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Sample records for acute nmda toxicity

  1. Acute NMDA toxicity in cultured rat cerebellar granule neurons is accompanied by autophagy induction and late onset autophagic cell death phenotype

    Kobeissy Firas H

    2010-02-01

    Full Text Available Abstract Background Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA. Results NMDA exposure induced light chain-3 (LC-3-immunopositive and monodansylcadaverine (MDC fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment. Conclusions Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.

  2. Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury.

    Kai Kysenius

    Full Text Available The global incidence of metabolic and age-related diseases, including type 2 diabetes and Alzheimer's disease, is on the rise. In addition to traditional pharmacotherapy, drug candidates from complementary and alternative medicine are actively being pursued for further drug development. Berberine, a nutraceutical traditionally used as an antibiotic, has recently been proposed to act as a multi-target protective agent against type 2 diabetes, dyslipidemias, ischemic brain injury and neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. However, the safety profile of berberine remains controversial, as isolated reports suggest risks with acute toxicity, bradycardia and exacerbation of neurodegeneration. We report that low micromolar berberine causes rapid mitochondria-dependent toxicity in primary neurons characterized by mitochondrial swelling, increased oxidative stress, decreased mitochondrial membrane potential and depletion of ATP content. Berberine does not induce caspase-3 activation and the resulting neurotoxicity remains unaffected by pan-caspase inhibitor treatment. Interestingly, inhibition of NMDA receptors by memantine and MK-801 completely blocked berberine-induced neurotoxicity. Additionally, subtoxic nanomolar concentrations of berberine were sufficient to sensitize neurons to glutamate excitotoxicity and rotenone injury. Our study highlights the need for further safety assessment of berberine, especially due to its tendency to accumulate in the CNS and the risk of potential neurotoxicity as a consequence of increasing bioavailability of berberine.

  3. BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A

    David Lau

    2015-08-01

    Full Text Available The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating synaptic NMDA-receptor/nuclear-calcium-driven adaptogenomics, leading to increased expression of inhibin β-A (inhba. Inhibin β-A (its homodimer is known as activin A in turn reduces neurotoxic extrasynaptic NMDA-receptor-mediated calcium influx, thereby shielding neurons against mitochondrial dysfunction, a major cause of excitotoxicity. Thus, BDNF induces acquired neuroprotection by enhancing synaptic activity and lowering extrasynaptic NMDA receptor death signaling through a nuclear calcium-inhibin β-A pathway. This process, which confers protection against ischemic brain damage in a mouse stroke model, may be compromised in Huntington’s disease, Alzheimer’s disease, or aging-related neurodegenerative conditions that are associated with reduced BDNF levels and/or enhanced extrasynaptic NMDA receptor signaling.

  4. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  5. BDNF prevents NMDA-induced toxicity in models of Huntington's disease: the effects are genotype specific and adenosine A2A receptor is involved.

    Martire, Alberto; Pepponi, Rita; Domenici, Maria Rosaria; Ferrante, Antonella; Chiodi, Valentina; Popoli, Patrizia

    2013-04-01

    NMDA receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain-derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A2 ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA-induced effects in HD models, and the possible involvement of A2ARs. In corticostriatal slices from wild-type mice and age-matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e., toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/mL) potentiated NMDA effects in wild-type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A2 AR blockade. The protective effect of BDNF against NMDA-induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A2 AR ligands in HD.

  6. Hydroxyaluminosilicates and acute aluminium toxicity in fish

    Exley; Pinnegar; Taylor

    1997-11-21

    The essentiality of silicon in biology might be explained in the terms of its chemistry with aluminium. In a previous study we demonstrated the elimination of acute aluminium toxicity in fish by silicon. We suggested that the reaction of silicic acid with aluminium to form hydroxyaluminosilicates reduced the biological availability, and hence toxicity, of aluminium. Though assumed in a burgeoning number of studies and contended in others this detoxification mechanism has remained unproven. Herein we have tested the toxicity of hydroxyaluminosilicates in fish and in doing so we have provided evidence which strongly supports a role for hydroxyaluminiosilicates in the elimination of acute aluminium toxicity in fish by silicon.Copyright 1997 Academic Press Limited Copyright 1997 Academic Press Limited

  7. Anti-NMDA (a-NMDAR) receptor encephalitis related to acute consumption of metamphetamine: Relevance of differential diagnosis.

    Iriondo, O; Zaldibar-Gerrikagoitia, J; Rodríguez, T; García, J M; Aguilera, L

    2017-03-01

    A 19-year-old male came to the Emergency Room of our hospital due to an episode of dystonic movements and disorientation 4 days after consuming methamphetamine, which evolved to a catatonic frank syndrome and eventually to status epilepticus. Definitive diagnosis was anti-NMDA receptor encephalitis, an acute inflammation of the limbic area of autoimmune origin in which early diagnosis and treatment are key elements for the final outcome. In this case, initial normal tests and previous methamphetamine poisoning delayed diagnosis, because inhaled-methamphetamine poisoning causes similar clinical symptoms to anti-NMDA receptor encephalitis. Methamphetamine poisoning may have caused an immune response in the patient, bringing on the progress of the pathology.

  8. CDP-choline: acute toxicity study.

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

    1983-01-01

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

  9. Acute methanol toxicity in minipigs

    Dorman, D.C.; Dye, J.A.; Nassise, M.P.; Ekuta, J.; Bolon, B.

    1993-01-01

    The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.

  10. Acute inhalation toxicity of carbonyl sulfide

    Benson, J.M.; Hahn, F.F.; Barr, E.B. [and others

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  11. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  12. Acute Liver Failure Secondary to Niacin Toxicity

    Marc A. Ellsworth

    2014-01-01

    Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

  13. Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

    Walailuk Kerdsan

    2009-01-01

    Full Text Available Methamphetamine (METH is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1 in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P=.036 but not in the acute group (P=.580. Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P=.025 and subacute groups (P=.023. However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

  14. Methotrexate-induced acute toxic leukoencephalopathy

    Parag R Salkade

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX, as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS. Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced ′acute toxic leukoencephalopathy′ has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted and FLAIR (Fluid-Attenuated Inversion recovery sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up

  15. Methotrexate-induced acute toxic leukoencephalopathy.

    Salkade, Parag R; Lim, Teh Aun

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX), as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS). Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced 'acute toxic leukoencephalopathy' has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI) is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted) and FLAIR (Fluid-Attenuated Inversion recovery) sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted) sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up over a 2 year

  16. Anti-NMDA Receptor Encephalitis Presenting as an Acute Psychotic Episode in a Young Woman: An Underdiagnosed yet Treatable Disorder

    Shikma Keller

    2014-01-01

    Full Text Available Anti-NMDA receptor (NMDAR encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias, and autonomic instability. In female patients an ovarian teratoma is often identified. We describe a 32-year-old woman who presented with acute psychosis. Shortly after admission, she developed generalized seizures and deteriorated into a catatonic state. Although ancillary tests including MRI, electroencephalogram, and cerebrospinal fluid (CSF analysis were unremarkable, the presentation of acute psychosis in combination with recurrent seizures and a relentless course suggested autoimmune encephalitis. The patient underwent pelvic ultrasound which disclosed a dermoid cyst and which led to an urgent cystectomy. Plasmapheresis was then initiated, yielding partial response over the next two weeks. Following the detection of high titers of anti-NMDAR antibodies in the CSF, the patient ultimately received second line immunosuppressive treatment with rituximab. Over several months of cognitive rehabilitation a profound improvement was eventually noted, although minor anterograde memory deficits remained. In this report we call for attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. Prompt diagnosis is critical as early immunotherapy and tumor removal could dramatically affect outcomes.

  17. Acute Toxicity of Four Organophosphorus Pesticide Products

    2012-01-01

    Acute toxicity of phoxim,acephate,isofenphos-methyl and isocarbophos on male SD rats of clean grade was carried out by gastric lavage method at room temperature of 18℃. These rats are 4 to 5 months old with body weight of 180 to 220 kg. The results indicate that the orders of the toxicity of these four pesticides on SD rats are isofenphos-methyl,isocarbophos,acephate,phoxim. We found that the median lethal concentration of phoxim in 24 h,48 h,72 h and 96 h is 3. 892 g /kg,3. 051 g /kg,2. 618 g /kg and 2. 458 g /kg respectively; the median lethal concentration of isofenphos-methyl in 24 h,48 h,72 h and 96 h is 0. 015 g /kg,0. 013g /kg,0. 012g /kg and 0. 011 g /kg respectively; the median lethal concentration of isocarbophos in 24 h,48 h,72 h and 96 h is 0. 049 g /kg,0. 046 g /kg,0. 043 g /kg,0. 041 g /kg respectively; and the median lethal concentration of acephate in 24 h,48 h,72 h and 96 h is 0. 137 g /kg,0. 113 g /kg,0. 100 g /kg,0. 085 g /kg respectively. Finally,we evaluated the characteristics of toxicity effect and safe concentration of these pesticides to SD rats.

  18. Acute Toxicity of Justicia gendarussa Burm. Leaves

    Juheini Amin

    2010-11-01

    Full Text Available Acute Toxicity of Justicia gendarussa Burm. Leaves. Preminelary experiment showed that ethanolic extract ofgandarusa leaves (Justicia gendarussa Burm. could decreased uric acid blood level on rats. The aim of this experimentwas to determine of the value LD50 and liver function based on activities of aminotransferase. Animals test which wereused in this experiment were 50 males and 50 females white mice. They were divided into 5 groups. Group 1 as controlgroup was given aquadest. Group 2-5 were treated by ethanolic extract of gandarusa leaves with dosage 4, 8, 16, and 32g/kg bw. The LD50 value was determined by the amount of death in group during 24 hours after giving a single dose oftest substance. The result showed that the highest dose was practically non toxic with LD50 value of 31.99 g/kg bw(male groups and 27.85 g/kg bw (female groups. Measurement of aminotransferase activity was done by usingcolorimetric method. The result of ANOVA analysis for liver function showed that the giving test substance 4 g/kg bw–16 g/kg bw was not significantly different between treated groups and control group.

  19. [Acute toxicity of different type pesticide surfactants to Daphnia magna].

    Li, Xiu-huan; Li, Hua; Chen, Cheng-yu; Li, Jian-tao; Liu, Feng

    2013-08-01

    By using the standard test methods in Experimental Guideline for Environmental Safety Evaluation of Chemical Pesticide to aquatic organisms, a comparative study was conducted on the acute toxicity of 39 nonionic, 6 anionic, and 3 cationic surfactants to Daphnia magna. The acute toxicity of three cationic surfactants 1427, 1227 and C8-10 to D. magna belonged to virulent level, and the toxicity of 1427 was the highest, with the EC50 value being 0.97 x 10(-2) mg x L(-1). The acute toxicity of nonionic surfactants polyoxyethylene ether castor oil EL, Tween, and Span emulsifiers belonged to low level, but the toxicity of alkylphenol polyoxyethylene ether and fatty alcohol polyoxyethylene ether surfactants was relatively high, of which, AEO-7 and AEO-5 displayed high toxicity, with the EC50 value being 0.82 and 0.97 mg x L(-1), respectively. In these surfactants, the more liposolubility, the higher the toxicity was. Most of the anionic surfactants were medium in toxicity, but the acute toxicity of NNO belonged to high toxicity, with the EC50 value being 0.17 mg x L(-1).

  20. Acute psychosis due to non-paraneoplastic anti-NMDA-receptor encephalitis in a teenage girl: Case report.

    Kramina, Sandra; Kevere, Laura; Bezborodovs, Nikita; Purvina, Santa; Rozentals, Guntis; Strautmanis, Jurgis; Viksna, Zane

    2015-12-01

    Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a disease occurring when antibodies produced by the body's own immune system attack NMDA-type glutamate receptors in the brain. Most anti-NMDAR encephalitis cases are associated with paraneoplastic syndrome. We analyze the case of a 15-year-old girl who was hospitalized in a child psychiatry clinic in Riga, Latvia, with de novo acute polymorphic psychotic disorder gradually progressing to a catatonic state. The patient received antipsychotic and electroconvulsive therapy with no beneficial effect. The council of doctors discussed differential diagnoses of schizophrenia-induced catatonia and the autoimmune limbic encephalitis-induced catatonic condition. When the diagnosis of anti-NMDAR autoimmune encephalitis was finally confirmed by repeated immunological assays (specific immunoglobulin [Ig] G and IgM in her blood serum and cerebrospinal fluid), and a paraneoplastic process was ruled out, she was started on immunomodulating therapy (methylprednisolone, Ig, plasmapheresis, rituximab), which changed the course of her disease. On immunomodulating treatment, her physical and mental health have gradually improved to almost complete reconvalescence. Psychiatrists should consider anti-NMDAR encephalitis as a differential diagnosis in first-episode psychosis patients presenting with disorientation, disturbed consciousness, pronounced cognitive deficits, movement disorder, dysautonomia, or rapid deterioration, and test for specific IgG NR1 autoantibodies, even if there are no specific findings on routine neuroimaging, electroencephalography (EEG), or cerebrospinal fluid tests.

  1. 40 CFR 797.1050 - Algal acute toxicity test.

    2010-07-01

    .... Also note any unusual cell shapes, color differences, flocculations, adherence of algae to test... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Algal acute toxicity test. 797.1050... toxicity test. (a) Purpose. The guideline in this section is intended for use in developing data on...

  2. Amiodarone-induced acute lung toxicity in an ICU setting.

    Skroubis, G; Skroubis, T; Galiatsou, E; Metafratzi, Z; Karahaliou, A; Kitsakos, A; Nakos, G

    2005-04-01

    Amiodarone is a highly effective antiarrhythmic drug, albeit notorious for its serious pulmonary toxicity. The incidence of amiodarone-induced pulmonary toxicity (APT) appears to be 1% per year (1). We report a case of very acute APT in a man suffering from postoperative atrial fibrillation.

  3. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute dermal toxicity. 799.9120 Section 799.9120 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...) Preparations. Healthy young adult animals are acclimatized to the laboratory conditions for at least 5...

  4. 40 CFR 799.9110 - TSCA acute oral toxicity.

    2010-07-01

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

  5. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute inhalation toxicity. 799.9130 Section 799.9130 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals...

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

    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.

  7. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    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 ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/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.

  8. DETERMINATION OF ACUTE TOXICITY OF BIO HUMATES

    Zholobova I. S.

    2016-05-01

    Full Text Available In the work, we present the results of the investigation of acute toxicity of bio humates obtained by the method vermicultivation on laboratory animals. In the diets of farm animals and Pets to fill in the missing nutrients in the past years, we had an extensive use of various feed additives. Among them, mineral (macro - and micronutrients, protein and fat supplements, vitamins, biostimulants, complex natural compounds (sapropel, peat, synthetic products (enzymes, hormones, antibiotics, adaptogens, antioxidants. The search for new ways of improvement and increase of efficiency of agricultural animals using feed additives with high demands on ecology of meat and dairy foods naturally led to increased studies on the use in livestock farming of water-soluble alkaline salts of natural humic acids - humates. Their environmental safety and the unique ability to improve metabolism and increase energy cells very positively manifested in living organisms. Numerous studies Russian and foreign scientists installed a high efficiency natural humates as biostimulators and immunomodulators in animal husbandry and veterinary medicine. Accumulated extensive experimental material, proving that the use of humates leads to faster growth of animals, reducing morbidity and mortality, increase the body's resistance to toxins in feed and resistance to adverse environmental conditions. Improving with the help of humates ecological purity of the ecosystems "water — soil — plant", as well as the health of birds, animals and fish will ultimately lead to strengthen health and to prolong human life as a consumer of agricultural products. Currently, the livestock market is intensively increasing the humates produced in Russia and abroad from brown coal, peat, sapropel. A special place among them has been occupied by the newest formulations because of a unique combination of safety, efficiency, and value, which, thanks to its amazing properties to increase energy cells

  9. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    Popov, Dmitri; Maliev, Slava

    . Radiation Toxins (SRD-1)had been isolated from Central Lymph of irradiated animals (cows, sheep, pigs). Experiments to study toxicity of Radiation Neurotoxins had been performed. Intravenous (IV) and intramuscular (IM) administration of RT SRD-1 to radiation naive animals had induced acute toxicity which referred to the harmful effects generated by high doses of radiation. In-jection of toxic doses of RT SRD-1 (Toxic doses: 0,1 mg/kg, 0,5mg/kg, 1 mg/kg, 10mg/kg,30 mg/kg, 50mg/kg,70 mg/kg,100 mg/kg, 110mg/kg)were compared to the similar effects caused by high doses of radiation. Results: Injection of SRD-1 ( Neurotoxin Cv ARS)of all ten tested toxic doses had caused a death of radiation naive animals within the first hours after admin-istration of toxins. For all animals in all experiments, a short period of extreme agitation was replaced by deep coma, and suppression of blood circulation and breathing. The results of postmortem section had showed characteristics of intra-cortical hemorrhage. Conclusions: Acute radiation injury induces a disorder of blood supply of the Central Nervous System (CNS). However, administration of SRD-1 Radiation Toxins to radiation naive animals produces crit-ically important inflammatory reactions with hemorrhagic stroke development. Neurotoxicity and Excitotoxicity are two stages of the pathological processes resulted in damaging and killing nerve cells thorough apoptotic necrosis. Excitotoxicity is well known as a pathological process that occurs when important excitatory neurotransmitters (glutamate, serotonin) over-activate the receptors -NMDA, AMPA, 5HT1, 5HT2, 5H3. Radiation Neurotoxins possibly act on the same receptors and activate the cell death mechanisms through direct or indirect excessive activation of same receptors.

  10. Acute toxicity and toxic interaction of chromium and nickel to common guppy Poecilia reticulata (Peters)

    Khangarot, B.S.; Ray, P.K. (Industrial Toxicology Research Centre, Lucknow (India))

    1990-06-01

    The acute toxicity of heavy metals in combination to the common guppy has been reported. Information on the combined effects of chromium and nickel to fish is rather scarce. Toxicity of nickel and chromium to fish is generally low. These two elements are usually less toxic than silver, cadmium, copper and thallium; depending on test conditions, these may also be less hazardous than zinc, lead and arsenic. The present study was undertaken to investigate the acute toxicity of Ni and Cr singly and the toxic interaction of these two metal ions on survival of the common guppy, Poecilia reticulata (Peters). This species was selected for static bioassays because it can be easily cultured and raised under laboratory conditions through a complete life cycle, and it is one of the most common fish used for laboratory toxicity studies.

  11. Review of Quantitative Structure - Activity Relationships for Acute Mammalian Toxicity

    Iglika Lessigiarska

    2006-12-01

    Full Text Available This paper reviews Quantitative Structure-Activity Relationship (QSAR models for acute mammalian toxicity published in the last decade. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate system for predicting acute toxicity to mammals. On the basis of the review, the following conclusions can be made: i a relatively small number of models for in vivo toxicity are published in the literature. This is due to the nature of the endpoint - acute systemic toxicity is usually related to whole body phenomena and therefore is very complex. The complexity of the mechanisms involved leads to difficulties in the QSAR modelling; ii most QSAR models identify hydrophobicity as a parameter of high importance for the modelled toxicity. In addition, many models indicate the role of the electronic and steric effects; iii most of the literature-based models are restricted to single chemical classes. Models based on more heterogeneous data sets are those incorporated in expert systems. In general, the QSAR models for mammalian toxicity identified in this review are considered useful for investigating the mechanisms of toxicity of defined chemical classes. However, for predictive purposes in the regulatory assessment of chemicals most of the models require additional information to satisfy internationally agreed validation principles. In addition, the development of new models covering larger chemical domains would be useful for the regulatory assessment of chemicals.

  12. Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

    Francisco J. Carvajal

    2016-01-01

    Full Text Available N-Methyl-D-aspartate receptors (NMDARs have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases.

  13. A mechanism for acute aluminium toxicity in fish.

    Exley, C; Chappell, J S; Birchall, J D

    1991-08-07

    Aluminium is acutely toxic to fish in acid waters. The gill is the principal target organ and death is due to a combination of ionoregulatory, osmoregulatory and respiratory dysfunction. The toxic mechanism has hitherto received little direct consideration and is unknown. In this paper the mechanism of acute aluminium toxicity is approached from a chemical perspective. Symptomatic evidence of toxicity is taken from the literature and combined with our own research to elucidate a biochemically sound model to describe a possible mechanism of acute aluminium toxicity in fish. The proposed model delineates the chemical conditions immediately adjacent to the gill surface and emphasizes their importance in aluminium's toxic mode of action. The mechanism is shown to be bipartite. Aluminium binding to functional groups both apically located at the gill surface and intracellularly located within lamellar epithelial cells disrupts the barrier properties of the gill epithelium. The concomitant iono- and osmoregulatory dysfunction results in accelerated cell necrosis, sloughing and death of the fish. The mechanism of epithelial cell death is proposed as a general mechanism of aluminium-induced accelerated cell death.

  14. Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

    Idris Bello

    2016-03-01

    Full Text Available Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD rats. The methanolic extract of Alstonia scholaris stem bark (ASME was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.. Histopathological studies revealed slight degeneration (lesion and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg. The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

  15. Acute and late toxicity in radical radiotherapy of prostate cancer

    Josifovski Tatjana

    2009-01-01

    Full Text Available Introduction. Although radical radiotherapy has proved to be a successful method in prostate cancer treatment, the conventional (box technique can result in significant adverse events. Objective. The objective of our study was to estimate the frequency, type and severity of acute and late toxicity in radical radiotherapy of prostate cancer. Methods. In a clinical retrospective study, we included 283 patients with histologically confirmed prostate cancer. All our patients received radical, conventional radiotherapy using the four-field technique. The study was performed at the Radiotherapy Department of the Institute for Oncology and Radiology of Serbia between January 1991 and December 2005. During regular follow-up, we analyzed the frequency, type and severity of acute and late toxicity. Results. Two thirds (71% of our patients had acute toxicity of at least one organ within the radiation field. Most frequent complication was radiation dermatitis (10.5%, and enteritis (9%, cystitis (6% and proctitis (2.5%. Acute adverse events were mostly low grade (I and II, 28-61%. Late complications were registered in 20.5% of patients. Skin fibrosis was most frequent (12%. Chronic proctitis was detected in 4% and urethral stricture in 4.5% of our patients. All late complications were low grade. Conclusion. Treatment tolerance of radical radiotherapy is relatively good. Although most patients develop acute toxicity, it is commonly low grade and requires the interruption of radiotherapy treatment in 20% of patients only. Late toxicity is rarer than acute and, in most cases, it does not affect the quality of life.

  16. Butachlor-induced acute toxic hepatitis.

    Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

    2007-01-01

    Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

  17. Acute aqueous toxicities of diesel-biodiesel blends

    Hollebone, B.P.; Ho, N.; Landriault, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science and Technology Division, Science and Technology Branch, Environmental Science and Technology Centre; Harrison, S. [Science Applications International Corp., SAIC Canada, Ottawa, ON (Canada); Doe, K.; Jackman, P. [Environment Canada, Moncton, NB (Canada). Toxicology Laboratory, Environmental Science Centre

    2008-07-01

    The renewed interest in biodiesels as a new transportation fuel was discussed. Although there are several advantages to using biodiesels, their environmental behaviours and effects need to be evaluated along with the risks associated with their use, such as accidental releases of these biodiesels to the environment. The wide variability of biodiesels may result in different toxicological impacts, depending on the fuel feedstock. This study evaluated the aqueous effects of biodiesels from several commonly available feedstocks and their blends with petroleum diesel. Since most of the commercial uses of these products are currently focused on road-use, this study focused on the effects of these fuels in fresh-water. Biodiesels derived from soy, canola and waste restaurant oil feedstocks were used in the study. The acute toxicities of these biodiesels and biodiesel/petroleum diesel fuel blends were reported for 3 test species used by Environment Canada for toxicological evaluation, notably rainbow trout, the water flea, and a luminescent bacterium. The correlations between acute toxicity, water accommodated fractions (WAF) concentrations and fuel property data were examined. The study revealed that biodiesel is significantly less acutely toxic than petroleum diesels in potential ecological impacts. However, the biodiesel-diesel blends were found to be more acutely toxic than a linear dilution model predicts. 11 refs., 6 tabs., 3 figs.

  18. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

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

    2000-01-01

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

  19. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  20. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    Arbabi Bidgoli S

    2011-04-01

    Full Text Available M Korani1, SM Rezayat1,2,4, K Gilani3, S Arbabi Bidgoli4, S Adeli11Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences; 2Department of Nanotechnology, Faculty of Advanced Sciences and Technology in Medicine, Tehran University of Medical Sciences; 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences; 4Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS, Tehran, IranAbstract: Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 µg/mL in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 µg/mL in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater

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

    Anurag Payasi

    2010-06-01

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

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

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

    2013-11-01

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

  3. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  4. Protection against oxaliplatin acute neurosensory toxicity by venlafaxine.

    Durand, Jean-Philippe; Brezault, Catherine; Goldwasser, François

    2003-07-01

    Venlafaxine (Effexor; Wyeth Lederlé) has previously shown therapeutic effects for the management of chronic and neuropathic pains. We report here the efficacy of venlafaxine upon acute neurosensory symptoms secondary to oxaliplatin toxicity. A dose of 50 mg of venlafaxine was given orally at the beginning of the oxaliplatin infusion. Patients did not experience any or very low paresthesias, even in the cold. As the results were very dramatic and reproducible, we propose that venlafaxine may be of use in the daily management of oxaliplatin-related neurosensory toxicity.

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

    Arunachalam Muthuraman; Nirmal Singh

    2012-01-01

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

  6. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  7. An evaluation of acute toxicity of colloidal silver nanoparticles.

    Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

    2011-11-01

    Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

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

    Jin Yu

    2013-01-01

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

  9. Acute and delayed toxicities of total body irradiation

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  10. Acute and subacute toxicity of {sup 18F}-FDG

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A., E-mail: danielle_2705@hotmail.com, E-mail: jaossoj@yahoo.com.br, E-mail: ngsilva@ipen.br, E-mail: apaulasp2008@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the {sup 18}F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

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

    Surender Singh

    2017-01-01

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

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

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

    2009-01-01

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

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

    Wuen Yew Teoh

    2013-01-01

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

  14. Data on acute toxicity of the progestin STS 557.

    Hillesheim, H G; Hoffmann, H

    1983-02-01

    In mice and rabbits of both sexes the acute toxicity of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was determined after its oral or parenteral (i.p., s.c.) administration. In rabbits increasing lethality was observed following STS 557 suspended in tylose solution at the dose range of 1.0 to 3.0 g/kg p.o. or i.p. The approximate LD50-values were 1.0 to 1.5 g/kg for the i.p. route and 1.0 to 2.0 g/kg for the oral route. Levonorgestrel injected i.p. did not cause any lethality up to the dose of 3.0 g/kg. After oral or s.c. administration to mice, doses of 4.0 g/kg STS 557 were well tolerated. A dose-related toxicity occurred only after i.p. doses between 0.5 and 1.0 g/kg (STS 557), and between 2.0 and 4.0 g/kg (levonorgestrel), respectively. Using an oily vehicle for the oral route in mice, the lethal threshold dose for STS 557 was lowered to about 2.0 g/kg. In conclusion, a low oral acute toxicity was determined for STS 557 corresponding to that of other progestagens like levonorgestrel or norethisterone.

  15. Acute toxicity of TBT and IRGAROL in Artemia salina.

    Panagoula, Bakoulia; Panayiota, Marcouli; Iliopoulou-Georgudaki, Joan

    2002-01-01

    A 24-hour LC(50) bioassay method was carried out to study acute toxicity of Tributyltin (TBT) and IRGAROL (C(11)H(19)N(5)S) in Artemia salina. Five graded levels of both biocides were tested. According to the range test, the doses of TBT were 11.6 ng x l(-1), 21.0 ng x l(-1), 37.3 ng x l(-1), 65.2 ng x l(-1), and 116.5 ng x l(-1), and for IRGAROL were 1.0 mg x l(-1), 1.8 mg x l(-1), 3.2 mg x l(-1), 5.6 mg x l(-1), and 10 mg x l(-1). The determined LC(50) values were 41.41 ng x l(-1) and 1.62 mg x l(-1) respectively. These results indicate that in this system TBT is acutely more toxic than IRGAROL; however, both are proven environmentally toxic substances.

  16. Identifying and designing chemicals with minimal acute aquatic toxicity.

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

    2015-05-19

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

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

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

    1979-01-01

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

  18. Non-animal Replacements for Acute Toxicity Testing.

    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.

  19. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    Varalaxmi Bhavani Nannaka

    2016-01-01

    Full Text Available Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses.

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

    Akram Ghadirkhomi

    2016-08-01

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

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

    Preeti Bagri

    2013-12-01

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

  2. [Acute Toxicity of Coptis chinensis Rhizome Extracts to Daphnia carinata].

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

    Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems.

  3. Acute and subchronic toxicity of hydroxylammonium nitrate in Wistar rats

    An Hui; Liu Jinyi; Yang Lujun; Liu Shengxue; Zhou Yanhong; Yang Huan; Jia Qingjun; Cui Zhihong; Cao Jia

    2008-01-01

    Hydroxylammonium nitrate (HAN) is a major constituent in a class of liquid monopropellants and is extensively used in nuclear industry and space propulsion. Previous toxicological studies have focused on oral, inhalation and dermal routes of exposure to HAN-based propellant blends. In this study, acute and subchronic toxicity of HAN in Wistar rats by intraperitoneal injections were evaluated. In this acute study, doses of HAN at 115, 125, 135, 147, 160 or 174 mg/kg were administered. No adverse effects were observed during a 14-day period and at gross histopathological examination. In the subchronic study, HAN at 7, 14 or 28 mg/kg were administered for 13 weeks. The treatment with HAN caused significant changes in the weight of spleen, in the level of hematological parameters, total bilirubin, direct bilirubin, uric acid and carbondioxidecombining power and histopathological damages of the lung, liver, spleen and kidney. Overall, the study suggests that 13-week HAN treatment caused abnormal hematological changes and tissue lesions, and the risk of toxicity to mammals is not negligible.

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

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

    1996-12-01

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

  5. Stereotactic radiotherapy of meningiomas. Symptomatology, acute and late toxicity

    Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R. [Dept. of Radiation Oncology, Univ. of Gisssen (Germany); Dept. of Radiation Oncology, Marburg Univ. (Germany); Hamm, K.; Surber, G.; Kleinert, G. [Dept. of Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

    2006-07-15

    Background and purpose: stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. Patients and methods: between 1997-2003, 224 patients were treated with SRT (n= 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. Results: the median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III ) was rarely seen (2.5%). Clinically significant late morbidity (III -IV ) or new cranial nerve palsies did not occur. Conclusion: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended. (orig.)

  6. Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors

    Maya-López, Marisol; Colín-González, Ana Laura; Aguilera, Gabriela; de Lima, María Eduarda; Colpo-Ceolin, Ana; Rangel-López, Edgar; Villeda-Hernández, Juana; Rembao-Bojórquez, Daniel; Túnez, Isaac; Luna-López, Armando; Lazzarini-Lechuga, Roberto; González-Puertos, Viridiana Yazmín; Posadas-Rodríguez, Pedro; Silva-Palacios, Alejandro; Königsberg, Mina; Santamaría, Abel

    2017-01-01

    The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington’s disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

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

    Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

    2016-01-01

    Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

  8. Relatively spared central multifocal electroretinogram responses in acute quinine toxicity

    Saeed, Muhammad Usman; Noonan, Carmel; Hagan, Richard; Brown, Malcolm

    2011-01-01

    A 71-year-old man was investigated with electrodiagnostic testing 4 months after a deliberate quinine overdose. Initially he was admitted to intensive care unit with visual acuity (VA) of perception of light in both eyes. VA recovered to 6/6 right eye and 6/12 left eye, though severely constricted fields were noted. Slow stimulus (base period of 83 ms) multifocal electroretinogram (ERG) showed electronegative responses outside the inner 5 degrees, with a reduced but electropositive response seen in this central area. It appears that in this case of bilaterally negative ERGs that the macula/fovea (which has a vascular supply through the choroid) is relatively spared as is seen in bilateral vascular electronegative ERGs. This may indicate that quinine toxicity to the retina may be secondary to effects similar to vascular occlusion or severe ischemia during the acute phase of quinine poisoning. PMID:22693278

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

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

    2016-01-01

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

  10. Mustard gas toxicity: the acute and chronic pathological effects.

    Ghabili, Kamyar; Agutter, Paul S; Ghanei, Mostafa; Ansarin, Khalil; Shoja, Mohammadali M

    2010-10-01

    Ever since it was first used in armed conflict, mustard gas (sulfur mustard, MG) has been known to cause a wide range of acute and chronic injuries to exposure victims. The earliest descriptions of these injuries were published during and in the immediate aftermath of the First World War, and a further series of accounts followed the Second World War. More recently, MG has been deployed in warfare in the Middle East and this resulted in large numbers of victims, whose conditions have been studied in detail at hospitals in the region. In this review, we bring together the older and more recent clinical studies on MG toxicity and summarize what is now known about the acute and chronic effects of the agent on the eyes, skin, respiratory tract and other physiological systems. In the majority of patients, the most clinically serious long-term consequences of MG poisoning are on the respiratory system, but the effects on the skin and other systems also have a significant impact on quality of life. Aspects of the management of these patients are discussed.

  11. Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes.

    Li, Min; Wei, Dongbin; Du, Yuguo

    2014-09-01

    Acute toxicity of 21 quinolone antibiotics was monitored using photobacterium Vibrio fischeri assay. The minimum IC20 (inhibitory concentration for 20% luminescence elimination) was obtained at the least 18.86μmol/L for the tested quinolones. A quantitative structure-activity relationship model was established to investigate the possible mechanism for the acute toxicity. The critical physicochemical descriptors, describing σ and π atom electronegativity, implied that the electron transfer might occur between the quinolones and photobacterium V. fischeri. Although the quinolones exhibited limited acute toxicity to photobacterium, toxicity elevation was detected after their chlorination. Hence, chlorination disinfection treatment of quinolone-containing water should be of concerns.

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

    Thit, Amalie; Huggins, Krista; Selck, Henriette;

    2016-01-01

    The acute toxicity of monodispersed 6 nm and <100 nm poly-dispersed copper oxide nanoparticles toward Daphnia magna was assessed using 48 h immobilization tests. CuSO4 was used as a reference. Four different exposure conditions were tested, to study whether the toxicity of the nanoparticle suspen...... model MINTEQ. These findings show that the acute toxicity of copper oxide nanoparticles is governed by test water composition and the chemical species Cu2+....

  13. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

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

    2012-11-01

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

  14. Rosette nanotubes show low acute pulmonary toxicity in vivo

    W Shane Journeay

    2008-10-01

    Full Text Available W Shane Journeay1, Sarabjeet S Suri1, Jesus G Moralez2, Hicham Fenniri2, Baljit Singh11Immunology Research Group, Toxicology Graduate Program and Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada; 2National Institute of Nanotechnology, National Research Council (NINT-NRC and Department of Chemistry, University of Alberta, 11421 Saskatchewan Drive, Edmonton, AB, T6G 2M9, CanadaAbstract: Nanotubes are being developed for a large variety of applications ranging from electronics to drug delivery. Common carbon nanotubes such as single-walled and multi-walled carbon nanotubes have been studied in the greatest detail but require solubilization and removal of catalytic contaminants such as metals prior to being introduced to biological systems for medical application. The present in vivo study characterizes the degree and nature of inflammation caused by a novel class of self-assembling rosette nanotubes, which are biologically inspired, naturally water-soluble and free of metal content upon synthesis. Upon pulmonary administration of this material we examined responses at 24 h and 7d post-exposure. An acute inflammatory response is triggered at 50 and 25 μg doses by 24 h post-exposure but an inflammatory response is not triggered by a 5 μg dose. Lung inflammation observed at a 50 μg dose at 24 h was resolving by 7d. This work suggests that novel nanostructures with biological design may negate toxicity concerns for biomedical applications of nanotubes. This study also demonstrates that water-soluble rosette nanotube structures represent low pulmonary toxicity, likely due to their biologically inspired design, and their self-assembled architecture.Keywords: nanotoxicology, biocompatibility, nanomedicine, pulmonary drug delivery, lung inflammation

  15. Toxicological evaluation of ferrous N-carbamylglycinate chelate: Acute, Sub-acute toxicity and mutagenicity.

    Wan, Dan; Zhou, Xihong; Xie, Chunyan; Shu, Xugang; Wu, Xin; Yin, Yulong

    2015-11-01

    Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD50) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity.

  16. Comparison of organics and heavy metals acute toxicities to Vibrio fischeri

    Yang Xuepeng

    2016-01-01

    Full Text Available Vibrio fischeri bioluminescence inhibition has been widely used to test acute toxicities of metals and organics contaminants. However, the differences of metals and organics acute toxicities to V. fischeri have not been compared. Here, four heavy metals (Zn2+, Cu2+, Cd2+, Cr6+ and five organics (phenol, benzoic acid, p-hydroxy benzoic acid, nitro-benzene and benzene acute toxicities to V. fischeri were investigated. Heavy metals toxicities to V. fischeri were increased along with the reaction time, while the organics toxicities kept the same level in different reaction times. In order to explain the difference, the relative cell death rate of V. fischeri was detected. In metals toxicities tests, the bioluminescence inhibition rate of V. fischeri was found to be significantly higher than the relative cell death rate (P<0.05, while for the organics toxicities tests, the cell death rate was similar to the bioluminescence inhibition rate. These results indicated that organics acute toxicities to V. fischeri could reflect the death of cell, but metals acute toxicities to V. fischeri may not lead to the death of cell, just represent the bioluminescence inhibition.

  17. ACUTE TOXICITY OF METHOMYL ON POECILIA LATIPINNA (LESUEUR 1821 (POECILIDAE

    Napan, K.

    2010-01-01

    Full Text Available Methomyl is a chemical compound acetylcholinesterase inhibitor that acts by contact system and is one of the most widely used chemicals such as insecticide-acaricide for control of a wide range of agricultural pests. The following study aims to assess the acute toxicity of methomyl on introduced fish Poecilia latipinna (Lesueur 1821 (Poecilidae at 2, 4, 6, 8, 24, 48, 72 and 96 h of exposure. Bioassays were carried out with 5 levels and 4 treatments, temperature was 21.8 ° C ± 1, pH 7.34 ± 0.31, conductivity 0.54 mS ± 0.03, and average dissolved solutes in the middle 267.39 mg.L-1. The data obtained during tests were evaluated using the statistical method analytic Probit ver. 1.5. The results of the median Lethal Concentration (LC of methomyl on P. latipinna were: 2 h = 13.95 mg IA.L-1, 4 h 50 =10.39 mg IA.L-1, 6 h = 8.12 mg IA.L-1, 8 h = 5.81 mg IA.L-1, 24 h 3.99 mg IA.L-1, 48 h = 2.61 mg IA.L-1, 72 h = 2.24 mg IA.L-1 and finally 96 h = 2.08 IA.L mg-1. At the highest concentration was observed a change of skin color intensity of silver to black.

  18. Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

    Kouloulias, Vassilis; Zygogianni, Anna; Kypraiou, Efrosini; Georgakopoulos, John; Thrapsanioti, Zoi; Beli, Ivelina; Mosa, Eftychia; Psyrri, Amanta; Antypas, Christos; Armbilia, Christina; Tolia, Maria; Platoni, Kalliopi; Papadimitriou, Christos; Arkadopoulos, Nikolaos; Gennatas, Costas; Zografos, George; Kyrgias, George; Dilvoi, Maria; Patatoucas, George; Kelekis, Nikolaos; Kouvaris, John

    2014-01-01

    AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ2 test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions. PMID:25405195

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

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  20. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  1. Acute toxicity and effect of some petroleum hydrocarbon on the metabolic index in Etroplus suratensis

    Ansari, Z.A.; Farshchi, P.

    Acute toxicity (LC sub(50)) and effect of some petroleum hydrocarbons (Toluene, Quinoline, Pyridine and Naphthalene) on the metabolic index (oxygen consumption rate) of an estuarine fish. Etroplus suratensis is reported. The LC sub(50) values were...

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

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

    2013-08-01

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

  3. Understanding how data triangulation identifies acute toxicity of novel psychoactive drugs.

    Wood, D M; Dargan, P I

    2012-09-01

    Over the last decade, there has been an increase in the availability and use of novel psychoactive substances (also known as "legal highs"). There is limited information available on the potential acute toxicity (harms) associated with the use of these novel psychoactive substances. Gold standard evidence, such as animal studies or human clinical trials, is rarely available to users or healthcare professionals. However, it is possible to use triangulation of data on the acute toxicity from multiple sources to describe the overall pattern of toxicity associated with a novel psychoactive substance. In this review, we will describe these potential data sources, which include self-reported toxicity on internet discussion fora, data from sub-population user surveys, data from regional and national poisons information services and published case reports and case series. We will then describe how pattern of acute toxicity associated with the use of the cathinone mephedrone (4-methylmethcathinone) was established using triangulation of these different data sources.

  4. Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

    Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

    2014-12-01

    A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies.

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

    Alsop, Derek, E-mail: alsopde@mcmaster.ca; Wood, Chris M.

    2013-09-15

    Highlights: •Zebrafish larvae were used to test the acute toxicity of contaminant mixtures. •Interactions were observed between metals, ammonia and pharmaceuticals. •Larval Na{sup +} loss was observed with exposure to all acutely toxic contaminants tested. •Water quality criteria should recognize the toxic interactions between contaminants. -- Abstract: The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4–8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC{sub 50}, one third of the LC{sub 01}) to all copper treatments decreased the copper 96 h LC{sub 50} by 58%, while sublethal copper exposure (6% of the copper LC{sub 50}, 13% of the LC{sub 01}) decreased the cadmium 96 h LC{sub 50} by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na{sup +} followed by K{sup +} (as high as 19% and 9%, respectively, in 24 h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na{sup +} and K{sup +}. Overall, whole body Na{sup +} loss showed the greatest correlation with mortality across a

  6. [Anti-NMDA-receptor encephalitis].

    Engen, Kristine; Agartz, Ingrid

    2016-06-01

    BACKGROUND In 2007 a clinical disease caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor was described for the first time. Anti-NMDA-receptor encephalitis is a subacute, autoimmune neurological disorder with psychiatric manifestations. The disease is a form of limbic encephalitis and is often paraneoplastic. The condition is also treatable. In this review article we examine the development of the disease, clinical practice, diagnostics and treatment.MATERIAL AND METHOD The article is based on references retrieved from searches in PubMed, and a discretionary selection of articles from the authors' own literature archive.RESULTS The disease most frequently affects young women. It may initially be perceived as a psychiatric condition, as it usually presents in the form of delusions, hallucinations or mania. The diagnosis should be suspected in patients who later develop neurological symptoms such as various movement disorders, epileptic seizures and autonomic instability. Examination of serum or cerebrospinal fluid for NMDA receptor antibodies should be included in the assessment of patients with suspected encephalitis. MRI, EEG and assessment for tumours are important tools in diagnosing the condition and any underlying malignancy.INTERPRETATION If treatment is initiated early, the prognosis is good. Altogether 75 % of patients will fully recover or experience significant improvement. Apart from surgical resection of a possible tumour, the treatment consists of immunotherapy. Because of good possibilities for treatment, it is important that clinicians, particularly those in acute psychiatry, are aware of and alert to this condition.

  7. Acute and chronic toxicity of short chained perfluoroalkyl substances to Daphnia magna

    Barmentlo, S.H.; Stel, J.M.; van Doorn, M.; Eschauzier, C.; de Voogt, P.; Kraak, M.H.S.

    2015-01-01

    The aim of this study was to evaluate the aquatic toxicity of a C4-C6 chemistry based fluoroalkylated polymer and the perfluoroalkyl carboxylic acids, PFBA, PFHxA and PFOA to Daphnia magna. The acute toxicity decreased with decreasing carbon chain length, but the polymer did not show a dose related

  8. Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity

    Srinivas Kakhandki

    2012-01-01

    Full Text Available A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

  9. Staphylococcal toxic shock syndrome presenting as acute respiratory distress and cor pulmonale.

    Zaki, S A; Shanbag, P; Chavan, V; Shenoy, P

    2010-01-01

    We describe a 7-year-old boy with staphylococcal toxic shock syndrome who presented with acute respiratory distress and cor pulmonale. We wish to highlight this unusual presentation as the diagnosis of toxic shock syndrome depends chiefly on a high degree of clinical suspicion. Early diagnosis and prompt institution of appropriate therapy will significantly reduce morbidity and mortality.

  10. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity.

    Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  11. Comparative acute toxicity of DDT metabolites among American and European species of planarians.

    Bonner, J C; Wells, M R

    1987-01-01

    1. DDT metabolism in a North American species of planarian leads to the formation of metabolites more toxic than the parent compound. 2. The increased toxicity of DDT metabolites is similar to acute toxicity data reported previously in a European species. 3. It is suggested that planarians lack a direct mechanism for DDT detoxification, since two North American and one European species are known to metabolize DDT initially to DDE and DDD.

  12. Acute toxicity of furazolidone on Artemia salina, Daphnia magna, and Culex pipiens molestus larvae

    Macri, A.; Stazi, A.V.; Dojmi di Delupis, G.

    1988-10-01

    As a result of evidence of the ecotoxicity of nitrofurans, the acute toxicity of furazolidone was tested in vivo on two aquatic organisms, Artemia salina and Daphnia magna, which are both crustaceans. Toxicity studies were also performed on larvae of Culex pipiens molestus. Results indicated a significant toxicity of the compound on Culex pipiens and Daphnia magna, while Artemia salina proved to be the least sensitive.

  13. Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

    A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC.

  14. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  15. Principal component and causal analysis of structural and acute in vitro toxicity data for nanoparticles.

    Wang, Xue Z; Yang, Yang; Li, Ruifa; McGuinnes, Catherine; Adamson, Janet; Megson, Ian L; Donaldson, Kenneth

    2014-08-01

    Structure toxicity relationship analysis was conducted using principal component analysis (PCA) for a panel of nanoparticles that included dry powders of oxides of titanium, zinc, cerium and silicon, dry powders of silvers, suspensions of polystyrene latex beads and dry particles of carbon black, nanotubes and fullerene, as well as diesel exhaust particles. Acute in vitro toxicity was assessed by different measures of cell viability, apoptosis and necrosis, haemolytic effects and the impact on cell morphology, while structural properties were characterised by particle size and size distribution, surface area, morphology, metal content, reactivity, free radical generation and zeta potential. Different acute toxicity measures were processed using PCA that classified the particles and identified four materials with an acute toxicity profile: zinc oxide, polystyrene latex amine, nanotubes and nickel oxide. PCA and contribution plot analysis then focused on identifying the structural properties that could determine the acute cytotoxicity of these four materials. It was found that metal content was an explanatory variable for acute toxicity associated with zinc oxide and nickel oxide, while high aspect ratio appeared the most important feature in nanotubes. Particle charge was considered as a determinant for high toxicity of polystyrene latex amine.

  16. Acute toxicity of pyraclostrobin and trifloxystrobin to Hyalella azteca.

    Morrison, Shane A; McMurry, Scott T; Smith, Loren M; Belden, Jason B

    2013-07-01

    Fungicide application rates on row crop agriculture have increased across the United States, and subsequently, contamination of adjacent wetlands can occur through spray drift or field runoff. To investigate fungicide toxicity, Hyalella azteca amphipods were exposed to 2 fungicide formulations, Headline and Stratego, and their active strobilurin ingredients, pyraclostrobin and trifloxystrobin. Water-only exposures resulted in similar median lethal concentration (LC50; 20-25 µg/L) values for formulations and strobilurin ingredients, suggesting that toxicity is due to strobilurin ingredients. These values were below concentrations that could occur following spray drift over embedded cropland wetlands. When fungicides were added to overlying water of sediment-water microcosms, toxicity was reduced by 500% for Headline and 160% for Stratego, compared with water-only exposures, based on the total amount of fungicide added to the systems. In addition, when fungicides were added to sediment prior to the addition of water, the reduction in toxicity was even greater, with no toxicity occurring at environmentally relevant levels. Differences in toxicity among exposure groups were explained by dissipation from water as toxicity values based on measured water concentrations were within 20% between all systems. The present study reinforces previous studies that Headline and Stratego are toxic to nontarget aquatic organisms. However, the presence of sediment is likely to ameliorate some toxicity of fungicide formulations, especially if spraying occurs prior to wetland inundation.

  17. Acute toxicity of combined photon IMRT and carbon ion boost for intermediate-risk prostate cancer - Acute toxicity of 12C for PC

    Nikoghosyan, Anna V.; Herfarth, Klaus; Didinger, Bernd; Muenter, Marc W.; Jensen, Alexandra D.; Debus, Juergen (Dept. of Radiation Oncology, Univ. of Heidelberg (Germany)), e-mail: a.nikoghosyan@med.uni-heidelberg.de; Schulz-Ertner, Daniela (Radiological Inst. (Medical Care Unit), Markus Hospital, Frankfurt/Main (Germany)); Jaekel, Oliver (Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg (Germany); Heidelberg Ion Beam Therapy Centre of the Univ. Hospital Heidelberg (Germany)); Hoess, Angelika; Haberer, Thomas (Heidelberg Ion Beam Therapy Centre of the Univ. Hospital Heidelberg (Germany))

    2011-08-15

    Background. Carbon ion (12C) therapy in the treatment of prostate cancer (PC) might result in an improved outcome as compared to low linear energy transfer irradiation techniques. In this study, we present the first interim report of acute side effects of the first intermediate-risk PC patients treated at the GSI (Gesellschaft fuer Schwerionenforschung) and the Univ. of Heidelberg in an ongoing clinical phase I/II trial using combined photon intensity modulated radiation therapy (IMRT) and 12C carbon ion boost. Material and methods. Fourteen patients (planned accrual: 31 pts) have been treated within this trial so far. IMRT is prescribed to the median PTV at a dose of 30 x 2 Gy; 12C boost is applied to the prostate (GTV) at a dose of 6 x 3 GyE using raster scan technique. Safety margins added to the clinical target volume were determined individually for each patient based on five independent planning computed tomography (CT)-scans. Acute gastrointestinal (GI) and genitourinary (GU) toxicity was assessed and documented according to the CTCAE Version 3.0. Results. Radiotherapy was very well tolerated without any grade 3 or higher toxicity. Acute anal bleeding grade 2 was observed in 2/14 patients. Rectal tenesmus grade 1 was reported by three other patients. No further GI symptoms have been observed. Most common acute symptoms during radiotherapy were nocturia and dysuria CTC grade 1 and 2 (12/14). There was no severe acute GU toxicity. Conclusion. The combination of photon IMRT and carbon ion boost is feasible in patients with intermediate-risk PC. So far, the treatment has been well tolerated. Acute toxicity rates were in good accordance with data reported for high dose IMRT alone

  18. Acute and Subacute Oral Toxicity of Periodate in Rats

    2014-11-17

    Inflammation - Minimal, Subacute Necrosis, glandular stomach - Minimal Testes (Required) Degeneration - Mild, Germinal Epithelium Thymus (Required...diagnosed separately). Necrosis, glandular stomach- Minimal, Acute Testes (Required) Degeneration - Mild, Germinal Epithelium Thymus (Required...Stomach (Required) Necrosis, glandular stomach - :tvfinimal, Acute Testes (Required) Degeneration - Mild, Germinal Epithelium Thymus (Required) Atrophy

  19. An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes

    Huang, Xiao-Ting; Li, Chen; Peng, Xiang-Ping; Guo, Jia; Yue, Shao-Jie; Liu, Wei; Zhao, Fei-Yan; Han, Jian-Zhong; Huang, Yan-Hong; Yang-Li, Y -L; Cheng, Qing-Mei; Zhou, Zhi-Guang; Chen, Chen; Feng, Dan-Dan; Luo, Zi-Qiang

    2017-01-01

    In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia. PMID:28303894

  20. Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats

    Janet Mobolaji Olaniyan; Hadiza Lami Muhammad; Hussaini Anthony Makun; Musa Bola Busari; Abubakar Siddique Abdullah

    2016-01-01

    Objective: To evaluate the acute and sub-acute toxicity of aqueous and methanol ex-tracts of Nelsonia campestris (N. campestris) in rats. Methods: Acute oral toxicity study of aqueous and methanol extracts was carried out by administration of 10, 100, 1 000, 1 600, 2 900 and 5 000 mg/kg body weight of N. campestris extracts to rats in the respective groups. Sub-acute toxicity study was conducted by oral administration of the extracts at daily doses of 100, 300 and 600 mg/kg body weight to another group of rats for 28 days, while rats in the control group received 0.5 mL of normal saline. Results: The LD50 of the N. campestris extracts in rats was determined to be greater than 5 000 mg/kg body weight. There was no significant difference (P>0.05) between the test groups administered with aqueous and methanol extracts in relation to the control group for serum electrolytes (Na+, K+, Cl−, HCO3−), serum albumin, total and conjugated bili-rubin. Similarly, mean organ-to-body weight ratio and all haematological parameters (white blood cell, red blood cell, mean cell volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, packed cell volume) evaluated were not significantly different (P > 0.05) from the control. There was a significant increase (P Conclusions: Intake of high doses of this plant extracts may exhibit mild organ toxicity.

  1. Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

    Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

    2014-08-01

    Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively.

  2. Influences of water chemistry on the acute toxicity of lead to Pimephales promelas and Ceriodaphnia dubia.

    Mager, Edward M; Esbaugh, Andrew J; Brix, Kevin V; Ryan, Adam C; Grosell, Martin

    2011-01-01

    The acute toxicity of lead (Pb) was examined for fathead minnows (Pimephales promelas; 96-h) and daphnids (Ceriodaphnia dubia; 48-h) in waters modified for hardness (as CaSO₄), dissolved organic carbon (DOC; as Aldrich humic acid) and alkalinity (as NaHCO₃) for parameterization of an acute freshwater biotic ligand model (BLM). Additionally, acute (96-h) and chronic (30-d) bioassays were performed for P. promelas to more clearly define the influence of pH (5.5-8.3) on Pb toxicity as modified by addition of HCl or NaOH using an automated titration system. Results indicate that Ca(2+) is protective against acute Pb toxicity to P. promelas but not C. dubia. Strong protection was afforded by DOC and NaHCO(3) against acute Pb toxicity to P. promelas, whereas milder protection was observed for C. dubia with both parameters. Dissolved Pb LC50s from the P. promelas pH bioassays revealed a complex effect of pH on Pb toxicity, likely explained in part by Pb speciation and the competitive interaction of H(+) with ionic Pb(2+). Chronic pH bioassays also demonstrated that 30-d growth is not impaired in fathead minnows at relevant Pb concentrations. The findings reported herein suggest that development of separate BLMs for P. promelas and C. dubia should be considered.

  3. Acute toxicity tests on raw leachate from a Malaysian dumping site.

    Sujá, Fatihah; Yusof, Arij; Osman, Md Anuar

    2010-01-01

    Leachate samples collected from the Ampar Tenang open dumping site at Dengkil, Malaysia, were analyzed for acute toxicity. Two in vivo toxicity tests, Acute Oral Toxicity (AOT) and Primary Skin Irritation (PSI), were performed using Sprague Dawley rats and New Zealand Albino rabbits, respectively. The leachate samples were also analyzed chemically for nitrate and phosphate, ammonia-nitrogen, Kjeldahl-nitrogen and Chemical Oxygen Demand (COD). Results from both the AOT and PSI tests showed that the leachate did not contribute to acute toxicity. The AOT test yielded a negative result: no effect was observed in at least half of the rat population. The PSI test on rabbits produced effects only at a leachate concentration of 100%. However, the skin irritation was minor, and the test returned a negative result. The four chemical tests showed high levels of nutrient pollution in the leachate. The nitrate and phosphate concentrations were 2.1 mg/L and 23.6 mg/L, respectively. Further, the ammonia-nitrogen concentration was 1,000 mg NH(3)-N/L the Kjeldahl-nitrogen level was 446 mg NH(3)-N/L, and the Chemical Oxygen Demand was 1,300 mg/L. The in vivo toxicity and chemical analyses showed that the leachate is polluted but not acutely toxic to organisms.

  4. Acute toxicity of commonly used forestry herbicide mixtures to Ceriodaphnia dubia and Pimephales promelas.

    Tatum, Vickie L; Borton, Dennis L; Streblow, William R; Louch, Jeffrey; Shepard, James P

    2012-12-01

    Because many herbicides selectively control specific species or types of vegetation, they are often applied as mixtures to achieve better control over undesirable vegetation. When herbicides are applied in forest ecosystems, streams, ponds, and other bodies of water are typically protected by buffer zones in which no herbicide is applied. However, in some landscapes, small wetlands and streams are difficult to see and avoid, thus the potential acute toxicity of herbicide mixtures to aquatic organisms is of interest, yet it has not been well-studied. We examined the acute toxicity of 23 different herbicide mixtures to Ceriodaphnia dubia and fathead minnows (Pimephales promelas) at environmentally relevant concentrations, and, where possible, characterized mixture interactions using Marking's Additive Index. Maximum exposure concentrations were equivalent to applying the maximum allowable rate for each component directly to the surface of a 6-in. deep pond with no dissipation following application. Under the conditions of this study, herbicide formulations containing Accord Concentrate (glyphosate), Arsenal AC (imazapyr), Chopper (imazapyr), Escort (metsulfuron methyl), Oust XP (sulfometuron methyl), and Velpar L (hexazinone) were not associated with appreciable acute toxicity to fathead minnows or C. dubia when used alone or in mixtures with each other and various surfactants and adjuvants. Herbicide mixtures for which Additive Indexes could be calculated exhibited primarily antagonistic or simple additive toxicity. In the few cases where synergistic toxicity was observed, the degree of synergism was slight, never exceeding approximately twice the effect estimated based on additive toxicity. Based on the results of this study, neither acute toxicity nor enhanced acute aquatic toxicity due to synergistic mixture effects appears to be a significant concern for applications of the herbicide mixtures most commonly used in forestry.

  5. Characterisation of acute toxicity, genotoxicity and oxidative stress posed by textile effluent on zebrafish

    Wenjuan Zhang; Wei Liu; Jing Zhang; Huimin Zhao; Yaobin Zhang; Xie Quan; Yihe Jin

    2012-01-01

    Textile industries are important sources of toxic discharges and contribute enormously to water deterioration,while little attention has been paid to the toxicity of textile effluents in discharge regulation.Bioassays with zebrafish were employed to evaluate the toxicity of wastewater samples collected from different stages at a textile factory and sewage treatment plants (STPs).Physico-chemical parameters,acute toxicity,genotoxicity and oxidative stress biomarkers were analyzed.The wastewater samples from bleaching,rinsing and soaping of the textile factory exhibited high acute toxicity and genotoxicity.The coexisting components of dye compounds,as assistants and oxidants,seemed to cause some effect on the toxic response.After treatment employing the anoxic-oxic (A/O) process in STPs,the color and the chemical oxygen demand (COD) were reduced by 40% and 84%,respectively,falling within the criteria of the Chinese Sewage Discharge Standard.In contrast,increases in acute toxicity and genotoxicity were observed in the anaerobic tank,indicating the formation of toxic intermediates.The genotoxicity of the effluent of the STP was not significantly different from that of the influent,suggesting the wastewater treatment processes were not effective in removing the genotoxicity of the dye wastewater.Results indicated that the effluent contains pro-oxidants since the activities of glutathione (GSH),malondialdehyde (MDA),and total anti-oxidation capacity (T-AOC) were all elevated.In addition,decreases in superoxide dismutase (SOD) and glutathione-S transferase (GST) activities observed can be interpreted as a cytotoxicity sign due to an over-production of reactive oxygen species (ROS).The results of the present study suggest that the STPs were not capable of reducing the toxicity of wastewater sufficiently.Further treatment is needed to remove the potential risks posed by textile effluent to ecosystems and human health,and employing a toxicity index is necessary for

  6. Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

    Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

    2011-10-15

    All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

  7. Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

    Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

    2016-02-01

    Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

  8. Inhibition effect of glyphosate on the acute and subacute toxicity of cadmium to earthworm Eisenia fetida.

    Zhou, Chui-Fan; Wang, Yu-Jun; Sun, Rui-Juan; Liu, Cun; Fan, Guang-Ping; Qin, Wen-Xiu; Li, Cheng-Cheng; Zhou, Dong-Mei

    2014-10-01

    The acute and subacute toxicities of cadmium (Cd) to earthworm Eisenia fetida in the presence and absence of glyphosate were studied. Although Cd is highly toxic to E. fetida, the presence of glyphosate markedly reduced the acute toxicity of Cd to earthworm; both the mortality rate of the earthworms and the accumulation of Cd decreased with the increase of the glyphosate/Cd molar ratio. The subcellular distribution of Cd in E. fetida tissues showed that internal Cd was dominant in the intact cells fraction and the heat-stable proteins fraction. The presence of glyphosate reduced the concentration of Cd in all fractions, especially the intact cells. During a longer period of exposure, the weight loss of earthworm and the total Cd absorption was alleviated by glyphosate. Thus, the herbicide glyphosate can reduce the toxicity and bioavailability of Cd in the soil ecosystems at both short- and long-term exposures.

  9. Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

    Yang Yu; Yang Li; Wen Wang; Minghua Jin; Zhongjun Du; Yanbo Li; Junchao Duan; Yongbo Yu; Zhiwei Sun

    2013-01-01

    This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the l...

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

    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.

  11. Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems.

    Woehrling, E K; Hill, E J; Coleman, M D

    2010-02-01

    Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

  12. Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

    Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Striecker, Thorbjoern; Kessel, Kerstin [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Habl, Gregor [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Edler, Lutz [Department of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Debus, Juergen [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Herfarth, Klaus [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany)

    2014-11-15

    Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

  13. Acute toxicity assessment of ANAMMOX substrates and antibiotics by luminescent bacteria test.

    Ding, Shuang; Wu, Junwei; Zhang, Meng; Lu, Huifeng; Mahmood, Qaisar; Zheng, Ping

    2015-12-01

    Acute toxicities of anaerobic ammonia oxidation (ANAMMOX) substrates and four antibiotics from pharmaceutical wastewaters on ANAMMOX process were reported. Individual and joint acute toxicity assays were performed using 50% inhibitory concentration (IC50). Results showed that IC50 values and their 95% confidence interval of ammonium chloride (A), sodium nitrite (B), penicillin G-Na (C), polymyxin B sulfate (D), chloramphenicol (E) and kanamycin sulfate (F) were 2708.9 (2247.9-3169.9), 1475.4 (1269.9-1680.9), 5114.4 (4946.4-5282.4), 10.2 (1.8-18.6), 409.9 (333.7-486.1) and 5254.1 (3934.4-6573.8) mgL(-1) respectively, suggesting toxicities were in the order of D>E>B>A>C>F. Joint acute toxicities of bicomponent mixtures A and B, C and D, C and F, D and F were independent; D and E, E and F were additive while C and E were synergistic. Joint acute toxicities of multicomponent mixtures were synergistic or additive. Luminescent bacteria test is an easy and robust method for forecasting the feasibility of ANAMMOX process for pharmaceutical wastewater treatment.

  14. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

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

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

    2010-01-01

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

  16. Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically.

    Gable, R S

    1993-01-01

    A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances. Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments.

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

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

    2013-11-01

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

  18. Acute toxicity of organic solvents on Artemia salina

    Barahona-Gomariz, M.V.; Sanz-Barrera, F.; Sanchez-Fortun, S. (Complutense Univ. of Madrid (Spain))

    1994-05-01

    Organic solvents can make their way into the environment as industrial wastes and components of pesticide formulation. In laboratory bioassays, the use of organic formulations. In laboratory bioassays, the use of organic solvents is often unavoidable, since many pesticides and organic pollutants have low water solubility and must be dissolved in organic solvents prior to addition into experimental systems. In the toxicant bioassays, invertebrates with special reference to aquatic arthropod species are of recent interest as test models due to the need for developing nonmammalian test systems. Toxic effects of organic solvents have been tested with a few aquatic species, but information on the comparative toxicity of solvents towards Artemia salina is not available. Artemia salina have, within recent years, gained popularity as test organisms for short-term toxicity testing. Because Artemia salina exhibit rapid development and growth within 48 hr after hatch, their potential as a model organism for toxicology screening has been considered. To do this, synchronous populations of Artemia salina at different development intervals must be available.

  19. Draft Test Guideline: Fish Acute Toxicity Test, Freshwater And Marine

    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.

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

    Badakhshan Mahdi Pour

    2011-05-01

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

  1. Evaluation of acute toxicity and teratogenic effects of plant growth regulators by Daphnia magna embryo assay.

    Wang, Kai-Sung; Lu, Chi-Yuan; Chang, Shih-Hsien

    2011-06-15

    This study selected common plant growth regulators (Atonik, Cytokinin, Ethephon, Gibberellic acid and Paclobutrazol) to investigate their biological toxicity to the waters of the important biological indicator Daphnia magna. The methods used in this study included traditional neonate acute toxicity test, new Daphnia embryo toxicity test, and teratogenic embryo test. The study concluded that the acute toxicity of the five PGRs to Daphnia neonate had EC(50) value range of 1.9-130.5 mg l(-1), while acute toxicity of PGRs on Daphnia embryo had EC(50) value range of 0.2-125 mg l(-1); the Daphnia embryos' LOEC values (0.05-48 mg l(-1)) for the five PGRs were lower than embryo EC(50) values. The toxic ratios of 48 h EC(50) (neonate)/48 h LOEC (embryo) for 5 PGRs were 19-512 times. The study found that teratogenic effects of Paclobutrazol and Cytokinin induced in embryo were higher than those of most other PGRs. Microscopic observation of the teratogenic effects showed that all 5 PGRs induced malformations of the second antenna, rostrum, Malpighian tube, sensory bristles, and tail spine as well as function loss and death.

  2. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols.

    Chen, Min-Yu; Ike, Michihiko; Fujita, Masanori

    2002-02-01

    Although abundant data are available on the toxicity of bisphenol-A (2,2-bis (4-hydroxydiphenyl)propane; BPA), little is known about the toxicities of the structurally similar compounds, namely bisphenols (BPs). A variety of BPs were examined for their acute toxicity against Daphnia magna, mutagenicity, and estrogenic activity using the Daphtoxkit (Creasel Ltd.), the umu test system, and the yeast two-hybrid system, respectively, in comparison with BPA. BPA was moderately toxic to D. magna (48-h EC50 was 10 mg/l) according to the current U.S. EPA acute toxicity evaluation standard, and it was weakly estrogenic with 5 orders of magnitude lower activity than that of the natural estrogen 17 beta-estradiol in the yeast screen, while no mutagenicity was observed. All seven BPs tested here showed moderate to slight acute toxicity, no mutagenicity, and weak estrogenic activity as well as BPA. Some of the BPs showed considerably higher estrogenic activity than BPA, and others exhibited much lower activity. Among the tested BPs, two compounds, i.e., bisphenol-S (bis(4-hydroxydiphenyl)sulfone) and bis(4-hydroxyphenyl)sulfide, have never been reported for their estrogenic activity previously.

  3. The NMDA receptor ion channel: a site for binding of Huperzine A.

    Gordon, R K; Nigam, S V; Weitz, J A; Dave, J R; Doctor, B P; Ved, H S

    2001-12-01

    inhibition of [3H]QNB or [3H]NMS binding) or nicotinic [3H]epibatidine binding) receptors; also, HUP-A did not perturb adenosine receptor binding [3H]PIA or [3H]NECA). Therefore, HUP-A most likely attenuates excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites. Thus, on the one hand, HUP-A could be used as a pretreatment against OPs and it might also be a valuable therapeutic intervention in a variety of acute and chronic disorders by protecting against overstimulation of the excitatory amino acid pathway. By blocking NMDA ion channels without psychotomimetic side-effects, HUP-A may protect against diverse neurodegenerative states observed during ischemia or Alzheimer's disease.

  4. Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

    Rashmee Patil

    2015-01-01

    Full Text Available The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir-associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral.

  5. Acute Toxicity of Sodium Fluorescein to Ashy Pebblesnails Fluminicola fuscus

    Stockton, Kelly A.; Moffitt, Christine M.; Blew, David L.; Farmer, C. Neil

    2011-01-01

    Water resource agencies and groundwater scientists use fluorescein dyes to trace ground water flows that supply surface waters that may contain threatened or endangered mollusk species. Since little is known of the toxicity of sodium fluorescein to mollusks, we tested the toxicity of sodium fluorescein to the ashy pebblesnail Fluminicola fuscus. The pebblesnail was selected as a surrogate test species for the threatened Bliss Rapid snail Taylorcocha serpenticola that is endemic to the Snake River and its tributaries in the Hagerman Valley, Idaho. In laboratory tests, we expose replicated groups of snails to a series of concentrations of fluorescein in a static 24 h exposure at 15 degrees C. Following the exposure, we removed snails, rinsed them, and allowed a 48 h recovery in clean water before recording mortality. We estimated 377 mg/L as the median lethal dose. Mortality to snails occurred at concentrations well above those expected in test wells during the monitoring efforts.

  6. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    To support approval of pharmaceuticals for long term use in humans it is required that product safety is supported by acute and chronic toxicity studies in rodents and non-rodents. The duration of acute toxicity studies (S4A) and chronic rodent studies (S4B) were harmonised between the three ICH ...

  7. Assessment of Acute Toxicity of Hexachloroethane in Laboratory Animals

    1978-01-09

    camphoraceous odor, readily sublimes without meltinq and is solubl,: in alcohol. benzene, chloroform, ether and oil: insoluble in water. It is used as a solvent...in explosives, as ý camphor suostitute in celluloid, and as a rubber vulcanizing accelerator.’ It is used in veterinary practice as an anthelminthic...moderately toxic orally, produced reversible eye irritation and little or no skin irritation. Although it sublimes at room temperature

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

    2010-01-01

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

  9. Acute toxicity evaluation of cutting fluids used in manufacturing processes to Poecilia reticulata and Daphnia magna

    William Gerson Matias

    2006-09-01

    Full Text Available Grinding operations are very significant among the manufacturing processes of the metal-mechanic industry. In conventional grinding, cutting fluids are of great concern for improving productivity, but also for being hazardous to the environment. In order to contribute to the knowledge of the actual toxic effects of these products in aquatic environments, the present work assesses the toxicity potential through acute toxicity tests of three different kinds of cutting fluids, with three different usage times. The tests were carried out using the fish Poecilia reticulate and the microcrustacean Daphnia magna as test organisms. These tests made it possible to determine the Median Lethal Concentration (LC50 for the fish and the Median Effective Concentration (EC50 for the microcrustacean. The results indicate that, after storage, the toxicity potential of cutting fluids decreases. However, in the three situations investigated, the product presented a high toxicity potential, which reinforces the need of special care in its handling, usage and disposal.

  10. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  11. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

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

    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 se

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

    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.

  14. Reduction of acute toxicity of the pharmaceutical fluoxetine (Prozac) submitted to ionizing radiation to Vibrio fischeri

    Santos, Dymes R.A.; Garcia, Vanessa S.G.; Vilarrubia, Anna C.S.; Borrely, Sueli I., E-mail: vanessagarcia@usp.br, E-mail: sborrely@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L{sup -1}, 2.34 mg.L{sup -1}, 2.35 mg.L{sup -1} and 1.80 mg.L{sup -1}, respectively, showing a notable reduction of the acute toxicity for this organism. (author)

  15. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  16. ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

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

  17. Acute and chronic toxicity of lead in water and diet to the amphipod Hyalella azteca

    Besser, J.M.; Brumbaugh, W.G.; Brunson, E.L.; Ingersoll, C.G.

    2005-01-01

    We evaluated the influence of waterborne and dietary lead (Pb) exposure on the acute and chronic toxicity of Pb to the amphipod Hyalella azteca. Test solutions were generated by a modified diluter with an extended (24-h) equilibration period. Acute (96-h) toxicity of Pb varied with water hardness in the range of 71 to 275 mg/L as CaCO3, despite similar dissolved Pb concentrations. Acute toxicity was greatest in soft test water, with less than 50% survival at the lowest dissolved Pb concentration (151 ??g/L). Survival also was significantly reduced in medium-hardness water but not in hard test water. In chronic (42-d) studies, amphipods were exposed to waterborne Pb and fed either a control diet or a diet equilibrated with waterborne Pb levels. For animals fed the control diet, the median lethal concentration (LC50) for Pb was 24 ??g/L (as dissolved Pb), and significant reductions in survival occurred at 16 ??g/L. Exposure to Pb-treated diets significantly increased toxicity across a wide range of dissolved Pb concentrations, with a LC50 of 16 ??g/L and significant reductions in growth and reproduction at 3.5 ??g/L. Significant effects on growth and reproduction occurred at dissolved Pb concentrations close to the current U.S. chronic water-quality criterion. Our results suggest that both aqueous- and dietary-exposure pathways contribute significantly to chronic Pb exposure and toxic effects in aquatic biota. ?? 2005 SETAC.

  18. A summary of the acute toxicity of 14 phthalate esters to representative aquatic organisms

    Adams, W.J. [ABC Labs. (United States), Inc., Columbia, MO (United States); Biddinger, G.R. [Exxon Biomedical Sciences Inc., Benecia, CA (United States); Robillard, K.A.; Gorsuch, J.W. [Eastman Kodak Co., Rochester, NY (United States)

    1995-09-01

    Acute aquatic toxicity studies were performed with 14 commercial phthalate esters and representative freshwater and marine species. The 14 esters were dimethyl phthalate; diethyl phthalate; di-n-butyl phthalate; butyl benzyl phthalate; dihexyl phthalate; butyl 2-ethylhexyl phthalate; di-(n-hexy, n-octyl, n-decyl) phthalate; di-(2-ethylhexyl) phthalate; diisooctyl phthalate; diisononyl phthalate; di-(heptyl, nonyl, undecyl) phthalate; diisodecyl phthalate; diundecyl phthalate; and ditridecyl phthalate. Phthalate esters with alkyl chain lengths of four carbon atoms or fewer were determined to be actually toxic at concentrations ranging from 0.21 to 377 mg/L depending on the ester and the solubility of the test chemical in water. Three was a general trend for the lower-molecular-weight phthalate esters (C{sub 1} to C{sub 4} alkyl chain lengths: dimethyl phthalate; diethyl phthalate; di-n-butyl phthalate; and butyl benzyl phthalate) to become more toxic with decreasing water solubility for all species tested. There were only minor differences in species sensitivity to each of the phthalate esters. Phthalate esters with alkyl chain lengths of six carbon atoms or more were not acutely toxic at concentrations approaching their respective aqueous solubilities. Insufficient mortality occurred to calculate either LC50 or EC50 values or acute no-observed-effect concentrations for these higher-molecular-weight phthalate esters. The lack of toxicity observed for the higher-molecular-weight phthalate esters resulted from their limited water solubility ({le}1.1 mg/L).

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

    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.

  20. Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

    Behrensmeier Frank

    2008-10-01

    Full Text Available Abstract Background To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT and organ tracking. Methods From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU was 29 months. Results Acute and maximal late grade 2 gastrointestinal (GI toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU morbidity (PGUM was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025, absence of HT (P = .016 and higher PGUM (P Discussion GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

  1. [Clinical and immunological features of acute hepatitis B in patients with concomitant chronic toxic liver damage].

    Furyk, E; Ryabokon, E

    2013-02-01

    The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.

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

    K S Sim

    2010-01-01

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

  3. Whole effluent toxicity of agricultural irrigation drainwater entering Stillwater National Wildlife Refuge, NV : Acute toxicity studies with fish and aquatic invertebrates

    US Fish and Wildlife Service, Department of the Interior — This report covers the acute toxicity studies conducted with samples collected from Stillwater National Wildlife Refuge. The objective of these studies was to...

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

    1982-09-01

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

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

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

    2012-01-01

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

  6. Acute toxicity and hepatotoxicokinetic studies of Tamarindus indica extract.

    Nwodo, Uchechukwu U; Ngene, Augustine A; Anaga, Aruh O; Chigor, Vincent N; Henrietta, Igbinosa I; Okoh, Anthony I

    2011-08-31

    Tamarindus indica is widely used as a food and beverage and in traditional medicine. The apparent lack of dose standardization in herbal medicine necessitates the evaluation of the lethality T. indica on Artemia salina nauplii and chicken embryos via in vitro and in vivo techniques. Furthermore, hepatotoxicokinetics of the crude extract and fractions on Wister rats was also assessed. At concentrations of 200, 20 and 2 µg/mL, crude extract and fractions showed brine shrimp death percentages ranging from 86.70% to 3.30% and the sub-fractions showed death percentage ranges of 46.70% to 3.30%. Calculated LD₅₀ values ranged from 832 µg/mL to 5,019 µg/mL. Dosing Wister rats with 25% and 50% concentration of LD₅₀ determined for crude extract and fractions on chicken embryos showed an elevation in the ALT and AST levels in the serum. Brine shrimps and chicken embryos showed a positive correlation, with R² values of 0.541 and 0.588 (P ≤ 0.05) for fractions and subfractions, respectively, as media for the lethality assay. Dose standardization in folk herbal medicine is imperative as T. indica used as food and medicine has been shown to be toxic at high doses. Brine shrimp and chicken embryos may be comparably used as medium for toxicity assay.

  7. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures.

    Wang, Ning; Dorman, Rebecca A; Ingersoll, Christopher G; Hardesty, Doug K; Brumbaugh, William G; Hammer, Edward J; Bauer, Candice R; Mount, David R

    2016-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1 mg K/L to 3 mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  8. Extracorporeal Membrane Oxygenation in a Patient With Refractory Acute Respiratory Distress Syndrome Secondary to Toxic Epidermal Necrolysis.

    2014-12-01

    life support (ECLS) in adults with acute respiratory distress syndrome (ARDS) has increased markedly during the past few years after suc- cessful...Extracorporeal Membrane Oxygenation in a Patient With Refractory Acute Respiratory Distress Syndrome Secondary to Toxic Epidermal Necrolysis Christy...COVERED - 4. TITLE AND SUBTITLE Extracorporeal Membrane Oxygenation in a Patient With Refractory Acute Respiratory Distress Syndrome Secondary to

  9. Anti-NMDA Receptor Encephalitis and Vaccination

    Wang, Hsiuying

    2017-01-01

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint. PMID:28106787

  10. Anti-NMDA Receptor Encephalitis and Vaccination

    Hsiuying Wang

    2017-01-01

    Full Text Available Anti-N-methyl-d-aspartate (Anti-NMDA receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  11. Anti-NMDA Receptor Encephalitis and Vaccination.

    Wang, Hsiuying

    2017-01-18

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  12. Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy

    Swapnil Chavan

    2015-05-01

    Full Text Available A k-nearest neighbor (k-NN classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS database chemicals, employing two acute toxicity (LD50-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL. We have successfully predicted the LOELs of 54 of 70 training set chemicals (77% and 14 of 19 test set chemicals (74% to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity.

  13. Metallothionein does not sequester arsenic(III) ions in condition of acute arsenic toxicity.

    Garla, Roobee; Ganger, Renuka; Mohanty, Biraja P; Verma, Shivcharan; Bansal, Mohinder P; Garg, Mohan L

    2016-07-29

    The major cause of toxicity of trivalent arsenicals is due to their interaction with the sulfhydryl groups in proteins. Because of its high content, Metallothionein (MT) provides one of the most favorable conditions for the binding of As(III) ions to it. MT has long been anticipated for providing resistance in case of arsenic (As) toxicity with similar mechanism as in case of cadmium toxicity. The present study investigates whether the sequestration of As ions by MT is one of the mechanisms in providing protection against acute arsenic toxicity. A rat model study on the metal stoichiometric analysis of MT1 isoform isolated from the liver of arsenic treated, untreated and zinc treated animals has been carried out using the combination of particle induced X-ray emission (PIXE) and electrospray ionisation mass spectrometry (ESI-MS). The results revealed the absence of arsenic bound MT1 in the samples isolated from arsenic treated animals. Although, both Cu and Zn ions were present in MT1 samples isolated from all the treatment groups. Moreover, only partially metallated MT1 with varying number of Zn ions were observed in all the groups. These results suggest that the role of MT during acute arsenic toxicity is different from its already established role in case of cadmium toxicity.

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

    Rasuli Farhang

    2015-06-01

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

  15. The acute toxicity of major ion salts to Ceriodaphnia dubia: I. ...

    The ions Na+, K+, Ca2+, Mg2+, Cl-, SO42-, and HCO3-/CO32- (referred to as “major ions”) are present in all fresh waters and are physiologically required by aquatic organisms, but can be increased to harmful levels by a variety of anthropogenic activities that speed geochemical weathering or otherwise introduce or concentrate ions. While toxicity of these ions to aquatic organisms has been previously shown, it is also known that their toxicity can vary depending on the concentrations of other co-occurring anions, and understanding these relationships is key to predicting toxicity and establishing appropriate environmental limits. In this paper we conduct a series of experiments with Ceriodaphnia dubia to evaluate the acute toxicity of all twelve major ionsalts (pairing one of the cations with one of the anions) and to determine how toxicity of these salts varies as a function of background water chemistry. All salts except CaSO4 and CaCO3 were acutely toxic to C. dubia below saturation, with the lowest LC50s found for K salts. Of the remaining salts, all but CaCl2 showed some degree of decreased toxicity as the ionic content of the background water increased. Experiments that independently varied Ca:Mg ratio, Na:K ratio, Cl:SO4 ratio, and alkalinity/pH were used to show that Ca concentration was the primary factor influencing the toxicities of Na and Mg salts. In contrast, the toxicities of K salts were primarily influenced by the concentration of Na. Th

  16. Comparative and combined acute toxicity of butachlor, imidacloprid and chlorpyrifos on earthworm, Eisenia fetida.

    Chen, Chen; Wang, Yanhua; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

    2014-04-01

    Various pesticides have become widespread contaminants of soils due to their large applications in agriculture and homes. An earthworm assay was used to assess the acute toxicity of butachlor, imidacloprid and chlorpyrifos with different modes of action. Ecotoxicities of these pesticides were compared for earthworm Eisenia fetida separately and in combination in artificial soil and contact filter paper tests. Imidacloprid was the most toxic for E. fetida with LC₅₀ (lethal concentration 50) values three orders magnitude lower than that of butachlor and chlorpyrifos in both tests. The toxicity of the mixtures was compared to that predicted by the concentration addition (CA) model. According to the CA model, the observed toxicities of all binary mixtures were less than additive. However, for all the mixtures in 14 d artificial soil test, and mixtures of butachlor plus chlorpyrifos and imidacloprid plus chlorpyrifos in 48 h contact filter paper test, the difference in toxicity was less than 30%, hence it was concluded that the mixtures conformed to CA. The combined effects of the pesticides in contact filter paper tests were not consistent with the results in artificial soil toxicity tests, which may be associated with the interaction of soil salts with the pesticides. The CA model provides estimates of mixture toxicity that did not markedly underestimate the measured toxicity, and therefore the CA model is the most suitable to use in ecological risk assessments of the pesticides.

  17. Joint acute toxicity of the herbicide butachlor and three insecticides to the terrestrial earthworm, Eisenia fetida.

    Wang, Yanhua; Cang, Tao; Yu, Ruixian; Wu, Shenggan; Liu, Xinju; Chen, Chen; Wang, Qiang; Cai, Leiming

    2016-06-01

    The herbicide butachlor and three insecticides phoxim, chlorpyrifos, and lambda-cyhalotrhin are widely used pesticides with different modes of action. As most previous laboratory bioassays for these pesticides have been conducted solely based on acute tests with a single compound, only limited information is available on the possible combined toxicity of these common chemicals to soil organisms. In this study, we evaluated their mixture toxicity on the terrestrial earthworm, Eisenia fetida, with binary, ternary, and quaternary mixtures. Two different types of bioassays were employed in our work, including a contact filter paper toxicity test and a soil toxicity test. Mixture toxicity effects were assessed using the additive index method. For all of the tested binary mixtures (butachlor-phoxim, butachlor-chlorpyrifos, and butachlor-lambda-cyhalothrin), significant synergistic interactions were observed after 14 days in the soil toxicity assay. However, greater additive toxicity was found after 48 h in the contact toxicity bioassay. Most of the ternary and quaternary mixtures exhibited significant synergistic effects on the worms in both bioassay systems. Our findings would be helpful in assessing the ecological risk of these pesticide mixtures to soil invertebrates. The observed synergistic interactions underline the necessity to review soil quality guidelines, which are likely underestimating the adverse combined effects of these compounds.

  18. The value of brain CT findings in acute methanol toxicity

    Taheri, Morteza Sanei [Department of Radiology, Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)], E-mail: saneim@yahoo.com; Moghaddam, Hossein Hassanian [Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Moharamzad, Yashar; Dadgari, Shahrzad [Department of Radiology, Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Nahvi, Vahideh [Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2010-02-15

    Objective: Due to depressant effects of methanol on the central nervous system, brain computed tomography (CT) scan has been introduced as a diagnostic device in methanol intoxication. The authors aimed to present brain CT findings in patients with acute methanol intoxication and to determine signs associated with death. Materials and methods: This cohort study involved 42 consecutive patients with acute methanol intoxication. Inclusion criteria were consisted of characteristic clinical presentation of methanol poisoning, and metabolic acidosis with increased anion and osmolar gaps. Brain CT scans without contrast medium were obtained. To determine the association between the CT findings and death, the chi-square test or the Fisher's exact test, odds ratio (OR) and its 95% confidence interval (95% CI) were calculated. Results: Twenty-eight patients (66.6%) had a total of 55 abnormal findings on brain CT, in which bilateral putaminal hypodense lesions was the most common manifestation (27 cases, 96.4%). Putaminal hemorrhage with varying degrees was observed in 7 patients (25%). Six patients (21.4%) had low attenuation lesions in the subcortical white matter of the insula. A significant association was observed between putaminal hemorrhage (OR = 8, 95% CI = 1.187-53.93, P = 0.018) and subcortical necrosis of the insula (OR = 11, 95% CI = 1.504-80.426, P = 0.007) with death. Conclusion: In addition to clinical and laboratory findings, presence of putaminal hemorrhage and insular subcortex white matter necrosis are associated with a poor clinical outcome in patients with methanol poisoning.

  19. Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity

    Beltrán César

    2011-08-01

    Full Text Available Abstract Background Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. Methods In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. Results The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%, abdomen (17% and thorax (6%. The most prevalent histological types were: medulloblastoma (16 patients, neuroblastoma (9 patients and rhabdomyosarcoma (7 patients. A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72% were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy. In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6% of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6% had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases were significantly associated with severe toxicity (grade 3 or more, whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. Conclusion HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of

  20. Acute and chronic toxicity of selected disinfection byproducts to Daphnia magna, Cyprinodon variegatus, and Isochrysis galbana.

    Fisher, Daniel; Yonkos, Lance; Ziegler, Gregory; Friedel, Elizabeth; Burton, Dennis

    2014-05-15

    Ballast water treatment has become a major issue in the last decade due to the problem of invasive species transported and released by the uptake and discharge of ballast water for shipping operations. One of the important issues considering ballast water treatment is to determine whether treated ballast water, once discharged, is safe to the aquatic environment. The International Maritime Organization (IMO) Marine Environmental Protection Committee (MEPC) has determined that prior to approval of a ballast water management system, aquatic toxicity data must be available for both the active substance and relevant byproducts. Many proposed ballast water treatment systems use chlorine as the active ingredient. Although there are sufficient toxicity data concerning active substances such as chlorine, there are limited toxicity data concerning disinfection (halogenated) byproducts including dibromochloromethane, four haloacetic acids and sodium bromate. Acute and chronic toxicity were determined for these disinfection byproducts (DBPs). Acute toxicity values ranged from 96-h LC50s of 46.8 mg/l for Daphnia magna for both dibromochloromethane and sodium bromate to a 96-h LC50 of 376.4 mg/l for Cyprinodon variegatus for tribromoacetic acid. Acute Isochrysis galbana population growth effect values ranged from a 72-h EC10 of 39.9 mg/l for dichloroacetic acid to a 72-h EC50 of 15,954 mg/l for sodium bromate. Chronic toxicity mortality/reproduction effects values for D. magna ranged from a 21-d IC25 of 160.9 mg/l for tribromoacetic acid to a 21-d LOEC of 493.0 mg/l for trichloroacetic acid. Chronic toxicity mortality/growth values for C. variegatus ranged from a 32-d IC25 of 246.8 mg/l for trichloroacetic acid to a 32-d LOEC of 908.1 mg/l for tribromoacetic acid. I. galbana 96-h chronic population growth effects values ranged from an EC10 of 38.5 mg/l for trichloroacetic acid to an LOEC of 500.0 mg/l for tribromoacetic acid. Acute to chronic ratios for all of these

  1. Assessment of acute toxicity of carbofuran in Macrobrachium olfersii (Wiegmann, 1836) at different temperature levels.

    Barbieri, Edison; Moreira, Priscila; Luchini, Luiz Alberto; Hidalgo, Karla Ruiz; Muñoz, Alejandro

    2016-01-01

    Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity - median lethal concentration - of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L(-1), respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control.

  2. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

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

    Deka Manalisha

    2012-02-01

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

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

    Deka Manalisha

    2011-12-01

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

  5. Acute and chronic toxicity of the benzoylurea pesticide, lufenuron, in the fish, Colossoma macropomum.

    Rafaela Leão Soares, Priscila; Lucas Corrêa de Andrade, André; Pinheiro Santos, Thamiris; Caroline Barros Lucas da Silva, Stephannie; Freitas da Silva, Jadson; Rodrigues Dos Santos, Amanda; Hugo Lima da Silva Souza, Elton; Magliano da Cunha, Franklin; Wanderley Teixeira, Valéria; Sales Cadena, Marilia Ribeiro; Bezerra de Sá, Fabrício; Bezerra de Carvalho Júnior, Luiz; Gonçalves Cadena, Pabyton

    2016-10-01

    Lufenuron is a benzoylurea insecticide that interfere in chitin synthesis in insects. Although lufenuron is widely used in agriculture and aquaculture, rare are studies described that relates to possible toxic effects in fish. This work aimed to evaluate acute and chronic toxic effects of benzoylurea pesticide (lufenuron) on biological parameters of Colossoma macropomum (Tambaqui). In the acute test, juveniles of Tambaqui were divided into control group and five experimental groups with exposure from 0.1 to 0.9 mg/L of lufenuron for 96 h. Animals were also submitted to chronic toxicity test for four months in concentrations of 0.1 and 0.3 mg/L of lufenuron, the concentration used in the treatment of ectoparasites in fish and 50% of LC50 96 h, respectively. The presence of hemorrhages was observed in eyes, fins and operculum of fish exposed to 0.7 and 0.9 mg/L of lufenuron. Histological analysis showed changes in the morphology of fish gills submitted to acute toxicity test, as lamellar aneurysm and blood congestion inside lamellae. Lufenuron promoted damage in fish retina as in ability to respond to stimuli in photoreceptors and in ON-bipolar cells in acute test. In chronic test, blood glucose analysis and morphometric parameters showed no significant differences (p > 0.05). In general, Tambaqui exhibited behaviors associated with stress when exposed to lufenuron. Thus, lufenuron showed several toxic effects in relation to biological parameters in Tambaqui. This concerns about the use and discard of lufenuron, and indicates the requirement of environmental actions to prevent potential contamination of aquatic biota.

  6. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

    Rashid Ali

    2012-01-01

    Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

  7. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W

    1983-04-01

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  8. [Acute toxicity by methotrexate used for abortion purpose. Case report].

    Estrada-Altamirano, Ariel; Chacón-Solís, Rogerio Armando; Hernández-Pacheco, José Antonio; Belmont-Gómez, Aurora; Valenzuela-Jirón, Arlen; Carvajal-Valencia, Javier Andrés; Maya-Quiñones, José Luis

    2011-01-01

    We report the case of a 16 years old female patient, with a pregnancy history of 11.4 weeks by ultrasound and intrauterine fetal death. In a private clinic were prescribed methotrexate 500 mg intramuscular single dose, and vaginal misoprostol. She had a clinical feature of five days of evolution characterized by fever of 39 degrees C, nausea, general attack and vomiting. The initial diagnosis was severe sepsis secondary to septic abortion, oral candidiasis and acute poisoning by methotrexate. After that, she was referred to the Instituto Nacional de Perinatologia, where stayed with fever for four days, and was managed with hydration, antibiotics, folinic acid and alkalizing. Her recovery was gradual. She was discharged after 12 days with significant clinical improvement. The literature review describes that the use of methotrexate for abortion purpose with therapeutic-dose presents a similar adverse effects to those found in our patient, however there are no case reports that describe the use of this drug in macrodosis for the same purpose, and their cytotoxic effects. We present this case because the patient used a macrodosis of this antimetabolite and due to the premature and empirical management with folinic acid, joined with alkalinization of urine, is the ideal treatment and as it is illustrated in our case.

  9. Acute isoniazid toxicity and the need for adequate pyridoxine supplies.

    Morrow, Lee E; Wear, Robert E; Schuller, Dan; Malesker, Mark

    2006-10-01

    A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (> or = 20 g) are available for effective treatment of isoniazid poisonings.

  10. Cellular prion protein and NMDA receptor modulation: protecting against excitotoxicity

    Stefanie A.G. Black

    2014-08-01

    Full Text Available Although it is well established that misfolding of the cellular prion protein (PrPC into the beta-sheet-rich, aggregated scrapie conformation (PrPSc causes a variety of transmissible spongiform encephalopathies (TSEs, the physiological roles of PrPC are still incompletely understood. There is accumulating evidence describing the roles of PrPC in neurodegeneration and neuroinflammation. Recently, we identified a functional regulation of NMDA receptors by PrPC that involves formation of a physical protein complex between these proteins. Excessive NMDA receptor activity during conditions such as ischemia mediates enhanced Ca2+ entry into cells and contributes to excitotoxic neuronal death. In addition, NMDA receptors and/or PrPC play critical roles in neuroinflammation and glial cell toxicity. Inhibition of NMDA receptor activity protects against PrPSc-induced neuronal death. Moreover, in mice lacking PrPC, infarct size is increased after focal cerebral ischemia, and absence of PrPC increases susceptibility of neurons to NMDA receptor-dependent death. Recently, PrPC was found to be a receptor for oligomeric beta-amyloid (Abeta peptides, suggesting a role for PrPC in Alzheimer’s disease. Our recent findings suggest that Abeta peptides enhance NMDA receptor current by perturbing the normal copper- and PrPC-dependent regulation of these receptors. Here, we review evidence highlighting a role for PrPC in preventing NMDA receptor-mediated excitotoxicity and inflammation. There is a need for more detailed molecular characterization of PrPC-mediated regulation of NMDA receptors, such as determining which NMDA receptor subunits mediate pathogenic effects upon loss of PrPC-mediated regulation and identifying PrPC binding site(s on the receptor. This knowledge will allow development of novel therapeutic interventions for not only TSEs, but also for Alzheimer’s disease and other neurodegenerative disorders involving dysfunction of PrPC.

  11. Helical tomotherapy in cervical cancer patients. Simultaneous integrated boost concept: technique and acute toxicity

    Marnitz, Simone; Stromberger, Carmen; Kawgan-Kagan, Michael; Wlodarczyk, Waldemar; Jahn, Ulrich; Budach, Volker [Dept. of Radiooncology, Charite - Univ. Medicine, Berlin (Germany); Schneider, Achim; Koehler, Christhardt [Dept. of Gynecology Charite - Univ. Medicine, Berlin (Germany); Ulrich, Uwe [Dept. of Gynecology and Obstetrics, Martin Luther Hospital, Berlin (Germany)

    2010-10-15

    Purpose: To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy (HT) in patients with locally advanced cervical cancer. Patients and Methods: 20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic pelvic and para-aortic lymphadenectomy was performed. A boost region was defined using titanium clips during staging for planning target volume (PTV-B). Patients were treated with five weekly fractions of 1.8 Gy to a total dose of 50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (PTV-A), and five weekly fractions of 2.12 Gy to a total dose of 59.36 Gy to the PTV-B. Chemotherapy consisted of weekly cisplatin 40 mg/m{sup 2}. 19 patients underwent brachytherapy. Dose-volume histograms were evaluated and acute gastrointestinal (GI), genitourinary (GU), and hematologic toxicity were documented (CTCAE v3.0). Results: Pelvic and para-aortic lymph node metastases were confirmed in nine and four patients, respectively. Five patients refused laparoscopic staging. The mean volume of PTV-A and PTV-B was 1,570 {+-} 404 cm{sup 3} and 341 {+-} 125 cm{sup 3}, respectively. The mean dose to the bladder, rectum, and small bowel was 47.85 Gy, 45.76 Gy, and 29.71 Gy, respectively. No grade 4/5 toxicity was observed. Grade 2/3 hematologic toxicity occurred in 50% of patients and 5% experienced grade 3 diarrhea. There was no grade 3 GU toxicity. 19 patients underwent curettage 6-9 weeks after chemoradiation without any evidence of tumor. Conclusion: The concept of SIB for dose escalation in patients with locally advanced cervical cancer is feasible with a low rate of acute toxicity. Whether dose escalation can translate into improved outcome will be assessed after a longer follow-up. (orig.)

  12. Intensity modulated whole pelvic radiotherapy in patients with cervix cancer: analysis of acute toxicity

    Choi, Young Min; Lee, Hyung Sik; Hur, Won Joo; Cha, Moon Seok; Kim, Hyun Ho [School of Medicine, Dong-A University, Busan (Korea, Republic of)

    2006-12-15

    To evaluate acute toxicities in cervix cancer patients receiving intensity modulated whole pelvic radiation therapy (IM-WPRT). Between August 2004 and April 2006, 17 patients who underwent IM-WPRT were analysed. An intravenous contrast agent was used for radiotherapy planning computed tomography (CT). The central clinical target volume (CTV) included the primary tumor, uterus, vagina, and parametrium. The nodal CTV was defined as the lymph nodes larger than 1 cm seen on CT and the contrased-enhanced pelvic vessels. The planning target volume (PTV) was the 1-cm expanded volume around the central CTV, except for a 5-mm expansion from the posterior vagina, and the nodal PTV was defined as the nodal CTV plus a 1.5 cm margin. IM-WPRT was prescribed to deliver a dose of 50 Gy to more than 95% of the PTV. Acute toxicity was assessed with common toxicity criteria up to 60 days after radiotherapy. Grade 1 nausea developed in 10 (58.9%) patients, and grade 1 and 2 diarrhea developed in 11 (64.7%) and 1 (5.9%) patients, respectively. No grade 3 or higher gastrointestinal toxicity was seen. Leukopenia, anemia, and thrombocytopenia occurred in 15 (88.2%). 7 (41.2%), and 2 (11.8%) patients, respectively, as hematologic toxicities. Grade 3 leukopenia developed in 2 patients who were treated with concurrent chemoradiotherapy. IM-WPRT can be a useful treatment for cervix cancer patients with decreased severe acute toxicities and a resultant improved compliance to whole pelvic irradiation.

  13. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

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

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

    2015-10-01

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

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

    Basak Ozlem Perk

    2013-01-01

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

  16. Acute toxicity of live and decomposing green alga Ulva (Enteromorpha) prolifera to abalone Haliotis discus hannai

    WANG Chao; YU Rencheng; ZHOU Mingjiang

    2011-01-01

    From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides")occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva (Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

  17. Acute toxicity of mixture of acetaminophen and ibuprofen to Green Neon Shrimp, Neocaridina denticulate.

    Sung, Hung-Hung; Chiu, Yuh-Wen; Wang, Shu-Yin; Chen, Chien-Min; Huang, Da-Ji

    2014-07-01

    In recent years, numerous studies have indicated that various long-term use drugs, such as antibiotics or analgesics, not only cannot be completely decomposed via sewage treatment but also exhibit biological toxicity if they enter the environment; thus, the release of these drugs into the environment can damage ecological systems. This study sought to investigate the acute toxicity of two commonly utilized analgesics, ibuprofen (IBU) and acetaminophen (APAP), to aquatic organisms after these drugs have entered the water. To address this objective, the acute toxicity (median lethal concentration, LC₅₀, for a 96-h exposure) of IBU alone, APAP alone, and mixtures containing different ratios of IBU and APAP in green neon shrimp (Neocaridina denticulata) were measured. The results of four tests revealed that the 96-h LC₅₀ values for IBU and APAP alone were 6.07 mg/L and 6.60 mg/L, respectively. The 96-h LC₅₀ for a 1:1 mixture of IBU and APAP was 6.23 mg/L, and the toxicity of this mixture did not significantly differ from the toxicity of either drug alone (pneon shrimp.

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

    Chatchai Chaotham

    2013-01-01

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

  19. Correlation between TCDD acute toxicity and aryl hydrocarbon receptor structure for different mammals.

    Wang, Yonghua; Wang, Qiuying; Wu, Bing; Li, Yi; Lu, Guanghua

    2013-03-01

    The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity has large species differences, and TCDD exerts its toxicity by binding into aryl hydrocarbon receptor (AHR). In this study, we applied bioinformatics approaches to quantitatively analyze the correlation between TCDD acute toxicity and AHRs. Seven mammalian AHRs were chosen as target receptors. Low conserved functional domains of AHRs were identified and quantitatively characterized. Linear regression was applied to determine the relationships of different mammalian AHRs and TCDD LD(50) values. The results indicated that ligand binding domain and glutamine-rich domain of mammalian AHRs showed a low degree of conservation. Based on previous literatures, the number of glutamine residues (NOQ) and binding free energy with TCDD were applied to quantitatively represent the differences of glutamine-rich domain and ligand binding domain, respectively. Then, regression equations between studied mammalian AHR structures and TCDD LD(50) were constructed, and high linear correlation was found (R(2)=0.986). This study indicated that mammalian differences of TCDD acute toxicity might be partly determined by the differences of glutamine-rich domain and ligand binding domain of AHR, which provides a potential insight to analyze the species differences of TCDD toxicity.

  20. Acute isoniazid toxicity--report of 2 cases and review of literature.

    Gilhotra, R; Malik, S K; Singh, S; Sharma, B K

    1987-05-01

    Accidental or intentional isoniazid (INH) overdose is not uncommon. Two patients suffering from pulmonary tuberculosis ingested INH (9 g and 12 g respectively) intentionally following acute personal stress. One patient presented with oliguria and coma whereas seizures were the dominant feature in the second case. Serum levels of INH were high in both cases. Satisfactory clinical recovery followed after the administration of intravenous pyridoxine. Literature on the subject was reviewed and the manifestations and recommendations for the management of acute INH toxicity are highlighted.

  1. Emergency planning and the acute toxic potency of inhaled ammonia.

    Michaels, R A

    1999-08-01

    Ammonia is present in agriculture and commerce in many if not most communities. This report evaluates the toxic potency of ammonia, based on three types of data: anecdotal data, in some cases predating World War 1, reconstructions of contemporary industrial accidents, and animal bioassays. Standards and guidelines for human exposure have been driven largely by the anecdotal data, suggesting that ammonia at 5,000-10,000 parts per million, volume/volume (ppm-v), might be lethal within 5-10 min. However, contemporary accident reconstructions suggest that ammonia lethality requires higher concentrations. For example, 33,737 ppm-v was a 5-min zero-mortality value in a major ammonia release in 1973 in South Africa. Comparisons of secondary reports of ammonia lethality with original sources revealed discrepancies in contemporary sources, apparently resulting from failure to examine old documents or accurately translate foreign documents. The present investigation revealed that contemporary accident reconstructions yield ammonia lethality levels comparable to those in dozens of reports of animal bioassays, after adjustment of concentrations to human equivalent concentrations via U.S. Environmental Protection Agency (EPA) procedures. Ammonia levels potentially causing irreversible injury or impairing the ability of exposed people to escape from further exposure or from coincident perils similarly have been biased downwardly in contemporary sources. The EPA has identified ammonia as one of 366 extremely hazardous substances subject to community right-to-know provisions of the Superfund Act and emergency planning provisions of the Clean Air Act. The Clean Air Act defines emergency planning zones (EPZs) around industrial facilities exceeding a threshold quantity of ammonia on-site. This study suggests that EPZ areas around ammonia facilities can be reduced, thereby also reducing emergency planning costs, which will vary roughly with the EPZ radius squared.

  2. Kinetic constraints in acute aluminium toxicity in the rainbow trout (Oncorhynchus mykiss).

    Exley, C; Wicks, A J; Hubert, R B; Birchall, J D

    1996-03-07

    We have designed a laboratory bioassay to expose fish to kinetically determined differences in aluminium hydroxide solution chemistry. We have used this system to demonstrate the hitherto unexpected result of an acute aluminium toxicity in the fish at a pH of 6.5. Supporting experiments have demonstrated that the mechanism of toxicity at this pH was probably an asphyxiation brought about by aluminium-induced changes in the rheological and diffusional properties of the mucus lining of the gill epithelium.

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

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

    2016-10-01

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

  4. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day.

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

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

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible m...

  6. Acute toxicity of whole-pelvis IMRT in 87 patients with localized prostate cancer

    Sanguineti, Giuseppe; Bicquart, Celine; Little, Michael; Chen, George; Berilgen, Jason (Dept. of Radiation Oncology, Univ. of Texas Medical Branch, Galveston, TX (US)); Endres, Eugene J.; Parker, Brent C. (Dept. of Physics, Univ. of Texas Medical Branch, Galveston, TX (US))

    2008-02-15

    Purpose. To assess the acute toxicity profile of whole pelvis IMRT (WP-IMRT) for localized prostate cancer. Materials. Eighty seven patients treated with definitive WP-IMRT at UTMB from May 2002 to November 2006 were retrospectively reviewed. Treatment consisted of two sequential phases, WP-IMRT to 54 Gy at 1.8 Gy per fraction to the pelvic nodes and seminal vesicles and 60 Gy at 2 Gy to the prostate, and a separate external beam boost, 3DCRT or IMRT, to bring the dose to the prostate to 76 Gy. Acute toxicity was prospectively scored weekly during treatment and at 3 month follow-up according to CTC v2.0 for 10 genitourinary (GU) and gastrointestinal (GI) domains. The proportion of patients experiencing a given level of peak acute toxicity at a given point is reported. Results. Treatment was feasible with delivered doses to PTVs not significantly lower than planned ones and with only two patients experiencing treatment gaps longer than 5 days. About 2/3 and 1/10 of the patients experienced peak grade 2 and grade 3 reactions at least once during RT, respectively. Frequency/urgency (Grade 2+: 37.9%) and diarrhea (36.7%) were the most prevalent symptoms followed by proctitis (21.8%) and dysuria (16.1%). GI reactions were generally shorter lasting compared to GU ones which accumulated progressively during treatment. At 3 months, almost half of the patients were asymptomatic and most of observed reactions (89.2%) were mild, with GI ones more likely to be fully resolved (92.5%) than GU ones (68.7%, 2, p=0.001). Conclusion. Our approach is dosimetrically and clinically feasible with intense, but transient, acute toxicity

  7. Bioconcentration and acute toxicity of polycyclic musks in two benthic organisms (Chironomus riparius and Lumbriculus variegatus)

    Artola-Garicano, E.; Sinnige, T.L.; Holsteijn, I. van; Vaes, W.H.J.; Hermens, J.L.M.

    2003-01-01

    In the current study, the bioconcentration behavior and acute toxicity of two polycyclic musks, Tonalide® 7-acetyl-1,1,3,4,4,6,-hexamethyl-1,2,3,4,-tetrahydronaphthalene (AHTN) and Galaxolide® 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methyl-cyclopenta[γ]-2- benzopyran (HHCB), were studied in two benth

  8. Acute Inhalation Toxicity Study of 1, 4-Dioxane in Rats (Rattus norvegicus)

    2012-07-01

    of degenerative and/or toxic nephropathy . Degenerative nephropathy is not uncommon in rats and is due to the predisposing factors of age, sex...was attributed to early and more acute progression of chronic progressive glomerular nephropathy . 4.2.6 Statistical Analysis: A statistical...0.6084 Degeneration 1 day M - - - - - - - F 0.0011 - - 0.0256 - 0.0256 0.0256 2 wk M - - - - - - - F - - - - - - - Kidney Nephropathy

  9. Acute embryo toxicity and teratogenicity of three potential biofuels also used as flavor or solvent

    Bluhm, Kerstin; Seiler, Thomas-Benjamin [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Anders, Nico [RWTH Aachen University, Aachener Verfahrenstechnik — Enzyme Process Technology, Worringerweg 1, 52074 Aachen (Germany); Klankermayer, Jürgen [RWTH Aachen University, Institut für Technische und Makromolekulare Chemie, Worringerweg 1, 52074 Aachen (Germany); Schaeffer, Andreas [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Hollert, Henner, E-mail: Henner.Hollert@bio5.rwth-aachen.de [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Tongji University, College of Environmental Science and Engineering and State Key Laboratory of Pollution Control and Resource Reuse, Shanghai 200092 (China)

    2016-10-01

    The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC{sub 50}: 83 mg/L) compared to 2-MTHF (LC{sub 50}: 2980 mg/L), 2-MF (LC{sub 50}: 405 mg/L) and water accommodated fractions of the reference fuels including gasoline (LC{sub 50}: 244 mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. - Highlights: • The demand for biofuels increases but their (eco)toxicological effects are unknown. • Acute fish embryo toxicity and teratogenicity of potential biofuels were evaluated. • Ethyl levulinate induced a higher acute toxicity compared to WAFs of gasoline. • Ethyl levulinate caused

  10. Acute toxicity reduction and toxicity identification in pigment-contaminated wastewater during anaerobic-anoxic-oxic (A/A/O) treatment process.

    Deng, Minjie; Zhang, Ying; Quan, Xie; Na, Chunhong; Chen, Shuo; Liu, Wei; Han, Shuping; Masunaga, Shigeki

    2017-02-01

    In China, a considerable part of industrial wastewater effluents are discharged into the municipal wastewater treatment plants (WWTPs) after pretreatment in their own wastewater treatment plants. Even though the industrial effluents meet the professional emission standards, many micro-pollutants still remained, and they could be resistant in the municipal WWTPs with conventional activated sludge process. Pigment wastewater was chosen in this study, and the acute toxicity reduction and identification of the pigment-contaminated wastewater treated by the conventional anaerobic-anoxic-oxic (A/A/O) process were evaluated. Results indicated that the raw pigment-contaminated wastewater was acutely toxic to Photobacterium phosphoreum (P. phosphoreum), Daphnia magna (D. magna) and Danio rerio (D. rerio). The acute toxicity was decreased in some degree after A/A/O treatment, but the final effluent still exhibited acute toxicity to D. magna and D. rerio with the toxic units (TU) of 1.1 and 2.0, respectively. Chemical analyses showed the presence of various refractory and toxic nitrogen-containing polycyclic and heterocyclic compounds in the pigment-contaminated wastewater. Toxicity identification by combining chemical analyses and correlation analysis showed that N-containing refractory organic toxicants were the main toxicity source for the pigment-contaminated wastewater, and several toxicants showed significant correlation with P. phosphoreum and D. magna. This study indicated that the A/A/O process was not efficient for pigment-contaminated wastewater treatment, and it was irradiative for technology improvement in the WWTPs receiving pretreated industrial wastewater effluents.

  11. Acute toxicity of fire-retardant and foam-suppressant chemicals to yalella azteca (Saussure)

    McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

    1997-01-01

    Acute toxicity tests were conducted with Hyalella azteca Saussure (an amphipod) exposed in soft and hard waters to three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two foam suppressants (Phos-Chek WD-881 and Silv-Ex). The chemicals were slightly to moderately toxic to amphipods. The most toxic chemical to amphipods in soft and hard water was Phos-Chek WD-881 (96-h mean lethal concentration [LC50] equal to 10 mg/L and 22 mg/L, respectively), and the least toxic chemical to amphipods in soft water was Fire-Trol GTS-R (96-h LC50 equal to 127 mg/L) and in hard water was Fire-Trol LCG-R (96-h LC50 equal to 535 mg/L). Concentrations of ammonia in tests with the three fire retardants and both water types were greater than reported LC50 values and probably were the major toxic component. Estimated un-ionized ammonia concentrations near the LC50 were frequently less than the reported LC50 ammonia concentrations for amphipods. The three fire retardants were more toxic in soft water than in hard water even though ammonia and un-ionized ammonia concentrations were higher in hard water tests than in soft water tests. The accidental entry of fire-fighting chemicals into aquatic environments could adversely affect aquatic invertebrates, thereby disrupting ecosystem function.

  12. Acute toxicity of agricultural pesticides to embryo-larval and juvenile African catfish Clarias gariepinus.

    Agbohessi, P T; Imorou Toko, I; Houndji, A; Gillardin, V; Mandiki, S N M; Kestemont, P

    2013-05-01

    Acute toxicities of Tihan 175 O-TEQ, as well as its active ingredients flubendiamide and spirotetramat, and of Thionex 350 EC (active compound endosulfan) were measured for embryo-larval and juvenile stages of the African catfish Clarias gariepinus to assess risks of pesticide use in the cotton basin in Benin (West Africa). For embryo-larval stages, Tihan was more toxic (LC5048h 20 ppm) than Thionex (LC5048h 56 ppm), and flubendiamide was more toxic (LC5048h 2.0 ppm) than spirotetramat (LC5048h 8.44 ppm). All decreased hatching rates. Tihan and spirotetramat disturbed larval swimming coordination; flubendiamide induced tail cleavage. For juvenile fish, Thionex was more toxic (LC5096h 0.22 ppm) than Tihan (LC5096h 8.8 ppm), and flubendiamide (LC5096h 4.7 ppm) was more toxic than spirotetramat (LC5096h 6.0 ppm). Eggs were more resistant than juvenile fish to all tested pesticides except flubendiamide. Although Thionex was more toxic to juvenile fish, replacing Thionex with Tihan may be undesirable for survival of eggs and larvae.

  13. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    Xinyan Zhao

    2013-12-01

    Full Text Available A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+, zinc (Zn2+, potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety.

  14. Acute toxicity bioassay of mercury and silver on Capoeta fusca (black fish).

    Mansouri, Borhan; Baramaki, Rahimeh; Ebrahimpour, Mohammad

    2012-06-01

    Since toxicity is based on the effect that a toxicant produces at a target site within an organism, establishing the relationship between the concentration of substance at the target site and the subsequent toxic effect can provide a tool for predicting toxicity. The behavior of a single toxicant could not be fully understood without the knowledge of the fact the physical and biochemical properties of substances that can change. To understand this, the acute toxicity of mercury (as HgSO₄) and silver (as AgSO₄) to Capoeta fusca (6 treatments in triplicate) was determined. During September 2009, C. fusca belonging to the family Cyprinidae, weighing 2.95 (±0.55) g, were obtained from qanats in Birjand, East of Iran. The fish were maintained in an aquarium system at a holding temperature of 21 (±0.2) and were allowed to adjust to lab conditions for 1 week before experimentation. The lethal concentration 50 (LC₅₀) values for HgSO₄ at 24, 48, 72, and 96 h of exposure were 0.32, 0.28, 0.26, and 0.24 mg L⁻¹, respectively. Also, the LC₅₀ values for AgSO₄ at 24, 48, 72, and 96 h of exposure were 0.014, 0.013, 0.013, and 0.013 mg L⁻¹, respectively. Results of this study showed that C. fusca was very sensitive to AgSO₄.

  15. Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.

    Svensson, B M; Mathiasson, L; Mårtensson, L; Bergström, S

    2005-03-01

    Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected.

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

    Kwan Yuet Ping

    2013-01-01

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

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

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

    2013-01-01

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

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

    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.

  19. Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

    Williams Scott

    2011-10-01

    Full Text Available Abstract Background Image-guided radiotherapy (IGRT increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically. Methods Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment. Results In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188. Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174. Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271. The median number of days with a toxicity was higher for ≥G2 (p = 0.0179 and ≥G3 frequency (p = 0.0027, ≥G2 diarrhoea (p = 0.0033 and ≥G2 fatigue (p = 0.0088 in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference. Conclusions In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment

  20. Acute Toxicity Comparison of Single-Walled Carbon Nanotubes in Various Freshwater Organisms

    Eun Kyung Sohn

    2015-01-01

    Full Text Available While the commercialization of single-walled carbon nanotubes (SWCNTs is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris, a microcrustacean (Daphnia magna, and a fish (Oryzias latipes based on OECD test guidelines (201, 202, and 203. According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50 of 29.99 and 30.96 mg/L, respectively, representing “acute category 3” in the Globally Harmonized System (GHS of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish.

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

    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.

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

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

    2015-05-01

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

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

    Uvarajan Sampath

    2012-09-01

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

  4. Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3 academic hospitals.

    Jang, Hak-Soo; Kim, Jung-Youn; Choi, Sung-Hyuk; Yoon, Young-Hoon; Moon, Sung-Woo; Hong, Yun-Sik; Lee, Sung-Woo

    2013-10-01

    Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.

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

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

    2015-03-01

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

  6. Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

    Fuma, S. E-mail: fuma@nirs.go.jp; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G

    2003-07-01

    The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of {gamma}-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation.

  7. Mycophenolate mofetil toxicity mimicking acute cellular rejection in a small intestinal transplant

    Apostolov, Ross; Asadi, Khashayar; Lokan, Julie; Kam, Ning; Testro, Adam

    2017-01-01

    Mycophenolate mofetil (MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal (GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant (SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection (ACR). Concurrent biopsies of the patient’s native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graft-versus-host disease in SITs. PMID:28280702

  8. The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

    Ki-Rok, Kwon

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

  9. Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers

    Geeta S

    2006-01-01

    Full Text Available Background: Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior. Purpose: To compare acute toxicities of two chemotherapy schedules for head and neck cancers. Materials and Methods: A total of 83 head and neck cancer patients treated with two schedules of concurrent chemo RT were analyzed, retrospectively, for treatment toxicity. In group A [51 patients], chemotherapy [CT] was administered on week 1, 4 and 7 [cisplatin 100 mg/m2] over a period of 2-3 days. In group B [32 patients], CT was delivered weekly [cisplatin 40 mg/m2]. Radiotherapy dose was 7000 cGy in 35 fractions for definitive concurrent chemo-radiation and 6600 cGy in 33 fractions for adjuvant treatment. Results: Group B patients had increased grade III skin and hematological toxicity, where as patients in group A had more pharyngeal toxicity. Treatment interruptions and percentage of weight loss were higher in group B. Weekly CT schedule had higher rate of severe mucositis, which was statistically significant on both univariate [ P =0.005] and multivariate [ P =0.007] analysis. Conclusions: Three weekly CT is less toxic than weekly. Weekly CT can be made more acceptable by reducing the dose and using feeding tubes for nutrition.

  10. Acute toxicity of binary and ternary mixtures of Cd, Cu, and Zn to Daphnia magna.

    Meyer, Joseph S; Ranville, James F; Pontasch, Mandee; Gorsuch, Joseph W; Adams, William J

    2015-04-01

    Standard static-exposure acute lethality tests were conducted with Daphnia magna neonates exposed to binary or ternary mixtures of Cd, Cu, and Zn in moderately hard reconstituted water that contained 3 mg dissolved organic carbon/L added as Suwannee River fulvic acid. These experiments were conducted to test for additive toxicity (i.e., the response to the mixture can be predicted by combining the responses obtained in single-metal toxicity tests) or nonadditive toxicity (i.e., the response is less than or greater than additive). Based on total metal concentrations (>90% dissolved) the toxicity of the tested metal mixtures could be categorized into all 3 possible additivity categories: less-than-additive toxicity (e.g., Cd-Zn and Cd-Cu-Zn mixtures and Cd-Cu mixtures when Cu was titrated into Cd-containing waters), additive toxicity (e.g., some Cu-Zn mixtures), or more-than-additive toxicity (some Cu-Zn mixtures and Cd-Cu mixtures when Cd was titrated into Cu-containing waters). Exposing the organisms to a range of sublethal to supralethal concentrations of the titrated metal was especially helpful in identifying nonadditive interactions. Geochemical processes (e.g., metal-metal competition for binding to dissolved organic matter and/or the biotic ligand, and possibly supersaturation of exposure waters with the metals in some high-concentration exposures) can explain much of the observed metal-metal interactions. Therefore, bioavailability models that incorporate those geochemical (and possibly some physiological) processes might be able to predict metal mixture toxicity accurately.

  11. Acute toxicity of fire control chemicals to Daphnia magna (Straus) and Selenastrum capricornutum (Printz).

    McDonald, S F; Hamilton, S J; Buhl, K J; Heisinger, J F

    1996-02-01

    Acute toxicity tests were conducted exposing Daphnia magna Straus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), and Selenastrum capricornutum Printz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Check WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC50 7 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50 848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC50 10 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC50 79 mg/liter). Un-ionized ammonia concentrations near the EC50 or IC50 value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50 un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

  12. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States); Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J. [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States)

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

  13. Evaluation of the detoxication efficiencies for acrylonitrile wastewater treated by a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT) process: Acute toxicity and zebrafish embryo toxicity.

    Na, Chunhong; Zhang, Ying; Deng, Minjie; Quan, Xie; Chen, Shuo; Zhang, Yaobin

    2016-07-01

    Acrylonitrile (ACN) wastewater generated during ACN production has been reported to be toxic to many aquatic organisms. However, few studies have evaluated toxicity removal of ACN wastewater during and after the treatment process. In this study, the detoxication ability of an ACN wastewater treatment plant (WWTP) was evaluated using Daphnia magna, Danio rerio and zebrafish embryo. This ACN WWTP has a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT) process upgraded from the traditional anaerobic oxic (A/O) process. Moreover, the potential toxicants of the ACN wastewaters were identified by gas chromatography-mass spectrometry (GC-MS). The raw ACN wastewater showed high acute and embryo toxicity. 3-Cyanopyridine, succinonitrile and a series of nitriles were detected as the toxic contributors of ACN wastewater. The A/O process was effective for the acute and embryo toxicity removal, as well as the organic toxicants. However, the A/O effluent still showed acute and embryo toxicity which was attributed by the undegraded and the newly generated toxicants during the A/O process. The residual acute and embryo toxicity as well as the organic toxicants in the A/O effluent were further reduced after going through the downstream ABFT process system. The final effluent displayed no significant acute and embryo toxicity, and less organic toxicants were detected in the final effluent. The upgrade of this ACN WWTP results in the improved removal efficiencies for acute and embryo toxicity, as well as the organic toxicants.

  14. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

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

    Muhammad Kifayatullah; Mohd. Shahimi Mustafa; Pinaki Senguptha; Md. Moklesur Rahman Sarker; Arindam Das; Sreemoy Kanti Das

    2015-01-01

    Objective: To evaluate the safety dose range of ethanolic extract from the leaves of Pericampylus glaucus(Lam.) Merr. by acute and sub-acute oral toxicity study on animal model. Methods: The acute and sub-acute toxicity study was carried out as per Organization for Economic Co-operation and Development guidelines 423 and 407. In acute toxicity study, the oral dose (300, 2 000 and 4 000 mg/kg) of tested plant extract was administered to three groups in single dose and general behavior, adverse effects and mortality were determined up to 72 h and compared to normal group. In sub-acute study, the tested crude plant extract was administered orally at doses of 600 and 1 000 mg/kg for 28 days to the two animals groups and their body weight, hematological, serum hepatic biochemical parameters were evaluated and compared to normal group by sacrificing all group animals. Results: In acute toxicity, all treated groups’ revealed neither mortality nor any significant alteration in behavior only drowsiness, sedation and lethargy were observed in two group, i.e. 2 000 and 4 000 mg/kg of the tested plant extract. In sub-acute toxicity study no change in hematological, biochemical parameter and organ body weight were observed during study compared to the normal group. The kidney function parameters [serum glutamic-oxaloacetic transaminase (aspartate transaminase), serum glutamic pyruvic transaminase (alanine transaminase)] were significantly increased following administration of tested crude plant extract (600, 1 000 mg/kg). Conclusions:The result indicates that the oral administration ofPericampylus glaucus (Lam.) Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

  16. How closely do acute lethal concentration estimates predict effects of toxicants on populations?

    Stark, John D

    2005-04-01

    Acute lethal dose/concentration estimates are the most widely used measure of toxicity and these data often are used in ecological risk assessment. However, the value of the lethal concentration (LC50) as a toxicological endpoint for use in ecological risk assessment recently has been criticized. A question that has been asked frequently is how accurate is the LC50 for prediction of longer-term effects of toxicants on populations of organisms? To answer this question, Daphnia pulex populations were exposed to nominal concentrations equal to the 48-h acute LC50 of 6 insecticides, Actara, Aphistar diazinon, pymetrozine, Neemix, and Spinosad; and 8 agricultural adjuvants, Bond, Kinetic, Plyac, R-11, Silwet, Sylgard 309, Water Maxx, and X-77; for 10 d. None of the D. pulex populations exposed to the acute LC50 of these insecticides were 50% lower than the control populations at the end of the study; exposure to diazinon resulted in populations that were higher than expected (91% of the control). Exposure to Actara and Aphistar resulted in populations that were < 1 and 29% of the control, respectively. Exposure to Fulfill, Neemix, and Spinosad resulted in extinction. Extinction occurred after exposure to all of the adjuvants, except Silwet L-77 where the population was 31% of the control. These results corroborate other studies that indicate that the LC50 is not a good predictor of effects on population growth. Although lethal concentration estimates have their place in toxicology, namely to compare intrinsic toxicity of chemicals among species or susceptibility of a species to different chemicals over short time periods, population growth and growth-rate studies are necessary to predict toxicant effects on populations.

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

    Strupp, Christian

    2011-01-01

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

  18. The acute and chronic toxicity of major geochemical ions to Hyalella azteca Ion interactions and comparisons to other species

    We have previously reported that the acute and chronic toxicities of major geochemical ions (Na, K, Ca, Mg, Cl, SO4, HCO3) to Ceriodaphnia dubia can involve multiple, independent mechanisms. The toxicities of K, Mg, and Ca salts were best related to the chemical activity of the c...

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

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

    2016-01-01

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

  20. Combined anaerobic–ozonation process for treatment of textile wastewater: Removal of acute toxicity and mutagenicity

    Punzi, Marisa, E-mail: marisa.punzi@biotek.lu.se [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Nilsson, Filip [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Anbalagan, Anbarasan [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Svensson, Britt-Marie [School of Education and Environment, Kristianstad University, SE-291 88 Kristianstad (Sweden); Jönsson, Karin [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Mattiasson, Bo; Jonstrup, Maria [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden)

    2015-07-15

    Highlights: • COD and UV absorbance were effectively reduced. • The treated effluents were non-toxic to Artemia salina and Vibrio fischeri. • The real textile wastewater was mutagenic. • Mutagenicity persisted after bio treatment and even more after a short ozonation. • Higher ozone doses completely remove mutagenicity. - Abstract: A novel set up composed of an anaerobic biofilm reactor followed by ozonation was used for treatment of artificial and real textile effluents containing azo dyes. The biological treatment efficiently removed chemical oxygen demand and color. Ozonation further reduced the organic content of the effluents and was very important for the degradation of aromatic compounds, as shown by the reduction of UV absorbance. The acute toxicity toward Vibrio fischeri and the shrimp Artemia salina increased after the biological treatment. No toxicity was detected after ozonation with the exception of the synthetic effluent containing the highest concentration, 1 g/l, of the azo dye Remazol Red. Both untreated and biologically treated textile effluents were found to have mutagenic effects. The mutagenicity increased even further after 1 min of ozonation. No mutagenicity was however detected in the effluents subjected to longer exposure to ozone. The results of this study suggest that the use of ozonation as short post-treatment after a biological process can be beneficial for the degradation of recalcitrant compounds and the removal of toxicity of textile wastewater. However, monitoring of toxicity and especially mutagenicity is crucial and should always be used to assess the success of a treatment strategy.

  1. Acute toxicity when concentration varies with time: A case study with carbon monoxide inhalation by rats.

    Sweeney, Lisa M; Sommerville, Douglas R; Goodwin, Michelle R; James, R Arden; Channel, Stephen R

    2016-10-01

    Exposure to time-varying concentrations of toxic compounds is the norm in both occupational settings and daily human life, but little has been done to investigate the impact of variations in concentration on toxic outcomes; this case study with carbon monoxide helps fill that gap. Median acute lethality of 10-, 20-, 40-, and 60-min continuous exposures of rats to carbon monoxide was well described by the toxic load model (k = C(n) × t; k is constant, C = test concentration, n = toxic load exponent, and t = exposure duration) with n = 1.74. Dose response-relationships for 1-h exposures including a recovery period between 10- or 20-min pulses showed greater similarity (in both median lethality and steepness of dose-response curve) to continuous exposures with equivalent pulse duration and concentration, rather than a 60-min exposure with equivalent time-weighted average concentrations or toxic load. When pulses were of unequal concentration (3:1 ratio), only the high concentration pulse contributed to lethality. These findings show that fluctuations or interruptions in exposure over a short time scale (60 min or less) can have a substantial impact on outcomes (when n > 1), and thus high-resolution monitoring data are needed to aid interpretation of resulting outcomes.

  2. Ecotoxicological evaluation of leachate from the Limeira sanitary landfill with a view to identifying acute toxicity

    José Euclides Stipp Paterniani

    2007-12-01

    Full Text Available Final disposal of solid waste is still a cause for serious impacts on the environment. In sanitary landfills, waste undergoes physical, chemical, and biological decomposition, generating biogas and leachate. Leachate is a highly toxic liquid with a very high pollution potential. The purpose of this work is to evaluate toxicity of in natura leachate samples collected from Limeira Sanitary Landfill, in Limeira, SP. The ecotoxicological evaluation comprised acute toxicity assays using as test organisms Daphnia Similis, seeds of Eruca sativa (arugula, and Allium cepa roots (onion. Analyses of color, pH, turbidity, conductivity, hardness, nitrogen, total organic carbon (TOC, adsorbable organic halogen (AOX, and metals were also carried out. The main results for Eruca sativa (arugula and Allium cepa (onion indicated that the diluted leachate 50% presented similar toxicity to the phenol solution of 1000 mg.L-1 for arugula and 2000 mg.L-1 for onion. With the solution of Cr+6 concentrations of 3000 mg.L-1 for arugula and 2000 mg.L-1 for onion were found. For analyses with Daphnia Similis the EC50 was 9.3% on average. This way it was possible to observe that biological tests are necessary to evaluate the pollution in the effluents or water bodies. These tests serve to determine the toxic potential of a chemical agent or complex mixture.

  3. Conformal radiotherapy for prostate cancer - Longer duration of acute genitourinary toxicity in patients with prior history of invasive urological procedure

    Odrazka, Karel; Vanasek, Jaroslav; Vaculikova, Miloslava; Petera, Jiri; Zouhar, Milan; Zoul, Zdenk; Stejskal, Jan; Skrabkova, Zuzana; Kadeka, David [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Radiotherapy and Oncology

    2001-11-01

    The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.

  4. Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

    Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

    2013-09-01

    The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds.

  5. Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach.

    Vukov, Oliver; Smith, D Scott; McGeer, James C

    2016-01-01

    The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60mg CaCO3 mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23°C. Acute toxicity tests were done with azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (LogK values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The logK value for Dy(3+) toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific water quality guidelines and criteria for Dy and possibly REEs in general and offers insight into the complex bio-geochemical nature of this element.

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

    Dragica Brkić

    2009-01-01

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

  7. Joint acute toxicity of esfenvalerate and diazinon to larval fathead minnows (Pimephales promelas).

    Denton, Debra L; Wheelock, Craig E; Murray, Shauna A; Deanovic, Linda A; Hammock, Bruce D; Hinton, David E

    2003-02-01

    California (USA) agriculture employs pyrethroid and organophosphate insecticides to control insects in orchards and other crops. Diazinon and esfenvalerate were selected for this study because of their application overlaps. Toxicological and biochemical responses of larval fathead minnows (Pimephales promelas) exposed singly and in combinations to esfenvalerate and diazinon were determined. Exposures were 96-h static renewal tests that used standard U.S. Environmental Protection Agency acute toxicity test methods. After pesticide exposures, larvae were evaluated for carboxylesterase and acetylcholinesterase activity, and histopathological effects. Carboxylesterase activity was examined because of its potential influence on the toxicity of both organophosphates and pyrethroids. In vivo studies demonstrated that diazinon significantly inhibited carboxylesterase activity at nominal water concentrations as low as 50 microg/L. However, esfenvalerate did not affect carboxylesterase activity at any concentration tested. Liver glycogen depletion was the only histopathological effect observed; this effect was demonstrated with the individual pesticides and pesticide combinations (i.e., mixtures). The combinations of diazinon and esfenvalerate causing acute toxicity to fathead minnow larvae appeared to be greater than additive (i.e., synergistic) in all three tests.

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

    Ayman Goudah

    2015-05-01

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

  9. Acute toxic effects of fenpyroximate acaricide on Guppy (Poecilia reticulata Peters, 1859).

    Doğan, Nesli; Yazıcı, Zehra; Şişman, Turgay; Aşkin, Hakan

    2013-09-01

    Fenpyroximate (FP), an acaricide, is widely used in the prevention of acarids (mites) in fruit plant gardens. In this study, the acute toxic effects of different concentrations of FP were investigated using adult guppy (Poecilia reticulata Peters, 1859). Guppy adults were exposed to a range of FP concentrations (25, 50, 75, 100, 125, and 150 µg/L) during 48 h. Static method, which is one of the acute toxicity experiments, has been used in this study. According to probit analysis, the 48-h median lethal concentration (LC50) value of FP at 26°C was found to be 72.821 µg/L. Sublethal exposures were predetermined based on 48-h LC50 value. Guppies were exposed to low concentrations (15, 25, and 50 µg/L) of FP for 48 h. Signs of paralysis and behavior deformations were monitored every 12 h in a number of live and dead adults. Low concentrations of FP were also responsible for erratic swimming, loss of equilibrium, and being lethargic. Liver histology revealed several pathological damages including congestion, picnotic nucleus, sinusoidal dilatation, increase in melanomacrophagic centers, and endothelial degeneration. Finally, the toxicity test results provided 48-h LC50 value for FP, and low concentrations of FP can be highly detrimental to guppy adults with clear evidence of behavioral and histologic effects.

  10. EVALUATION OF ACUTE TOXICITY STUDY AND ANTI-ASTHMATIC ACTIVITY OF ZEAL HERBAL GRANULES

    Bhatt Swati

    2013-06-01

    Full Text Available Objective: To evaluate the Acute toxicity study and Anti-asthmatic activity of Zeal Herbal Granules. Materials & Methods: In the present study, acute toxicity study was carried out as per OECD guideline 423. Anti-asthmatic activity of Zeal Herbal Granules was investigated against compound 48/80-induced mast cell degranulation. Percentage mast cell degranulation was calculated at different concentration level i.e.1, 10, 100 and 1000μg/mL. Results: Zeal Herbal Granules showed significant protection of rat mesenteric mast cells from disruption caused by compound 48/80. Significant dose dependent effect was observed in percentage mast cell degranulation at different dose level of Zeal Herbal Granules in comparison to negative control. 26.83% mast cell degranulation was observed at 100μg/mL dose level of Zeal Herbal Granules. Conclusion: The present study revealed that Zeal Herbal Granules has significant anti-asthmatic activity against compound 48/80-induced mast cell degranulation comparable to that produced by Ketotifen fumarate. There was no lethal and toxic reactions found among the tested animals. Zeal Herbal Granules can be a safe and effective drug for patient with asthmatic complaints.

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

    K Jaijoy

    2010-03-01

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

  12. Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

    Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

    2014-07-01

    Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

  13. Acute toxicity of fire-control chemicals, nitrogenous chemicals, and surfactants to rainbow trout

    Buhl, Kevin J.; Hamilton, Steven J.

    2000-01-01

    Laboratory studies were conducted to determine the acute toxicity of three ammonia-based fire retardants (Fire-Trol LCA-F, Fire-Trol LCM-R, and Phos-Chek 259F), five surfactant-based fire-suppressant foams (FireFoam 103B, FireFoam 104, Fire Quench, ForExpan S, and Pyrocap B-136), three nitrogenous chemicals (ammonia, nitrate, and nitrite), and two anionic surfactants (linear alkylbenzene sulfonate [LAS] and sodium dodecyl sulfate [SDS]) to juvenile rainbow trout Oncorhynchus mykiss in soft water. The descending rank order of toxicity (96-h concentration lethal to 50% of test organisms [96-h LC50]) for the fire retardants was as follows: Phos-Chek 259F (168 mg/L) > Fire-Trol LCA-F (942 mg/L) = Fire-Trol LCM-R (1,141 mg/L). The descending rank order of toxicity for the foams was as follows: FireFoam 103B (12.2 mg/L) = FireFoam 104 (13.0 mg/L) > ForExpan S (21.8 mg/L) > Fire Quench (39.0 mg/L) > Pyrocap B-136 [156 mg/L). Except for Pyrocap B-136, the foams were more toxic than the fire retardants. Un-ionized ammonia (NH3; 0.125 mg/L as N) was about six times more toxic than nitrite (0.79 mg/L NO2-N) and about 13,300 times more toxic than nitrate (1,658 mg/L NO3-N). Linear alkylbenzene sulfonate (5.0 mg/L) was about five times more toxic than SDS (24.9 mg/L). Estimated total ammonia and NH3 concentrations at the 96-h LC50s of the fire retardants indicated that ammonia was the primary toxic component in these formulations. Based on estimated anionic surfactant concentrations at the 96-h LC50s of the foams and reference surfactants, LAS was intermediate in toxicity and SDS was less toxic to rainbow trout when compared with the foams. Comparisons of recommended application concentrations to the test results indicate that accidental inputs of these chemicals into streams require substantial dilutions (100-1,750-fold to reach concentrations nonlethal to rainbow trout.

  14. Estrogenicity and acute toxicity of selected anilines using a recombinant yeast assay.

    Hamblen, Elizabeth L; Cronin, Mark T D; Schultz, T Wayne

    2003-08-01

    Suspected estrogen modulators include industrial organic chemicals (i.e., xenoestrogens), and have been shown to consist of alkylphenols, bisphenols, biphenylols, and some hydroxy-substituted polycyclic aromatic hydrocarbons. The most prominent structural feature identified to be important for estrogenic activity is a polar group capable of donating hydrogen bonds (i.e., hydroxyl) on an aromatic system. The present study was undertaken to explore the estrogenic activity and acute toxicity of chemicals containing a weaker hydrogen bond donor group on aromatic systems, i.e., the amino substituent. There is a great deal of chemical similarity between aromatic amines (anilines) and aromatic alcohols (phenols). The chemicals chosen for the current study contained an amino-substituted benzene ring with hydrophobic constituents varying in size and shape. Thus, 37 substituted aromatic amines were assayed for estrogenic activity EC50 and acute toxicity LC50 using the Saccharomyces cerevisiae recombinant yeast assay. While the EC50 of 17-beta-estradiol occurs at the 10(-10) range, the aniline with the greatest activity had an EC50 of 10(-6) M. Thus, anilines, in general, are capable only of very weak estrogenic activity in this assay. A comparison of estrogenic potency between the present group of anilines and a set of previously tested analogous phenols indicated that anilines are consistently less estrogenic than phenols. A comparison of hazard indices (EC50/LC50) of these chemicals revealed that, for the vast majority of anilines, the EC50 and LC50 were in the same order of magnitude. More specifically, estrogenic activity of para-substituted alkylanilines increases with alkyl group size up to 5 carbons in length, after which the acute toxicity of the larger alkyl-substituents precluded the ability of the compound to induce the estrogenic response.

  15. Acute Amiodarone Pulmonary Toxicity after Drug Holiday: A Case Report and Review of the Literature

    Ahmed Abuzaid

    2015-01-01

    Full Text Available Amiodarone is reported to cause a wide continuum of serious clinical effects. It is often challenging to detect Amiodarone-induced pulmonary toxicity (AIPT. Typically, the diagnosis is made based on the clinical settings and may be supported by histopathology results, if available. We describe a 57-year-old patient who developed severe rapidly progressive respiratory failure secondary to AIPT with acute bilateral infiltrates and nodular opacities on chest imaging. Interestingly, Amiodarone was discontinued 3 weeks prior to his presentation. He had normal cardiac filling pressures confirmed by echocardiography. To our knowledge, this is the first case of isolated acute lung injury induced by Amiodarone, three weeks after therapy cessation, with adequate clinical improvement after supportive management and high dose steroid therapy.

  16. Environmental properties of long chain alcohols. Part 1: Physicochemical, environmental fate and acute aquatic toxicity properties

    Fisk, Peter; Sanderson, Hans; Wildey, Ross;

    2009-01-01

    This paper summarises the physicochemical, biodegradation and acute aquatic ecotoxicity properties of long chain aliphatic alcohols. Properties of pure compounds are shown to follow somewhat predictable trends, which are amenable to estimation by quantitative structure-activity relationships ((Q......)SARs). This allows predictions of data relating to human and environmental safety profiles and patterns. These alcohols have been shown to be rapidly degradable under standard conditions up to C18. Furthermore, evidence suggests that longer chain lengths are also rapidly biodegradable. While log Kow values suggest...... possible bioaccumulation potential, available data suggest that these substances are not as bioaccumulative as estimations would predict. For acute aquatic toxicity, solubility limits the possibility of effects being appropriately observed and become increasingly challenging above C12. Further, a model has...

  17. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  18. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Ying-Mei Niu

    2016-01-01

    Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  19. Acute Toxicity of Formalin to the Red-tide Dinoflagellate Prorocentrum minimum Schiller (Protozoa, Mastigophora)

    XU Henglong; SONG Weibo; ZHU Mingzhuang; QIU Yantao; MA Honggang

    2005-01-01

    The acute toxic levels of formalin to a marine red-tide dinoflagellate Prorocentrum minimum Schiller(Mastigophora,Dinoflagellida) were determined by linear regression analysis. The data obtained revealed that there is a close regression relationship between logarithmic concentrations of formalin and mortality probit scales of the organism whenexposure times are1, 2, 6, 12, 24 h. The median lethal concentrations (LC50 values) obtained from correlation analysis for these exposure times (with 95% confidence intervals), were 11.83, 6.76, 4.37, 4.27 and 3.98mgL-1, respectively. A toxicity curve was obtained to connect the exposure time and LC50 value from the correlation between them. The results indicated that P. minimum could be killed or fixed by formalin in the concentration range of 4-12 mgL-1 within 1-24 h.

  20. Acute toxic effects of two lampricides on twenty-one freshwater invertebrates

    Rye, Robert P.; King, Everett Louis

    1976-01-01

    We conducted laboratory static bioassays to determine acute toxicity of two lampricides -- a 70% 2-aminoethanol salt of 5,2'dichloro-4'-nitrosalicylanilide (Bayer 73) and a mixture containing 98% 3-trifluoromethyl-4-nitrophenol (TFM) and 2% Bayer 73 (TFM-2B) -- to 21 freshwater invertebrates. LC50 values were determined for 24-h exposure periods at 12.8 C. Organisms relatively sensitive to Bayer 73 were a turbellarian (Dugesia tigrina), aquatic earthworms (Tubifex tubifex and Lumbriculus inconstans), snails (Physa sp.) and (Pleurocera sp.), a clam (Eliptio dilatatus), blackflies (Simulium sp.), leeches (Erpobdellidae), and a daphnid (Daphnia pulex). The invertebrates most sensitive to TFM-2B were turbellarians, aquatic earthworms (Tubifex), snails (Physa), blackflies, leeches, and burrowing mayflies (Hexagenia sp.). Bayer 73 was generally much more toxic to the test organisms than TFM-2B. At lampricidal concentrations, TFM-2B was more highly selective than Bayer 73 against larval sea lampreys (Petromyzon marinus).

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

    Ghader Jalilzadeh-Amin

    2015-02-01

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

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

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

    2015-01-01

    High throughput testing according to the Fish Embryo Acute Toxicity (FET) test (OECD Testing Guideline 236) is usually conducted in well plates. In the case of hydrophobic test substances, sorptive and evaporative losses often result in declining and poorly controlled exposure conditions. Therefore......, 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...

  3. Acute silver toxicity in aquatic animals is a function of sodium uptake rate

    Bianchini, A.; Grosell, Martin Hautopp; Gregory, S.

    2002-01-01

    -specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from...... toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarus diogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above...

  4. Acute toxicity of alpha-cypermethrin to guppy (Poecilia reticulata, Pallas, 1859).

    Yilmaz, Mehmet; Gül, Ali; Erbaşli, Kazim

    2004-07-01

    Alpha-cypermethrin is a synthetic pyrethroid insecticide used to control pests in domestic, industrial and agricultural situations. Adult male guppy fish (Poecilia reticulata standard test species) were selected for the bioassay experiments. The experiments were performed in four series and the 96-h LC50 value was determined for guppies. The acute toxicity experiments were carried out by static method and behavioral changes in guppies were determined for each alpha-cypermethrin (98% technical grade) concentration. Data obtained from the alpha-cypermethrin investigation were evaluated by the use of probit analysis statistical method and the 96-h LC50 value for guppy was estimated as 9.43 microg/l.

  5. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Ying-Mei Niu; Xiao-Li Zhu; Bing Chang; Zhao-Hui Tong; Wen Cao; Pei-Huan Qiao; Lin-Yuan Zhang; Jing Zhao; Yu-Guo Song

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after expo...

  6. Combined anaerobic-ozonation process for treatment of textile wastewater: removal of acute toxicity and mutagenicity.

    Punzi, Marisa; Nilsson, Filip; Anbalagan, Anbarasan; Svensson, Britt-Marie; Jönsson, Karin; Mattiasson, Bo; Jonstrup, Maria

    2015-07-15

    A novel set up composed of an anaerobic biofilm reactor followed by ozonation was used for treatment of artificial and real textile effluents containing azo dyes. The biological treatment efficiently removed chemical oxygen demand and color. Ozonation further reduced the organic content of the effluents and was very important for the degradation of aromatic compounds, as shown by the reduction of UV absorbance. The acute toxicity toward Vibrio fischeri and the shrimp Artemia salina increased after the biological treatment. No toxicity was detected after ozonation with the exception of the synthetic effluent containing the highest concentration, 1 g/l, of the azo dye Remazol Red. Both untreated and biologically treated textile effluents were found to have mutagenic effects. The mutagenicity increased even further after 1 min of ozonation. No mutagenicity was however detected in the effluents subjected to longer exposure to ozone. The results of this study suggest that the use of ozonation as short post-treatment after a biological process can be beneficial for the degradation of recalcitrant compounds and the removal of toxicity of textile wastewater. However, monitoring of toxicity and especially mutagenicity is crucial and should always be used to assess the success of a treatment strategy.

  7. Acute toxicity of nitrofurazone to channel catfish Ictalurus punctatus, and goldfish, Carassius auratus

    Wise, M.L.; Stiebel, C.L.; Grizzle, J.M.

    1987-01-01

    Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) is a nitrofuran, a group of organic compounds which have inhibitory activity against many Gram-negative and Gram-positive bacteria and against some protozoan parasites. Although not approved by the United States Food and Drug Administration for use with food fish, nitrofurazone has been found effective in fish against external and internal infections by various species of Aeromonas, Pseudomonas and myxobacteria and can be administered either as a food additive or as a bath treatment. Attempts to control the microsporidian parasite Pleistophora ovariae in golden shiners, Notemigonus crysoleucas, with nitrofurazone met with equivocal results. The following experiment was performed to determine acute toxicity, including lesions, of nitrofurazone to channel catfish, Ictalurus punctatus, and goldfish, carassius auratus, fingerlings. Toxicity of nitrofurazone to channel catfish was determined with low dissolved oxygen concentrations (2 mg/L) to simulate conditions frequently encountered in channel catfish culture. Information abut toxic levels of drugs and the lesions occurring in exposed fish is important to determine the safety of treatment levels and the effects of toxic concentrations.

  8. Temperature-dependent acute toxicity of methomyl pesticide on larvae of 3 Asian amphibian species.

    Lau, Edward Tak Chuen; Karraker, Nancy Elizabeth; Leung, Kenneth Mei Yee

    2015-10-01

    Relative to other animal taxa, ecotoxicological studies on amphibians are scarce, even though amphibians are experiencing global declines and pollution has been identified as an important threat. Agricultural lands provide important habitats for many amphibians, but often these lands are contaminated with pesticides. The authors determined the acute toxicity, in terms of 96-h median lethal concentrations, of the carbamate pesticide methomyl on larvae of 3 Asian amphibian species, the Asian common toad (Duttaphrynus melanostictus), the brown tree frog (Polypedates megacephalus), and the marbled pygmy frog (Microhyla pulchra), at 5 different temperatures (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) to examine the relationships between temperature and toxicity. Significant interspecific variation in methomyl sensitivity and 2 distinct patterns of temperature-dependent toxicity were found. Because high proportions of malformation among the surviving tadpoles were observed, a further test was carried out on the tree frog to determine effect concentrations using malformation as the endpoint. Concentrations as low as 1.4% of the corresponding 96-h median lethal concentrations at 25 °C were sufficient to cause malformation in 50% of the test population. As the toxicity of pesticides may be significantly amplified at higher temperatures, temperature effects should not be overlooked in ecotoxicological studies and derivation of safety limits in environmental risk assessment and management.

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

    Yeng Chen

    2010-11-01

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

  10. QSARS for Acute Toxicity of Halogenated Benzenes to Bacteria in Natural Waters

    GUAN-GHUA LU; CHAO WANG; YU-MEI LI

    2006-01-01

    Objective To measure the acute toxicity of halogenated benzenes to bacteria in natural waters and to study quantitative relationships between the structure and activity of chemicals. Methods The concentration values causing 50% inhibition of bacteria growth (24h-IC50) were determined according to the bacterial growth inhibition test method. The energy of the lowest unoccupied molecular orbital and the net charge of carbon atom of 20 halogenated benzenes were calculated by the quantum chemical MOPAC program. Results The log1/IC50 values ranged from 4.79 for 2,4-dinitrochlorobenzene to 3.65 for chlorobenzene. A quantitative structure-activity relationship model was derived from the toxicity and structural parameters: log1/IC50 =-0.531(ELUMO)+1.693(Qc)+0.163(logP)+3.375. This equation was found to fit well (r2=0.860, s=0.106), and the average percentage error was only 1.98%. Conclusion Halogenated benzenes and alkyl halogenated benzenes are non-polar narcotics, and have hydrophobicity-dependent toxicity. The halogenated phenols and anilines exhibit a higher toxic potency than their hydrophobicity, whereas 2,4-dinitrochlorobenzene is electrophile with the halogen acting as the leaving group.

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

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

    2010-11-10

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

  12. Acute Toxicity of Double-Walled Carbon Nanotubes to Three Aquatic Organisms

    Lungile P. Lukhele

    2015-01-01

    Full Text Available This study investigated the toxicity of double walled carbon nanotubes (DWCNTs to three aquatic organisms, namely, Pseudokirchneriella subcapitata, Daphnia pulex, and Poecilia reticulata under the influence of exposure media properties specifically the ionic strength and organic matter represented by humic acid. Results indicated that ionic strength enhanced DWCNTs agglomeration whilst humic acid stabilized the CNTs and in turn inhibited the formation of aggregates. LC50s for D. pulex were higher at 2.81 and 4.45 mg/L for pristine and oxidised DWCNTs, respectively; however, P. reticulata had lower values of 113.64 mg/L and 214.0 mg/L for the same CNTs correspondingly. P. subcapitata had EC50s of 17.95 mg/L and 10.93 mg/L for the pristine and oxidised DWCNTs, respectively. In the presence of humic acid high DWCNTs acute toxicity towards D. pulex and P. reticulata was observed but ionic strength led to opposite effect irrespective of DWCNTs form. Both humic acid and ionic strength shielded the P. subcapitata from toxic effects of DWCNTs. Overall, our findings suggest that the toxicity of DWCNTs in the aquatic systems (i will be dependent on media properties and (ii is likely to proceed at different rates to organisms at different trophic levels.

  13. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Fortin, Andre; Wang, Chang Shu [Radiation Therapy Department, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Liu, Geoffrey [Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto (Canada); Bairati, Isabelle [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada)

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  14. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

    Sarbjeet S. Kalsi

    2011-04-01

    Full Text Available Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine.The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma.Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine.In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity.

  15. The Acute Toxicity and Hematological Characterization of the Effects of Tentacle-Only Extract from the Jellyfish Cyanea capillata

    Liming Zhang

    2011-03-01

    Full Text Available To investigate the hematologic changes and the activities of jellyfish venoms other than hemolytic and cardiovascular toxicities, the acute toxicity of tentacle-only extract (TOE from the jellyfish Cyanea capillata was observed in mice, and hematological indexes were examined in rats. The median lethal dose (LD50 of TOE was 4.25 mg/kg, and the acute toxicity involved both heart- and nervous system-related symptoms. Arterial blood gas indexes, including pH, PCO2, HCO3−, HCO3std, TCO2, BEecf and BE (B, decreased significantly. PO2 showed a slight increase, while SO2c (% had no change at any time. Na+ and Ca2+ decreased, but K+ increased. Biochemical indexes, including LDH, CK, CK-MB, ALT, AST and sCr, significantly increased. Other biochemical indexes, including BUN and hemodiastase, remained normal. Lactic acid significantly increased, while glucose, Hct% and THbc showed slight temporary increases and then returned to normal. These results on the acute toxicity and hematological changes should improve our understanding of the in vivo pathophysiological effects of TOE from C. capillata and indicate that it may also have neurotoxicity, liver toxicity and muscular toxicity in addition to hemolytic and cardiovascular toxicities, but no kidney or pancreatic toxicity.

  16. Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

    Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

    2016-06-01

    The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques.

  17. ACUTE AND CHRONIC TOXICITY OF PHENYL QUINOLINE ON WATER FLEA DAPHNIA MAGNA

    Hildebrando Ayala

    2012-06-01

    Full Text Available The aquatic ecotoxicological determination of phytonematicide products using the zooplanktonic cladoceran Daphnia magna is important for environmental risk assessment. Evaluations were made of the acute median lethal concentration (LC50 of phenyl quinoline on D. magna, that was 4.12 ug i.a. L-1 at 48 h of exposure. The chronic effects of phenyl quinoline in the mortality rate of the cladoceran D. magna at 17 d of exposure, with 0.18 ug ai L-1 of LOEC (Lowest Observed Effect Concentration and 0.072 ug ai L-1 of NOEC (No Observed Effect Concentration were determined. Evaluations of the chronic effect of phenyl quinoline on three parameters of growth of D. magna (total length, antenna length and caudal length to 17 d of exposure, only showed significant differences in length of the antenna between the control and 0.072 ug ai L-1 been this the value of LOEC and thus the lower concentration 0.0288 ug ai L-1, the NOEC value for phenyl quinoline. The ratio between acute and chronic toxicity (RAC for the relationship showed acute 48 h exposure on mortality NOEC 17 d a value of 57.22, and for the ratio of acute NOEC on of the length of the antenna to 17 d was a value of 143. The environmental risk assessment (ERA shows that the PEC (Probable Effect Concentration / PNEC (Predicted No-Effect Concentration for acute assay was 582 524 and for the PEC / PNEC for chronic test was 83 333 333. These results demonstrate that phenyl quinoline has a high impact on aquatic biota represented by the trophic level that belongs to D. magna, and therefore shows that the substance is a candidate for a comprehensive ecotoxicological assessment.

  18. Acute toxicity effects of Prunus avium fruit extract and selection of optimum dose against radiation exposure.

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

    The objective of the study was to evaluate the acute toxicity of different doses of the methanolic extract of the fruit pulp of Prunus avium (family Rosaceae), which is used ethno-medicinally for the treatment of various diseases, and to find out the optimal dose of Prunus avium extract against 10 Gy gamma-radiation exposure. To test acute toxicity in mice, different doses of PAE (Prunus avium fruit extract) were given orally for 15 consecutive days, after which the animals were observed for another 15 days; the LD50/15 of the methanolic extract was calculated to be 4.947 gm/kg body weight (b.wt). In optimum dose selection against radiation exposure, oral administration of 450 mg/kg b.wt/d of PAE for 15 consecutive days before exposure to 10 Gy of gamma-radiation was found to afford maximum protection in terms of body weight and survivability of the mice in comparison to other doses.

  19. Safety evaluation of turmeric polysaccharide extract: assessment of mutagenicity and acute oral toxicity.

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

    2013-01-01

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

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

    Chandrasekaran Chinampudur Velusami

    2013-01-01

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

  1. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

    Saad Musbah Alasil

    2014-01-01

    Full Text Available The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237, phospholipase A2 inhibitor C21H36O5 (MW 368.512, and an antibacterial agent C14H11N3O2 (MW 253.260. The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups P>0.05. Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections.

  2. Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

    Wang, Wen; Jin, Minghua; Du, Zhongjun; Li, Yanbo; Duan, Junchao; Yu, Yongbo; Sun, Zhiwei

    2013-01-01

    This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. PMID:23593469

  3. Acute toxicity of amorphous silica nanoparticles in intravenously exposed ICR mice.

    Yang Yu

    Full Text Available This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs in mice. The lethal dose, 50 (LD50, of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg. The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g, spleen (34.78%ID/g and lung (1.96%ID/g. TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process.

  4. Acute toxicity of runoff from sealcoated pavement to Ceriodaphnia dubia and Pimephales promelas

    Mahler, Barbara J.; Ingersoll, Christopher G.; Van Metre, Peter C.; Kunz, James L.; Little, Edward E.

    2015-01-01

    Runoff from coal-tar-based (CT) sealcoated pavement is a source of polycyclic aromatic hydrocarbons (PAHs) and N-heterocycles to surface waters. We investigated acute toxicity of simulated runoff collected from 5 h to 111 days after application of CT sealcoat and from 4 h to 36 days after application of asphalt-based sealcoat containing about 7% CT sealcoat (AS/CT-blend). Ceriodaphnia dubia (cladocerans) and Pimephales promelas (fathead minnows) were exposed in the laboratory to undiluted and 1:10 diluted runoff for 48 h, then transferred to control water and exposed to 4 h of ultraviolet radiation (UVR). Mortality following exposure to undiluted runoff from unsealed asphalt pavement and UVR was ≤10% in all treatments. Test organisms exposed to undiluted CT runoff samples collected during the 3 days (C. dubia) or 36 days (P. promelas) following sealcoat application experienced 100% mortality prior to UVR exposure; with UVR exposure, mortality was 100% for runoff collected across the entire sampling period. Phototoxic-equivalent PAH concentrations and mortality demonstrated an exposure-response relation. The results indicate that runoff remains acutely toxic for weeks to months after CT sealcoat application.

  5. Antibacterial, antioxidant and acute toxicity tests on flavonoids extracted from some medicinal plants

    Akroum Souâd

    2010-01-01

    Full Text Available Flavonoids are well-known for their many therapeutic and pharmaceutical effects. In this study, we tested the antibacterial activity of 11 flavonoids extracted from some medicinal plants by the agar diffusion method. Then, we measured their antioxidant activity using the DPPH (2,2′-diphenyl-1-picrylhydrazyl radical assay and we also tested their acute toxicity effect on mice. The results showed that apigenin-7-O-glucoside was more active against the Gram-positive bacteria and quercetin was more active against the Gram-negative ones. Also, quercetin and diosmin showed the best antioxidant activity. Quercetin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and luteolin-3′-O-glucuronide gave the best acute toxicity values. It can be concluded that quercetin was the most interesting compound for all the tested activities. Also, we observed that the presence or the absence of substitutions in flavonoids influenced significantly the results obtained, whereas the substitution type had a low impact.

  6. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

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

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

    2016-08-01

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

  8. Evaluating Systemic Toxicity in Rabbits after Acute Ocular Exposure to Irritant Chemicals

    Reshma Sebastian Cherian

    2014-01-01

    Full Text Available Acute systemic toxicity via ocular exposure route is not a well understood aspect. Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide for 24 h and scored. After a period of 72 h, blood was collected from the animals for examining the hematological and biochemical parameters. The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario.

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

    Feroz Ahmad; Nahida Tabassum

    2013-01-01

    Objective: To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods: Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Result: Phytochemical screening revealed that the roots ofP. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. Conclusions: The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

  10. A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

    Burgoon, Lyle D

    2016-06-01

    An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

  11. Acute Toxicity of Aluminium to the Fish (Catla catla, Labeo rohita and Cirrhina mrigala

    Hamda Azmat*, Muhammad Javed and Ghazala Jabeen

    2012-01-01

    Full Text Available Acute toxicity tests (96-hr LC50 and lethal concentration of aluminium (Al were conducted with three fish species viz. Catla catla, Labeo rohita and Cirrhina mrigala of 60, 120 and 240 days age groups at constant water temperature (30oC, pH (7.50 and total hardness (300 mg.L-1 in the wet laboratory. At termination of each trial, the fish were dissected and their organs viz. bones, gills, gut, intestine, kidney, liver, scales, skin, muscles and fats isolated for the determination of Al concentrations. At 60 days, all the three fish species showed significantly (P<0.05 higher sensitivity to Al while 240 days fish were significantly least sensitive. Among the three fish species, Catla catla were significantly (P<0.05 more sensitivity to Al with the mean 96-hr LC50 and lethal concentration of 81.68±28.54 and 129.81±30.95 mg.L-1, respectively. Fish organs showed significantly variable ability to concentrate metal during acute exposure of Al. However, liver and kidneys exhibited significantly higher potentials for metals accumulation. From the study it was concluded that all the three fish species responded differently towards Al toxicity.

  12. Acute and chronic toxicity of the methanolic extract of Ajuga iva in rodents

    Abdelouahab Diafat

    2016-03-01

    Full Text Available Summary. Ajuga iva, known as “Chendgoura”, is widely used in North African countries in the traditional medicine. However, there is little toxicological informations available regarding its safety following repeated exposure. The present investigation describes the toxicity of a methanolic extract of Ajuga iva. The administration of the Ajuga iva methanolic extract (AIME at 2 –14 g/kg of bodyweight (bwt did not produce mortality or significant changes in the general behavior of mice. However, single intraperitoneal injections of AIME (2–6 g/kg bwt produced a dose-dependent increase in adverse effects in the general behavior and the mortality rate. The LD50 by  intraperitoneal route  was 3.980 g/kg bwt. In chronic toxicological studies in rats, oral administration the AIME with daily doses of 100, 300 and 600 mg/kg bwt, did not cause any significant differences in the general conditions like growth, organ weights, hematological and biochemical parameters or in microscopic appearance of the organs (brain, liver and the kidney. In contrast, a transient rise in platelet counts and a decrease in serum glucose and cholesterol levels were noted. Therefore, the NOAEL for the AIME is 600 mg/kg/day administered orally for 13 weeks. So AI methanolic extract has low toxicity. Industrial relevance. The extract of the plant Ajuga iva can be used as herbal teas or for the treatment of several disease such as diabetes, high cholesterol and increased serum triglycerides. However, information regarding its toxicological properties is not available. In this study, we have shown that the methanolic extract of Ajuga iva has low toxicity in rodent models and may be considered for human use after further studies. Keywords. Ajuga iva; methanolic extract; acute toxicity; sub chronic toxicity

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

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

    2009-02-01

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

  14. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

    Pillai, Sekhar C; Gill, Deepak; Webster, Richard; Howman-Giles, Robert; Dale, Russell C

    2010-09-01

    N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

  15. Transformation pathways and acute toxicity variation of 4-hydroxyl benzophenone in chlorination disinfection process.

    Liu, Wei; Wei, Dongbin; Liu, Qi; Du, Yuguo

    2016-07-01

    Benzophenones compounds (BPs) are widely used as UV filters, and have been frequently found in multiple environmental matrices. The residual of BPs in water would cause potential threats on ecological safety and human health. Chlorination disinfection is necessary in water treatment process, in which many chemicals remained in water would react with disinfectant chlorine and form toxic by-products. By using ultra performance liquid phase chromatography quadrupole time of flight mass spectrometer (UPLC-QTOF-MS), nuclear magnetic resonance (NMR), the transformation of 4-hydroxyl benezophenone (4HB) with free available chlorine (FAC) was characterized. Eight major products were detected and seven of them were identified. Transformation pathways of 4HB under acid, neutral, and alkaline conditions were proposed respectively. The transformation mechanisms involved electrophilic chlorine substitution of 4HB, Baeyer-Villiger oxidation of ketones, hydrolysis of esters and oxidative breakage of benzene ring. The orthogonal experiments of pH and dosages of disinfectant chlorine were conducted. The results suggested that pH conditions determined the occurrence of reaction types, and the dosages of disinfectant chlorine affected the extent of reactions. Photobacterium assay demonstrated that acute toxicity had significant increase after chlorination disinfection of 4HB. It was proved that 3,5-dichloro-4HB, one of the major transformation products, was responsible for the increasing acute toxicity after chlorination. It is notable that, 4HB at low level in real ambient water matrices could be transformed during simulated chlorination disinfection practice. Especially, two major products 3-chloro-4HB and 3,5-dichloro-4HB were detected out, implying the potential ecological risk after chlorination disinfection of 4HB.

  16. Acute toxicity and metabolomics analysis of hypocholesterolemic effect of Mentha piperita aqueous extract in Wistar rats

    Nor Zaini Johari

    2015-01-01

    Full Text Available Summary. The oral acute toxicity of the aqueous peppermint extract (APE was assessed and the bio and/or chemo markers for hypocholesterolemic activity of APE were identified through metabolomics approach. No mortality resulted from the present oral acute toxicity study in which the histological changes observed in the selected organs and the biochemical deviation of blood compared to the normal range level were minimal. This study also explored the effect of 290 mg-1 kg body weight of APE against 5% cholesterol-enriched diet within 14 days treatment. Whereby after the treatment, there were reductions exhibited in plasma total cholesterol (44.32%, LDL-cholesterol (69.19% and total triglycerides (55.77%. 1H NMR-metabolomics approach was, employed for better sensitivity and accuracy in evaluating the  potential plasma biomarkers of hyper-and hypo-cholesterolemic properties. β-Hydroxybutarate and α-D-glucose have been identified as the possible hypercholesterolemic markers, whereas taurine, betaine, alanine, glycine and L-leucine were suggested to be the hypocholesterolemic markers of APE.  Industrial relevance. Due to various reports on the side effects of conventional drug-lowering cholesterol available in the market, aqueous peppermint extract at its recommended consumption dosage has been investigated over its toxicity of oral consumption and its efficacy against elevation of cholesterol level in blood. The evaluation of hypocholesterolemic activity of aqueous peppermint extract (APE, from which the potential biomarkers could be established, might be useful in the  development of new anti-cholesterol drug and also for quality control of peppermint-based products. Keywords. Mentha piperita; peppermint; hypercholesterolemia; metabolomics; 1H NMR; multivariate data analysis

  17. Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in rats.

    Dagenais, Simon; Mayer, John; Wooley, James R; Haldeman, Scott; Hite, Mark

    2007-01-01

    Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive human experience with similar drugs administered by intraligamentous injection for chronic musculoskeletal disorders, little is known concerning preclinical toxicity. The purpose of this study was to assess the acute toxicity of intramuscular Proliferol in 96 (48 male, 48 female) Charles River strain rats, which were randomly assigned to low- (1x), medium- (5x), or high- (10x) dose Proliferol (derived from a human dose of 20 ml on a volume per bodyweight basis), or high-dose saline placebo. Observations included clinical observations, biochemistry, hematology, urinalysis, and full histopathology after 24 h or 14 days. There were no signs of ill health or reaction to treatment, and gait and body temperature were within normal limits. Biochemistry findings at 24 h included elevated aspartate aminotransferase, alanine aminotransferase, and haptoglobin; at 14 days all values were within normal ranges. Urinalysis findings at 24 h included increased urobilinogen and blood in all dose groups compared with placebo. Urine concentrations of phenol and lidocaine were greatest at 2 h and absent at 24 h. Histopathology findings included localized acute inflammatory soft tissue changes at the injection sites at 24 h and skeletal muscle regeneration at 14 days, which were consistent with the anticipated mechanism of action of Proliferol. There was no evidence of systemic toxicity from intramuscular injection of Proliferol in rats at up to 10x the human dose.

  18. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  19. Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

    McGuire, S.A.

    1991-02-01

    The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

  20. Investigation of Acute Toxicity Diazinon, Deltamethrin, Butachlor and pretilachlor on Zebra Cichlid (Cryptoheros nigrofasciatus

    Ali Sadeghi

    2014-06-01

    Full Text Available Background: The presence of pesticide due to the huge demand for agricultural purposes is very prevalent in surface waters of Iran. These pesticides could finally accumulate in aquatic ecosystems and have been proved to have toxic effects on aquatic animals. The aim of this study was to assess the acute toxicity of Diazinon, Deltamethrin, Butachlor and Pretilachlor on Zebra Cichlid (Cryptoheros nigrofasciatus. Methods: Fish samples were exposed to different concentrations of Diazinon (60% (0, 2, 4, 8, 16 and 32 ppm, Deltamethrin (2.5% (0, 0.02, 0.04, 0.10, 0.20 and 0.40 ppm, butachlor (60% (0, 2, 4, 8, 16 and 32 ppm and pretilachlor (50% (0, 5, 10, 20, 30 and 40 ppm for 96 h within the 100 L glass aquaria and cumulative mortality of Zebra Cichlid fish was calculated in 24-h interval. Results: The very low LC50 obtained for diazinon (5.06±0.37 ppm, deltamethrin (0.15±0.39 ppm, butachlor (8.93±0.26 ppm and pretilachlor (20.72±0.58 ppm indicated that these are highly toxic chemicals. Conclusion: Our results demonstrate that deltamethrin and pretilachlor had the lowest and highest rate of mortality on the Zebra Cichlid respectively.

  1. Acute Toxicity of a Heavy Metal Cadmium to an Anuran, the Indian Skipper Frog Rana cyanophlyctis

    Ajai Kumar Srivastav

    2016-08-01

    Full Text Available Background: There has been increasing awareness throughout the world regarding the remarkable decrease in amphibian population. For such amphibian population decline several causes have been given. Cadmium, a heavy metal is released both from natural sources (leaching of cadmium rich soils and anthropogenic activities to the aquatic and terrestrial environments. This study evaluated the toxicity of heavy metal cadmium to Indian skipper frog Rana cyanophlyctis. Methods: For the determination of LC50 values for cadmium, four-day static renewal acute toxicity test was used. Five replicates each containing ten frogs were subjected to each concentration of cadmium chloride (15, 20, 25, 30, 35, 40, 45 and 50 mg/L. At different exposure periods (24, 48, 72 and 96 h, the mortality of the frog was subjected to Probit analysis with the POLO-PC software (LeOra Software to calculate the LC50 and 95% confidence level. Results: The LC50 values of cadmium chloride for the frog R. cyanophlyctis at 24, 48, 72, and 96 h are 32.586, 29.994, 27.219 and 23.048 mg/L, respectively. The results have been discussed with the toxicity reported for other aquatic vertebrate --fish. Conclusion: Cadmium caused mortality to the frog and this could be one of the reasons for population decline of frogs which inhabit water contaminated with heavy metals.

  2. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

    2011-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

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

    Sreenivasan Sasidharan

    2011-06-01

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

  4. Evaluation of acute copper toxicity to larval fathead minnows (Pimephales promelas) in soft surface waters.

    Van Genderen, Eric J; Ryan, Adam C; Tomasso, Joseph R; Klaine, Stephen J

    2005-02-01

    The hardness-based regulatory approach for Cu prescribes an extrapolation of the toxicity-versus-hardness relationship to low hardness (hardness surface waters. Seasonal water sampling was conducted at 24 sites throughout South Carolina, USA, to determine the site-specific influences of soft surface-water conditions on acute Cu toxicity. Concurrent toxicity tests in laboratory water, matched for hardness and alkalinity (modified method), also were conducted to allow calculation of water-effect ratios (WERs). In addition, tests were conducted at recommended hardness levels (recommended method) for comparison of WER methodology in soft water. Surface-water conditions (average+/-standard deviation, n = 53) were hardness of 16+/-8 mg/L as CaCO3, alkalinity of 18+/-11 mg/L as CaCO3, and dissolved organic carbon of 6+/-4 mg/L. Dissolved Cu 48-h median lethal concentration (LC50) values varied nearly 45-fold across the dataset and greater than four-fold at individual sites. Spatial (p hardness-based equation for Cu at 50 mg/L or less as CaCO3 would adequately protect fathead minnow populations in soft surface waters. The WER results presented here demonstrate the inconsistency between hardness-based criteria and the methodology for deriving site-specific water-quality criteria in low-hardness waters.

  5. Acute toxicity of ammonia and copper to the gastropod Potamopyrgus jenkinsi (Smith)

    Watton, A.J.; Hawkes, H.A.

    1984-01-01

    96-h acute toxicity tests were made, using a flow-through system, to determine the toxicity of ammonia and copper to Potamopyrgus jenkinsi. Both lethal and sub-lethal behavioral responses were monitored for three different age groups of snail - juvenile, prime adult and senescent. Juvenile snails were much less tolerant than adults of both toxicants. Senescent adults were also less tolerant of ammonia than prime adults. 96-h LC/sub 50/ values of 0.315, 0.49 and 0.85 mg N liter/sup -1/ unionized N - NH/sub 3/ and 0.054, 0.079 and 0.077 mg Cu liter/sup -1/ total copper were recorded for juveniles, senescent adults and prime adults, respectively, in separate experiments. EC/sub 50/ values were clearly lower in adult snails. Potamopyrgus jenkinsi was relatively intolerant of both ammonia and copper compared with other invertebrate taxa reported in the literature. It is concluded that Potamopyrgus jenkinsi could be a valuable indicator species of these pollutants. 29 references, 1 figure, 5 tables.

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

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

    2015-01-01

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

  7. Acute and chronic species toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to mammals

    Kuntsevich, A.D.; Troshkin, N.M.; Baulin, S.I. [Center of Ecotoxicometry, Moscow (Russian Federation)] [and others

    1995-01-01

    The problem of anthropogenic pollution of the environment by polychlorinated dibenzo-p-dioxins (PCDD) has currently become a central problem. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is reported to be the most hazardous. In light of this, the goal of this study was to examine acute and chronic toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to mammalian species. The results led us to conclude that TCDD is one of the most toxic and ecologically hazardous synthetic chemicals known to humans. It may cause acute and chronic intoxications and ecological catastrophies. 5 refs., 3 tabs.

  8. Predictors of Acute Gastrointestinal Toxicity During Pelvic Chemoradiotherapy in Patients With Rectal Cancer

    Yang, T. Jonathan; Oh, Jung Hun; Son, Christina H.; Apte, Aditya; Deasy, Joseph O.; Wu, Abraham

    2013-01-01

    ABSTRACT BACKGROUND: This study was conducted to identify the factors associated with acute gastrointestinal (GI) toxicity during pelvic chemoradiotherapy (PCRT) in patients with rectal cancer. METHODS: We analyzed 177 patients with rectal cancer treated from 2007 through 2010. Clinical information, including weekly diarrhea and proctitis toxicity grade during PCRT, was recorded. GI structures including bowel and anal canal were contoured. The associations between toxicity and clinical and dosimetric predictors were tested. RESULTS: The median age was 60; 76 patients were women; 98 were treated with intensity-modulated radiotherapy (IMRT) and 79 with 3D conformal RT (3DCRT). A higher rate of grade 2+ diarrhea was observed in the women, starting at week 4 (24% women vs. 11% men, P = .01; week 5: 33% vs. 12%, P = .002), as well as in all the patients treated with 3DCRT (22% vs. 12% IMRT, P = .03; week 5: 32% vs. 11%, P = .001). On multivariate analysis, the normal tissue complication probability (NTCP) model including bowel V45 (bowel volume receiving ≥45 Gy) showed that being female, and use of 3DCRT, was most predictive of grade 2+ diarrhea (area under the curve [AUC] = 0.76; RS = 0.35; P < .001). A higher rate of grade 2+ proctitis was seen in patients <60 years of age starting at week 3 (21% vs. 9%, P = .02; week 4: 35% vs. 16%, P = .003). The NTCP model including anal canal V15 and younger age was most predictive of grade 2+ proctitis (AUC = 0.67; RS = 0.25; P < .001). CONCLUSIONS: Women and all patients who were treated with 3DCRT had higher rates of grade 2+ diarrhea, and the younger patients had a higher rate of grade 2+ proctitis during PCRT. The use of more stringent dosimetric constraints in higher risk patients is a strategy for minimizing toxicity. PMID:24312686

  9. Subtle alterations in NMDA-stimulated cyclic GMP levels following lateral fluid percussion brain injury.

    Temple, M D; Delahunty, T M; Hamm, R J; Phillips, L L; Lyeth, B G; Povlishock, J T

    2001-01-01

    This study examined whether NMDA-stimulated cyclic GMP levels were altered at two different time points following lateral fluid percussion injury. At 60 min and 15 days postinjury, the left and right hippocampi were dissected and chopped into mini-prisms. Each hippocampus was divided into five equal parts and incubated with either the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine, 500 microM) alone, IBMX and N-methyl-D-aspartic acid (NMDA) OR IBMX, NMDA, and glycine (10 MM). Two concentrations of NMDA were used: 500 or 1,000 microM. Tissues were then assayed for levels of cyclic GMP. Results indicated that there were no changes in basal levels of cyclic GMP at either postinjury time point. At 60 min postinjury, there were no significant main effects for injury or drug concentration. There was a significant injury x side interaction effect with increased levels of NMDA-stimulated cyclic GMP in the hippocampus ipsilateral to the injury impact and decreased cyclic GMP levels in the contralateral hippocampus. There were no significant alterations in NMDA-stimulated cyclic GMP levels at 15 days postinjury. The data from this study indicated that NMDA-stimulated cyclic GMP accumulation is differentially altered in the hippocampus ipsilateral and contralateral to the site of the injury at 1 h after injury, but is normalized by 15 days postinjury. These findings implicate NMDA-mediated intracellular signaling processes in the acute excitotoxic response to injury.

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

    Yalena Prado

    2015-02-01

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

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

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

    1993-03-31

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

  12. Profiles and Time Course of Acute Radiation Toxicity Symptoms during Conformal Radiotherapy for Cancer of the Prostate

    Hovdenak, Nils; Karlsdottir, Aasa; Soerbye, Halfdan; Dahl, Olav [Univ. of Bergen (Norway). Div. of Gastroenterology

    2003-11-01

    Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining maximal tolerated doses, but tend to underestimate the total toxicity burden by excluding several minor complaints. We have applied a more detailed and quantitative recording of symptoms and related these scores to RT-induced endoscopic and histopathologic changes. Prevalence and severity of specific toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks after RT in 96 patients undergoing external beam RT for localized prostate cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were recorded. TTS scores were calculated by adding scores based on visual analog scale (VAS) grading of individual symptoms. Fifty of the patients also underwent sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but differed in prevalence and intensity during and after RT. TTS increased during the entire treatment course in spite of normalizing histopathologic and endoscopic changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity, four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The study demonstrates that multiple toxicity symptoms contribute to total toxicity in response to pelvic RT. TTS is a feasible and sensitive method for detecting and quantifying acute toxicity and unveils morbidity which remains hidden with the RTOG/EORTC score system. The development and timing of symptoms may give clues to pathogenesis, treatment, and prophylaxis.

  13. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  14. Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

    Turgut Topal

    2007-08-01

    Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

  15. Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

    Turgut Topal

    2007-08-01

    Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

  16. Pharmacological actions and acute toxicity of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones.

    Singh, G B; Leach, G D; Atal, C K

    1987-06-01

    Some pharmacological actions and acute toxicity effects of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones have been described in experimental animals. The compounds antagonised the contractions evoked by a variety of agonists on several smooth muscle preparations in vitro. They produced inhibitory effects on spontaneously contracting uteri from pregnant rats and relaxant effects on pendular movements of rabbit duodenum and on dog intestinal movements in vivo. The compounds inhibited the castor oil induced diarrhoea in rat and propulsion of charcoal test meal in mice. Phenylbutazone showed similar effect on castor oil diarrhoea. The compounds failed to modify gestation period or parturition in pregnant rats. They antagonised bradykinin-induced bronchospasm in guinea pig. The compounds showed no significant effect on cardiovascular and respiratory systems: CNS and general behaviour were not affected even at high doses. Oral LD50 for both the compounds was greater than 2 g/kg.

  17. Investigation of acute toxicity of pirimiphos-methyl (Actellic, 25%EC) on guppy (Poecilia reticulata, Peters, 1859).

    Lawal, M O; Samuel, O B

    2010-04-15

    Pirimiphos-methyl is a broad spectrum organophosphate insecticide and potential toxic pollutant in aquatic ecosystems. The acute toxicity of Pirimiphos-methyl (Actellic) was investigated using Guppy (Poecilia reticulata) in a 96 h static renewal laboratory bioassay. Based on probit analysis the LC50 was 0.026, 0.024, 0.022 and 0.019 ml L(-1) at 24, 48, 72 and 96 h, respectively. Analysis of Variance (ANOVA) showed that there was significant difference (p reticulata to different concentrations of Actellic at 24, 48, 72 and 96 h of exposure. Actellic insecticide is toxic to fish; therefore its indiscriminate use in aquatic environment should be discouraged.

  18. The effect of food on the acute toxicity of silver nitrate to four freshwater test species and acute-to-chronic ratios.

    Naddy, Rami B; McNerney, Gina R; Gorsuch, Joseph W; Bell, Russell A; Kramer, James R; Wu, Kuen B; Paquin, Paul R

    2011-11-01

    Acute silver toxicity studies were conducted with and without food for four common freshwater test species: Daphnia magna, Ceriodaphnia dubia, Pimephales promelas (fathead minnow-FHM), and Oncorhynchus mykiss (rainbow trout-RBT) in order to generate acute-to-chronic ratios (ACR). The studies were conducted similarly (i.e., static-renewal or flow-through) to chronic/early-life stage studies that were previously performed in this laboratory. The acute toxicity (EC/LC50 values) of silver without food ranged from 0.57 μg dissolved Ag/l for C.dubia to 9.15 μg dissolved Ag/l for RBT. The presence of food resulted in an increase in EC/LC50 values from 1.25× for RBT to 22.4× for C. dubia. Invertebrate food type was also shown to effect acute silver toxicity. Food did not affect EC/LC50s or ACRs as greatly in fish studies as in invertebrate studies. ACRs for both invertebrate species were <1.0 when using acute studies without food but were 1.22 and 1.33 when using acute studies with food. ACRs for FHMs ranged from 4.06 to 7.19, while RBT ACRs ranged from 28.6 to 35.8 depending on whether food was present in acute studies. The data generated from this research program should be useful in re-determining a final ACR for silver in freshwater as well as in risk assessments.

  19. Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

    Brown, Aaron P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Barney, Christian L. [Baylor College of Medicine, Houston, Texas (United States); Grosshans, David R.; McAleer, Mary Frances [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Groot, John F. de; Puduvalli, Vinay K. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crawford, Cody N.; Khan, Meena [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Khatua, Soumen [Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Mark R. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-06-01

    Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

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

    Feroz; Ahmad; Nahida; Tabassum

    2013-01-01

    Objective:To carry out a preliminary phytochemical,acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis(P.officinalis)L.Methods:Preliminary phytochemical investigation was done as per standard procedures.Acute oral toxicity study was conducted as per OECD 425 guidelines.The antihepatotoxic activity of aqueous extract of root of P.officinalis was evaluated against carbon tetrachloride(CCl4)induced hepatic damage in rats.Aqueous extract of P.officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals.Liver injury was induced chemically,by CCl4 administration(1 mL/kg i.p.).The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST),alanine aminotransferase(ALT),serum alkaline phosphatase(SALP),total bilirubin and total protein(TP)along with histopathological studies.Result:Phytochemical screening revealed that the roots of P.officinalis contain alkaloids,tannins,saponins,glycosides,carbohydrates,flavonoids,terpenes,steroids and proteins.The aqueous extract did not cause any mortality up to 2000 mg/kg.In rats that had received the root extract at the dose of 100 and 200 mg/kg,the substantially elevated AST,ALT,SALP,total bilirubin levels were significantly lowered,respectively,in a dose dependent manner,along with CCl4 while TP levels were elevated in these groups.Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal.Conclusions:The aqueous extract of P.officinalis is safe and possesses antihepatotoxic potential.

  1. Acute toxicity bioassays using Daphnia magna Straus (Cladocera, Daphniidae maintained in a modified culture medium

    Mónica Núñez

    2013-05-01

    Full Text Available Daphnia magna is a test organism used in ecotoxicological assays of freshwater; however, traditional culture systems for this organism could result expensive, for that the aim of this research was to developed a new economic culture medium. With this purpose, 10 strains of D. magna were isolated, their population development was evaluated by total count of organisms and pregnant females using 3 different culture media: (A alfalfa juice, (B solved yeast and (C a mixture of alfalfa juice plus solved yeast. Successful development of 4 strains was observed in the A medium, but the same strains failed to survive in the B and the C media. The 24h and 48h EC50 average values in acute ecotoxicological assays with potassium dicromate were 0,4045 mg/L ± 0,0389 and 0,1857 mg/L ± 0,0072 respectively. Also, acute ecotoxicological assays with these 4 strains were performed using potassium cyanide, which is a toxic reactive frequently used in mining operations. In this case 24h EC50 value was 1,5388 mg/L ± 0,1146 and 48h EC50 values were 0,6359 mg/L ± 0,0516. 48h EC50 values were lower than the cyanide permissible effluent values established by the Energy and Mining Authority.

  2. Acute toxicity of the antifouling compound butenolide in non-target organisms.

    Yi-Fan Zhang

    Full Text Available Butenolide [5-octylfuran-2(5H-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target organisms. According to OECD's guideline, the predicted no effect concentration (PNEC was 0.168 µg l(-1, which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK, Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

  3. Acute Toxicity of the Antifouling Compound Butenolide in Non-Target Organisms

    Zhang, Yi-Fan

    2011-08-29

    Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD\\'s guideline, the predicted no effect concentration (PNEC) was 0.168 µg l^(−1), which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

  4. Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

    Khoja, Leila; Maurice, Catherine; Chappell, MaryAnne; MacMillan, Leslie; Al-Habeeb, Ayman S; Al-Faraidy, Nada; Butler, Marcus O; Rogalla, Patrik; Mason, Warren; Joshua, Anthony M; Hogg, David

    2016-03-01

    Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab.

  5. Acute toxicity bioassay of dimethoate on freshwater airbreathing catfish, Heteropneustes fossilis (Bloch).

    Pandey, Rakesh K; Singh, Ram N; Singh, Sarika; Singh, Narendra N; Das, Vijai K

    2009-05-01

    Pesticides are chemicals used for pest control in the agricultural fields. They finally reach the surrounding water bodies through surface runoff affecting the aquatic fauna. Dimethoate is frequently used organophosphate pesticide due to its high effectiveness and rapid breakdown into environmentally safe products. A 96 hr static acute toxicity test was carried out to determine the LC50 value of dimethoate, on the freshwater airbreathing catfish Heteropneustes fossilis (Bloch). The fish were exposed to 7 different concentrations of dimethoate (2.50, 2.75, 3.00, 3.25, 3.50, 3.75 and 4.00 mg l(-1)) for toxicity bioassay. Control (0.00 mg l(-1)) was also carried out. The data were subjected to Finney's Probit analysis and processed with Trimmed Spearman-Karber statistical software. The LC50 values for dimethoate for 24, 48, 72 and 96 hr were 3.38, 3.23, 3.08 and 2.98 mg l(-1), respectively. At higher concentration of dimethoate (3.25 mg l(-1) and above) the fish showed uncoordinated behaviour such as erratic and jerky swimming, attempt to jump out of water, frequent surfacing and gulping of air, decrease in opercular movement and copious secretion of mucus all over the body.

  6. Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.

    Caixia Li

    Full Text Available Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS, we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury.

  7. Acute toxicity and histopathology in ornamental fish amazon bluespotted corydora (Corydoras melanistius) exposed to formalin.

    Santos, Rudã F B; Dias, Henrique M; Fujimoto, Rodrigo Y

    2012-12-01

    The objective of this work was to evaluate the acute toxicity of formalin and histopathological effects on the Amazon ornamental fish, bluespotted coridora (Corydoras melanistius). A randomized design was used, with ten concentrations of formalin (40%) (0, 3, 6, 12, 25, 50, 100, 150, 200 and 250 mg.L(-1)) with four replicates and five fish per container (3L) in static system for 96 hours. The moribund fish were killed and fixed in 10% formalin to proceed the histopathological analysis of gill, liver and kidney. At the end of this experiment the following mortality rates (%) were obtained in increasing order of exposure: 0, 0, 0, 0, 0, 65, 85, 100, 100 and 100%. The lethal concentration 50% (LC(50-96h (I))) estimated was 50.76 mg.L(-1) with regression of y = 0.51x, and r(2) = 0.80. Further, in higher concentrations morphological changes as gill hyperplasia, with filling of interlamellar spaces, disorganization of liver arrangement, and necrosis in kidney were observed. In this study, the formalin can be considered slightly toxic to bluespotted corydora, and cause morphological changes when exposed to high concentrations. The use of formalin to treat of ornamental fish in the inner river of capture with wrong concentration can provoke negative environmental and biological effects.

  8. Acute and additive toxicity of ten photosystem-II herbicides to seagrass

    Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

    2015-11-01

    Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm‧) by 50% at concentrations ranging from 3.5 μg l-1 (ametryn) to 132 μg l-1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm‧.

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

    Heshu Sulaiman Rahman

    2014-01-01

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

  10. Acute toxicity and mutagenic activity of Mexican plants used in traditional medicine.

    Déciga-Campos, Myrna; Rivero-Cruz, Isabel; Arriaga-Alba, Myriam; Castañeda-Corral, Gabriela; Angeles-López, Guadalupe E; Navarrete, Andrés; Mata, Rachel

    2007-03-21

    The present work was undertaken to determine safety parameters of selected Mexican medicinal plants chosen on the basis of their frequency of medicinal use and commercial importance. The medicinal herbs included Amphipteryngium adstringens, Hintonia standleyana, Hintonia latiflora, Piper sanctum, Haemathoxylon brasiletto, Iostephane heterophylla, Valeriana procera, Arracacia tolucensis, Brickellia veronicaefolia, Scaphyglottis livida, Exostema caribaeum, Hippocratea excelsa, Ligusticum porteri, Poliomintha longiflora and Gnaphalium sp. In the acute toxicity studies in mice performed according to the Lorke procedure, Exostema caribaeum, Hippocratea excelsa, Ligusticum porteri and Poliomintha longiflora were the most toxic with LD(50) values between 1085 and 2mg/kg. The Ames test revealed that Gnaphalium sp. and Valeriana procera extracts induced mutations of S. typhimurium TA98 with or without the S9 microsomal fraction, and TA100 in the presence of the enzymatic fraction, respectively. The tincture of Valeriana procera, however, was non-mutagenic. Finally, in the Artemia salina lethality test Brickellia veronicaefolia, Arracacia tolucensis, Poliomintha longiflora and Piper sanctum caused significant mortality of the crustacean larvae with LC(50) in the range of 37-227 microg/mL.

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

    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.

  12. Acute toxicity of cadmium, lead, zinc, and their mixtures to stream-resident fish and invertebrates.

    Mebane, Christopher A; Dillon, Frank S; Hennessy, Daniel P

    2012-06-01

    The authors conducted 150 tests of the acute toxicity of resident fish and invertebrates to Cd, Pb, and Zn, separately and in mixtures, in waters from the South Fork Coeur d'Alene River watershed, Idaho, USA. Field-collected shorthead sculpin (Cottus confusus), westslope cutthroat trout (Oncorhynchus clarkii lewisi), two mayflies (Baetis tricaudatus and Rhithrogena sp.), a stonefly (Sweltsa sp.), a caddisfly (Arctopsyche sp.), a snail (Gyraulus sp.), and hatchery rainbow trout (Oncorhynchus mykiss), were tested with all three metals. With Pb, the mayflies (Drunella sp., Epeorus sp., and Leptophlebiidae), a Simuliidae black fly, a Chironomidae midge, a Tipula sp. crane fly, a Dytiscidae beetle, and another snail (Physa sp.), were also tested. Adult westslope cutthroat trout were captured to establish a broodstock to provide fry of known ages for testing. With Cd, the range of 96-h median effect concentrations (EC50s) was 0.4 to >5,329 µg/L, and the relative resistances of taxa were westslope cutthroat trout ≈ rainbow trout ≈ sculpin fish size was observed. In metal mixtures, the toxicities of the three metals were less than additive on a concentration-addition basis.

  13. Acute toxicity evaluation of aminomethylnaphthoquinone (AMNQ 1 in BALB/c mice

    Valeria Garrido

    2016-06-01

    Full Text Available We report the first preclinical tests showing that aminomethylnaphthoquinone - 3-[N-(n-butyl amino-2,4-diclorobenzyl]-2-hydroxy-1,4-naphthoquinone (AMNQ 1 has low cytotoxicity and anti-HSV-1 activity in vitro in Vero cells. The aim of this study was to evaluate the acute toxicity of AMNQ 1 in BALB/c mice. We used BALB/c female mice to evaluate the median lethal dose (LD50 of AMNQ 1 with 2000 mg/kg body weight and other three concentrations using 550, 175 and 55 mg/kg. We compared this to acyclovir (ACV-50 mg/kg and 10% dimethyl sulfoxide (10% DMSO over a 14-day period. The BALB/c mice received a single oral dose by gavage. There were no deaths in either group and no change in the murine clinical signs. The hematological and biochemical analyses showed some changes that returned to reference levels without impairment of hemostasis. The AMNQ 1 treatment did not induce untoward changes in organs as shown by histological studies. The in vivo results showed that AMNQ 1 has low toxicity. In conclusion, AMNQ 1 is safe and can be potentially used as an anti-HSV-1 agent in future studies.

  14. Acute and Subchronic Toxicity Profile of Euphorbia pulcherrima Methanol Extract on Wistar Albino Rats

    H. B. Sharif

    2015-01-01

    Full Text Available This work was designed to evaluate the acute and subchronic toxicity of E. pulcherrima methanol extract. Mean lethal dose (LD50 and subchronic toxicity were determined using Lorke’s method to assess the effect of the extract on kidney and liver functions along histopathology assessment of the liver and kidney, respectively. The LD50 determined was 3807.89 mg/kg both orally and intraperitoneally. The kidney function parameters indicated elevation of the serum urea above the normal value in both control and the group treated with 10 mg/kg of the extract with mean values of 7.92 ± 1.19 and 7.86 ± 1.14 mMol/L, respectively. The creatinine and electrolytes were within the normal values. The results of ALAT, ASAT, ALP, T protein albumin, and bilirubin in all cases were within the normal values. Kidney, liver function parameters, and relative organ weight were statistically insignificant across all groups. This shows that various concentrations of E. pulcherrima extract did not influence negatively the liver and kidney function parameters. Further studies are required to rule out the observed mild hepatic histological changes among a few members of the groups treated with 100 and 1000 mg/kg/day and any possible hepatoprotective and nephron-protective potential the extract may possess.

  15. Acute toxicity of cadmium, lead, zinc, and their mixtures to stream-resident fish and invertebrates

    Mebane, Christopher A.; Dillon, Frank S.; Hennessy, Daniel P.

    2012-01-01

    The authors conducted 150 tests of the acute toxicity of resident fish and invertebrates to Cd, Pb, and Zn, separately and in mixtures, in waters from the South Fork Coeur d'Alene River watershed, Idaho, USA. Field-collected shorthead sculpin (Cottus confusus), westslope cutthroat trout (Oncorhynchus clarkii lewisi), two mayflies (Baetis tricaudatus and Rhithrogena sp.), a stonefly (Sweltsa sp.), a caddisfly (Arctopsyche sp.), a snail (Gyraulus sp.), and hatchery rainbow trout (Oncorhynchus mykiss), were tested with all three metals. With Pb, the mayflies (Drunella sp., Epeorus sp., and Leptophlebiidae), a Simuliidae black fly, a Chironomidae midge, a Tipula sp. crane fly, a Dytiscidae beetle, and another snail (Physa sp.), were also tested. Adult westslope cutthroat trout were captured to establish a broodstock to provide fry of known ages for testing. With Cd, the range of 96-h median effect concentrations (EC50s) was 0.4 to >5,329μg/L, and the relative resistances of taxa were westslope cutthroat trout ≈ rainbow trout ≈ sculpin toxicities of the three metals were less than additive on a concentration-addition basis.

  16. Acute and additive toxicity of ten photosystem-II herbicides to seagrass.

    Wilkinson, Adam D; Collier, Catherine J; Flores, Florita; Negri, Andrew P

    2015-11-30

    Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.

  17. Acute toxicity of two pesticides Diazinon and Deltamethrin on Tench (Tinca tinca larvae and fingerling

    Mohammad Forouhar Vajargah

    2013-05-01

    Full Text Available Diazinon and deltamethrin are common useful agricultural pesticides in the world. The present research compared the acute toxicity of diazinon and deltamethrin to tench larvae and fingerling. LC50 of 24 h, 48-h, 72 h and 96 h were determined using a probit. Fish samples (21 fish in each test group were exposed to different concentrations of diazinon and deltamethrin (diazinon: for fingerling between1-20 ppm and larvae 0.25-2 ppm, deltamethrin: for fingerling between 0.01-0.2 ppm and larvae 0.0025-0.02 for 96 h and mortality were recorded. The LC50 96 h of diazinon for fingerlings and larvae were 6.77 and 0.63, respectively. The LC50 96 h of deltamethrin for fingerlings and larvae were 0.07 and 0.005 ppm, respectively. According to the results, larvae are more sensitive than fingerlings, LC50 values indicated that deltamethrin is more toxic than diazinon to Tinca tinca, so we suggest to use diazinon instead of deltamethrin in agriculture.

  18. Acute toxicity of Opuntia ficus indica and Pistacia lentiscus seed oils in mice.

    Boukeloua, A; Belkhiri, A; Djerrou, Z; Bahri, L; Boulebda, N; Hamdi Pacha, Y

    2012-01-01

    Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD₅₀ values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opuntia ficus indica seeds were extracted and analyzed for its chemical and physical properties such as acid value, free fatty acid percentage (% FFA), iodine index, and saponification value as well as refractive index and density. LD₅₀ values obtained by single doses, orally and intraperitoneally administered in mice, were respectively 43 ± 0,8 ;[40.7- 45.4 ] ml/kg body wt. p.o. and 2.72 ± 0,1 ;[2.52-2.92] ml/kg body wt. i.p. for Opuntia ficus indica ; and 37 ± 1 ;[34.4 - 39.8 ] ml/kg body wt. p.o. and 2.52 ± 0,2 ;[2.22 - 2.81 ] ml/kg body wt. i.p. for Pistacia lentiscus respectively. The yields of seed oil were respectively calculated as 20.25% and 10.41%. The acid and free fatty acid values indicated that the oil has a low acidity.

  19. Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer

    Maduro, JH; Pras, E; Willemse, PHB; de Vries, EGE

    2003-01-01

    Randomised studies in locally advanced cervical cancer patients showed that cisplatin should be given concurrently with radiotherapy, because of a better long-term survival compared to radiotherapy alone. This increases the relevance of treatment related toxicity. This review summarises the acute an

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

    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.

  1. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.

    Robinson, Sally; Delongeas, Jean-Luc; Donald, Elizabeth; Dreher, David; Festag, Matthias; Kervyn, Sophie; Lampo, Ann; Nahas, Kamil; Nogues, Vicente; Ockert, Deborah; Quinn, Kirsty; Old, Sally; Pickersgill, Nigel; Somers, Kev; Stark, Claudia; Stei, Peter; Waterson, Lynne; Chapman, Kathryn

    2008-04-01

    Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.

  2. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  3. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice

    DAYANE K.D. NASCIMENTO

    2016-01-01

    Full Text Available ABSTRACT Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE. The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  4. Acute liver failure following cleft palate repair: a case of therapeutic acetaminophen toxicity.

    Iorio, Matthew L; Cheerharan, Meera; Kaufman, Stuart S; Reece-Stremtan, Sarah; Boyajian, Michael

    2013-11-01

    Background : Acetaminophen is a widely used analgesic and antipyretic agent in the pediatric population. While the hepatotoxic effects of the drug have been well recognized in cases of acute overdose and chronic supratherapeutic doses, the toxic effects of acetaminophen are rarely documented in cases where therapeutic guidelines are followed. Case : An 8-month-old boy underwent cleft palate repair and placement of bilateral myringotomy tubes. His anesthetic course was uneventful, consisting of maintenance with desflurane and fentanyl. He received acetaminophen for routine postoperative pain management and was tolerating liquids and discharged home on postoperative day 1. On day 3, the child was profoundly lethargic with multiple episodes of emesis and was taken to the emergency department. He suffered a 45-second tonic-clonic seizure in transport to the regional children's medical center, and initial laboratory results demonstrated acute hepatitis with AST 24,424 U/L, ALT 12,885 U/L, total bilirubin 3.1 mg/dL, and a serum acetaminophen level of 83 μg/mL. Aggressive supportive measures including blood products and periprocedural fresh frozen plasma, piperacillin/tazobactam, and intravenous infusions of N-acetylcysteine, sodium phenylacetate and sodium benzoate, carnitine, and citrulline were administered. His metabolic acidosis and acute hepatitis began to correct by day 4, and he was discharged home without further surgical intervention on day 15. Conclusion : Although acetaminophen is an effective and commonly used analgesic in pediatric practice, hepatotoxicity is a potentially devastating complication. This report challenges the appropriateness of existing guidelines for acetaminophen administration and emphasizes the importance of close follow-up and hydration after even relatively minor surgery.

  5. Large decrease in acute aquatic toxicity of linear alkylbenzene sulfonate in hard water and seawater by adding adsorbent.

    Oya, Masaru; Takemoto, Yuka; Ishikawa, Yusuke

    2008-01-01

    LAS (Linear Alkylbenzene Sulphonate) shows relatively high aquatic toxicity in hard freshwater or seawater. In this paper, we studied the effect of adsorbent on the aquatic toxicity of LAS in hard freshwater and seawater. Daphnia magna and Artemia salina were used for acute aquatic toxicity test in freshwater and seawater, respectively. Kaolin was used as a model adsorbent and toxic surface tension (gamma(tox)) was used as an indicator of toxic condition. Results showed that the values of gamma(tox) of LAS to D. magna and A. salina were about 45-55 mN/m and 35-40 mN/m, respectively. Surface tension of LAS solution decreased and its aquatic toxicity increased with increasing the water hardness or the salinity. By adding adsorbent into the solutions, the surface activity and the aquatic toxicity were decreased greatly, and the effect of water hardness or salinity on surface tension and aquatic toxicity were removed. That is to say, the surface tension curve of soft freshwater corresponds with that of hard freshwater containing adsorbent and the surface tension curve at low salinity corresponds with that obtained for high salinity solutions containing the adsorbent. Therefore, our experimental data leads to the conclusion that the relatively high aquatic toxicity of LAS in concentrated solution of inorganic salts disappears in the presence of adsorbents. This is an important viewpoint in conducting environmental risk assessment of surfactants.

  6. The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage in rat liver.

    Boveris, Alberto; Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Torti, Horacio; Massot, Francisco; Repetto, Marisa G

    2012-11-01

    The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C(50%)) of 110 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO(•) and RO(•) by a Fenton-like homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.

  7. Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

    Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

    2015-04-01

    Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

  8. Comparison of feeding strategies in acute toxicity tests of crude oil and commercial bioremediation agents

    Cavender, R.C.; Cherry, D.S.; Yeager, M.M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Biology Dept.; Bidwell, J.R. [Univ. of South Australia, Adelaide (Australia). School of Pharmacy and Medical Sciences

    1995-12-31

    Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan have prompted examinations of the methodology used in toxicity testing of the water soluble fraction (WSF) of oil, commercial bioremediation agents (CBA), and a combination of the two. The organisms currently used in acute (96 hr) testing of these agents are the inland silverside, Menidia beryllina, and an estuarine mysid, Mysidopsis bahia. The mysid is a carnivorous species that must be fed during a test in order to prevent predation within the test chambers. Currently proposed methodology for silverside testing also includes feeding. The high oxygen demand of CBAs and the WSF of oil causes dissolved oxygen to be a factor in toxicity. This effect can be intensified by the addition of brine shrimp (Artemia sp.) to the test chambers. The purpose of this study was to compare the toxicity of CBAs in combination with the WSF of oil to silversides with and without the addition of food. Tests were conducted using both 24-hour and 14-day spinning times for the CBA/WSF mixture. With the 24-hour spinning time, LC50 values from each day of the 4-day test were consistently lower in the Artemia fed test (47.8--22.6%) as compared to the unfed test (72.1--43.0%). A similar trend was seen in the 24 and 48 hour LC50`s in the 14-day spinning time. Overall, low dissolved oxygen was found to be most relevant at the highest CBA/WSF concentrations where D.O. dropped below 2 mg/l in Artemia fed tests.

  9. Role of glutamine versus placebo in prevention of acute gastrointestinal toxicity in pelvic radiotherapy: A randomized control study

    Kazi Sazzad Manir

    2014-01-01

    Full Text Available Context: Nausea, vomiting, diarrhoea, abdominal cramping, ano-proctitis are common acute gastrointestinal (GI toxicities during pelvic radiotherapy (RT, having important impact on treatment outcome. Glutamine has a major role in mucosal growth and function. This phase III study is conducted to evaluate the role of prophylactic glutamine supplementation in prevention of acute GI toxicities during pelvic RT. Materials and Methods: Eighty five nonmetastatic patients with pelvic malignancy needing pelvic RT are included in this double blind randomized control trial. During RT 42 patients (Arm A received 10 g glutamine oral supplementation 1 h before every RT fraction. Forty three patients received glycine as placebo (Arm B in same schedule. Patients were assessed weekly for common acute RT induced GI toxicities. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.02. Results: Two arms were well balanced with all baseline parameters. Median age was 57. 56.47% (n = 48 patients had cervical cancer. There was no significant difference between two arms in grade wise incidence of any of the GI toxicities. Trends of diarrhoea during weekly assessments also similar in both arms. Conclusion: There is no significant beneficial effect of glutamine during pelvic RT. As per our study data and our dose schedule glutamine should not be indicated in pelvic RT.

  10. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  11. Evaluation of the Acute and Subchronic Toxicities of Ethanol Leaf Extract of Spathodea campanulata P. Beauv.

    E E Ilodigwe

    2010-06-01

    Full Text Available Summary: The acute and subchronic toxicities of the ethanol leaf extract of Spathodea campanulata, a popular Nigerian traditional anti-convulsant remedy was investigated. For the acute toxicity study, 1000-5000 mg/kg of the ethanol leaf extract were administered to rats and obvious toxic symptoms and mortality 24 hours post-adminstration of the extract were determined. The median lethal dose (LD50 of the extract was determined. In the subchronic study, 750-3000 mg/kg of the extract were administered daily for 90 days. The food and water consumption, body weight changes, as well as heamatological and biochemical parameters were determined periodically. The phytotochemical constituents of the extract were also investigated. Phytochemical analysis revealed the presence of tannins, saponins, anthraquinone glycosides, and flavonoids.. The estimated LD50 of the extract was 4466.84 mg/kg. There was no mortality during the period of study but the animals showed signs of anorexia, weakness, sluggishness and significant (p<0.05 reduction in food and water intake and body weight. The effects on haemoglobin concentration, PCV, RBC and WBC counts were non significant (P>0.05. The extract caused significant (p<0.05 increases in serum liver enzymes, AST, ALP and ALT. These changes showed recovery after 28 days post-treatment. These results suggest that the leaf extract of S. campanulata is safe in the treatment of epilepsy. Industrial relevance: Epilepsy is a chronic disorder that requires life-long management. The available anti-epileptic drugs (AEDs are not only limited by adverse effects, but are not readily accessible in resource poor communities where this disease appears more prevalent. The use of medicinal plants especially Spathodea campanulata in the treatment of epilepsy is very popular in Nigeria. Compared to AEDs, it is very cheap, readily available and relatively free from adverse effects. The results of the present study will enable the industry

  12. Acute and Subacute Toxicity study of the Acetone Leaf extract of Centella asiatica in Experimental Animal Models

    PK Chauhan; V Singh

    2012-01-01

    Objective: To evaluate acute and subacute toxicity of the acetone extract of Centella asiatica (Brahmi). Methods: Toxicity of Centella asiatica was evaluated in Swiss mice after ingestion of the extract during one day (acute model) and during 15 days (subacute model). The Biochemical parameters evaluated included creatinine, calcium, inorganic phosphorous, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed using commercial kits. Results: The results of the present investigation revealed that the LD50 of the extract is higher than 4000mg/kg and subacute treatment did not shows any change in corporal weight and hematological parameters. However, a change in liver weight but not in hepatic enzymes was observed. This suggested that the liver function is not altered by Centella asiatica. Some changes in the creatinine content were observed but could not be relative with the extract dose.Conclusions:The results suggest that the plant seems to be destitute of toxic effects in mice.

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

    Chakravarty Sharmistha

    2012-04-01

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

  14. Intravenous Cobinamide, a Novel Cyanide Antidote, versus Hydroxocobalamin in the Treatment of Acute Cyanide Toxicity and Apnea in a Swine (Sus scrofa) Model

    2013-02-12

    treatment of acute, severe cyanide induced cardiotoxicity of severe hypotension and of cardiac arrest in a swine (Sus Scrofa ) model Intravenous...cobinamide, a novel cyanide antidote, versus hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model...hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model Background: Hydroxocobalamin (HOC) is an FDA approved

  15. The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna.

    Pérez, Sara; Beiras, Ricardo

    2010-01-01

    Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

  16. Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment.

    Shen, Ying; Kishimoto, Koji; Linden, David J; Sapirstein, Adam

    2007-04-03

    The arachidonic acid-generating enzyme cytosolic phospholipase A(2) alpha (cPLA(2)alpha) has been implicated in the progression of excitotoxic neuronal injury. However, the mechanisms of cPLA(2)alpha toxicity have yet to be determined. Here, we used a model system exposing mouse hippocampal slices to NMDA as an excitotoxic injury, in combination with simultaneous patch-clamp recording and confocal Ca(2+) imaging of CA1 pyramidal neurons. NMDA treatment caused significantly greater injury in wild-type (WT) than in cPLA(2)alpha null CA1 neurons. Bath application of NMDA evoked a slow inward current in voltage-clamped neurons (composed of both NMDA receptor-mediated and other conductances) that was smaller in cPLA(2)alpha null than in WT slices. This was not due to down-regulation of NMDA receptor function because NMDA receptor-mediated currents were equivalent in each genotype following brief photolysis of caged glutamate. Current-clamp recordings were made during and following NMDA exposure by eliciting a single action potential with a brief current injection. After NMDA exposure, WT CA1 neurons developed a spike-evoked plateau potential and an increased spike-evoked dendritic Ca(2+) transient. These effects were absent in CA1 neurons from cPLA(2)alpha null mice and WT neurons treated with a cPLA(2)alpha inhibitor. The Ca-sensitive K-channel toxins, apamin and paxilline, caused spike broadening and Ca(2+) enhancement in WT and cPLA(2)alpha null slices. NMDA application in WT and arachidonate applied to cPLA(2)alpha null cells occluded the effects of apamin/paxilline. These results indicate that cPLA(2)alpha activity is required for development of aberrant electrophysiologic events triggered by NMDA receptor activation, in part through attenuation of K-channel function.

  17. Acute and subchronic toxicity study of the water extract from the fruits of Piper chaba Hunter in rats

    K Jaijoy

    2010-12-01

    Full Text Available Summary: The water extract from the fruits of Piper chaba Hunter was evaluated for acute and subchronic toxicity in both male and female rats. For the study of acute toxicity, a single oral dose of 5,000 mg/kg body weight was administered in rats (five females, five males. The results showed no signs of toxicity such as general behavior change, mortality, or change in gross appearance of internal organs. Subchronic toxicity was studied by daily oral doses (ten females, ten males of 300, 600 and 1,200 mg/kg body weight for consecutive 90 days. The satellite group was treated with the extract at the dose of 1,200 mg/kg/day for 90 days and kept for other 28 days after treatment. The results showed no abnormalities in treated groups as compared to the controls. Although significantly different, all of the values were within normal limits. Neither gross abnormalities nor histopathological changes were observed. The results suggest that P. chaba extract does not produce acute or subchronic toxicity in either female or male rats. Industrial relevance: Herbal medicines are popular and extensively used in the developing world. In many places, they offer a more wide available and more affordable alternative to pharmaceutical drugs and natural food supplements. The data of the acute and subchronic toxicity studies on medicinal plants or preparations derived from them should be obtained in order to increase the confidence in its safety to human, particularly for use in the development of pharmaceutical.

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

    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

  19. Assessment of locomotion behavioral defects induced by acute toxicity from heavy metal exposure in nematode Caenorhabditis elegans

    WANG Dayong; XING Xiaojuan

    2008-01-01

    Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducted in the model organism of nematode Caenorhabditis elegans. In this study, the acute toxicity from heavy metal exposure on the locomotion behaviors was analyzed in nematodes. Endpoints of head thrash, body bend, forward turn, backward turn, and Omega/U turn were chosen to evaluate the locomotion behavioral defects. Our data suggest that the endpoints of head thrash, body bend, and forward turn will be useful for the evaluation of heavy metal toxicity in nematodes. The endpoint of head thrash could detect the toxicity from Cd, Co, Cr, Cu, Hg, and Pb exposures at a low concentration (2.5 μmol/L). The endpoint of body bend could be explored to evaluate the toxicity from all assayed heavy metal exposures at different concentrations, whereas the endpoint of forward turn will be more useful for the evaluation of heavy metal toxicity at high concentrations. Thus, endpoints of these locomotion behaviors establish a fast and economic way to assess the presence of acute toxicity from heavy metal exposure in nematode C. elegans.

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

    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

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

    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

  2. Influence of water chemistry on the acute toxicity of copper and zinc to the cladoceran Ceriodaphnia cf dubia.

    Hyne, Ross V; Pablo, Fleur; Julli, Moreno; Markich, Scott J

    2005-07-01

    This study determined the influence of key water chemistry parameters (pH, alkalinity, dissolved organic carbon [DOC], and hardness) on the aqueous speciation of copper and zinc and its relationship to the acute toxicity of these metals to the cladoceran Ceriodaphnia cf dubia. Immobilization tests were performed for 48-h in synthetic or natural waters buffered at various pH values from 5.5 to 8.4 (other chemical parameters held constant). The toxicity of copper to C. cf dubia decreased fivefold with increasing pH, whereas the toxicity of zinc increased fivefold with increasing pH. The effect of DOC on copper and zinc toxicity to C. cf dubia was determined using natural fulvic acid in the synthetic water. Increasing DOC was found to decrease linearly the toxicity of copper, with the mean effect concentration of copper that immobilized 50% of the cladocerans (EC50) value 45 times higher at 10 mg/L, relative to 0.1 mg/L DOC at pH 6.5. In contrast, the addition of 10 mg/L DOC only resulted in a very small (1.3-fold) reduction in the toxicity of zinc to C. cf dubia. Copper toxicity to C. cf dubia generally did not vary as a function of hardness, whereas zinc toxicity was reduced by a factor of only two, with an increase in water hardness from 44 to 374 mg CaCO3/L. Increasing bicarbonate alkalinity of synthetic waters (30-125 mg/L as CaCO3) decreased the toxicity of copper up to fivefold, which mainly could be attributed to the formation of copper-carbonate complexes, in addition to a pH effect. The toxicity of copper added to a range of natural waters with varying DOC content, pH, and hardness was consistent with the toxicity predicted using the data obtained from the synthetic waters.

  3. Acute and chronic toxicity of emerging contaminants, alone or in combination, in Chlorella vulgaris and Daphnia magna.

    Pablos, María Victoria; García-Hortigüela, Pilar; Fernández, Carlos

    2015-04-01

    This work presents the toxicity results of different compounds classified as emerging contaminants on primary producers and primary consumers in the aquatic compartment. The objectives were to (1) obtain acute and chronic toxicity results for algae and Daphnia magna using standardised or currently used tests, (2) study the relationship between the effects on the impaired feeding rate for daphnia and the effects of reproduction and (3) examine the responses on daphnia and algae after binary combinations of environmentally relevant compounds and perfluorooctane sulfonate (PFOS). Toxicity data on personal care products (PCPs), not reported in the scientific literature up to now, are presented. The results confirmed that the Daphnia feeding bioassay can be a sensitive, ecologically relevant endpoint to detect sublethal effects and could complement the information obtained with the reproduction test on Daphnia. The results also suggested that the concomitant occurrence of PFOS and other emerging contaminants in the aquatic compartment could affect the toxicity of some compounds according to their lipophilicity.

  4. Exposure medium: key in identifying free Ag+ as the exclusive species of silver nanoparticles with acute toxicity to Daphnia magna.

    Shen, Mo-Hai; Zhou, Xiao-Xia; Yang, Xiao-Ya; Chao, Jing-Bo; Liu, Rui; Liu, Jing-Fu

    2015-04-10

    It is still not very clear what roles the various Ag species play in the toxicity of silver nanoparticles (AgNPs). In this study, we found that traditional exposure media result in uncontrollable but consistent physicochemical transformation of AgNPs, causing artifacts in determination of median lethal concentration (LC50) and hindering the identification of Ag species responsible for the acute toxicity of AgNPs to Daphnia magna. This obstacle was overcome by using 8 h exposure in 0.1 mmol L(-1) NaNO3 medium, in which we measured the 8-h LC50 of seven AgNPs with different sizes and coatings, and determined the concentrations of various Ag species. The LC50 as free Ag(+) of the seven AgNPs (0.37-0.44 μg L(-1)) agreed very well with that of AgNO3 (0.40 μg L(-1)), and showed the lowest value compared to that as total Ag, total Ag(+), and dissolved Ag, demonstrating free Ag(+) is exclusively responsible for the acute toxicity of AgNPs to D. magna, while other Ag species in AgNPs have no contribution to the acute toxicity. Our results demonstrated the great importance of developing appropriate exposure media for evaluating risk of nanomaterials.

  5. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

    Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Miettinen, Hanna, E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, P.O. Box 95, FI-70701 Kuopio (Finland); Sankari, Satu, E-mail: satu.sankari@helsinki.fi [Central Laboratory of the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014 University of Helsinki (Finland); Hegde, Nagabhooshan [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Lindén, Jere, E-mail: jere.linden@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland)

    2012-07-15

    The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance.

  6. Phytochemical screening, acute toxicity, anxiolytic and antidepressant activities of the Nelumbo nucifera fruit.

    Rajput, Muhammad Ali; Khan, Rafeeq Alam

    2017-02-01

    Recently use of herbal therapies and diet rich in flavonoids and vitamin C have increased significantly to treat minor to modest anxiety disorders and various forms of depression. But further research and studies are necessary to evaluate the pharmacological & toxicological effects of plants. Hence present study was designed to conduct phytochemical screening, acute toxicity study, anxiolytic and antidepressant activities of the ethanol extract of Nelumbo nucifera fruit in order to ascertain its therapeutic potential. The qualitative phytochemical screening of the seed pods of the N. nucifera fruit extract exposed the existence of flavonoids, saponins, alkaloids, tannins and terpenoids in it. The acute toxicity of the N. nucifera fruit extract in mice revealed its LD50 value to be greater than 5000 mg/kg. Antianxiety activity was determined by elevated plus maze and light and dark test using 35 male Wister rats weighing 200-220 g which were equally divided in to 5 groups. The animals used in EPM underwent testing in light and dark box just 30 min after EPM. The antidepressant effect was assessed by forced swimming test using 35 male albino mice weighing 20-25 g equally divided in to 5 groups. In elevated plus maze, N. nucifera fruit extract exhibited substantial rise in number of open arm entries and time spent in open arms at dose 50 mg/kg while highly noteworthy increase in both parameters were observed at extract doses 100 and 200 mg/kg as compared to control. In light dark test highly significant increase in the percentage of time spent in light compartment was observed as compared to control. In forced swimming test highly noteworthy decline in duration of immobility was recorded at doses 100 and 200 mg/kg on 15th day i-e after administration of 14 doses, as compared to control; whereas same doses demonstrated significant decrease as compared to control in duration of immobility after single dose administration i-e on 2nd day of experiment. Thus N

  7. Habitat availability is a more plausible explanation than insecticide acute toxicity for U.S. grassland bird species declines.

    Hill, Jason M; Egan, J Franklin; Stauffer, Glenn E; Diefenbach, Duane R

    2014-01-01

    Grassland bird species have experienced substantial declines in North America. These declines have been largely attributed to habitat loss and degradation, especially from agricultural practices and intensification (the habitat-availability hypothesis). A recent analysis of North American Breeding Bird Survey (BBS) "grassland breeding" bird trends reported the surprising conclusion that insecticide acute toxicity was a better correlate of grassland bird declines in North America from 1980-2003 (the insecticide-acute-toxicity hypothesis) than was habitat loss through agricultural intensification. In this paper we reached the opposite conclusion. We used an alternative statistical approach with additional habitat covariates to analyze the same grassland bird trends over the same time frame. Grassland bird trends were positively associated with increases in area of Conservation Reserve Program (CRP) lands and cropland used as pasture, whereas the effect of insecticide acute toxicity on bird trends was uncertain. Our models suggested that acute insecticide risk potentially has a detrimental effect on grassland bird trends, but models representing the habitat-availability hypothesis were 1.3-21.0 times better supported than models representing the insecticide-acute-toxicity hypothesis. Based on point estimates of effect sizes, CRP area and agricultural intensification had approximately 3.6 and 1.6 times more effect on grassland bird trends than lethal insecticide risk, respectively. Our findings suggest that preserving remaining grasslands is crucial to conserving grassland bird populations. The amount of grassland that has been lost in North America since 1980 is well documented, continuing, and staggering whereas insecticide use greatly declined prior to the 1990s. Grassland birds will likely benefit from the de-intensification of agricultural practices and the interspersion of pastures, Conservation Reserve Program lands, rangelands and other grassland habitats into

  8. Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

    Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

    2015-12-01

    Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.

  9. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    Kwint, Margriet [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Uyterlinde, Wilma [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heuvel, Michel van den [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Knegjens, Joost; Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Belderbos, Jose, E-mail: j.belderbos@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  10. Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum.

    Zira, Athina; Mikros, Emmanuel; Giannioti, Konstantina; Galanopoulou, Panagiota; Papalois, Apostolos; Liapi, Charis; Theocharis, Stamatios

    2009-07-01

    The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by (1)H-NMR spectroscopy, on serum samples in acetaminophen (APAP)-induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote N-acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL/CIM was also investigated. A single dose of APAP (2 g kg(-1) b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC. Animals were sacrificed at 24 h post-APAP treatment. Healthy untreated animals served as controls. (1)H-NMR spectra of serum samples were acquired and underwent principal component analysis (PCA). Acute liver injury was verified by histopathological examination and the alterations of serum biochemical enzymes AST and ALT. (1)H-NMR spectroscopy revealed variations in the serum metabolic profile of APAP-intoxicated rabbits compared with controls. Co-administration of APAP with NAC, CIM and SIL + CIM seems to ameliorate the metabolic profile of animals compared with simply APAP-treated ones. In this study, the model of APAPinduced liver injury was successfully described using the (1)H-NMR based metabonomic approach in serum. Furthermore, the use of antidotes that reduced the toxic insult was also recorded using this technique. The combination of NMR spectroscopy and PCA is a rapid methodology, capable of detecting alterations in the metabolic profile, and produces adequate models that could be used for the characterization of unknown samples, both experimental and clinical, reinforcing its future use in clinical settings.

  11. The biofilm electrode sensor system for acute toxicity and viral screening

    Holodnick, S.E.

    1988-01-01

    The biofilm electrode sensor (BFE) is designed for the rapid and sensitive detection of toxic and pathogenic environmental contaminants and industrial effluents. It includes a dissolved oxygen electrode which senses respiration changes induced in a biomass film. This study assessed the effects of five chemical on biofilms of Saccharomyces cerevisiae, and polio virus on biofilms of Buffalo Green Monkey kidney cells (BGMk). Acute toxicity was assessed in 30 min, and viral infectivity in 15-20 hr. Potassium cyanide and cupric nitrate inhibited respiration in a similar manner, 2.5-68.2 %I and 30.2-68.8 %I, respectively. The response of the BFE to cyanide and cupric ions occurred within 5-20 sec. Cadmium ions affected the BFE over the range of 50.0-1000 mg/l, but complexed with components in the support medium at lower concentrations. 2,4-dinitrophenol enhanced respiration in the concentration range of 10.0-50.0 mg/l and inhibited respiration in the concentration range of 85.0-100.0 mg/l. A maximum response of 19 %I was noted at 1200 mg/l phenol, before dissolution of the polysulfone membrane filter occurred. Detection of viruses utilized BGMk cells exposed to 4.7 {times} 10{sup 4}{minus}4.7 {times} 10{sup 8} ID{sub 50}/ml poliovirus for 2 hr prior to immobilization. The response of the BFE was optimal at 15-20 hr, with a %I range of 5-40%.

  12. Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro

    Lee, Mu-Jin; Jung, Ho-Kyung; Kim, Min-Suk; Jang, Ji-Hun; Sim, Mi-Ok; Kim, Tea-Mook; Park, Ho; Ahn, Byung-Kwan; Cho, Hyun-Woo; Cho, Jung-Hee

    2016-01-01

    Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h. PMID:27729930

  13. EVALUATION OF ACUTE TOXICITY STUDY AND DIURETIC ACTIVITY OF URAL SYRUP

    Thakkar Tejas

    2013-08-01

    Full Text Available There are considerable amount of scientific evidences available for diuretic activity of individual ingredients of a polyherbal formulation Ural Syrup however no evidence has been found which proves overall safety and efficacy of the formulation. The present study was undertaken to investigate safety as well as Diuretic activity of this polyherbal formulation- Ural Syrup. Acute toxicity study was carried out as per OECD Guideline 420. The Ural syrup (1.8mL/kg and 3.6mL/kg was tested for its diuretic activity on rat model. Hydrochlorothiazide (HCTZ (10mg/kg was used as positive control in study. The diuretic effect of the Ural syrup was evaluated by measuring urine volume, pH and excretion of sodium and potassium content. In result, significant increase in urine volume was observed at both dosage levels of Ural syrup in comparison to normal control group. There was no significant change observed in pH of urine. The excretion of Sodium was also found significantly increased at both dosage levels but more in TEDx2 group with respect to TED group. Potassium excretion was found increased only at TEDx2 group as compared to normal control group. It can be concluded that Ural syrup produced considerable diuretic effect which appeared to be comparable to that produced by the reference diuretic HCTZ. There was no lethality and toxic reaction found among the tested animals. The present study provides scientific support that Ural syrup can be employed as a safe and effective diuretic drug.

  14. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

    Ong YS

    2016-11-01

    Full Text Available Yong Sze Ong,1 Latifah Saiful Yazan,1,2 Wei Keat Ng,1 Mustapha M Noordin,3 Sarah Sapuan,1 Jhi Biau Foo,1 Yin Sim Tor1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, 3Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Background: Thymoquinone (TQ, the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods: The in vivo toxicity (acute and subacute toxicity study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ

  15. Determination of acute and early life stage toxicity of fat-plant effluent using zebrafish (Danio rerio).

    Sişman, Turgay; Incekara, Umit; Yildiz, Yalçin Sevki

    2008-08-01

    The present study examines the effects of an effluent from a fat plant (FP) on zebrafish (Danio rerio) embryos and larvae using the whole effluent toxicity testing methods (WET). The method is based on acute toxicity using 96-h larval mortality and chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality, and sex ratio. On the basis of larval mortality the 96-h LC(50) (the concentration was lethal to 50% of newly hatching zebrafish larvae) was 68.9%. In chronic toxicity test, newly fertilized embryos (effluent concentrations in a 24-h static renewal system at (27 +/- 0.5) degrees C until 15-day posthatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution. Embryos began to show lesions on third day at higher concentrations (12, 25, 50% FP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. Morphological abnormalities were observed in newly hatched larvae at 25 and 50% FP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. On the basis of the study, the FP effluent tested here may cause increasing embryotoxicity in the zebrafish embryos. We conclude that the test using zebrafish is feasible to evaluate both acute and chronic toxicities of industrial effluents.

  16. Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum oxide nanoparticle toxicity in fresh water environment.

    Sunandan Pakrashi

    Full Text Available Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h in conjunction with the effects from the nano-sized particles in the initial phases (24 h puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake as substantiated through the transmission electron microscopy (TEM and inductively coupled plasma optical emission spectral (ICP-OES analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system.

  17. Cytotoxicity, hemolysis and in vivo acute toxicity of 2-hydroxy-3-anilino-1,4-naphthoquinone derivatives

    Valeska Santana de Sena Pereira

    2016-01-01

    Full Text Available The 1,4-naphthoquinones, important members of the family of quinones are used as both crude extracts and as compound manipulated by the pharmaceutical industry. They have gained great emphasis by presenting different pharmacological properties as antibacterial, antiviral, antiprotozoal and anthelmintic, and has antitumor activity. Our aim was to evaluate the cytotoxicity, hemolytic activity and in vivo acute toxicity of three derivatives of 2-hydroxy-1,4-naphthoquinones. The cell viability in vitro against RAW Cell Line displayed IC50 ranging of 483.5–2044.8 μM, whereas in primary culture tests using murine macrophages, IC50 were 315.8–1408.0 μM for naphthoquinones derivatives 4a and 4c respectively, besides no hemolysis was observed at the dose tested. The in vivo acute toxicity assays exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg, and at a dose of 1000 mg/kg the derivatives not triggering signs of toxicity although the compound 4a have promoted hepatic steatosis and hyperemia in kidney tissue. Thereby, these modifications decrease the toxicity of the tested derivatives naphthoquinones, providing a high potential for the development of news drugs.

  18. Evaluation of acute and subacute toxicity induced by methanol extract ofTerminalia citrina leaves in Sprague Dawley rats

    Narhari Das; Durajan Goshwami; Md. Sharif Hasan; Sheikh Zahir Raihan

    2015-01-01

    Objective: To evaluate acute and subacute toxicity of methanol extract ofTerminalia citrina leaves (family: Combretaceae) in Sprague Dawley rats. Methods: The acute toxicity studies were conducted where the limit test dose of 3 200 mg/kg body weight used. Observations were made and recorded systemically on 1, 2, 4, 24 and 48 h after dose administration for behavior, breathing, cutaneous effects, sensory nervous system response or gastrointestinal effects. For the subacute toxicity, four groups of 10 female rats were received; distilled water (control), 250, 500 and 1 000 mg/kg of extracts respectively every 24 h orally for 28 days. Results: No significant variation in the body and organ weights between the control and the treated group was observed after 28 days of treatment. Haematological analysis and biochemical parameters revealed no toxic effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed. No mortality was recorded in 28 days. Conclusions: It was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

  19. Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

    Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X. [Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Easson, Alexandra M. [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra; Cho, Charles [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John, E-mail: John.Kim@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-11-01

    Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

  20. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    Tassanee Eamkamon

    2012-01-01

    Full Text Available Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L and sub-lethal (0.019, 0.194, and 1.942 nmol/L concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in shrimp exposed to 0.194, and 1.942 µmol/L of chlorpyrifos were significantly lower (1.7 and 3.3 times than that of control shrimp after 30 min of exposure (p<0.05. In sub-lethal exposure tests, the AChE activity of shrimp was significantly lower (1.9 times than that of control shrimp after exposure to 1.942 nmol/L of chlorpyrifos for 72 h (p<0.05. The sensitive reduction of AChE activity at the sub-lethal concentration, which was 30 times lower than 96 h LC50 value found in this study, indicates the potential use as a biomarker of chlorpyrifos exposure.

  1. Functional nature of the spasmolytic effect, phytochemical composition and acute toxicity studies on Sauromatum guttatum

    Nabi Shah

    2014-06-01

    Full Text Available The aim of the present work was to study the functional nature of the potential spasmolytic effect of the crude extract of Sauromatum guttaum. It was found positive for the presence of alkaloid and tannins. In isolated rabbit jejunum preparation, S. guttaum caused inhibition of spontaneous and high K+ (80 mM-induced contractions, with respective EC50 values (95% confidence intervals of 1.50 mg/mL (0.69-3.02 and 1.17 mg/mL (0.81-1.61, similar to verapamil. Inhibition of high K+ -induced contractions suggests Ca++ antagonistic effect. The Ca++channel blocker activity of S. guttaum was confirmed when pre-treatment of the tissues with extract (0.3-3 mg/mL caused a rightward displacement in the Ca++ concentration-response curves. Moreover, in the acute toxicity test, S. guttaum was found safe up to the dose of 3 g/kg. The findings of the current study suggest that the S. guttaum exhibited spasmolytic activity, possibly mediated through inhibitory effect on Ca++ entry and was found safe and this current study provides first evidence to the potential use of this plant as antispasmodic and can play a possible role as antidiarrheal.

  2. Acute toxicity and sublethal effects of fipronil on detoxification enzymes in juvenile zebrafish (Danio rerio).

    Wu, Haihua; Gao, Cuie; Guo, Yaping; Zhang, Yuping; Zhang, Jianzhen; Ma, Enbo

    2014-10-01

    The acute toxicity of fipronil and its sublethal effects on detoxification enzymes (carboxylesterases (CarEs), glutathione S-transferases (GSTs), and 7-ethoxycoumarin O-deethylase (ECOD)) in zebrafish (Danio rerio) were investigated. The results indicated that the 24-h LC50 of fipronil for zebrafish was 220.4 μg/L (95% CI: 173.7-272.4 μg/L). Sublethal concentrations of fipronil did not cause significant changes in CarEs activities. In the liver and muscle tissues, GST activities at the tested concentrations did not significantly differ from those in the control. In the brain and gill tissues, GST activities at a concentration of 4 μg/L were significantly lower than those at a concentration of 2 μg/L. The results suggest that CarEs and GSTs were not suitable biomarkers for fipronil effects in D. rerio. A significant induction in the ECOD activities in the brain, gill, liver, and muscle tissues was observed compared with the control. Moreover, the dose-dependent responses of the ECOD activity were observed after treatment with sublethal concentrations of fipronil in the range of 2-20 μg/L. The results suggested that ECOD could be a suitable biomarker of fipronil effects in D. rerio.

  3. ACUTE TOXICITY OF MERCURY TO EMBRYOS OF Helisoma trivolvis (SAY, 1817 (MOLLUSCA: PLANORBIDAE

    Passuni, G.

    2008-01-01

    Full Text Available Mercury is a metal very employed at industry and mining in Peru. The aim of current research was to determine embryotoxic lethal acute toxicity of Hg2+, in form of chloride of mercury (HgCl on 2 Helisoma trivolvis (Say, 1817 at 24 h exposure. Concentrations assayed were 514, 51.4, 5.14 and 0.51 ug Hg2+ L-1, since salt on base of HgCl using dechlorined water as diluents. Snail embryos 2 were considered dead when none rotation movement during since 30 seconds. Percentage of mortality of embryonic stages of H. trivolvis increased with each of concentrations crescents of Hg2+ at 24 h exposure. At a concentration of 514.4 ug Hg2+ L-1 was observed significantly differences in relation to control. Moreover, concentration of 514.4 ug Hg2+ L-1 showed differences with relation to other three treatments. LC was 2.49 ug Hg2+ L-1. Embryos of H. trivolvis were 50 higher sensible to Hg2+ in comparison to other freshwater snail species was concluded.

  4. Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model.

    Glazer, Evan S; Zhu, Cihui; Hamir, Amir N; Borne, Agatha; Thompson, Catherine Shea; Curley, Steven A

    2011-12-01

    There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy.

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

    Vidya Sabbani

    2015-02-01

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

  6. Acute toxicity effects of perfluorooctane sulfonate on sperm vitality, kinematics and fertilization success in zebrafish

    Xia, Jigang; Niu, Cuijuan

    2016-08-01

    Perfluorooctane sulfonate (PFOS) has emerged as one of the most concerning contaminants in recent years. This study aimed to investigate the acute toxicity effect of PFOS on sperm viability, kinematics and fertilization success in zebrafish (Danio rerio). Sperm were activated in aqueous media containing a range of PFOS concentrations (0, 0.09, 0.9 and 9 mg/L). Viabilities and kinematics of the sperm exposed to different PFOS treatments were assessed via computer-assisted sperm analysis (CASA) at 20, 40 60 and 80 s after activation. PFOS exposure decreased the percentage of motile sperm, the curvilinear velocity (VCL), and the mean angular displacement (MAD) of spermatozoa, but showed no influence on the straight-line velocity (VSL) or the angular path velocity (VAP). Furthermore, a significant decrease in fertilization success was observed in spermatozoa that were exposed to 0.9 mg/L PFOS or more. These findings indicate that PFOS pollution in natural aquatic environment may be a potential threaten to successful reproduction of fish.

  7. Acute toxicity study of Vilocym Premix (herbal growth promoter for Livestockin Wistar Albino Rat

    A.H. Ahmad

    2009-06-01

    Full Text Available An experimental study with the objective of safety evaluation of Vilocym Premix, herbal growth promoter for Livestock (supplied by Ayurvet Ltd., Baddi, India, was done as per standard guidelines of OECD-423 for acute toxicity testing. Vilocym Premix is a scientifically developed combination of herbs that contains herbal ingredients namely Azadirachta indica, Curcuma longa & many more alongwith natural zeolites. The study was done in 3 males and 3 female Wistar Albino rats, which were administered an initial dose of 50 mg/kg body weight followed by dose rates of 300, 500 & 5000 mg/kg body weight of test compound. The animals were observed for signs of convulsions, tremors, circling, depression, excitement and mortality. Body weight was recorded at 0,7th and 14th day and plasma total protein, albumin; AST and ALT were measured after 3rd day of experiment. No abnormal sign of symptoms were observed in any of the animal fed with Vilocym Premix at the dose rate of 50, 300, 500 & 5000 mg/kg. No mortality was observed indicating safety of herbal premix. [Vet. World 2009; 2(3.000: 100-102

  8. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  9. Sub-acute toxicity studies of acetaminophen in Sprague Dawley rats.

    Venkatesan, Pachaiyappan Sampath; Deecaraman, Munuswamy; Vijayalakshmi, Melanathuru; Sakthivelan, Sigamany Masilamani

    2014-01-01

    The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.

  10. Antiulcerogenic effect and acute toxicity of a hydroethanolic extract from the cashew (Anacardium occidentale L.) leaves.

    Konan, Nzi André; Bacchi, Elfriede Marianne

    2007-06-13

    The antiulcerogenic effect of a hydroethanolic extract of Anacardium occidentale L. leaves was investigated. The extract inhibited gastric lesions induced by HCl/ethanol in female rats. A dose-response effect study showed that the ED50 was 150 mg/kgb.w. Extract doses higher than 100 mg/kgb.w. were more effective than 30 mg/kg of lansoprazol in inhibiting gastric lesions. A methanolic fraction (257.12 mg/kg) which reduced gastric lesion at 88.20% is likely to contain the active principle of the antiulcer effect. No signs of acute toxicity were observed when mice were treated with extract dose up to 2000 mg/kgb.w. A chemical analysis of the extract allowed the identification of phenolic compounds as the major components. Glycosylated quercetin, amentoflavone derivate and a tetramer of proanthocyanidin were identified by liquid chromatography coupled to mass spectrometry. The level of total phenolics in the extract was evaluated at 35.5% and flavonoid content was 2.58%.

  11. Large-scale Purification and Acute Toxicity of Hygromycin B Phosphotransferase

    QIN ZHUO; JIAN-HUA PIAO; YUAN TIAN; JIE XU; XIAO-GUANG YANG

    2009-01-01

    Objective To provide the acute toxicity data of hygromycin B phosphotransferase (HPT) using recombinant protein purified from E. coli. Methods Recombinant HPT protein was expressed and purified from E. coli. To exclude the potential adverse effect of bacteria protein in recombinant HPT protein, bacterial control plasmid was constructed, and bacteria control protein was extracted and prepared as recombinant HPT protein. One hundred mice, randomly assigned to 5 groups, were administrated 10 g/kg, 5 g/kg, or 1 g/kg body weight of HPT or 5 g/kg body weight of bacterial control protein or phosphate-buffered saline (PBS) respectively by oral gavage. Results All animals survived with no significant change in body weight gain throughout the study. Macroscopic necropsy examination on day 15 revealed no gross pathological lesions in any of the animals. The maximum tolerated dose (MTD) of HPT was 10 g/kg body weight in mice and could be regarded as nontoxic. Conclusion HPT protein does not have any safety problems to human health.

  12. Assessment of acute toxicity and histopathology of the fungicide captan in rainbow trout.

    Boran, Halis; Capkin, Erol; Altinok, Ilhan; Terzi, Ertugrul

    2012-03-01

    Acute toxicity of the fungicide, captan, to juvenile rainbow trout was evaluated under static-renewal test condition. Actual concentrations of captan ranged from 0.05 to 1.00 mg/L. The concentrations of captan that killed 50% of the rainbow trout (3.11±0.8 g) within 24 (24 h; LC(50)), 48, 72 and 96 h were 0.57±0.09, 0.49±0.10, 0.44±0.11 and 0.38±0.13 mg/L (95% confidence limits), respectively. None of the unexposed control fish died and the first fish died 6 h after exposure to captan (≥0.65 mg/L). Hypertrophy, separation of epithelium from lamellae, lamellar fusion, and epithelial cell necrosis were observed on captan exposed fish. Gills also had scattered areas of focal lamellar hyperplasia. Fish exposed to fungicide had inflammation and necrosis in liver, trunk kidney and spleen. In order, the most affected organs were gill, trunk kidney and liver.

  13. Protective effect of Sida cordata leaf extract against CCl4 induced acute liver toxicity in rats

    Sunil Mistry; KR Dutt; J Jena

    2013-01-01

    Objective: To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Methods: Wister albino rats were divided into 6 groups: Group Ⅰ served as control; Group Ⅱ served as hepatotoxic (CCl4 treated) group;Group Ⅲ, Ⅳ and Ⅴ served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group Ⅵ served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Results:Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. Conclusions: The results of this study strongly indicate the protective effect of SCLE against CCl4 induced acute liver toxicity in rats and thereby scientifically support its traditional use.

  14. Evaluation of Antioxidant Activity and Acute Toxicity of Clausena excavata Leaves Extract

    Shaymaa Fadhel Abbas Albaayit

    2014-01-01

    Full Text Available Clausena excavata (Lour., locally known as “Kemantu hitam,” is a common plant in Malaysian folklore medicine. This study evaluated the antioxidant properties of the solvent extracts of C. excavata leaves and determined the acute toxicity of methanolic extract C. excavata (MECE leaves in Sprague-Dawley rats. Harvested leaves were dried and subjected to solvent extraction using petroleum ether, chloroform, ethyl acetate and methanol in succession. The antioxidant activity of each extract was determined using the ferric-reducing antioxidant power (FRAP and 2,2-diphenyl-1-picryl dihydrazyl (DPPH radical scavenging activity. The total phenolic content (TPC and total flavonoids content (TFC were estimated by Folin-Ciocalteu and ethanolic aluminium chloride method, respectively. The chloroform extract was found to be highest in flavonoid content, while the methanolic extract showed the highest TPC and antioxidant activity. There was no mortality in rats treated with MECE leaves even at a high dose of 5000 mg/kg body weight. However, the MECE leaves produced mild to moderate pathological changes in the liver and kidneys, shown by mild degenerative changes and leucocyte infiltration. The extract did not affect the haematological parameters or relative weights of the liver or kidneys. Overall, the MECE leaves have potent antioxidant activity and are presumed safe to be used orally as health-promoting product at low to moderate doses.

  15. Lesser celandine (pilewort) induced acute toxic liver injury:The first case report worldwide

    Bulent Yilmaz; Bars Yilmaz; Bora Aktas; Ozan Unlu; Emir Charles Roach

    2015-01-01

    Lesser celandine, also known as Ranunculus ficaria , isa herbaceous perennial plant that commonly utilizespiles and is taken either internally or used externally.The causality assessment of several reports providedevidence for the existence of Greater Celandinehepatotoxicity. However, there hasn't been any casereport published thus far, about lesser celandineinduced liver injury. Here, we present a case of36-year-old woman admitted to the hospital with acutehepatitis and jaundice on her sclera with no historyof drug abuse or alcohol consumption. However, thepatient had a recent history of lesser celandine extractconsumption for hemorrhoids, for about 10 d, prior tothe admission. Viral hepatitis, autoimmune hepatitis,and drug induced toxic hepatitis were ruled out byfurther imaging studies and laboratory analysis. Usingthe Council for International Organizations of MedicalSciences scale, the type of liver injury was assumedas hepatocellular and was scored as 7 which showsprobable causality. Immediate discontinuation of lessercelandine extract resulted in rapid decrease of theelevated enzymes. Herbs have been reported to causeliver injury and therefore should be suspected in thecase of acute hepatitis with an unknown etiology. Thiscase is important to be the first to explain hepatotoxicitycaused by lesser celandine. Physicians should considerlesser celandine as a causative agent for hepatotoxicity.

  16. Assessment of acute toxicity of the ethanolic extract of Lychnophora pinaster (Brazilian arnica

    Simone A. Ferreira

    2014-10-01

    Full Text Available Species of the Lychnophora genus are plants native to Brazil, popularly known as "Brazilian arnica" and used in folk medicine as alcoholic and hydro-alcoholic preparations for the treatment of bruises, inflammation, pain, rheumatism and insect bites. The present study aimed to evaluate the safety of the use of Lychnophora pinaster Mart., Asteraceae. Acute toxicity of the crude ethanolic extract was evaluated by administration of the extract by oral route to male and female Swiss mice. A single extract dose of 125, 250 or 500 mg/kg was administered and the effects on spontaneous locomotor activity, exploratory behavior, muscle strength, body weight, food and water consumption, relative organ weight, histology, as well as hematological and biochemical parameters were evaluated. The three doses administered to the animals did not cause muscle tone alterations, but doses of 250 and 500 mg/kg induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals in open-field test. There was no alteration to hematological parameters and consumption of water and food, body weight variation and organs relative weight. Changes were observed in AST and ALT during assessment of biochemical parameters. The histopathological evaluation showed that the extract provoked cellular alterations, such as vacuolar degeneration and inflammation in kidneys and liver at all doses. Liver morphometric analyses of male and female mice showed that the extract did not have dose-dependent effects. Although females showed a significant increase in inflammatory cells, the effect was not dose-dependent.

  17. Toxicologic evaluation of DHA-rich algal oil: Genotoxicity, acute and subchronic toxicity in rats.

    Schmitt, D; Tran, N; Peach, J; Bauter, M; Marone, P

    2012-10-01

    DHA-rich algal oil ONC-T18, tested in a battery of in vitro and in vivo genotoxicity tests, did not show mutagenic or genotoxic potential. The acute oral LD50 in rats has been estimated to be greater than 5000 mg/kg of body weight. In a 90-day subchronic dietary study, administration of DHA-rich algal oil at concentrations of 0, 10,000, 25,000, and 50,000 ppm in the diet for 13 weeks did not produce any significant toxicologic manifestations. The algal 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 endpoints, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The no observed adverse effect level (NOAEL) was the highest level fed of 50,000 ppm which is equivalent to 3,305 and 3,679 mg/kg bw/day, for male and female rats, respectively. The studies were conducted as part of an investigation to examine the safety of DHA-rich algal oil. The results confirm that it possesses a toxicity profile similar to other currently marketed algal oils and support the safety of DHA-rich algal oil for its proposed use in food.

  18. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2014-06-15

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  19. Interclonal variation in the acute and delayed toxicity of cadmium to the European prosobranch gastropod Potamopyrgus antipodarum (Gray).

    Jensen, A; Forbes, V E

    2001-02-01

    The lethal responses of three European clones--A, B, and C-of the prosobranch snail Potamopyrgus antipodarum to acute cadmium exposure were examined by the use of a conventional LC50 test and a delayed toxicity test. The questions addressed were: (1) Are there differences in susceptibility (LC50 values and uniformity of response) among the three European clones of P. antipodarum? (2) Are the patterns of differences in susceptibility among clones observed in the LC50 test also observed for the delayed toxicity test? (3) Is there concordance in the ranking of susceptibility among clones under acute cadmium exposure and under chronic cadmium exposure? The results showed that the widths of the tolerance distribution differed among clones. Clones A and B had a steeper slope than clone C (for clone A the difference was marginally significant), which indicates that individuals from clones A and B showed a more uniform response to acute lethal cadmium stress than individuals from clone C. On the basis of the measured differences in LC50 values, clone A individuals showed the highest tolerance to acute cadmium (LC50 value: 1.92 mg Cd L(-1)) followed by clone B (LC50 value: 1.29 mg Cd L(-1)) and clone C (LC50 value: 0.56 mg Cd L(-1)). Clone C was significantly less tolerant than clones A and B. The delayed toxicity test showed a similar pattern to the LC50 test with regard to tolerance differences among clones; however, mortality continued following transfer to clean water, indicating that cadmium was lethal at much lower concentrations than indicated by the conventional LC50 test. Results of the LC50 test and the delayed toxicity test in the present study were in general agreement with results from chronic cadmium exposure experiments (Jensen et al. [2000] Ecol Appl [submitted]), i.e., the least susceptible clone A in the acute cadmium exposure test was also the least susceptible clone in the chronic cadmium exposure test. Based on the dramatic differences between the LC50

  20. Evaluation on acute toxicity of tetrabuthylammonium bromide ionic liquid at histological structure of some organs in zebrafish (Danio rerio

    Gabi Dumitrescu

    2010-12-01

    Full Text Available In this work, we evaluated the acute toxicity caused by zebrafish (Danio rerio exposure tovarious concentrations of tetrabuthylammonium bromide. The ionic liquid’s acute toxicity on zebrafishwas assessed according to the lethal effects after a 96-hour exposure. To perform the test ontetrabuthylammonium bromide’s acute toxicity, we carried out three series of experiments; during eachseries, we used five different ionic liquid concentrations, respectively: 10; 25; 50; 75; 100 mg L-1 for theexperiment I, 200; 400; 600; 800; 1000 mg L-1 for the experiment II and 1500; 2000; 3000, 4000 and5000 mg L-1 for the experiment III. All these batches were compared with the control variant. Thehistopathological examination was performed on individuals from the control group and on all the deadfish. The results of the acute toxicity test reveal that the LC50 value after 96 hours is between 2500 and3000 mg L-1. The fish exposed to 4000, respectively 5000 mg L-1 tetranuthylammonium bromide diedduring the first 24 hours after exposure. The values obtained for tetrabuthylammonium bromide aremuch smaller than the data obtained for LC50 at 96 hours for other solvents like acetone (30642 mg L-1, respectively DMF (12220 mg L-1, but much bigger than the toluene (60 – 313 mg L-1, benzene(203mg L-1, phenol (5 mg L-1, etc. The histopathological study on gill, skin, liver, kidney and intestinereveal that the changes occurred within the structure of these organs are intensified with the increase oftetrabuthylammonium bromide concentration.

  1. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    Gregers, J; Gréen, H; Christensen, I J;

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...... and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P

  2. Acute and chronic toxicity of sediment samples from Guanabara Bay (RJ during the rainy period

    Luciane Alves Maranho

    2010-06-01

    Full Text Available Guanabara Bay is a marine-estuarine environment of high ecological and socio-economic importance, subject to a variety of environmental impacts. Sediment is the eventual repository for most substances introduced into water bodies and may, therefore, provide an integrated measure of the environmental quality, which can be assessed by many different approaches. In this project, the quality of sediments from Guanabara Bay was evaluated by the ecotoxicological approach: whole-sediment toxicity tests, using Tiburonella viscana, and porewater, elutriate and sediment-water interface chronic toxicity tests, using embryos of Lytechinus variegatus, were applied. Sediments were collected at 14 sampling stations, distributed across the bay. Chronic tests showed significant toxicity in most of the sediment samples. Sediments from stations 1, 2, 3, 6, 8, 10, 11, 12 and 15 showed acute toxicity as well. The results of the different tests were well correlated, and their integration showed that the sediments analyzed were considered unsuitable for aquatic life, resulting in the environmental degradation of Guanabara Bay. In this context, the control of pollution sources and multi-purpose management are required to improve the environmental quality.A Baía de Guanabara é um ambiente marinho-estuarino de grande relevância ecológica e sócio-econômica, e sujeita a uma ampla gama de impactos ambientais. O sedimento é o principal destino para a maioria das substâncias introduzidas nos corpos d'água, podendo fornecer uma medida integrada da qualidade ambiental, a qual pode ser avaliada por várias abordagens. Neste projeto, a qualidade de sedimentos da Baía de Guanabara foi por uma abordagem ecotoxicológica, por meio de testes de toxicidade aguda de sedimento integral, utilizando Tiburonella viscana, e testes de toxicidade crônica de água intersticial, elutriato e interface sedimento-água, utilizando embriões de Lytechinus variegatus. Os sedimentos foram

  3. A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

    Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

    2017-01-01

    Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

  4. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    Kim, Yeon Joo; Park, Jin-hong; Yun, In-Ha; Kim, Young Seok

    2016-01-01

    Purpose To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. PMID:27022287

  5. Acute toxicity of dispersed crude oil on the cold-water copepod Calanus finmarchicus: Elusive implications of lipid content.

    Hansen, Bjørn Henrik; Jager, Tjalling; Altin, Dag; Øverjordet, Ida B; Olsen, Anders J; Salaberria, Iurgi; Nordtug, Trond

    2016-01-01

    In this investigation, acute toxicity data were used from two previously reported studies where cold-water copepods were exposed to mechanically dispersed (MD) and chemically (CD) dispersed oil. In one of these studies, concentration-dependent mortality was observed, whereas no apparent relationship between exposure concentration and mortality was found in the other. The only marked difference between the studies is that copepods in the first experiment displayed a lower lipid sac volume (on average) than in the second one. In this study additional biometric data on lipid content were utilized and observed effects and toxicokinetics modeling applied in order to investigate whether differences in sensitivity between copepod cohorts might be explained by differences in lipid content. Results suggest that although a considerable lipid sac might retard toxicokinetics, the observed differences in lipid volume are not sufficient to explain differences in toxicity. Further, there are no apparent indications that acute toxic stress leads to lipid depletion, or that acute increased mortality rate selectively affects lipid-poor individuals. It is conceivable that other potential explanations exist, but the causal relationship between lipid content and increased mortality frequency remains elusive.

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

    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.

  7. Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotectio

    Mustak Sayyad

    2017-02-01

    Full Text Available Swietenia macrophylla (SM is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

  8. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

    2015-12-15

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  9. (Toxic hepatitis and acute renal failure after inhalation of chloride solvents: report of one case (author's transl))

    Teixido Planas, J.; Martinez-Castelao, A.; Romero Gonzalez, R.; Grino Boira, J.; Gonzalez Segura, C.; Caralps Riera, A.

    1981-06-25

    Due to a combination of ingested ethanol and inhaled trichloroethylene (Tri) a 28 year old man developed toxic hepatitis and acute oliguric renal failure, both of which had a favorable evolution. Tri has been described as a cause of hepatic disfunction and acute renal failure due to acute tubular necrosis, although some of the cases described are controversial, because Tri was either contaminated by other dissolvents or could not be proven pure, with the exception of one case. In many there was ethanol ingestion. The Tri inhaled by our patient was found to contain less than 1% of carbon tetrachloride (C-Tchl). This would suggest the C-Tchl to be responsible for the clinical picture although the combination Tri/ethanol cannot be discarded as the causal agent, due to the small amount of contaminant present.

  10. Acute and Subacute Toxicity In Vivo of Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia

    Masatsugu Tsukamoto

    2014-01-01

    Full Text Available To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA containing silver (Ag. This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment and subacute phase (4–12 weeks after treatment. Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

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

    Ramgopal Mopuri; Balaji Meriga

    2014-01-01

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

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

    Kanjana Jaijoy

    2007-03-01

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

  13. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

    Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille

    2015-01-01

    , desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12...... prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100μg; ≥1.4mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6μg; ≥0.3mg/kg) elicited acute toxicity in terms of reduced weight gain...

  14. Quantum chemistry based quantitative structure-activity relationships for modeling the (sub)acute toxicity of substituted mononitrobenzenes in aquatic systems

    Zvinavashe, E.; Murk, A.J.; Vervoort, J.; Soffers, A.E.M.F.; Freidig, A.; Rietjens, I.M.C.M.

    2006-01-01

    Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria (Phosphoba

  15. Effect of chlorination and ozone pre-oxidation on the photobacteria acute toxicity for dissolved organic matter from sewage treatment plants

    2010-01-01

    The effect of chlorination and ozone pre-oxidation on the photobacteria acute toxicity for dissolved organic matter(DOM) from sewage treatment plants was investigated in this study.The results show that ozone pre-oxidation enhanced the photobacteria acute toxicity of the water samples.DOM before and after ozone pre-oxidation was fractionated by resins into six kinds of hydrophobic and hydrophilic organics.The six fractions were chlorinated individually and the photobacteria acute toxicity before and after chlorination was tested.It was found that the percentage of hydrophilic organics in DOM significantly increased after ozone pre-oxidation and hydrophilic organics exhibited remarkably higher acute toxicity than hydrophobic organics.In view of potentiometric titration and fourier transform infrared(FTIR) analysis,the hydrophilic organics showed a rather higher content of ph-OH structures than hydrophobic organics.

  16. Phytochemical screening and acute toxicity evaluation of Telfairia occidentalis aqueous extracts on rats.

    Anthony, Ogbonnaya Enyinnaya; Ojeifo, Uadia Patrick

    2016-05-01

    The phytochemical composition and acute toxicity of Telfairia occidentalis aqueous extracts were investigated in this study. Phytochemical screening was carried out on the pulverized leaf, root, pod and stem samples. Proximate analysis was also conducted for the root to ascertain the effect of drying procedures on its composition. Fifty-six (56) Wister albino rats, male and female were divided into two broad groups of 28 animals per group. The first group was randomly separated into seven (7) groups of four (4) animals per group. The control group received distilled water alone while the other groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of the Soluble and Insoluble Tefairia occidentalis root fraction. The second group of 28 animals was also distributed into 7 groups of 4 animals per group. Six test groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of Telfairia occidentalis fruit and stem extracts. The animals were observed for the first 12hr for any toxic symptoms and for 48 hr for mortality rate. Surviving animals were sacrificed after 48 hours. Phytochemical screening results reveal the presence of tannins, flavonoid, steroid, terpenoids, saponin, alkaloid, glycosides, proteins and carbohydrates. Flavonoid and saponin was not detected in stem sample; alkaloid is present in all samples except pod; and cyanogenic glycoside was found in both root and pod samples. Except for the fibre content, the method of preparation of the root had no significant effect on the proximate composition of the sample. The root extracts cause insignificant reduction in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) activities, except for the significant reduction in ALT activity at highest dose. The pod extract significantly increased the ALT and AST activities, which is dose dependent, while the stem extract only caused increased activity of ALT, but not AST. None of the extracts administered had any significant effect on the

  17. High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer

    Wolff, Hendrik Andreas; Herrmann, Markus Karl Alfred; Hennies, Steffen; Rave-Fraenk, Margret; Hess, Clemens Friedrich; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Gaedcke, Jochen; Liersch, Torsten [Dept. of Surgery, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Hermann, Robert Michael [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Dept. of Radiotherapy and Radiooncology, Aerztehaus am Diako, Bremen (Germany); Rothe, Hilka [Dept. of Pathology, Univ. Medicine Goettingen (Germany); Schirmer, Markus [Dept. of Clinical Pharmacology, Univ. Medicine Goettingen (Germany)

    2010-01-15

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer. Patients and Methods: From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) {>=} grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells. Results: A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity {>=} grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]). Conclusion: Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group. (orig.)

  18. Toxicity of formulated glyphosate (glyphos) and cosmo-flux to larval Colombian frogs 1. Laboratory acute toxicity.

    Bernal, M H; Solomon, K R; Carrasquilla, G

    2009-01-01

    The spraying of coca (Erythroxylum coca) with glyphosate in Colombia has raised concerns about possible impacts on amphibians. There are few toxicity data for species other than those from temperate regions, and these have not been generated with the combination of formulated glyphosate (Glyphos) and the adjuvant, Cosmo-Flux (coca mix) as used in coca control in Colombia. In order to characterize toxicity of the spray mixture to frogs from Colombia, Gosner stage-25 tadpoles of Scinax ruber, Dendropophus microcephalus, Hypsiboas crepitans, Rhinella granulosa, Rhinella marina, Rhinella typhonius, Centrolene prosoblepon, and Engystomops pustulosus were exposed to the coca mix at concentrations of glyphosate ranging from 1 to 4.2 mg a.e./L diluted in dechlorinated tap water in glass containers. Cosmo-Flux was added to Glyphos in the proportion of 2.3% v/v, as used in aerial application for coca control. Exposures were for 96 h at 23 +/- 1.5 degrees C with 12:12-h light/dark cycle. Test solutions were renewed every 24 h. Concentrations, measured within the first hour and at 24 and 96 h using enzyme-linked immunosorbent assay (ELISA) (Abraxis, LLC), ranged from 70 to 130% of nominal values. LC50 values ranged from 1200 to 2780 microg glyphosate acid equivalents (a.e.)/L for the 8 species tested. Data suggest that sensitivity to Roundup-type formulations of glyphosate in these species is similar to that observed in other tropical and temperate species. In addition, sensitivity of larval amphibians to Roundup-type formulations spans a relatively narrow range. Finally, toxicity of the mixture as used to spray coca was likely driven by the surfactant in the glyphosate formulation, as the addition of Cosmo-Flux did not enhance toxicity above those reported for Vision = Roundup.

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

    LYW Kevin; AH Hussin; I Zhari; JH Chin

    2012-01-01

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

  20. Acute toxicities and sublethal effects of some conventional insecticides on Trichogramma chilonis (Hymenoptera: Trichogrammatidae).

    Wang, De-Sen; He, Yu-Rong; Guo, Xiang-Ling; Luo, Yong-Li

    2012-08-01

    The acute toxicity of 10 conventional insecticides to adult of Trichogramma chilonis Ishii (Hymenoptera: Trichogrammatidae) was bioassayed by membrane method, and then their sublethal effects on the parasitoid were evaluated in the laboratory. Based on sublethal concentration (LC30) values at 8 h after treatment, we determined that adult T. chilonis were the most susceptible to chlorfenapyr, followed by fipronil, spinosad, avermectins, beta-cypermethrin, and cartap, with lethal concentration (LC)30 values of 0.3133, 0.3269, 1.5408, 3.2961, 6.1469, and 9.021 mg/liter, respectively. The field-recommended concentrations of chlorfluazuron, indoxacarb, Bacillus thuringiensis, and tebufenozide caused Cartap and spinosad also reduced longevity (8 and 7.9 d) and fecundity (110.77 and 117.2) of treated adults, but cartap enhanced the female percentage of F1 offspring (61.6%), resulting a statistical higher R0, r(m), and lambda of treated T. chilonis. In contrast, chlorfluazuron and tebufenozide increased longevity (16.4 and 15.4 d) and fecundity (248 and 256.9) of treated adults but slightly decreased the female percentage of F1 offspring (31.4 and 38.1%). Although chlorfenapyr showed no adverse influence on longevity and fecundity, it remarkably reduced the female percentage of F1 offspring (13.5%), leading to a lower R0, r(m), and lambda of treated T. chilonis. Indoxacarb, B. thuringiensis, and beta-cypermethrin had no obvious sublethal effects on the longevity and fecundity of treated adults. Based on these results, we consider B. thuringienesis, chlorfluazuron, indoxacarb, beta-cypermethrin, and tebufenozide safe to T. chilonis, suggesting that these insecticides are compatible with this parasitoid when being used in the field. However, fipronil, chlorfenapyr, spinosad, and avermectins were very harmful to T. chilonis. Timing of application of these insecticides was critical.

  1. The effects of water quality and age on the acute toxicity of copper to the Florida apple snail, Pomacea paludosa.

    Rogevich, E C; Hoang, T C; Rand, G M

    2008-05-01

    Copper (Cu)-containing compounds have been used in Florida as fungicides, herbicides, and soil amendments, resulting in elevated Cu in the aquatic ecosystem. The Florida apple snail (Pomacea paludosa), a key species in south Florida, may be adversely affected by Cu. Water-quality parameters, such as hardness, dissolved organic carbon (DOC), pH, and alkalinity, affect metal bioavailability and toxicity in aquatic organisms; however, it is uncertain to what extent these factors affect Cu toxicity in the Florida apple snail. The research presented here characterized the acute (96-hour) toxicity of Cu in water to the Florida apple snail at various life stages and under different water-quality parameters. Cu was more toxic to juvenile than adult apple snails. There was no difference between the 96-hour LC(50) at pH 5.5 and 6.5; however, the 96-hour LC(50 )values at pH 7.5 and 8.5 were greater than at lower pHs. The decrease in Cu(2+) above pH 7, as predicted by the MINTEQ model, accounted for the pH effect. Cu toxicity decreased as DOC increased from 0.2 to 30 mg/L. Unlike other aquatic organisms, hardness had no effect on Cu toxicity to the Florida apple snail, suggesting another mechanism of toxicity. Whole-body tissue analysis indicated that the lethal body burden of 120-day-old snails exposed to Cu for 4 days was 30 mg/kg Cu dry weight. Multiple regression analysis indicated that Cu toxicity was a function of organism age, DOC, and pH.

  2. Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

    Lechuga, M; Fernández-Serrano, M; Jurado, E; Núñez-Olea, J; Ríos, F

    2016-03-01

    The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment.

  3. MOAtox: A Comprehensive Mode of Action and Acute Aquatic Toxicity Database for Predictive Model Development

    tThe mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity andas an alternative to chemical class-based predictive toxicity modeling. However, the development ofquantitative structure activity relationship (QSAR) and other models has been limite...

  4. Preliminary studies of acute and sub-chronic toxicity of the aqueous extract of Guibourtia tessmannii(Harms) J.Leonard stem barks (Caesalpiniaceae) in mice and rats

    Noreen Orianna Koumba Madingou; Aristide Traore; Alain Souza; Marlaine Michelle Boukandou Mounanga; Raissa Reine Aworet Samseny; Sylvin Ouedraogo; Alfred Sababenedyo Traore

    2016-01-01

    Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii(Harms) J. Leonard(G. tessmannii) and evaluate its safety.Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii.Increasing concentrations of the plant extracts were administered intraperitoneally or by force-feeding. General behavior and death were monitored and recorded daily for 7 days.In order to determine the sub-acute toxicity of the extract, several doses were administered by oral gavage daily for 28 days in adult Wistar rats. Different parameters were assessed including body weight, food and water intake, biochemical parameters and several vital organ weights.Results: LD50 of 328.78 mg/kg was obtained by i.p. route and more than 5 000 mg/kg was obtained in acute toxicity by oral route. In sub-acute toxicity, no significant alteration was observed in body weight or vital organs, food and water intake, and biochemical parameters.Conclusions: The results showed that the aqueous extract of G. tessmannii has low toxicity intraperitoneally and no sub-acute toxicity via oral intake.

  5. Preliminary studies of acute and sub-chronic toxicity of the aqueous extract of Guibourtia tessmannii (Harms) J. Leonard stem barks (Caesalpiniaceae) in mice and rats

    Noreen Orianna Koumba Madingou; Aristide Traore; Alain Souza; Raissa Reine Aworet Samseny; Sylvin Ouedraogo; Alfred Sababenedyo Traore

    2016-01-01

    Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii (Harms) J. Leonard (G. tessmannii) and evaluate its safety. Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii. Increasing concentrations of the plant extracts were administered intraperitoneally or by force-feeding. General behavior and death were monitored and recorded daily for 7 days. In order to determine the sub-acute toxicity of the extract, several doses were adminis-tered by oral gavage daily for 28 days in adult Wistar rats. Different parameters were assessed including body weight, food and water intake, biochemical parameters and several vital organ weights. Results: LD50 of 328.78 mg/kg was obtained by i.p. route and more than 5 000 mg/kg was obtained in acute toxicity by oral route. In sub-acute toxicity, no significant alteration was observed in body weight or vital organs, food and water intake, and biochemical parameters. Conclusions: The results showed that the aqueous extract of G. tessmannii has low toxicity intraperitoneally and no sub-acute toxicity via oral intake.

  6. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    Kim YJ

    2016-03-01

    Full Text Available Yeon Joo Kim, Jin-hong Park, In-Ha Yun, Young Seok KimDepartment of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of KoreaPurpose: To compare the acute intestinal toxicity of whole pelvic (WP and small field (SF intensity-modulated radiotherapy (IMRT for prostate cancer using dosimetric and metabolic parameters as well as clinical findings.Methods: Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50 and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy.Results: Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF and were not relevant to the irradiated doses.Conclusion: Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages.Keywords: prostate cancer, intensity-modulated radiotherapy, intestinal toxicity, citrulline

  7. Evaluation of acute copper toxicity to juvenile freshwater mussels (fatmucket, lampsilis siliquoidea) in natural and reconstituted waters

    Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; May, T.W.; Arnold, W.R.; Santore, R.C.; Augspurger, T.; Dwyer, F.J.; Barniiart, M.C.

    2009-01-01

    The influence of dissolved organic carbon (DOC) and water composition on the toxicity of copper to juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) were evaluated in natural and reconstituted waters. Acute 96-h copper toxicity tests were conducted at four nominal DOC concentrations (0, 2.5, 5, and 10 mg/L as carbon [C]) in dilutions of natural waters and in American Society for Testing and Materials (ASTM) reconstituted hard water. Toxicity tests also were conducted in ASTM soft, moderately hard, hard, and very hard reconstituted waters (nominal hardness 45-300 mg/L as CaCO3). Three natural surface waters (9.5-11 mg/L DOC) were diluted to obtain a series of DOC concentrations with diluted well water, and an extract of natural organic matter and commercial humic acid was mixed with ASTM hard water to prepare a series of DOC concentrations for toxicity testing. Median effective concentrations (EC50s) for dissolved copper varied >40-fold (9.9 to >396 ??g Cu/L) over all 21 treatments in various DOC waters. Within a particular type of DOC water, EC50s increased 5- to 12-fold across DOC concentrations of 0.3 to up to 11 mg C/L. However, EC50s increased by only a factor of 1.4 (21 30 ??g Cu/L) in the four ASTM waters with wide range of water hardness (52-300 mg CaCO 3/L). Predictions from the biotic ligand model (BLM) for copper explained nearly 90% of the variability in EC50s. Nearly 70% of BLM-normalized EC50s for fatmucket tested in natural waters were below the final acute value used to derive the U.S. Environmental Protection Agency acute water quality criterion for copper, indicating that the criterion might not be protective of fatmucket and perhaps other mussel species. ?? 2009 SETAC.

  8. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species - SETAC Abstract

    We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...

  9. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

  10. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

    T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

    2010-01-01

    textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

  11. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

    Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

    2017-02-01

    Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

  12. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy.

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (PPAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.

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

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

    2017-01-01

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

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

    王月明; 刘宇峰; 马若波; 韩秋菊

    2015-01-01

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

  15. Study on the Acute Toxicity and Genetics Toxicity of Bensulfuronk-methyl on Danio rerio%苄嘧磺隆对斑马鱼的急性毒性和遗传毒性研究

    姜罡丞

    2009-01-01

    [Objective] The aim was to study the effect of bensulfuron-methyl herbicide on acute toxicity and genetics toxicity of Danio rerio. [Method] Median lethal concentration was calculated by acute toxicity test, and analyzing the herbicide whether existing in potential toxicity to aquatic organisms or not. Based on the study of acute toxicity, genetics toxicity was carried out, by calculating the micronucleus rate to judge bensulfuron-methyl herbicide whether existing in potential toxicity or not. [Result] The LD50 (24 h and 48 h) of bensulfuron-methyl herbicide are 0.698 ml/L and 0.637 ml/L respectively, the safe concentration was 0.159 ml/L. The results on the effects of micronucleus (MN) in erythrocytes of Danio rerio induced by bensulfuron-methyl at different times and different concentrations showed that the MN rate of control group was 0.010 3%, the highest MN rate of experimental group reached to 0.372%, it also indicated that bensulfuron-methyl herbicide had genetics toxicity to Danio rerio. At the same detection time, there was dose-effect relationship of MN rate in erythrocytes between treatment and control groups with different concentrations. In the same treatment group, the MN rate in erythrocytes reached to peak value at 24 h, and decreased at 48 h and 72 h with the infection time was prolonged. [Conclusion] The study provides some basis for scientifically selecting and reasonably using herbicide.

  16. Intermittent use of amifostine during postoperative radiochemotherapy and acute toxicity in rectal cancer patients

    Dunst, J.; Semlin, S.; Pigorsch, S.; Mueller, A.C.; Reese, T. [Halle-Wittenberg Univ., Halle (Germany). Abt. fuer Radiotherapie

    2000-09-01

    From September 1997 through October 1998, 30 patients with stage II/III rectal cancer underwent postoperative radiochemotherapy at our department. All patients had undergone curative (R0) resection and received 50.4 Gy to the pelvis with a 3-field technique using a belly board followed by a boost of 5.4 Gy to the presacral space in conventional fractionation with 1.8 Gy per fraction. 5-FU chemotherapy was administered as 120-hours continuous infusion in the first and fifth radiation week via a central venous catheter in a daily dosage of 1000 mg/m{sup 2}. All patients were offered to participate in a phase-II study using additional amifostine. Fifteen patients participated and received 500 mg amifostine daily on chemotherapy days (days 1 to 5 and 29 to 33) immediately prior to the daily radiation fraction. Fifteen patients did not participate and served as non-randomized control. The study was approved by the ethical committee of the Martin-Luter-University and informed consent was obtained from all patients. Results: The distribution of patients' characteristics and prognostic parameters was comparable in both groups. Side effects of amifostine were mild and included hypotension (53% grade I, 7% grade II) and nausea (47% grade I, 13% grade II). Antiemetics were not routinely used. All patients completed radiochemotherapy plus amifostine without unplanned breaks or dose reductions. One patients developed a cerebral infraction which was considered to be not related to the use of amifostine. As compared to the non-randomized control group, patients with additional amifostine had less acute skin and bowel toxicity (maximum erythema score 1.47{+-}0.64 without vs 0.87{+-}0.52 with amifostine, p=0.009 and maximum diarrhea score 1.07{+-}1.03 vs 0.40{+-}0.63, p=0.044). Oral 5-FU-related mucositis and hematological toxicity were not significantly different. (orig.) [German] Zwischen September 1997 und Oktober 1998 wurden 15 Patienten mit postoperativer

  17. Acute toxicity and histopathology in ornamental fish amazon bluespotted corydora (Corydoras melanistius exposed to formalin

    Rudã F.B. Santos

    2012-12-01

    Full Text Available The objective of this work was to evaluate the acute toxicity of formalin and histopathological effects on the Amazon ornamental fish, bluespotted coridora (Corydoras melanistius. A randomized design was used, with ten concentrations of formalin (40% (0, 3, 6, 12, 25, 50, 100, 150, 200 and 250mg.L-1 with four replicates and five fish per container (3L in static system for 96 hours. The moribund fish were killed and fixed in 10% formalin to proceed the histopathological analysis of gill, liver and kidney. At the end of this experiment the following mortality rates (% were obtained in increasing order of exposure: 0, 0, 0, 0, 0, 65, 85, 100, 100 and 100%. The lethal concentration 50% (LC50-96h (I estimated was 50.76 mg.L-1 with regression of y = 0.51x, and r² = 0.80. Further, in higher concentrations morphological changes as gill hyperplasia, with filling of interlamellar spaces, disorganization of liver arrangement, and necrosis in kidney were observed. In this study, the formalin can be considered slightly toxic to bluespotted corydora, and cause morphological changes when exposed to high concentrations. The use of formalin to treat of ornamental fish in the inner river of capture with wrong concentration can provoke negative environmental and biological effects.O objetivo do trabalho foi determinar a toxicidade aguda de formalina e os efeitos histopatológicos para o peixe ornamental amazônico corredora bicuda (Corydora melanistius. Foi utilizado um delineamento inteiramente casualizado; com dez concentrações de formalina 40% (0, 3, 6, 12, 25, 50, 100, 150, 200 e 250mg.L-1, com quatro repetições e cinco peixes por recipiente de água (3 L em sistema estático durante 96 horas. Os peixes moribundos foram mortos e fixados em formol 10% procedendo à análise histopatológica das brânquias e do fígado. Ao final desse experimento, obtiveram-se as seguintes taxas de mortalidades em ordem crescente de exposição (%: 0, 0, 0, 0, 0, 65, 85

  18. Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice.

    Wang, Bing; Feng, Wei-Yue; Wang, Tian-Cheng; Jia, Guang; Wang, Meng; Shi, Jun-Wen; Zhang, Fang; Zhao, Yu-Liang; Chai, Zhi-Fang

    2006-02-20

    The purpose of this study is to evaluate the acute toxicity of oral exposure to nanoscale zinc powder in mice. The healthy adult male and female mice were gastro-intestinally administered at a dose of 5 g/kg body weight with two size particles, nanoscale zinc (N-Zn) and microscale zinc (M-Zn) powder, while one group mice treated with sodium carboxy methyl cellulose was used as the control. The symptoms and mortality after zinc powder treatment were recorded. The effects of particles on the blood-element, the serum biochemical level and the blood coagulation were studied after 2 weeks of administration. The organs were collected for histopathological examination. The N-Zn treated mice showed more severe symptoms of lethargy, vomiting and diarrhea in the beginning days than the M-Zn mice. Deaths of two mice occurred in the N-Zn group after the first week of treatment. The mortalities were confirmed by intestinal obstruction of the nanoscale zinc aggregation. The biochemical liver function tests of serum showed significantly elevated ALT, AST, ALP, and LDH in the M-Zn mice and ALT, ALP, and LDH in the N-Zn mice compared with the controls (Pnano-scale zinc powders. The clinical changes were observed in the two treated group mice as well. The levels of the above enzymes were generally higher in the M-Zn mice than in the N-Zn mice, which implied that M-Zn powder could induce more severe liver damage than N-Zn. The biochemical renal function tests of serum BUN and CR in the M-Zn mice markedly increased either compared with the N-Zn mice or with the controls (P<0.05), but no significant difference was found between the N-Zn and the control mice. However, severe renal lesions were found by the renal histopathological examination in the N-Zn exposed mice. Therefore, we concluded that severe renal damage could occur in the N-Zn treated mice, though no significant change of blood biochemical levels occurred. Blood-element test showed that in the N-Zn mice, PLT and RDW

  19. ACUTE TOXICITY OF METALS: NICKEL AND ZINC TO PARAMECIUM BURSARIA AND ITS ENDOSYMBIONTS

    Patrycja Zagata

    2015-02-01

    Full Text Available Paramecium bursaria is an unicellular organism, widely distributed in the freshwater environment, where heavy metals are common contaminants. The ciliates, also including Paramecium bursaria, are a very abundant group in aquatic ecosystems, what makes them effective biological indicators of water pollutants. Paramecium bursaria is the only Paramecium which has evolved a mutualistic relationship with algae and it harbors these endosymbionts in its own cytoplasm. The algae are also very effective bioindicators of some pollutants because of their ability to biosorption and bioaccumulation of heavy metals. The aim of this study was to determine the acute toxicity of two metals’ compounds: nickel chloride (NiCl2 and zinc chloride (ZnCl2 to Paramecium bursaria and its endosymbionts. The ciliates were incubated in solutions with 5x10-8 to 5x10-2g/dm3 of NiCl2 and with 5x10-8 to 5x10-2g/dm3 of ZnCl2, at the temperature of 180C, in the light/dark conditions (12L/12D. Microscopic observations of cell divisions rate, cell shape changes as well as the swimming behavior, were conducted after 24, 48, 72 and 120 hours of incubation in the tested solutions and were compared to the control sample. Microscopic observations revealed the lethal doses for both compounds, for nickel chloride 5x10-5g/dm3 and for zinc chloride 5x10-3. These observations also revealed that in lesser concentrations than the lethal one, the slowdown and characteristic movements occur after metal addition. The PEA measurements of Fv/Fm parameter were carried out within 4 days, the first one after 24 hours of incubations. The results of this investigation has given us a view of a fluorescence efficiency by revealing that both compounds solutions can have the stimulating effect on Photosystem II, because the lowest fluorescence efficiency was measured in control samples.

  20. Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results

    Birkenhake, S.; Leykamm, S.; Sauer, R. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Radiooncology; Martus, P. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Medical Statistics

    1999-03-01

    Purpose: To evaluate acute toxicity and efficacy of simultaneous radiochemotherapy for invasive urothelial cancer of the bladder. Patients and Methods: From September 1993 to July 1997, 61 patients with invasive bladder cancer were treated with a transurethral resection (TURB) followed by radiochemotherapy (RCT). Twenty-five received a combination of 5-FU and cisplatin. The prescribed doses were 600 mg/m{sup 2} 5-FU daily as continuous infusion over 5 days each in the 1st and 5th treatment week and 20 mg/m{sup 2} cisplatin daily at the same days as a short infusion. The pelvis was irradiated with 54 Gy, the bladder with 59.4 Gy and the paraortic nodes in 7 cases with 45 Gy, respectively. Six to 8 weeks after RCT a second TURB was performed for reasons of restaging. Results: Twenty out of 25 patients received at least 80% of the prescribed chemotherapy, in 13 cases the full dose could be given. Gastrointestinal toxicity of Grade I and II occurred in 10 cases, 1 patient developed severe diarrhea (Grade VI). After the 1st course of chemotherapy 7 patients had leuco- or thrombopenia of Grade III. One patient had a leucopenia of Grade IV. After the 2nd course 4 patients developed Grade III leuko- and thrombopenia, 1 of Grade IV. Two Grade II anemia were found. All more severe toxicities and necessary dose reductions were related to radiation of the paraaortic nodes. No life threatening infections, bleedings or cardiotoxicity was found. Restaging TURBs resulted in 22 complete remissions, 1 patient had a de-novo-carcinoma (Tis) at this time, 2 were non-responders (8%). After a median follow-up of 38 months 20 patients are alive (80%). Conclusions: 1. If irradiation of paraaortic nodes is necessary, 5-FU should not be applied, because the gastrointestinal toxicity is too extensive. In all other cases side effects are tolerable and can be managed by supportive care. 2. The first results are promising and should be evaluated in a prospective study. (orig.) [Deutsch

  1. DOSE RESPONSE DEETERMINATION OF NMDA ANTAGONISTS AND GABA AGONIST ON SUSTAINED ATTENTION.

    We have shown that acute inhalation of toluene impairs sustained attention as assessed with a visual signal detection task (SDT). In vitro studies indicate that the NMDA and GABA systems are primary targets of anesthetic agents and organic solvents such as toluene. Pharmacologica...

  2. HMX: Analysis of Dosing Formulations Used in Acute, Sub-Acute and Sub-Chronic Toxicity Studies.

    1985-07-31

    finding studies were prepared in 0.5% low viscosity carboxymethylcellulose (CMC). Aliquots for analysis were removed at intervals during the dosing of each...diets prepared for toxicity studies by reverse phase HPLC. Dietary preparations were stable for at least 21 days when stored in ambient conditions in...the dark. Almost all the dosing solutions and diets prepared for a range of studies were shown to contain dose to the desired concentrations of HMX

  3. Acute toxicity of oxygenated and nonoxygenated imidazolium-based ionic liquids to Daphnia magna and Vibrio fischeri.

    Samorì, Chiara; Pasteris, Andrea; Galletti, Paola; Tagliavini, Emilio

    2007-11-01

    Room-temperature ionic liquids (RTILs) recently have generated great interest as a result of their potential commercial applications. In particular, because of their negligible vapor pressure and low inflammability, they have been suggested as green alternatives to traditional organic solvents. The toxicity and potential environmental risk of this heterogeneous class of chemicals, however, are poorly understood. An alkyl-substituted RTIL, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)]), is one of the most widely used cations of RTILs, and information regarding its toxicity is relatively extensive. On the other hand, oxygenated chain-substituted ionic liquids, 1-methoxyethyl-3-methylimidazolium salts (moemims), are a new class of RTILs that have been poorly studied. Here, we compared the acute toxicity of [bmim][BF(4)] and moemims to the crustacean Daphnia magna (end point, 48-h immobilization) and the bacterium Vibrio fischeri (end point, 15-min inhibition of bioluminescence). The concentrations of [bmim][BF(4)] resulting in 50% of the maximum adverse effect (EC50s) for D. magna and V. fischeri were 5.18 and 300 mg/L, respectively, and were consistent with previously published values. The EC50s of the two moemims for D. magna are very similar, ranging from 209 to 222 mg/L in different experimental trials, and are higher by two orders of magnitude than the EC50 of [bmim][BF(4)]. The EC50s of 1-methoxyethyl-3-methylimidazolium tetrafluoroborate ([moemim][BF(4)]) and 1-methoxyethyl-3-methylimidazolium dicyanamide ([moemim][dca]) for V. fischeri are 3,196 and 2,406 mg/L, respectively. Results indicate that introduction of an oxygenated side chain in the imidazolium cation can greatly reduce the toxicity of RTILs and that these RTILs are less toxic than commonly used chlorinated solvents, such as tricloromethane, but are more toxic than nonchlorinated solvent, such as methanol and acetone.

  4. Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

    Shah Ismail

    2011-10-01

    Full Text Available Abstract Background Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. Methods The crude methanol extract was obtained by maceration with distilled water (500 ml three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent. Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Results Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD50 value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4 mg/ml. Similarly, EC50 value for brine shrimp

  5. Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM.

    Kostyniak, P J; Nakeeb, S M; Schopp, E M; Maccubbin, A E; John, E K; Green, M A; Kung, H F

    1990-12-01

    Cu-PTSM is a potential imaging agent for the heart and brain when labeled with either 64Cu or 62Cu. Unlabeled Cu-PTSM was evaluated for its acute toxicity and mutagenicity. Cu-PTSM had an i.v. LD50 of 26 mg kg-1 in the rat and 2 mg kg-1 in the rabbit. At necropsy, rats exhibited severely hemorrhagic lungs, histological findings of acute pulmonary congestion, hemorrhage and edema, and mild congestion in kidney, liver and brain. The rabbit displayed marked polymorphonuclear infiltration in alveoli, peribronchial and periarterial areas with marked macrophage hyperplasia, congestion and mild hemorrhage into alveolar spaces. No effects were found in kidney, liver, testes or brain. Administration of 2.16 micrograms kg-1 day-1 for 5 days per week for 2 weeks resulted in no changes in histopathology, hematology or clinical chemistry parameters. This daily dose is at least 300 times the diagnostic dose intended for use in man. Cu-PTSM was not mutagenic when tested in the absence of S9 supernatant, but elicited a weakly mutagenic response in the presence of S9. Since acute effects in the lung occur at doses approaching 300,000 times the diagnostic dose, it is highly unlikely that the clinical use of Cu-PTSM would result in any acute adverse effects.

  6. The acute toxicity of selected alkylphenols to young and adult Daphnia magna

    Gerritsen, A.; Hoeven, N. van der; Pielaat, A.

    1998-01-01

    Differences in sensitivity toward toxicants between young and adult individuals in a population are assumed to be primarily associated with their difference in body size. This assumption plays a key role in the modeling of effects of variable concentrations of toxicants on nonhomogeneous populations

  7. Use of solar advanced oxidation processes for wastewater treatment: Follow-up on degradation products, acute toxicity, genotoxicity and estrogenicity.

    Brienza, M; Mahdi Ahmed, M; Escande, A; Plantard, G; Scrano, L; Chiron, S; Bufo, S A; Goetz, V

    2016-04-01

    Wastewater tertiary treatment by advanced oxidation processes is thought to produce a treated effluent with lower toxicity than the initial influent. Here we performed tertiary treatment of a secondary effluent collected from a Waste Water Treatment Plant via homogeneous (solar/HSO5(-)/Fe(2+)) and heterogeneous (solar/TiO2) solar advanced oxidation aiming at the assessment of their effectiveness in terms of contaminants' and toxicity abatement in a plain solar reactor. A total of 53 organic contaminants were qualitatively identified by liquid chromatography coupled to high-resolution mass spectrometry after solid phase extraction. Solar advanced oxidation totally or partially removed the major part of contaminants detected within 4.5 h. Standard toxicity tests were performed using Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata and Brachionus calyciflorus organisms to evaluate acute and chronic toxicity in the secondary or tertiary effluents, and the EC50% was calculated. Estrogenic and genotoxic tests were carried out in an attempt to obtain an even sharper evaluation of potential hazardous effects due to micropollutants or their degradation by-products in wastewater. Genotoxic effects were not detected in effluent before or after treatment. However, we observed relevant estrogenic activity due to the high sensitivity of the HELN ERα cell line.

  8. Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

    Gupta, S; Shukla, R; Prabhu, K M; Aggrawal, S; Rusia, U; Murthy, P S

    2002-01-01

    Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

  9. Acute toxicity of drainage ditch water from a Washington State cranberry-growing region to Daphnia pulex in laboratory bioassays.

    Wood, Barbara; Stark, John D

    2002-10-01

    High concentrations of organophosphorous insecticides resulting from cranberry bog applications were detected in the Grayland Drainage Ditch (GDD) system in Grayland, Washington State, during the 1994-1996 Washington State Department of Ecology Pesticide Monitoring Program. This drainage ditch system drains cranberry bogs and enters the Pacific Ocean via the North Cove and Supon Inlet. Concerns about the impact of these pesticides on human and environmental health led to this investigation of the potential impact on an indicator species, Daphnia pulex. To determine the toxic effects of multiple pesticides entering the GDD, standardized laboratory toxicity tests with D. pulex were conducted concurrently with the Washington State Department of Ecology pesticide sampling. Concentrations of three insecticides, diazinon, chlorpyrifos, and azinphosmethyl, were the highest ever detected in state waters. The GDD water was found to cause acute toxicity in 33% of the laboratory bioassays conducted. Regression analysis, however, detected a poor correlation between total insecticide detected and percentage mortality of D. pulex at the two drainage ditch sites studied, Grays Harbor County site and the Pacific County site. However, the relationship between mortality of D. pulex and detected concentrations of diazinon and chlorpyrifos were significant. Sampling schedules for chemical analysis and bioassay testing appear to be the primary reason that statistical analysis failed to correlate mortality with detected OP pesticide concentrations. Grab samples used in toxicity testing may over- or underestimate actual concentrations of contaminants present in the system being studied.

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

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

    2010-04-22

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

  11. Influence of acclimation and exposure temperature on the acute toxicity of cadmium to the freshwater snail Potamopyrgus antipodarum (Hydrobiidae)

    Moeller, V.; Forbes, V.E.; Depledge, M.H. (Odense Univ. (Denmark). Ecotoxicology Group)

    1994-09-01

    Forty-eight-hour acute toxicity tests were performed to determine the influence of acclimation temperature (5, 15, and 20 C) and exposure temperature (5, 15, and 20 C) on the toxicity of cadmium to the freshwater gastropod Potamopyrgus antipodarum. Mortality varied with cadmium concentration and treatment conditions, but did not conform to conventional sigmoid concentration-response relationships. Because the shapes of the concentration-response curves were treatment dependent, a nontraditional approach for data analysis was employed. Regardless of acclimation temperature, mortality increased with increasing exposure temperature, and at all exposure temperatures snails acclimated at 15 C were most susceptible to cadmium toxicity. Estimated LC50 values were within 1 to 4 mg Cd/L. Although the shapes of the concentration-response curves were different for each treatment, the slopes were generally quite steep, indicating a uniform response for the whole population. At a given Cd concentration, acclimation temperature and exposure temperature accounted for 57 and 40%, respectively, of the variation in mortality, and LC50s changed by a factor of four. The results indicate that changes in environmental variables can alter both the degree of response and the response distribution of a population, and that past as well as prevailing environmental conditions can influence organismic responses to toxicants.

  12. Rectal planning risk volume correlation with acute and late toxicity in 3-dimensional conformal radiation therapy for prostate cancer.

    Dias, R S; Giordani, A J; Souhami, L; Segreto, R A; Segreto, H R C

    2011-12-01

    The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥ 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications ≥ grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.

  13. Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma

    Fan, Katherine Y.; Gogineni, Hrishikesh; Zaboli, David; Lake, Spencer; Zahurak, Marianna L.; Best, Simon R.; Levine, Marshall A.; Tang, Mei; Zinreich, Eva S.; Saunders, John R.; Califano, Joseph A.; Blanco, Ray G.; Pai, Sara I.; Messing, Barbara; Ha, Patrick K.

    2013-01-01

    Purpose The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs. Methods We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m2/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months. Results Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1–2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11). Conclusions With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required. PMID:22290566

  14. High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

    Wolff, Hendrik Andreas; Bosch, Jan; Hennies, Steffen; Hess, Clemens F.; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Overbeck, Tobias [Dept. of Haematology and Oncology, Univ. Medicine Goettingen (Germany); Matthias, Christoph; Roedel, Ralph M. [Dept. of Otorhinolaryngology, Univ. Medicine Goettingen (Germany)

    2010-05-15

    Purpose: to test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and methods: from 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC {>=} 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis. Results: a statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC {>=} 3 acute organ toxicity had a 5-year overall survival rate of 4% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure. Conclusion: these data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials. (orig.)

  15. Acute toxicity, genetic toxicity and sub-chronic toxicity of apigenin%芹菜素的急性毒性、遗传毒性及亚慢性毒性试验研究

    刘海波; 隋海霞; 支媛; 耿桂英; 余强; 高芃; 徐海滨

    2011-01-01

    Objective To evaluate the safety of apigenin, so as to provide scientific support for the reasonable use and development of apigenin. Methods According to the procedure and methods in the Food Toxicological Safety Evaluation, a series of toxicological studies on the ingestion of apigenin were conducted, including acute toxicity, genetic toxicity as well as sub-chronic toxicity experiments. Results For the acute toxicity, the maximum tolerated dose (MTD) was higher than 8 g/kg BW. No apigenin-related genetic toxicity was observed. There were no apigenin-related adverse effects on body weight, food intake, food consumption, hematology, serum biochemistry, urine routine as well as histopathology in rats. Conclusion The no observed adverse effect level (NOAEL) of apigenin was 8 g/kg BW. Apigenin belongs to actually non-toxic substance with no genetic toxicity.%目的 研究芹菜素的安全性,为其合理开发利用提供科学依据.方法 根据《食品安全性毒理学评价程序和方法》,进行了芹菜素急性毒性试验、小鼠骨髓微核实验、Ames试验、小鼠精子畸变试验、大鼠90天喂养试验.结果 芹菜素大鼠急性毒性的MTD大于8 g/kg BW,遗传毒性试验结果为阴性,未见芹菜素对大鼠体重、摄食量、食物利用率、血常规、血生化、尿常规有生物学意义的影响.芹菜素对大鼠脏器无明显影响.结论 芹菜素属实际无毒物,无遗传毒性,芹菜素的大鼠90天喂养实验的NOAEL为8 g/kg BW.

  16. Effects of polycyclic aromatic hydrocarbons (PAHs) on an aquatic ecosystem: acute toxicity and community-level toxic impact tests of benzo[a]pyrene using lake zooplankton community.

    Ikenaka, Yoshinori; Sakamoto, Masaki; Nagata, Takamaru; Takahashi, Hirokazu; Miyabara, Yuichi; Hanazato, Takayuki; Ishizuka, Mayumi; Isobe, Tomohiko; Kim, Jun-Woo; Chang, Kwang-Hyeon

    2013-02-01

    We estimated acute toxicity of benzo[a]pyrene (B[a]P) using two cladoceran species, Ceriodaphnia reticulata and Daphnia magna, and also analyzed its impact on zooplankton community throughout an exposure experiment using small-scale mesocosms. LC(50) of B[a]P for C. reticulata and D. magna was 4.3 and 4.7 µg/l, respectively. However, individuals fed with Chlorella showed higher LC(50), 6.1 µg/l for C. reticulata and 8.0 µg/l for D. magna. In the exposure experiment, we examined the impact of B[a]P on zooplankton community using conceivable concentrations in the environment (5 and 10 µg/l) using typical zooplankton community in eutrophicated systems. Despite the residence time of B[a]P in the water column was short as impacts, suppressing cladoceran populations and inducing the dominance of rotifers particularly under high concentration (10 µg/l). Results have suggested that, even such short duration of B[a]P in the water body can have impact on zooplankton abundance and community structure. Since B[a]P easily precipitate to the bottom and rapidly disappears from the water body, careful monitoring and further assessment of the potential toxicity of polycyclic aromatic hydrocarbons are necessary.

  17. NMDA receptors and memory encoding.

    Morris, Richard G M

    2013-11-01

    It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can

  18. Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry, E-mail: lkestin@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Ghilezan, Mihai; Krauss, Daniel; Vicini, Frank; Brabbins, Donald; Gustafson, Gary; Ye Hong; Martinez, Alavaro [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2012-01-01

    Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

  19. Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae.

    Sánchez-Fortún, S; Sanz, F; Barahona, M V

    1996-10-01

    The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion salina 24- and 72-h old it was methylparathion = parathion Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a

  20. Determination of acute toxicity and the effects of sub-acute concentrations of CuO nanoparticles on blood parameters in Rutilus rutilus

    Abdolreza Jahanbakhshi

    2015-07-01

    Full Text Available Objective(s:Copper oxidenanoparticles have different industrial applications so it is inevitable that nanoparticulate products finally find their way into aquatic ecosystems. Nevertheless there is little information available about their effects on some of edible fish. The present study aims to determine the acute toxicity and evaluate the effect of two sub-acute concentrations (50 and 70% 96 h LC50 of CuO-NPs on some hematological and biochemical parameters of R. rutilus. Materials and Methods:225 healthy specimen of R. rutilus (mean weight 5.52±1.2 g; mean length 6.20±0.2 cm were transported to the laboratory. In order to prepare the stock solution, CuO-NPs was dispersed in pure water with ultrasonication (50-60 kHz for 15 min every day before dosing. At first, R. rutilus was exposed to CuO-NPs to determine the lethal concentration (LC50 value. Following acute test, fish were treated with sub-acute concentrations of CuO-NPs (50 and 70% 96 h-LC50 at with one control group (no CuO-NPs for a week to determine the changes in the level of some plasma hematological and biochemical parameters. Results:The 96 h-LC50 values of CuO-NPs was 2.19±0.003 mg/l. R. rutilus exhibited significantly lower RBC count, Hb and Hct values and a significant increase in the WBC numbers, MCH, MCHC and MCV indices (p

  1. A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma. A report on acute toxicity

    Norkus, Darius; Miller, Albert; Kurtinaitis, Juozas; Valuckas, Konstantinas Povilas [Dept. of Radiotherapy, Inst. of Oncology, Vilnius Univ. (Lithuania); Haverkamp, Uwe [Dept. of Radiology, Clemenshospital, Muenster (Germany); Popov, Sergey [Dept. of Radiotherapy, Riga Eastern Hospital, Latvian Oncology Center, Riga (Latvia); Prott, Franz-Josef [Inst. of Radiology and Radiotherapy (RNS), St. Josefs Hospital, Wiesbaden (Germany)

    2009-11-15

    Purpose: to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). Patients and methods: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. Results: no acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% ({chi}{sup 2}-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). Conclusion: in this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term. (orig.)

  2. Acute Neurobehavorial Toxicity of Flame Retardant Replacement Compounds in Zebrafish Larvae

    As polybrominated diphenyl ethers (PBDEs) are phased out, numerous compounds areemerging as potential replacement flame retardants for use in consumer and electronicproducts. Little is known, however, about the neurobehavioral toxicity of thesereplacements. This study evaluated t...

  3. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation

    HUMBERTO M. BARBOSA

    Full Text Available ABSTRACT Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C and animal treated single doses of 300mg/Kg (EEStb300 or 2.000mg/kg body weight (ESStb2.000 of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml−1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  4. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation.

    Barbosa, Humberto M; Nascimento, Jailson N DO; Araújo, Thiago A S; Duarte, Filipe S; Albuquerque, Ulysses P; Vieira, Jeymesson R C; Santana, Edson R B DE; Yara, Ricardo; Lima, Cláudia S A; Gomes, Dayane A; Lira, Eduardo C

    2016-01-01

    Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb) in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C) and animal treated single doses of 300mg/Kg (EEStb300) or 2.000mg/kg body weight (ESStb2.000) of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml-1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  5. Acute toxicity of the pesticide methomyl on the topmouth gudgeon (Pseudorasbora parva): mortality and effects on four biomarkers.

    Li, Huixian; Jiang, Hui; Gao, Xiwu; Wang, Xiaojun; Qu, Weigang; Lin, Ronghua; Chen, Jiao

    2008-09-01

    In this study, the acute toxicity of the pesticide methomyl on the topmouth gudgeon (Pseudorasbora parva) was evaluated using mortality and the activity of the enzymes acetylcholinesterase (AChE), glutathione S-transferases (GSTs), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as endpoints. LC50 values were 1.228, 0.782, 0.538, and 0.425 mg/l at 24, 48, 72, and 96 h of exposure, respectively. Methomyl caused a sharp decrease in specific activity of brain AChE around 48% at concentrations between 0.043 and 0.213 mg/l. A reduction higher than 40% in liver GST activity at concentrations between 0.085 and 0.213 mg/l was found, whereas no significant effects were observed in intestinal GST. A significant concentration-dependent decrease of GOT activity was found after 24 h of exposure to the pesticide but not after 96 h. No significant effects on GPT activity were observed. These results indicate that at the concentrations tested, methomyl is acutely toxic to the species P. parva, causing mortality, neurotoxic effects, and changes in some hepatic enzymes.

  6. Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

    Paixão, S M; Anselmo, A M

    2002-01-01

    The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems.

  7. Platelets can neutralize hydrogen peroxide in an acute toxicity model with cells involved in granulation tissue formation.

    Kandler, Barbara; Maitz, Philipp; Fischer, Michael B; Watzek, Georg; Gruber, Reinhard

    2005-04-01

    Platelets play a key role in the replacement of the blood clot with granulation tissue during the early steps of bone regeneration. We hypothesized that activated platelets can neutralize locally produced reactive oxygen species, thereby protecting cells involved in granulation tissue formation. The potential of platelet-released supernatant (PRS) to neutralize hydrogen peroxide (H(2)O(2)) was tested in an acute toxicity model with osteogenic, inflammatory, and endothelial cells. In the human fetal osteoblastic cell line 1.19 (hFOB), considerable morphological changes, cell shedding, and dysfunction of the respiratory chain were observed when cells were exposed to 3 mM H(2)O(2). Caspase-3 and poly-(ADP-ribose)-polymerase were not activated, suggesting that cell death occurred by necrosis. Preincubation of osteogenic cells, leukocytes, or endothelial cells with PRS decreased the acute toxicity of H(2)O(2). The capacity of platelets to release H(2)O(2)-detoxifying activity was retained for up to 72 h. Aminotriazole, an inhibitor of catalase, decreased the cytoprotective activity of PRS, whereas blocking of glutathione peroxidase by mercaptosuccinate had no effect. These results suggest that platelet-released catalase can rapidly neutralize cytotoxic amounts of H(2)O(2), a process that may play a role during the early stages of bone regeneration.

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

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

    2016-02-13

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

  9. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    Zhu, Liye; Yu, Tao; Qi, Xiaozhe; Gao, Jing; Huang, Kunlun; He, Xiaoyun; Luo, Haoshu; Xu, Wentao

    2016-01-01

    Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD) and livers (SOD and GSH). DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model. PMID:27983637

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

    María Guadalupe Prado-Ochoa

    2014-01-01

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

  11. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    Liye Zhu

    2016-12-01

    Full Text Available Ochratoxin A (OTA displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD and livers (SOD and GSH. DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

  12. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  13. Substitution of methotrexate with corticosteroid for acute graft-versus-host disease prevention in transplanted patients who develop methotrexate toxicity.

    Kim, Sung-Yong; Kim, Ah Ran; Yoon, So Young; Cho, Yo-Han; Lee, Mark Hong

    2016-02-01

    Methotrexate (MTX) toxicity can hamper the administration of all planned doses in acute graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic stem cell transplantation. Reduction or omission of MTX doses results in an increased risk of acute GVHD. In this prospective observational study, we compared the incidence of GVHD and the transplant outcomes between patients who received the full treatment course of MTX (group 1), patients in whom MTX doses were omitted if MTX toxicity developed (group 2), and patients receiving corticosteroid instead of MTX if MTX toxicity developed (group 3). The cumulative incidence of grades II-IV acute GVHD at 100 days post-transplantation was 22.2 % in group 1, 43.6 % in group 2, and 25.0 % in group 3 (P = 0.132). The risk of grades II-IV acute GVHD in group 2 was higher than that in group 1 (hazard ratio (HR) 3.262, P = 0.016), but the risk in group 3 was similar to that in group 1 (HR 0.960, P = 0.890). Group 3 also showed a trend towards a lower risk of chronic GVHD compared to the other groups. The cumulative risk of chronic GVHD at 2 years was 73.9, 71.6, and 33.3 % in groups 1, 2, and 3, respectively (P = 0.084). However, a likely higher relapse incidence and infection-related mortality in group 3 produced a trend towards the lowest relapse-free survival (2-year RFS, 46.3, 49.3, and 25.0 % in groups 1, 2, and 3, respectively; P = 0.329) and overall survival (2-year OS, 45, 52.3, and 25 %, respectively; P = 0.322) in group 3. Although the substitution of MTX with corticosteroid ameliorates the increased risk of GVHD in patients in which it is imperative to omit its dose, its negative impact on relapse and infection risk does not result in favorable transplant outcomes.

  14. Acute sensitivity of a broad range of freshwater mussels to chemicals with different modes of toxic action.

    Wang, Ning; Ivey, Christopher D; Ingersoll, Christopher G; Brumbaugh, William G; Alvarez, David; Hammer, Edward J; Bauer, Candice R; Augspurger, Tom; Raimondo, Sandy; Barnhart, M Christopher

    2017-03-01

    Freshwater mussels, one of the most imperiled groups of animals in the world, are generally underrepresented in toxicity databases used for the development of ambient water quality criteria and other environmental guidance values. Acute 96-h toxicity tests were conducted to evaluate the sensitivity of 5 species of juvenile mussels from 2 families and 4 tribes to 10 chemicals (ammonia, metals, major ions, and organic compounds) and to screen 10 additional chemicals (mainly organic compounds) with a commonly tested mussel species, fatmucket (Lampsilis siliquoidea). In the multi-species study, median effect concentrations (EC50s) among the 5 species differed by a factor of ≤2 for chloride, potassium, sulfate, and zinc; a factor of ≤5 for ammonia, chromium, copper, and nickel; and factors of 6 and 12 for metolachlor and alachlor, respectively, indicating that mussels representing different families or tribes had similar sensitivity to most of the tested chemicals, regardless of modes of action. There was a strong linear relationship between EC50s for fatmucket and the other 4 mussel species across the 10 chemicals (r(2)  = 0.97, slope close to 1.0), indicating that fatmucket was similar to other mussel species; thus, this commonly tested species can be a good surrogate for protecting other mussels in acute exposures. The sensitivity of juvenile fatmucket among different populations or cultured from larvae of wild adults and captive-cultured adults was also similar in acute exposures to copper or chloride, indicating captive-cultured adult mussels can reliably be used to reproduce juveniles for toxicity testing. In compiled databases for all freshwater species, 1 or more mussel species were among the 4 most sensitive species for alachlor, ammonia, chloride, potassium, sulfate, copper, nickel, and zinc; therefore, the development of water quality criteria and other environmental guidance values for these chemicals should reflect the sensitivity of mussels. In

  15. Acute sensitivity of a broad range of freshwater mussels to chemicals with different modes of toxic action

    Wang, Ning; Ivey, Chris D.; Ingersoll, Christopher G.; Brumbaugh, William G.; Alvarez, David; Hammer, Edward J.; Bauer, Candice R.; Augspurger, Tom; Raimondo, Sandy; Barnhart, M.Christopher

    2017-01-01

    Freshwater mussels, one of the most imperiled groups of animals in the world, are generally underrepresented in toxicity databases used for the development of ambient water quality criteria and other environmental guidance values. Acute 96-h toxicity tests were conducted to evaluate the sensitivity of 5 species of juvenile mussels from 2 families and 4 tribes to 10 chemicals (ammonia, metals, major ions, and organic compounds) and to screen 10 additional chemicals (mainly organic compounds) with a commonly tested mussel species, fatmucket (Lampsilis siliquoidea). In the multi-species study, median effect concentrations (EC50s) among the 5 species differed by a factor of ≤2 for chloride, potassium, sulfate, and zinc; a factor of ≤5 for ammonia, chromium, copper, and nickel; and factors of 6 and 12 for metolachlor and alachlor, respectively, indicating that mussels representing different families or tribes had similar sensitivity to most of the tested chemicals, regardless of modes of action. There was a strong linear relationship between EC50s for fatmucket and the other 4 mussel species across the 10 chemicals (r2 = 0.97, slope close to 1.0), indicating that fatmucket was similar to other mussel species; thus, this commonly tested species can be a good surrogate for protecting other mussels in acute exposures. The sensitivity of juvenile fatmucket among different populations or cultured from larvae of wild adults and captive-cultured adults was also similar in acute exposures to copper or chloride, indicating captive-cultured adult mussels can reliably be used to reproduce juveniles for toxicity testing. In compiled databases for all freshwater species, 1 or more mussel species were among the 4 most sensitive species for alachlor, ammonia, chloride, potassium, sulfate, copper, nickel, and zinc; therefore, the development of water quality criteria and other environmental guidance values for these chemicals should reflect the sensitivity of mussels. In

  16. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  17. Acute toxicity and environmental risk of teflubenzuron to Daphnia magna, Poecilia reticulata and Lemna minor in the absence and presence of sediment.

    Medeiros, Louise S; Souza, Jaqueline P; Winkaler, Elissandra U; Carraschi, Silvia P; Cruz, Claudinei; Souza-Júnior, Severino C; Machado-Neto, Joaquim G

    2013-01-01

    This study aimed to estimate the acute toxicity of teflubenzuron (1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea) (TFB) for Daphnia magna, Lemna minor and Poecilia reticulata, in the absence and presence of sediment; evaluate the effect of sediment on the TFB bioavailability; and to classify this insecticide according to its environmental poisoning risk for agricultural and aquaculture uses. The tests of TFB acute toxicity were conducted in static system in a completely randomized design with increasing TFB concentrations, and a control group. The TFB has been classified according to the estimated values of EC50 and LC50 by its acute toxicity and environmental risk. The sediment significantly reduced toxicity and bioavailability of TFB in water column. Therefore, the insecticide can be classified as being highly toxic to Daphnia magna, which means the agricultural and aquacultural uses of TFB pose a high risk of environmental toxicity to non-target organisms. However, it was practically non-toxic to L. minor and P. reticulata.

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

    辛玲歌

    2014-01-01

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

  19. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  20. Acute toxicity and vascular properties of seed of Parkia biglobosa (JACQ) R. Br Gift (Mimosaceae) on rat aorta.

    Ouédraogo, Sylvin; Somé, Noya; Ouattara, Sounkalo; Kini, Félix B; Traore, Aristide; Bucher, Bernard; Guissou, I Pierre

    2012-01-01

    The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD50) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1-10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC50 values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1-4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10⁻⁵M), and not by L-NAME (310⁻⁴M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.

  1. Comparison of the acute toxicity for gamma-cyhalothrin and lambda-cyhalothrin to zebra fish and shrimp.

    Wang, Wei; Cai, D J; Shan, Z J; Chen, W L; Poletika, Nick; Gao, X W

    2007-03-01

    Gamma-cyhalothrin 15CS (GCH) contains only the active stereoisomer of the two isomers found in lambda-cyhalothrin 25EW (LCH). GCH (0.5 x rate) provides equivalent overall insect control as LCH (1 x rate). Both formulations showed high acute toxicity to zebra fish (Brachydanio rerio H.B.) and shrimp (Macrobrachium nippoensis de Haan). The 96-h LC(50(zebra fish,GCH)) is 1.93 microg a.i/L and LC(50(zebra fish,LCH)) is 1.94 microg a.i/L. LC(50(shrimp,GCH)) is 0.28 microg a.i./L and LC(50(shrimp,LCH)) 0.04 microg a.i./L. This indicates that the toxicity to shrimp is likely stereochemistry-dependent. The fates of GCH and LCH are similar in laboratory simulated rice paddy water and their concentrations decrease rapidly, with no GCH or LCH detected after 3 or 4 days. Both are toxic to shrimp in a simulated paddy irrigation reservoir even though treated return water is diluted 5 times. No shrimp fatality is shown in the GCH-treated paddy water after a 4-day holding period, and longer than 5 days is necessary to reach a zero fatality rate for LCH. This is compatible with the 7-day water holding period considered reasonable in agricultural practice.

  2. Acute toxicity of arsenic and oxidative stress responses in the embryonic development of the common South American toad Rhinella arenarum.

    Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Ferrari, Ana; Bongiovanni, Guillermina Azucena; Venturino, Andrés

    2015-05-01

    Arsenic (As), a natural element of ecological relevance, is found in natural water sources throughout Argentina in concentrations between 0.01 mg/L and 15 mg/L. The autochthonous toad Rhinella arenarum was selected to study the acute toxicity of As and the biochemical responses elicited by the exposure to As in water during its embryonic development. The median lethal concentration (LC50) value averaged 24.3 mg/L As and remained constant along the embryonic development. However, As toxicity drastically decreased when embryos were exposed from heartbeat-stage on day 4 of development, suggesting the onset of detoxification mechanisms. Given the environmental concentrations of As in Argentina, there is a probability of exceeding lethal levels at 1% of sites. Arsenic at sublethal concentrations caused a significant decrease in the total antioxidant potential but generated an increase in endogenous glutathione (GSH) content and glutathione S-transferase (GST) activity. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with GSH for its excretion. The authors conclude that toad embryos are more sensitive to As during early developmental stages and that relatively high concentrations of this toxic element are required to elicit mortality, but oxidative stress may be an adverse effect at sublethal concentrations.

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

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

    2009-09-01

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

  4. A comparative study on the relationship between acetylcholinesterase activity and acute toxicity in Daphnia magna exposed to anticholinesterase insecticides.

    Printes, Liane Biehl; Callaghan, Amanda

    2004-05-01

    Acetylcholinesterase (AChE) activity was measured in Daphnia magna that had been exposed to four organophosphates (OPs; parathion, chlorpyrifos, malathion, and acephate) and one carbamate (propoxur) for 48 h. These results were related to acute toxicity (median effective concentration [EC50] for immobility). For the four OPs, the EC50s were 7.03 pM, 3.17 pM, 10.56 pM, and 309.82 microM, respectively. The EC50 for propoxur was 449.90 pM. Reduction in AChE activity was directly related to an increase in immobility in all chemicals tested. However, the ratio between the EC50 and the AChE median inhibiting concentration ranged from 0.31 to 0.90. A 50% reduction in AChE activity generally was associated with detrimental effects on mobility. However, for acephate, high levels of AChE inhibition (70%) were observed in very low concentrations and were not associated with immobility. In addition, increasing the concentration of acephate further had a slight negative effect on AChE activity but a strong detrimental effect on mobility. Binding sites other than AChE possibly are involved in acephate toxicity to D. magna. Our findings demonstrate different associations between AChE inhibition and toxicity when different chemicals are compared. Therefore, the value of using AChE activity as a biomarker in D. magna will be dependent on the chemical tested.

  5. Acute toxicities of potassium permanganate, formalin, and Lugol's iodine solution to a marine ciliate, Pleuronema coronatum (ciliophora, scuticociliatida)

    Yantao, Qiu; Weibo, Song

    2002-10-01

    Acute toxicities of potassium permanganate, formalin, and Lugol’s iodine solution to a commonly occurred marine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of the results highlighted the close relationships between doses of the medicines and mortalities of the organisms, thus providing a capability to predict toxicity effects from the dose. Toxic effects of the medicines on the ciliates were described in the present paper, and the median lethal concentrations (LC50 values) were given. Results of measurements indicated that 2 h-LC50 and 12 h-LC50 values of formalin on P. coronatum were 59.00×10-6 and 43.57×10-6, while those of Lugol’s solutions were 90.13 and 67.84×10-6 respectively. The tolerance of P. coronatum to formalin is apparently lower than that to Lugol’s iodine solution and potassium permanganate is a suitable medicine to kill ciliates in short time.

  6. Acute Toxicities of Potassium Permanganate, Formalin, and Lugol's Iodine Solution to a Marine Ciliate,Pleuronema coronatum ( Ciliophora, Scuticociliatida)

    QIU Yantao; SONG Weibo

    2002-01-01

    Acute toxicities of potassium permanganate, formalin, and Lugol's iodine solution to a commonly occurred ma-rine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of the resultshighlighted the close relationships between doses of the medicines and mortalities of the organisms, thus providing a capabili-ty to predict toxicity effects from the dose. Toxic effects of the medicines on the ciliates were described in the present paper,and the median lethal concentrations (LC50 values) were given. Results of measurements indicated that 2 h-LC50 and 12 h-LC50 values of formalin on P. coronatum were 59.00 × 10-6 and 43.57 × 10 6, while those of Lugol's solutions were 90.13 and67.84 × 10 6 respectively. The tolerance of P. coronatum to formalin is apparently lower than that to Lugol' s iodine solutionand potassium permanganate is a suitable medicine to kill ciliates in short time.

  7. Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol.

    Franca, R; Rebora, P; Bertorello, N; Fagioli, F; Conter, V; Biondi, A; Colombini, A; Micalizzi, C; Zecca, M; Parasole, R; Petruzziello, F; Basso, G; Putti, M C; Locatelli, F; d'Adamo, P; Valsecchi, M G; Decorti, G; Rabusin, M

    2017-01-01

    Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.

  8. A Case of Anti-NMDA Receptor Encephalitis Treated with ECT.

    Jones, Kristin C; Schwartz, Ann C; Hermida, Adriana P; Kahn, David A

    2015-09-01

    We describe the case of a 17-year-old male who presented with acute onset of seizures and malignant catatonia with psychosis, agitation, and hypermetabolism, who responded to electroconvulsive therapy (ECT). Soon after he began to respond, he was diagnosed with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis and then given immunosuppressive therapy. Anti-NMDA receptor encephalitis is an increasingly recognized autoimmune disorder that often presents with neuropsychiatric symptoms. The mainstays for treatment have been early diagnosis, tumor work-up and removal if found, and initiation of immunosuppressive therapy. Treatment response is often slow and residual symptoms common. In this case, ECT produced clinical stabilization before the underlying diagnosis of anti-NMDA receptor encephalitis was made and standard treatment initiated. We suggest that ECT may be highly beneficial for stabilizing life-threatening neuropsychiatric symptoms in this syndrome and should be considered as a potentially additive treatment to immunotherapy when rapid relief is sought.

  9. Acute toxicity of butachlor and atrazine to freshwater green alga Scenedesmus obliquus and cladoceran Daphnia carinata.

    He, Hongzhi; Yu, Jing; Chen, Guikui; Li, Wenyang; He, Jinbo; Li, Huashou

    2012-06-01

    Both single and joint toxicity of atrazine and butachlor to freshwater green alga Scenedesmus obliquus and cladoceran Daphnia carinata isolated from South China were investigated in the present study. The 96 h-EC(50) values of atrazine and butachlor to S. obliquus were 0.0147 and 2.31 mg L(-1), while the 48 h-LC(50) values to D. carinata were 60.6 and 3.40 mg L(-1), respectively. These results suggest that atrazine could be highly toxic to S. obliquus and slightly toxic to D. carinata, while butachlor exhibits moderate toxicity to both organisms. The additive indexes of atrazine and butachlor mixtures were -2.68 (-3.02 to -2.32) to S. obliquus and 0.054 (-0.025 to 0.238) to D. carinata, respectively. Therefore, the joint action of two herbicides was significant antagonism to S. obliquus, while significant synergism was not shown to D. carinata. Moreover, significant linear correlation between the natural logarithm of herbicide concentrations and growth rates of alga S. obliquus was observed. Taken together, it is the first study reporting the toxicity endpoints for mixture of atrazine and butachlor against S. obliquus and D. carinata isolated from south China. The present results would be helpful to provide data to assess the ecological risk of both herbicides to aquatic organisms.

  10. Can Artemia Hatching Assay Be a (Sensitive) Alternative Tool to Acute Toxicity Test?

    Rotini, A; Manfra, L; Canepa, S; Tornambè, A; Migliore, L

    2015-12-01

    Artemia sp. is extensively used in ecotoxicity testing, despite criticisms inherent to both acute and long-term tests. Alternative endpoints and procedures should be considered to support the use of this biological model. The hatching process comprises several developmental steps and the cyst hatchability seems acceptable as endpoint criterion. In this study, we assessed the reliability of the hatching assay on A. franciscana by comparing with acute and long-term mortality tests, using two chemicals: Diethylene Glycol (DEG), Sodium Dodecyl Sulphate (SDS). Both DEG and SDS tests demonstrated a dose dependent hatching inhibition. The hatching test resulted more sensitive than acute mortality test and less sensitive than the long-term one. Results demonstrate the reliability and high sensitivity of this hatching assay on a short time lag and support its useful application in first-tier risk assessment procedures.

  11. Colon-derived uremic biomarkers induced by the acute toxicity of Ka