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Sample records for acute toxic response

  1. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: Acute toxicity, tumor response, and sphincter preservation

    Purpose: To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control. Methods and Materials: Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. Results: Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a

  2. The value of acute toxicity testing of pharmaceuticals for estimation of human response.

    Barle, Ester Lovšin; Looser, Roland; Cerne, Manica; Bechter, Rudolf

    2012-04-01

    The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID:22306828

  3. Acute toxicity, biochemical and histopathological responses of endosulfan in Chanos chanos.

    Kumar, Neeraj; Ambasankar, K; Krishnani, K K; Gupta, S K; Bhushan, Shashi; Minhas, P S

    2016-09-01

    This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile. PMID:27213563

  4. Acute toxicity of eight oil spill response chemicals to temperate, boreal, and Arctic species.

    Hansen, Bjørn Henrik; Altin, Dag; Bonaunet, Kristin; Overjordet, Ida Beathe

    2014-01-01

    The objectives of this study were to (1) determine the acute toxicity of selected shoreline washing agents (SWA) and dispersants, and (2) assess interspecies differences in sensitivity to the products. Eight shoreline washing agents (Hela saneringsvæske, Bios, Bioversal, Absorrep K212, and Corexit 9580) and chemical dispersants (Corexit 9500, Dasic NS, and Gamlen OD4000) were tested on five marine species, algae Skeletonema costatum, planktonic copepod species Acartia tonsa (temperate species), Calanus finmarchicus (boreal species) and Calanus glacialis (Arctic species), and benthic amphipod Corophium volutator. For most products, A. tonsa was the most sensitive species, whereas C. volutator was the least sensitive; however, these species were exposed through different media (water/sediment). In general, all copepod species displayed a relatively similar sensitivity to all products. However, A. tonsa was somewhat more sensitive than other copepods to most of the tested products. Thus, A. tonsa appears to be a candidate species for boreal and Arctic copepods for acute toxicity testing, and data generated on this species may be used as to provide conservative estimates. The benthic species (C. volutator) had a different sensitivity pattern relative to pelagic species, displaying higher sensitivity to solvent-based SWA than to water-based SWA. Comparing product toxicity, the dispersants were in general most toxic while the solvent-based SWA were least toxic to pelagic species. PMID:24754387

  5. Acute Methylenedioxypyrovalerone Toxicity.

    Froberg, Blake A; Levine, Michael; Beuhler, Michael C; Judge, Bryan S; Moore, Philip W; Engebretsen, Kristin M; Mckeown, Nathanael J; Rosenbaum, Christopher D; Young, Amy C; Rusyniak, Daniel E

    2015-06-01

    The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation. PMID:25468313

  6. Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response

    To investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2-resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+). From November 2009, all patients with MSGT treated with carbon ion therapy were evaluated. Acute side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable. 103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC°III toxicity. Rates of CTC°III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up. 47 patients showed good treatment responses (CR/PR) according to RECIST. Acute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2-resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control

  7. Plant-derived compounds: acute toxicity, synergism, and effects on insect enzyme activity and flight motor responses.

    Waliwitiya, Ranil

    2011-01-01

    Botanical extracts may contain compounds that have insecticidal properties that may be developed as inexpensive insecticides. In this thesis, I used a series of techniques to identify the acute toxicities and modes of action of plant-derived compounds against the Yellow Fever mosquito Aedes aegypti and the blowfly Phaenicia sericata. Initially I evaluated the acute toxicity of 16 phytochemicals on aquatic and terrestrial insects alone or with the synergist piperonyl butoxide (PBO) to quantify...

  8. Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

    Appelt, Ane L.; Bentzen, Søren M.; Jakobsen, Anders;

    2015-01-01

    radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above...

  9. Acute and chronic arsenic toxicity

    Ratnaike, R.

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

  10. Acute toxicity of carbamazepine to juvenile rainbow trout (Oncorhynchus mykiss): effects on antioxidant responses, hematological parameters and hepatic EROD.

    Li, Zhi-Hua; Zlabek, Vladimir; Velisek, Josef; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2011-03-01

    Awareness of residual pharmaceutically active compounds (PhACs) in the aquatic environment is growing as investigations into these pollutants are increasing and analytical detection techniques are improving. However, the toxicological effects of PhACs have not been adequately researched. In this study, the toxic effects of carbamazepine (CBZ), an anticonvulsant drug commonly present in surface and groundwater, was studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute semi-static bioassay. Blood parameters, liver xenobiotic-metabolizing response and tissue antioxidant status were evaluated. Compared to the control group, fish exposed to CBZ (96 h LC50) showed significantly higher Er, Hb, MCHC, monocytes, neutrophil granulocytes and plasma enzymes activity, and significantly lower MCV and lymphocytes. CF and HSI were not significantly different among groups such as hepatic EROD. SOD, CAT, GPx and GR activity was significantly higher in liver of experimental groups, but decreased significantly in brain and gill. In general, antioxidant enzyme activity in intestine and muscle was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill and brain, despite a trend to increased values were manifested in the remaining tissues. In short, CBZ-induced stress responses in different tissues were reflected in the oxidant stress indices and hematological parameters. However, before those parameters are used as special biomarkers for monitoring residual pharmaceuticals in aquatic environment, more detailed experiments in laboratory need to be performed in the future. PMID:20971511

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

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

    2013-09-15

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

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

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

  13. 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).

  14. Acute toxicity of oil sands wastewater: A toxic balance

    A study was conducted to identify and determine the relative importance of the acutely toxic fractions of wastewater from oil sands extraction using a bioassay directed toxicity identification evaluation (TIE), to use these data to construct a toxic balance, and to determine whether the same fractions were acutely toxic to Microtox, Daphnia, and rainbow trout. Samples of extraction wastewater were obtained from the Mildred Lake tailings pond in Alberta during summer 1991 and 1992. The samples were centrifuged to remove suspended solids and the toxicity of the supernatant was evaluated. Seven manipulations, each of which was designed to remove a different class of compounds, was performed on the supernatant samples. A complete TIE was performed using the Microtox bacterial bioassay. All acute toxicity of the surface tailings pond water to Microtox was removed by precipitation of organic acids or by removal of nonpolar organics. These results suggest that the main toxic fraction was a surfactant. In the interstitial water of the fine tails, volatiles accounted for 15% of the acute toxicity. However, all the acute toxicity of interstitial water was removed by precipitation of organic acids or by removal of nonpolar organics. Organic acids accounted for all the acute toxicity of tailings pond water to Daphnia and rainbow trout. Differences in relative sensitivity of test organisms to the toxic fraction demonstrate the importance of using more than one test organism to evaluate acute toxicity. Daphnia was 0.4 times less sensitive and rainbow trout 3 times more sensitive than Microtox. 20 refs., 6 tabs

  15. Acute toxicity of methyl isocyanate: a preliminary study of the dose response for eye and other effects.

    Salmon, A G; Kerr Muir, M; Andersson, N

    1985-12-01

    Acute toxic effects of methyl isocyanate in the rat were determined for two hour exposures to concentrations in the range 11 ppm (very slight effect) to 65 ppm (lethality: pulmonary oedema). Changes in the eye, lungs, and behaviour were noted. Eye changes were confined to erosions of the corneal epithelium and were most severe at intermediate levels of exposure. A comparison was made of the effects noted in rats with reported effects on survivors of the Bhopal disaster. Urinary thiocyanate concentrations in exposed rats were found to be reduced relative to control values. PMID:4074650

  16. Acute toxicity of gasoline and some additives.

    Reese, E.; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these ch...

  17. ACUTE AND SUBCHRONIC TOXICITY OF MULBERRY FRUITS

    Jintanaporn Wattanathorn

    2012-01-01

    Full Text Available At present, the application of phytomedicine worldwide is substantial increase. The data of the acute and subchronic toxicity studies on medicinal plants or fruits and vegetables used for medicinal purposes should be obtained in order to increase the confidence in its safety to human, particularly for the application as functional food. Despite the widely consumption of mulberry (Morus alba L, Maraceae family fruits both as fruit and as medicine, no systematic evaluation of the toxicity of mulberry fruits is available until now. This study aimed to determine the acute and subchronic oral toxicities of mulberry fruits in male and female Wistar rats. A single acute mulberry fruits extract dose of 2000 mg kg-1 dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 2, 10 and 500 mg kg-1 day-1 were also administered the same way for 90 days. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights and histopathological examinations. In addition, we also examined hematological and clinical chemistry values. The results showed no abnormalities in treated groups as compared to the controls. Although significantly different BUN and glucose were also observed, all of the values were within normal limits. Neither gross abnormalities nor histopathological changes were observed. The results suggest that mulberry fruits do not produce acute or subchronic toxicity in either female or male rats. Therefore mulberry fruits have the potential to be use as functional food. However, a chronic toxicity study should be further carried out to assure the safety for repetitive administration of this fruit before the application of functional food.

  18. Mechanisms of acute cocaine toxicity

    Heard, Kennon; Palmer, Robert; Zahniser, Nancy R.

    2008-01-01

    Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporters, neurotransmitter receptors and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine an...

  19. 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.

  20. Acute and subchronic toxicity of sucralose.

    Goldsmith, L A

    2000-01-01

    The toxicity of sucralose has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female mice and male rats documented no deaths or treatment-related signs at doses of 16g/kg for mice and 10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8 weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794-6406. There were no toxicologically significant effects observed at the 1.0% or 2.5% dietary levels. However, decreases in food consumption, body weight gain and selected organ weights and ratios as well as splenic and thymic histopathologic changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and female rats for 26 weeks investigated further the observations from the dietary study as well as general subchronic toxicity. The gavage study documented no sucralose-related toxicity. These results implicate the reduced palatability and digestibility of diets containing high concentrations of sucralose seen in the diet study as the cause for the decreased food consumption and other accompanying alterations. Dose selection for chronic toxicity studies in rats took into consideration the effect of high concentrations of sucralose on digestion and food consumption and the limitations that would be imposed on subsequent studies. In male and female dogs, no sucralose-related adverse effects were observed following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving doses of approximately 90, 300 and 900mg/kg/day respectively. These studies establish that sucralose is non-toxic in rodents following acute oral administration. The rat no-observed-adverse-effect level ranged between 2.5 and 5.0% following subchronic dietary administration. A 3.0% dietary concentration equivalent to a dose of 900mg

  1. USE OF RESPIRATORY-CARDIOVASCULAR RESPONSES OF RAINBOW TROUT (SALMO GAIRDNERI) IN IDENTIFYING ACUTE TOXICITY SYNDROMES IN FISH: PART 3. POLAR NARCOTICS

    The physiological responses of rainbow trout to acutely lethal aqueous concentrations of the suspected polar narcotics phenol, 2,4,-dimethylphenol, aniline, 2-chloroaniline and 4-chloroaniline were examined. Visible signs of intoxication included tremors that progressed to whole-...

  2. 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

  3. 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

  4. Acute Toxic Myocarditis and Pulmonary Oedema Developing from Scorpion Sting

    Cem Sahin; Ethem Acar; Halil Beydilli; Kadir Ugur Mert; Fatih Akin; Ibrahim Altun

    2015-01-01

    The majority of scorpion stings are generally seen with a set of simple clinical findings, such as pain, oedema, numbness, and tenderness in the area of the sting. However, occasionally events, such as toxic myocarditis, acute heart failure, acute pulmonary oedema, and Acute Respiratory Distress Syndrome (ARDS), which occur in scorpion sting cases are a significant problem which determine mortality and morbidity. The case presented here was a 38-year-old man who developed acute toxic myocardi...

  5. 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.

  6. [Acute toxicity testing (LD50) of Chinese mineral drugs].

    Yue, W; Liu, W H; Wang, L F; Fu, S X; Li, Y S; Kong, Z K; Tang, Z X; Chen, Z L

    1989-02-01

    Acute toxicity and LD50 of 62 mineral drugs were determined by ig, ip or iv in mice, in order to provide some guidelines for safety in clinical use, as well as for pharmacological and toxicological studies. In the present investigation, the difference in the acute toxicity and LD50 between raw drugs and medicines prepared by roasting is explained. PMID:2506896

  7. 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.

  8. ACUTE TOXICITY STUDY FOR TINOSPORA CORDIFOLIA

    Shirish Sadashiv Pingale

    2011-05-01

    Full Text Available The aim of the present work is to examine acute toxicity studies for decoction of aerial parts (leaves and stem as well as whole plant powder of Tinospora cordifolia in the form of aqueous slurry as per OECD guidelines in Swiss mice weighing 35 to 45gm. The dose of 3, 5, 7 and 9 ml per kg body weight of decoction and 2, 4, 6 and 8 gm/kg body weight of the whole plant powder were administered orally. All the groups of animals were almost continuously observed for mortality and behavioral changes during first 24 hrs and then daily for a fortnight. The observations of behavioral changes and changes in body weight, food and water intake as well as cage side observations were reported. There was no abnormality observed in all groups. The decoction of fresh leaves and stem as well as whole plant powder have no any significant toxic effect in Swiss mice and the plant material was found to be nontoxic.

  9. Phenytoin toxicity presenting as acute meningo-encephalitis in children

    Vijay Gupta

    2011-01-01

    Full Text Available Phenytoin can produce significant dose-related toxicity because of its zero order pharmacokinetics and is an important issue in pediatric emergency medicine. It is important to differentiate phenytoin toxicity manifesting with symptoms like fever, vomiting, seizures, ataxia masquerading as acute meningo-encephalitic illness, more so at centers where facilities to measure serum phenytoin levels are not available. Here we describe two children with phenytoin toxicity, presenting to the emergency department with features suggestive of acute meningo-encephalitis.

  10. Acute oral toxicity test of chemical compounds in silkworms.

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

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. PMID:26971557

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

    Swapnil Chavan; Ran Friedman; Ian A. Nicholls

    2015-01-01

    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 7...

  12. ACUTE AND CHRONIC TOXICITY OF CHLORDANE TO FISH AND INVERTEBRATES

    The acute and chronic toxicity of technical chlordane to bluegill (Lepomis macrochirus), fathead minnow (Pimephales promelas), brook trout (Salvelinus fontinalis), Daphnia magna, Hyallela azteca, and Chironomus No. 51 were determined with flow-through conditions. The purpose was ...

  13. 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...

  14. A New Method for Determining Acute Toxicity in Animal Models

    Chinedu, Enegide; Arome, David; Ameh, Fidelis Solomon

    2013-01-01

    Background: The intake of pharmacological substances by man has solely increased and this may be in the form of food, medicines and beverages, other industrial and household products. These substances are capable of eliciting chronic and acute toxicity, which may be mild or severe, depending upon their nature. Acute toxicity is defined as the unwanted effect(s) that occurs either immediately or at a short time interval after a single or multiple administration of such substance within 24 hour...

  15. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO2 and by observing the disappearance of test substance with gas chromatography. Additional BOD5 and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population

  16. INFLAMMATION AND ACUTE PHASE RESPONSE

    Farah Aziz Khan

    2010-10-01

    Full Text Available Inflammation caused by infection takes place by the cooperative cascade of cytokines and leukocytes. Tumor necrosis factor, interlukin-1, and interlukin-6 play important roles as proinflammatory cytokines to mediate local inflammation and activate other inflammatory cells e.g. neutrophils, monocytes, and macrophages. At least 15 different low molecular weight cytokine are secreted by activated leukocytes and are responsible for triggering acute phase response in the form of fever, leukocytosis, increased secretion of adreno corticotropic hormones, and production of acute phase proteins. Acute phase proteins are produced in liver under the influence of cytokines, which through blood stream passes to the site of inflammation and kill the pathogens by opsonization and activating complement pathways. The changes in the concentrations of positive acute-phase proteins and negative acute-phase proteins are due to the changes in their production by liver. Three of the best known acute phase proteins are C-reactive protein, serum anyloid A, and haptoglobin. Some disease states are casually related to acute phase proteins. C-reactive protein mediated compliment activation has a key role in some forms of tissue alteration such as cardiac infarction. Elevated S amyloid A levels are seen in chronic arthritis and tuberculosis. Other acute phase proteins show more moderate rise, usually less than fivefold.

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

    Luciano Rezende Vilela; Lindisley Ferreira Gomides; Bruna Araújo David; Maísa Mota Antunes; Ariane Barros Diniz; Fabrício de Araújo Moreira; Gustavo Batista Menezes

    2015-01-01

    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 hyd...

  18. EURL ECVAM Recommendation on the Zebrafish Embryo Acute Toxicity Test Method (ZFET) for Acute Aquatic Toxicity Testing

    HALDER MARIA ELISABETH; GRIESINGER Claudius; AMCOFF SVEN PATRIK; ZUANG Valerie; Whelan, Maurice

    2014-01-01

    Acute fish toxicity testing is an important component of the environmental hazard assessment of chemicals. Since many years, (zebra-)fish embryo-based methods have been proposed as alternatives to the acute fish toxicity test carried out with juvenile or adult fish. On behalf of the Organisation for Economic Cooperation and Development (OECD), the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) coordinated during 2008-2012 the validation of the zebrafish em...

  19. Randomized clinical trial on seven-day-per-week continuous accelerated irradiation for patients with esophageal carcinoma:Preliminary report on tumor response and acute toxicity

    Su-Ping Sun; Ya-Zhou Liu; Tao Ye; Wen Zhang; Wen-Bin Shen; Jing-Lei Shi; Hai-Ting Xu; Wei-Dong Wang

    2006-01-01

    AIM: Tumor response and normal tissue toxicity of seven-day-per-week continuous accelerated irradiation (CAIR) for patients with esophageal carcinoma were evaluated and compared to conventional irradiation (CR).METHODS: Sixty patients with squamous cell carcinoma of the esophagus were randomized into two groups:the CAIR group (30 patients) and the CR group (30 pa(RT) with 2 Gy/fraction per day at 7 d/wk with a total dose of 50-70 Gy (average dose 64.2 Gy). The overall time of irradiation was 3.6-5.0 wk (average 4.6 wk). RT in the CR group was 2 Gy/fraction per day at 5 d/wk with a total dose of 40-70 Gy (average dose 61.7 Gy).The overall time of irradiation was 4.0-7.0 wk (average 6.4wk).RESULTS: The data showed that the immediate tumor response to RT was better in the CAIR group than in the CR group. Efficiency rates (CR plus PR) were 82.8%(24/29) and 58.6% (17/29), respectively (P = 0.047). In both groups the incidences of esophagitis and tracheitis were insignificant (P = 0.376, 0.959), and no patient received toxicity that could not be tolerated.CONCLUSION: CAIR shortens overall treatment time and is well tolerated by patients. It may be superior to CR in enhancing the local response of tumor, but its remote effect for esophageal carcinoma awaits further follow-up.

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

    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 effect. In a chronic toxicity test performed with PFHxA, mortality was observed at similar concentrations as in the acute toxicity test, indicating that toxicity did not increase with increasing exposure time. Effects on mortality, reproduction and population growth rate occurred at similar concentrations, indicating no specific effect of PFHxA on sublethal endpoints. C4–C6 chemistry is thus less hazardous to daphnids than C7–C8 chemistry. Yet, these compounds are persistent, hard to remove from the environment and production volumes are increasing. - Highlights: • This study provides toxicity data of newly used, shorter PFAAs and a fluoropolymer. • Capstone© P-620HS did not show a dose–response relationship. • PFHxA toxicity did not increase with increasing exposure time. • Acute toxicity to Daphnia magna decreased with decreasing carbon chain length. - Toxicity to Daphnia magna of perfluoroalkyl substances decreased with decreasing carbon chain length and did not increase with exposure time

  1. Acute toxicity of seeds of the sapodilla (Achras sapota L.).

    Singh, P D; Simon, W R; West, M E

    1984-01-01

    An aqueous extract of the sapodilla seed (Achras sapota L.) was acutely toxic to mice and rats (i.p. LD50 = 190 and 250 mg/kg, respectively) with symptoms of dyspnoea, apnoea and convulsions. Soxhlet extraction and chromatographic separation of the seed constituents yielded a brown amorphous solid containing saponin. This was heat-stable and toxic by the i.p. route (LD50 = 30-50 mg/kg) but non-toxic by the oral route in mice and rats. It is proposed that the toxicity of the sapodilla seed is due mainly to the saponin content. PMID:6719472

  2. 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.

  3. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  4. [Synthesis, structures, and acute toxicity of gossypol nonsymmetrical aldehyde derivatives].

    Tiliabaev, K Z; Kamaev, F G; Vypova, N L; Iuldashev, A M; Ibragimov, B T; Talipov, S A

    2010-01-01

    Nonsymmetrical aldehyde derivatives of gossypol, a yellow polyphenolic pigment of cottonseed, were synthesized by reactions with ammonia, aniline, 4-aminoantipyrine, and barbituric acid. Their structures were determined by UV spectrophotometry and IR and (1)H NMR spectroscopy methods. Their acute toxicities in white mice were compared with those of gossypol and the corresponding symmetrical analogues. It was demonstrated that in general, the fewer free aldehyde groups that contained the gossypol derivative, the lower its acute toxicity. Only in the case of a nonsymmetrical gossypol derivative bearing a 4-aminoantipyrine residue did we observe a deviation from the above correlation: its symmetrical counterpart was even more toxic, but still less toxic than gossypol. PMID:20644599

  5. INFLAMMATION AND ACUTE PHASE RESPONSE

    Farah Aziz Khan; Mohd Fareed Khan

    2010-01-01

    Inflammation caused by infection takes place by the cooperative cascade of cytokines and leukocytes. Tumor necrosis factor, interlukin-1, and interlukin-6 play important roles as proinflammatory cytokines to mediate local inflammation and activate other inflammatory cells e.g. neutrophils, monocytes, and macrophages. At least 15 different low molecular weight cytokine are secreted by activated leukocytes and are responsible for triggering acute phase response in the form of fever, leukocytosi...

  6. ACUTE ORAL TOXICITY OF MUCUNA PRURIENS IN SWISS ALBINO MICE

    Parekar Sushant Shahaji; Somkuwar Arju Parnu

    2011-01-01

    Mucuna pruriens, belonging to the botanical family Fabaceae, has been used in traditional Ayurvedic Indian medicine for various ailments including Parkinson’s disease. The current study reports the outcome of acute oral toxicity investigation of ethanolic extract of M. pruriens (whole plant) on Swiss albino mice. No mortalities or evidence of adverse effects have been observed in Swiss albino mice following acute oral administration of ethanolic extract of M. pruriens at the dose of 2000 mg/...

  7. ECVAM's ongoing activities in the area of acute oral toxicity.

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

    2009-12-01

    The 7th Amendment of the Cosmetics Directive (2003/15/EC) set up timelines for banning animal testing and marketing of cosmetic products and their ingredients tested on animals. For most of the human health effects, including acute toxicity, the deadline for these bans was in March 2009. Moreover, the new Regulation EC 1907/2006 on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) provided a strong impetus towards the application of alternative approaches to reduce the number of animals used for toxicological testing. Therefore, the European Centre for the Validation of Alternative Methods (ECVAM) is currently putting considerable effort into developing and validating alternative methods in the field of acute toxicity. The main activities in this area include: (1) the Integrated Project ACuteTox, funded by the European Commission's 6th Framework Programme in 2005 with the aim to develop and pre-validate a testing strategy to fully replace acute oral toxicity testing in vivo; (2) a follow-up validation study to assess the predictive capacity of the validated BALB/3T3 Neutral Red Uptake cytotoxicity assay to discriminate between toxic/hazardous (LD(50)2,000 mg/kg); (3) an approach to identify compounds with LD(50)>2,000 mg/kg using information from 28-days repeated dose toxicity studies. PMID:19591916

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

    Preeti Bagri; Vinod Kumar; Anil Kumar Sikka; Joginder Singh Punia

    2013-01-01

    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 ...

  9. ACUTE TOXICITY OF LEAD NITRATE ON FRESHWATER CRAB BARYTELPHUSA GUERINI

    DUBE, KAUSHAL V

    2012-01-01

    Industrial effluents contributing to aquatic pollution contain vast array of toxic substances including heavy metals.  Indiscriminate discharge of these wastes alters the quality of water and cause hazards to aquatic fauna including important members of food chain of man. Hence, in present investigation the freshwater crab, Barytelphusa guerini was exposed to acute toxicity of lead nitrate for 0, 24, 48, 72 and 96 hours exposure. The percentage mortality of crab was studied and the LC50 deter...

  10. Acute and subacute toxicity of 18F-FDG

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  11. Cytokines and the hepatic acute phase response

    Moshage, H

    1997-01-01

    The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncont

  12. 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

  13. Acute toxicity of pinnatoxins E, F and G to mice.

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  14. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    2010-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... minimize the need for animal testing, the Agency encourages the review of existing acute toxicity... need for further animal testing. (ii) Limit test. When data on structurally related chemicals...

  15. 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.

  16. ACUTE ORAL TOXICITY OF MUCUNA PRURIENS IN SWISS ALBINO MICE

    Parekar Sushant Shahaji

    2011-05-01

    Full Text Available Mucuna pruriens, belonging to the botanical family Fabaceae, has been used in traditional Ayurvedic Indian medicine for various ailments including Parkinson’s disease. The current study reports the outcome of acute oral toxicity investigation of ethanolic extract of M. pruriens (whole plant on Swiss albino mice. No mortalities or evidence of adverse effects have been observed in Swiss albino mice following acute oral administration of ethanolic extract of M. pruriens at the dose of 2000 mg/ kg. This is the first report on the acute oral toxicity of M. pruriens and thus the findings of this study provide scientific validation on the use of the M. pruriens as a medicine for treating various ailments.

  17. 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.

  18. Acute toxicity of 50 metals to Daphnia magna.

    Okamoto, Akira; Yamamuro, Masumi; Tatarazako, Norihisa

    2015-07-01

    Metals are essential for human life and physiological functions but may sometimes cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were Mo) were > 100,000 µg l(-1) ; and. 7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd adhered to the body of D. magna and physically retarded the movement of D. magna. These metals formed hydroxides after adjusting the pH. Therefore, here, we distinguished this physical effect from the physiological toxic effect. The acute toxicity results of 40 elements obtained in this study were not correlated with electronegativity. Similarly, the acute toxicity results of metals including the rare metals were also not correlated with first ionization energy, atomic weight, atomic number, covalent radius, atomic radius or ionic radius. PMID:25382633

  19. Acute and subacute toxicity of 18F-FDG

    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 18F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18F-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)

  20. Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    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. PMID:25999668

  1. 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.

  2. Acute toxicity of uranium hexafluoride, uranyl fluoride and hydrogen fluoride

    Uranium hexafluoride (UF6) released into the atmosphere will react rapidly with moisture in the air to form the hydrolysis products uranyl fluoride (UO2F2) and hydrogen fluoride (HF). Uranium compounds such as UF6 and UO2F2 exhibit both chemical toxicity and radiological effects, while HF exhibits only chemical toxicity. This paper describes the development of a methodology for assessing the human health consequences of a known acute exposure to a mixture of UF6, UO2F2, and HF. 4 refs., 2 figs., 5 tabs

  3. Acute Phase Response in Animals: A Review

    Cray, Carolyn; Zaias, Julia; Altman, Norman H

    2009-01-01

    The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins, an integral part of the acute phase response, have been a focus...

  4. Severe hypotension and hypothermia caused by acute ethanol toxicity

    Wilson, E; W. S. Waring

    2007-01-01

    This article reports the time course and clinical features of acute ethanol poisoning in an elderly man who had previously abstained from alcohol. Several hours after ingestion, severe hypotension and hypothermia developed, and the consciousness level was reduced. Supportive measures were sufficient to allow the patient's blood pressure and temperature to recover by 24 h post ingestion. The clinical manifestations of ethanol toxicity are often confounded by coexistent drug ingestion and varia...

  5. ACUTE TOXICITY STUDY OF TOMATO POMACE EXTRACT IN RODENT

    Wathita Phachonpai; Supaporn Muchimapura; Terdthai Tong-Un; Jintanaporn Wattanathorn; Wipawee Thukhammee; Chonlathip Thipkaew; Bungorn Sripanidkulchai; Panakaporn Wannanon

    2013-01-01

    Tomato and tomato products are considered to be healthy food for the human diet. Although tomatoes have been widely studied for their phenolic content, less emphasize has been laid on toxicological effect of this plant. Thus, the purpose of the present study is to determine the acute toxicity effect of Lycopersicon esculentum, or commonly known as tomato, was administered orally in the form of dried tomato pomace extract in vivo. Adult male rats were orally administrated single dose of 1000 a...

  6. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

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

    2012-01-01

    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 g...

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

    Wuen Yew Teoh; Kae Shin Sim; Jaime Stella Moses Richardson; Norhanom Abdul Wahab; See Ziau Hoe

    2013-01-01

    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 adenocarci...

  8. Evaluation of acute toxicity of babassu mesocarp in mice

    Elizabeth S. B. Barroqueiro; Fernanda S. B. Barroqueiro; Mayara T. Pinheiro; Márcia C. G. Maciel; Priscila S. Barcellos; Silva, Lucilene A.; Adelson de S. Lopes; Flávia R.F. Nascimento; Rosane N. M. Guerra

    2011-01-01

    The safety of babassu mesocarp (Orbignya phalerata Mart., Arecaceae), which exhibited anti-inflammatory and antithrombotic activities, was evaluated by determining the potential acute toxicity in mice. A lyophilized ethanol extract of babassu mesocarp (BME) was administered to C3H/HePas mice (10/group) in a single dose of 1000, 3000 and 5000 mg/kg, by gavage. General behavior adverse effects and mortality were determined for up to fourteen days. Selected biochemical parameters including gluco...

  9. 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.

  10. Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

    Wik, Anna; Dave, Göran

    2006-09-01

    Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment. PMID:16466775

  11. Evaluation of acute toxicity potential of water hyacinth leaves.

    Wu, Wenbiao; Guo, Xiaoguang; Huang, Mingliang

    2014-06-01

    Although higher protein yield per hectare of water hyacinth than that of soy, high protein content of its leaves and good essential amino acid pattern have been proven, its dietary toxicity for human or animal consumption has not yet been evaluated. Therefore, the acute toxicity of water hyacinth leaves has been evaluated by an animal feeding test. The concentrations of common toxic metals including cadmium, lead, platinum, palladium, tin, mercury, barium, silver, stibium and aluminum in the water hyacinth leaf powder (WHLP) used for the animal feeding test were within their maximum limits in food additives as reported by the World Health Organization. The median lethal dose (LD50) of WHLP was more than 16 g kg(-1) body weight. In the study, after feeding for 7 and 28 days, the body weight of all the mice increased. The results of hematological analysis, clinical biochemical analysis, histopathological evaluation, general dissection or investigations of internal organs, appearance and behavior observations did not indicate any adverse effects from the diet containing WHLP. It is therefore concluded that water hyacinth leaves are not acutely toxic. PMID:22933551

  12. 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.

  13. Acute and delayed toxicities of total body irradiation

    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

  14. Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

    2013-08-01

    The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. PMID:23606235

  15. Radiation therapy in prostate cancer: evaluation of acute toxicity

    Goals: The present work documents the increasing demand of curative intent radiation therapy (CIRT) for localized prostate cancer and assesses acute reactions caused by ionizing radiation to intrapelvic organs. Patients and methods: From January 1995 to December 2001, 166 patients with prostatic cancer received radiation therapy, 70% of them (n=116) with curative intent. Treatment was completed as planned in 108 patients: 55 with pelvic irradiation and prostatic boost (PRT), 42 with three-dimensional conformal radiotherapy (3DCRT), 10 with a permanent 125 I implant (IPI) and 1 with combined radiotherapy. Patients were classified as at high- or low-risk according to tumor volume, Gleason score, regional lymph node status and pretreatment specific prostatic antigen level. High-risk patients were assigned to PRT and low-risk patients to local treatment only (either 3DCRT or IPI). Mean doses were 46 Gy for pelvis and 73 Gy for prostate with PRT; 75 Gy with 3DCRT and 127 Gy with IPI and combined radiation therapy. Acute rectal toxicity (ART) and acute urinary toxicity (AUT) were assessed according to the RTOG scale. Statistical analysis was performed with Fischer's exact test. Results: The proportion of patients receiving CIRT increased from 46% (n=28) in 1995-1998 to 84% (n=88) in 1999-2001; p < 0.0001. No patient developed ART or AUT beyond degree 2. ART was lower with 3DCRT (71% degree 0 or 1) than with PRT (45% degree 0 or 1); p= 0.0134. No significant difference was found in AUT. Conclusions: In recent years the demand for CIRT has almost doubled, with a concomitant decrease in palliative radiotherapy. In high-risk patients, pelvic irradiation increased mild and moderate ART, without compromising their life quality. None of the techniques employed was associated with severe acute toxicity. (author)

  16. 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)

  17. 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

  18. Acute toxicity of inorganics associated with irrigation drainwater, singly and in mixtures, to endangered fish

    Two early life stages of three federally-endangered fish, Colorado squawfish (Ptychocheiluslucius), razorbacksucker (Xyrauchen texanus), and bonytail (Gila elegans) were exposed for 96 hours to copper, selenate, selenite, and zinc singly, and two mixtures of nine inorganics simulating environmental ratios in two tributaries, Ashley Creek and Stewart Lake outlet, of the Green River, Utah. Acute tests were conducted in a water quality simulating the Green River. Colorado squawfish larvae were consistently more sensitive to the four inorganics and two mixtures than the juveniles, whereas there was no consistent response between these two life stages for the other two species. There was no consistent difference in sensitivity to the inorganics among the three species. The toxicity of the two mixtures exhibited either additive or greater than additive toxicity to the fish. The primary toxic components in the mixtures were copper and zinc based on toxic units. Arsenate, boron, molybdenum, selenate, selenite, uranium, and vanadium contributed ≤ 10% of the summed toxic units for each mixture. Comparison of acute toxicity values, as the biological effects concentration, with measured environmental concentrations in the two tributaries produced margin of uncertainty values of 12 for the Ashley Creek mixture and 9 for the Stewart Lake outlet mixture. These low margins of uncertainty suggest that inorganics derived from irrigation activities may be adversely affecting endangered fish in the Green River

  19. Development of a biotic ligand model to predict the acute toxicity of cadmium to Daphnia pulex

    The goal of this study was to develop a biotic ligand model (BLM) to predict the acute toxicity of cadmium to Daphnia pulex. Organisms were cultured in moderately soft water and standard 48 h acute toxicity tests were used to determine EC50s in various water chemistries where the effects of Ca2+, Na+, Mg2+, Cl-, K+, pH, and two sources of natural organic matter (Suwannee River and Nordic Reservoir) were evaluated. Overall, toxicity responses were consistent with the free-ion activity model and the principles inherent in the BLM. Increases in Ca2+ resulted in higher EC50s, indicating that Cd2+ competes with Ca2+ for uptake at the biotic ligand. Similar cation competition effects were observed when Mg2+ was varied but with a less pronounced protective effect relative to Ca2+. Changes in Na+ and K+ concentrations had no significant effect on Cd toxicity. EC50 values did not change significantly when pH was adjusted over a range from 8.0 to 6.1. Additions of natural organic matter resulted in elevated dissolved organic carbon (DOC) concentrations that significantly reduced Cd bioavailability via complexation of Cd2+. An existing biotic ligand model (HydroQual BLM ver 2.2.3) was tested for its ability to predict acute Cd toxicity to D. pulex. Once the BLM was adjusted for the relatively sensitivity of D. pulex the protective effects of Ca and DOC could be predicted reasonably well but other test chemistries did not match with measured EC50s. Binding constants derived from the test results were used to develop a modified BLM for the effects of Cd on D. pulex that accounted for the moderating effect of Ca and Mg on acute toxicity but overestimated the protective effect of DOC.

  20. Development of a biotic ligand model to predict the acute toxicity of cadmium to Daphnia pulex

    Clifford, Matthew [Department of Biology, Wilfrid Laurier University, Waterloo, ON N2L 3C5 (Canada); McGeer, James C., E-mail: jmcgeer@wlu.ca [Department of Biology, Wilfrid Laurier University, Waterloo, ON N2L 3C5 (Canada)

    2010-06-01

    The goal of this study was to develop a biotic ligand model (BLM) to predict the acute toxicity of cadmium to Daphnia pulex. Organisms were cultured in moderately soft water and standard 48 h acute toxicity tests were used to determine EC50s in various water chemistries where the effects of Ca{sup 2+}, Na{sup +}, Mg{sup 2+}, Cl{sup -}, K{sup +}, pH, and two sources of natural organic matter (Suwannee River and Nordic Reservoir) were evaluated. Overall, toxicity responses were consistent with the free-ion activity model and the principles inherent in the BLM. Increases in Ca{sup 2+} resulted in higher EC50s, indicating that Cd{sup 2+} competes with Ca{sup 2+} for uptake at the biotic ligand. Similar cation competition effects were observed when Mg{sup 2+} was varied but with a less pronounced protective effect relative to Ca{sup 2+}. Changes in Na{sup +} and K{sup +} concentrations had no significant effect on Cd toxicity. EC50 values did not change significantly when pH was adjusted over a range from 8.0 to 6.1. Additions of natural organic matter resulted in elevated dissolved organic carbon (DOC) concentrations that significantly reduced Cd bioavailability via complexation of Cd{sup 2+}. An existing biotic ligand model (HydroQual BLM ver 2.2.3) was tested for its ability to predict acute Cd toxicity to D. pulex. Once the BLM was adjusted for the relatively sensitivity of D. pulex the protective effects of Ca and DOC could be predicted reasonably well but other test chemistries did not match with measured EC50s. Binding constants derived from the test results were used to develop a modified BLM for the effects of Cd on D. pulex that accounted for the moderating effect of Ca and Mg on acute toxicity but overestimated the protective effect of DOC.

  1. 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.

  2. Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

    Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

    2011-11-01

    Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios. PMID:21789673

  3. 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.

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

    Teoh, Wuen Yew; Sim, Kae Shin; Moses Richardson, Jaime Stella; Abdul Wahab, Norhanom; Hoe, See Ziau

    2013-01-01

    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. PMID:24369485

  5. 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

  6. Transcriptomic responses of European flounder (Platichthys flesus) to model toxicants

    The temporal transcriptomic responses in liver of Platichthys flesus to model environmental pollutants were studied over a 16-day time span after intraperitoneal injection with cadmium chloride (50 μg/kg in saline), 3-methylcholanthrene (25 mg/kg in olive oil), Aroclor 1254 (50 mg/kg in olive oil), tert-butyl-hydroperoxide (5 mg/kg in saline), Lindane (25 mg/kg in olive oil), perfluoro-octanoic acid (100 mg/kg in olive oil) and their vehicles, olive oil (1 ml/kg) or saline (0.9%). Statistical, gene ontology and supervised analysis clearly demonstrated the progression from acute effects, biological responses to and recovery from the treatments. Key biological processes disturbed by the individual treatments were characterised by gene ontology analyses and individual toxicant-responsive genes and pathways were identified by supervised analyses. Responses to the polyaromatic and chlorinated aromatic compounds showed a degree of commonality but were distinguishable and they were clearly segregated from the responses to the pro-oxidants cadmium and the organic hydroperoxide, as well as from the peroxisomal proliferator, perfluoro-octanoic acid. This study demonstrated the utility of the microarray technique in the identification of toxicant-responsive genes and in discrimination between modes of toxicant action

  7. Assessing acute toxicities of pre- and post-treatment industrial wastewaters with Hydra attenuata: A comparative study of acute toxicity with the fathead minnow, Pimephales promelas

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. (E.I. DuPont de Nemours and Co., Newark, DE (United States). Haskell Lab. for Toxicology and Industrial Medicine)

    1994-04-01

    This study was undertaken to (a) determine wastewater treatment effectiveness using two freshwater organisms, (b) compare acute toxicity results from the two species exposed to the wastewaters, and (c) link acute and potential developmental toxicity of wastewaters in one organism. The acute toxicities of several pretreatment and post-treatment industrial waste-water samples wee evaluated with adult Hydra attenuata and fathead minnows. The acute LC50s agreed closely when results in Hydra attenuata were compared with those from fathead minnow tests. Acute LC50s ranged from 3 to >100% of samples with hydra, and from 1.0 to >100% of sample with fathead minnows. The results provided strong evidence of treatment effectiveness because toxicity decreased with progressive stages of treatment. Previously the Hydra Developmental Toxicity Assay was used as a prescreen mainly for in vitro assessment of developmental toxicity with pure compounds and to prioritized toxicants according to selective toxicity to the developing embryo. Recently the authors modified the assay for testing natural waters and wastewaters; hence, some of the wastewater samples also were tested for their developmental toxicity. In this case, the relative selective toxicity of these wastewater samples ranged from 0.7 to 2.1, indicating that no sample was uniquely toxic to the developing embryo, although acute toxicity was manifested. Overall, their results indicate the Hydra Assay functions appropriately in assessments of acute and developmental toxicity of industrial wastewaters and may be a simple and useful tool in a battery of tests for broader scale detection of environmental hazards.

  8. 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.

  9. A test of the additivity of acute toxicity of binary-metal mixtures of ni with Cd, Cu, and Zn to Daphnia magna, using the inflection point of the concentration-response curves.

    Traudt, Elizabeth M; Ranville, James F; Smith, Samantha A; Meyer, Joseph S

    2016-07-01

    Mixtures of metals are often present in surface waters, leading to toxicity that is difficult to predict. To provide data for development of multimetal toxicity models, Daphnia magna neonates were exposed to individual metals (Cd, Cu, Ni, Zn) and to binary combinations of those metals in standard 48-h lethality tests conducted in US Environmental Protection Agency moderately hard reconstituted water with 3 mg dissolved organic carbon (DOC)/L added as Suwannee River fulvic acid. Toxicity tests were performed with mixtures of Ni and 1) Cd, which is considerably more toxic than Ni; 2) Cu, which is less toxic than Cd but more toxic than Ni; and 3) Zn, which has a toxicity threshold similar to Ni. For each combination of metals in the binary mixtures, the concentration of 1 metal was held constant while the second metal was varied through a series that ranged from nonlethal to lethal concentrations; then the roles of the metals were reversed. Inflection points of the concentration-response curves were compared to test for additivity of toxicity. Sublethal concentrations of Ni caused less-than-additive toxicity with Cd, slightly less-than-additive toxicity with Zn, and greater-than-additive toxicity with Cu. One explanation of these results might be competition among the metals for binding to biological ligands and/or dissolved organic matter. Therefore, models might have to incorporate sometimes competing chemical interactions to accurately predict metal-mixture toxicity. Environ Toxicol Chem 2016;35:1843-1851. © 2015 SETAC. PMID:26681657

  10. 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. PMID:26256397

  11. Toxicity levels to humans during acute exposure to hydrogen fluoride

    A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

  12. 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.

  13. 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 ...

  14. ACUTE TOXICITY STUDY OF TOMATO POMACE EXTRACT IN RODENT

    Wathita Phachonpai

    2013-01-01

    Full Text Available Tomato and tomato products are considered to be healthy food for the human diet. Although tomatoes have been widely studied for their phenolic content, less emphasize has been laid on toxicological effect of this plant. Thus, the purpose of the present study is to determine the acute toxicity effect of Lycopersicon esculentum, or commonly known as tomato, was administered orally in the form of dried tomato pomace extract in vivo. Adult male rats were orally administrated single dose of 1000 and 5000 mg kg-1 dried tomato pomace extract. There were 10 rats in each group. All animals were sacrificed after 2 weeks of treatment. Seven parameters were tested: cage side observation, body weight gain measurement, food and water consumption, absolute organ weight, hematology, biochemical analysis and histopathology, to look for evidence of acute toxicity. No mortality was observed when varying doses of the extracts were administered per day for a period of 2 weeks. There were no significant differences in body weight, behavior, food consumption, absolute organ weights between controls and treated animals. Hematological analysis showed no differences in most parameters examined. In the biochemistry parameter measurement, no significant change occurred. Pathologically, neither gross abnormalities nor histopathological changes were observed. These finding suggest that none of the organs appeared to be target and the data could provide satisfactory preclinical evidence of safety to launch clinical trial on standardized formulation of tomato pomace extracts to be the dietary supplement.

  15. 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.

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

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit;

    2016-01-01

    toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall......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...

  17. 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.

  18. Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

    Sherry, J.; Scott, B.; Dutka, B. [National Water Research Inst., Burlington, Ontario (Canada)

    1997-11-01

    The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents.

  19. Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

    The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents

  20. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    Ellerbrock Malte

    2011-04-01

    Full Text Available Abstract Purpose To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Methods Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Results Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc, mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR. Conclusion Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted.

  1. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted

  2. Chemical toxicity approach for emergency response

    In the event of an airborne release of chemical agent or toxic industrial chemical by accidental or intentional means, emergency responders must have a reasonable estimate of the location and size of the resulting hazard area. Emergency responders are responsible for warning persons downwind of the hazard to evacuate or shelter-in-place and must know where to look for casualties after the hazard has passed or dissipated. Given the same source characterization, modern hazard assessment models provide comparable concentration versus location and time estimates. Even urban hazard assessment models often provide similar predictions. There is a major shortcoming, though, in applying model output to estimating human toxicity effects. There exist a variety of toxicity values for non-lethal effects ranging from short-term to occupational to lifetime exposures. For health and safety purposes, these estimates are all safe-sided in converting animal data to human effects and in addressing the most sensitive subset of the population. In addition, these values are usually based on an assumed 1 hour exposure duration at constant concentration and do not reflect either a passing clouds concentration profile or duration. Emergency responders need expected value toxicity parameters rather than the existing safe-sided ones. This presentation will specify the types of toxicity values needed to provide appropriate chemical hazard estimates to emergency responders and will demonstrate how dramatically their use changes the hazard area.(author)

  3. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R.

    2014-01-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary test...

  4. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  5. Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data

    Background and purpose: The 'Registry for the evaluation of side effects after radiation in childhood and adolescence' (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects. Materials and methods: Since 2001, patients receiving radiotherapy in one of the German pediatric therapy trials have been registered in RiSK with detailed information regarding radiation doses to organs at risk and characterization of acute toxicities. Results: From 2001 to May 2009, 690 patients have been characterized for acute toxicity in primary therapy. Acute toxicity ≥ grade 1 was observed in 506 patients. In patients irradiated in their lung and liver, patients with grade 1 or 2 acute toxicities showed higher organ volumes exposed to radiation doses <20 Gray (Gy) compared to patients without toxicities. For the salivary glands, there was a positive correlation between the acute toxicity grade and the maximum radiation dose to the organ; the lower GI tract showed a similar trend. The impact of different chemotherapy regimens on these acute side effects remains unclear. Age did not have any impact on side effects. Conclusion: This analysis gives a comprehensive overview of the acute toxicities of radiotherapy in children and adolescents. With prolongation of follow-up, detailed analyses regarding late toxicities will be possible with the characterization of dose-volume-effect relationships.

  6. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  7. Acute toxicity and practical value of extended field radiotherapy

    The course of supradiaphragmatic and/or infradiaphragmatic irradiation, which was carried out using the extended field technique in 198 patients diagnosed with non-hodgkin lymphomas or hodgkins disease, was investigated for side-effect levels and required interruptions and withdrawals of treatment. Further studies had the aim to elucidate the acute toxicity of field-integrated dose modification as compared to that associated with the conventional diaphragmatic technique. The available body of evidence appears to suggest that dose-modified irradiation, rather than giving rise to a greater number of acute side-effects, permitted a stricter adherence to treatment plans and reduced the need for interruptions and withdrawals, even though the individual dose and, thus, the oncolytic effect of irradiation was increased. Using field-integrated dose modification, more stringent therapeutic strategies could be followed even in complicated cases. As fas as radiobiology is concerned, it is to be expected for dose-modified irradiation that the frequency of delayed effects will be reduced. (orig./Vhe)

  8. Feasibility and acute toxicities of radioimmunoguided prostate brachytherapy

    Purpose: We present a technique that fuses pelvic CT scans and ProstaScint images to localize areas of disease within the prostate gland to customize prostate implants. Additionally, the acute toxicity results from the first 43 patients treated with this technique are reviewed. Methods and Materials: Between 2/97 and 8/98, 43 patients with clinical stage II prostate adenocarcinoma received ultrasound-guided transperineal implantation of I-125 or Pd-103 seeds. The median patient age was 70 years (range 49-79). Prior to treatment, the median Gleason score and prostate-specific antigen (PSA) were 6 (range 3-8) and 7.5 (range 1.8-16.6 ng/mL), respectively. The median follow-up was 10 months (range 2.9-20.4 months). Results: The median PSA value at 10 months is 0.7 ng/mL. Significant acute complications within the first month following implantation included 13 Grade I urinary symptoms, 24 Grade II urinary symptoms, 6 Grade III symptoms, and no Grade IV complications. Beyond 4 months, complications included 12 Grade I urinary symptoms, 17 Grade II urinary symptoms, 1 Grade III, and 1 Grade IV complications. Conclusions: The image fusion of the pelvic CT scan and ProstaScint scans helped identify regions within the prostate at high risk of local failure, which were targeted with additional seeds during implantation

  9. CT and MR manifestations of acute methyl alcohol toxic encephalopathy

    Objective: To analyze the CT and MR manifestations of methyl alcohol toxic encephalopathy and to improve the diagnosing value of CT and MRI. Methods: 40 patients with methyl alcohol intoxication were collected in this study, in which CT scan was performed on 40 cases and MRI on 4 cases. All CT and MRI radiological data of brain were retrospectively studied. Results: 13 of 40 cases showed abnormal findings on brain CT and MRI. The most common manifestation (6/13, 46%)was hypodensity in frontal parietal white matter and external capsule-putamen on CT, which showed long or short T1 and long T2 on MR. Hemorrhage in right putamen was found only in 1 patient (1/13,7%). CT showed low density inbilateral external capsule in 4 cases (4/13,31%), in which MR showed long or short T1 and long T2. Low density lesions in subcortical white matter of bilateral frontal and parietal lobes, cingulate gyms and insular lobes were found in 2 patients (2/13,15%). The more severe clinic manifestation, the more obvious brain lesion CT and MRI showed. Conclusion: Brain CT and MR manifestations have great diagnostic value of acute methyl alcohol toxic encephalopathy. MRI was more sensitive and better than CT in finding early brain damage caused by methanol intoxication. (authors)

  10. Acute toxicity of heavy metals towards freshwater ciliated protists

    The acute toxicity of five heavy metals to four species of freshwater ciliates (Colpidium colpoda, Dexiotricha granulosa, Euplotes aediculatus, and Halteria grandinella) was examined in laboratory tests. After exposing the ciliates to soluble compound of cadmium, copper, chromium, lead, and nickel at several selected concentrations, the mortality rate was registered and the LC5 values (with 95% confidence intervals) were calculated. Large differences appeared in sensitivities of the four species to the metals. H. grandinella showed the highest sensitivity for cadmium (0.07 mg l-1, LC5) and lead (0.12 mg l-1, LC5), whilst E. aediculatus showed the highest sensitivity for nickel (0.03 mg l-1, LC5). The comparison with data obtained with other species indicate that Halteria grandinella and Euplotes aediculatus are excellent and convenient bioindicator for evaluating the toxicity of waters and wastewaters polluted by heavy metals. The short time (24 h) and simplicity of the test procedure enable this test to be used in laboratory studies. - Ciliated protozoa are suitable bioindicators of heavy metal pollution in freshwater environments

  11. Acute toxicity and laxative activity of Aloe ferox resin

    Vanessa R. L. Celestino

    2013-04-01

    Full Text Available Aloe ferox Mill., Xanthorrhoeaceae, resin is the solid residue obtained by evaporating the latex that drains from the leaves transversally cut. Aloe ferox has been used in folk medicine as anti-inflammatory, immunostimulant, anti-bacterial, anti-fungal, antitumor, laxative and to heal wounds and burns. The effects of the oral administration of A. ferox resin (10, 25, 50, 100 and 200 mg/kg were evaluated on intestinal transit in mice and its acute toxicity (5.0 g/kg in Wistar rats. The hydroxyanthracene derivatives present in the resin were expressed as aloin, identified by thin layer chromatography and quantified by spectrophotometry. The aloin (Rf 0.35 was identified and the percentage of hydroxyanthracene derivates expressed as aloin was 33.5%. A. ferox resin extract (50, 100 and 200 mg/kg increased the gastrointestinal motility at a 30 min interval at 93.5, 91.8 and 93.8%, respectively, when compared to control group (46.5%. A single oral dose of the A. ferox resin extract did not induce signs of toxicity or death. Thus, the results demonstrate that A. ferox has laxative activity and that it is nontoxic, since LD50 could not be estimated and it is possibly higher than 5.0 g/kg.

  12. Acute toxicity study of stone-breaker (Phyllanthus tenellus Roxb.

    Tássia Campos de Lima e Silva

    2012-04-01

    Full Text Available Phyllanthus tenellus Roxb. is a herbaceous plant native to Brazil and appears frequently in humid environments. This plant is used to treat urolithiasis, inflammatory bowel disease, diabetes and hepatitis B. The acute toxicity and LD50 of an aqueous extract of P. tenellus were determined in laboratory mice and their behavior was analyzed. The intraperitoneal LD50 was calculated by the Karber & Behrens (1964 method, for which a 96% alcoholic extract was concentrated in a rotary evaporator. Male albino mice (Mus musculus were divided into three batches of six animals and observed for 24 hours after administration of the extract, diluted in 0.9% saline, at doses of 500, 1000, 1500, 2000 and 2500 mg / kg. Short-term studies have demonstrated this plant to be non-toxic; however, we found that this species induced agitation in animals, with stereotyped movements, spasms and increased respiratory frequency, as well as signs of depression, such as sleepiness, prostration, dyspnea and a reduction in respiratory frequency.

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

    Highlights: •Zebrafish larvae were used to test the acute toxicity of contaminant mixtures. •Interactions were observed between metals, ammonia and pharmaceuticals. •Larval Na+ 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 LC50, one third of the LC01) to all copper treatments decreased the copper 96 h LC50 by 58%, while sublethal copper exposure (6% of the copper LC50, 13% of the LC01) decreased the cadmium 96 h LC50 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+ followed by K+ (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+ and K+. Overall, whole body Na+ loss showed the greatest correlation with mortality across a variety of toxicants. We theorize that a disruption of ion homeostasis

  14. Evaluation of the acute and sub acute toxicity ofAnnona senegalensis root bark extracts

    Theophine C Okoye; Peter A Akah; Adaobi C Ezike; Maureen O Okoye; Collins A Onyeto; Frankline Ndukwu; Ejike Ohaegbulam; Lovelyn Ikele

    2012-01-01

    ABSTRACT Objective:To investigate the safety profile ofAnnona senegalensis (A. senegalensis).Methods:Dried powdered root-bark of A. senegalensis was prepared by Sohxlet extraction using methanol-methylene chloride (1:1) solution and concentrated to obtain the methanol-methylene chloride extract (MME).MME was fractionated to obtain then-hexane (HF), ethylacetate (EF) and methanol (MF) fractions. Acute toxicity (LD50) test was performed withMME, HF, EF andMF in mice by oral route. The sub acute toxicity studies were performed in rats after14 days ofMME administration while haematological and biochemical parameters were monitored.Results:Medium lethal (LD50) values of1 296, 3 808, 1 265 and 2 154mg/kg were obtained for theMME, MF, HF andEF, respectively. The sub-acute toxicity studies indicated a significant (P<0.05) increase in the body weight of both the treated rats and the control. The haematological tests indicated no change in the packed cell volume values but a significant (P<0.05) increase in the totalWBC count at100and 400 mg/kg doses. The differential analysis showed a decrease in the nutrophils and a non-significant increase in the lymphocyte counts. The liver transaminase enzymes, alanin transaminase and aspartate transaminase showed no significant increase compared to the control. Histopathological examination of the liver sections also indicted no obvious signs of hepatotoxicity except with the400 mg/kg dose that showed degeneration and necrosis of the hepatocytes.Conclusions:These results indicated that the root bark extracts ofA. Senegalensis are safe at the lower doses tested, and calls for caution in use at higher doses in treatment.

  15. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    Matthew Sean Peach

    2015-01-01

    Full Text Available A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.

  16. Acute phase protein response during acute ruminal acidosis in cattle

    Danscher, A. M.; Thoefner, M. B.; Heegaard, Peter M. H.;

    2011-01-01

    The aim of the study was to describe the acute phase protein and leukocyte responses in dairy heifers during acute, oligofructose-induced ruminal acidosis. The study included 2 trials involving oral oligofructose overload (17g/kg BW) to nonpregnant Danish Holstein heifers. Trial 1 included 12...... performed.Heifers receiving oligofructose developed a profound ruminal and systemic acidosis (in Trial 1 and 2 lowest ruminal pH was 4.3±0.2 and 3.8±0.02, respectively, and minimum SBE was −9.3±4.1 and −8.9±2.8, respectively). In Trial 1, SAA concentrations were higher than baseline concentrations on all...... than control heifers at 18 and 24h after overload (max. 13.7±4.3 billions/L). Feeding had no effect on plasma fibrinogen concentrations or WBC in Trial 1.Acute ruminal and systemic acidosis caused by oligofructose overload resulted in distinct acute phase protein and leukocyte responses in dairy...

  17. Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

    Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years operation of the Hanford Site of the US Department of Energy near Richland, Washington. The current strategy for the disposal of the low-level radioactive portion of these wastes involves immobilization of the waste in the form of grout. Because the potential risk of animal and plant exposure to grouts is unknown, acute toxicity screening of grouts is needed. Grouts were prepared by mixing a surrogate nonradioactive liquid waste with a blend consisting of cement, fly ash, and clay. Aqueous extracts of the grout were then screened for acute toxicity using aquatic invertebrates as test organisms and a fluorogenic substrate as the toxic stress indicator. After a 1-hour exposure of juvenile daphnids (D, magna, D. pulex, and C. dubia) to the grout extracts followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The EC50 values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The slight difference in the responses may be attributed to the subjective pass-fail scoring of the fluorescence criterion. The results indicated that the grout studied is nonhazardous and nondangerous

  18. 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.

  19. Phytochemical and acute toxicity studies of ethanol extract from Pedada (Sonneratia caseolaris) fruit flour (PFF)

    Jariyah Jariyah; Simon B Widjanarko; Yunianta Yunianta; T. Estiasih

    2015-01-01

    Studies on the phytochemical and acute toxicity of pedada fruit flour (PFF) were carried out. In acute toxicity test, oral administration of the extract to Swiss albino mice at four levels dose, i.e. 0, 10.50; 15.75 and 21.00 g/kg body weight.  Phytochemical analysis of the ethanol extract of PFF showed the presence of saponins, sapogenins, terpenoids, flavonoids, tannins,  polyphenols. Phytochemicals such as alkaloids were not detected. The results of acute toxicity (LD50) showed that the et...

  20. Medical image of the week: acute amiodarone pulmonary toxicity

    Mazursky K

    2015-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 71 year old man with a medical history significant for chronic obstructive pulmonary disease, coronary artery disease with post-operative status coronary artery bypass grafting, heart failure with reduced ejection fraction (25% and atrial fibrillation/flutter underwent an elective ablation of the tachyarrhythmia at another facility and was prescribed amiodarone post procedure. He started complaining of cough and dyspnea one day post procedure and was empirically treated with 2 weeks of broad spectrum antibiotics. He subsequently was transferred to our facility due to worsening symptoms. He also complained of nausea, anorexia with resultant weight loss since starting amiodarone, which was stopped 5 days prior to transfer. Infectious work up was negative. On arrival to our facility, he was diagnosed with small sub-segmental pulmonary emboli, pulmonary edema and possible acute amiodarone toxicity. His was profoundly hypoxic requiring high flow nasal cannula or 100% non-rebreather mask at all times. His symptoms persisted despite ...

  1. The joint effects of sulfonamides and quorum sensing inhibitors on Vibrio fischeri: Differences between the acute and chronic mixed toxicity mechanisms.

    Wang, Ting; Liu, Yuewei; Wang, Dali; Lin, Zhifen; An, Qingqing; Yin, Chunsheng; Liu, Yin

    2016-06-01

    Quorum sensing inhibitors (QSIs) are considered to be promising antibiotic alternatives and will be increasingly exposed to the environment together with antibiotics after their research and development process; it is therefore necessary to study the joint effects of QSIs and antibiotics. In this study, single and mixed toxicity of sulfonamide (SAs) and QSIs under acute and chronic conditions and their corresponding toxicity mechanisms were investigated. The results indicated that the acute joint effect was extremely complex, ranging from an antagonistic to synergistic response, while the chronic joint effect was primarily an antagonistic response. Using a molecular docking and regression model, we found that the acute joint effect could be determined by the hydrion's, ability to be oxidized, as well as the binding energy. The chronic joint effect was primarily an antagonistic response, which was due to the QSI competing against AHL for luxR generated by SAs, leading to negative effects of the QSI-luxR complexes on luxI. This phenomenon eventually weakened the stimulatory effect caused by SAs. Finally, the main differences between acute and chronic mixtures were analyzed: (1) The target protein was different between acute and chronic toxicity mixtures, and (2) effective concentration in acute and chronic toxicity mixtures was also different. These deep insights into mixed toxicity mechanisms will play an important role in the study of antibiotic resistance genes in response to antibiotic replacements. PMID:26897575

  2. Evaluation of Acute and Subacute Oral Toxicity of the Ethanol Extract from Antidesma Acidum Retz.

    Sireeratawong, Seewaboon; Thamaree, Sopit; Ingkaninan, Kornkanok; Piyabhan, Pritsana; Vannasiri, Supaporn; Khonsung, Parirat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    Toxicity tests of 95% ethanol extract of the root of Antidesma acidum were studied in male and female rats. The oral acute toxicity test at 5,000 mg/kg revealed that the ethanol extract did not produce toxic effects on signs, general behavious, mortality and gross appearance of internal organs of rats. Furthermore, the oral sub-acute toxicity test at the dose of 1,000 mg/kg/day displayed no significant changes in body and internal organs' weights, normal hematological and clinical blood chemi...

  3. Importance of structural information in predicting human acute toxicity from in vitro cytotoxicity data

    In this study, we tried to assess the utility of the structural information of drugs for predicting human acute toxicity from in vitro basal cytotoxicity, and to interpret the informative quality and the pharmacokinetic meaning of each structural descriptor. For this, human acute toxicity data of 67 drugs were taken from literature with their basal cytotoxicity data, and used to develop predictive models. A series of multiple linear regression analyses were performed to construct feasible regression models by combining molecular descriptors and cytotoxicity data. We found that although the molecular descriptors alone had only moderate correlation with human acute toxicity, they were highly useful for explaining the discrepancy between in vitro cytotoxicity and human acute toxicity. Among many possible models, we selected the most explanatory models by changing the number and the type of combined molecular descriptors. The results showed that our selected models had high predictive power (R2: between 0.7 and 0.87). Our analysis indicated that those successful models increased the prediction accuracies by providing the information on human pharmacokinetic parameters which are the major reason for the difference between human acute toxicity and cytotoxicity. In addition, we performed a clustering analysis on selected molecular descriptors to assess their informative qualities. The results indicated that the number of single bonds, the number of hydrogen bond donors and valence connectivity indices are closely related to linking cytotoxicity to acute toxicity, which provides insightful explanation about human toxicity beyond cytotoxicity.

  4. FISH ACUTE TOXICITY SYNDROMES IN THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS.

    The focus of this report is to summarize the development and status of the fish acute toxicity syndrome (FATS) research effort. hus far, FATS associated with nonpolar narcotics, oxidative phosphorylation uncouplers, respiratory membrane irritants, acetylcholinesterase (AChE) inhi...

  5. 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...

  6. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

    2011-01-01

    BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving vin

  7. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6–79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of ≥2 were considered “sensitive” (n = 141, 39%) and patients reporting scores <2 were considered “nonsensitive” (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70–82%) of the “nonsensitive” patients were failure free, compared with only 53% (CI 43–62%) of the “sensitive” patients (log–rank test, p < 0.0001). This difference was also observed using the Phoenix definition; “nonsensitive” 5-year BFFR was 81% (CI 74–86%) vs. “sensitive” BFFR was 68% (CI 58–76%; log–rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop ≥Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated

  8. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    Vesprini, Danny [Radiation Medicine Program, Princess Margaret Hospital (University Health Network) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario (Canada); Catton, Charles [Radiation Medicine Program, Princess Margaret Hospital (University Health Network) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Jacks, Lindsay; Lockwood, Gina [Department of Biostatistics, Princess Margaret Hospital (University Health Network), Toronto, Ontario (Canada); Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig [Radiation Medicine Program, Princess Margaret Hospital (University Health Network) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Bristow, Robert G., E-mail: robert.bristow@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Hospital (University Health Network) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2012-06-01

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further

  9. Oilseed rape genotypes response to boron toxicity

    Savić Jasna

    2013-01-01

    Full Text Available Response of 16 oilseed rape genotypes to B (boron toxicity was analyzed by comparing the results of two experiments conducted in a glasshouse. In Experiment 1 plants were grown in standard nutrient solutions with 10 µMB (control and 1000 µM B. Relative root and shoot growth varied from 20-120% and 31-117%, respectively. Variation in B concentration in shoots was also wide (206.5-441.7 µg B g-1 DW as well as total B uptake by plant (62.3-281.2 µg B g1. Four selected genotypes were grown in Experiment 2 in pots filled with high B soil (8 kg ha-1 B; B8. Shoot growth was not affected by B8 treatment, while root and shoot B concentration was significantly increased compared to control. Genotypes Panther and Pronto which performed low relative root and shoot growth and high B accumulation in plants in Experiment 1, had good growth in B8 treatment. In Experiment 2 genotype NS-L-7 had significantly lower B concentration in shots under treatment B8, but also very high B accumulation in Experiment 1. In addition, cluster analyses classified genotypes in three groups according to traits contrasting in their significance for analyzing response to B toxicity. The first group included four varieties based on their shared characteristics that have small value for the relative growth of roots and shoots and large values of B concentration in shoot. In the second largest group were connected ten genotypes that are heterogeneous in traits and do not stand out on any characteristic. Genotypes NS-L-7 and Navajo were separated in the third group because they had big relative growth of root and shoot, but also a high concentration of B in the shoot, and high total B uptake. Results showed that none of tested genotypes could not be recommended for breeding process to tolerance for B toxicity. [Projekat Ministarstva nauke Republike Srbije, br. OI 173028

  10. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  11. ACUTE TOXICITY, PHYTOCHEMISTRY AND ANTIBACTERIAL ACTIVITY OF AQUEOUS AND ETHANOLIC LEAF EXTRACTS OF CASSIA ALATA LINN

    Timothy SY; Lamu FW; Rhoda AS; Adati RG; Maspalma ID; Askira M

    2012-01-01

    Cassia alata Linn is an important medicinal plant as well as an ornamental flowering plant that has diverse reported medicinal values. This study focused on the evaluation of the phytochemical components, antibacterial as well as acute toxicity studies. The leaves of the plant were collected, dried, ground and extracted using 95% ethanol and water. The extracts were used for acute toxicity study, phytochemical screening and antibacterial assay using cup-plate method. The result from this stud...

  12. Acute toxicity, brine shrimp cytotoxicity, anthelmintic and relaxant potentials of fruits of Rubus fruticosus Agg

    Ali, Niaz; Aleem, Umer; Ali Shah, Syed Wadood; Shah, Ismail; Junaid, Muhammad; Ahmed, Ghayour; Ali, Waqar; Ghias, Mehreen

    2013-01-01

    Background Rubus fruticosus is used in tribal medicine as anthelmintic and an antispasmodic. In the current work, we investigated the anthelmintic and antispasmodic activities of crude methanol extract of fruits of R. fruticosus on scientific grounds. Acute toxicity and brine shrimp cytotoxicity activity of the extract were also performed. Methods Acute toxicity study of crude methanol extract of R. fruticosus was performed on mice. In vitro Brine shrimp cytotoxicity assay was performed on sh...

  13. Acute toxicity assessment of Osthol content in bio-pesticides using two aquatic organisms

    Yim, Eun-Chae; Kim, Hyeon Joe; Kim, Seong-Jun

    2014-01-01

    Objectives This study focused on the assessment of acute toxicity caused by Osthol, a major component of environment-friendly biological pesticides, by using two aquatic organisms. Methods The assessment of acute toxicity caused by Osthol was conducted in Daphnia magna and by examining the morphological abnormalities in Danio rerio embryos. Results The median effective concentration value of Osthol in D. magna 48 hours after inoculation was 19.3 μM. The median lethal concentration of D. rerio...

  14. Acute Toxicity Study and Antipyretic Effect of the Brown Alga Turbinaria Conoides (J. Agardh) Kuetz

    Kumar, S Sadish; Kumar, Y; Khan, M. S. Y; J Anbu; Sam, K G

    2009-01-01

    The active principles of brown alga, Turbinaria conoides (J.Agardh) Kuetz. (Sargassaceae) was extracted with n-hexane, cyclohexane, methanol and ethanol-water (1:1) and investigated for acute toxicity and antipyretic activity. Phytochemical analysis of the extracts revealed the presence of steroids, flavonoids and reducing sugars. Acute toxicity study was performed in Wistar rats after administration of extracts orally. No mortality was observed up to the dose of 5g/kg for methanol and ethano...

  15. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    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, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, 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 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  16. 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

    2015-04-01

    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.

  17. 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. PMID:25259848

  18. 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

  19. Influence of sulfate, Ca, and Mg on the acute toxicity of potassium dichromate to Daphnia similis

    Hosokawa, Mamoru; Kuroda, Koichi (Osaka City Inst. of Public Health and Environmental Sciences (Japan)); Endo, Ginji; Horiguchi, Shunichi (Osaka City Univ. Medical School (Japan))

    1991-03-01

    In the Daphnia test which is commonly employed for assessing effects of chemicals to aquatic environments, it is well known that the toxicity of chemicals is variable with test animals and also with the chemistry of test waters. However, it is not clear what constituents in water affect toxicity of chemicals. The authors report here experimental results which show that sulfate, calcium and magnesium, commonly contained in aquatic environments, decrease the toxicity of K{sub 2}Cr{sub 2}O{sub 7} which is recommended as a reference toxicant in the acute toxicity test.

  20. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE. PMID:25345248

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

    José Euclides Stipp Paterniani; Ronaldo Teixeira Pelegrini; Núbia Natália de Brito Pelegrini

    2007-01-01

    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 or...

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

    William Gerson Matias; Cátia Regina Silva de Carvalho-Pinto; Débora Monteiro Brentano; Alexandre Magno de Paula Dias

    2006-01-01

    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 differe...

  3. Comparisons of antidotal efficacy of chelating drugs upon acute toxicity of Ni(II) in rats

    Horak, E.; Sunderman, F.W. Jr.; Sarkar, B.

    1976-05-01

    Six chelating drugs were administered to rats by im injection at equimolar dosages in order to compare their relative effectiveness in prevention of death after a single parenteral injection of NiCl/sub 2/. Triethylenetetramine and d-penicillamine were the most effective antidotes for acute Ni(II)-toxicity. In order of decreasing antidotal effectiveness, diglycyl-L-histidine-N-methylamide, sodium diethyldithiocarbamate and calcium disodium versenate significantly reduced the acute mortality of rats following ip injection of Ni(II). ..cap alpha..-Lipoic acid was not effective as an antidote for acute Ni(II)-toxicity.

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

    Budin, Siti Balkis; Siti Nor Ain, Seri Masran; Omar, Baharuddin; Taib, Izatus Shima; Hidayatulfathi, Othman

    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. elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats. For the acute toxicity study, L. elliptica essential oil was administered in doses from 500 to 4 000 mg/kg (single dose), and in the subacute toxicity test, the following doses were used: 125, 250, and 500 mg/kg, for 28 consecu...

  5. 5-FU induced acute toxic leukoencephalopathy: early recognition and reversibility on DWI-MRI.

    Maheen Anwar, Shayan Sirat; Mubarak, Fatima; Sajjad, Zafar; Azeemuddin, Muhammad

    2014-03-01

    Acute toxic leukoencephalopathy (ATL) is a rare adverse effect of 5-Fluorouracil (5-FU) chemotherapeutic agent. It is imperative for the radiologist to confidently identify the white matter changes caused by this agent in case of toxicity. This will help in early detection and appropriate management of patient, as the condition is reversible both clinically and on imaging. We report a case of a 29 years old gentleman, known case of carcinoma of esophagus who suffered from acute toxic leukoencephalopathy secondary to leukotoxic therapeutic agent 5-FU, and illustrate the reversible imaging findings of this condition on withdrawal of the inciting agent. PMID:24718016

  6. 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.

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

    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

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

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

  9. Toxicity of 8-Hydroxyquinoline in Cryprinus carpio Using the Acute Toxicity Test, Hepatase Activity Analysis and the Comet Assay.

    Yan, Shuaiguo; Chen, Lili; Dou, Xiaofei; Qi, Meng; Du, Qiyan; He, Qiaoqiao; Nan, Mingge; Chang, Zhongjie; Nan, Ping

    2015-08-01

    To evaluate the environmental toxicity of 8-hydroxyquinoline (8-HOQ), an important industrial raw material found in China's major ornamental fish, Cryprinus carpio, using the acute toxicity test, hepatase activity analysis and the comet assay. The results indicated that 8-HOQ had significant acute toxicity in adult C. carpio with a 96 h-LC50 of 1.15 and 0.22 mg L(-1) hepatic quinoline residues as assessed by HPLC. 8-HOQ also induced genotoxicity in the form of strand breaks in the DNA of hepatic cells as shown by the comet assay. With regard to physiological toxicity, 8-HOQ induced a decrease in the activities of hepatic GOT and GPT with increased exposure concentration and time. These data suggest that 8-HOQ may be toxic to the health of aquatic organisms when accidentally released into aquatic ecosystems. The data also suggest that the comet assay may be used in biomonitoring to determine 8-HOQ genotoxicity and hepatic GPT and GOT activities may be potential biomarkers of physiological toxicity. PMID:26067700

  10. 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. PMID:27085063

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

    Popov, Dmitri

    found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels, etc. [Beutler et al. 2000 ] Potential mechanisms responsible for radiation-acquired marrow cell failure include direct toxicity , direct damage of hematopoietic multipotential cells or cellular or humoral immune suppression of the marrow multipotential cells. [ Beutler et al. 2000] Methods: These studies were conducted at several different research institutions and laboratories listed as follows: Kazan All-Union Scientific Research Veterinary, Biotechnology Centre of Russian Academy of Science (North Osetia), Institute Belarussian Scientific and Research Institute for Radiobiology in Gomel, the St. Petersburg Veterinary Institute, the Advanced Medical Technology and Systems Inc., Ontario, Canada. The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. A critically important volume of purified Radiation Toxins (RT) was isolated from larger mammalian irradiated animals. Subsequently the RT were characterized chemically and biologically. The experimental design of later studies compared relative toxicity, potential for development of acute radiation hematopoietic syndrome, and potential cloning disorder of multipotential hematopoietic progenitors and their derivative and lethality after intravenous or intramuscular injections of SRD containing Hematopoietic Radiation Toxins. These experiments have employed a wide variety of experimental animals. The animals were irradiated in RUM-17, Puma, and Panorama devices. The dose varied from 0.7Gy to 100Gy. The methods of immune depletion, immuno-lympho plasmasabsorption, as well as direct extraction, were used to refine and purify the specific Radiation Toxins from the central lymph of animals with Hematopoietic forms of Radiation Toxins. Experiments include administration of Hematopoietic

  12. Investigation of acute toxicity of chlorpyrifos-methyl on Nile tilapia (Oreochromis niloticus L.) larvae.

    Gül, Ali

    2005-04-01

    Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated for acute toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.) were selected for the bioassay experiments. The experiments were repeated three times and the 96 h LC50 was determined for the larvae. The static test method for assessing acute toxicity was used. Water temperature was maintained at 25+/-1 degrees C. In addition, behavioral changes at each chlorpyrifos-methyl concentration were observed for the individual fish. Data obtained from the chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was calculated to be 1.57 mg/l. PMID:15722087

  13. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements. PMID:20144136

  14. Acute neuromuscular responses to car racing

    Backman, Jani

    2005-01-01

    Purpose: The primary purpose of this study was to determine racing car drivers’ acute neuromuscular responses to race driving. The secondary purpose was to compare the cardiovascular loading of driving to that of maximal rowing action. Methods: The subjects of the present cross-sectional study (n = 9) were international level karting drivers. The study was performed in two parts; the laboratory tests and driving test. All subjects took part to the laboratory tests and five of the subjects per...

  15. 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.

  16. Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

    Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that are elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition

  17. 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. PMID:26822024

  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. Systemic inflammatory response following acute myocardial infarction

    Lu FANG; Xiao-Lei Moore; Anthony M Dart; Le-Min WANG

    2015-01-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial in-farction, and heart failure) in patients with AMI.

  20. ADMET evaluation in drug discovery: 15. Accurate prediction of rat oral acute toxicity using relevance vector machine and consensus modeling

    Lei, Tailong; Li, Youyong; Song, Yunlong; Li, Dan; Sun, Huiyong; Hou, Tingjun

    2016-01-01

    Background Determination of acute toxicity, expressed as median lethal dose (LD50), is one of the most important steps in drug discovery pipeline. Because in vivo assays for oral acute toxicity in mammals are time-consuming and costly, there is thus an urgent need to develop in silico prediction models of oral acute toxicity. Results In this study, based on a comprehensive data set containing 7314 diverse chemicals with rat oral LD50 values, relevance vector machine (RVM) technique was employ...

  1. Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.

    Jonsson, Martina; Jestoi, Marika; Nathanail, Alexis V; Kokkonen, Ulla-Maija; Anttila, Marjukka; Koivisto, Pertti; Karhunen, Pirkko; Peltonen, Kimmo

    2013-03-01

    Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health. PMID:23201451

  2. Safety evaluation of the ethyl acetate extract on irradiated tea parasite: Acute toxicity study on mice

    Many studies of the pharmacological efficacy of tea parasite and the use of ionizing radiation for decontamination of microbes and extending shelf life have been reported, but there is no information on its safety, such as the acute toxicity. In this study, the acute toxicity of two ethyl acetate extracts from unirradiated and irradiated (irradiation dose of 10 kGy) tea parasites Scurrula atropurpurea on Swiss Webster mice have been examined. The observation was done after the treatment of a single oral dose of ethyl acetate extract in various dose groups, i.e.: control (0 g/kg of mice body weight), D1 (0.625 g/kg), D2 (1.25 g/kg), D3 (2.5 g/kg) D4 (5 g/kg), D5 (10 g/kg) by observing the effect on behavioral response (pharmacological profile), the body weight gains and mortality until the day 14th. At the last day, the observation of vital organs has also been done. The result showed that no acute toxicity was found in mice treated with a single oral dose of ethyl acetate extract from unirradiated tea parasite and irradiated tea parasite at the dose of 10 kGy. At the dose up to 10 g/kg (equivalent to 77.6 g of extract which administered to human), the normal body weight gains were observed in mice of all dose groups, no mice deaths in any of the dose groups, and no significant change (p > 0.05) in organ weights relative to the body weight i.e.: liver, spleen, kidneys, lung, heart, testes and seminal vesicle (for male), and ovaries and uterus (for female). The approximate lethal doses for male and female mice were determined to be higher than 10 g/kg of mice body weight. It is suggested that the treatment of ethyl acetate extract from unirradiated and irradiated tea parasites until dose up to 10 g/kg of mice body weight was still safe. (author)

  3. Aqueous CO2 vs. aqueous extraction of soils as a preparative procedure for acute toxicity testing

    This study was to determine if contaminated soils extracted with supercritical CO2 (SFE) would yield different results from soils extracted with an aqueous media. Soil samples from an abandoned oil refinery were subjected to aqueous and SFE extraction. Uncontaminated control sites were compared with contaminated sites. Each extract was analyzed for 48 hour acute Ceriodaphnia LC50s and Microtox reg-sign EC50s. Comparisons were then made between the aqueous extracts and the SFE extracts. An additional study was made with HPLC chromatographs of the SFE contaminated site extracts to determine if there was a correlation between LC50 results and peak area of different sections of the chromatograph. The 48 hour Ceriodaphnia LC50 of one contaminated site showed a significant increase in toxicity with the supercritical extract compared to the aqueous extract. All contaminated sites gave toxic responses with the supercritical procedure. The Microtox reg-sign assay showed a toxic response with 2 of the 3 contaminated sites for both aqueous and SFE extracts. Results indicate that the Ceriodaphnia assays were more sensitive than Microtox reg-sign to contaminants found in the refinery soil. SFE controls did not show adverse effects with the Ceriodaphnia, but did have a slight effect with Microtox reg-sign. The best correlation (r2 > 0.90) between the Ceriodaphnia LC50s and the peak areas of the chromatographs was obtained for sections with an estimated log Kow of 1 to 5. SFE extraction provided a fast, efficient and inexpensive method of collecting and testing moderately non-polar to strongly non-polar organic contaminants from contaminated soils

  4. Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

    The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA's Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity

  5. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m2total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m2/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of ≥3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of ≥3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  6. [18F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using 18F-labeled fluorodeoxyglucose positron emission tomography [18F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [18F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BMTOT). Active bone marrow (BMACT) was contoured based on SUV greater than the mean SUV of BMTOT. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V10, V20, V30, and V40, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BMTOT and BMACT were 27% and 38%, respectively. BMACT volume was significantly reduced after treatment (from 651.5 to 231.6 cm3, respectively; P<.0001). BMACT V30 was significantly correlated with a reduction in BMACT SUV (R2, 0.14; P<.001). The reduction in BMACT SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R2, 0.27; P=.04) and at last follow-up (R2, 0.25; P=.04). Different dosimetric parameters of BMTOT and BMACT correlated with long-term hematological outcome. Conclusions: The volumes of BMTOT and BMACT that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in

  7. [{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    Elicin, Olgun [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Callaway, Sharon [Velocity Medical Solutions, Atlanta, Georgia (United States); Prior, John O. [Department of Nuclear Medicine, Lausanne University Hospital, Lausanne (Switzerland); Bourhis, Jean [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Ozsahin, Mahmut, E-mail: mahmut.ozsahin@chuv.ch [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Herrera, Fernanda G., E-mail: fernanda.herrera@chuv.ch [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland)

    2014-12-01

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}). Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM

  8. The Study on Acute and Subacute Toxicity and Sarcoma-180 Anti-cancer Effects of Vermilionum

    Ki-Rok Kwon

    2003-12-01

    Full Text Available Background & Methods : In order to measure the acute and subacute toxicity of Vermilionum and it's anti-cancer effects, Sarcoma-180 abdominal cancer cells were injected intravenously. The following results were obtained after measuring the survival rate, toxicity of the NK cells, and IL-2 productivity. Results : 1. It was impossible to measure LD50 value in the acute toxicity test and no toxic effects were witnessed in the clinical observation. 2. No significant differences were shown in the weight changes between the experiment groups and the control group in the acute toxicity test. 3. No peculiar toxic effects were shown in the subacute toxicity test and the weight changes were insignificant between the experiment groups and the control group. 4. In measuring the survival rate after inducing abdominal cancer by Sarcoma-180, the experiment groups showed increased of 9,52% compared to the control group. 5. In measuring the activity of NK cells, no significant changes were shown between the experiment groups and the control group. 6. In measuring the productivity of IL-2, significant reduction was shown in the experiment groups compared to the normal group, but no significance was witnessed compared to the control group.

  9. Fluid therapy for severe acute pancreatitis in acute response stage

    MAO En-qiang; TANG Yao-qing; FEI Jian; QIN Shuai; WU Jun; LI Lei; MIN Dong; ZHANG Sheng-dao

    2009-01-01

    Background Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. Methods Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n=36) and a controlled fluid expansion group (Group Ⅱ, n=40). Hemodynamic disorders were either quickly (fluid infusion rate was 10-15 ml·kg-1·h-1, Group Ⅰ) or gradually improved (fluid infusion rate was 5-10 ml·kg-1·h-1, Group Ⅱ) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE Ⅱ scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained. Results The two groups had statistically different (P 0.05). Total amount of fluid sequestration within 4 days was higher in Group Ⅰ ((5378±2751)ml) than in Group Ⅱ ((4215±1998)ml, P<0.05). APACHE Ⅱ scores were higher in Group Ⅰ on days 1,2, and 3 (P<0.05). Rate of mechanical ventilation was higher in group Ⅰ (94.4%) than in group Ⅱ (65%, P<0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group Ⅱ (P <0.05). Survival rate was remarkably lower in Group Ⅰ (69.4%) than in Group Ⅱ (90%, P <0.05). Conclusions Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.

  10. Phytochemical and acute toxicity studies of ethanol extract from Pedada (Sonneratia caseolaris fruit flour (PFF

    Jariyah Jariyah

    2015-01-01

    Full Text Available Studies on the phytochemical and acute toxicity of pedada fruit flour (PFF were carried out. In acute toxicity test, oral administration of the extract to Swiss albino mice at four levels dose, i.e. 0, 10.50; 15.75 and 21.00 g/kg body weight.  Phytochemical analysis of the ethanol extract of PFF showed the presence of saponins, sapogenins, terpenoids, flavonoids, tannins,  polyphenols. Phytochemicals such as alkaloids were not detected. The results of acute toxicity (LD50 showed that the ethanol extract of PFF in mice was found more than 21.00 g/kg body weight. It could be concluded that the PFF belongs to relatively less dangerous category ‘non toxic’ and ‘safe’ for food products.

  11. Developing acute-to-chronic toxicity ratios for lead, cadmium, and zinc using rainbow trout, a mayfly, and a midge

    Mebane, C.A.; Hennessy, D.P.; Dillon, F.S.

    2008-01-01

    In order to estimate acute-to-chronic toxicity ratios (ACRs) relevant to a coldwater stream community, we exposed rainbow trout (Oncorhynchus mykiss) to cadmium (Cd), lead (Pb), and zinc (Zn) in 96-h acute and 60+ day early-life stage (ELS) exposures. We also tested the acute and sublethal responses of a mayfly (Baetis tricaudatus) and a midge (Chironomus dilutus, formerly C. tentans) with Pb. We examine the statistical interpretation of test endpoints and the acute-to-chronic ratio concept. Increasing the number of control replicates by 2 to 3x decreased the minimum detectable differences by almost half. Pb ACR estimates mostly increased with increasing acute resistance of the organisms (rainbow trout ACRs trout and Cd were 0.6 and 0.95; Zn about 1.0; and for Pb 3.3 and 11. The comparable Pb ACRs for the mayfly and Chironomus were 5.2 and 51 respectively. Our rainbow trout ACRs with Pb were about 5-20x lower than earlier reports with salmonids. We suggest discounting previous ACR results that used larger and older fish in their acute tests. ?? 2007 GovernmentEmployee: U.S. Geological Survey.

  12. Macroinvertebrate response to acid mine drainage: community metrics and on-line behavioural toxicity bioassay

    The hypothesis is tested that toxicity of acid mine drainage can be detected by a selection of existing macroinvertebrate community and bioindicator metrices supplemented by toxicity tests with the local mosquitofish Gambusia holbrooki Girard and the shrimp Atyaephyra desmaresti Millet. The behavioural responses of A. desmaresti to acid mine drainage were recorded in the Multispecies Freshwater Biomonitor[reg], based on behaviour and survival as parameters. Bioassessment methods were based on community diversity, structure, function, and bioindicators and supplemented by chemical analysis (temperature, pH, metals). The Biological Monitoring Working Party adapted for the Iberian Peninsula, the number of predators (Coleoptera, Hemiptera) and the number of Ephemeroptera and Trichoptera taxa differentiated the sites well. The on-line toxicity test revealed pH-dependent acute toxicity of the acid mine drainage for the shrimp (LC50-48 h: pH-AMD=5.8) and a pH- dependent decrease in locomotory activity with the lowest-observed-response-times (LORTs) within 5 h of exposure. Shrimp were more sensitive to acid mine drainage than fish (LC50-48 h: pH-AMD=4.9). A new multimetric index combining toxicity testing and bioassessment methods is proposed. - Toxicity of acid mine drainage was evaluated by macroinvertebrate bioassessment and a new on-line rapid behavioural toxicity test with Atyaephyra desmaresti (Crustacea)

  13. 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. PMID:26408031

  14. 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

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

    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

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

    Basak Ozlem Perk; Sinem Ilgin; Ozlem Atli; Hale Gamze Duymus; Basar Sirmagul

    2013-01-01

    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 t...

  17. High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

    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.)

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

    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

  19. 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.

  20. 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.

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

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

    2010-01-01

    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 be...

  2. Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract

    Geethaa Sahgal; Surash Ramanathan; Sreenivasan Sasidharan; Mohd. Nizam Mordi; Sabariah Ismail; Sharif Mahsufi Mansor

    2010-01-01

    Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract. Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice. Results: The brine shrimp lethality bioassay shows a moderate cytotoxicity at high co...

  3. Acute Toxicity of Opuntia Ficus Indica and Pistacia Lentiscus Seed Oils in Mice

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

    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 Opunti...

  4. Evaluation of Acute Chromium (III) Toxicity in Relation to Daphnia Similis

    Petr Melnikov; Tânia C. M. de Freitas

    2011-01-01

    Acute chromium (III) toxicity in relation to Daphnia similis, most appropriate for Brazilian environment has been evaluated. The preliminary toxicity test showed that the median effective concentration was 10 mg/l. After having performed the final test, the immobility percentage was calculated for each concentration in relation to the total number of the used organisms within the chosen pH range. It was shown that the proposed methodology rendered realistic results and the 48-h CE50 value und...

  5. 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.

  6. Topic acute toxicity of Bioenraiz in honey bees (Apis mellifera

    Odette Beiro Castro

    2007-05-01

    Full Text Available Introduction. Bioenraiz is a phytohormone which active ingredient is indolacetic acid (AIA, an auxina that promotes vegetable vegetable growth. The most important feature is that it regulates growth by inducing the synthesis of ribonucleic acid (RNA or specific enzymes, which in turn are linked into a central genetic as biological modulators.Objective. To evaluate the potential toxicity of Bioenraiz when is administered to honey bees. Method. The product was applied in single and topic doses of 0.650 mg/ bee; equivalent to a concentration of 130 mg/ L. Two hundred honey bees of the Apis mellifera specie were used and distributed in two experimental groups: a control one (non treated and a group treated with Bioenraiz. The mortality of the bee and the appearance of toxicity signs at the 4, 24 and 48 hours of the test, were the variables analyzed. Results and Discussion. Bioenraiz caused a 2 percent of mortality, a non biological and statistical significant value according to the validation criteria of the test. Concerning clinical observations, the animals did not show toxic signs nor alterations in their behavor attribute to the administration of the test substance. Conclusions. According to the results obtained in this highly sensitive specie for ecotoxicological tests, this product did not provoke neither mortality, nor toxicity for the Apis mellifera bee.

  7. ACUTE TOXICITY OF AMMONIA AND NITRITE TO CUTTHROAT TROUT FRY

    The toxicity of ammonia and of nitrite was tested on cutthroat trout (Salmo clarki) fry (1-3 g) for periods up to a month in eight laboratory flow-through bioassays. Median lethal concentration (LC50) values for ammonia (mg/liter un-ionized NH3) were 0.5-0.8 for 96 hours, and 0.3...

  8. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

  9. Acute bilateral ureteral obstruction secondary to guaifenesin toxicity.

    Cockerill, Patrick A; de Cógáin, Mitra R; Krambeck, Amy E

    2013-10-01

    Several medications or their metabolites have been associated with urolithiasis, although overall they remain an infrequent cause of urolithiasis. Guaifenesin stones were originally reported as complexed with ephedrine, and subsequent reports have demonstrated pure guaifenesin stones, occurring after long term abuse. We report a case of a 23-year-old male who ingested a large, one time dose of guaifenesin, resulting in acute bilateral ureteral obstruction, which, to our knowledge, is the first such reported case in the literature. PMID:24128843

  10. 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.

  11. Acute toxicity of mosquitocidal compounds to young mosquitofish, Gambusia affinis.

    Tietze, N S; Hester, P G; Hallmon, C F; Olson, M A; Shaffer, K R

    1991-06-01

    Toxicity of Florida mosquito larvicides and adulticides to 3-5 day old Gambusia affinis was determined in the laboratory. After 24-h exposure, the larvicides, temephos, fenoxycarb and petroleum distillates had LC50 values of 5.60, 1.05 and 593.4 ppm, respectively. After 24 h the adulticides resmethrin, fenthion, naled and malathion had LC50 values of 0.007, 2.94, 3.50 and 12.68 ppm, respectively. The only compound toxic to young mosquitofish at maximum field application rates was resmethrin. However, in the light of earlier tests, aerially applied adulticides generally reach the water surface at reduced concentrations and thus probably pose little or no risk to mosquitofish populations. PMID:1716659

  12. Using acute bioassay screens to predict compliance with chronic toxicity permit limits

    Acute bioassay screens can be cost-effective surrogates for chronic toxicity tests for screening a large number of discharges. Other uses of acute bioassay screens include real time measurement of effluent toxicity and variability, prioritizing discharges for TIE/TRE studies, and evaluating effluent treatability studies. A study was conducted to assess the utility of using 48-hour LC50 data to predict the probability of complying with new chronic toxicity permit limits for produced water discharges from Outer Continental Shelf (OCS) oil and gas platforms in the Gulf of Mexico. Although mysid 48-hour LC50s were correlated with 7-day mysid NOECS, the variability was too great to enable accurate prediction of sub-lethal NOECs based on growth and fecundity. Instead, a decision flowchart was constructed to classify OCS produced water discharges into three categories based on the probability of achieving compliance with future chronic toxicity permit limits. Using toxicity test results from over 50 platforms, the 48-hour LC50 data correctly classified approximately 85% of the discharges. Most importantly, there were no cases where a discharge classified as having a high probability of compliance would have failed its chronic toxicity permit limit. The classification results were used to prioritize platforms for additional toxicity testing and for evaluating improvements to produced water treatment systems

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

    Gui Mi Ko; Adela Rosenkranz; Clélia Rejane Antonio Bertoncini; Neide Hyppolito Jurkiewicz; Mirian Ghiraldini Franco; Aron Jurkiewicz

    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...

  14. 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.

  15. Acute toxicity of four heavy metals to benthic fish food organisms from the River Khan, Ujjain

    Qureshi, S.A.; Saksena, A.B.; Singh, V.P.

    1980-01-01

    The acute toxicity of four heavy metals (Hg, Zn, Cd and Pb) to two benthic invertebrates viz. Tubifex tubifex and 4th instar larvae of chironomous sp. from the River Khan (Ujjain) have been determined by static bioassay experiments. Although both Tubifex tubifex and chironomous larvae have been found to be resistant to heavy metals (Hg, Zn, Cd and Pb), the experiments led to an observation that chironomous larvae are comparatively less tolerant than Tubifex tubifex. However, when the individual toxicity of heavy metals is considered it seems that the toxicity of metals is in the following order viz. Hg>Zn>Cd>Pb. The investigations reveal variation in the sensitivity of different organisms to the same toxicant and the same organisms to different toxicants.

  16. Diffusion-weighted magnetic resonance imaging in acute reversible toxic leukoencephalopathy: A report of two cases

    Acute toxic leukoencephalopathy may be caused by endogenous or exogenous toxins. It may reverse clinically if the offending agent is withdrawn or the underlying condition is treated. However, demonstration of reversibility on imaging, especially with diffusion-weighted MRI, has been reported only very recently. We report two such cases

  17. EVALUATION OF MINIMUM DATA REQUIREMENTS FOR ACUTE TOXICITY VALUE EXTRAPOLATION WITH AQUATIC ORGANISMS

    Buckler, Denny R., Foster L. Mayer, Mark R. Ellersieck and Amha Asfaw. 2003. Evaluation of Minimum Data Requirements for Acute Toxicity Value Extrapolation with Aquatic Organisms. EPA/600/R-03/104. U.S. Environmental Protection Agency, National Health and Environmental Effects Re...

  18. Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

    Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

    1989-12-01

    The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

  19. 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

  20. Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels

    Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...

  1. 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 ...

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

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

  3. 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)

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

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

    2011-12-15

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

  5. 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.

  6. THE ACUTE TOXICITY OF PRAZIQUANTEL TO GRASS CARP AND GOLDEN SHINERS

    Acute praziquantel toxicity and no observable effect concentrations (NOEC), were determined in the laboratory for grass carp and golden shiners, two commercially raised cyprinids known to harbor Asian tapeworm Bothriocephalus acheilognathi. Praziquantel is an anthelmintic used to treat fish with ta...

  7. Acute toxicity of praziquantel (an anthelmintic) to grass carp and golden shiners

    Praziquantel is an anthelmintic that can be applied to the water to kill tapeworm and trematode parasites in fish. Effective praziquantel treatment rates have been determined but there is little information on the toxicity of this chemical to fish hosts of the parasites. Acute praziquantel toxicit...

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

    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-1, 2.34 mg.L-1, 2.35 mg.L-1 and 1.80 mg.L-1, respectively, showing a notable reduction of the acute toxicity for this organism. (author)

  9. Acute urinary toxicity following transperineal prostate brachytherapy using a modified Quimby loading method

    Purpose: To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity. Methods and Materials: One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) ≤6, Gleason score (GS) ≤6, clinical stage 6, PSA>6, or Stage>T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale. Results: Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p=0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p=0.002), and those with more seeds implanted (p<0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p=0.01), with larger prostate volumes (p=0.01), and those with more seeds implanted (p<0.001). Conclusion: Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest

  10. Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment

    To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule (C-ARM) with 78 Gy/39 fractions and hypofractionation conformal treatment (H-ARM) with 69 Gy/23 fractions. This prospective double arm study consisted of 217 patients with prostate cancer, 112 in H-ARM and 105 in C-ARM arm. C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions. Weekly assessment of acute reactions was done during treatment and with one, and 3 months using RTOG scale. Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms. Variables with p value less than 0.1 were included in the multivariated logistic regression. There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary (GU) and gastrointestinal (GI) acute toxicity. During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity (grade 0–3; H-ARM = 45.5%, 34%, 18.7% and 1.8% versus C-ARM = 47.6%, 35.2%, 17.2% and 0). For acute GU toxicity no difference was detected between H-ARM (grade 0–3; 22.3%, 54.5%, 18.7% and 4.5%) and C-ARM (grade 0–3; 25.8%, 53.3%, 17.1% and 3.8%). At the 3- months follow-up, persistent Grade > =2 acute GU and GI toxicity were 2.5% and 1.8% in H-ARM versus 5.7% and 3% in C-ARM (p > 0.05). In univariated and multivariated analyses, there was not any dosimetric predictor for GI and GU toxicity. Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer, being well tolerated with minimal severe acute toxicity

  11. The acute toxicity of ethanol extract from irradiated Temulawak (curcuma xanthorrizha roxb.) which have anticancer activity

    Pasteurization of herbs and herbal medicinal products have been carried out by several herbal industries, but information about the safety of irradiated herbal medicine is still a little, even the influence of gamma irradiation for pasteurization purpose on the toxicity of crude Temulawak has never been investigated. The ethanol extract of Curcuma xanthorrizha Roxb. has cytotoxic activity which potential as an anticancer. In this research, the acute toxicity tests were carried out to the ethanol extract from Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy. The acute toxicity tests of ethanol extract were conducted in mice by observing the effect of extracts on animal behavior (pharmacologic profile) after a single dose of test material, the development of animal body weight and death every day for 14 days and observed several organ weights on day 14. Acute toxicity test results after administration of extracts on male and female mice a dose up to 7500 mg/kg body weight (BW) showed that no deaths and no significant toxic effect, so that the ethanol extract of Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy can be declared safe. Thus LD50 from ethanol extract of Curcuma xanthorrizha without irradiation and irradiated (5 and 10 kGY) in mice was greater than 7500 mg/kg body weight. (author)

  12. Acute toxic encephalopathies: CT and MR imaging features

    An endless variety of toxins can cause degenerative brain lesions both by chronic use of small amounts and by acute exposures from industrial accidents or suicide attempts. The more commonly occurring toxins encountered clinically include carbon monoxide, cyanide, methanol, and ethylene glycol. CT and MR imaging are of great importance in the assessment of the comatose patient. Some of these toxins have a propensity for selective bilateral and symmetric involvement of the basal ganglia as well as the white matter. CT and MR can demonstrate the extent and distribution of the morphologic brain changes

  13. 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.

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

    To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. 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. 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 < .001). GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM

  15. 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.

  16. 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...

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

    Brink, van den, R.B.A.; Smeden, Van, J.M.; Bekele, R.S.; Dierick, Wiebe; Gelder, de, B.; 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 C. dipterum and 5 other invertebrate species. Imidacloprid and thiamethoxam showed equal acute and chronic toxicity to a winter generation of C. dipterum, whereas thiacloprid was approximately twice ...

  18. 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 animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

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

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

    2015-01-01

    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 1mg K/L to 3mg 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.

  20. 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.

  1. Increased RO concentrate toxicity following application of antiscalants – Acute toxicity tests with the amphipods Gammarus pulex and Gammarus roeseli

    In reverse osmosis, a frequently used technology in water desalination processes, wastewater (RO concentrate) is generated containing the retained solutes as well as so-called antiscalants (AS), i.e. chemical substances that are commonly applied to prevent membrane-blocking. In this study, a risk assessment of a possible discharge of concentrate into a small stream was conducted. The acute toxicity of two concentrates containing two different ASs and of concentrate without AS to the amphipods Gammarus pulex and Gammarus roeseli was studied. Mortality of gammarids exposed to the concentrate without AS was not different to the control, whereas concentrates including ASs caused mortality rates up to 100% at the highest test concentrations after 168 h. Resulting EC50-values were 36.2–39.4% (v/v) after 96 h and 26.6–58.0% (v/v) after 168 h. These results suggest that the ecotoxicological relevance of antiscalants is greater than currently assumed. - Highlights: • Antiscalants used in drinking water treatment interact with RO concentrate. • RO concentrate without antiscalant was not toxic to Gammarids. • Antiscalants increased concentrate toxicity to Gammarus pulex and G. roeseli. • No difference in sensitivity of the Gammarus species was evident. • Ecotoxicological effects of antiscalants seem to be underestimated. - Antiscalants – officially containing no environmentally hazardous ingredients – increased toxicity of reverse osmosis concentrate to Gammarus pulex and Gammarus roeseli

  2. Acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine.

    Hoffmann, Marc S; Overman, Michael J; Nates, Joseph L

    2016-04-01

    Improvements in antiemetic therapy constitute a major advance in oncology. A recent poll of the oncology community by the American Society of Clinical Oncology ranked it as one of the top 5 advances in cancer in the last 50 years. Emetogenicity of chemotherapy is defined by risk of emesis in the patient given no antiemetics; high-risk regimens cause nausea and vomiting in >90% of patients, moderate risk in 30%-90%, and low risk in <30%. This risk profile serves as the basis for empiric antiemetic prophylaxis and offers alternatives to refractory patients. Modern antiemetic prophylaxis is extremely effective for high-risk chemotherapy, reducing the risk for breakthrough nausea and vomiting to 0%-13% in the acute setting (<24 hours from receipt of chemotherapy) and to 25%-30% in the delayed setting (24-72 hours from receipt of chemotherapy). PMID:27152518

  3. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    Bælum, Jesper

    1991-01-01

    symptoms. The pharmacokinetics of toluene is complex and there is a large individual variation in the excretion of the metabolites. This variation can only to a limited extend be related to known variables. Intake of alcohol during exposure inhibits the metabolism of toluene and increases the internal dose...... exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed to the...... most frequent solvent, toluene. Toluene in alveolar air and the urinary excretion of the metabolites were measured and the acute effects of toluene were assessed by the performance in a series of test of the perceptual and psychomotor functions as well as a standardized registration of annoyance and...

  4. 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. PMID:26650419

  5. 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.

  6. 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. PMID:26946506

  7. Environmental effects of produced water from offshore petroleum industry 2: Identification of acute toxicity

    The purpose of the present study was to identify the sources of acute toxicity in produced water from two North Sea oilfields, Statfjord and Gullfaks. The experiments were designed in a way that has not previously been employed in such studies, including the combination of statistical experimental design and multivariate statistical analysis. Produced waters were synthesized by adding the components identified as possible toxicants to sea water in different concentrations reflecting their presence in real produced water. The selected components were: oil (represented by dissolved aromatic hydrocarbons), phenol and alkylated phenols, production chemicals and heavy metals (Cu, Cr, Mn, Zn, Hg, Pb, Sr and Ba). The toxicity of the mixtures were determined by the Microtox test. The effects of single components and their first and second order interactions were identified. The results show that the aromatic fraction is the most important contributor to the produced water toxicity, measured by Microtox. Within the aromatic fraction, the naphthalenes are the most toxic group, while the volatile (benzene, toluene and xylenes) and the heavy fractions (3--6 ring aromatics) only influence the observed toxicity to a minor degree. The results also suggest that alkylated phenols are of significant importance to the total produced water toxicity, with C3-phenols as the most toxic compounds. The heavy metals and the process chemicals play a minor role in the production water from the two fields

  8. Colon-derived uremic biomarkers induced by the acute toxicity of Kansui radix: A metabolomics study of rat plasma and intestinal contents by UPLC-QTOF-MS(E).

    Yang, Zhou; Hou, Jin-Jun; Qi, Peng; Yang, Min; Yan, Bing-Peng; Bi, Qi-Rui; Feng, Rui-Hong; Yang, Wen-Zhi; Wu, Wan-Ying; Guo, De-An

    2016-07-15

    Kansui radix (KR) is a poisonous Chinese herbal medicine recorded in the Chinese Pharmacopoeia, and the acute toxicity obstructs its clinical applications. To explore its acute toxicity mechanism to enhance clinical safety, a metabolomics study based on UPLC-ESI-QTOF-MS(E) was performed. Wistar rats were exposed for 4h to the aqueous and ethyl acetate extracts prepared from KR at a high dose (25g/kg). The contents of six different sections of rat intestine, including the duodenum, jejunum, ileum, cecum, colon, and rectum were collected as samples for the first time, as well as the rat plasma. The interesting results showed that only those rats exposed to the ethyl acetate extract showed a watery diarrhea, similar to the observed acute human toxicity. The identified biomarkers found in the plasma, such as phenol sulfate, indoxyl sulfate, and p-cresol sulfate were significantly perturbed in the rats. These biomarkers are known as colon-derived uremic compounds, which were first reported with respect to KR. The three essential amino acids which produced these biomarkers were only found in the contents of colon and rectum. A hypothesis was proposed that only the colon-derived uremic compounds induced by KR might be responsible for the acute toxicity. Three traditional process methods to reduce the toxicity of KR were compared based on these biomarkers, and different levels of toxicity modulation were observed. These results may be helpful to further understand the mechanism of acute toxicity, and the relevance of the traditional process methods to ameliorate the adverse effects of KR. PMID:26433353

  9. 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

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

    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. 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. 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. HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly

  11. Endosulfan acute toxicity in Bufo bufo gills: Ultrastructural changes and nitric oxide synthase localization

    Endosulfan is an organochlorine pesticide used in agriculture for a wide range of crops. Endosulfan concentrations of up to 0.7 mg/L can be found in ponds and streams near sprayed agricultural fields. We investigated the short-term toxicity of endosulfan in common toad (Bufo bufo) tadpoles after 24, 48, and 96 h of exposure. Acute toxicity was evaluated at nominal concentrations ranging from 0.01 to 0.6 mg/L: concentrations that could be found after the application of pesticide. Our results show that 0.43 mg/L of endosulfan caused 50% mortality (LC50). The effects of a sublethal endosulfan concentration (0.2 mg/L) on gill apparatus morphology were evaluated by scanning and transmission electron microscopy. Immunohistochemical methods were also applied to detect the expression pattern of the inducible isoform of nitric oxide synthase (iNOS) in the gills using the confocal laser scanner microscope. Exposure to 0.2 mg/L of endosulfan caused an apparent increase in mucus production, the occurrence of secretory vesicles and lamellar bodies, a widening of intercellular spaces and additionally there was evidence of an inflammatory response in the gill apparatus. The morphological alterations occurred after 24 h and were more pronounced after 48 and 96 h of exposure. Altered morphology and increased mucus secretion indicate impaired gas exchange and osmoregulation in the gills. In addition, there was an increase of iNOS expression after 24 and 48 h which may reflect hypoxia and inflammation in the gill epithelium. Our results clearly indicate that short-term exposure to a sublethal concentration of endosulfan, near the high end of the environmental range, disrupts gill morphology and function in B. bufo tadpoles

  12. Acute Toxicity Assessment of Reactive Red 120 to Certain Aquatic Organisms.

    Darsana, R; Chandrasehar, G; Deepa, V; Gowthami, Y; Chitrikha, T; Ayyappan, S; Goparaju, A

    2015-11-01

    Laboratory experiments were conducted to evaluate the acute toxicity of a widely used textile dye namely Reactive Red 120 (RR 120) on certain aquatic species such as Pseudokirchneriella subcapitata (green alga), Lemna gibba (duck weed), Daphnia magna (water flea) and Oncorhynchus mykiss (Rainbow trout). All experiments were performed as per the OECD Guidelines for Testing of Chemicals. The toxicity end points of EC50, LC50, NOEC and LOEC for RR 120 were determined with 95% confidence limits using TOX STAT version 3.5. The EC50 of RR 120 for green alga, duck weed and water flea are >100.00, 64.34, 10.40 mg L(-1), respectively and LC50 for Rainbow trout is 78.84 mg L(-1). Based on the results, the test item RR 120 could be classified as non-toxic to green alga, harmful to duck weed and Rainbow trout, toxic to water flea. PMID:26350898

  13. Acute toxicity study of the oil from Azadirachta indica seed (neem oil).

    Gandhi, M; Lal, R; Sankaranarayanan, A; Banerjee, C K; Sharma, P L

    1988-01-01

    The seed oil of Azadirachta indica (neem oil) is well known for its medicinal properties in the indigenous Indian system of medicine. Its acute toxicity was documented in rats and rabbits by the oral route. Dose-related pharmacotoxic symptoms were noted along with a number of biochemical and histopathological indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24 ml/kg in rabbits. Prior to death, animals of both species exhibited comparable pharmacotoxic symptoms in order and severity, with lungs and central nervous system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was tested in the same manner to document the degree to which the physical characteristics of an oil could contribute to the oral toxicity of neem oil. PMID:3419203

  14. Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

    Costa-Silva, J H; Lima, C R; Silva, E J R; Araújo, A V; Fraga, M C C A; Ribeiro E Ribeiro, A; Arruda, A C; Lafayette, S S L; Wanderley, A G

    2008-03-28

    Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity. PMID:18281172

  15. Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses.

    Pinto, Flávia Cristina Morone; De-Oliveira, Ana Cecília A X; De-Carvalho, Rosangela R; Gomes-Carneiro, Maria Regina; Coelho, Deise R; Lima, Salvador Vilar C; Paumgartten, Francisco José R; Aguiar, José Lamartine A

    2016-02-10

    The acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of BC were studied. Cytotoxicity of BC was evaluated in cultured C3A hepatoma cells (HepG2/C3A) using a lactate dehydrogenase (LDH) activity assay. Acute toxicity was tested in adults Wistar rats treated with a single dose of BC. The genotoxicity of BC was evaluated in vivo by the micronucleus assay. BC (0.33-170 μg/mL) added to C3A cell culture medium caused no elevation in LDH release over the background level recorded in untreated cell wells. The treatment with the BC in a single oral dose (2000 mg/kg body weight) caused no deaths or signs of toxicity. BC attenuated CP-induced and inhibition the incidence of MNPCE (female: 46.94%; male: 22.7%) and increased the ratio of PCE/NCE (female: 46.10%; male: 35.25%). There was no alteration in the LDH release in the wells where C3A cells were treated with increasing concentrations of BC compared to the wells where the cells received the cell culture medium only (background of approximately 20% cell death), indicated that in the dose range tested BC was not cytotoxic. BC was not cytotoxic, genotoxic or acutely toxic. BC attenuated CP-induced genotoxic and myelotoxic effects. PMID:26686163

  16. 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.

  17. Acute toxicity modeling of rainbow trout and silver sea bream exposed to waterborne metals.

    Liao, C M; Lin, M C

    2001-01-01

    Of three proposed acute toxicity models, the uptake-depuration (UD) model, the time-integrated concentration (TIC) model, and the concentration-time (CT) model are derived and verified with acute toxicity data to estimate the internal residues of waterborne metals in fish as a function of a few constants and variables. The main factors are the exposure time, the external exposure concentration, the bioconcentration factor (BCF), and the depuration rate constant (k2). The UD model is based on the concept of residue levels at the cell membrane well correlating with the whole-body concentrations, whereas the TIC and the CT models are based on the idea of irreversible inhibition of the enzyme acetylcholinesterase (AChE) governing the metal acute toxicity in that metals in the entire fish or in the aqueous phase can be described by the critical area under the time-concentration curve that is associated with a critical TIC of toxicant in the target tissue. A highly significant correlation (r2 > 0.9) was found between predictions and LC50(t) data for both the TIC and the CT models, indicating successfully describe 4- to 18-d LC50(t) data of arsenic (As), cobalt (Co), copper (Cu), and Co/Cu mixture in rainbow trout (Oncorhyuchus mykiss) and of Cu in fingerlings and subadults of silver sea bream (Sparus sarba). The time-dependent lethal internal concentration at the site of action that causes 50% mortality is also predicted for a given compound and species. It concludes that the TIC and the CT models can be applied to regulate the acute toxicity and to estimate incipient LC50 values and internal residues of waterborne metals in fish. PMID:11501285

  18. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  19. Variation in toxicity response of Ceriodaphnia dubia to Athabasca oil sands coke leachates.

    Puttaswamy, Naveen; Turcotte, Dominique; Liber, Karsten

    2010-07-01

    Coke from the Athabasca (Alberta, Canada) oil sands operations may someday be integrated into reclamation landscapes. It is hypothesized that the metals associated with the solid coke may leach into the surrounding environment. Therefore, the main objectives of this study were to characterize the toxicity and chemistry of coke leachates collected from two field lysimeters (i.e. shallow lysimeter and deep lysimeter) over a period of 20months, as well as from other oil sands coke storage sites. In addition, a batch renewal leaching of coke was conducted to examine the rate of metals release. Chronic toxicity of key metals (e.g. Al, Mn, Ni and V) found in lysimeter coke leachate was evaluated separately. Toxicity test results revealed that whole coke leachates (100% v/v) were acutely toxic to Ceriodaphnia dubia; the 7-day LC50 values were always coke leachate. The deep lysimeter leachate was generally more toxic than the shallow lysimeter leachate, likely because of significantly higher concentrations of vanadium (V) found in the deep lysimeter leachate at all sampling times. Vanadium concentrations were higher than all other metals found in the leachate from both lysimeters, and in the batch renewal leaching study. Furthermore, V found in leachates collected from other oil sands field sites showed a concentration-response relationship with C. dubia survival. Mass balance calculations indicated that 94-98% of potentially leachable V fraction was still present in the coke from two field lysimeters. Evidence gathered from these assessments, including toxic unit (TU) calculations for the elements of concern, suggests that V was the likely cause of toxicity of the deep lysimeter leachate, whereas in the shallow lysimeter leachate both Ni and V could be responsible for the observed toxicity. PMID:20553931

  20. 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 complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. 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. PMID:26655658

  1. Kinetics, intermediates and acute toxicity of arsanilic acid photolysis.

    Zhu, Xiang-Dong; Wang, Yu-Jun; Liu, Cun; Qin, Wen-Xiu; Zhou, Dong-Mei

    2014-07-01

    Arsanilic acid (4-amino phenyl arsenic acid, ASA) is widely used in poultry production as feed additives, while most of ASA in the feed is excreted in the animal manure and released into the environment. However, the environmental behaviors of ASA were not well understood. In the present study, the photolysis behaviors of ASA and the toxicity of its metabolites to luminescent bacterium were studied. The results showed that ASA could be photodegraded and this process was strongly affected by solution pH, humic acid and dissolved oxygen. Upon UV irradiation for 360 min, ASA could be completely eliminated, but the reduction of total organic carbon (TOC) was not significant. In addition, NH4(+) ions and inorganic arsenic including arsenite and arsenate were identified as the predominant end-products. The conversion of ASA included both direct and indirect photolysis involving radicals, and its possible photolysis pathways were proposed on the basis of the identified intermediates. Unfortunately, higher adverse effects of the conversion products of ASA on bacteria were observed during the photolysis reaction. The results of present study might be helpful for assessing the environmental persistence and risks of ASA. PMID:24405966

  2. ACUTE AND SUBACUTE TOXICITY STUDIES ON SHODHANA PROCESSED GUGGUL

    Poonam Taru, Mukta Abhyankar*, Vaishali Undale and Ashok Bhosale

    2013-02-01

    Full Text Available Ayurveda– The science of life is known to the mankind since time immemorial. It prolongs life span, maintains positive health and cures diseases. Due to its high effectiveness, popularity and the socio-economic status it was recognized as an independent branch of learning and has been known as “Rasa Shastra” and “Rasa chikitsa” in the field of Ayurveda. After the development of rasa Shastra it was made possible for the minerals and metals, precious and semiprecious stones to pass through various pharmaceutical processes like shodhana, Marana etc. for several times so as to convert these in to a form or compound which may suit to the human body and could be observed and assimilated easily into the system without exhibiting any toxic symptom. There are two objectives to purify a natural herb. There are two objectives of purification. First is to remove the external and internal impurities. The second reason is to increase the medicinal value. The shodhana processes of guggul can be done by general purification and specific purification. Present work involves study of hematological, biochemical, Histopathological changes in mice treated with Guggul before and after shodhana process.

  3. Variation in animal response to different toxicants

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    The variation in response of different lots of male Swiss albino mice to pyrolysis effluents from surgical cotton and from bisphenol A polycarbonate, and to pure carbon monoxide, is discussed. The variation appeared to be less with the pyrolysis gases from polycarbonate than with pure carbon monoxide.

  4. Isolation and characterization of the acutely toxic compounds in oil sands process water from Syncrude and Suncor

    The hot water process for the extraction of bitumen from oil sands leads to the production of large volumes of wastewater and the formation of a large inventory of fine clay tailings. This fine tailings material and its associated water are acutely toxic to various aquatic test organisms during bioassays. A study was carried out to assess the acute toxicity of wastewater from tailings ponds and to identify the acutely toxic fraction of the wastewater. The Microtox bacterial bioassay was used to assess the acute toxicity before and after various treatments. Where significant reductions in acute toxicity were found, further tests were carried out using Daphnia magna and rainbow trout. The Microtox effective concentration (EC50; analogous to the LC50, lethal concentration at which 50% mortality occurs) of all centrifuged tailings pond water samples varied between 265 and 460 ml of sample water per liter of test solution. Daphnia LC50 varied between 760-980 ml/l and rainbow trout LC50 was 125 ml/l. All, or part of the acute toxicity of the process water can be accounted for by the following classes of compounds. Organic compounds that have a non-polar component, removed by solid phase extraction with C18 sorbent account for 100% of acute toxicity of all samples. Organic acids, as removed by precipitation at pH 2.5, also account for 100% of acute toxicity except from pond 1A at Suncor. In this pond organic acids account for 55-60% of acute toxicity and non-polar organic volatile compounds account for 20-35% with the balance being composed of non-polar organic compounds that are neither volatile nor organic acids that precipitate at pH 2.5. 22 refs., 17 figs

  5. 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.

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

    Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

    2011-05-01

    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.

  7. Acute and chronic oral toxicity of a partially purified plaunotol extract from Croton stellatopilosus Ohba.

    Chaotham, Chatchai; Chivapat, Songpol; Chaikitwattana, Anan; De-Eknamkul, Wanchai

    2013-01-01

    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. PMID:24286075

  8. 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.

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

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    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. PMID:24369482

  10. Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

    Cho, MyoungLae; Shin, Gi-Hae; Kim, Jae-Min; Lee, Jin-Ha; Park, Sun-Ok; Lee, Sang-Jong; Shin, HyunMu; Lee, Boo-Yong; Kang, Il-Jun; Lee, Ok-Hwan

    2016-06-01

    The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats. PMID:26925497