed during 1997-1999 (Long and others, 2003; Wilson and Partridge, 2007). Sediment samples were collected by personnel from the Washington Department of Ecology, in June of 2010 and shipped to the U. S. Geological Survey (USGS) laboratory in Corpus Christi, Texas (not shown), where the tests were performed. Sediment pore water was extracted with a pneumatic apparatus and was stored frozen. Just before testing, water-quality measurements were made and salinity adjusted, if necessary. Tests were performed on a dilution series of each sample consisting of 100-, 50-, and 25-percent pore-water concentrations. The specific objectives of this study were to: * Extract sediment pore water from a total of 30 sediment samples from the Bellingham Bay, Washington area within a day of receipt of the samples. * Measure water-quality parameters (salinity, dissolved oxygen, pH, sulfide, and ammonia) of thawed pore-water samples before testing and adjust salinity, temperature and dissolved oxygen, if necessary, to obtain optimal ranges for the test species. * Conduct the fertilization toxicity test with pore water using sea urchin (Stronylocentrotus purpuratus) (S. purpuratus) gametes. * Perform quality control assays with reference pore water, dilution blanks and a positive control dilution series with sodium dodecyl sulfate (SDS

  15. Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

    Science.gov (United States)

    Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

    2017-02-01

    Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

  16. Toxicity testing and chemical analyses of recycled fibre-based paper for food contact

    DEFF Research Database (Denmark)

    Binderup, Mona-Lise; Pedersen, Gitte Alsing; Vinggaard, Anne

    2002-01-01

    of different qualities as food-contact materials and to Perform a preliminary evaluation of their suitability from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B......Food-contact materials, including paper, have to comply with a basic set of criteria concerning safety. This means that paper for food contact should not give rise to migration of components, which can endanger human health. The objectives of this pilot study were, first, to compare paper...

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

    Directory of Open Access Journals (Sweden)

    Débora Rebechi

    2014-09-01

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

  18. Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

    Science.gov (United States)

    Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

    2017-02-01

    The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

  19. Controlling silver nanoparticle exposure in algal toxicity testing - A matter of timing

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard; Baun, Anders

    2015-01-01

    (AgNPs), by reducing the incubation time and by aging the AgNPs in algal medium prior to testing. The freshwater green algae Pseudokirchneriella subcapitata were exposed to AgNO3, NM-300 K (a representative AgNP) and citrate stabilized AgNPs from two different manufacturers (AgNP1 and AgNP2......The aquatic ecotoxicity testing of nanoparticles is complicated by unstable exposure conditions resulting from various transformation processes of nanoparticles in aqueous suspensions. In this study, we investigated the influence of exposure timing on the algal test response to silver nanoparticles......) in a standard algal growth inhibition test (ISO 8692:2004) for 48 h and a short-term (2 h) 14C-assimilation test. For AgNO3, similar responses were obtained in the two tests, whereas freshly prepared suspensions of citrate stabilized AgNPs were less toxic in the 2-h tests compared to the 48-h tests. The 2-h...

  20. Uptake, translocation and elimination in sediment-rooted macrophytes: A model-supported analysis of whole sediment toxicity test data

    NARCIS (Netherlands)

    Diepens, N.J.; Arts, G.H.P.; Focks, A.; Koelmans, A.A.

    2014-01-01

    Understanding bioaccumulation in sediment-rooted macrophytes is crucial for the development of sediment toxicity tests using macrophytes. Here we explore bioaccumulation in sediment-rooted macrophytes by tracking and modelling chemical flows of chlorpyrifos, linuron, and six PCBs in

  1. Pollution-induced community tolerance of freshwater biofilms: Measuring heterotrophic tolerance to Pb using an enzymatic toxicity test

    OpenAIRE

    2012-01-01

    This study aims at investigating the impacts of Pb on freshwater biofilms with a pollution-induced community tolerance (PICT) approach using a recently developed short-term toxicity test based on b-glucosidase activity to measure biofilms' tolerance to Pb. We first investigated more closely the influence of the total suspended solids (TSS) concentrations of biofilm suspensions used for shortterm toxicity tests performed to assess Pb tolerance. The Pb EC50 values of four dilutions of the same ...

  2. 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.

  3. 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.

  4. Comparison of four chronic sediment toxicity tests using selected marine/estuarine tests species

    Energy Technology Data Exchange (ETDEWEB)

    Sims, I.; Fleming, R. [WRc Medmenham, Marlow (United Kingdom)

    1995-12-31

    Several draft standard guidelines exist for acute marine/estuarine sediment bioassays which measure lethality over a 4 to 14 day exposure period. Although these are very useful tools for certain applications, such tests may not be useful for discriminating between sediments with the low levels of contaminants most likely to be found in UK estuaries. For this application, chronic sediment bioassays are required which allow the measurement of both lethal and sublethal effects (growth, development and reproduction). Some chronic bioassays are currently being developed for estuarine sediments by workers in Europe, America and Canada. The objectives of the study presented here were to compare four bioassays, currently in development, in terms of their sensitivity to sediment-bound lindane and to differences in particle size. The test species selected for the study were Corophium volutator, Arenicola marina, Macoma Balthica and Neanthes arenaceodentata. Three sediment types were used: high, medium and low percentage of fine material, These were achieved using mixtures of silica sand and a fine, natural, estuarine sediment, and spiked with lindane using a spiking protocol developed at WRc. The results of the study will be presented.

  5. Assessment of Grape, Plum and Orange Synthetic Food Flavourings Using in vivo Acute Toxicity Tests

    Directory of Open Access Journals (Sweden)

    Ila Monize Sousa Sales

    2017-01-01

    Full Text Available The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

  6. Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests.

    Directory of Open Access Journals (Sweden)

    Robin Mesnage

    Full Text Available The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured, heavy metals (2-3 out of 4, mostly lead and cadmium, PCDD/Fs (1-13 out of 17 and PCBs (5-15 out of 18. Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1 varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology.

  7. A Novel Experimental and Modelling Strategy for Nanoparticle Toxicity Testing Enabling the Use of Small Quantities

    Directory of Open Access Journals (Sweden)

    Marinda van Pomeren

    2017-11-01

    Full Text Available Metallic nanoparticles (NPs differ from other metal forms with respect to their large surface to volume ratio and subsequent inherent reactivity. Each new modification to a nanoparticle alters the surface to volume ratio, fate and subsequently the toxicity of the particle. Newly-engineered NPs are commonly available only in low quantities whereas, in general, rather large amounts are needed for fate characterizations and effect studies. This challenge is especially relevant for those NPs that have low inherent toxicity combined with low bioavailability. Therefore, within our study, we developed new testing strategies that enable working with low quantities of NPs. The experimental testing method was tailor-made for NPs, whereas we also developed translational models based on different dose-metrics allowing to determine dose-response predictions for NPs. Both the experimental method and the predictive models were verified on the basis of experimental effect data collected using zebrafish embryos exposed to metallic NPs in a range of different chemical compositions and shapes. It was found that the variance in the effect data in the dose-response predictions was best explained by the minimal diameter of the NPs, whereas the data confirmed that the predictive model is widely applicable to soluble metallic NPs. The experimental and model approach developed in our study support the development of (ecotoxicity assays tailored to nano-specific features.

  8. Lithium protects against toxic effects of cadmium in the rat testes

    Science.gov (United States)

    Omu, Florence E.; Kehinde, Elijah O.; Anim, Jeroham T.; Oriowo, Mabayoje A.; Omu, Alexander E.

    2010-01-01

    Purpose To investigate the protective effect of Lithium against the toxic effect of Cadmium in the rat testes. Methods Twenty four adult male Sprague-Dawley rats were treated with four different regimens: Cadmium only, Cadmium and lithium, lithium only and controls. Rats were sacrificed after 6 weeks and testicular levels of pro-inflammatory cytokine (IL-4), anti-inflammatory cytokine (TNF-α), Pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) were measured by ELISA while serum levels of FSH, LH, Prolactin and Testosterone were measured using the Vidas parametric system. Antioxidant status (MDA, SOD) was also assessed in serum. Histopathological changes of testes were examined using light and electron microscopy. Immunohistochemical staining for Bax, Bcl-2 and Caspase 3 were performed. Results Treatment with lithium was associated with significant reduction in the toxic effects of Cadmium as shown by reduced testicular levels of TNF-α, serum levels of Malondialdehyde and testicular level of Bax, and increased levels of IL-4, Zn-Cu SOD, Bcl-2 and Testosterone. Testicular histopathology showed that Cadmium produced an extensive germ cells apoptosis and the addition of lithium in Cadmium-treated rats significantly reduced cadmium-induced testicular damage. Conclusion(s) Lithium has a protective effect against cadmium-induced testicular apoptosis in the rat. PMID:20455018

  9. 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.

  10. 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.

  11. Toxicity of two imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], to standard aquatic test organisms: Role of acetone in the induced toxicity.

    Science.gov (United States)

    Tsarpali, Vasiliki; Dailianis, Stefanos

    2015-07-01

    The main goal of this study was to investigate the toxicity of the imidazolium-based ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium tetrafluoroborate) and [omim][BF4] (1-octyl-3-methylimidazolium tetrafluoroborate), in battery of standard aquatic toxicity test organisms. Specifically, exposure of the algae Scenedesmus rubescens, crustaceans Thamnocephalus platyurus and Artemia franciscana, rotifers Brachionus calyciflorus and Brachionus plicatilis and bivalve Mytilus galloprovincialis to different concentrations of [bmim][BF4], [omim][BF4] and/or a binary mixture of [bmim][BF4]-[omim][BF4] (1:1) with or without acetone (carrier solvent), revealed that solvent can differentially mediate ILs' toxic profile. Acetone's ability to differentially affect ILs' cation's alkyl chain length, as well as the hydrolysis of [BF4(-)] anions was evident. Given that the toxic potency of the tested ILs seemed to be equal or even higher (in some cases) than those of conventional organic solvents, the present study revealed that the characterization of imidazolium-based ILs as "green solvents" should not be generalized, at least in case of their natural occurrence in mixtures with organic solvents, such as acetone. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

    Science.gov (United States)

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

    2016-07-01

    Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC. © 2015 SETAC.

  13. Toxicity of an herbicide and adjuvant to saltmarsh invertebrates in the management of invasive grass; Comparative laboratory and field tests.

    Science.gov (United States)

    Kleinhenz, Linda S; Nugegoda, Dayanthi; Verspaandonk, Emily R; Coombes, Darcy C; Howe, Steffan; Shimeta, Jeff

    2016-08-15

    Coastal weeds are often treated with herbicides without knowledge of non-target impacts, and toxicity data from standardized test species can have limited applicability. We evaluated toxicity to invertebrates from Fusilade Forte® and the adjuvant Hasten® in the control of invasive salt marsh grass, Spartina anglica. For 3 of 4 local invertebrates, Fusilade Forte® was moderately toxic (96h LC50 5.4-144mgL(-1)), whereas Hasten® was less toxic (14.2-450mgL(-1)). For most species, the mixture was more toxic than the herbicide alone, with 96h LC50 reduced 23-45%. However, a field experiment applying typical concentrations (1000×the lowest 96h LC50) showed low concentrations of herbicide residues and no detrimental impacts on invertebrates over 6months. The results reveal the importance of testing locally relevant species for potential toxicity, and of comparison tests with field exposures to determine the realised toxicity in nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Seasonal changes in the tests of fish Puntius ticto, and their relation to heavy metal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pundir, R. (Holkar Science College, Indore (India)); Saxena, A.B. (Vikram Univ., Ujjain (India))

    1990-08-01

    An integrated hypothesis explaining the implications of environmental influence on the reproductive process has not emerged owing to paucity of data. Nevertheless, evidence is at hand to show that favorable physiological disposition for reproduction is brought about with external and internal factors through the mediation of the neuroendocrine mechanisms. It is now clear that the environmental factors impinge on the exteroreceptors and through them affect the central nervous system, the hypothalamus, the pituitary and finally the gonad. Another endogenous factor is the internal rhythm, which is known to regulate at least in part the seasonal reproductive activity. A review of literature reveals that comparatively much work has been done on the structure and seasonal changes of the testes of fishes. The aim of the present study is to observe seasonal changes in the testes of fish Puntius ticto and their relation to heavy metal toxicity.

  15. Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials.

    Science.gov (United States)

    Ignasiak, Katarzyna; Maxwell, Anthony

    2017-08-29

    Infectivity trials and toxicity testing in rodents are important prerequisites to the use of compounds in man. However, trials in rats and mice are expensive and there are ethical considerations. Galleria mellonella (greater wax moth) larvae are a potential alternative. We have assessed the use of these insects in infectivity trials and toxicity testing. Using four bacterial species (two Gram-negative and two Gram-positive) we have assessed the efficacy of four antibiotics against infections in Galleria and compared the antibiotic susceptibility with that in humans. In general, we find a good correlation. Similarly, we have assessed 11 compounds (initially tested blind) for their toxicity in Galleria and compared this with toxicity trials in mice and rats. Again we found a good correlation between toxicity in Galleria and that in rodents. We have found, in our hands, that G. mellonella larvae can be used in infectivity trials and toxicity testing, and that these assays represent an inexpensive and readily executable alternative to testing in rodents.

  16. Anodonta imbecillis copper sulfate reference toxicant/food test, Clinch River - Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1997-06-01

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Two different foods, phytoplankton and YCT-Selenastrum (YCT-S), were tested in side by side tests to compare food quality. Toxicity testing of copper sulfate reference toxicant was conducted from July 6-15, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed LC{sub 50} values of 0.97 and 0.84 mg Cu/L for phytoplankton and YCT-S, respectively. Previously obtained values for phytoplankton tests are 2.02 and 1.12 mg Cu/L. Too few tests have been conducted with copper as the toxicant to determine a normal range of values. Although significant reduction in growth, compared to the phytoplankton control, was seen in all treatments, including the YCT-S Control, the consequence of this observation has not been established. Ninety-day testing of juvenile mussels exhibited large variations in growth within treatment and replicate groups.

  17. Heterocyclic compounds: toxic effects using algae, daphnids, and the Salmonella/microsome test taking methodical quantitative aspects into account.

    Science.gov (United States)

    Eisentraeger, Adolf; Brinkmann, Corinna; Hollert, Henner; Sagner, Anne; Tiehm, Andreas; Neuwoehner, Judith

    2008-07-01

    Heterocyclic aromatic hydrocarbons containing nitrogen, sulfur, or oxygen (NSO-HET), have been detected in air, soil, sewage sludge, marine environments, and freshwater sediments. Since toxicity data on this class of substances are scarce, the present study focuses on possible implications NSO-HET have for ecotoxicity (algae and daphnids) and mutagenicity (Salmonella/microsome test). A combination of bioassays and chemical-analytical quantification of the test compounds during toxicity assays should aid in determination of the hazard potential. Samples of the test concentrations of 14 NSO-HET were taken at the beginning and end of the bioassays; these samples were then quantified by high-performance liquid chromatography. The toxicity potential of the substances was evaluated and compared with the toxicity calculated with the nominal concentrations. Significantly different results were obtained primarily for volatile or highly hydrophobic NSO-HET. The concentration of heterocyclic hydrocarbons can change significantly during the algae and Daphnia test. The EC50 values (effective concentration value: the concentration of a chemical that is required to produce a 50% effect) calculated with the nominal concentrations underestimate the toxicity by a factor of up to 50. Prioritizing the tested compounds according to toxicity, the mutagenic and toxic compounds quinoline, 6-methylquinoline, and xanthene have to be listed first. The greatest ecotoxic potential on algae and daphnids was determined for dibenzothiophene followed by acridine. In the Daphnia magna immobilization test, benzofuran, dibenzofuran, 2-methylbenzofuran, and 2,3-dimethylbenzofuran and also carbazole are ecotoxicologically relevant with EC50 values below 10 mg/L. These substances are followed by indole with a high ecotoxic effect to daphnids and less effect to algae. Only minor toxic effects were observed for 2-methylpyridine and 2,4,6-trimethylpyridine.

  18. Estuarine sediment acute toxicity testing with the European amphipod Corophium multisetosum Stock, 1952.

    Science.gov (United States)

    Ré, Ana; Freitas, Rosa; Sampaio, Leandro; Rodrigues, Ana Maria; Quintino, Victor

    2009-09-01

    This study assessed the use of the European amphipod Corophium multisetosum Stock [Stock, J.H., 1952. Some notes on the taxonomy, the distribution and the ecology of four species of the genus Corophium (Crustacea, Malacostraca). Beaufortia 21, 1-10] in estuarine sediment acute toxicity testing. The sensitivity of adults to the reference toxicant CdCl(2) was determined in water-only 96 h exposures in salinity 2. LC(50) values ranged from 0.33mgCd(2+)L(-1) at 22 degrees C to 0.57mgCd(2+)L(-1) at 15 degrees C. Adult survival was studied in control sediment with water salinity from 0 to 36 and with fine particles content (sediment, dry weight. Experiments were conducted at 15, 18 and 22 degrees C and the results indicate that the species can be used under the full salinity range although higher mortality was observed at the lower salinity in the higher water temperature, and at the higher salinity in the lower water temperature. The species also tolerated the studied range of sediment fines content and showed the highest sensitivity at intermediate values of fines, especially at the higher temperature, thus advising that tests which have to accommodate sediments with a wide range in fines content should preferably be conducted at 15 degrees C rather than at 22 degrees C. The response in natural sediments was studied in samples collected yearly from 1997 to 2006, at a site located off the Tagus Estuary, western Portugal. A major flood event in winter 2000-2001 induced detectable alterations in sediment baseline descriptors (grain-size, redox potential and total volatile solids), organic contaminants (PAHs, PCBs, DDT metabolites and gamma-HCH) and the macrofauna benthic community. Mortality of the amphipod diminished significantly from the before to the after flood period, in close agreement with diminishing sediment contamination and increasing benthic fauna diversity, in the same time period. C. multisetosum is suitable to conduct acute sediment toxicity tests and

  19. Toxicity testing of NCSRP priority substances for the development of soil quality criteria

    Energy Technology Data Exchange (ETDEWEB)

    Cureton, P.M. [Environment Canada, Ottawa, Ontario (Canada). Evaluation and Interpretation Branch; Balch, G.; Lintott, D.; Poirrier, K.; Goudey, S. [HydroQual Labs. Ltd., Calgary, Alberta (Canada)

    1994-12-31

    The effects of 14 National Contaminated Sites Remediation Program (NCSRP) priority substances was measured on emergence and root elongation in lettuce (Lactuca saliva) and radish (Raphanus saliva) and on survival of the earthworm Eisenia foetida. The worm and seedling emergence tests were conducted in an artificial soil mixture composed of 10% peat moss, 20% kaolinite clay, and 70% silica sand (70 mesh) spiked with the contaminant. The root elongation tests were conducted on filter paper moistened with the contaminant solution. The following endpoints were derived on nominal and measured concentrations: NOEC, LOEC, the LC{sub 50} and LC{sub 25} for earthworm mortality and the EC{sub 50} and EC{sub 25} for emergence and root elongation. The contaminants tested included: arsenic, cadmium, chromium, copper, lead, mercury, zinc, vanadium, benzo(a)pyrene, cyanide, naphthalene, ethylene glycol, pentachlorophenol, and phenol. Each test was repeated three times using different batches of freshly prepared soil, seed lots and worm cultures. The authors will present the findings and discuss the application of toxicity test results in developing generic soil quality criteria.

  20. A field assessment of long-term laboratory sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Christopher G.; Wang, Ning; Hayward, Jeannie M. R.; Jones, John R.; Jones, Susan B.; Ireland, D. Scott

    2005-01-01

    Response of the amphipod Hyalella azteca exposed to contaminated sediments for 10 to 42 d in laboratory toxicity tests was compared to responses observed in controlled three-month invertebrate colonization exposures conducted in a pond. Sediments evaluated included a sediment spiked with dichlorodiphenyldichloroethane (DDD) or dilutions of a field sediment collected from the Grand Calumet River (GCR) in Indiana (USA) (contaminated with organic compounds and metals). Consistent effects were observed at the highest exposure concentrations (400 ??g DDD/goc [DDD concentrations normalized to grams of organic carbon (goc) in sedimentl or 4% GCR sediment) on survival, length, and reproduction of amphipods in the laboratory and on abundance of invertebrates colonizing sediments in the field. Effect concentrations for DDD observed for 10-d length and 42-d reproduction of amphipods (e.g., chronic value [ChV] of 66 ??g DDD/goc and 25% inhibition concentration [IC25] of 68 ??g DDD/goc for reproduction) were similar to the lowest effect concentrations for DDD measured on invertebrates colonizing sediment the field. Effect concentrations for GCR sediment on 28-d survival and length and 42-d reproduction and length of amphipods (i.e., ChVs of 0.20-0.66% GCR sediment) provided more conservative effect concentrations compared to 10-d survival or length of amphipods in the laboratory or the response of invertebrates colonizing sediment in the field (e.g., ChVs of 2.2% GCR sediment). Results of this study indicate that use of chronic laboratory toxicity tests with H. azteca and benthic colonization studies should be used to provide conservative estimates of impacts on benthic communities exposed to contaminated sediments. Bioaccumulation of DDD by oligochaetes colonizing the DDD-spiked sediment was similar to results of laboratory sediment tests previously conducted with the oligochaete Lumbriculus variegates, confirming that laboratory exposures can be used to estimate

  1. Concurrent evaluation of general, immune, and genetic toxicity endpoints as part of an integrated testing strategy.

    Science.gov (United States)

    Schisler, Melissa R; Sura, Radhakrishna; Visconti, Nicolo R; Sosinski, Lindsay K; Murphy, Lynea A; LeBaron, Matthew J; Boverhof, Darrell R

    2014-08-01

    Integrated testing strategies involve the assessment of multiple endpoints within a single toxicity study and represent an important approach for reducing animal use and streamlining testing. The present study evaluated the ability to combine general, immune, and genetic toxicity endpoints into a single study. Specifically, this study evaluated the impact of sheep red blood cell (SRBC) immunization, as part of the T-cell dependent antibody response (TDAR) assay, on organ weights, micronuclei (MN) formation (bone marrow and peripheral blood), and the Comet assay response in the liver of female F344/DuCrl rats treated with cyclophosphamide (CP) a known immunosuppressive chemical and genotoxicant. For the TDAR assay, treatment with CP resulted in a dose-dependent decrease in the antibody response with a suppression of greater than 95% at the high dose. Injection with SRBC had no impact on evaluated organ weights, histopathology, hematology, and clinical chemistry parameters. Analysis of MN formation in bone marrow and peripheral blood revealed a dose-dependent increase in response to CP treatment. Injection with SRBC had no impact on the level of MN in control animals and did not alter the dose response of CP. There was a slight increase in liver DNA damage in response to CP as measured by the Comet assay; however, injection with SRBCs did not alter this endpoint. Overall these data provide strong support for the concurrent assessment of general, immune, and genetic toxicology endpoints within a single study as part of an integrated testing strategy approach. © 2014 Wiley Periodicals, Inc.

  2. 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.

  3. Alternative acute inhalation toxicity testing by determination of the concentration-time-mortality relationship : experimental comparison with standard LC50 testing

    NARCIS (Netherlands)

    Zwart, A.; Arts, J.H.E.; Berge, W.F. ten; Appelman, L.M.

    1992-01-01

    A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a

  4. The Acute toxicity of alpha-branched phenylsulfonyl acetates in Photobacterium phosphoreum test.

    Science.gov (United States)

    Liu, X; Wu, C; Han, S; Wang, L; Zhang, Z

    2001-07-01

    The acute toxicity (15-min EC(50)) of 20 alpha-substituted phenylsulfonyl acetates was measured using the Microtox test with Photobacterium phosphoreum. On the basis of TLSER, quantitative structure-activity relationships (QSARs) were calculated for the inhibition of bioluminescence. With the parameters molecular volume (V(mc)), dipolarity/polarizability (pi*), and the covalent contribution to Lewis basicity (epsilon(b)), a squared correlation coefficient (r(2)(adj)) of 0.868 and standard error of 0.094 for log EC(50) were obtained. By introducing a structural indicator variable (I), the regressive quality was improved (correlation coefficient of 0.948 and standard error of 0.059); the descriptors V(mc), pi*, and the electrostatic basicity contribution (q(-)) were significant. -NO(2)-- and -SO(2)--groups are active centers of these compounds. The strong hydrogen bonding effects between the compound active centers and FMNH(2) play an important role in the greater toxicity of these chemicals. Copyright 2001 Academic Press.

  5. Metal toxicity and biodiversity in serpentine soils: application of bioassay tests and microarthropod index.

    Science.gov (United States)

    Visioli, Giovanna; Menta, Cristina; Gardi, Ciro; Conti, Federica Delia

    2013-01-01

    Eco-toxicological or bioassay tests have been intensively discussed as tools for the evaluation of soil quality. Tests using soil organisms, including microarthropods and plants, allow direct estimates to be made of important soil characteristics and functions. In this study we compared the results obtained by two in vitro standard bioassays following ISO or OECD guidelines: (i) the short term-chronic phytotoxicity germination and root elongation test using three different plant species Cucumis sativus L. (Cucurbitaceae), Lepidium sativum L. (Brassicaceae), and Medicago sativa L. (Fabaceae) and (ii) the inhibition of reproduction of Folsomia candida (Collembola) by soil pollutants to investigate the toxicity of a serpentine soil present in the Italian Apennines, rich in heavy metals such as Ni, Cr, and Co. In addition, microarthropod communities were characterised to evaluate the effects of metal contents on the soil fauna in natural conditions. Abundances, Acari/Collembola ratio, biodiversity indices and the QBS-ar index were calculated. Our results demonstrate that the two in vitro tests distinguish differences correlated with metal and organic matter contents in four sub-sites within the serpentinite. Soil fauna characterisation, not previously performed on serpentine soils, revealed differences in the most vulnerable and adapted groups of microarthropods to soil among the four sub-sites: the microarthropod community was found to be rich in term of biodiversity in the sub-site characterised by a lower metal content and a higher organic matter content and vegetation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. TOXICITY TESTING OF RESTORATIVE DENTAL MATERIALS USING BRINE SHRIMP LARVAE (ARTEMIA SALINA)

    Science.gov (United States)

    Milhem, Manar M.; Al-Hiyasat, Ahmad S.; Darmani, Homa

    2008-01-01

    This study investigated the effect of extracts of different composites, glass ionomer cement (GIC)s and compomers on the viability of brine shrimp larvae. Ethanolic extracts of four dental composites (Z-100; Solitaire 2; Filtek P60 and Synergy), a conventional GIC (Ketac-Fil), a resin-modified glass ionomer cement (Vitremer), two compomers (F2000; Dyract AP), and a flowable compomer (Dyract Flow) were prepared from each material. Following evaporation of the ethanol, the extracts were resuspended in distilled water, which was then used to test the effects on the viability of brine shrimp larvae. For the composites, the extract of Synergy was the least toxic (88% viability) followed by the extracts of Solitaire 2, Z100 and P60 (75%, 67.5% and 50% viability, respectively). One-way ANOVA revealed highly significant differences between the resin composite materials (pbrine shrimp larvae followed by GICs and then composites. PMID:19089264

  7. Bio-testing integral toxicity of corrosion inhibitors, biocides and oil hydrocarbons in oil-and gas-processing industry

    Energy Technology Data Exchange (ETDEWEB)

    Chugunov, V.A.; Kholodenko, V.P.; Irkhina, I.A.; Fomchenkov, V.M.; Novikov, I.A. [State Research Center for Applied Microbiology, Obolensk, Moscow (Russian Federation)

    2004-07-01

    In recent years bioassays have been widely used for assessing levels of contamination of the environment. This is due to the fact that test-organisms provide a general response to toxicants present in samples. Based on microorganisms as test objects, it is possible to develop cheap, sensitive and rapid assays to identify environmental xenobiotics and toxicants. The objective of the research was to develop different microbiological assays for assessing integral toxicity of water environments polluted with corrosion inhibitors, biocides and hydrocarbons in oil- and gas-processing industry. Bio-luminescent, electro-orientational, osmo-optic and microorganism reducing activity assays were used for express evaluation of integral toxicity. They are found to determine promptly integral toxicity of water environments containing various pollutants (oil, oil products, corrosion inhibitors, biocides). Results conclude that the assays may be used for analyzing integral toxicity of water polluted with hydrocarbons, as well as for monitoring of water changes as a result of biodegradation of pollutants by microorganisms and their associations. Using a kit of different assays, it is also possible to evaluate ecological safety of biocides, corrosion inhibitors, and their compositions. Bioassays used as a kit are more effective than each assay individually, allowing one to get complete characterization of a reaction of bacterial test organisms to different environments. (authors)

  8. The SOS-LUX-LAC-FLUORO-Toxicity-test on the International Space Station (ISS)

    Science.gov (United States)

    Rabbow, E.; Rettberg, P.; Baumstark-Khan, C.; Horneck, G.

    In the 21 st century, an increasing number of astronauts will visit the International Space Station (ISS) for prolonged times. Therefore it is of utmost importance to provide necessary basic knowledge concerning risks to their health and their ability to work on the station and during extravehicular activities (EVA) in free space. It is the aim of one experiment of the German project TRIPLE-LUX (to be flown on the ISS) to provide an estimation of health risk resulting from exposure of the astronauts to the radiation in space inside the station as well as during extravehicular activities on one hand, and of exposure of astronauts to unavoidable or as yet unknown ISS-environmental genotoxic substances on the other. The project will (i) provide increased knowledge of the biological action of space radiation and enzymatic repair of DNA damage, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation and (iii) examine the space craft milieu with highly specific biosensors. For these investigations, the bacterial biosensor SOS-LUX-LAC-FLUORO-Toxicity-test will be used, combining the SOS-LUX-Test invented at DLR Germany (Patent) with the commercially available LAC-FLUORO-Test. The SOS-LUX-Test comprises genetically modified bacteria transformed with the pBR322-derived plasmid pPLS-1. This plasmid carries the promoterless lux operon of Photobacterium leiognathi as a reporter element under control of the DNA-damage dependent SOS promoter of ColD as sensor element. This system reacts to radiation and other agents that induce DNA damages with a dose dependent measurable emission of bioluminescence of the transformed bacteria. The analogous LAC-FLUORO-Test has been developed for the detection of cellular responses to cytotoxins. It is based on the constitutive expression of green fluorescent protein (GFP) mediated by the bacterial protein expression vector pGFPuv (Clontech, Palo Alto, USA). In response to cytotoxic agents, this system

  9. Static renewal tests using Anodonta imbecillis (freshwater mussels). Anodonta imbecillis copper sulfate reference toxicant/food test, Clinch River-Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1993-12-31

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Two different foods, phytoplankton and YCT-Selenastrum (YCT-S), were tested in side by side tests to compare food quality. Toxicity testing of copper sulfate reference toxicant was conducted from July 6--15, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Although significant reduction in growth, compared to the phytoplankton control, was seen in all treatments, including the YCT-S Control, the consequence of this observation has not been established. Ninety-day testing of juvenile mussels exhibited large variations in growth within treatment and replicate groups. Attachments to this report include: Toxicity test bench sheets and statistical analyses; and Copper analysis request and results.

  10. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    Science.gov (United States)

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  11. Toxicity evaluation of single and mixed antifouling biocides using the Strongylocentrotus intermedius sea urchin embryo test.

    Science.gov (United States)

    Wang, Heng; Li, Yan; Huang, Honghui; Xu, Xue; Wang, Yonghua

    2011-03-01

    The present study evaluated the single and mixed toxicities of commonly used antifouling biocides (copper pyrithione, Sea nine 211, dichlofluanid, tolylfluanid, and Irgarol 1051) on the early embryogenesis of sea urchin Strongylocentrotus intermedius. Their toxicities were quantified in terms of the median effective concentration (EC50) reducing the embryogenesis success by 50%. For individual biocides to the embryos, the toxicity was in order of copper pyrithione>Sea nine 211> tolylfluanid>dichlofluanid>Irgarol 1051. The toxicities of mixture (binary, ternary, quaternary, and quinary) of compounds, evaluated by toxic unit, additivity index, and mixture toxicity index, showed that the copper pyrithione-Sea nine 211 combination was the most toxic with the EC50 value of 7.87 nM in all mixtures. Synergistic enhancements of toxicity were observed for all mixtures except the combination of tolylfluanid-Sea nine 211, revealing antagonistic effect. Both the concentration addition and independent action concepts failed to accurately predict the mixture toxicities of the antifouling combinations; thus, a new log K(OW)-based model was developed to predict the combined toxicities of these antifouling chemicals, which were capable of predicting the mixture toxicities of antifouling biocides (R(2)=0.33). Copyright © 2011 SETAC.

  12. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    Science.gov (United States)

    2012-07-23

    ... significant pain and distress to test animals (ICCVAM, 2008). The acute dermal systemic toxicity UDP protocol... products and that reduce, refine (enhance animal well-being and lessen or avoid pain and distress), or... (OECD) Test Guideline 425 in 2001 (OECD, 2001). The oral UDP reduces animal use by up to 70% compared to...

  13. An optimized gene set for transcriptomics based neurodevelopmental toxicity prediction in the neural embryonic stem cell test

    NARCIS (Netherlands)

    Pennings, J.L.A.; Theunissen, P.T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    The murine neural embryonic stem cell test (ESTn) is an in vitro model for neurodevelopmental toxicity testing. Recent studies have shown that application of transcriptomics analyses in the ESTn is useful for obtaining more accurate predictions as well as mechanistic insights. Gene expression

  14. Comparative Toxicity of Louisiana Sweet Crude Oil (LSC) and Chemically Dispersed LSC to Two Gulf of Mexico Aquatic Test Species.

    Science.gov (United States)

    Environmental Protection Agency released peer reviewed results from the second phase of its independent toxicity testing on mixtures of eight oil dispersants with Louisiana Sweet Crude Oil. EPA conducted the tests as part of an effort to ensure that EPA decisions remain grounded ...

  15. Effect-based interpretation of toxicity test data using probability and comparison with alternative methods of analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gully, J.R.; Baird, R.B.; Markle, P.J.; Bottomley, J.P.

    2000-01-01

    A methodology is described that incorporates the intra- and intertest variability and the biological effect of bioassay data in evaluating the toxicity of single and multiple tests for regulatory decision-making purposes. The single- and multiple-test regulatory decision probabilities were determined from t values (n {minus} 1, one-tailed) derived from the estimated biological effect and the associated standard error at the critical sample concentration. Single-test regulatory decision probabilities below the selected minimum regulatory decision probability identify individual tests as noncompliant. A multiple-test regulatory decision probability is determined by combining the regulatory decision probability of a series of single tests. A multiple-test regulatory decision probability is determined by combining the regulatory decision probability of a series of single tests. A multiple-test regulatory decision probability below the multiple-test regulatory decision minimum identifies groups of tests in which the magnitude and persistence of the toxicity is sufficient to be considered noncompliant or to require enforcement action. Regulatory decision probabilities derived from the t distribution were compared with results based on standard and bioequivalence hypothesis tests using single- and multiple-concentration toxicity test data from an actual national pollutant discharge incorporated the precision of the effect estimate into regulatory decisions at a fixed level of effect. Also, probability-based interpretation of toxicity tests provides incentive to laboratories to produce, and permit holders to use, high-quality, precise data, particularly when multiple tests are used in regulatory decisions. These results are contrasted with standard and bioequivalence hypothesis tests in which the intratest precision is a determining factor in setting the biological effect used for regulatory decisions.

  16. Toxicity test procedures for Hyalella azteca, and chronic toxicity of cadmium and pentachlorophenol to H. azteca, Gammarus fasciatus, and Daphnia magna.

    Science.gov (United States)

    Borgmann, U; Ralph, K M; Norwood, W P

    1989-09-01

    Survival, growth, and reproduction of Hyalella azteca were determined under various test conditions. Reproduction by a cohort begins when the amphipods are 5 to 6 weeks old, peaks at 8 to 12 weeks, and then declines due to continuing adult mortality. Full life-cycle tests can be completed in 12 to 14 weeks at 25 degrees C. Reproduction is poor when only artificial plastic substrate is provided. A substrate of cotton gauze results in dramatic improvements in both reproduction and growth. Better reproduction can be obtained by culturing the amphipods in some sediments, but this makes weekly enumeration difficult. Increased mortality during chronic exposure to cadmium was observed at 1 microgram/L for H. azteca and 3.2 micrograms/L for Gammarus fasciatus. Reproduction during longer exposure was not reduced at concentrations lower than those causing increased mortality within six weeks. Chronic toxicity of pentachlorophenol was observed at 100 micrograms/L for both species. Chronic toxicity to Daphnia magna was similar to that of the amphipods for cadmium, but lower for pentachlorophenol. Amphipods are at least as sensitive as Daphnia to a variety of toxicants during chronic exposure.

  17. Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high throughput alternatives to animal tests.

    Science.gov (United States)

    Lee, Dong Woo; Oh, Woo-Yeon; Yi, Sang Hyun; Ku, Bosung; Lee, Moo-Yeal; Cho, Yoon Hee; Yang, Mihi

    2016-09-30

    Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate. We applied a total of 28 different enzymes to each chip, including 10 cytochrome P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme mixtures, phase II enzyme mixtures, and a combination of phase I and phase II enzymes were also applied to the chip. BPA toxicity was higher in samples containing CYP2E1 than controls, which contained no enzymes (IC50, 184±16μM and 270±25.8μM, respectively, palternative to animal testing for estimating BPA toxicity via human metabolic systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Variability of sediment-contact tests in freshwater sediments with low-level anthropogenic contamination - Determination of toxicity thresholds

    Energy Technology Data Exchange (ETDEWEB)

    Hoess, S., E-mail: hoess@ecossa.d [Ecossa, Giselastr. 6, 82319 Starnberg (Germany); Institute of Biodiversity - Network (IBN), Dreikronengasse 2, 93047 Regensburg (Germany); Ahlf, W., E-mail: ahlf@tu-harburg.d [Institute of Environmental Technology and Energy Economics, Technical University Hamburg-Harburg, Eissendorfer Str. 40, 21071 Hamburg (Germany); Fahnenstich, C. [Institute of Environmental Technology and Energy Economics, Technical University Hamburg-Harburg, Eissendorfer Str. 40, 21071 Hamburg (Germany); Gilberg, D., E-mail: d-gilberg@ect.d [ECT Oekotoxikologie, Boettgerstr. 2-14, 65439 Floersheim (Germany); Hollert, H., E-mail: henner.hollert@bio5.rwth-aachen.d [Department of Ecosystem Analysis, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Melbye, K. [Dr. Fintelmann and Dr. Meyer, Mendelssohnstr. 15D, 22761 Hamburg (Germany); Meller, M., E-mail: m-meller@ecotox-consult.d [ECT Oekotoxikologie, Boettgerstr. 2-14, 65439 Floersheim (Germany); Hammers-Wirtz, M., E-mail: hammers-wirtz@gaiac.rwth-aachen.d [Research Institute for Ecosystem Analysis and Assessment (gaiac), RWTH Aachen University, Worringerweg 1, 52056 Aachen (Germany); Heininger, P., E-mail: heininger@bafg.d [Federal Institute of Hydrology (BfG), Am Mainzer Tor 1, 56070 Koblenz (Germany); Neumann-Hensel, H., E-mail: hensel@fintelmann-meyer.d [Dr. Fintelmann and Dr. Meyer, Mendelssohnstr. 15D, 22761 Hamburg (Germany); Ottermanns, R., E-mail: ottermanns@bio5.rwth-aachen.d [Chair for Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Ratte, H.-T., E-mail: toni.ratte@bio5.rwth-aachen.d [Chair for Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany)

    2010-09-15

    Freshwater sediments with low levels of anthropogenic contamination and a broad range of geochemical properties were investigated using various sediment-contact tests in order to study the natural variability and to define toxicity thresholds for the various toxicity endpoints. Tests were performed with bacteria (Arthrobacter globiformis), yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), oligochaetes (Lumbriculus variegatus), higher plants (Myriophyllum aquaticum), and the eggs of zebrafish (Danio rerio). The variability in the response of some of the contact tests could be explained by particle size distribution and organic content. Only for two native sediments could a pollution effect not be excluded. Based on the minimal detectable difference (MDD) and the maximal tolerable inhibition (MTI), toxicity thresholds (% inhibition compared to the control) were derived for each toxicity parameter: >20% for plant growth and fish-egg survival, >25% for nematode growth and oligochaete reproduction, >50% for nematode reproduction and >60% for bacterial enzyme activity. - Sediment-contact tests require toxicity thresholds based on their variability in native sediments with low-level contamination.

  19. Automated Lab-on-a-Chip Technology for Fish Embryo Toxicity Tests Performed under Continuous Microperfusion (μFET).

    Science.gov (United States)

    Zhu, Feng; Wigh, Adriana; Friedrich, Timo; Devaux, Alain; Bony, Sylvie; Nugegoda, Dayanthi; Kaslin, Jan; Wlodkowic, Donald

    2015-12-15

    The fish embryo toxicity (FET) biotest has gained popularity as one of the alternative approaches to acute fish toxicity tests in chemical hazard and risk assessment. Despite the importance and common acceptance of FET, it is still performed in multiwell plates and requires laborious and time-consuming manual manipulation of specimens and solutions. This work describes the design and validation of a microfluidic Lab-on-a-Chip technology for automation of the zebrafish embryo toxicity test common in aquatic ecotoxicology. The innovative device supports rapid loading and immobilization of large numbers of zebrafish embryos suspended in a continuous microfluidic perfusion as a means of toxicant delivery. Furthermore, we also present development of a customized mechatronic automation interface that includes a high-resolution USB microscope, LED cold light illumination, and miniaturized 3D printed pumping manifolds that were integrated to enable time-resolved in situ analysis of developing fish embryos. To investigate the applicability of the microfluidic FET (μFET) in toxicity testing, copper sulfate, phenol, ethanol, caffeine, nicotine, and dimethyl sulfoxide were tested as model chemical stressors. Results obtained on a chip-based system were compared with static protocols performed in microtiter plates. This work provides evidence that FET analysis performed under microperfusion opens a brand new alternative for inexpensive automation in aquatic ecotoxicology.

  20. Amphipod and Sea Urchin tests to assess the toxicity of Mediterranean sediments: the case of Portmán Bay

    Directory of Open Access Journals (Sweden)

    A. Cesar

    2004-04-01

    Full Text Available The sediment formed by the tailings of an abandoned mine, which discharged into Portmán Bay, Murcia, SE-Spain, was tested to establish a possible gradient of heavy metals. The results were compared with tolerance limits of what was calculated from control sites. Whole sediment toxicity tests were performed on two amphipod species, Gammarus aequicauda and Microdeutopus gryllotalpa, while sediment-water interface and porewater toxicity tests were performed on three sea urchins species, Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis. The sensitivity of these marine organisms was evaluated by exposure tests using the reference substances: ammonium chloride (NH4Cl, cadmium chloride (CdCl2, potassium dichromate (K2Cr2O7, sodium dodecyl sulfate (C12H25NaO4S and zinc sulfate (ZnSO4. The concentration of heavy metals decreased along the pollution gradient. Amphipod 10 day acute toxicity tests clearly demonstrated the gradient of toxicity. The sediment-water interface tests conducted with sea urchins also pointed to a pollution gradient and were more sensitive than the tests involving amphipods.

  1. Testing the toxicity of metals, phenol, effluents, and receiving waters by root elongation in Lactuca sativa L.

    Science.gov (United States)

    Lyu, Jie; Park, Jihae; Kumar Pandey, Lalit; Choi, Soyeon; Lee, Hojun; De Saeger, Jonas; Depuydt, Stephen; Han, Taejun

    2018-03-01

    Phytotoxicity tests using higher plants are among the most simple, sensitive, and cost-effective of the methods available for ecotoxicity testing. In the present study, a hydroponic-based phytotoxicity test using seeds of Lactuca sativa was used to evaluate the water quality of receiving waters and effluents near two industrial sites (Soyo and Daejon) in Korea with respect to the toxicity of 10 metals (As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, Zn) and phenol, and of the receiving waters and effluents themselves. First, the L. sativa hydroponic bioassay was used to determine whether the receiving water or effluents were toxic; then, the responsible toxicant was identified. The results obtained with the L. sativa bioassay ranked the EC 50 toxicities of the investigated metal ions and phenol as: Cd > Ni > Cu > Zn > Hg > phenol > As > Mn > Cr > Pb > Fe. We found that Zn was the toxicant principally responsible for toxicity in Daejeon effluents. The Daejeon field effluent had a higher Zn concentration than permitted by the effluent discharge criteria of the Ministry of Environment of Korea. Our conclusion on the importance of Zn toxicity was supported by the results of the L. sativa hydroponic assay, which showed that the concentration of Zn required to inhibit root elongation in L. sativa by 50% (EC 50 ) was higher in the Daejeon field effluent than that of pure Zn. More importantly, we proved that the L. sativa hydroponic test method can be applied not only as an alternative tool for determining whether a given waste is acceptable for discharge into public water bodies, but also as an alternative method for measuring the safety of aquatic environments using EC 20 values, with respect to the water pollutants investigated (i.e., Cd, Cr, Cu, Pb, Mn, Hg, Ni, Zn, and phenol). Copyright © 2017. Published by Elsevier Inc.

  2. 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.

  3. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States); Wappel, Robert L.; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M. [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States); Kramer, James W.; Brown, Arthur M. [ChanTest Corporation, 14656 Neo Parkway, Cleveland, OH 44128 (United States); Shell, Scott A.; Bacus, Sarah [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States)

    2013-10-01

    Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether-à-go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channel function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: • TKi with known adverse effects show unique cardiotoxicity profiles in this panel. • Crizotinib increases ROS, apoptosis, and

  4. The Influence of Test Conditions on the Performance of Chironomus dilutus and Hyalella azteca in Sediment Toxicity Tests

    Science.gov (United States)

    In most all sediment toxicity assessments, the performance of organisms in control sediments is a key parameter in defining sediment toxicity, whether through direct statistical comparison to control or by normalizing to control performance to compare results across sites or batc...

  5. Toxic Emissions from a Military Test Site in the Territory of Sardinia, Italy

    Science.gov (United States)

    Cristaldi, Mauro; Foschi, Cristiano; Szpunar, Germana; Brini, Carlo; Marinelli, Fiorenzo; Triolo, Lucio

    2013-01-01

    This work assesses the environmental impact from chemical emissions due to military tests and routine activities in the area occupied by the Italian Inter-force Test Range (PISQ), located at Salto di Quirra, Sardinia, Italy. After reviewing the military activities carried out at PISQ, such as rocket launching, blasting and armament destruction, projectile and mortar fire impact, the associated pollution is evaluated. Chemical analyses were performed by means of Scanning Electronic Microscopy and Energy Dispersion Spectrometry on biotic and abiotic matrices. Residues of Rb, Tl, W, Ti and Al were found in matrices collected in the PISQ areas and environs. A review of experimental data on air, water, soil, milk, forage and animal tissues obtained by various Public Agencies of Sardinia proved that toxic element residues often exceeded the legal limits. PM10 and PM2.5 air concentrations also exceeded the legal limits after military blasting. Cd and Pb contents in the liver and kidneys of sheep living in farms at PISQ and in control farms that were located more than 20 km away from PISQ were higher than the legal limits. This work was performed to investigate concentration of xenobiotics in ecosystems emitted from PISQ activities. This assessment could be useful to focus future epidemiological studies carried out in PISQ and its neighbouring areas. PMID:23603867

  6. Body-on-a-chip systems for animal-free toxicity testing.

    Science.gov (United States)

    Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

    2016-10-01

    Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

  7. Preparation and characterization of nickel-spiked freshwater sediments for toxicity tests: toward more environmentally realistic nickel partitioning.

    Science.gov (United States)

    Brumbaugh, William G; Besser, John M; Ingersoll, Christopher G; May, Thomas W; Ivey, Chris D; Schlekat, Christian E; Garman, Emily Rogevich

    2013-11-01

    Two spiking methods were compared and nickel (Ni) partitioning was evaluated during a series of toxicity tests with 8 different freshwater sediments having a range of physicochemical characteristics. A 2-step spiking approach with immediate pH adjustment by addition of NaOH at a 2:1 molar ratio to the spiked Ni was effective in producing consistent pH and other chemical characteristics across a range of Ni spiking levels. When Ni was spiked into sediment having a high acid-volatile sulfide and organic matter content, a total equilibration period of at least 10 wk was needed to stabilize Ni partitioning. However, highest spiking levels evidently exceeded sediment binding capacities; therefore, a 7-d equilibration in toxicity test chambers and 8 volume-additions/d of aerobic overlying water were used to avoid unrealistic Ni partitioning during toxicity testing. The 7-d pretest equilibration allowed excess spiked Ni and other ions from pH adjustment to diffuse from sediment porewater and promoted development of an environmentally relevant, 0.5- to 1-cm oxic/suboxic sediment layer in the test chambers. Among the 8 different spiked sediments, the logarithm of sediment/porewater distribution coefficient values (log Kd ) for Ni during the toxicity tests ranged from 3.5 to 4.5. These Kd values closely match the range of values reported for various field Ni-contaminated sediments, indicating that testing conditions with our spiked sediments were environmentally realistic. © 2013 SETAC.

  8. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    Science.gov (United States)

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. Copyright © 2011 SETAC.

  9. Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

    Science.gov (United States)

    Twaddle, Nathan C; Churchwell, Mona I; McDaniel, L Patrice; Doerge, Daniel R

    2004-06-30

    Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of

  10. Standardizing acute toxicity data for use in ecotoxicology models: influence of test type, life stage, and concentration reporting.

    Science.gov (United States)

    Raimondo, Sandy; Vivian, Deborah N; Barron, Mace G

    2009-10-01

    Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. However, the extent to which data standardization is necessary remains unclear, particularly when data transformations are used in model development. An extensive acute toxicity database was compiled for aquatic species to comprehensively assess the variation associated with acute toxicity test type (e.g., flow-through, static), reporting concentrations as nominal or measured, and organism life stage. Three approaches were used to assess the influence of these factors on log-transformed acute toxicity: toxicity ratios, log-linear models of factor groups, and comparison of interspecies correlation estimation (ICE) models developed using either standardized test types or reported concentration type. In general, median ratios were generally less than 2.0, the slopes of log-linear models were approximately one for well-represented comparisons, and ICE models developed using data from standardized test types or reported concentrations did not differ substantially. These results indicate that standardizing test data by acute test type, reported concentration type, or life stage may not be critical for developing ecotoxicological models using large datasets of log-transformed values.

  11. 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

  12. Interlaboratory validation of organism recovery for use in 42-day sediment toxicity tests with Hyalella azteca.

    Science.gov (United States)

    Taylor, Lisa N; Novak, Lesley

    2017-04-01

    Environment and Climate Change Canada has developed a 42-d sediment toxicity test that includes a reproduction endpoint with the freshwater amphipod Hyalella azteca. The new methodology conducts the entire exposure in sediment, in contrast to existing standardized methods whereby adults are transferred to a water-only exposure before release of their first brood at day 28. This midtest transfer to clean water was because of the results of a juvenile H. azteca recovery trial conducted in the 1990s concluding that reproductive endpoints could be biased because of low recovery of young amphipods from sediment. Using a new procedure and reduced volume of sediment, an interlaboratory recovery trial was conducted using 2-d to 5-d old H. azteca added to control sediment. A total of 29 technicians from 8 laboratories participated in the present study. The average recovery for all laboratories and all technicians was 76% (coefficient of variation [CV] = 30%). Based on an initial target recovery of at least 80%, 19 of 29 (66%) technicians met this criterion, with an average recovery for this group of 88% (CV = 8.3%). Factors that reduced recovery success included: not using a light table, technicians with minimal sediment testing experience, and the use of imported young amphipods with limited acclimation. Excluding those results, the overall average recovery, which included 17 participating technicians, increased from 76% to 88% and lowered the CV from 30% to 8.6%. Based on these results, Environment and Climate Change Canada will recommend ≥85% average recovery of young in control sediment and require ≥80% as a technician performance criterion in its new test design for the reproduction methodology. Environ Toxicol Chem 2017;36:1085-1089. © 2016 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC. 2016 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.

  13. The pH dependent toxicity and bioaccumulation of chloroquine tested on S. viminalis (basket willow)

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Trapp, Stefan; Legind, Charlotte Nielsen

    2010-01-01

    (hydroxymethyl) – aminomethane (pH 8 and 9). Concentrations were determined with spectrophotometer. Toxicity was derived from calculations of normalized transpiration over time, and RCF (root concentration factor) values were calculated. Increasing BCF values were found for increasing pH levels, and the toxicity...

  14. Toxicity testing of human assisted reproduction devices using the mouse embryo assay.

    NARCIS (Netherlands)

    Punt-Van der Zalm, J.P.; Hendriks, J.C.M.; Westphal, J.R.; Kremer, J.A.M.; Teerenstra, S.; Wetzels, A.M.M.

    2009-01-01

    Systems to assess the toxicity of materials used in human assisted reproduction currently lack efficiency and/or sufficient discriminatory power. The development of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst rate (BR), is used to measure toxicity. The embryos were

  15. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  16. Estimation of the critical effect level for pollution prevention based on oyster embryonic development toxicity test: the search for reliability.

    Science.gov (United States)

    da Cruz, A C S; Couto, B C; Nascimento, I A; Pereira, S A; Leite, M B N L; Bertoletti, E; Zagatto, P

    2007-05-01

    In spite of the consideration that toxicity testing is a reduced approach to measure the effects of pollutants on ecosystems, the early-life-stage (ELS) tests have evident ecological relevance because they reflect the possible reproductive impairment of the natural populations. The procedure and validation of Crassostrea rhizophorae embryonic development test have shown that it meets the same precision as other U.S. EPA tests, where EC(50) is generally used as a toxicological endpoint. However, the recognition that EC(50) is not the best endpoint to assess contaminant effects led U.S. EPA to recently suggest EC(25) as an alternative to estimate xenobiotic effects for pollution prevention. To provide reliability to the toxicological test results on C. rhizophorae embryos, the present work aimed to establish the critical effect level for this test organism, based on its reaction to reference toxicants, by using the statistical method proposed by Norberg-King (Inhibition Concentration, version 2.0). Oyster embryos were exposed to graded series of reference toxicants (ZnSO(4) x 7H(2)O; AgNO(3); KCl; CdCl(2)H(2)O; phenol, 4-chlorophenol and dodecyl sodium sulphate). Based on the obtained results, the critical value for C. rhizophorae embryonic development test was estimated as EC(15). The present research enhances the emerging consensus that ELS tests data would be adequate for estimating the chronic safe concentrations of pollutants in the receiving waters. Based on recommended criteria and on the results of the present research, zinc sulphate and 4-chlorophenol have been pointed out, among the inorganic and organic compounds tested, as the best reference toxicants for C. rhizophorae ELS-test.

  17. Rapid in situ toxicity testing with luminescent bacteria Photorhabdus luminescens and Vibrio fischeri adapted to a small portable luminometer.

    Science.gov (United States)

    Masner, Petr; Javůrková, Barbora; Bláha, Luděk

    2017-02-01

    The present study demonstrates development of a rapid testing protocol based on a small portable luminometer using flash kinetic assessment of bacterial bioluminescence. The laboratory comparisons based on six model organic toxicants and two metals showed significant correlations between responses of freshwater bacteria Photorhabdus luminescens and standard marine bacterial species Vibrio fisheri. While P. luminescens was less sensitive in standard arrangements, the responses of both organisms were comparable in the newly introduced portable luminometer setup. The applicability and reproducibility of the portable luminometer protocol was further demonstrated in the assessment of 43 European wastewater effluents that were simultaneously tested for toxicity and analysed for 150 organic and 20 inorganic contaminants grouped into 13 major chemical classes. Clear association between the toxic responses in both compared bacterial species and the elevated levels of inorganic compounds (toxic metals), chlorophenols and benzotriazole anticorrosives was observed. The new protocol with a portable luminometer provides a fast (30 s) response and may be used as a tool for rapid in situ toxicity evaluation of freshwater environmental samples such as effluents.

  18. Descriptive and mechanistic toxicity of conazole fungicides using the model test alga Dunaliella tertiolecta (Chlorophyceae).

    Science.gov (United States)

    Baird, Thomas D; DeLorenzo, Marie E

    2010-06-01

    Conazole fungicides are commonly used to prevent fungal growth on turf grass and agricultural crops. As many of these sites are adjacent to coastal waterways and estuaries, there exists the potential for nontarget effects of runoff on marine organisms. This study reports 96 h EC(50) values for four selected conazole fungicides (triadimefon = 5.98 mg/L; triadimenol = 5.51 mg/L; propiconazole = 2.33 mg/L; hexaconazole = 0.91 mg/L) to the model test alga Dunaliella tertiolecta. We further investigated possible mechanisms of toxicity by examining sublethal effects of exposure on cell morphology, osmoregulatory function, and lipid composition. These mechanistic studies revealed that conazole exposure does not inhibit synthesis of the cell's glycerol osmolyte, but does result in an overall increase in cellular volume and total lipid content. Both fungi and chlorophytes rely on ergosterol to maintain membrane structure and fluidity, and we provide evidence that the sterol-inhibiting conazoles may interfere with ergosterol biosynthesis in the cell membrane of Dunaliella. These findings suggest that green algae may be especially susceptible to nontarget effects of sterol-inhibiting fungicides in marine systems. Published 2009 by Wiley Periodicals, Inc.

  19. Morphology-based mammalian stem cell tests reveal potential developmental toxicity of donepezil.

    Science.gov (United States)

    Lau, Caroline G Y; Marikawa, Yusuke

    2014-11-01

    Various compounds, including therapeutic drugs, can adversely impact the survival and development of embryos in the uterus. Identification of such development-interfering agents is a challenging task, although multi-angle approaches--including the use of in vitro toxicology studies involving embryonic stem cells--should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose-dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse-transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior-posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development. © 2014 Wiley Periodicals, Inc.

  20. Occurrence and potential combined toxicity of dissolved organic contaminants in the Forth estuary and Firth of Forth, Scotland assessed using passive samplers and an algal toxicity test.

    Science.gov (United States)

    Emelogu, Emmanuel S; Pollard, Pat; Dymond, Peter; Robinson, Craig D; Webster, Lynda; McKenzie, Craig; Dobson, Judy; Bresnan, Eileen; Moffat, Colin F

    2013-09-01

    As an alternative procedure to conventional water quality assessment, the presence and combined toxicity of dissolved organic contaminants in water at five sites in the Forth estuary and the Firth of Forth, Scotland, United Kingdom was investigated using silicone rubber passive sampling devices (SR-PSDs) and an algal growth inhibition bioassay. SR-PSDs were deployed in water at the five sites for ~2 months. Following retrieval, extracts from the deployed SR-PSDs were assessed for both algal growth inhibition and the occurrence of a wide range of organic contaminants, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and a variety of plant protection products (PPPs; commonly referred to collectively as 'pesticides'). The 72 h algal growth inhibition test was performed using a native marine phytoplankton (Diacronema lutheri) in 24 well microplates. Freely dissolved (e.g. bioavailable) concentrations of PAHs and PCBs were determined using performance reference compounds (PRCs). The algal toxicity tests exhibited varied effects at the five sites indicating the presence of, and exposure to, phytotoxic compounds and their potential toxicity in the Forth. The individual and total dissolved concentrations of 40 PAHs and 32 PCBs measured in the study were relatively low and showed input of petrogenic, atmospheric and sewage related sources. Several pesticides of diverse polarities were identified in the water suggesting sources from both riverine input and direct discharges. The study thus illustrates the value of combining bioassays and chemical analysis (with effective sampling technique) for a realistic and rapid assessment of organic contaminants in the aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Acute sensitivity of freshwater mollusks and commonly tested invertebrates to select chemicals with different toxic models of action

    Science.gov (United States)

    Previous studies indicate that freshwater mollusks are more sensitive than commonly tested organisms to some chemicals, such as copper and ammonia. Nevertheless, mollusks are generally under-represented in toxicity databases. Studies are needed to generate data with which to comp...

  2. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.|info:eu-repo/dai/nl/068359802; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as

  3. An evaluation of the osmole gap as a screening test for toxic alcohol poisoning

    Directory of Open Access Journals (Sweden)

    Abu-Laban Riyad B

    2008-04-01

    Full Text Available Abstract Background The osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, particularly when the ability to measure serum concentrations of the substances is not available. The objectives of this study were: 1 to measure the diagnostic accuracy of the osmole gap for screening for ethylene glycol and methanol exposure, and 2 to identify whether a recently proposed modification of the ethanol coefficient affects the diagnostic accuracy. Methods Electronic laboratory records from two tertiary-care hospitals were searched to identify all patients for whom a serum ethylene glycol and methanol measurement was ordered between January 1, 1996 and March 31, 2002. Cases were eligible for analysis if serum sodium, blood urea nitrogen, glucose, ethanol, ethylene glycol, methanol, and osmolality were measured simultaneously. Serum molarity was calculated using the Smithline and Gardner equation and ethanol coefficients of 1 and 1.25 mOsm/mM. The diagnostic accuracy of the osmole gap was evaluated for identifying patients with toxic alcohol levels above the recommended threshold for antidotal therapy and hemodialysis using receiver-operator characteristic curves, likelihood ratios, and positive and negative predictive values. Results One hundred and thirty-one patients were included in the analysis, 20 of whom had ethylene glycol or methanol serum concentrations above the threshold for antidotal therapy. The use of an ethanol coefficient of 1.25 mOsm/mM yielded higher specificities and positive predictive values, without affecting sensitivity and negative predictive values. Employing an osmole gap threshold of 10 for the identification of patients requiring antidotal therapy resulted in a sensitivity of 0.9 and 0.85, and a specificity of 0.22 and 0. 5, with equations 1 and 2 respectively. The sensitivity increased to 1 for both equations for the

  4. Meta-Analysis of Fish Early Life Stage Tests - Association of Toxic Ratios and Acute-To-Chronic Ratios with Modes of Action

    DEFF Research Database (Denmark)

    Scholz, Stefan; Schreiber, Rene; Armitage, James

    2018-01-01

    Fish early life stage (FELS) tests (OECD test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stage. In order to analyse whether certain modes of action are related to high toxic ratios (TR, i.e., rati...

  5. 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

  6. Testing nanomaterial toxicity in unicellular eukaryotic algae and fish cell lines.

    Science.gov (United States)

    Kroll, Alexandra; Kühnel, Dana; Schirmer, Kristin

    2013-01-01

    ways of deriving a mass balance and quantitative/qualitative information on the uptake and distribution of NM in cells.As NM have a high surface-to-volume ratio and possess specific physical-chemical properties, which make them prone to interfere with various compounds and certain types of toxicity tests, potential interferences and appropriate controls are introduced. Furthermore, different types of dose metrics, which is still a strongly debated issue in nanotoxicology, are highlighted. We also consider laboratory safety regarding NM handling and disposal.

  7. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    OpenAIRE

    Basketter, D.A.; Clewell, H.; Kimber, I; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M; Eskes, C.; Goldberg, A; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds esp...

  8. The chick embryo test as used in the study of the toxicity of certain dithiocarbamates

    NARCIS (Netherlands)

    Gebhardt, D.O.E.; Logten, M.J. van

    1968-01-01

    The toxicities of six dithiocarbamates: bis(dimethyl thiocarbamoyl) disulfide (thiram), zinc dimethyldithiocarbamate (ziram), ferric dimethyldithiocarbamate (ferbam), bis(dimethyl thiocarbamoyl) ethylene bis(dithiocarbamate) (triaram), sodium diethyl dithiocarbamate (NaDEDC), and sodium ethylene

  9. Toxicity estimation of treated coke plant wastewater using the luminescent bacteria assay and the algal growth inhibition test

    Energy Technology Data Exchange (ETDEWEB)

    Peters, S.; Siersdorfer, C.; Kaltwasser, H.; Geiger, M. [University of Saarland, Saarbruecken (Germany)

    1995-08-01

    Among several bioassays, the Scendesmus subspicatus chlorophyll fluorescence test and the Photobacterium phosphoreum bioluminescence assay were selected to examine their applicability for toxicity evaluation of changes in coke plant effluent quality. In addition to the ecotoxicological parameters, a chemical analysis of dissolved organic carbon (DOC), ammonia-N and nitrate-N was performed. It was demonstrated that the toxicity values obtained from the bioassays give a first indication on potential hazard and successful treatment. Decreasing toxicity values went along with decreasing DOC or ammonia-N values, but the sensitivity toward DOC reduction was higher. Sensitivity toward pure compounds was assessed by comparing the EC{sub 50} values of the luminescent bacteria assay with the corresponding EC{sub 50} values of the algal bioassay. The data showed a poor correlation between the two bioassays.

  10. Including Bioconcentration Kinetics for the Prioritization and Interpretation of Regulatory Aquatic Toxicity Tests of Highly Hydrophobic Chemicals

    DEFF Research Database (Denmark)

    Kwon, Jung-Hwan; Lee, So-Young; Kang, Hyun-Joong

    2016-01-01

    propagation and model assumptions into account, we thus propose a revision of data requirements for highly hydrophobic chemicals with log Kow > 7.4: Short-term toxicity tests can be limited to algae that generally have the highest uptake rate constants, whereas the primary focus of the assessment should......Worldwide, regulations of chemicals require short-term toxicity data for evaluating hazards and risks of the chemicals. Current data requirements on the registration of chemicals are primarily based on tonnage and do not yet consider properties of chemicals. For example, short-term ecotoxicity data...... are required for chemicals with production volume greater than 1 or 10 ton/y according to REACH, without considering chemical properties. Highly hydrophobic chemicals are characterized by low water solubility and slow bioconcentration kinetics, which may hamper the interpretation of short-term toxicity...

  11. Field testing for toxic algae with a microarray: initial results from the MIDTAL project

    OpenAIRE

    McCoy, G.R.; Raine, R.; Medlin, L.; Chen, J.; Kooistra, W.; Barra, L.; Ruggiero, M.V.; Graneli, E.; Hagström, J.A.; Salomon, P.S.; Reguera, B.; Rodríguez, F.; Escalera, L.; Edvardsen, B.; Dittami, S.M.

    2013-01-01

    One of the key tasks in MIDTAL (MIcroarrays for the Detection of Toxic ALgae) is to demonstrate the applicability of microarrays to monitor harmful algae across a broad range of ecological niches and toxic species responsible for harmful algal events. Water samples are collected from a series of sites used in national phytoplankton and biotoxin monitoring across Europe. The samples are filtered; rRNA is extracted, labelled with a fluorescent dye and applied to a mi...

  12. Toxicity testing of heavy-metal-polluted soils with algae Selenastrum capricornutum: a soil suspension assay.

    Science.gov (United States)

    Aruoja, Villem; Kurvet, Imbi; Dubourguier, Henri-Charles; Kahru, Anne

    2004-08-01

    A small-scale Selenastrum capricornutum (Rhapidocelis subcapitata) growth inhibition assay was applied to the toxicity testing of suspensions of heavy-metal-polluted soils. The OECD 201 standard test procedure was followed, and algal biomass was measured by the fluorescence of extracted chlorophyll. The soils, which contained up to (per kilogram) 1390 mg of Zn, 20 mg of Cd, and 1050 mg of Pb were sampled around lead and zinc smelters in northern France. The water extractability of the metals in suspensions (1 part soil/99 parts water w/v) was not proportional to the pollution level, as extractability was lower for soil samples that were more polluted. Thus, the same amount of metals could be leached out of soils of different levels of pollution, showing that total concentrations of heavy metals in soil (currently used for risk assessment purposes) are poor predictors of the real environmental risk via the soil-water path. Despite high concentrations of water-extracted zinc (0.6-1.4 mg/L of Zn in the test), exceeding by approximately 10-fold the EC(50) value for S. capricornutum (0.1 mg Zn/L), 72-h algal growth in the soil extracts was comparable or better than growth in the standard control OECD mineral medium. The soil suspension stimulated the growth of algae up to eightfold greater than growth using the OECD control medium. Growth stimulation of algae was observed even when soil suspensions contained up to 12.5 mg Zn/L and could not be explained by supplementary nitrogen, phosphorous, and carbonate leached from the soil. However, if the growth of algae in suspensions of clean and polluted soils was compared, a dose-dependent inhibitory effect of metals on algal growth was demonstrated. Thus, as soil contains nutrients/supplements that mask the adverse effect of heavy metals, a clean soil that has properties similar to the polluted soils should be used instead of mineral salt solution as a control for analysis of the ecotoxicity of soils. Copyright 2004 Wiley

  13. 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.

  14. Using equilibrium passive dosing to maintain stable exposure concentrations of triclosan in a 6-week toxicity test

    DEFF Research Database (Denmark)

    Sobek, A.; Ribbenstedt, A.; Mustajärvi, L.

    2015-01-01

    toxicity tests. Yet, the European Commission’s criteria for chemicals’ risk assessments aim at protecting higher levels in the environment. To achieve protection of populations and ecosystems, reliable long-term ecotoxicologial tests are needed. In this study, we used equilibrium passive dosing to maintain...... hundred individuals in each vial. The increasing biomass of the test organisms can again lead to declining exposure concentrations, but such loss was buffered by passive dosing. Quality assurance tests showed that a) the loading and passive dosing procedures resulted in exposure concentrations with little...

  15. Toxicity tests on native and recombinant Bordetella pertussis adenylate cyclase toxin preparations.

    Science.gov (United States)

    Hormozi, K; Parton, R; Coote, J

    1999-01-01

    Bordetella pertussis produces a cell-invasive adenylate cyclase toxin which is synthesised from the cyaA gene as an inactive protoxin that is post-translationally activated by the product of the cyaC gene. Active and inactive CyaA proteins were prepared in crude and purified form from B. pertussis or from recombinant E. coli expressing both cyaA and cyaC genes or the cyaA gene alone, respectively. The specific AC activities of all the crude or all the purified toxins were similar. The toxins produced in the absence of CyaC activity had no cell invasive, haemolytic or cytotoxic activity. The cell invasive and cytotoxic activities of native and recombinant active CyaA preparations were similar, but the haemolytic activity of the recombinant toxin was lower than that of the native protein. As part of mouse protection tests, mice were injected subcutaneously with 15 microg per mouse of crude or purified CyaA preparations plus alhydrogel or with 1/5 human dose of adsorbed DPT vaccine (Wellcome Trivax-AD) using two doses at a two week interval. Control groups of mice were injected with alhydrogel in PBS alone or left unvaccinated. The toxin preparations had little or no effect on mouse weight gain, and there were no marked differences between mice vaccinated with the active toxin and those given the inactive form. Thus, at the dose used, there was no clear toxic physiological response caused specifically by active CyaA.

  16. Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Lee

    2015-12-01

    Full Text Available Objectives: Bufonis venonum (BV is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. Results: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. Conclusion: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal.

  17. Rapid bioassessment methods for assessing vegetation toxicity at the Savannah River Site - germination tests and root elongation trials

    Energy Technology Data Exchange (ETDEWEB)

    Specht, W.L.; Klaine, S.J.; Hook, D.D. [and others

    1996-01-01

    Plants form the basis of all ecosystems including wetlands. Although they are the most abundant life form and are the primary producers for all other organisms, they have received the least attention when it comes to environmental matters. Higher plants have rarely been used in ecotoxicity testing and may not respond in the same manner as algae, which have been used more frequently. The introduction of hazardous waste materials into wetland areas has the potential to alter and damage the ecological processes in these ecosystems. Measuring the impact of these contaminants on higher plants is therefore important and needs further research. Higher plants are useful for detecting both herbicidal toxicity and heavy metal toxicity. For phytotoxicity tests to be practical they must be simple, inexpensive, yet sensitive to a variety of contaminants. A difference between seed germination and root elongation tests is that seed germination tests measure toxicity associated with soils directly, while root elongation tests consider the indirect effects of water-soluble constituents that may be present in site samples.

  18. 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.

  19. Toxicity of sediments potentially contaminated by coal mining and natural gas extraction to unionid mussels and commonly tested benthic invertebrates

    Science.gov (United States)

    Wang, Ning; Ingersoll, Christopher G.; Kunz, James L.; Brumbaugh, William G.; Kane, Cindy M.; Evans, R. Brian; Alexander, Steven; Walker, Craig; Bakaletz, Steve

    2013-01-01

    Sediment toxicity tests were conducted to assess potential effects of contaminants associated with coal mining or natural gas extraction activities in the upper Tennessee River basin and eastern Cumberland River basin in the United States. Test species included two unionid mussels (rainbow mussel, Villosa iris, and wavy-rayed lampmussel, Lampsilis fasciola, 28-d exposures), and the commonly tested amphipod, Hyalella azteca (28-d exposure) and midge, Chironomus dilutus (10-d exposure). Sediments were collected from seven test sites with mussel communities classified as impacted and in proximity to coal mining or gas extraction activities, and from five reference sites with mussel communities classified as not impacted and no or limited coal mining or gas extraction activities. Additional samples were collected from six test sites potentially with high concentrations of polycyclic aromatic hydrocarbons (PAHs) and from a test site contaminated by a coal ash spill. Mean survival, length, or biomass of one or more test species was reduced in 10 of 14 test samples (71%) from impacted areas relative to the response of organisms in the five reference samples. A higher proportion of samples was classified as toxic to mussels (63% for rainbow mussels, 50% for wavy-rayed lampmussels) compared with amphipods (38%) or midge (38%). Concentrations of total recoverable metals and total PAHs in sediments did not exceed effects-based probable effect concentrations (PECs). However, the survival, length, or biomasses of the mussels were reduced significantly with increasing PEC quotients for metals and for total PAHs, or with increasing sum equilibrium-partitioning sediment benchmark toxic units for PAHs. The growth of the rainbow mussel also significantly decreased with increasing concentrations of a major anion (chloride) and major cations (calcium and magnesium) in sediment pore water. Results of the present study indicated that (1) the findings from laboratory tests were generally

  20. 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

  1. Comparison of the up-and-down method and the fixed-dose procedure for acute oral toxicity testing.

    Science.gov (United States)

    Yam, J; Reer, P J; Bruce, R D

    1991-04-01

    The acute oral toxicity data for 10 compounds, generated by using two alternative methods in rats, the up-and-down method and the fixed-dose procedure, were compared with those obtained from the classical LD50 test. In this evaluation, both alternative methods offered a reduction in animal use, while providing adequate information to rank the compounds according to the EEC classification for acute oral toxicity. In addition to the ranking, these alternative methods also provided useful information on signs of toxicity and gross autopsy findings, although the results varied depending on the method used. Of the three methods, the up-and-down method required the fewest animals. Although the up-and-down method used only females, the LD50 values obtained were in good agreement with those obtained by the classical method, which used both sexes. It is concluded that the up-and-down method and the fixed-dose procedure are acceptable alternative methods to the classical LD50 test, and the choice of method depends on the type of toxicity information required.

  2. Reflections on a career and on the history of genetic toxicity testing in the National Toxicology Program.

    Science.gov (United States)

    Zeiger, Errol

    2017-07-01

    One of the highly visible aspects of the U.S. National Toxicology Program (NTP) has been its genetic toxicity testing program, which has been responsible for testing, and making publicly available, in vitro and in vivo test data on thousands of chemicals since 1979. What is less well known, however, is that this NTP program had its origin in two separate testing programs that were initiated independently at the National Cancer Institute (NCI) and the National Institute of Environmental Health Sciences (NIEHS) before the NTP was established. The NCI program was in response to the 1971 National Cancer Act which dramatically increased the NCI budget. In contrast, the NIEHS testing program can be traced back to a publication by Bruce Ames, not the one describing the mutagenicity assay he developed that became known as the Ames test, but because in 1975 he published an article showing that hair dyes were mutagenic. The protocols developed for these NCI contracts became the basis for the NTP Salmonella testing contracts that were awarded a few years later. These protocols, with their supporting NTP data, strongly influenced the initial in vitro OECD Test Guidelines. The background and evolution of the NTP genetic toxicity testing program is described, along with some of the more significant milestone discoveries and accomplishments from this program. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Comparison of three marine screening tests and four Oslo and Paris Commission procedures to evaluate toxicity of offshore chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Weideborg, M.; Vik, E.A.; Oefjord, G.D.; Kjoennoe, O. [Aquateam-Norwegian Water Technology Centre A/S, Oslo (Norway)

    1997-02-01

    The results from the screening toxicity tests Artemia salina, Microtox{reg_sign}, and Mitochondria RET test were compared with those obtained from OSPAR (Oslo and Paris Commissions)-authorized procedures for testing of offshore chemicals (Skeletonema costatum, Acartia tonsa, Abra alba, and Corophium volutator). In this study 82 test substances (26 non-water soluble) were included. The Microtox test was found to be the most sensitive of the three screening tests. Microtox and Mitochondria RET test results showed good correlation with results from Acartia and Skeletonema testing, and it was concluded that the Microtox test was a suitable screening test as a base for assessment of further testing, especially regarding water-soluble chemicals. Sensitivity of Artemia salina to the tested chemicals was too low for it to be an appropriate bioassay organism for screening testing. A very good correlation was found between the results obtained with the Skeletonema and Acartia tests. The results indicated no need for more than one of the Skeletonema or Acartia tests if the Skeletonema median effective concentration or Acartia median lethal concentration was greater than 200 mg/L. The sediment-reworker tests (A. Alba or C. volutator) for chemicals that are likely to end up in the sediments (non-water soluble or surfactants) should be performed, independent of results from screening tests and other OSPAR species.

  4. 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.

  5. Optimizing the performance of the amphipod, Hyalella azteca, in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod, Hyalella azteca, is a common organism used for sediment toxicity testing. Standard methods for 10-d and 42-d sediment toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. While Hyalella azteca methods exist for sediment tox...

  6. 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.

  7. 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.

  8. Current standing and future prospects for the technologies proposed to transform toxicity testing in the 21st century.

    Science.gov (United States)

    van Vliet, Erwin

    2011-01-01

    The National Academy of Sciences publication, Toxicity Testing in the 21st Century: A Vision and a Strategy, proposes a paradigm shift in toxicology from current animal-based testing towards the application of emerging technologies, i.e., assays based on human cells or non-mammalian models, high throughput testing, omics approaches, systems biology, and computational modeling. These technologies should be used to identify how chemicals interact with cellular response networks and alter them to toxicity pathways. According to the authors, such a new paradigm would provide a better scientific understanding and more adequate data to predict the adverse effects of chemicals on human health. As expected from a vision document, the report enthusiastically and optimistically describes a radical transformation of toxicology from current practices to a new approach. Several toxicologists have commented on the report, and although they generally confirm the importance of the vision, they pose critical questions regarding its feasibility. Unlike the theoretical concepts, which are carefully described, many practical aspects of how to establish the vision are less well defined. Today's technologies provide great opportunities, although many challenges remain regarding their development, implementation, and validation to adequately assess human health effects. To bring the envisioned toxicology closer to concrete implementation, it is important to identify the current knowledge gaps in the vision and develop solutions. The goal of this review is to evaluate the technologies proposed as to their maturation to transform toxicity testing in the 21st century. This paper will provide an overview of the current standing by defining advantages, limitations, and developmental needs. In doing so, I do not intend to point out obstacles but, rather, to focus on current opportunities to advance toxicity testing for human risk assessment.

  9. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    Science.gov (United States)

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.

    Science.gov (United States)

    Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

    2015-03-01

    Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process.

  11. Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Goñi-de-Cerio, Felipe [GAIKER Technology Centre (Spain); Mariani, Valentina [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Cohen, Dror [Dead Sea Laboratories, AHAVA (Israel); Madi, Lea [Tel-Aviv University, Department of Physiology and Pharmacology, Sackler School of Medicine (Israel); Thevenot, Julie; Oliveira, Hugo [ENSCPB, Université de Bordeaux (France); Uboldi, Chiara; Giudetti, Guido; Coradeghini, Rosella [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Garanger, Elisabeth [ENSCPB, Université de Bordeaux (France); Rossi, François [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Portugal-Cohen, Meital; Oron, Miriam [Dead Sea Laboratories, AHAVA (Israel); Korenstein, Rafi [Tel-Aviv University, Department of Physiology and Pharmacology, Sackler School of Medicine (Israel); Lecommandoux, Sébastien [ENSCPB, Université de Bordeaux (France); Ponti, Jessica [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Suárez-Merino, Blanca; Heredia, Pedro, E-mail: heredia@gaiker.es [GAIKER Technology Centre (Spain)

    2013-11-15

    Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)-block–poly(l-glutamic acid) (PTMC-b–PGA) and poly(ethylene glycol)-block–poly(γ-benzyl-l-glutamate) (PEG-b–PBLG) with sizes between 113 and 131 nm. Low blood–serum–protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMC-b–PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG-b–PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.

  12. Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing

    Science.gov (United States)

    Goñi-de-Cerio, Felipe; Mariani, Valentina; Cohen, Dror; Madi, Lea; Thevenot, Julie; Oliveira, Hugo; Uboldi, Chiara; Giudetti, Guido; Coradeghini, Rosella; Garanger, Elisabeth; Rossi, François; Portugal-Cohen, Meital; Oron, Miriam; Korenstein, Rafi; Lecommandoux, Sébastien; Ponti, Jessica; Suárez-Merino, Blanca; Heredia, Pedro

    2013-11-01

    Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)- block-poly( l-glutamic acid) (PTMC- b-PGA) and poly(ethylene glycol)- block-poly( γ-benzyl- l-glutamate) (PEG- b-PBLG) with sizes between 113 and 131 nm. Low blood-serum-protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMC- b-PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG- b-PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.

  13. Quantitative structure-activity relationships and mixture toxicity of organic chemicals in Photobacterium phosphoreum: the Microtox test

    Energy Technology Data Exchange (ETDEWEB)

    Hermens, J.; Busser, F.; Leeuwangh, P.; Musch, A.

    1985-02-01

    Quantitative structure-activity relationships were calculated for the inhibition of bioluminescence of Photobacterium phosphoreum by 22 nonreactive organic chemicals. The inhibition was measured using the Microtox test and correlated with the partition coefficient between n-octanol and water (Poct), molar refractivity (MR), and molar volume (MW/d). At log Poct less than 1 and greater than 3, deviati