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Sample records for acute toxic class

  1. Acute toxicity of Daphnia pulex to six classes of chemical compounds potentially hazardous to Great Lakes aquatic biota

    USGS Publications Warehouse

    Smith, Stephen B.; Savino, Jacqueline F.; Blouin, Marc A.

    1988-01-01

    Of the six classes of chemicals potentially hazardous to Great Lakes aquatic biota, derivatives of polyaromatic hydrocarbons (PAHs) were the most acutely toxic (48-h EC 50) to Daphnia pulex. The other classes, listed in order of decreasing toxicity were alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, silicon-containing compounds. O f the 41 compounds representing the six chemical classes, 6 were extremely toxic (> 0.01 - 0.1 mg/L), 11 highly toxic (> 01. - 1.0 mg/L), 20 moderately toxic (> 1.0 - 10.0 mg/L), and 4 slightly toxic (>10 - 100 mg/L). The reference compound, p, p'DDT, was super toxic (< 0.01 mg/L). Based on toxicity and relative abundance (hazard ranking) of the 21 compounds that were detected in tissue of Great Lakes fishes, the classes of compounds that present the greatest threat to Great Lakes aquatic biota are PAH derivatives, alkyl halides, and cyclic aklanes.

  2. Acute toxicity of arsenobetaine

    SciTech Connect

    Kaise, T.; Watanabe, S.; Itoh, K.

    1985-01-01

    The acute toxicity of arsenobetaine was studied in male mice. No deaths were observed with oral administration of 10 g/kg of arsenobetaine. Therefore the LD/sub 50/ value was higher than 10 g/kg. This compound was found in urine in the non-metabolized form. No particular toxic symptoms were observed following administration. These suggest that arsenobetaine has low toxicity and is not metabolized in mice.

  3. Acute toxicity of ingested fluoride.

    PubMed

    Whitford, Gary Milton

    2011-01-01

    This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve.

  4. Acute and chronic arsenic toxicity

    PubMed Central

    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 occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water. PMID:12897217

  5. Acute copper toxicity following copper glycinate injection.

    PubMed

    Oon, S; Yap, C-H; Ihle, B U

    2006-11-01

    We present a patient who developed multi-organ failure due to severe copper toxicity following attempted suicide by s.c. injection of copper glycinate. Acute copper toxicity is rare in the developed world, although it occurs more frequently in developing world countries, where it is a common mode of suicide. Acute toxicity usually results from oral ingestion and there are several local and systemic effects. Specific management can be difficult as there is little evidence regarding the efficacy of chelating agents in acute toxicity.

  6. Alternative acute oral toxicity assessment under REACH based on sub-acute toxicity values.

    PubMed

    Gissi, Andrea; Louekari, Kimmo; Hoffstadt, Laurence; Bornatowicz, Norbert; Aparicio, Alberto Martin

    2016-11-08

    The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one tonne per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e. NO(A)EL at or above the classification threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e. LD₅₀ above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD₅₀. According to the REACH regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral study by using this adaptation.

  7. Acute aquatic toxicity of biodiesel fuels

    SciTech Connect

    Wright, B.; Haws, R.; Little, D.; Reese, D.; Peterson, C.; Moeller, G.

    1995-12-31

    This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in a flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.

  8. Acute toxicity of gasoline and some additives.

    PubMed Central

    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 chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

  9. Acute toxicity of gasoline and some additives

    SciTech Connect

    Reese, E.; Kimbrough, R.D.

    1993-12-01

    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 chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. 128 refs., 7 tabs.

  10. [An acute toxicity study of bromantane].

    PubMed

    Bugaeva, L I; Verovskiĭ, V E; Iezhitsa, I N; Spasov, A A

    2000-01-01

    The toxicity of bromantan was evaluated by conventional acute tests (according to Belen'kiĭ) and by the behavioral activity data (according to Irvin). A method of integral graphical representation of the behavioral activity data is suggested, according to which the results are plotted as a "dose trajectory." Using the dose trajectory constructed for bromantan, the levels of therapeutic, toxic, and lethal doses were calculated. It was established that catecholaminergic effects account for the mechanism of therapeutic action of bromantan, while cholinergic effects determine the drug action in toxic doses.

  11. Olanzapine overdose presenting with acute muscle toxicity

    PubMed Central

    Keyal, Niraj; Shrestha, Gentle Sunder; Pradhan, Saurabh; Maharjan, Ramesh; Acharya, Subhash Prasad; Marhatta, Moda Nath

    2017-01-01

    Olanzapine is an atypical antipsychotic drug that is being increasingly used as an intentional overdose. It usually presents with reduced and fluctuating level of consciousness and coma. It may rarely present with muscle toxicity by binding to HT2A receptor in skeletal muscle and increasing its permeability. We report a case of such poisoning which had no obvious symptoms but was brought to emergency due to overdose and was found to have acute muscle toxicity as evidenced by raised creatine phosphokinase (CPK) levels. From this, we also want to emphasize that CPK levels should be checked in all the patient's prescribed olanzapine to look for muscle toxicity.

  12. CDP-choline: acute toxicity study.

    PubMed

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

    1983-01-01

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

  13. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  14. Acute methanol toxicity in minipigs

    SciTech Connect

    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.

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

    PubMed

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

    2008-05-01

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

  16. Acute aquatic toxicity of alkyl phenol ethoxylates

    SciTech Connect

    Schueuermann G2 )

    1991-04-01

    The recently derived log Kow (octanol/water partition coefficient in logarithmic form) increment for a nonterminal oxyethylene unit was used to calculate a quantitative structure-activity relationships for literature data on the acute crustacean toxicity of polyoxyethylene surfactants. The resulting log Kow regression parameters are between the corresponding values for nonpolar and polar narcosis, which supports an interpretation of the surfactants' aquatic toxicity on the basis of another distinct mode of action. Furthermore, a comparison with calculated water solubility data indicates that for log Kow greater than 5 an aquatic toxicity decrease due to a solubility limit is expected, which gets support from two other sets on toxicity data of nonyl phenol polyethoxylates.

  17. Acute toxicity of gymnodimine to mice.

    PubMed

    Munday, Rex; Towers, Neale R; Mackenzie, Lincoln; Beuzenberg, Veronica; Holland, Patrick T; Miles, Christopher O

    2004-08-01

    The acute toxicity of the phycotoxin gymnodimine to female Swiss mice by intraperitoneal injection and by oral administration has been determined. Gymnodimine was highly toxic by injection, the LD50 being only 96 microg/kg. Animals either died within 10 min of injection or made a full recovery with no perceptible long-term effects. Gymnodimine was also toxic after oral administration by gavage (LD50 755 microg/kg), but was much less toxic when administered with food. No signs of toxicity were seen in mice voluntarily ingesting food containing gymnodimine at a level sufficient to give a dose of approximately 7500 microg/kg. Pre-treatment with physostigmine or neostigmine protected against injected gymnodimine, suggesting that the latter exerts its toxic effects via blockade of nicotinic receptors at the neuromuscular junction. The low toxicity of gymnodimine when ingested with food suggests that this compound is of low risk to humans, a conclusion that is consonant with anecdotal evidence for the absence of harmful effects in individuals consuming shellfish contaminated with gymnodimine.

  18. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect

    Benson, J.M.; Hahn, F.F.; Barr, E.B.

    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).

  19. Acute toxicity from baking soda ingestion.

    PubMed

    Thomas, S H; Stone, C K

    1994-01-01

    Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

  20. Quinolone arthropathy--acute toxicity to immature articular cartilage.

    PubMed

    Gough, A W; Kasali, O B; Sigler, R E; Baragi, V

    1992-01-01

    A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP). Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown. This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis. Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction. Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage.

  1. Measuring the acute toxicity of estuarine sediments

    SciTech Connect

    DeWitt, T.H.; Swartz, R.C.; Lanberson, J.O.

    1989-01-01

    Estuarine sediments frequently are repositories and sources of anthropogenic contaminants. Toxicity is one method of assessing the environmental quality of sediments, yet because of the extreme range of salinities that characterize estuaries few infaunal organisms have both the physiological tolerance and sensitivity to chemical contaminants to serve in estuarine sediment toxicity tests. The study describes research on the estuarine burrowing amphipod, Eohaustorius estuarius Bosworth, 1973, whose survival was >95% in control sediments across a 2 to 28% salinity range over 10-d periods. E. estuarius also was acutely sensitive to low sediment concentrations of the polycyclic aromatic hydrocarbon, fluoranthene (LC50 approximately = 10.6 mg/kg), and its sensitivity to fluoranthene was not affected by salinity. E. estuarius was almost as sensitive as Rhepoxynius abronius to fluoranthene and to field-collected sediments from Puget Sound urban and industrial bays. E. estuarius was also more tolerant of very fine, uncontaminated sediments than R. abronius. Furthermore, E. estuarius was more sensitive to sediments spiked with fluoranthene than the freshwater amphipod, Hyalella azteca. E. estuarius, and possibly other estuarine haustoriid species, appears to be an excellent candidate for testing the acute toxicity if estuarine and marine sediments.

  2. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos.

  3. Acute Oral Toxicity Up-And-Down-Procedure

    EPA Pesticide Factsheets

    The Up-and-Down Procedure is an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps. Find out about this test procedure.

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

    USGS Publications Warehouse

    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.

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

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h 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 2000mg 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.

  6. Electrophiles and acute toxicity to fish.

    PubMed Central

    Hermens, J L

    1990-01-01

    Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms. PMID:2269228

  7. Acute toxicity of methanol to mytilus edulis

    SciTech Connect

    Helmstetter, A.; Gamerdinger, A.P.; Pruell, R.J.

    1996-12-31

    Methanol is being promoted as an alternative fuel because of the clean air benefits of reduced carbon monoxide and other by-product emissions. In the event of an accidental spill or leakage from a storage tank, there is limited data available on the impact of alternative fuels on marine ecosystems. Before considering the impact of methanol on ecosystem processes, it is necessary to establish the acute toxicity. The blue mussel (Mytilus edulis) was selected for study because of its use as an indicator species of marine ecosystem health (Widdows and Donkin 1992). Our primary objective was to determine the LC-50 value of methanol to adult Mytilus edulis. We also not sublethal effects that were observed during the course of the 96-hr exposure. 16 refs., 1 fig. 3 tabs.

  8. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

  9. Acute and environmental toxicity studies with hexazinone.

    PubMed

    Kennedy, G L

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

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

    2013-08-01

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

  11. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development.

    PubMed

    Barron, M G; Lilavois, C R; Martin, T M

    2015-04-01

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limited by the availability of comprehensive high quality MOA and toxicity databases. The current study developed a dataset of MOA assignments for 1213 chemicals that included a diversity of metals, pesticides, and other organic compounds that encompassed six broad and 31 specific MOAs. MOA assignments were made using a combination of high confidence approaches that included international consensus classifications, QSAR predictions, and weight of evidence professional judgment based on an assessment of structure and literature information. A toxicity database of 674 acute values linked to chemical MOA was developed for fish and invertebrates. Additionally, species-specific measured or high confidence estimated acute values were developed for the four aquatic species with the most reported toxicity values: rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas), bluegill (Lepomis macrochirus), and the cladoceran (Daphnia magna). Measured acute toxicity values met strict standardization and quality assurance requirements. Toxicity values for chemicals with missing species-specific data were estimated using established interspecies correlation models and procedures (Web-ICE; http://epa.gov/ceampubl/fchain/webice/), with the highest confidence values selected. The resulting dataset of MOA assignments and paired toxicity values are provided in spreadsheet format as a comprehensive standardized dataset available for predictive aquatic toxicology model development.

  12. Ratios between acute aquatic toxicity and effects on population growth rates in relation to toxicant mode of action

    SciTech Connect

    Roex, E.W.M.; Gestel, C.A.M. Van; Wezel, A.P. Van; Straalen, N.M. Van

    2000-03-01

    Environmental risk assessment of chemicals is mostly based on the results of standardized toxicity tests. To obtain environmental quality criteria, extrapolation factors are used that depend on the amount and quality of available data. These extrapolation factors do not, however, take into account the mode of action of the compound tested or the life history of the test organism. In this study, the authors analyzed the variability in acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action. Chemicals were classified as nonpolar narcotics, polar narcotics, specifically acting compounds, and heavy metals. As an acute endpoint, the LC50 was used; as a chronic endpoint, the lowest test concentration at which the natural rate of population increase (r) is affected, or LOEC(r), was used. Data were derived from the on-line literature. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class. For the other classes, the variation in ACRs is larger. Fish species especially show a relatively large ACR. For heavy metals, differences in the mode of action may play an important role in explaining differences in ACRs. For the other three classes, however, it is less reliable to predict chronic toxicity using the results of acute tests. In general, differences in species sensitivity rather than in mode of action for the chemical seem to determine differences in ACRs.

  13. Towards global QSAR model building for acute toxicity: Munro database case study.

    PubMed

    Chavan, Swapnil; Nicholls, Ian A; Karlsson, Björn C G; Rosengren, Annika M; Ballabio, Davide; Consonni, Viviana; Todeschini, Roberto

    2014-10-09

    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.

  14. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    SciTech Connect

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-12-31

    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 CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} 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.

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

    SciTech Connect

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

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

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

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; Schalie, W.H. van der; Leather, G.R.

    1995-05-01

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

  17. Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

    USGS Publications Warehouse

    Dahlich, G.M.; Larson, R.E.; Gingerich, W.H.

    1982-01-01

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity. Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish. The LC50 of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.

  18. Towards a scheme of toxic equivalency factors (TEFs) for the acute toxicity of PAHs in sediment.

    PubMed

    Fisher, Tom T; Law, Robin J; Rumney, Heather S; Kirby, Mark F; Kelly, Carole

    2011-11-01

    Toxic equivalency factors/quotients (TEF/TEQs) express the toxicity of complex mixtures. For PAHs, TEF values are available for assessing their carcinogenic potential and are expressed as benzo[a]pyrene equivalents. This study develops a similar approach for their acute toxicity in sediments. Acute toxicity (10 day EC₅₀) values were generated using the marine amphipod Corophium volutator bioassay for twelve low molecular weight PAHs. The results ranged from 24 to > 1000 mg/Kg sediment dry weight for 4-methyldibenzothiophene and anthracene, respectively. Phenanthrene was used as the reference compound (TEF=1) and so the TEQ values derived are expressed as phenanthrene equivalents. In order to illustrate the applicability of this approach to the development of marine indicators we plotted TEQ values for acute toxicity to UK environmental monitoring data. Further work is required to validate the TEF values produced and to extend the TEQ approach to include a wider range of low molecular weight PAHs.

  19. Identification of acute toxicants in New Bedford Harbor sediments

    SciTech Connect

    Ho, K.T.; McKinney, R.A.; Kuhn, A.; Pelletier, M.C.; Burgess, R.M.

    1997-03-01

    New Bedford Harbor (NBH) is a marine Superfund site contaminated with high concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and metals. Experiments were conducted to determine the causal toxic agent(s) in pore waters from New Bedford Harbor sediments to amphipods and mysid shrimp. Chemical manipulations to characterize toxicity revealed that pore-water toxicity was organic in nature. Fractionation and subsequent mass spectral identification of peaks in the toxic fraction indicated that PCBs. PAHs, and unknown compounds were present. Comparisons of PAH LC50s and PAH concentrations in this fraction indicated that the toxicity was not due to PAHs because the PAH concentrations were much lower than the reported PAH LC50s. One unknown peak was positively identified as bis(2-ethylhexyl) phthalate, and the other tentatively identified as pyrazole. Toxicity tests and comparison of toxicity in the blank and toxic fractions eliminated the two unknowns as toxic causal agents. The authors determined the range of PCB LC50s to fall between 10 and 110 ppb for Mysidopsis bahia and Ampelisca abdita. Concentrations of PCBs for the toxic fractions ranged from 12 to 27 ppb. This range falls within the observed PCB LC50s for M. bahia and A. abdita. Based upon these PCB concentrations, they concluded that PCBs were the acute toxic agents in NBH pore waters. Other compounds in the toxic fractions, or compounds that coeluted and were undistinguished from PCBs had minor contributions to the measured toxicity.

  20. Acute toxicity of the herbicide bromoxynil to Daphnia magna

    USGS Publications Warehouse

    Buhl, Kevin J.; Hamilton, Steven J.; Schmulbach, James C.

    1993-01-01

    The acute toxicities of technical-grade bromoxynil octanoate (BO) and two commercial formulations, Buctril® and Bronate®, to < 24-h-old neonate Daphnia magna (Straus) were determined in soft, hard, and oligosaline water. In addition, effects of life stage, feeding, aging the herbicide, and exposure duration on BO toxicity to daphnids were investigated. Regardless of formulation, life stage, and water quality, BO was found to be extremely to highly toxic to daphnids in standard tests; 48-h EC50 values ranged from 41 to 161 m̈g/L. Bromoxynil octanoate was the most toxic to neonates in soft water and the least toxic in hard water. The acute toxicities of the three bromoxynil herbicides to a given age group of daphnids were similar within the same water type. Overall, neonates and 7-d-old adults were more sensitive than 14- or 15-d-old adults to each herbicide. Feeding daphnids during the toxicity test significantly decreased BO toxicity compared to not feeding them. Aging BO (as Buctril) in hard water decreased its toxicity, and the rate of deactivation was rapid, with an estimated half-life of biological activity of 13 h. Daphnids immobilized by exposures to toxic BO concentrations for ≤ 6 h recovered their mobility, whereas exposures of 18 and 24 h to BO produced toxic effects in daphnids similar to those exposed for 48 h. These results indicated that standard continuous exposure tests may not adequately predict the acute toxicity of BO to freshwater animals in the field.

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

    PubMed

    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.

  2. [Acute toxic hepatitis due to drinking water].

    PubMed

    Martínez Amate, Eva; Rodríguez Manrique, Marco A; González Sánchez, Mercedes; Casado Martin, Marta

    2010-11-01

    Toxic-induced liver disease is uncommon, although the true proportion of cases of hepatotoxicity is unknown, as this entity is underdiagnosed and underreported. The main reasons why toxic-induced liver disease goes unnoticed is the lack of pathognomonic data and the lack of spontaneous reporting by doctors and pharmacists. In some cases, the toxic substance can leave its «signature» in the form of clinical semiology suggestive of an underlying toxic cause. We present a case of hepatotoxicity induced by drinking water (chlorinated), which produced a reactive metabolites syndrome (trihalomethanes from the reaction of chlorine with organic products). Although the clinical presentation was typical, the case posed a diagnostic challenge for the various professionals involved.

  3. Acute toxicity prediction to threatened and endangered ...

    EPA Pesticide Factsheets

    Evaluating contaminant sensitivity of threatened and endangered (listed) species and protectiveness of chemical regulations often depends on toxicity data for commonly tested surrogate species. The U.S. EPA’s Internet application Web-ICE is a suite of Interspecies Correlation Estimation (ICE) models that can extrapolate species sensitivity to listed taxa using least-squares regressions of the sensitivity of a surrogate species and a predicted taxon (species, genus, or family). Web-ICE was expanded with new models that can predict toxicity to over 250 listed species. A case study was used to assess protectiveness of genus and family model estimates derived from either geometric mean or minimum taxa toxicity values for listed species. Models developed from the most sensitive value for each chemical were generally protective of the most sensitive species within predicted taxa, including listed species, and were more protective than geometric means models. ICE model estimates were compared to HC5 values derived from Species Sensitivity Distributions for the case study chemicals to assess protectiveness of the two approaches. ICE models provide robust toxicity predictions and can generate protective toxicity estimates for assessing contaminant risk to listed species. Reporting on the development and optimization of ICE models for listed species toxicity estimation

  4. On the performance of acute toxicity tests using the National Reference Toxicant Database

    SciTech Connect

    Zaidhk, B.

    1995-12-31

    The US National Reference Toxicant Database was used to compile data from 158 Ceriodaphnia dubia, and 187 fathead minnow acute toxicity tests. The data are analyzed using the EPA flow-chart for acute toxicity tests to determine the distribution of test methods selected. The data are reanalyzed using maximum likelihood estimation assuming probit, logit and Gompertz tolerance distributions and non-parametrically using the Spearman-Karber method with and without trimming. The results of these analyses are compared with respect to mean square error for the parametric methods and confidence intervals for the point estimate for all analyses.

  5. [Acute toxicity and bioavailability of nano red elemental selenium].

    PubMed

    Gao, X; Zhang, J; Zhang, L

    2000-01-30

    The reaction ratio of nano red elemental selenium (nanose) with GSH in vitro was one-tenth of that of sodium selenite. Mice were fed with nanose and sodium selenite separately at 50 micrograms/kg BW for 30 days. Both selenium forms could significantly increased Se concentration of blood, liver and activity of blood GSH-Px. Acute toxicity experiment of mice implied that the acute toxicity of nanose was nearly one-seventh of that of sodium selenite. The LD50 for nanose se was 112.98 mg kg BW, and the LD50 for sodium selenite was Se 15.72 mg/kg BW. The acute toxicity of nanose was low for mice.

  6. Support Vector Machine (SVM) as Alternative Tool to Assign Acute Aquatic Toxicity Warning Labels to Chemicals.

    PubMed

    Michielan, Lisa; Pireddu, Luca; Floris, Matteo; Moro, Stefano

    2010-01-12

    Quantitative structure-activity relationship (QSAR) analysis has been frequently utilized as a computational tool for the prediction of several eco-toxicological parameters including the acute aquatic toxicity. In the present study, we describe a novel integrated strategy to describe the acute aquatic toxicity through the combination of both toxicokinetic and toxicodynamic behaviors of chemicals. In particular, a robust classification model (TOXclass) has been derived by combining Support Vector Machine (SVM) analysis with three classes of toxicokinetic-like molecular descriptors: the autocorrelation molecular electrostatic potential (autoMEP) vectors, Sterimol topological descriptors and logP(o/w) property values. TOXclass model is able to assign chemicals to different levels of acute aquatic toxicity, providing an appropriate answer to the new regulatory requirements. Moreover, we have extended the above mentioned toxicokinetic-like descriptor set with a more toxicodynamic-like descriptors, as for example HOMO and LUMO energies, to generate a valuable SVM classifier (MOAclass) for the prediction of the mode of action (MOA) of toxic chemicals. As preliminary validation of our approach, the toxicokinetic (TOXclass) and the toxicodynamic (MOAclass) models have been applied in series to inspect both aquatic toxicity hazard and mode of action of 296 chemical substances with unknown or uncertain toxicodynamic information to assess the potential ecological risk and the toxic mechanism.

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

    SciTech Connect

    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.

  8. Resolving some practical questions about Daphnia acute toxicity tests

    SciTech Connect

    Barera, Y.; Adams, W.J.

    1981-10-01

    Acute toxicity tests were performed with six age groups of Daphnia magna, ranging from less than or equal to6 h to 216 h, and with five chemicals, selected on the basis of their physical and chemical properties as well as their acute toxicity to D. magna. The age of the daphnids did not significantly alter the 48-h EC/sub 50/ values for the chemicals tested. The maximum difference observed in the 48-h EC/sub 50/ values between the 6-h and 216-h age groups was a factor of 3.9 for linear alkylbenzene sulfonate (LAS). For purposes of standardization, it appears that D. magna up to 48 h of age at the beginning of the test can be used to conduct acute toxicity tests with most chemicals. The results of static acute toxicity tests conducted with butylbenzyl phthalate (BBP) and D. magna in the presence and absence of several commonly used solvents indicate that the acute toxicity of this chemical is not altered by the use of a solvent carrier. The 48-h EC/sub 50/ value for BBP without a solvent was 1.0 mg/L, compared with a range of 1.6 to 2.2 mg/L when acetone, dimethylformamide, ethanol, or triethylene glycol were used as solvent carriers. The acute toxicities of the solvents in the absence of BBP were also determined for D. magna. The values ranged from 9.3 to 52.4 g/L. The results of static acute tests performed with D. magna and BBP in the presence of various concentrations of daphnid foods (algae or trout chow), indicate that the 48-h EC/sub 50/ values increase proportionally with an increase in food concentrations. These results suggest that acute toxicity tests with D. magna should be conducted in the presence of food with chemicals with a high Ksigma if the results are to be used to select the test concentrations for a chronic study with daphnids. The type of food and the concentration used in the acute test should be the same as those used in a chronic test.

  9. Acute toxicity and QSAR of chlorophenols on Daphnia magna

    SciTech Connect

    Devillers, J.; Chambon, P.

    1986-10-01

    Chlorophenols which are released into natural waters from various industrial processes and from agricultural uses have been recognized as a group of chemical substances potentially hazardous to the aquatic environment. Therefore it is important to estimate their toxic impact on biota. Thus, the scope of this research was to obtain acute toxicity data for seventeen chlorophenols towards Daphnia magna and to explore the possibilities of deriving QSAR's (quantitative structure-activity relationship) from the above values.

  10. Degradation and acute toxicity studies of degradable implant materials

    NASA Astrophysics Data System (ADS)

    Taylor, Michelle Suzette

    The present study investigated the acute toxicities of the degradation product components of six degradable polymers, the acute toxicities of nine metallic ions and accelerated degradation of one degradable polymer. Prior to these studies, the effect of the anticipated test conditions on the Microtox acute toxicity assay was determined. It was shown that the Microtox is unaffected by pH of water within the range of 5 to 10 and that the test is unaffected by tris buffer at physiologic pH and concentration. The toxicity and rates of degradation of poly(glycolic acid), PGA; two samples of poly(L-lactic acid), PLLA; samples of different molecular weights, poly(caprolactone), PCL; poly(ortho ester), POE; and poly(hydroxybutyrate-cohydroxyvalerate), PHBV, were compared, along with the toxicity of their degradation product components. The toxic concentrations ranged from 100 muM (lactic acid) to 125,000 muM (pentaerythritol). The degradation product components in order of most toxic to least toxic are lactic acid, caproic acid, glycolic acid, cyclohexanedimethanol, propionic acid, hydroxybutyric acid, 1,6-hexanediol, pentaerythritol dipropionate, pentaerythritol and hydroxyvaleric acid. Acute toxicity was determined for metallic ions in water and buffer. The toxic concentrations ranged from 33 muM (Tisp{4+} in water) to 3,580 muM (Wsp{6+} in buffer). The four most toxic ions in water (Tisp{4+}, Mosp{5+}, Fesp{3+}, Crsp{3+}) caused solution pH to decrease markedly. The six other ions (Vasp{3+}, Cosp{3+}, Alsp{3+,} Tisp{4+} adjusted to pH 6.1, Nisp{2+} and Wsp{6+}) markedly. The six other ions (Vasp{3+}, Cosp{3+}, Alsp{3+}, Tisp{4+} adjusted to pH 6.1, Nisp{2+} and Wsp{6+}) did not appreciably affect pH. In buffer, Alsp{3+}, Nisp{2+}, Wsp{6+} and Vsp{3+} became much less toxic, suggesting formation of complexes. In general the least toxic ions do not create an acid environment and/or do form protective complexes. PHBV has good mechanical properties and, compared with the

  11. Acute toxicity of peracetic acid to fish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA; also called peroxyacetic acid) is a promising new therapeutant for parasites and fungus. It is registered with the U.S. Environmental Protection Agency (EPA) as an antimicrobial compound approved for indoor use on hard, non-porous surfaces. This study determined the acute toxi...

  12. Draft Test Guideline: Gammarid Acute Toxicity Test

    EPA Pesticide Factsheets

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

  13. Draft Test Guideline: Penaeid Acute Toxicity Test

    EPA Pesticide Factsheets

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

  14. Draft Test Guideline: Mysid Acute Toxicity Test

    EPA Pesticide Factsheets

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

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

    PubMed

    Wollenberger, L; Halling-Sørensen, B; Kusk, K O

    2000-04-01

    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), streptomycin (ST), sulfadiazine (SU), tetracycline (TC), tiamulin (TI) and tylosin (TY) was tested in accordance to the ISO (1989) and OECD (1996) standard procedures. The acute toxicities (48-h EC50 value, mg/l) in decreasing order were OA (4.6), TI (40), SU (221), ST (487), TY (680) and OTC (approximately 1000). NOECs were 340 mg/l for TC and 1000 mg/l for M and OL. Toxic effect on reproduction occurred generally at concentrations, which were one order of magnitude below the acute toxic levels. The chronic toxicity (EC50 values, mg/l) in the D. magna reproduction test in decreasing order were TI (5.4), SU (13.7), TC (44.8) and OTC (46.2). The NOECs (mg/l) obtained in the reproduction test with OA, ST, TY and M were 0.38 for OA, 32 for ST, 45 for TY and 250 for M. The observed toxicity of OA to D. magna indicates that this substance, which is a commonly used feed additive in fish farms, has a potential to cause adverse effects on the aquatic environment.

  16. Extrapolation of acute toxicity across bee species.

    PubMed

    Thompson, Helen

    2016-10-01

    In applying cross-species extrapolation safety factors from honeybees to other bee species, some basic principles of toxicity have not been included, for example, the importance of body mass in determining a toxic dose. The present study re-analyzed published toxicity data, taking into account the reported mass of the individuals in the identified species. The analysis demonstrated a shift to the left in the distribution of sensitivity of honeybees relative to 20 other bee species when body size is taken into account, with the 95(th) percentile for contact and oral toxicity reducing from 10.7 (based on μg/individual bee) to 5.0 (based on μg/g bodyweight). Such an approach results in the real drivers of species differences in sensitivity-such as variability in absorption, distribution, metabolism, and excretion in and target-receptor binding-being more realistically reflected in the revised safety factor. Body mass can also be used to underpin the other parameter of first-tier risk assessment, that is, exposure. However, the key exposure factors that cannot be predicted from bodyweight are the effects of ecology and behavior of the different species on exposure to a treated crop. Further data are required to understand the biology of species associated with agricultural crops and the potential consequences of effects on individuals at the levels of the colony or bee populations. This information will allow the development of appropriate higher-tier refinement of risk assessments and testing strategies rather than extensive additional toxicity testing at Tier 1. Integr Environ Assess Manag 2016;12:622-626. © 2015 SETAC.

  17. [Acute toxicity of bemithyl and bromithyl].

    PubMed

    Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

    2000-01-01

    The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range.

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

    PubMed

    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.

  19. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia.

    PubMed

    Hijiya, Nobuko; van der Sluis, Inge M

    2016-01-01

    Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with asparaginase use include hypersensitivity (clinical and subclinical), pancreatitis, thrombosis, encephalopathy, and liver dysfunction. Depending on the nature and severity of the toxicity, asparaginase therapy may be altered or discontinued in some patients. Clinical hypersensitivity is the most common asparaginase-associated toxicity requiring treatment discontinuation, occurring in up to 30% of patients receiving Escherichia coli-derived asparaginase. The ability to rapidly identify and manage asparaginase-associated toxicity will help ensure patients receive the maximal benefit from asparaginase therapy. This review will provide an overview of the common toxicities associated with asparaginase use and recommendations for treatment management.

  20. Acute toxicities to larval rainbow trout of representative compounds detected in Great Lakes fish

    USGS Publications Warehouse

    Edsall, Carol Cotant

    1991-01-01

    In recent years the National Fisheries Research Center-Great Lakes has ranked the potential hazard to fish and invertebrates of various chemical compounds detected in two Great Lakes fishes-- lake trout, Salvelinus namaycush, and walleye, Stizostedion vitreum vitreum (Hesselberg and Seelye 1982). This hazard assessment has included the identification of the potential sources of the compounds, determination of the occurrence and abundance of the compounds in Great Lakes fish, and the determination of acute toxicities of representative compounds of 19 chemical classes (Passino and Smith 1987a). In further studies Smith et al. (1988) focused on 6 of the 19 classes of compounds using the zooplankter Daphnia pulex as the test organism. They ranked the six classes as follows (in decreasing order of toxicity): polycyclic aromatic hydrocarbons (PAHs), alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, and silicon-containing compounds.

  1. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... acute toxicity of chemical substances and mixtures (“chemicals”) subject to environmental effects test... per volume of nutrient medium or test solution in a specified period of time. (5) Static system means a test container in which the test solution is not renewed during the period of the test. (c)...

  2. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS... mixtures. In order to minimize the need for animal testing, the Agency encourages the review of existing acute toxicity information on mixtures that are substantially similar to the mixture under...

  3. Acute Toxicity of Thionyl Chloride Vapor for Rats

    DTIC Science & Technology

    1984-11-19

    C. and H. V. Davis (1971), The Acute Toxicity of Brief Exposures to Hydrogen Fluoride, Hydrogen Chloride, Nitrogen Dioxide, and Hydrocyanic Acid ...ELECTRODE • • •WAITE ’SOLENOID VALVE P V|TOW ACID -FLEX - ELECTRICAL INTERCONNECTIONS CHART RECORDER Figure 2. Analysis system for total chloride

  4. Acute toxicity of peracetic acid (PAA) to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

  5. Acute toxicity of karlotoxins to mice

    PubMed Central

    Place, Allen R.; Munday, R.; Munday, J.S.

    2015-01-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 μg/kg or with KmTx 1 or KmTx 3 at up to 4000 μg/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 μg/kg showed a pronounced decrease in food and water intake, lasting 3–4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 μg/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

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

    PubMed

    Korani, M; Rezayat, S M; Gilani, K; Arbabi Bidgoli, S; Adeli, S

    2011-01-01

    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 tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner.

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

    PubMed

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

    1991-01-01

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

  8. Sediment acute toxicity testing utilizing short-term bioassays

    SciTech Connect

    Campbell, M.G.

    1991-01-01

    The purpose of this study was to investigate the usefulness of two new bioassays for acute toxicity assessments of sediments. A bacterial bioassay based on inhibition of alpha-glucosidase biosynthesis in Bacillus licheniformis and a 48-hour lethality bioassay employing the benthic cladoceran, Chydorus sphaericus. were evaluated by direct comparisons with standard bioassays, using sediment samples collected from various sites in Florida. This study showed that the bioassay based on inhibition of alpha-glucosidase biosynthesis in Bacillus licheniformis was useful in the acute toxicity screening of sediment elutriates. In regards to Escambia County, Florida samples, the assay was comparable with the Microtox assay and was especially sensitive for samples containing metals. To determine an appropriate procedure for assessing hydrophobic contaminants of sediments in the B. licheniformis bioassay, two extracting procedures were compared. Based on the responses in the Microtox bioassay, shaking sediment samples in methylene chloride produced extracts that were significantly higher in toxicity than extracts obtained by sonication for eight of the ten sediment samples tested. Comparisons of methanol and dimethyl sulfoxide (DMSO) as exchange solvents revealed that there was generally no significant difference between these solvents in terms of toxicity in the Microtox assay. Solvent extracts prepared by shaking and exchanged into methanol showed lower toxicity in the B. licheniformis bioassay than in the Microtox assay. Observed sediment toxicity in both bioassays was expressed in terms of the equivalent dry weight concentration of sediment causing 50% inhibition of the assay organism.

  9. Acute toxicity value extrapolation with fish and aquatic invertebrates.

    PubMed

    Buckler, Denny R; Mayer, Foster L; Ellersieck, Mark R; Asfaw, Amha

    2005-11-01

    Assessment of risk posed by an environmental contaminant to an aquatic community requires estimation of both its magnitude of occurrence (exposure) and its ability to cause harm (effects). Our ability to estimate effects is often hindered by limited toxicological information. As a result, resource managers and environmental regulators are often faced with the need to extrapolate across taxonomic groups in order to protect the more sensitive members of the aquatic community. The goals of this effort were to 1) compile and organize an extensive body of acute toxicity data, 2) characterize the distribution of toxicant sensitivity across taxa and species, and 3) evaluate the utility of toxicity extrapolation methods based upon sensitivity relations among species and chemicals. Although the analysis encompassed a wide range of toxicants and species, pesticides and freshwater fish and invertebrates were emphasized as a reflection of available data. Although it is obviously desirable to have high-quality acute toxicity values for as many species as possible, the results of this effort allow for better use of available information for predicting the sensitivity of untested species to environmental contaminants. A software program entitled "Ecological Risk Analysis" (ERA) was developed that predicts toxicity values for sensitive members of the aquatic community using species sensitivity distributions. Of several methods evaluated, the ERA program used with minimum data sets comprising acute toxicity values for rainbow trout, bluegill, daphnia, and mysids provided the most satisfactory predictions with the least amount of data. However, if predictions must be made using data for a single species, the most satisfactory results were obtained with extrapolation factors developed for rainbow trout (0.412), bluegill (0.331), or scud (0.041). Although many specific exceptions occur, our results also support the conventional wisdom that invertebrates are generally more sensitive to

  10. Acute toxicity value extrapolation with fish and aquatic invertebrates

    USGS Publications Warehouse

    Buckler, Denny R.; Mayer, Foster L.; Ellersieck, Mark R.; Asfaw, Amha

    2005-01-01

    Assessment of risk posed by an environmental contaminant to an aquatic community requires estimation of both its magnitude of occurrence (exposure) and its ability to cause harm (effects). Our ability to estimate effects is often hindered by limited toxicological information. As a result, resource managers and environmental regulators are often faced with the need to extrapolate across taxonomic groups in order to protect the more sensitive members of the aquatic community. The goals of this effort were to 1) compile and organize an extensive body of acute toxicity data, 2) characterize the distribution of toxicant sensitivity across taxa and species, and 3) evaluate the utility of toxicity extrapolation methods based upon sensitivity relations among species and chemicals. Although the analysis encompassed a wide range of toxicants and species, pesticides and freshwater fish and invertebrates were emphasized as a reflection of available data. Although it is obviously desirable to have high-quality acute toxicity values for as many species as possible, the results of this effort allow for better use of available information for predicting the sensitivity of untested species to environmental contaminants. A software program entitled “Ecological Risk Analysis” (ERA) was developed that predicts toxicity values for sensitive members of the aquatic community using species sensitivity distributions. Of several methods evaluated, the ERA program used with minimum data sets comprising acute toxicity values for rainbow trout, bluegill, daphnia, and mysids provided the most satisfactory predictions with the least amount of data. However, if predictions must be made using data for a single species, the most satisfactory results were obtained with extrapolation factors developed for rainbow trout (0.412), bluegill (0.331), or scud (0.041). Although many specific exceptions occur, our results also support the conventional wisdom that invertebrates are generally more

  11. Acute toxicity of cyanogen chloride to Daphnia magna

    SciTech Connect

    Kononen, D.W.

    1988-09-01

    The destruction of cyanide in waste waters by chlorination has been shown to result in the formation of the extremely toxic compound, cyanogen chloride. Industrial cyanide-containing waste waters may be treated by a batch chlorination process under highly alkaline conditions prior to being discharged into a receiving water systems. Alternatively, if the concentration of cyanide is relatively low, and such waste waters may be diverted to municipal waste treatment facilities where they may be subjected to a process of chlorination which may not be sufficient for the complete oxidative destruction of the available cyanide. Although a large body of literature exists concerning the toxicity of HCN and metallic cyanide compounds to aquatic organisms, there is a comparative scarcity of information concerning cyanogen chloride toxicity. This study was designed to determine the acute toxicity of CNCl to Daphnia magna neonates under static bioassay conditions.

  12. Acute toxicity of 50 metals to Daphnia magna.

    PubMed

    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 < 100 µg l(-1) ; EC50s of 13 elements (Al, Sc, Cr, Co, Ni, Zn, Se, Rb, Y, Rh, Pt, Tl and Pb) were between 100 and 1000 µg l(-1) ; EC50s of 14 elements (Li, V, Mn, Fe, Ge, As, In, Sn, Sb, Te, Cs, Ba, W and Ir) were between 1,001 and 100,000 µg l(-1) ; EC50s of six elements (Na, Mg, K, Ca, Sr and 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.

  13. Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans.

    PubMed

    Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Fiumano, Vittorio; Isidori, Marina

    2014-11-01

    The growing use of cytostatic drugs is gaining relevance as an environmental concern. Environmental and distribution studies are increasing due to the development of accurate analytical methods, whereas ecotoxicological studies are still lacking. The aim of the present study was to investigate the acute and chronic toxicity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to five classes of Anatomical Therapeutic Classification (ATC) on primary consumers of the aquatic chain (Daphnia magna, Ceriodaphnia dubia, Brachionus calyciflorus, and Thamnocephalus platyurus). Acute ecotoxicological effects occurred at concentrations in the order of mgL(-)(1), higher than those predicted in the environment, and the most acutely toxic drugs among those tested were cisplatin and doxorubicin for most aquatic organisms. For chronic toxicity, cisplatin and 5-fluorouracil showed the highest toxic potential in all test organisms, inducing 50% reproduction inhibition in crustaceans at concentrations on the order of μgL(-)(1). Rotifers were less susceptible to these pharmaceuticals. On the basis of chronic results, the low effective concentrations suggest a potential environmental risk of cytostatics. Thus, this study could be an important starting point for establishing the real environmental impact of these substances.

  14. Acute toxicity of saline produced waters to marine organisms

    SciTech Connect

    Pillard, D.A.; Evans, J.M.; DuFresne, D.L.

    1996-11-01

    Produced waters from oil and gas drilling operations are typically very saline, and may cause acute toxicity to marine organisms due imbalances as well as to an excess or deficiency of to osmotic specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow, (Cyprinodon variegatus), and inland silvemide (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Individual ions (sodium, potassium, calcium, magnesium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. Organisms were exposed for 48 hours. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that salinity of the test solution may play an important role in the responses of the organisms to produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in produced water is a result of common ions, salinity, or some other unknown toxicant.

  15. Protection against oxaliplatin acute neurosensory toxicity by venlafaxine.

    PubMed

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

    2003-07-01

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

  16. Acute toxicity of nickel nanoparticles in rats after intravenous injection

    PubMed Central

    Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2014-01-01

    This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

  17. Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test.

    PubMed

    Klüver, Nils; Vogs, Carolina; Altenburger, Rolf; Escher, Beate I; Scholz, Stefan

    2016-12-01

    Fish embryos have become a popular model in ecotoxicology and toxicology. The fish embryo acute toxicity test (FET) with the zebrafish embryo was recently adopted by the OECD as technical guideline TG 236 and a large database of concentrations causing 50% lethality (LC50) is available in the literature. Quantitative Structure-Activity Relationships (QSARs) of baseline toxicity (also called narcosis) are helpful to estimate the minimum toxicity of chemicals to be tested and to identify excess toxicity in existing data sets. Here, we analyzed an existing fish embryo toxicity database and established a QSAR for fish embryo LC50 using chemicals that were independently classified to act according to the non-specific mode of action of baseline toxicity. The octanol-water partition coefficient Kow is commonly applied to discriminate between non-polar and polar narcotics. Replacing the Kow by the liposome-water partition coefficient Klipw yielded a common QSAR for polar and non-polar baseline toxicants. This developed baseline toxicity QSAR was applied to compare the final mode of action (MOA) assignment of 132 chemicals. Further, we included the analysis of internal lethal concentration (ILC50) and chemical activity (La50) as complementary approaches to evaluate the robustness of the FET baseline toxicity. The analysis of the FET dataset revealed that specifically acting and reactive chemicals converged towards the baseline toxicity QSAR with increasing hydrophobicity. The developed FET baseline toxicity QSAR can be used to identify specifically acting or reactive compounds by determination of the toxic ratio and in combination with appropriate endpoints to infer the MOA for chemicals.

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

    PubMed

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

    2011-11-01

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

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

    PubMed

    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.

  20. Aquatic acute toxicity assessments of molybdenum (+VI) to Daphnia magna.

    PubMed

    Wang, Chi-Wei; Liang, Chenju; Yeh, Hui-Ju

    2016-03-01

    Generally, molybdenum (Mo) metals in the environment are very rare, but wastewater discharges from industrial processes may contain high concentrations of Mo, which has the potential to contaminate water or soil if not handled properly. In this study, the impact of three common compounds of hexavalent Mo (sodium molybdate (Na2MoO4‧2H2O), ammonium molybdate ((NH4)6Mo7O24‧4H2O) and molybdenum trioxide (MoO3)) in an aquatic system were assessed based on 48-h exposure acute toxicity to Daphnia magna (D. magna). The LC50 toxicities for associated conjugate ions including Na(+), Cl(-), SO4(2-), and NH4(+) were determined. Furthermore, the LC50 values for the three forms of hexavalent Mo were determined, and the acute toxicities of the Mo forms were found to follow the order: (NH4)6Mo7O24‧4H2O > MoO3 > Na2MoO4‧2H2O in solution. (NH4)6Mo7O24‧4H2O exhibited the lowest LC50 of 43.3 mg L(-1) (corresponding to 23.5 mg Mo L(-1)) among the three molybdenum salts. The research confirmed that the toxicity of molybdenum in the aquatic system is highly dependent on the form of molybdenum salts used, and is also associated with the influence of the background water quality.

  1. Acute toxicity testing in cultures of mouse neuroblastoma cells.

    PubMed

    Walum, E; Peterson, A

    1983-01-01

    Cultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterparts in vivo. In order to test the possibility of using C1300 cells as alternative to experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2,HgCl2 ppDDT, n-butanol, benzene, dioxan, n-propanol, aceton and t-butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50 values. In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25 values and LD50 values. Good correlations between in vitro and in vivo tests have also been reported by others. One possible explanation to these findings could be simplified in vivo toxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simple in vitro tests may be used for predicting acute toxicity of certain groups of substances.

  2. Acute and delayed toxicities of total body irradiation

    SciTech Connect

    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.

  3. Determination of acute oral toxicity of flumethrin in honey bees.

    PubMed

    Oruc, H H; Hranitz, J M; Sorucu, A; Duell, M; Cakmak, I; Aydin, L; Orman, A

    2012-12-01

    Flumethrin is one of many pesticides used for the control and treatment of varroatosis in honey bees and for the control of mosquitoes and ticks in the environment. For the control of varroatosis, flumethrin is applied to hives formulated as a plastic strip for several weeks. During this time, honey bees are treated topically with flumethrin, and hive products may accumulate the pesticide. Honey bees may indirectly ingest flumethrin through hygienic behaviors during the application period and receive low doses of flumethrin through comb wax remodeling after the application period. The goal of our study was to determine the acute oral toxicity of flumethrin and observe the acute effects on motor coordination in honey bees (Apis mellifera anatoliaca). Six doses (between 0.125 and 4.000 microg per bee) in a geometric series were studied. The acute oral LD50 of flumethrin was determined to be 0.527 and 0.178 microg per bee (n = 210, 95% CI) for 24 and 48 h, respectively. Orally administered flumethrin is highly toxic to honey bees. Oral flumethrin disrupted the motor coordination of honey bees. Honey bees that ingested flumethrin exhibited convulsions in the antennae, legs, and wings at low doses. At higher doses, partial and total paralysis in the antennae, legs, wings, proboscises, bodies, and twitches in the antennae and legs were observed.

  4. The pattern of acute toxic nephropathy in Ife, Nigeria.

    PubMed

    Adelekun, T A; Ekwere, T R; Akinsola, A

    1999-01-01

    All cases of acute renal failure (ARF) seen over a two year (1993-94) period were evaluated. Those that had acute toxic nephropathy were further studied to determine the aetiologic agents involved, the clinical features and the effect of available treatment on its prognosis. Ten cases (33.3%) out of 30 ARF had toxins responsible for their renal failure. They were 8 males and 2 females. Agents responsible were green water in 2, naphthalene containing remedies in 2 and analgesic combination in 1 while herbal remedies were implicated in 5 cases. Anuria was a prominent feature occurring in 9 (90%) of the patients. The patients were uraemic with a mean serum creatinine of 1460 +/- 485.0 umol/1 and urea of 33.1 +/- 5.3 mmol/1 on admission. They were all anaemic with packed cell volume less than 18% in eight of the patients. Six (60%) of the patients required haemodialysis while 4 were managed conservatively. Prognosis was good as 8 (80%) of the patients survived and were followed up in the clinic for periods anging 6 to 18 months and their serum creatinine and urea levels normalised. It is concluded that acute toxic nephropathy is common in our practice, and it is eminently preventable. The prognosis is good if dialytic therapy is available.

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

    PubMed

    Hillesheim, H G; Hoffmann, H

    1983-02-01

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

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

    PubMed

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

    2015-05-19

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

  7. Acute toxicities of six manufactured nanomaterial suspensions to Daphnia magna

    NASA Astrophysics Data System (ADS)

    Zhu, Xiaoshan; Zhu, Lin; Chen, Yongsheng; Tian, Shengyan

    2009-01-01

    The rapid growth of nanotechnology is stimulating research on the potential environmental impacts of manufactured nanomaterials (MNMs). This paper summarizes a comprehensive study on the 48-h acute toxicity of water suspensions of six MNMs (i.e., ZnO, TiO2, Al2O3, C60, SWCNTs, and MWCNTs) to Daphnia magna, using immobilization and mortality as toxicological endpoints. The results show that the acute toxicities of all MNMs tested are dose dependent. The EC50 values for immobilization ranged from 0.622 mg/L (ZnO NPs) to 114.357 mg/L (Al2O3 NPs), while the LC50 values for mortality ranged from 1.511 mg/L (ZnO NPs) to 162.392 mg/L (Al2O3 NPs). In these tests, TiO2, Al2O3, and carbon-based nanomaterials were more toxic than their bulk counterparts. Moreover, D. magna were found to ingest nanomaterials from the test solutions through feeding behaviors, which indicates that the potential ecotoxicities and environmental health effects of these MNMs cannot be neglected.

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

    PubMed

    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.

  9. The submitochondrial particle assay as a screening test for acute aquatic toxicity of surfactant molecules

    SciTech Connect

    Bookland, E.A.; Bettermann, A.D.

    1995-12-31

    Two complementary protocols of the submitochondrial particle assay (SMP) were evaluated as screening tools for predicting the acute aquatic toxicity of various classes and chain lengths of surfactant molecules. SMP contain the functionally intact mitochondrial enzyme systems responsible for electron transport and oxidative phosphorylation. Both the Electron Transfer Assay (ETR) and the Reverse Electron Transfer Assay (RET) have been shown in prior work to generally be sensitive to agents capable of membrane and protein interactions, both suspected mechanisms of action for surfactants. The toxicity of ten compounds; four anionic surfactants, C{sub 12} alkyl sulfate (C{sub 12}AS), C{sub 12} and C{sub 15} alkyl ethoxy sulfate (C{sub 12}E{sub 4}S, C{sub 15}E{sub 4}S), linear alkyl benzene sulfonate (C{sub 12.3}LAS); one nonionic surfactant, alkyl ethoxylate (C{sub 12}E{sub 3}); three cationic surfactants, C{sub 8}, C{sub 12}, and C{sub 16} alkyl trimethyl ammonium chloride (C{sub 8}TMAC, C{sub 12}TMAC, C{sub 16}TMAC); an alcohol (C{sub 12}OH); and an amine, alkyl dimethylamine (C{sub 12}DMA); was determined. In all cases, both the ETR and the RET gave results showing equal or greater sensitivity than previously reported acute fish and invertebrate LC{sub 50}`s. In addition, increasing toxicity with increasing alkyl chain length was observed. As a rapid screening tool, the SMP bioassay avoids exposure concerns such as degradation of test material, a common concern for acute in vivo toxicity testing with rapidly degradable materials. Results indicate that the SMP bioassay can be useful as a predictive screening tool for the aquatic toxicity of surfactants.

  10. DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

    EPA Science Inventory

    Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

  11. Acute Toxicity Estimation and Operational Risk Management of Chemical Warfare Agent Exposures

    DTIC Science & Technology

    2004-05-01

    December 2001 Deputy Assistant to The Secretary of Defense Chemical and Biological (Warfare Agent) Defense ((DATSD- CBD ) interim-certified acute...avoidance (detection), protection, decontamination, and medical intervention. d. Compares the DATSD- CBD interim-certified acute toxicity values...defense. 2. CONCLUSIONS AND RECOMMENDATIONS. a. Translating Toxicity Information into ORM Terminology. The 2001 DATSD- CBD toxicity

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

    USGS Publications Warehouse

    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.

  13. Assessment of sediment contamination, acute toxicity, and population viability of the estuarine amphipod Leptocheirus plumulosus in Baltimore Harbor, Maryland, USA

    SciTech Connect

    McGee, B.L.; Fisher, D.J.; Yonkos, L.T.; Ziegler, G.P.; Turley, S.

    1999-10-01

    In Chesapeake Bay, Maryland, USA, some of the most contaminated sediments are found in the highly industrialized Baltimore Harbor-Patapsco River area. As part of a comprehensive assessment of sediment quality in this system, sediment toxicity was assessed in 10-d acute tests with the estuarine amphipod Leptocheirus plumulosus. Mean amphipod survival was significantly reduced in 7 of the 25 samples tested despite the occurrence of minor experimental artifacts. The most toxic sediments were collected from Bear Creek; other areas exhibiting toxicity included the Inner Harbor and Colgate Creek. Marginal toxicity was observed in samples from Curtis Creek, Lazeretto Point, and Back River. Negative relationships were detected between survival and concentrations of select sediment-associated contaminants, whereas a very strong positive association existed between survival in laboratory exposures and density of L. plumulosus at the test sites. A weight of evidence approach, including correlation analyses, a model of polycyclic aromatic hydrocarbon bioavailability, and comparisons to benchmark sediment levels, was used to tentatively identify classes of contaminants that contributed to the observed toxicity. Analysis of results suggested that toxicity at stations in Bear Creek and Colgate Creek may have been driven by sediment-associated metals, whereas toxicity at stations in the Inner Harbor was likely due to both metal and organic contaminants. The observed relationships among toxicity test results, concentrations of sediment-associated contaminants, and abundance of L. plumulosus at the test sites suggests that acute toxicity tests with this species are indicative of adverse biological effects in the field.

  14. 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

    SciTech Connect

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. . 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.

  15. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    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.

  16. Acute renal toxicity after ingestion of Lava light liquid.

    PubMed

    Erickson, T B; Aks, S E; Zabaneh, R; Reid, R

    1996-06-01

    A 65-year-old man with a history of alcohol abuse and seizure disorder presented to the emergency department with altered mental status, increased anion gap acidosis, phenytoin toxicity, and acute kidney failure. The patient had ingested the liquid contents of a Lava light, which contained chlorinated paraffin, polyethylene glycol (molecular weight 200), kerosene, and micro-crystalline wax. Gas chromatography-mass spectrophotometry of the patient's blood produced results consistent with the same analysis of the Lava light contents. After 3 days of declining mental status and worsening kidney function, the patient required hemodialysis. After a prolonged hospitalization, the patient was discharged home with residual renal insufficiency. Although multifactorial, the associated renal toxicity was most probably related to the low molecular weight polyethylene glycol content of the lamp's liquid contents.

  17. Acute renal insufficiency and toxic hepatitis following scorpions sting.

    PubMed

    Krkic-Dautovic, Sajma; Begovic, Begler

    2007-01-01

    Scorpion sting is a huge medical problem in countries of South America, Arabian Peninsula and Africa. In countries of Mediterranean region, where Bosnia and Herzegovina belongs, this problem is sporadic. Following the sting of very poisonous red scorpions, death may occur inside of 48 hours by reason of cardiac arrest and acute renal insufficiency (ARI). In our work we represent a case of 54-years old man. In his case, ARI and toxic hepatitis developed inside of 24 hours after the scorpion sting. Applied conservative therapy was not sufficient enough to solve ARI, so patient needed haemodialysis. With intensive conservative therapy and haemodialysis applied every other day, ARI and toxic hepatitis were solved within 25 days. After that, patient was released from hospital for ambulant treatment.

  18. Residual Acute Toxicity of Some Modern Insecticides Toward Two Mirid Predators of Tomato Pests.

    PubMed

    Wanumen, Andrea C; Carvalho, Geraldo A; Medina, Pilar; Viñuela, Elisa; Adán, Ángeles

    2016-03-31

    The successful integration of chemical and biological control strategies for crop pests depends on a thorough evaluation of the effects of pesticides on the natural enemies of pests. A case-by-case review is difficult to achieve because of the many combinations of pests, natural enemies, and crops that need to be tested. Within this framework, we tested and compared seven insecticides representative of four different modes of action (MoAs) groups on closely related predators (Miridae): flubendiamide, spirotetramat, metaflumizone, and sulfoxaflor onNesidiocoris tenuisReuter and flubendiamide, spiromesifen, indoxacarb, and imidacloprid onMacrolophus basicornis(Stal). We follow the standardized methodology of the International Organization for Biological Control, a sequential testing exposure scheme. The lethal effect of each insecticide was evaluated in adults after three days of contact with treated surfaces in the laboratory, extended laboratory, and semifield tests (inert substrate, tomato leaves, and tomato plant as the treated surface, respectively). Flubendiamide, spiromesifen, and spirotetramat were classified as harmless (class 1), metaflumizone was slightly harmful (class 2) but persistent, indoxacarb was harmless (class 1), and sulfoxaflor and imidacloprid were toxic (class 4) and exhibited a long residual activity. Our results suggest similarities in the acute toxicities of insecticides from the same MoA group on related species of natural enemies.

  19. Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.

    PubMed

    Abal, Paula; Louzao, M Carmen; Cifuentes, José Manuel; Vilariño, Natalia; Rodriguez, Ines; Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

    2017-04-01

    Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers.

  20. INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

  1. Myelin-associated glycoprotein (MAG) protects neurons from acute toxicity using a ganglioside-dependent mechanism.

    PubMed

    Mehta, Niraj R; Nguyen, Thien; Bullen, John W; Griffin, John W; Schnaar, Ronald L

    2010-03-17

    Myelin-associated glycoprotein (MAG), a protein expressed on the innermost wrap of myelin, contributes to long-term axon stability as evidenced by progressive axon degeneration in Mag-null mice. Recently, MAG was also found to protect axons from acute toxic insults. In the current study, rat dorsal root ganglion neurons were cultured on control substrata and substrata adsorbed with myelin proteins. Neurons on myelin-adsorbed surfaces were resistant to acute degeneration of neurites induced by vincristine, a cancer chemotherapeutic agent with neuropathic side effects. Myelin-mediated protection was reversed by anti-MAG antibody and was absent when cells were cultured on extracts from Mag-null mouse myelin, confirming the protective role of MAG. Gangliosides (sialylated glycosphingolipids) are one functional class of axonal receptors for MAG. In the current studies, a direct role for gangliosides in mediating the acute protective effects of MAG was established. Treatment of neurons with sialidase, an enzyme that cleaves the terminal sialic acids required for MAG binding, reversed MAG's protective effect, as did treatment with (1R,2R)-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol, an inhibitor of glycosphingolipid biosynthesis. In contrast, treatment with phosphatidylinositol-specific phospholipase C, an enzyme that cleaves Nogo receptors (NgR, another class of MAG receptor), or with a peptide inhibitor of an NgR-associated signaling molecule p75(NTR), failed to diminish MAG-mediated protection. Inhibiting the Rho-associated protein kinase ROCK reversed protection. We conclude that MAG protects neurites from acute toxic insult via a ganglioside-mediated signaling pathway that involves activation of RhoA. Understanding MAG-mediated protection may provide opportunities to reduce axonal damage and loss.

  2. Predicting fish acute toxicity using a fish gill cell line-based toxicity assay.

    PubMed

    Tanneberger, Katrin; Knöbel, Melanie; Busser, Frans J M; Sinnige, Theo L; Hermens, Joop L M; Schirmer, Kristin

    2013-01-15

    The OECD test guideline 203 for determination of fish acute toxicity requires substantial numbers of fish and uses death as an apical end point. One potential alternative are fish cell lines; however, several studies indicated that these appear up to several orders of magnitude less sensitive than fish. We developed a fish gill cell line-based (RTgill-W1) assay, using several measures to improve sensitivity. The optimized assay was applied to determine the toxicity of 35 organic chemicals, having a wide range of toxicity to fish, mode of action and physicochemical properties. We found a very good agreement between in vivo and in vitro effective concentrations. For up to 73% of the tested compounds, the difference between the two approaches was less than 5-fold, covering baseline toxicants but as well compounds with presumed specific modes of action, including reactivity, inhibition of acetylcholine esterase or uncoupling of oxidative phosphorylation. Accounting for measured chemical concentrations eliminated two outliers, the hydrophobic 4-decylaniline and the volatile 2,3-dimethyl-1,3-butadiene, with an outlier being operationally defined as a substance showing a more than 10-fold difference between in vivo/in vitro effect concentrations. Few outliers remained. The most striking were allyl alcohol (2700-fold), which likely needs to be metabolically activated, and permethrin (190-fold) and lindane (63-fold), compounds acting, respectively, on sodium and chloride channels in the brain of fish. We discuss further developments of this assay and suggest its use beyond predicting acute toxicity to fish, for example, as part of adverse outcome pathways to replace, reduce, or refine chronic fish tests.

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

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

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

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

    PubMed

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

    1996-12-01

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

  5. Influence of water quality parameters on acute silver toxicity

    SciTech Connect

    Bills, T.; Forsythe, B. II; Wenholz, M.; Jeffers, R.; Waldrop, V.; La Point, T.; Bens, C.; Cobb, G.; Klaine, S.J.

    1995-12-31

    The data to adequately characterize the influence of water quality on silver toxicity in freshwater are lacking or poorly developed. Current attempts to extrapolate existing data sets to many sites result in extremely low silver limits. The error associated with these extrapolations dictate that a silver toxicity data set, accounting for various water quality parameters, be generated. The interactive effects of chloride, hardness, alkalinity, total organic carbon, and pH on the acute toxicity of silver (AgNO{sub 3}) were measured using juvenile fathead minnows (Pimephales promelas) and Daphnia magna. The 96-hr LC50 for fathead minnows at the lowest tested levels of water quality parameters was 1.4 ug/L. At the highest levels tested, the 96-hr LC50 for fathead minnows was 3.8 ug/L. Preliminary results suggest the 48-hr LC50 values for Daphnia magna were similar to those of the fish. These results indicate a mitigating effect of certain water quality parameters.

  6. Acetone potentiation of acute acetonitrile toxicity in rats

    SciTech Connect

    Freeman, J.J.; Hayes, E.P.

    1985-01-01

    The purpose of these studies was to investigate the nature and mechanism of a toxicologic interaction between acetonitrile and acetone. Results of oral doe-response studies utilizing 1:1 (w/w) mixture of acetonitrile and acetone, or varying doses of acetonitrile administered together with a constant dose of acetone, indicated that acetone potentiated acute acetonitrile toxicity three- to fourfold in rats. The onset of severe toxicity (manifested by tremors and convulsions) was delayed in the groups dosed with both solvents compared to the groups that received acetonitrile or acetone alone. Blood cyanide (a metabolite of acetonitrile) and serum acetonitrile and acetone concentrations were measured after oral administration of 25% aqueous solutions of acetonitrile, acetone, or acetonitrile plus acetone. Concentrations of cyanide in the blood of rats given acetonitrile plus acetone remained near baseline, in contrast to the high concentrations found in rats dosed with acetonitrile alone. At 34-36 h, high blood cyanide concentrations were found in rats dosed with both of the solvents. This delayed onset of elevation of blood cyanide coincided with the occurrence of clinical signs and with the disappearance of serum acetone. In further pharmacokinetic studies, blood cyanide concentrations were measured after similar dosage regimens of acetone and acetonitrile. Peak cyanide concentrations were found to be significantly greater in rats dosed with both solvents than in rats given only acetonitrile. Administration of either sodium thiosulfate or a second dose of acetone prevented the toxicity associated with exposure to both solvents.

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    EPA Science Inventory

    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...

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

    PubMed

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

    2016-09-01

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

  11. Toxicity of white phosphorus to waterfowl: acute exposure in mallards

    USGS Publications Warehouse

    Sparling, D.W.; Gustafson, M.; Klein, P.; Karouna-Renier, N.

    1997-01-01

    As part of an effort to understand extensive, white phosphorus (P4)-induced waterfowl mortality at Eagle River Flats, Fort Richardson, Alaska, we conducted a number of acute toxicity tests using penned mallards (Anas platyrhynchos) in 1993 and 1994. The 24-hr median lethal dose (LD50) for P4 dissolved in oil was 6.46 mg/kg in adult males and 6.96 mg/kg in adult females. Although the median lethal doses were not statistically different, the female dose-response curve had a statistically shallower slope than that of males. The LD50 for the ecologically more relevant pelletized form of P4 in adult males was 4.05 mg/kg. In mallards, one mechanism of P4 toxicity caused rapid (3 to 10 hr) mortality and had signs consistent with anoxia. A second, slower acting mechanism resulted in hepatic and renal pathology including extensive fat deposition in the liver and cellular necrosis. White phosphorus accumulated in adipose tissues, but only for a few days.

  12. Influence of chemical and environmental stressors on acute cadmium toxicity

    SciTech Connect

    Baer, K.N.; Benson, W.H.

    1987-01-01

    Previous investigations have demonstrated that the cytosolic protein metallothionein (MT) is induced not only by exposure to certain heavy metals but also by a variety of other factors, including environmental stress. While MT synthesis has been observed with exposure to cold temperatures, there is a paucity of data concerning the influence of cold on heavy-metal toxicity. The present investigation focused on the influence of metal and cold pretreatments on the acute toxicity of cadmium. Mortalities of 80% and 100% were observed for mice orally administered challenge doses of 100 mg Cd/kg and 150 mg Cd/kg, respectively. To determine a protective cadmium pretreatment dose, animals were administered 2.5, 5, 10, 20, 25, and 50 mg Cd/kg 24 h prior to cadmium challenge. In animals pretreated with 10 mg Cd/kg, mortalities of 20% and 70% were observed with the respective challenge doses. Immediately following cold stress (4/sup 0/C, 12 h), mortalities of 30% and 90% were observed with cadmium challenge doses of 100 and 150 mg Cd/kg, respectively. Significant correlations were demonstrated between induced hepatic MT concentrations and cadmium pretreatment, as well as cold pretreatment. The induced tolerance to cadmium was attributed, in part, to the induction of MT synthesis. Furthermore, the induced levels of MT resulting from cold stress may confound the simplistic approach of using MT as a biological monitor of occupational exposure to cadmium.

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

    PubMed

    Li, Min; Wei, Dongbin; Du, Yuguo

    2014-09-01

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

  14. Reduction of acute toxicity and genotoxicity of dye effluent using Fenton-coagulation process.

    PubMed

    Zhang, Jing; Chen, Shuo; Zhang, Ying; Quan, Xie; Zhao, Huimin; Zhang, Yaobin

    2014-06-15

    Dye wastewater exhibits significant ecotoxicity even though its physico-chemical parameters meet the discharge standards. In this work, the acute toxicity and genotoxicity of dye effluent were tested, and the Fenton-coagulation process was carried out to detoxify this dye effluent. The acute toxicity was evaluated according to the mortality rate of zebrafish, and genotoxicity was evaluated by micronucleus (MN) and comet assays. Removal of color and chemical oxygen demand (COD) was also investigated. The results indicated that the dye effluent showed strong acute toxicity and genotoxicity to zebrafish. After 4h of treatment by Fenton-coagulation process, the dye effluent exhibited no significant acute toxicity and genotoxicity to zebrafish. In addition, its COD was less than 50mg/L, which met the discharge standard. It demonstrates that Fenton-coagulation process can comprehensively reduce the acute toxicity and genotoxicity as well as the COD of the dye effluent.

  15. Acute Selenium Toxicity Associated With a Dietary Supplement

    PubMed Central

    MacFarquhar, Jennifer K.; Broussard, Danielle L.; Melstrom, Paul; Hutchinson, Richard; Wolkin, Amy; Martin, Colleen; Burk, Raymond F.; Dunn, John R.; Green, Alice L.; Hammond, Roberta; Schaffner, William; Jones, Timothy F.

    2011-01-01

    Background Selenium is an element necessary for normal cellular function, but it can have toxic effects at high doses. We investigated an outbreak of acute selenium poisoning. Methods A case was defined as the onset of symptoms of selenium toxicity in a person within 2 weeks after ingesting a dietary supplement manufactured by “Company A,” purchased after January 1, 2008. We conducted case finding, administered initial and 90-day follow-up questionnaires to affected persons, and obtained laboratory data where available. Results The source of the outbreak was identified as a liquid dietary supplement that contained 200 times the labeled concentration of selenium. Of 201 cases identified in 10 states, 1 person was hospitalized. The median estimated dose of selenium consumed was 41 749 μg/d (recommended dietary allowance is 55 μg/d). Frequently reported symptoms included diarrhea (78%), fatigue (75%), hair loss (72%), joint pain (70%), nail discoloration or brittleness (61%), and nausea (58%). Symptoms persisting 90 days or longer included fingernail discoloration and loss (52%), fatigue (35%), and hair loss (29%). The mean initial serum selenium concentration of 8 patients was 751 μg/L (reference range, ≤125 μg/L). The mean initial urine selenium concentration of 7 patients was 166 μg/24 h (reference range, ≤55 μg/24 h). Conclusions Toxic concentrations of selenium in a liquid dietary supplement resulted in a widespread outbreak. Had the manufacturers been held to standards used in the pharmaceutical industry, it may have been prevented. PMID:20142570

  16. Isolation and characterization of acutely toxic fractions in oil sands wastewater

    SciTech Connect

    Verbeek, A.; Mackay, W.; MacKinnon, M.

    1995-12-31

    Extraction of oil from oil sand using the hot water flotation method results in the production of large volumes of wastewater that are acutely toxic to aquatic organisms. At Syncrude Canada Ltd. and Suncor Oil Sands Group Inc., this wastewater is stored in large tailings ponds that must eventually be reclaimed. The acute toxicity of these wastewaters was assessed and the acutely toxic fractions were identified. Samples were collected from the surface and fine tails zones of the Syncrude and Suncor tailings ponds during the summers of 1991 and 1992. The Microtox bioassay was used to assess the acute toxicity before and after various treatments. Where significant reductions in acute toxicity were found, further acute toxicity tests were carried out using Daphnia magna and rainbow trout. The Microtox IC{sub 50} of all centrifuged tailings pond water samples varied between 26.5 and 46%. Daphnia LC{sub 50}s varied between 76 and 98% and a rainbow trout LC{sub 50} was 12.5 %. Organic compounds that have a non-polar component, as removed by solid phase extraction with C{sub 18} sorbent, accounted for all the acute toxicity (100%) of all samples. Organic ``acids``, as removed by precipitation at pH 2.5, also accounted for all the acute toxicity (100%) of all samples except those from pond 1A of Suncor. In pond 1A, organic ``acids`` accounted for approximately 55--60% of the acute toxicity, nonpolar organic volatile compounds accounted for approximately 20--35% and the balance of the acute toxicity was due to non-polar organic compounds that were neither volatile nor organic ``acids``, as removed by precipitation at pH 2.5.

  17. Acute toxicity of methyl mercury to the larval lamprey, Petromyzon marinus

    SciTech Connect

    Mallatt, J.; Barron, M.G.; McDonough, C.

    1986-08-01

    Mercury compounds pollute many aquatic habitats and are extremely toxic to aquatic organisms. Acute toxicity of waterborne methyl mercury has been studied in several teleost species. Lampreys are taxonomically distant from teleosts and are used for comparative toxicological purposes. Landlocked sea lampreys, Petromyzon marinus, inhabit the Great Lakes region, and their larvae (ammocoetes) burrow in stream sediments. In this study, the authors present toxicity curves for ammocoetes exposed acutely to methyl mercuric chloride solutions. Susceptibility was related to temperature and animal size.

  18. Potential contribution of inorganic ions to whole effluent acute toxicity and genotoxicity during sewage tertiary treatment.

    PubMed

    Sun, Jian; Quan, Ying; Wang, Wei; Zheng, Shaokui; Liu, Xinchun

    2015-09-15

    Two acute toxicity tests (luminescent bacteria assay and cladoceran assay) and one genotoxicity test (broad bean assay) were used to evaluate whole effluent toxicity during the standard anion exchange resin-based pilot-scale sewage tertiary treatment that stably achieved significant dissolved organic carbon and inorganic ions reduction. The effect of six representative inorganic ions (i.e., Cl(-), SO4(2-), NO3(-)-N, NO2(-)-N, NH4(+)-N and PO4(3-)-P) on the acute toxicity and genotoxicity was further investigated. Significant whole effluent genotoxicity reduction was observed as an ∼ 57% micronucleated cell frequency reduction and ∼ 46% mitotic index increment during the pilot-scale periods, which should be attributed to significant organic removal since no significant (p ≥ 0.116) increase in genotoxicity was observed with the increase in these ionic concentrations. However, no significant (p ≥ 0.14) reductions were observed for whole effluent acute toxicity using two acute toxicity assays during the pilot-scale periods, and these inorganic ions, especially NH4(+)-N, contributed considerably to the acute toxicity. Based on Pearson correlation coefficients, whole effluent acute toxicity showed significant positive (p < 0.001, r ≥ 0.758) correlations with the NH4(+)-N concentration. Two optimal models were finally developed using step-wise multiple linear regression to predict the whole effluent acute toxicity via NH4(+)-N concentrations.

  19. Tungsten speciation and toxicity: acute toxicity of mono- and poly-tungstates to fish.

    PubMed

    Strigul, Nikolay; Koutsospyros, Agamemnon; Christodoulatos, Christos

    2010-02-01

    Tungsten is a widely used transition metal for which very limited information on environmental and toxicological effects is available. Of particular interest is the lack of information linking tungsten speciation and environmental effects. Tungsten anions may polymerize (depending upon concentration, pH, and aquatic geochemistry) in aquatic and soil systems. However, to this date, of all soluble tungstate species only monotungstates have been scrutinized to a fair extent in toxicological studies. The objective of this work is a comparative assessment of the acute toxicity of monotungstates (sodium tungstate, Na(2)WO(4)) and polytungstates (sodium metatungstate, 3Na(2)WO(4).9WO(3)) to Poecilia reticulate. The experiments have been performed according to the OEDC protocols 203 and 204. LD50 values for 1-14 days show that sodium metatungstate is significantly more toxic to fish than sodium tungstate. Based on LD50 (0.86-3.88gL(-1) or 4.67-21.1x10(-3)molNa(2)WO(4)L(-1)), sodium tungstate may be classified as a chemical of low toxicity to fish. Sodium metatungstate caused similar fish mortality to sodium tungstate when it was introduced in 55-80 times lower concentrations (in terms of molL(-1)) than sodium tungstate. LD50 values for sodium metatungstate range from 0.13 to 0.85gWL(-1) or 5.69 to 38.71x10(-5)mol 3Na(2)WO(4).9WO(3)L(-1). Based on these values sodium metatungstate can be classified as a moderate toxic agent to fish.

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

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    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. PMID:26697225

  1. Acute pulmonary toxicity of urban particulate matter and ozone.

    PubMed Central

    Vincent, R.; Bjarnason, S. G.; Adamson, I. Y.; Hedgecock, C.; Kumarathasan, P.; Guénette, J.; Potvin, M.; Goegan, P.; Bouthillier, L.

    1997-01-01

    We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals. Images Figure 1 PMID:9403707

  2. ASSESSING CONTAMINANT SENSITIVITY OF ENDANGERED AND THREATENED SPECIES: TOXICANT CLASSES

    EPA Science Inventory

    Under the Federal Insecticide, Fungicide and Rodenticide Act, the Toxic Substances Control Act and the Clean Water Act, the U.S. Environmental Protection Agency (EPA) is charged with determining if the manufacture, use, or disposal of a chemical will present an unreasonable risk ...

  3. Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: acute toxicity, genotoxicity and subchronic toxicity.

    PubMed

    Yang, Hui; Jia, Xudong

    2014-12-01

    The significant toxicity of selenium emphasizes the need to assess the health risk of various selenocompounds as nutritional supplements. Se-methylselenocysteine (SeMC) was recently reported to be more bioactive but the toxicological effects have not been sufficiently characterized. This study aimed to evaluate the safety of SeMC and provide the Acceptable Daily Intake (ADI) for its use in human diet. Our results demonstrated that SeMC, with the Median Lethal Dose (LD50) of 12.6 and 9.26mg/kg BW in female and male mice, was of high potent of health hazard under acute oral exposure, but a battery of tests including Ames test, micronucleus assay and mouse sperm malformation assay suggested that SeMC was not genotoxic. The repeated dose study indicated little systemic toxicity of SeMC at supernutritional levels (0.5, 0.7, 0.9mg/kg BW/day) after 90-day oral exposure. Importantly, the 95% lower confidence value of Benchmark Dose (BMDL) was estimated as 0.34mg/kg BW/day according to the elevated relative liver weight. The ADI for human was established at 3.4μg/kg BW/day. The results suggested greater safety of SeMC as a nutritional selenium supplement, but health risk needs to be further evaluated when SeMC is applied beyond this level to achieve cancer chemoprevention.

  4. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  5. Acute toxicity of biodiesel to freshwater and marine organisms

    SciTech Connect

    Reece, D.; Peterson, C.

    1995-11-01

    Biodiesel fuels are reported to be nontoxic resulting in less potential hazard to fish and other aquatic life in case of accidental spills. This paper reports on static tests with rapeseed methyl ester (RME) and rapeseed ethyl ester (REE) performed according to EPA/600/4-90/027. The acute aquatic toxicity tests were conducted with both rainbow trout and daphnia magna by CH2M Hill in Corvallis, Oregon under contract to the University of Idaho. The LC50 (the point at which 50% have died and 50% are still alive determined by interpolation) values for each of the substrates tested with daphnia magna in parts per million were as follows: control(table salt (NaCl)) = 3.7, D2 = 1.43, RME = 23, REE = 99, and Methyl Soyate = 332. Duplicate tests with rainbow trout were run with 10 organisms per replicate. LC50 numbers were not reported because of the failure to kill a sufficient number of fish at the concentrations tested, even with the diesel control fuel. The 20 percent and 50 percent blends had scattered losses of fish but none of the tests had less than 85 percent survival at any concentrations after 96 hours.

  6. Pathology of acute 3-acetyldeoxynivalenol toxicity in mice.

    PubMed Central

    Schiefer, H B; Nicholson, S; Kasali, O B; Hancock, D S; Greenhalgh, R

    1985-01-01

    Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3-acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3-acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes. Images Fig. 1a. Fig. 1b. Fig. 2. Fig. 3. PMID:4041976

  7. MOAtox: A Comprehensive Mode of Action and Acute Aquatic Toxicity Database for Predictive Model Development

    EPA Science Inventory

    tThe mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity andas an alternative to chemical class-based predictive toxicity modeling. However, the development ofquantitative structure activity relationship (QSAR) and other models has been limite...

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

    SciTech Connect

    Lee, Soyoung; Park, Keunwan; Ahn, Hee-Sung; Kim, Dongsup

    2010-07-15

    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 (R{sup 2}: 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.

  9. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  10. Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

    PubMed

    Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

    2015-06-02

    The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

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

    PubMed Central

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

    2010-01-01

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

  12. Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part I. Acute Toxicity of Five Chemicals

    EPA Science Inventory

    This paper reports on the results of acute toxicity tests conducted with common surrogate species, and several species of threatened and endangered species for which there were excess artificially propagated stock to allow direct testing.

  13. Acute toxicity of selected crude and refined shale oil derived and petroleum-derived substances

    SciTech Connect

    Smith, L.H.; Haschek, W.M.; Witschi, H.

    1980-01-01

    General information was obtained on the toxicity of selected samples of crude Paraho shale oil and some of its derivatives, some crude petroleums, and 3 refined petroleum products. Five tests were used to determine the acute toxicity of these substances: acute lethality in mice following oral or intraperitoneal administration of a single dose; acute dermal toxicity of a single dose in rats; delayed-type allergic contact hypersensitivity in guinea pigs; primary eye irritation and primary skin irritation of a single dose in rabbits. Histopathologic changes induced in mice following intraperitoneal injection of a single large dose of crude shale oil and two of its hydrotreated derivatives were examined. Studies also have been initiated to examine the tumor inducing potential of selected samples. The test system used was the mouse lung adenoma bioassay. The present report describes our findings and shows that all compounds tested have very low or no acute toxic effects in laboratory animals.

  14. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

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

    PubMed

    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.

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

    PubMed

    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.

  17. Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

    PubMed

    Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

    2010-09-17

    Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms.

  18. Acute toxicity, twenty-eight days repeated dose toxicity and genotoxicity of vanadyl trehalose in kunming mice.

    PubMed

    Jiang, Pingzhe; Ni, Zaizhong; Wang, Bin; Ma, Baicheng; Duan, Huikun; Li, Xiaodan; Ma, Xiaofeng; Wei, Qian; Ji, Xiangzhen; Liu, Qiqi; Xing, Shuguang; Li, Minggang

    2017-04-01

    A new trend has been developed using vanadium and organic ligands to form novel compounds in order to improve the beneficial actions and reduce the toxicity of vanadium compounds. In present study, vanadyl trehalose was explored the oral acute toxicity, 28 days repeated dose toxicity and genotoxicity in Kunming mice. The Median Lethal Dose (LD50) of vanadyl trehalose was revealed to be 1000 mg/kg body weight in fasted Kunming mice. Stomach and intestine were demonstrated to be the main target organs of vanadyl trehalose through 28 days repeated dose toxicity study. And vanadyl trehalose also showed particular genotoxicity through mouse bone marrow micronucleus and mouse sperm malformation assay. In brief, vanadyl trehalose presented certain, but finite toxicity, which may provide experimental basis for the clinical application.

  19. Acute to chronic estimation of Daphnia magna toxicity within the QSAAR framework.

    PubMed

    Furuhama, A; Hayashi, T I; Tatarazako, N

    2016-10-21

    We constructed models for acute to chronic estimation of the Daphnia magna reproductive toxicities of chemical substances from their Daphnia magna acute immobilization toxicities. The models combined the acute toxicities with structural and physicochemical descriptors. We used multiregression analysis and selected the descriptors for the models by means of a genetic algorithm. Of the best 100 models (as indicated by the lack of fit score), 90% included the following descriptors: acute toxicity (i.e. an activity parameter), distribution coefficient (log D) and structural indicator variables that indicate the presence of -NH2 attached to aromatic carbon and the presence of a chlorine atom. We compared the predictive abilities of five of these quantitative structure-activity-activity relationship (QSAAR) acute to chronic estimation models with the predictive ability of a simple linear regression model. The comparison revealed that inclusion of structural and physicochemical descriptors such as those in QSAAR models can improve models for extrapolation from acute to chronic toxicity. Our results also provide a QSAAR framework that is expected to be useful for the further development of chronic toxicity estimation models.

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

    SciTech Connect

    Hosokawa, Mamoru; Kuroda, Koichi ); Endo, Ginji; Horiguchi, Shunichi )

    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.

  1. Qsars for photoinduced toxicity: 1. acute lethality of polycyclic aromatic hydrocarbons to daphnia magna'

    SciTech Connect

    Mekenyan, O.G.; Ankley, G.T.; Veith, G.D.; Call, D.J.

    1994-01-01

    Research with a variety of aquatic species has shown that while polycyclic aromatic hydrocarbons (PAHs) are generally not acutely toxic in conventional laboratory tests, many are extremely toxic in the presence of sunlight. In an effort to develop a model for predicting which PAHs may exhibit photo-induced toxicity, Newsted and Giesy (1987) reported a parabolic relationship between the toxicity and the energy of the triplet state of a variety of PAHs. The authors have reexamined these data and propose a more mechanistic explanation for the prediction of photo-induced PAH toxicity. They sought a molecular descriptor which could be computed from structure rather than measured empirically.

  2. Acute Electrocardiographic ST Segment Elevation May Predict Hypotension in a Swine Model of Severe Cyanide Toxicity

    DTIC Science & Technology

    2012-04-21

    induced shock, 30 swine were anesthetized and monitored and then intoxicated with a continuous cyanide infusion until severe hypotension (50 % of...TOXICOLOGY INVESTIGATION Acute Electrocardiographic ST Segment ElevationMay Predict Hypotension in a Swine Model of Severe Cyanide Toxicity Tylan A...Toxicology 2012 Abstract Cyanide causes severe cardiac toxicity resulting in tachycardia, hypotension, and cardiac arrest; however, the clinical diagnosis can

  3. Toxic Epidermal Necrolysis and Acute Kidney Injury due to Glyphosate Ingestion

    PubMed Central

    Indirakshi, J.; Sunnesh, A.; Aruna, M.; Reddy, M. Hari Krishna; Kumar, Anil C. V.; Chandra, V. Sarat; Sangeetha, B.; Katyarmal, D. T.; Ram, R.; Kumar, V. Siva

    2017-01-01

    The literature, particularly from India, is scarce on the renal effects of glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but also after dermal exposure by inhalation route and on eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis – the first report after glyphosate consumption and acute kidney injury.

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

    PubMed

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

    2010-01-01

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

  5. Acute management of autoimmune toxicity in cancer patients on immunotherapy: Common toxicities and the approach for the emergency physician.

    PubMed

    Lomax, Anna J; McNeil, Catriona

    2017-01-16

    When a patient receiving anti-cancer treatment presents acutely unwell, an understanding of associated side effects of their therapy is critical. This review will discuss the approach to patients receiving anti-cancer treatment with immunotherapy presenting with autoimmune toxicities in the emergency setting. These toxicities are commonly referred to as immune-related adverse events (irAE). IrAE might consist of, but are not limited to, dermatologic, gastrointestinal (diarrhoea, colitis), hepatic, endocrine (thyroid dysfunction, hypophysitis, adrenal crisis), renal, ocular and pulmonary toxicity. General principles of managing these irAE in the acute setting will be outlined. Steroid therapy is a critical component of the treatment algorithm, being administered at high doses and for prolonged periods to switch off immune over-activation. Prompt intervention might prevent multi-organ failure and fatality, and allow patients to remain on effective anti-cancer therapy.

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

    SciTech Connect

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

    1988-10-01

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

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

    PubMed

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

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

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

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    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.

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

    SciTech Connect

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-06-01

    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.

  10. Acute and chronic toxicity of boron to a variety of freshwater organisms.

    PubMed

    Soucek, David J; Dickinson, Amy; Koch, Brian T

    2011-08-01

    Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far.

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

    PubMed

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

    2013-07-01

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

  12. Influence of light in acute toxicity bioassays of imidacloprid and zinc pyrithione to zooplankton crustaceans.

    PubMed

    Sánchez-Bayo, Francisco; Goka, Kouichi

    2006-06-30

    The acute toxicity of imidacloprid, a neonicotinoid insecticide, and zinc pyrithione (Zpt), a biocide used in anti-dandruff shampoos and protective antifouling paints, to three species of ostracods and two waterfleas, including Daphnia magna, was determined and compared under light and dark conditions. Under normal laboratory conditions, UV light had no significant influence on the outcome of toxicity bioassays, although in the case of imidacloprid both EC(50) and LC(50) calculated values were twice as high under the light as in the dark. No influence of UV light was observed on bioassays conducted with Zpt, in spite of the fast aqueous photolysis exhibited by this compound. Imidacloprid 48-h LC(50) for cladocerans (65-133mg/L) were two orders of magnitude higher than for ostracods (301-715microg/L); values of EC(50) for cladocerans and ostracods were 2-6mg/L and 3-16microg/L, respectively. Toxicity of Zpt to both ostracod and cladoceran species appears to be similar, with 48-h LC(50) in the range 137-524 and 75-197microg/L for ostracods and cladocerans, respectively, and similar values for EC(50)s. The mortality endpoint (LC(50)), however, is not a reliable predictor of the effects of imidacloprid under field situations (e.g. rice paddies), because the paralysis effect induced by this insecticide takes place at much lower concentrations than those required to cause the death of the animals: regardless of the taxa, differences as large as 100- or 600-fold were observed between the EC(50) and LC(50) for the same exposures. As a consequence, immobilization tests and EC(50) values are recommended for this class of compounds, while caution should be exercised in environmental risk assessments of this and possibly other related neonicotinoid insecticides with similar activity.

  13. Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia.

    PubMed

    Fraysse, Benoit; Garric, Jeanne

    2005-10-01

    Acute toxicity of beta-adrenoceptor blockers (beta-blockers) was studied with beta-blockers as single compounds or in mixture using the standardized acute 2-d Ceriodaphnia dubia immobility test. The tested compounds were selected according to their selectivity for the beta1-adrenoceptor, with three beta1-selective blockers (acebutolol, atenolol, and metoprolol) and three non-beta1-selective blockers (nadolol, oxprenolol, and propranolol). The acute toxicity (median effective concentration) of the six single compounds ranged from 1.4 mg/L for propranolol to 163 mg/L for nadolol. According to European Union directive 93/67EEC, these values range from toxic for aquatic organisms to nonclassified. The more toxic compounds, propranolol and oxprenolol, are both characterized by a membrane-stabilizing activity, a strong affinity for the beta1-adrenoceptor, and a high octanol-water partition coefficient (log Kow). The property of beta-receptor selectivity seems not to be involved in the observed acute toxicity of the single compounds for C. dubia. Nevertheless, the toxicity of the selected compounds in mixture can be defined according to the beta1-selectivity. Two main joint effects have been detected: An independent action for the beta1-selective blockers, and an additive effect when either the nonselective beta1-selective blockers or the six compounds are tested together. The concentration addition model seems to be appropriate, providing a reasonable worst-case estimation of beta-blocker mixture toxicity for regulatory purposes.

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

    PubMed

    Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

    2014-08-01

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

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

    PubMed

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

    2010-03-01

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

  16. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  17. Acute oral toxicity of ja-2 solid propellant in sprague-dawley rats. Report for 12 November-19 December 1985

    SciTech Connect

    Brown, L.D.; Justus, J.D.; Wheeler, C.R.; Korte, D.W.

    1989-12-01

    The acute oral toxicity of JA-2 Solid Propellant was determined in male and female Sprague-Dawley rats by using an oral gavage split-dose method. The MLD was 3990.6 + or - 349.7 mg/kg for male rats and 2545.9 + or - 421.1 mg/kg for female rats. JA-2 produced clinical signs that were attributed to its nitrate ester components, diethyleneglycol dinitrate and nitroglycerin. These signs included tremors and twitching, cyanosis, and increases in respiratory rate and depth. Other clinical signs observed were associated with the general malaise of the animals following dosing and included hunched posture, rough coat, reddish stains around the eyes and nose, and perianal staining. Most animals exhibited signs by 4 hours after dosing and either had died or the signs had cleared by 96 hours after dosing. According to the classification scheme of Hodge and Sterner, these results place JA-2 in the slightly toxic class.

  18. Acute oral toxicity of JA-2 solid propellant in icr mice. Report for 17 December 1985-17 January 1986

    SciTech Connect

    Morgan, E.W.; Frost, D.F.; Wheller, C.R.; Korte, D.W.

    1989-12-01

    The acute oral toxicity of JA-2 Solid Propellant was determined in male and female ICR mice by using an oral gavage, split-dose method. The MLD was 3774.6 + or - 150.5 mg/kg for male mice and 3528.8 + or - 133.8 mg/kg for female mice. JA-2 produced component, diethyleneglycol dinitrate and nitroglycerin. These signs included tremors, inactivity, depression of reflexes, loss of equilibrium, opisthotonus, and increased respiratory activity. Other clinical signs observed were associated with the general malaise of the animals following dosing and included perianal staining, hunched posture, squinting, and rough coat. Most animals exhibited signs by 2 hours after dosing and either had died or the signs had cleared within 5 days of dosing. According to the classification scheme of Hodge and Sterner, these results place JA-2 in the slightly toxic class.

  19. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

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

    PubMed

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

    2017-01-06

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

  1. Comparison of methods for evaluating acute and chronic toxicity in marine sediments.

    PubMed

    Greenstein, Darrin; Bay, Steven; Anderson, Brian; Chandler, G Thomas; Farrar, J Daniel; Keppler, Charles; Phillips, Bryn; Ringwood, Amy; Young, Diana

    2008-04-01

    Sublethal test methods are being used with increasing frequency to measure sediment toxicity, but little is known about the relative sensitivity of these tests compared to the more commonly used acute tests. The present study was conducted to compare the sensitivity of several acute and sublethal methods and to investigate their correlations with sediment chemistry and benthic community condition. Six sublethal methods (amphipod: Leptocheirus plumulosus survival, growth, and reproduction; polychaete: Neanthes arenaceodentata survival and growth; benthic copepod: Amphiascus tenuiremis life cycle; seed clam: Mercenaria mercenaria growth; oyster: Crassostrea virginica lysosome destabilization; and sediment-water interface testing with mussel embryos, Mytilus galloprovincialis) and two acute methods (amphipod survival with Eohaustorius estuarius and L. plumulosus) were used to test split sediment samples from stations in California. The test with Amphiascus proved to be the most sensitive sublethal test and the most sensitive overall, identifying 90% of the stations as toxic. The Leptocheirus 10-d test was the most sensitive of the acute tests, identifying 60% of the stations as toxic. In general, the sublethal tests were not more sensitive to sediments than the acute tests, with the sublethal tests finding an average of 35% of the stations to be toxic while the acute found 44%. Of the sublethal tests, only the Amphiascus endpoints and Neanthes growth significantly (p toxicity endpoints and the indicators of benthic community condition. Differences in test characteristics such as mode of exposure, species-specific contaminant sensitivity, changes in contaminant bioavailability, and influence of noncontaminant stressors on the benthos may have been responsible for variation in response among the tests and low correspondence with benthic community condition. The

  2. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  3. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  4. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  5. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  6. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  7. Acute and Subacute Oral Toxicity of Periodate in Rats

    DTIC Science & Technology

    2014-11-17

    sodium periodate via oral gavage resulted in a cascade of effects that were secondary to kidney toxicity. Decreased mass of ovaries and epididymides and...testicular degeneration were observed in sodium periodate groups with signs of kidney toxicity. These groups also exhibited decreased T3 and T4 in the...presence of decreased TSH, a pattern associated with uremia. Sodium periodate exposed rats exhibited both activation of the innate immune system and

  8. PRN 2001-2: Acute Toxicity Data Requirements For Granular Pesticide Products, Including Those With Granular Fertilizers in the Product.

    EPA Pesticide Factsheets

    This PR Notice announces guidance intended to streamline the acute toxicity review and classification process for certain granular pesticide products, including those products that contain granular fertilizers.

  9. Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of “Zapote” Pouteria mammosa (L.) Cronquist

    PubMed Central

    Dutok, Carlos M. S.; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M. C.

    2015-01-01

    The common use of Pouteria mammosa (L.) Cronquist, “Mamey or Zapote,” in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating. PMID:26273696

  10. Mitigation of malathion's acute toxicity by four submersed macrophyte species.

    PubMed

    Brogan, William R; Relyea, Rick A

    2013-07-01

    Some submersed macrophyte species rapidly sorb some insecticides from the water, potentially reducing exposure for aquatic species. The rates at which macrophytes remove insecticides, however, can differ widely among plant species. Furthermore, few studies have examined how much macrophytes actually influence insecticide toxicity to sensitive animals. The authors quantified the ability of several macrophyte species to mitigate insecticide toxicity by comparing the survival of the aquatic herbivore, Daphnia magna, following exposure to a factorial combination of 3 malathion concentrations (0 µg/L, 3 µg/L, and 24 µg/L) and 7 macrophyte treatments (no macrophytes, 4 different macrophyte monocultures, and 2 inert substrates: plastic plants and polypropylene rope). The authors also quantified the rate that different macrophytes reduced malathion's toxicity by exposing D. magna to water samples collected from each treatment after 2 h, 8 h, and 48 h of exposure. The results revealed that whereas 3 µg/L and 24 µg/L of malathion decimated D. magna in the no-macrophyte, plastic plant, and rope treatments, all 4 macrophyte species strongly mitigated these effects. When the authors compared the rate at which malathion's toxicity decreased, they found that all macrophytes negated malathion's toxicity within 2 h, whereas it took more than 8 h in the absence of macrophytes or in the presence of inert substrates. These results demonstrate that numerous macrophyte species can equally and strongly mitigate insecticide toxicity, whereas inert substrates cannot.

  11. Toxicity of TNT Wastewaters to Aquatic Organisms. Volume 1. Acute Toxicity of LAP Wastewater and 2,4,6-Trinitrotoluene

    DTIC Science & Technology

    1983-03-01

    used to assess the adequacy of current pollution abatement technologies and thus influence research and development in this area. This report...wastewater samples, was defined as a 1.6-to-I mixture o! TNT and RDX. "The results of flow-through acute toxicity terzs with the inverte - brate Daphniamagna...The "unadjusted" confidence interval for the LCSO is derived by inverting the likelihood ratio test for determining whether any specified

  12. Investigations in Fish Control: 92. Acute and Chronic Toxicity of Rotenone to Daphnia magna, 93. Toxicity of Rotenone to Developing Rainbow Trout, 94. Oral Toxicity of Rotenone to Mammals.

    DTIC Science & Technology

    1988-01-01

    completed as part of the EPA requirements. One of the studies required consisted of acute and chronic toxicity tests on Daphnia magna , the organism chosen because it is sensitive to toxic substances.

  13. Acute toxicity and effects analysis of endosulfan sulfate to freshwater fish species.

    PubMed

    Carriger, John F; Hoang, Tham C; Rand, Gary M; Gardinali, Piero R; Castro, Joffre

    2011-02-01

    Endosulfan sulfate is a persistent environmental metabolite of endosulfan, an organochlorine insecticide-acaricide presently registered by the United States Environmental Protection Agency. There is, however, limited acute fish toxicity data for endosulfan sulfate. This study determines the acute toxicity (LC₅₀s and LC₁₀s) of endosulfan sulfate to three inland Florida native fish species (mosquitofish [Gambusia affinis]; least killifish [Heterandria formosa]; and sailfin mollies [Poecilia latipinna]) as well as fathead minnows (Pimephales promelas). Ninety-six-h acute toxicity tests were conducted with each fish species under flow-through conditions. For all of the above-mentioned fish species, 96-h LC₅₀ estimates ranged from 2.1 to 3.5 μg/L endosulfan sulfate. The 96-h LC₁₀ estimates ranged from 0.8 to 2.1 μg/L endosulfan sulfate. Of all of the fish tested, the least killifish appeared to be the most sensitive to endosulfan sulfate exposure. The above-mentioned data were combined with previous acute toxicity data for endosulfan sulfate and freshwater fish for an effects analysis. The effects analysis estimated hazardous concentrations expected to exceed 5, 10, and 50% of the fish species' acute LC₅₀ or LC₁₀ values (HC₅, HC₁₀, and HC₅₀). The endosulfan sulfate freshwater-fish acute tests were also compared with the available freshwater-fish acute toxicity data for technical endosulfan. Technical endosulfan is a mixture of α- and β-endosulfan. The LC₅₀s had a wider range for technical endosulfan, and their distribution produced a lower HC₁₀ than for endosulfan sulfate. The number of freshwater-fish LC₅₀s for endosulfan sulfate is much smaller than the number available for technical endosulfan, reflecting priorities in examining the toxicity of the parent compounds of pesticides. The toxicity test results and effects analyses provided acute effect values for endosulfan sulfate and freshwater fish that might be applied

  14. Acute toxicity of Headline® fungicide to Blanchard's cricket frogs (Acris blanchardi).

    PubMed

    Cusaac, J Patrick W; Morrison, Shane A; Belden, Jason B; Smith, Loren M; McMurry, Scott T

    2016-04-01

    Previous laboratory studies have suggested that pyraclostrobin-containing fungicide formulations are toxic to amphibians at environmentally relevant concentrations. However, it is unknown if all pyraclostrobin formulations have similar toxicity and if toxicity occurs in different amphibian species. We investigated the acute toxicity of two formulations, Headline(®) fungicide and Headline AMP(®) fungicide, to Blanchard's cricket frogs (Acris blanchardi) based on a direct overspray scenario. In addition, we examined body residues of fungicide active ingredients in A. blanchardi following direct exposure to Headline AMP fungicide. Headline fungicide and Headline AMP fungicide had similar toxicity to A. blanchardi with calculated median lethal doses of 2.1 and 1.7 µg pyraclostrobin/cm(2), respectively, which are similar to the suggested maximum label rate in North American corn (2.2 and 1.52 µg pyraclostrobin/cm(2), respectively). Tissue concentrations of pyraclostrobin were lower than predicted based on full uptake of a direct dose, and did not drop during the first 24 h after exposure. Headline fungicides at corn application rates are acutely toxic to cricket frogs, but acute toxicity in the field will depend on worst-case exposure.

  15. Sensitivity of Danio rerio (Teleostei, Cyprinidae) during two stages of development based on acute toxicity tests.

    PubMed

    Freiry, R; Stelzer, J A A; Maltchik, L; Arenzon, A

    2014-10-01

    The sensitivity of Danio rerio to three chemicals was compared at two growth stages [larval (10 ± 2 after hatching) and post-larval (60 ± 4 days after hatching)] based on acute toxicity tests. Thirty-nine 48 h acute toxicity tests were performed with the substances CuSO4, NaCl and KCl. The 48 h LC50 values at the two growth stages were compared by independent samples t-tests. The results showed a clear decrease in sensitivity when post-larval organisms were used. Since acute toxicity test methods for D. rerio that recommend using post-larval stage fish do not represent the most sensitive stage of the test organism, our study suggests a revision of the methods to use larval fish.

  16. Acute and Subchronic Toxicity of Inhaled Toluene in Male ...

    EPA Pesticide Factsheets

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n = 6 per group) at a concentration of 0 or l 019 ± 14 ppm for 6 h in the acute study and at 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm for 6 h/d, 5 d/week for 13 weeksin the subchronic study. For the acute study, brains were dissected on ice within 30 min of the end of exposure, while for the subchronic study, brains were dissected 18 h after the last exposure. Frontal cortex, hippocampus, cerebellum, and striatum were assayed for a variety of oxidative stress (OS) parameters including total aconitase (TA), protein carbonyls, glutathione peroxidase (GPX), glutathione reductase (GRD), glutathione transferase (GST), y-­glutamylcysteine synthetase (GCS), superoxide dismutase (SOD), total antioxidants (TAS), NADPH quinone oxidoreductase- 1 (NQO1 ), and NADH ubiquinone reductase (UBIQ-RD) activities using commercially available kits. Following acute exposure, UBIQ-RD, GCS and GRD were increased significantly only in the cerebellum, while TAS was increased in frontal cortex. On the other

  17. Case of acute lead toxicity associated with Ayurvedic supplements.

    PubMed

    Breyre, Amelia; Green-McKenzie, Judith

    2016-06-30

    Use of traditional folkloric remedies not disclosed to the physician may be difficult to identify as a source of lead toxicity. This report illustrates the presentation of a 26-year-old man who, during his 1 month vacation in India, was treated for low back pain with Ayurvedic herbal medicine. On his return to the USA, he presented to the emergency department with epigastric pain, weight loss, dark stools, nausea and vomiting. He was admitted and noted to be anaemic with a blood lead level (BLL) of 94.8 µg/dL. Peripheral blood smear demonstrated basophilic stippling. Chelation therapy with succimer was initiated. The patient became asymptomatic within months. Three years later, he remained asymptomatic with BLL <20 µg/dL. Physicians should be cognisant of potential toxicity from these Ayurvedic medications and have a heightened level of suspicion for lead toxicity in the face of anaemia and abdominal pain without obvious cause.

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

    PubMed

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

    2014-10-01

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

  19. Acute toxicity and accumulation of zinc in the crayfish, Orconectes virilis (Hagen)

    SciTech Connect

    Not Available

    1986-09-01

    Zinc produces acute toxicity to freshwater organisms over a range of concentrations from 90 to 58, 100..mu..g Zn/L; with the range of acute median effect concentrations being similar for freshwater fish and invertebrates. The capacity to regulate internal zinc concentrations in decapod crustaceans has been described. Studies with the crayfish Austropotambius pallipes suggested a relatively high degree of tolerance to zinc by this animal. The present study is designed to describe the toxicity of zinc to the crayfish Orconectes virilis over a 2-wk exposure period. In addition, whole animal and tissue analyses were performed on the test organisms and compared to previous results.

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

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    2015-12-01

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

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

    SciTech Connect

    Katayama, Sonja; Striecker, Thorbjoern; Kessel, Kerstin; Sterzing, Florian; Habl, Gregor; Edler, Lutz; Debus, Juergen; Herfarth, Klaus

    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.

  3. Acute Toxicity and Cytotoxicity of Pereskia aculeata, a Highly Nutritious Cactaceae Plant.

    PubMed

    Silva, Debora O; Seifert, Mauricio; Nora, Fabiana R; Bobrowski, Vera L; Freitag, Rogerio A; Kucera, Heidi R; Nora, Leonardo; Gaikwad, Nilesh W

    2017-04-01

    Pereskia aculeata is a Cactaceae plant with valuable nutritional properties, including terrific amounts of protein, minerals, vitamins, and fiber. However, P. aculeata is reported to contain antinutrients and alkaloids in its leaves. In addition, in a study on growth and development, Wistar rats fed with P. aculeata and casein as protein source grew less than the control group (fed with casein only). Therefore, in this study, we evaluated, for the first time, the oral acute toxicity of P. aculeata in rats and also the cytotoxicity behavior of the plant on lettuce seeds. The acute toxicity research was carried out using dried P. aculeata ethanolic extract, in three different doses, administered by gavage to 24 female Wistar rats. The rats were then examined for signs of toxicity, food intake, body weight, and fecal excretion fluctuations, as well as histopathological alterations, using eight different body tissues. The acute toxicity study did not show any difference among the groups in either clinical evaluation or histopathological analyses. For the cytotoxicity study, dried P. aculeata ethanolic extract was applied on lettuce seeds in five different concentrations. These seeds were evaluated for germination, root and shoot length, and mitotic index. The results show that P. aculeata extract affects lettuce root and shoot growth, but not germination or mitotic index. In conclusion, the acute toxicity on rats and the cytogenotoxicity on lettuce of P. aculeata are neglectable, validating the potential of this plant to be used as a functional food.

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

    PubMed

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

    2010-02-01

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

  5. In vitro cytotoxicity testing for prediction of acute human toxicity.

    PubMed

    Barile, F A; Dierickx, P J; Kristen, U

    1994-06-01

    This study was designed to compare the cytotoxic concentrations of chemicals, determined with three independent in vitro cytotoxicity testing protocols, with each other and with established animal LD50 values, and against human toxic concentrations for the same chemicals. Ultimately, these comparisons allow us to evaluate the potential of in vitro cell culture methods for the ability to screen a variety of chemicals for prediction of human toxicity. Each laboratory independently tested 50 chemicals with known human lethal plasma concentrations and LD50 values. Two of the methods used monolayer cell cultures to measure the incorporation of radiolabeled amino acids into newly synthesized proteins and cellular protein content, while the third technique used the pollen tube growth test. The latter is based on the photometric quantification of pollen tube mass production in suspension culture. Experiments were performed in the absence or presence of increasing doses of the test chemical, during an 18- to 24-h incubation. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxic concentrations confirms previous independent findings that the experimental IC50 values are more accurate predictors of human toxicity than equivalent toxic blood concentrations (HETC values) derived from rodent LD50s. In addition, there were no conclusive statistical differences among the methods. It is anticipated that, together, these procedures can be used as a battery of tests to supplement or replace currently used animal protocols for human risk assessment.

  6. Acute toxicity of pesticides in adult and weanling rats.

    PubMed

    Gaines, T B; Linder, R E

    1986-08-01

    LD50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Thirty-six of the chemicals were also tested by the oral route in one sex of weanlings. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and four tested by the dermal route (bufencarb, chlordimeform, dichlofenthion, leptophos) were more toxic to females than to males whereas famphur and 2,4,5-T (oral route) were less toxic to females. Eighteen of the test chemicals were more toxic to the adult than to the weanling and four compounds (leptophos, methidathion, pyrazon, and sulfoxide) were more toxic to the weanling. In additional studies the variability of the LD50 value over a 1-year period was examined for two typical insecticides. Six consecutive bimonthly oral LD50 determinations for parathion and DDT in adults of both sexes indicated that the LD50 values were little affected by the time of year that the tests were done.

  7. Draft Test Guideline: Oyster Acute Toxicity Test (Shell Deposition)

    EPA Pesticide Factsheets

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

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

    EPA Pesticide Factsheets

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

  9. Draft Test Guideline: Bivalve Acute Toxicity Test (Embryo Larval)

    EPA Pesticide Factsheets

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

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

    EPA Pesticide Factsheets

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

  11. Draft Test Guideline: Aquatic Invetebrate Acute Toxicity, Test, Freshwater Daphnids

    EPA Pesticide Factsheets

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

  12. Draft Test Guideline: Fish Acute Toxicity Mitigated By Humic Acid

    EPA Pesticide Factsheets

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

  13. Draft Test Guideline: Whole Sediment Acute Toxicity Invertebrates, Freshwater

    EPA Pesticide Factsheets

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

  14. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

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

    PubMed

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

    2002-02-01

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

  16. Dispersant and salinity effects on weathering and acute toxicity of South Louisiana crude oil.

    PubMed

    Kuhl, Adam J; Nyman, J Andrew; Kaller, Michael D; Green, Christopher C

    2013-11-01

    Chemical dispersants are an important technology in the remediation of oil spills in the aquatic environment, facilitating degradation of crude oil and salinity is an important factor in dispersant effectiveness. The aim of the present study was to explore the role of salinity on the degradation chemistry of crude oil polycyclic aromatic hydrocarbons (PAHs) and acute toxicity of the water accommodated fraction (WAF) of the dispersant COREXIT 9500A and chemically dispersed crude oil on a common estuarine fish. Laboratory microcosms were designed at salinities of 4 parts per thousand (ppt), 12 ppt, or 18 ppt and spiked with crude oil, COREXIT 9500A, or a combined exposure to crude oil and COREXIT and allowed to biodegrade for 1 wk, 4 wk, and 16 wk. The WAF was harvested for analytical PAH analysis and acute toxicity testing in juvenile Fundulus grandis. Compared with undispersed oil, COREXIT exponentially increased the PAH concentrations in the WAF for up to 16 wk; hopane-normalized concentrations indicated that biodegradation was slowed for the first 4 wk. Dispersed crude oil and COREXIT were acutely toxic following 1 wk of biodegradation with no correlation between PAH concentrations and crude oil WAF mortality. Both dispersant and dispersant oil mixtures remained toxic for at least 4 wk at the lowest salinity tested, suggesting increased sensitivity or reduced biodegradation of toxic components in low-saline environments. At the lowest salinity, oil dispersed with COREXIT was more toxic than either the COREXIT alone or oil alone, even after 16 wk of biodegradation.

  17. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

  18. Acute toxicity during external-beam radiotherapy for localized prostate cancer: Comparison of different techniques

    SciTech Connect

    Vijayakumar, S.; Awan, A.; Karrison, T.; Culbert, H.; Chan, S.; Kolker, J.; Low, N.; Halpern, H.; Rubin, S.; Chen, G.T.Y.; Weicheselbaum, R.R. )

    1993-01-15

    The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). The incidence of acute toxicities was significantly less with the beams eye view-based technique than with the other two methods. A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen.

  19. Acute toxicity bioassays of mercuric chloride and malathion on air-breathing fish Channa punctatus (Bloch).

    PubMed

    Pandey, Sanjay; Kumar, Ravindra; Sharma, Shilpi; Nagpure, N S; Srivastava, Satish K; Verma, M S

    2005-05-01

    Acute toxicity tests (96 h) were conducted in flow-through systems to determine the lethal toxicity of a heavy metal compound, mercuric chloride, and an organophosphorus pesticide, malathion, to air-breathing teleost fish, Channa punctatus (Bloch) and to study their behavior. The 96-h LC50 values were determined, as well as safe levels. The results indicate that mercuric chloride is more toxic than malathion to the fish species under study. Dose- and dose-time-dependent increases in mortality rate were also observed in response to both test chemicals.

  20. Acute tellurium toxicity from ingestion of metal-oxidizing solutions.

    PubMed

    Yarema, Mark C; Curry, Steven C

    2005-08-01

    Tellurium is an element used in the vulcanization of rubber and in metal-oxidizing solutions to blacken or tarnish metals. Descriptions of human toxicity from tellurium ingestion are rare. We report the clinical course of 2 children who ingested metal-oxidizing solutions containing substantial concentrations of tellurium. Clinical features included vomiting, black discoloration of the oral mucosa, and a garlic odor to the breath. One patient developed corrosive injury to the esophagus secondary to the high concentration of hydrochloric acid in the solution. Both patients recovered without serious sequelae, which is typical of tellurium toxicity. An awareness of situations in which children may be exposed to tellurium and its clinical presentation may assist clinicians in the diagnosis of this rare poisoning.

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

    USGS Publications Warehouse

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

    2011-01-01

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

  2. Determination of acute toxicity of polychlorinated biphenyls to photobactrium phosphoreum

    SciTech Connect

    Chu, S.; Xu, X.; He, Y.

    1997-02-01

    Polychlorinated biphenyls (PCBs) are a highly lipophilic group of global pollutants, consisting of 209 congeners. PCBs were discovered before the turn of the century and their usefulness for industry, because of their physical properties, was recognized early. The distribution of PCBs in the environment was not noticed until Jensen and his colleagues found PCBs in wildlife samples. Since then, investigations in many parts of the world have revealed the widespread distribution of PCBs in environmental samples and PCVs are persistent and accumulate in food webs. Thus, determination of toxicities of commercial PCB mixtures and PCB congeners are required. Toxicity tests using luminous bacteria have shown high correlation to traditional bioassays. This study compared the EC50 values of the commercial mixtures, PCB3 and PCB5, with those of Aroclor 1242 and Aroclor 1254. 12 refs., 2 tabs.

  3. Physiology is pivotal for interactions between salinity and acute copper toxicity to fish and invertebrates.

    PubMed

    Grosell, M; Blanchard, J; Brix, K V; Gerdes, R

    2007-08-30

    The present paper presents original data and a review of the copper (Cu) toxicity literature for estuarine and marine environments. For the first time, acute Cu toxicity across the full salinity range was determined. Killifish, Fundulus heteroclitus, eggs were hatched in freshwater (FW), 2.5, 5, 10, 15, 22 and 35 ppt (seawater, SW) and juveniles were allowed to acclimate for 7 days prior to acute toxicity testing. Sensitivity was highest in FW (96 h LC50: 18 microg/l), followed by SW (96 h LC50: 294 microg/l) with fish at intermediate salinities being the most tolerant (96 h LC50 > 963 microg/l at 10 ppt). This approximately 50-fold, non-linear variation in sensitivity could not be accounted for by Cu speciation or competition among cations but can be explained by physiology. The relative Na(+) gradient from the blood plasma to the water is greatest in FW followed by SW and is smallest at 10 ppt. Regression of Cu toxicity versus the equilibrium potential for Na(+), which reflects the relative Na(+) gradient, revealed that 93% of the variation can be attributed to Na(+) gradients and thus osmoregulatory physiology. Examination of the existing literature on acute Cu toxicity in SW (defined as >25 ppt) confirmed that early life stages generally are most sensitive but this pattern may be attributable to size rather than developmental stage. Regardless of developmental stage and phylogeny, size clearly matters for Cu sensitivity. The existing literature on the influence of salinity on acute Cu toxicity as well as studies of mechanisms of Cu toxicity in fish and invertebrates are reviewed.

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

    PubMed

    Artola-Garicano, Elsa; Sinnige, Theo L; van Holsteijn, Ineke; Vaes, Wouter H J; Hermens, Joop L M

    2003-05-01

    In the current study, the bioconcentration behavior and acute toxicity of two polycyclic musks, Tonalide 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) and Galaxolide 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta[gamma]-2-benzopyran (HHCB), were studied in two benthic organisms. Polycyclic musks are frequently used fragrances, and they have been detected in different compartments of the environment. The aim of this study was to fill some empirical data gaps for AHTN and HHCB for benthic organisms. Results show that differences exist between both organisms. Chironomus riparius exhibited bioconcentration factors (BCFs) for AHTN and HHCB substantially lower than predicted for nontransformed organics. The BCFs for both chemicals increased after coexposure of the organism to the cytochrome P450 inhibitor piperonyl butoxide. Thus, the low BCF values were the result of rapid biotransformation of AHTN and HHCB in the midge larvae. Bioconcentration kinetics indicated that both chemicals induced their own cytochrome P450-mediated metabolism. Acute toxicity of AHTN to midge larvae was reduced compared to predicted baseline toxicity and was similar for HHCB. Bioconcentration of AHTN and HHCB in the worm (Lumbriculus variegatus) is in agreement with predictions based on the octanol-water partition coefficients of these chemicals. Acute toxicity was found to be similar to predicted values for baseline toxicity. Summarizing, for AHTN and HHCB, acute toxicity and bioconcentration behavior in L. variegatus was in accordance with predicted data for nontransformed organics. In C. riparius, bioconcentration as well as toxicity were reduced.

  5. The Acute, Aquatic Toxicity of Selected Mineral Particles

    DTIC Science & Technology

    1988-11-01

    COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP Graphite; Daphnia magna " 06 1i Nickel...whiskers, nickel-graphite fibers, and synthetic graphite Micro-260 (M-260). Each compound was tested against the cladoceran, Daphnia magna (D. Magna ...graphite fibers, polycrystalline iron whiskers, and graphite Micro-260 (M-260) were tested to determine their toxicities to Daphnia mag . The

  6. Assessment of Acute Toxicity of Hexachloroethane in Laboratory Animals

    DTIC Science & Technology

    1978-01-09

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

  7. Toxic and teratogenic effects of chemical class fractions of a coal-gasification electrostatic precipitator tar.

    PubMed

    Schultz, T W; Dumont, J N; Buchanan, M V

    1983-12-01

    Dimethyl sulfoxide slurries of a coal gasifier electrostatic precipitator tar and its chemical class fractions were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Of the 5 tar fractions the ether-soluble base and polyaromatic were found to be the most teratogenic and the ether-soluble acid and ether-soluble base were the most toxic. The teratogenic effects of the raw tar suggest synergism. The toxic effects to newly metamorphosed froglets is 1-2 orders of magnitude less than those observed for embryos. Chemical analysis shows dihydroxybenzenes and organonitrogen compounds to be the major components of the acid and base fractions, respectively. The neutral fractions contain mainly alkyl-substituted two-ring hydrocarbons.

  8. Primary chemical and physical characterization of acute toxic components in wastewaters

    SciTech Connect

    Svenson, A.; Linlin, Z.; Kaj, L. )

    1992-10-01

    A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.

  9. The acute toxicity of chemically and physically dispersed crude oil to key Arctic species under Arctic conditions during the open water season.

    PubMed

    Gardiner, William W; Word, Jack Q; Word, Jack D; Perkins, Robert A; McFarlin, Kelly M; Hester, Brian W; Word, Lucinda S; Ray, Collin M

    2013-10-01

    The acute toxicity of physically and chemically dispersed crude oil and the dispersant Corexit 9500 were evaluated for key Arctic species. The copepod Calanus glacialis, juvenile Arctic cod (Boreogadus saida), and larval sculpin (Myoxocephalus sp.) were tested under conditions representative of the Beaufort and Chukchi Seas during the ice-free season. The toxicity of 3 water-accommodated fractions (WAF) of Alaska North Slope crude oil was examined with spiked, declining exposures. A dispersant-only test was conducted with the copepod C. glacialis. Each preparation with oil (WAF, breaking wave WAF [BWWAF], and chemically enhanced WAF [CEWAF]) produced distinct suites of hydrocarbon constituents; the total concentrations of oil were lowest in WAF and highest in CEWAF preparations. The relative sensitivity for the different species and age classes was similar within each WAF type. Median lethal concentration values based on total petroleum hydrocarbons ranged from 1.6 mg/L to 4.0 mg/L for WAF and BWWAF treatments and from 22 mg/L to 62 mg/L for CEWAF. For Corexit 9500 exposures, median lethal concentration values ranged from 17 mg/L to 50 mg/L. The differences in the relative toxicity among the accommodated fractions indicated that the majority of petroleum hydrocarbons in the CEWAF are in less acutely toxic forms than the components that dominate the WAF or BWWAF. Further evaluation showed that the parent polycyclic aromatic hydrocarbon compounds, specifically naphthalene, were highly correlated to acute toxicity.

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

    EPA Science Inventory

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

  11. T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer

    PubMed Central

    Reichardt, Sybille D.; Rave-Fränk, Margret; Schirmer, Markus A.; Stadelmann, Christine; Canis, Martin; Wolff, Hendrik A.

    2016-01-01

    Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity. In contrast, the frequency and absolute numbers of selected leukocyte subpopulations measured in samples of peripheral blood mononuclear cells (PBMCs) directly before the beginning of CRT were significantly different in patients with HGAOT as compared to those without. When we validated several potential markers including the abundance of T cells in a small prospective study with 16 HNSCC patients, we were able to correctly predict acute organ toxicity in up to 81% of the patients. We conclude that analysis of PBMCs by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing HGAOT caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome. PMID:27589568

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

    EPA Science Inventory

    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...

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

    EPA Science Inventory

    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...

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

    EPA Science Inventory

    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 ...

  15. EXTRAPOLATION OF ACUTE TOXICITY AMONG AQUATIC SPECIES BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    Presentation provides inter-species QSARs for acute toxicity to ciliates, fish and daphnia...The inter-species QSARs can be also useful in the analysis of the relative species sensitivity to a variety of pollutants and will be useful in assisting in risk assessments of potential ...

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

    EPA Science Inventory

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

  17. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    EPA Science Inventory

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  18. Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

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

    USGS Publications Warehouse

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

    2005-01-01

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

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

    PubMed

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

    2012-06-01

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

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

    USGS Publications Warehouse

    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.

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

    PubMed

    Furyk, E; Ryabokon, E

    2013-02-01

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

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

    PubMed Central

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

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  4. Acute Exposure Guideline Levels (AEGLs) for Time Varying Toxic Plumes

    DTIC Science & Technology

    2014-09-12

    package, which we are calling EAGLE, in the sections below. The package contains the tabulated AEGL data for chlorine (CL2) and ammonia (NH3) at...200C. The molecular weight for chlorine (CL2) is MW = 70.9 and for ammonia (NH3), MW = 17.03. Figure 1 just below reproduces the chlorine table...below shows the same information as Table 1, but for ammonia . The toxicity levels are 50 or 60 times lower than for chlorine, but the behavior with

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

    DTIC Science & Technology

    1982-09-01

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

  6. Acute and chronic toxicity toward the bacteria Vibrio fischeri of organic narcotics and epoxides: structural alerts for epoxide excess toxicity.

    PubMed

    Blaschke, Ulrike; Paschke, Albrecht; Rensch, Ines; Schüürmann, Gerrit

    2010-12-20

    The acute and chronic bacterial toxicity of 34 organic compounds comprising 19 baseline narcotics and 15 epoxides has been determined with regard to 30-min bioluminescence and 24-h growth inhibition in terms of EC50 (effective concentration 50%) values employing Vibrio fischeri. For the narcotics, linear regression of log EC50 on log Kow (octanol/water partition coefficient) yields r2 (squared correlation coefficient) and rms (root-mean-square error) values of 0.95 and 0.44 (30-min), and 0.94 and 0.34 (24-h), respectively. Employing the resultant baseline narcosis models, toxicity enhancement (Te) values were derived as a ratio of narcosis-predicted over experimental EC50 for the epoxides. For seven aliphatic epoxides, log Te was below 1 in both assays, indicating narcosis-range toxicity with regard to 30-min bioluminescence and 24-h growth inhibition. Concerning eight nonaliphatic epoxides, log Te values up to 2.4 were observed, reflecting excess toxicity through an enhanced electrophilic reactivity of the compounds. Here, however, the intercorrelation between both assays was very low (r2 = 0.09). The results are discussed in terms of electronic substituent effects activating an SN2-type epoxide reaction with nucleophilic protein sites and side-chain activation offering alternative electrophile-nucleophile reaction routes at side-chain sites, leading to respective structural alerts as indicators of excess toxicity. Surprisingly, 30-min bioluminescence appears to be slightly more sensitive to chemical stress than 24-h growth, which holds both for baseline narcotics and for most of the epoxides. This is also reflected by effective narcosis doses 50%, ED50, of 7.1 mmol/kg (30-min) and 7.7 mmol/kg (24-h) estimated from narcosis theory. Keeping in mind the different end points (bioluminescence vs growth) involved, this finding demonstrates that chronic toxicity is not always more sensitive than acute toxicity, calling for analyses with regard to further respective

  7. Prediction of acute toxicity of chemicals in mixtures: worms Tubifex tubifex and gas/liquid distribution.

    PubMed

    Tichý, M; Borek-Dohalský, V; Matousová, D; Rucki, M; Feltl, L; Roth, Z

    2002-03-01

    The aim of this contribution is to support our proposal of the procedure for predicting acute toxicity of binary mixtures by QSAR analysis techniques. The changes of a mixture composition are described by molar ratio R and visualized in the R-plot (QCAR--quantitative composition-activity relationships). The approach was inspired by Rault and Dalton's laws, their positive and negative deviations in the behavior of a mixture of real gases, by Loewe and Muischnek isoboles and by the Finney test of additivity. Acute toxicity was determined by the laboratory test with woms Tubifex tubifex. The additivity of the acute toxicity in the binary mixture benzene + nitrobenzene was confirmed and a new interaction is described: "mixed interaction" with the binary mixture aniline + ethanol. The "mixed interaction" means that depending on mixture composition, both potentiation and inhibition can occur. As the first physicochemical descriptor of the changes caused by the changing composition of binary mixtures, the gas/liquid equilibrium was studied and a composition of the gaseous phase was determined by a gas chromatographic method. The method for determination of concentrations in the gaseous phase was described. The gaseous phase composition of benzene + nitrobenzene. benzene + ethanol, benzene + aniline and ethanol + aniline mixtures was analyzed. It was found that if the concentrations of the mixture's components in the gaseous phase behave nonideally (they are not additive), the acute toxicity of the same mixture is not additive as well. Another descriptor to distinguish between potentiation and inhibition will be, however, necessary. The properties, both gaseous phase composition and the acute toxicity, of the benzene + nitrobenzene mixture are additive. In mixtures with the mixed interaction, the R-plot of the composition of the gaseous phase is complex with a large variation of results.

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

    PubMed Central

    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 consecutive days. In the acute toxicity study, L. elliptica essential oil caused dose-dependent adverse behaviours and mortality. The median lethal dose value was 3 488.86 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. elliptica 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. PMID:23024045

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

    PubMed

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

    2015-01-01

    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 < 0.05). Biochemical analysis of 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.

  10. Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Drodge, C.S.; Boychak, O.; Patel, S.; Usmani, N.; Amanie, J.; Parliament, M.B.; Murtha, A.; Field, C.; Ghosh, S.; Pervez, N.

    2015-01-01

    Background Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Methods Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. Results For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50–76 years). Disease was organ-confined (T1c–T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose–volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. Conclusions This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes. PMID:25908924

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

    USGS Publications Warehouse

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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 < 0.05). Biochemical analysis of 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.

  14. Acute toxicity of selected herbicides and surfactants to larvae of the midge Chironomus riparius

    USGS Publications Warehouse

    Buhl, Kevin J.; Faerber, Neil L.

    1989-01-01

    The acute toxicities of eight commercial herbicides and two surfactants to early fourth instar larvae of the midgeChironomus riparius were determined under static conditions. The formulated herbicides tested were Eradicane® (EPTC), Fargo® (triallate), Lasso® (alachlor), ME4 Brominal® (bromoxynil), Ramrod® (propachlor), Rodeo® (glyphosate), Sencor®(metribuzin), and Sutan (+)® (butylate); the two surfactants were Activator N.F.® and Ortho X-77®. In addition, technical grade alachlor, metribuzin, propachlor, and triallate were tested for comparison with the formulated herbicides. The relative toxicity of the commercial formulations, based on percent active ingredient, varied considerably. The EC50 values ranged from 1.23 mg/L for Fargo® to 5,600 mg/L for Rodeo®. Fargo®, ME4 Brominal®, and Ramrod®were moderately toxic to midge larvae; Lasso®, Sutan (+)®, and Eradicane® were slightly toxic; and Sencor® and Rodeo® were practically non-toxic. The 48-hr EC50 values of the two surfactants were nearly identical and were considered moderately toxic to midges. For two of the herbicides in which the technical grade material was tested, the inert ingredients in the formulations had a significant effect on the toxicity of the active ingredients. Fargo® was twice as toxic as technical grade triallate, whereas Sencor® was considerably less toxic than technical grade metribuzin. A comparison of the slope function values indicated that the toxic action of all the compounds occurred within a relatively narrow range. Published acute toxicity data on these compounds for other freshwater biota were tabulated and compared with our results. In general, the relative order of toxicity toC. riparius was similar to those for other freshwater invertebrates and fish. Maximum concentrations of each herbicide in bulk runoff during a projected “critical” runoff event were calculated as a percentage of the application rate lost in a given volume of runoff. A comparison

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

    EPA Pesticide Factsheets

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

  16. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    PubMed Central

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver. PMID:9125564

  17. Effects of Treatment Intensification on Acute Local Toxicity During Radiotherapy for Head and Neck Cancer: Prospective Observational Study Validating CTCAE, Version 3.0, Scoring System

    SciTech Connect

    Palazzi, Mauro Tomatis, Stefano; Orlandi, Ester; Guzzo, Marco; Sangalli, Claudia; Potepan, Paolo; Fantini, Simona; Bergamini, Cristiana; Gavazzi, Cecilia; Licitra, Lisa; Scaramellini, Gabriele; Cantu', Giulio; Olmi, Patrizia

    2008-02-01

    Purpose: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. Methods and Materials: Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventional fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. Results: Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the 'low-burden' class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the 'high-burden' class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. Conclusions: The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant.

  18. Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of acrylonitrile.

    PubMed

    Benz, Frederick W; Nerland, Donald E

    2005-10-01

    Some of the more striking expressions of toxicity are the tremors and seizures observed approximately 100 min after exposure of rats to an acutely toxic dose of acrylonitrile (AN). These early events are followed by a second wave of severe clonic convulsions that occur just prior to death at about 3-4 h. For AN, at least two chemical entities could produce these toxic effects, namely the parent AN molecule, the metabolically-released cyanide, or both. Which of these two agents is responsible for each of the symptoms of acute intoxication is not known. To help dissect the toxicity, it was anticipated that an effective inhibitor of the oxidative metabolism of AN to cyanide could help us to understand which toxic symptoms might be associated with each agent. Three inhibitors of oxidative metabolism were tested, namely SKF-525A, 1-benzylimidazole and metyrapone and one alternative substrate, ethanol. As compared to SKF-525A and metyrapone, both 1-benzylimidazole and ethanol were highly effective in reducing blood cyanide levels to insignificant levels in rats treated with an LD90 dose of AN. In addition, both agents abolished the early seizure activity, suggesting that this first phase of seizures is due to cyanide and not the parent molecule. 1-Benzylimidazole did not prevent the severe clonic convulsive phase preceding death, suggesting that these terminal convulsions are due to the toxic effects of the parent AN molecule. The CNS depressant ethanol was only partially effective in attenuating the terminal convulsions. None of these agents affected the incidence of AN-induced mortality, clearly establishing that, even in the absence of cyanide, the parent AN molecule is acutely toxic. The partial effectiveness of ethanol suggested that anticonvulsants might be of benefit. Both phenobarbital and phenytoin protected rats from both the early and terminal convulsions, while valproic acid was ineffective. These effects were not related to a reduction in blood cyanide

  19. Development of a salinity/toxicity relationship to predict acute toxicity of saline waters to freshwater organisms. Interim final report, June 1990-March 1992

    SciTech Connect

    Mount, D.R.; Gulley, D.D.

    1992-04-01

    Discharge of produced water to surface waters is generally regulated as part of the NPDES permit problem and, therefore, may be subject to discharge limits for aquatic toxicity. Most produced waters contain elevated (relative to fresh water) concentrations of major ions (e.g., sodium, chloride) that can be toxic to fresh water organisms regardless of other organic and inorganic constituents. The objective of the research was to develop a Salinity/Toxicity Relationship (STR) that predicts the acute toxicity of saline waters to freshwater organisms based on the concentrations of major ions in solution. Laboratory toxicity tests were conducted to measure the acute toxicity of major ions to three freshwater species (Ceriodaphnia dubia, Daphnia magna, and fathead minnows). These laboratory toxicity data were then incorporated into multi-variate logistic regression equations that predict the acute toxicity of any combination of major ions. Logistic regression equations represented the toxicity data quite well, generally explaining in excess of 80 percent of the overall variance in survival. Application of the Ceriodaphnia STR to field data collected from surface waters receiving produced water discharges showed very strong correlation of STR predictions with the results of toxicity tests conducted on field-collected samples.

  20. Acute aquatic toxicity of nine alcohol ethoxylate surfactants to fathead minnow and Daphnia magna

    SciTech Connect

    Wong, D.C.L.; Dorn, P.B.; Chai, E.Y.

    1995-12-31

    The aquatic toxicity of nine commercial-grade alcohol ethoxylate surfactants was studied in acute exposures to fathead minnow (Pimephales promelas) and Daphnia magna. All studies were conducted in accordance with USEPA TSCA Good Laboratory Practice Standards. Mean measured surfactant concentrations in exposure solutions showed good agreement with nominal concentrations for both fathead minnow and daphnid tests. Surfactant recoveries ranged from 59 to 97% and 67 to 106% in the fathead minnow and daphnid solutions, respectively. The response of both species to the surfactants was generally similar with the daphnids being slightly more sensitive to a few surfactants. Surfactant toxicity tended to increase with increasing alkyl chain lengths. The effect of low average EO groups on increased surfactant toxicity was more evident in the daphnid exposures. Quantitative structure-activity relationship (QSAR) models were developed form the data which relates surfactant structure to toxicity. The models predict increasing toxicity with decreasing EO number and increasing alkyl chain length. The models also indicate that alkyl chain length has a greater effect on toxicity than EO groups. Further, the models indicate that both species did not differ markedly in their sensitivity to alkyl chain length effects, while the number of EO groups had a stronger effect on daphnids than fathead minnow. Good agreement was found between QSAR model-predicted toxicity and reported toxicity values from the literature for several surfactants previously studied.

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

    PubMed

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

    2014-04-01

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

  2. Acute acetaminophen toxicity in transgenic mice with elevated hepatic glutathione.

    PubMed

    Rzucidlo, S J; Bounous, D I; Jones, D P; Brackett, B G

    2000-06-01

    Previous studies demonstrated that elevation of hepatic glutathione (GSH) concentrations protect against acetaminophen (APAP) hepatotoxicity in mice. Employing transgenic mice overexpressing glutathione synthetase, this study was conducted to determine if sustained elevation of hepatic GSH concentrations could ameliorate or prevent APAP toxicity. International Cancer Research transgenic mouse males and matched (ie same strain, sex, and age) control nontransgenic mice were pretreated ip with GSH synthetase substrate gamma-glutamylcysteinyl ethyl ester (gamma-GCE) or with saline. After a 16-h fast, mice received a single dose of 500 mg APAP/kg bw in saline ip and were sacrificed 4 h later. Other mice similarly pretreated were killed without APAP challenge. The elevated GSH concentrations in transgenic mice livers did not lessen APAP hepatotoxicity. Instead higher degrees of hepatotoxicity and nephrotoxicity were observed in transgenic mice than in controls as indicated by higher serum alanine aminotransferase activity and more severe histopathological lesions in transgenic mice livers and kidneys. Pretreatment with gamma-GCE did not affect either initial or post-APAP treatment tissue GSH concentrations or observed degrees of toxicity. Detection of a higher level of serum APAP in transgenic mice and the histopathological lesions found in transgenic mice kidneys together with no observable nephrotoxicity in control mice indicated early kidney damage in transgenic mice. Our findings suggest that high levels of GSH-APAP conjugates resulting from increased GSH concentrations in the livers of transgenic mice caused rapid kidney damage. Compromised excretory ability may have caused retention of APAP, which, in effect, elicited higher hepatotoxicity than that observed in nontransgenic mice.

  3. Acute and Subacute Oral Toxicity Evaluation of Eriobotrya japonica Leaf Triterpene Acids in ICR Mice

    PubMed Central

    Shi, Xianai

    2017-01-01

    The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has increased recently because of its beneficial effects on health. However, there has been a lack of experimental data on its toxicity. The present study therefore was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA produced neither mortality nor toxicity of the main organs in ICR male and female mice in both acute (0.30, 0.65, 1.39, and 3.00 g·kg−1 body weight) and subacute (150, 300, and 600 mg·kg−1 BW) 28-day toxicity studies. Because of lacking apparently adverse effects found in the hematology, clinical biochemistry, and histopathology evaluation, results of the present study together with the beneficial effects make ELTA as a promising dietary supplement and indicated that ELTA administered orally might have a large safety margin for human.

  4. Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish.

    PubMed

    Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto

    2016-08-15

    Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a(fh318). After treatment with 1mM sodium arsenite, the survival of nrf2a(fh318) larvae was significantly shorter than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity.

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

    PubMed

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

    2007-09-25

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

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

    PubMed

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

    2016-01-01

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

  7. Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

    SciTech Connect

    Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C. )

    1990-12-01

    The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).

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

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    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.

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

    PubMed

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

    2016-10-01

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

  10. Estimation of acute oral toxicity in rat using local lazy learning

    PubMed Central

    2014-01-01

    Background Acute toxicity means the ability of a substance to cause adverse effects within a short period following dosing or exposure, which is usually the first step in the toxicological investigations of unknown substances. The median lethal dose, LD50, is frequently used as a general indicator of a substance’s acute toxicity, and there is a high demand on developing non-animal-based prediction of LD50. Unfortunately, it is difficult to accurately predict compound LD50 using a single QSAR model, because the acute toxicity may involve complex mechanisms and multiple biochemical processes. Results In this study, we reported the use of local lazy learning (LLL) methods, which could capture subtle local structure-toxicity relationships around each query compound, to develop LD50 prediction models: (a) local lazy regression (LLR): a linear regression model built using k neighbors; (b) SA: the arithmetical mean of the activities of k nearest neighbors; (c) SR: the weighted mean of the activities of k nearest neighbors; (d) GP: the projection point of the compound on the line defined by its two nearest neighbors. We defined the applicability domain (AD) to decide to what an extent and under what circumstances the prediction is reliable. In the end, we developed a consensus model based on the predicted values of individual LLL models, yielding correlation coefficients R2 of 0.712 on a test set containing 2,896 compounds. Conclusion Encouraged by the promising results, we expect that our consensus LLL model of LD50 would become a useful tool for predicting acute toxicity. All models developed in this study are available via http://www.dddc.ac.cn/admetus. PMID:24959207

  11. Metal uptake and acute toxicity in zebrafish: common mechanisms across multiple metals.

    PubMed

    Alsop, Derek; Wood, Chris M

    2011-10-01

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

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

    PubMed

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

    2014-07-01

    In recent years, numerous studies have indicated that various long-term use drugs, such as antibiotics or analgesics, not only cannot be completely decomposed via sewage treatment but also exhibit biological toxicity if they enter the environment; thus, the release of these drugs into the environment can damage ecological systems. This study sought to investigate the acute toxicity of two commonly utilized analgesics, ibuprofen (IBU) and acetaminophen (APAP), to aquatic organisms after these drugs have entered the water. To address this objective, the acute toxicity (median lethal concentration, LC₅₀, for a 96-h exposure) of IBU alone, APAP alone, and mixtures containing different ratios of IBU and APAP in green neon shrimp (Neocaridina denticulata) were measured. The results of four tests revealed that the 96-h LC₅₀ values for IBU and APAP alone were 6.07 mg/L and 6.60 mg/L, respectively. The 96-h LC₅₀ for a 1:1 mixture of IBU and APAP was 6.23 mg/L, and the toxicity of this mixture did not significantly differ from the toxicity of either drug alone (p<0.05). The experimental results for mixtures containing unequal ratios of IBU and APAP indicated that mixtures with high APAP concentrations and low IBU concentrations exhibited markedly greater toxicity in N. denticulata (LC₅₀=4.78 mg/L) than APAP or IBU alone. However, mixtures with high IBU concentrations and low APAP concentrations exhibited lower toxicity in N. denticulata (LC₅₀=6.78 mg/L) than IBU or APAP alone. This study demonstrated that different mixtures of IBU and APAP were associated with different toxic effects in green neon shrimp.

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

    PubMed

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

    2011-01-01

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

  14. Acute oral toxicity of sodium cyanide in birds

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

    1986-01-01

    Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

  15. Antidotal treatment of the acute cardiovascular toxicity of verapamil.

    PubMed

    Strubelt, O

    1984-09-01

    Rats anaesthetized with pentobarbital and ventilated artificially were infused with 0.15 mg/kg/min. verapamil; without antidotal treatment, they died after 51.1+/-7.1 min. The survival time more than trebled upon an additional infusion with calcium chloride, epinephrine, isoprenaline, orciprenaline or prenalterol and nearly doubled upon administration of a plasma expander. It was not increased, however, by treatment with angiotensin or atropine. The infusion of verapamil declined the arterial blood pressure by 75%, and heart rate, cardiac output and peripheral resistance by about 50%; in the ECG, sinus bradycardia followed by AV-dissociation with nodal rhythm occurred. All antidotes that raised the lethal dose of verapamil increased the cardiac output. Calcium and the sympathomimetics with alpha-adrenergic activity also counteracted the verapamil-induced hypotension. Calcium did not influence the ECG alterations produced by verapamil, while the sympathomimetics restored the sinus rhythm or accelerated the nodal pacemaker. Calcium, epinephrine and isoprenaline also antagonized the strong decrease of left-ventricular dp/dt max. induced by verapamil. In conclusion, calcium as well as sympathomimetic amines are potent antidotes against the cardiovascular toxicity of verapamil, the latter being superior to calcium in their ability to improve pacemaker activity and AV-conduction.

  16. Acute ecological toxicity and environmental persistence of simulants

    SciTech Connect

    Cataldo, D.A.; Ligotke, M.W.; McVeety, B.D.; Fellows, R.J.; Bolton, H. Jr.; Li, S.W.; Van Voris, P.; Wentsel, R.S.

    1988-06-01

    The objectives of these studies are to establish the comparative environmental behavior and chemical fate of chemical simulants. Laboratory studies were undertaken to establish: (1) deposition efficiency (deposition velocities, Vd) for receptor surfaces including plant foliage and soils; (2) dose/response relationships for important environmental components including plants and soil microflora; and (3) the environmental persistence of the simulants. Chemical agent simulants are employed for a range of testing and training activities where use of chemical agents is less than suitable from a safety and environmental standpoint. A variety of chemical simulant materials are used to simulate either nerve agents or blister agents. The following research describes the environmental effects and persistence of four simulants. These are the nerve agent stimulants diisopropyl methylphosphonate (DIMP), diisopropyl fluorophosphate (DFP), and bis (2-ethylhexyl) phosphonate (BIS), and the mustard stimulant 2-chloroethyl ethyl sulfide (CEES). The vapor pressures for DIMP, DFP, and CEES are relatively high, reported to be 0.17, 0.58 and 3.4 mm Hg, respectively; while that of BIS is substantially less at 5.8 /times/ 10/sup /minus/5/ mm Hg at 25/degree/C. The chemical characteristics of DFP and CEES are very similar to G/VX-agents and mustard, respectively, and are employed for materials evaluation under controlled conditions. However, their toxicity precludes their use in the environment. DIMP and BIS are currently used for testing in the open air. 3 figs., 3 tabs.

  17. MHC class I protects motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis (ALS)

    PubMed Central

    Braun, Lyndsey; Meyer, Kathrin; Frakes, Ashley E.; Ferraiuolo, Laura; Likhite, Shibi; Bevan, Adam K.; Foust, Kevin D.; McConnell, Michael J.; Walker, Christopher M.; Kaspar, Brian K.

    2016-01-01

    Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic towards motor neurons (MNs) and play a non-cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of motor neurons to cell death remains unclear. Here, we report that astrocytes derived from mice bearing ALS mutations and from individuals with ALS reduce expression of major histocompatibility complex class I (MHCI) on MNs. Reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MN against astrocyte toxicity. A single MHCI molecule, HLA-F, protects MNs from ALS astrocyte-mediated toxicity, while knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, an inhibitory receptor that recognizes MHCI, on astrocytes results in enhanced MN death. These data indicate that in ALS upon loss of MHCI expression MNs become vulnerable to astrocyte-mediated toxicity. PMID:26928464

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

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    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

  19. Assessing contaminant sensitivity of endangered and threatened aquatic species: Part I. Acute toxicity of five chemicals

    USGS Publications Warehouse

    Dwyer, F.J.; Mayer, F.L.; Sappington, L.C.; Buckler, D.R.; Bridges, C.M.; Greer, I.E.; Hardesty, D.K.; Henke, C.E.; Ingersoll, C.G.; Kunz, J.L.; Whites, D.W.; Augspurger, T.; Mount, D.R.; Hattala, K.; Neuderfer, G.N.

    2005-01-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  20. Assessing contaminant sensitivity of endangered and threatened aquatic species: part I. Acute toxicity of five chemicals.

    PubMed

    Dwyer, F J; Mayer, F L; Sappington, L C; Buckler, D R; Bridges, C M; Greer, I E; Hardesty, D K; Henke, C E; Ingersoll, C G; Kunz, J L; Whites, D W; Augspurger, T; Mount, D R; Hattala, K; Neuderfer, G N

    2005-02-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  1. Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment

    SciTech Connect

    McKim, J.M.; Bradbury, S.P.; Niemi, G.J.

    1987-04-01

    Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and predictive screening tools to select more potentially hazardous chemicals for in-depth laboratory evaluation has been proposed. Further implementation and refinement of quantitative structure-toxicity relationships in aqueous toxicology and hazard assessment requires the development of a mode-of-action database. With such a database, a qualitative structure-activity relationship can be formulated to assign the proper mode of action, and respective QSAR, to a given chemical structure. In this review, the development of fish acute toxicity syndromes (FATS), which are toxic-response sets based on various behavioral and physiological-biochemical measurements, and their projected use in the mode-of-action database are outlined. Using behavioral parameters monitored in the fathead minnow during acute toxicity testing, FATS associated with acetylcholinesterase (AChE) inhibitors and narcotics could be reliably predicted. However, compounds classified as oxidative phosphorylation uncouplers or stimulants could not be resolved. Refinement of this approach by using respiratory-cardiovascular responses in the rainbow trout, enabled FATS associated with AChE inhibitors, convulsants, narcotics, respiratory blockers, respiratory membrane irritants, and uncouplers to be correctly predicted.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  4. Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment.

    PubMed Central

    McKim, J M; Bradbury, S P; Niemi, G J

    1987-01-01

    Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and predictive screening tools to select more potentially hazardous chemicals for in-depth laboratory evaluation has been proposed. Further implementation and refinement of quantitative structure-toxicity relationships in aquatic toxicology and hazard assessment requires the development of a "mode-of-action" database. With such a database, a qualitative structure-activity relationship can be formulated to assign the proper mode of action, and respective QSAR, to a given chemical structure. In this review, the development of fish acute toxicity syndromes (FATS), which are toxic-response sets based on various behavioral and physiological-biochemical measurements, and their projected use in the mode-of-action database are outlined. Using behavioral parameters monitored in the fathead minnow during acute toxicity testing, FATS associated with acetylcholinesterase (AChE) inhibitors and narcotics could be reliably predicted. However, compounds classified as oxidative phosphorylation uncouplers or stimulants could not be resolved. Refinement of this approach by using respiratory-cardiovascular responses in the rainbow trout, enabled FATS associated with AChE inhibitors, convulsants, narcotics, respiratory blockers, respiratory membrane irritants, and uncouplers to be correctly predicted. PMID:3297660

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

    PubMed

    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.

  6. Effect of sulfate concentration on acute toxicity of selenite and selenate to invertebrates and fish. Final report

    SciTech Connect

    McIntyre, D.O.; McCauley, D.J.; McCool, P.; Winkler, N.; DeGraeve, M.

    1998-12-01

    The effect of sulfate concentration on the acute toxicity of selenite (Se IV) and selenate (Se VI) to freshwater organisms was evaluated using toxicity test data generated from this study and toxicity data obtained from the open literature. The acute toxicity of Se IV and Se VI to fathead minnows and two amphipod species, Gammarus pseudolimnaeus and Hyalella azteca, were determined in four different sulfate concentrations. The newly generated toxicity data combined with the data obtained from the literature were evaluated using analysis of covariance to determine if there was a significant relationship between acute toxicity and sulfate concentration. The analysis of the Se IV data indicated that there was not a significant relationship between the acute toxicity of Se IV and sulfate concentration. A significant relationship was found between the acute toxicity of Se VI to freshwater organisms and sulfate concentration. Statistically significant slopes describing the relationship between Se VI toxicity and sulfate concentration were determined for individual species and for the combined data. A sulfate-based equation was constructed using the pooled slope to modify the criterion maximum concentration (CMC) for selenate: CMC = e{sup [0.4259(ln[sulfate]) + 4.6305]}.

  7. Acute toxicity of cadmium and sodium pentachlorophenate to daphnids and fish

    SciTech Connect

    Hall, W.S.; Paulson, R.L.; Hall, L.W. Jr.; Burton, D.T.

    1986-08-01

    When estimating the toxicity of effluents it is desirable to use organisms sensitive to a wide range of pollutants. Currently, the US Environmental Protection Agency (US EPA) recommends the use of Daphnia pulex, Daphnia magna, and Pimephales promelas to assess the toxicity of freshwater effluents. Ceriodaphnia sp. has also received increased attention as a standard toxicity test organism due to its sensitivity, short generation time, and ubiquitous distribution. Comparison of toxicity data generated by different investigators is often difficult because of differences in test procedures, dilution waters, or nutritional history of test organisms. The primary objectives of this research were to compare the sensitivity of Daphnia magna, Daphnia pulex, Ceriodaphnia reticulata, and Pimephales promelas to the reference toxicants CdCl/sub 2/ and sodium pentachlorophenate (NaPCP) and to compare results with those obtained by other investigators. A secondary objective of this study was to evaluate the effect of different dilution waters on the acute toxicity of these reference toxicants to the above test organisms.

  8. Acute Dermal Toxicity of CHF1, CHR2 and Saline in Rabbits.

    DTIC Science & Technology

    1982-09-01

    yellowish-white foci in the liv*-r that are typical (f lecions caused by Eimeria stiedae , a coccidia that infects in-rahentic bile ducts of rabbits . Thene...AD-A12i 944 ACUTE DERI1ALTTOXICITY OF CHFi CHR2 AND SALINE IN / RABBITS (U) LETTERMAN ARMY INST OF RESEARCH PRESIDIO OF SAN FRANCISCO CA M A HANES ET...NdATIONiAL 3SPIA OF SITiOAM - 963 -A - INSTITUTE REPORT NO. 130 S ACUTE DERMAL TOXICITY OF CHF 1, CHR 2 AND SALINE IN RABBITS MARTHA A. HANES, DVM, CPT VC JOHN

  9. Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

    PubMed

    Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

    2012-11-01

    The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

  10. Evaluation of the annual killifish Nothobranchius guentheri as a tool for rapid acute toxicity screening

    SciTech Connect

    Shedd, T.R.; Widder, M.W.; Toussaint, M.W.; Sunkel, M.C.; Hull, E.

    1999-10-01

    This study evaluated the use of Nothobranchius guentheri as a novel organism for rapid acute toxicity screening. A major advantage of the species is that there is no need to maintain a continuous culture to have organisms immediately available for testing. Rather, the embryos are viable under long-term storage conditions and can be hatched within a few hours. The tests require only 24 h with standard laboratory equipment. Sensitivity levels for 11 representative toxicants were comparable to those reported for five of the standard US Environmental Protection Agency test species requiring continuous culture.

  11. Acute toxicity of PCB congeners to Daphnia magma and Pimephales promelas

    SciTech Connect

    Dillon, T.M. ); Burton, W.D.S. )

    1991-02-01

    The acute toxicity (EC50/LC50) of commercial PCB mixtures has been reported to range from 2.0 to 283 ug/L. Because PCBs are very hydrophobic most biological studies have utilized a carrier solvent to facilitate introduction of PCBs into aqueous solution. As a result, biological effects are often reported at exposure concentrations exceeding water solubility. The purpose of this work was to evaluate the comparative toxicity of selected PCB congeners without carrier solvents. These tests were conducted on early life stages of two sensitive freshwater organisms, Daphnia magna and Pimephales promelas.

  12. Evaluation of acute toxicity, cytotoxicity and genotoxicity of a nickel mining waste to Oreochromis niloticus.

    PubMed

    Oliveira-Filho, Eduardo Cyrino; Muniz, Daphne Heloisa de Freitas; Ferreira, Maria Fernanda Nince; Grisolia, Cesar Koppe

    2010-11-01

    The pyrometallurgical process of mining for obtaining ferronickel involves a stage of calcinations. At this stage a residue is generated described as a calcination dust of fine black grains. Analysis of this material revealed a significant presence of Fe, around 53,000 ppm and Ni, around 14,000, beyond of other metals as Al, Mn, and Cr. Adults and larvae of Oreochromis niloticus were used to evaluate acute toxicity, cytotoxicity and genotoxicity, and histopathological effects. The data obtained show absence of toxicity in concentrations of 5, 10 and 50% but a considerable potential for bioaccumulation in the fish's body.

  13. Acute toxicity of cypermethrin to the non target organism Hyalella curvispina.

    PubMed

    Mugni, Hernán; Paracampo, Ariel; Marrochi, Natalia; Bonetto, Carlos

    2013-01-01

    The acute toxicity of cypermethrin to the amphipod Hyalella curvispina was evaluated by means of a toxicity test under laboratory conditions. Cypermethrin is one of the most widely used insecticides in Argentina. H. curvispina is a widely distributed and commonly abundant component of the invertebrate assemblages in shallow waters of southern South America. The experiments were repeated three times. The mean 48-h LC(50) value for H. curvispina was estimated at 0.066μg/l. H. curvispina represents a good model for exotoxicological risk assessment.

  14. HMX: Analysis of Dosing Formulations Used in Acute, Sub-Acute and Sub-Chronic Toxicity Studies.

    DTIC Science & Technology

    1985-07-31

    14.72 - 1 50 78 1 79 1 1 I I 72 15.30 1 I 50 781 I I I 3 1 1 1 1 5 0 1 1 1 I i 15.07 -5 1 112 1 ,? 3 1 4,3 74 15.251 " 1 1 50 1 114 1 113 0 I I I 75...NUMBER 2. GOVT ACCESSION NO 3 . RECIPIENT’S CATALOG NUMBER 4. TITLE (end Subtitle) S. TYPE OF REPORT & PERIOD COVERED HMX: Analysis of dosing formulations...HMX: Analysis of Dosing Formulations Used in Acute, Sub-acute and Sub-chronic Toxicity Studies Final Report by: M.S. Henderson 3 , July,, 1985 Supported

  15. Multiple factors govern the association between pharmacology and toxicity in a class of drugs: toward a unification of class effect terminology.

    PubMed

    Smith, Dennis A; Harrison, Anthony; Morgan, Paul

    2011-04-18

    The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class effect, especially if one or more of the others shows findings even slightly related or at very much lower incidence. This is particularly problematic when the term is used loosely or speculatively on initial events that are themselves of low incidence and serious. This speculation exaggerates and distorts the scientific process in establishing the true benefit risk of the individual drugs and can lead to lengthy development times, or highly restrictive labeling, to the detriment of patient welfare. To provide better definition and application of the term, we suggest that the term class effect toxicity is only used when a clear mechanistic link has been established between a safety concern and drug class based on (I) where the primary pharmacology delivers a clear rationale for the observed findings and toxicities; and (II) where the secondary pharmacology is obligate to the class of the molecule and not subject to variation of structure, and the selectivity cannot be impacted significantly by variations in potency introduced by structural manipulation. With these categorizations, we believe class effect toxicity will be mainly confined to I with examples such as the tetracycline class of antibacterials which inhibit protein synthesis both as a mechanism of antibacterial activity and to produce hepatic injury by mitochondrial injury in the liver.

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2013-03-01

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

  18. Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules.

    PubMed Central

    Scholl, P; Diez, A; Mourad, W; Parsonnet, J; Geha, R S; Chatila, T

    1989-01-01

    Toxic shock syndrome toxin 1 (TSST-1) is a 22-kDa exotoxin produced by strains of Staphylococcus aureus and implicated in the pathogenesis of toxic shock syndrome. In common with other staphylococcal exotoxins, TSST-1 has diverse immunological effects. These include the induction of interleukin 2 receptor expression, interleukin 2 synthesis, proliferation of human T lymphocytes, and stimulation of interleukin 1 synthesis by human monocytes. In the present study, we demonstrate that TSST-1 binds with saturation kinetics and with a dissociation constant of 17-43 nM to a single class of binding sites on human mononuclear cells. There was a strong correlation between the number of TSST-1 binding sites and the expression of major histocompatibility complex class II molecules, and interferon-gamma induced the expression of class II molecules as well as TSST-1 binding sites on human skin-derived fibroblasts. Monoclonal antibodies to HLA-DR, but not to HLA-DP or HLA-DQ, strongly inhibited TSST-1 binding. Affinity chromatography of 125I-labeled cell membranes over TSST-1-agarose resulted in the recovery of two bands of 35 kDa and 31 kDa that comigrated, respectively, with the alpha and beta chains of HLA-DR and that could be immunoprecipitated with anti-HLA-DR monoclonal antibodies. Binding of TSST-1 was demonstrated to HLA-DR and HLA-DQ L-cell transfectants. These results indicate that major histocompatibility complex class II molecules represent the major binding site for TSST-1 on human cells. Images PMID:2542966

  19. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  20. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development (SETAC abstract)

    EPA Science Inventory

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limit...

  1. [Acute toxicity of 10 Moroccan plants reported to be hypoglycemic agents].

    PubMed

    Jaouhari, J T; Lazrek, H B; Jana, M

    1999-01-01

    An acute toxicity study of twelve medicinal plants on Swiss albino mice has been carried out. The extracts were administered orally at a dose of 1 g/kg body weight. Animals were observed for 7 days and changes in weight and behaviour were noted. On the eighth day, the animals were sacrificed and an anatomo-histopathologic survey was undertaken. The results showed a change in behaviour and some histologic modifications following the administration of certain plant extracts.

  2. COMPUTATIONAL INVESTIGATION OF CHEMICAL REACTIVITY IN RELATION TO BIOACTIVATION AND TOXICITY ACROSS CLASSES OF HALOORGANICS: BROMINATION VS. CHLORINATION

    EPA Science Inventory

    COMPUTATIONAL INVESTIGATION OF CHEMICAL REACTIVITY IN RELATION TO BIOACTIV A TION AND TOXICITY ACROSS CLASSES OF HALOORGANICS: BROMINATION VS. CHLORINATION.

    Halogenation is a common feature of many classes of environmental contaminants, and often plays a crucial role in po...

  3. The acute whole effluent toxicity of storm water from an international airport

    SciTech Connect

    Fisher, D.J.; Turley, S.D.; Turley, B.S.; Yonkos, L.T.; Ziegler, G.P.; Knott, M.H.

    1995-06-01

    In October 1990, the US Environmental Protection Agency promulgated application requirements with deadlines for storm-water discharges associated with industrial activity and certain municipal systems. Major airports have a number of hydrocarbon-based contaminants that could appear in storm-water runoff. In addition, ethylene, diethylene, and propylene glycol deicing and anti-icing mixtures are used during freezing and near-freezing weather. The objective of this study was to characterize the potential acute impact on aquatic life from industrial storm-water discharges from an international airport. Samples from winter storm events caused acute toxicity to both the fathead minnow (Pimephales promelas) and the daphnid (Daphnia magna), with LC50 values for both species as low as 1.0 and 2.0% effluent. The toxicity of the samples was due to the various glycol-based deicer/anti-icer mixtures used during these events. High oxygen demands and elevated total nitrogen levels are other potential problems during anti-icing/deicing activities. Samples from rain events during the nonwinter months at the airport did not cause acute toxicity unless associated with fuel spills. As a result of this study, a new discharge permit has been issued for this airport, requiring the implementation of plans for the collection and recycling and/or disposal of the deicer/anti-icer mixtures.

  4. Enantioselective acute toxicity effects and bioaccumulation of furalaxyl in the earthworm (Eisenia foetida).

    PubMed

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

    2014-06-01

    The enantioselectivities of individual enantiomers of furalaxyl in acute toxicity and bioaccumulation in the earthworm (Eisenia foetida) were studied. The acute toxicity was tested by filter paper contact test. After 48 h of exposure, the calculated LC50 values of the R-form, rac-form, and S-form were 2.27, 2.08, and 1.22 µg cm(-2), respectively. After 72 h of exposure, the calculated LC50 values were 1.90, 1.54, and 1.00 µg cm(-2), respectively. Therefore, the acute toxicity of furalaxyl enantiomers was enantioselective. During the bioaccumulation experiment, the enantiomer fraction of furalaxyl in earthworm tissue was observed to deviate from 0.50 and maintained a range of 0.55-0.60; in other words, the bioaccumulation of furalaxyl was enantioselective in earthworm tissue with a preferential accumulation of S-furalaxyl. The uptake kinetic of furalaxyl enantiomers fitted the first-order kinetics well and the calculated kinetic parameters were consistent with the low accumulation efficiency.

  5. A simultaneous multiple species acute toxicity test comparing relative sensitivities of six aquatic organisms to HgCl{sub 2}

    SciTech Connect

    McCrary, J.E.; Heagler, M.G.

    1995-12-31

    In the last few years there has been concern in the scientific community about observed declines in some amphibian species. These population declines could be reflecting a global phenomenon due to a general class sensitivity or may be part of a natural cycle. The suggestion of an overall greater sensitivity of amphibians is not supported. Studies show that amphibians, as a class, are neither more or less susceptible than fish to environmental conditions. Mercury has been found to be one of the most toxic of the heavy metals introduced into amphibian breeding waters. Six aquatic species were simultaneously exposed in a comparative acute toxicity test with mercury chloride: three amphibians, Rana catesbeiana (bullfrog), R. clamitans (green frog), and R. sphenocephala (southern leopard frog, formally classified as R. utricularia); two fish, Gambusia affinis (mosquitofish) and Notemigonus crysoleucas (golden shiner); one aquatic aligochaete, Lumbriculus variegatus (aquatic earthworm). The five test concentrations used were 1.4, 3.9, 12.0, 110.0, and 487.0 {micro}g Hg/L respectively. Ten organisms per species were randomly placed into the six test tanks (control and five concentrations), each species in a separate chamber. The resultant LC50-96hr values produced the following rank order: R. sphenocephala, 6.59 {micro}g Hg/L; R. clamitans, 14.7 {micro}g Hg/L; N. crysoleucas, 16.75 {micro}g Hg/L; L. variegatus, 43.72,ug Hg/L; G. affinis, 52.62 {micro}g Hg/L; R. catesbeiana, 63.36 {micro}g Hg/L. No general organism class sensitivity trend, for amphibians, was developed from this data, contrary to the implicit suggestions of some researchers.

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

    PubMed

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

    2017-02-01

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

  7. Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures of polycyclic aromatic hydrocarbons in zebrafish.

    PubMed

    Willis, Alison M; Oris, James T

    2014-09-01

    The present study examined photo-induced toxicity and toxicokinetics for acute exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo-enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of magnitude below effects observed in the absence of UV. Because environmental exposure to PAHs is usually in the form of complex mixtures, the present study examined the photo-induced toxicity of both single compounds and mixtures of PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene, carbazole, and phenanthrene) to examine the hypothesis that phototoxic (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways of mixtures could be predicted from single exposures. Anthracene and pyrene were phototoxic as predicted; however, carbazole exhibited moderate photo-induced toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of each chemical alone was used to compare the toxicity of mixtures in binary, tertiary, and quaternary combinations of these PAHs, and a predictive model for environmental mixtures was generated. The results indicated that the acute toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the magnitude of photo-enhancement. Based on PAH concentrations found in water and circumstances of high UV dose to aquatic systems, there exists potential risk of photo-induced toxicity to aquatic organisms.

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

    PubMed

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

    2005-03-01

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

  9. A microfluidic device for continuous sensing of systemic acute toxicants in drinking water.

    PubMed

    Zhao, Xinyan; Dong, Tao

    2013-12-03

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

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

    PubMed Central

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

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity. PMID:24386634

  11. Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats

    PubMed Central

    Koontongkaew, Sittichai; Poachanukoon, Orapan; Sireeratawong, Seewaboon; Dechatiwongse Na Ayudhya, Thaweephol; Khonsung, Parirat; Jaijoy, Kanjana; Soawakontha, Ruedee; Chanchai, Monraudee

    2014-01-01

    Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females. PMID:27379341

  12. Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats.

    PubMed

    Koontongkaew, Sittichai; Poachanukoon, Orapan; Sireeratawong, Seewaboon; Dechatiwongse Na Ayudhya, Thaweephol; Khonsung, Parirat; Jaijoy, Kanjana; Soawakontha, Ruedee; Chanchai, Monraudee

    2014-01-01

    Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

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

    PubMed

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

    2014-09-01

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

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

    USGS Publications Warehouse

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

    1997-01-01

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

  15. Laboratory Evaluation of Toxicity of Insecticide Formulations from Different Classes against American Cockroach (Dictyoptera: Blattidae)

    PubMed Central

    Syed, Ruhma; Manzoor, Farkhanda; Adalat, Rooma; Abdul-Sattar, Abida; Syed, Azka

    2014-01-01

    Background The present study was designed to investigate the insecticidal efficacy of four different classes of insecticides: pyrethroids, organophosphates, phenyl-pyrazoles and neo-nicotenoids. One representative chemical from each class was selected to compare the toxicity: deltamethrin from pyrethroids, Dichlorovinyl Dimethyl Phosphate (DDVP) from organophosphates, fipronil from phenyl-pyrazoles and imidacloprid from neo-nicotenoids. The objective of this study was to determine which of these insecticides were most effective against American cockroach. Methods: These insecticides were tested for their LC50 values against Periplaneta americana under topical bioassay method, using different concentrations for each chemical. Results: Fipronil 2.5% EC was highly effective at all concentrations applied, while DDVP 50% EC was least toxic amongst all. One way analysis of variance confirmed significant differences between mortality of P. americana and different concentrations applied (P< 0.05). Conclusion: Locality differentiation is an important factor in determining the range of resistance between various localities, as all three localities behaved differently in terms of their levels of resistance. PMID:25629062

  16. Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

    PubMed

    Gissi, F; Binet, M T; Adams, M S

    2013-11-01

    Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute

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

    PubMed Central

    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 embryo at 96 hours was 30.6 μM. No observed effect concentration and predicted no effect concentration values of Osthol in D. magna and D. rerio were calculated as 5.4 and 0.19 μM, respectively. There was an increase in the morphological abnormalities in D. rerio embryo due to Osthol over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation were observed in embryos at 24–48 hours. Symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects, and symptoms of collapse were observed in fertilized embryo tissue within 96 hours. Ocular defects and pigmentation were the additional symptoms observed in this study. Conclusions Because Osthol showed considerable toxicity levels continuous toxicity evaluation in agro-ecosystems is necessary when bio-pesticides containing Osthol are used. PMID:25518842

  18. The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

    NASA Technical Reports Server (NTRS)

    Carter, V. L., Jr.; Bafus, D. A.; Warrington, H. P.; Harris, E. S.

    1974-01-01

    Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

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

    PubMed

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

    2015-05-01

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

  20. Acute toxicity assessment of explosive-contaminated soil extracting solution by luminescent bacteria assays.

    PubMed

    Xu, Wenjie; Jiang, Zhenming; Zhao, Quanlin; Zhang, Zhenzhong; Su, Hongping; Gao, Xuewen; Ye, Zhengfang

    2016-11-01

    Explosive-contaminated soil is harmful to people's health and the local ecosystem. The acute toxicity of its extracting solution was tested by bacterial luminescence assay using three kinds of luminescent bacteria to characterize the toxicity of the soil. An orthogonal test L 16 (4(5)) was designed to optimize the soil extracting conditions. The optimum extracting conditions were obtained when the ultrasonic extraction time, ultrasonic extraction temperature, and the extraction repeat times were 6 h, 40 °C, and three, respectively. Fourier transform infrared spectroscopy (FTIR) results showed that the main components of the contaminated soil's extracting solution were 2,4-dinitrotoluene-3-sulfonate (2,4-DNT-3-SO3(-)); 2,4-dinitrotoluene-5-sulfonate (2,4-DNT-5-SO3(-)); and 2,6-dinitrotoluene (2,6-DNT). Compared with Photobacterium phosphoreum and Vibrio fischeri, Vibrio qinghaiensis sp. Nov. is more suitable for assessing the soil extracting solution's acute toxicity. Soil washing can remove most of the contaminants toxic to luminescent bacterium Vibrio qinghaiensis sp. Nov., suggesting that it may be a potential effective remediation method for explosive-contaminated soil.

  1. CerioFAST{trademark}: An acute toxicity test based on Ceriodaphnia dubia feeding behavior

    SciTech Connect

    Bitton, G.; Rhodes, K.; Koopman, B.

    1996-02-01

    The authors have developed a rapid acute toxicity test (CerioFAST{trademark}) based on suppression of feeding activity of Ceriodaphnia dubia in the presence of toxicants. The bioassay consists of a 1-h exposure period to a given toxicant. Yeast cells, stained with a fluorescent dye, are added 20 min before the end of the exposure period. Response to a toxic sample is indicated by the absence of fluorescence in the gut of the daphnids. CerioFAST was compared to the standard 48-h C. dubia acute bioassay, using heavy metals and organic compounds.CerioFAST EC50s of Cd, Cu, Pb, Ag, Zn, and carbofuran were in the 0.01--0.1-mg/L range, whereas EC50s of hexachloroethane, pentachlorophenol, trichlorophenol, and lindane were in the 1--10-mg/L range. CerioFAST EC50s of the heavy metals and organics were well correlated with Ec50s obtained with the 48-h C. dubia bioassay.

  2. Acute toxicity and toxicokinetics of dipfluzine hydrochloride, a novel calcium channel blocker.

    PubMed

    Hu, Huiqing; Wang, Yongli; Pei, Tingmei; Dong, Lei; Xu, Yanfang

    2009-06-01

    Dipfluzine hydrochloride, diphenylpiperazine calcium channel blocker, is a promising candidate to treat ischemic stroke. The purpose of the study is to evaluate the acute toxicity and toxicokinetics of dipfluzine hydrochloride after single intravenous doses in rats. Acute toxicity study was performed in rats at doses of 5, 6, 10, 15, 25, 30, 35, and 40mg/kg. Concentrations of dipfluzine in plasma and tissues were determined with a reverse-phase HPLC method after single doses of 5, 15 and 30mg/kg. The results demonstrated that no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL), maximal tolerance dose (MTD), and minimal lethal dose (MLD) were respectively 5, 6, 30, 35mg/kg for i.v. administration of dipfluzine hydrochloride. The toxicokinetic study revealed that the severity of toxicity was linear with the level of systemic exposure. The highest tissue exposure was detected in lung tissue and it may primarily contribute to the pulmonary congestion in dead rats. Longer elimination half-lives of dipfluzine in kidney, brain, liver, and pancreas imply a possible accumulation of dipfluzine in these tissues for long-term exposure. In addition, a temporary impairment in liver and heart was observed for clinical chemistry in 30mg/kg dose group. The findings will help to design further studies to characterize the repeat-dose toxicity of dipfluzine hydrochloride.

  3. Acute toxicity of some hydrazine compounds to salamander larvae, Ambystoma spp

    SciTech Connect

    Slonim, A.R.

    1986-11-01

    Although hydrazine compounds have been used extensively by industry for a very long time, they have become important in recent years as propellants for aerospace operations. The study of hydrazine compounds in this laboratory began about two decades ago and developed into a large pharmacological and toxicological research program that included also environmental considerations. Subsequently, acute toxicity studies were conducted on the common guppy (Lebistes reticulatus Peters) using four hydrazine compounds of interest. The toxicity of these propellants were evaluated next on other species of aquatic organisms such as mosquito fish (Gambusia affinis) and amphibians. Two different studies were conducted on amphibians: One utilized amphibian eggs and the other amphibian larvae. The larvae of spotted and marbled salamanders (Ambystoma maculatum and A. opacum, respectively) were used primarily in numerous static bioassays to determine the acute toxicity of hydrazine, UDMH and Aerozine-50 on these organisms. The remaining larvae were used in other tests mainly to corroborate previous experimental results (e.g., to see whether toxicity is affected by organism size, aeration of test solutions, and water hardness). The results on the larvae are presented in this paper.

  4. Effect of copper status on acute toxicity of cocaine in rats

    SciTech Connect

    Smith, J.C.; Reddy, P.P.; Seung, S.K.; Combs, G.F.; Dulin, A.M.; Danford, D.E. )

    1989-02-09

    Both copper (Cu) nutriture and cocaine (Coc) ingestion have been shown to affect cardiovascular integrity. Therefore, the purpose of these studies was to determine if Cu status affects the acute toxicity of Coc. 20 weanling male rats (45 {plus minus} 5 g) were randomly assigned to 2 groups, 1 fed a copper deficient (CuD) (<1ppmCu) and the other a copper supplemented (CuS) diet (ca.6ppm, Cu). After 7 wks, the rats, paired for Cu status, were injected (ip) with Coc-HCl at reported LD{sub 50} doses ranging from 80-90 mg/kg bw. The CuD was established by cardiac hypertrophy, depressed hematocrit, lowered serum, liver and heart Cu compared to the CuS controls. The acute toxicity resulted in tachycardia and hyperactivity followed by ataxia with isolated muscle twitchings and violent grand-mal type seizures. For those animals that died, death was apparently due to respiratory arrest followed by ventricular fibrillation; animals that survived were killed by exsanguination. The severity of toxicity was greater for the CuD rats as evidenced by 100% exhibiting seizures compared to 80% for the CuS group. In addition, the incidence of death was 60% for the CuD group compared to 20% for the CuS rats. Although these results suggest that CuD exacerbates the toxic effects of Coc, it is not established that the effects are specific for this essential nutrient.

  5. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    PubMed

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats.

  6. Safety assessment of vitacoxib: Acute and 90-day sub-chronic oral toxicity studies.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Lv, Pengyue; Li, Jing; Cao, Xingyuan

    2017-02-24

    Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5-20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD50 was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions.

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2017-01-01

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

  9. Toxicity classification and evaluation of four pharmaceuticals classes: antibiotics, antineoplastics, cardiovascular, and sex hormones.

    PubMed

    Sanderson, Hans; Brain, Richard A; Johnson, David J; Wilson, Christian J; Solomon, Keith R

    2004-10-15

    Four different classes of environmental concern are quantitatively and qualitatively assessed for environmental hazards; antibiotics (n = 226), antineoplastics (n = 81), cardiovascular (n = 272), and sex hormones (n = 92). These along with an ECOSAR scan of all pharmaceuticals (n = 2848) were then classified according to the OECD aquatic toxicity classification system. The predicted species susceptibility is: daphnid > fish > algae, and the predicted rank order of relative toxicity: sex hormones > cardiovascular = antibiotics > antineoplastics (Table 1). Generally, a relatively large proportion (1/3) of all pharmaceuticals are potentially very toxic to aquatic organisms (Table 2). The qualitative risk assessment ranking relative to probability and potential severity for human and environmental health effects is: antibiotics > sex hormones > cardiovascular > antineoplastics. (Q)SARs and pharmacodynamic information should be used to prioritize and steer experimental risk assessments of pharmaceuticals, and potentially, also be used in new drug discovery optimizing efficacy and in minimising environmental hazards of new products. Nuclear receptors are relatively well conserved in evolution. Currently, antibacterial resistance represents the most significant human health hazard, and potentially the largest non-target organism hazard is sex hormones acting as endocrine modulators in wildlife. Data for the individual compounds are accessible via.

  10. Influence of water hardness and sulfate on the acute toxicity of chloride to sensitive freshwater invertebrates.

    PubMed

    Soucek, David J; Linton, Tyler K; Tarr, Christopher D; Dickinson, Amy; Wickramanayake, Nilesh; Delos, Charles G; Cruz, Luis A

    2011-04-01

    Total dissolved solids (TDS) represent the sum of all common ions (e.g., Na, K, Ca, Mg, chloride, sulfate, and bicarbonate) in freshwater. Currently, no federal water quality criteria exist for the protection of aquatic life for TDS, but because the constituents that constitute TDS are variable, the development of aquatic life criteria for specific ions is more practical than development of aquatic life criteria for TDS. Chloride is one such ion for which aquatic life criteria exist; however, the current aquatic life criteria dataset for chloride is more than 20 years old. Therefore, additional toxicity tests were conducted in the current study to confirm the acute toxicity of chloride to several potentially sensitive invertebrates: water flea (Ceriodaphnia dubia), fingernail clams (Sphaerium simile and Musculium transversum), snail (Gyraulus parvus), and worm (Tubifex tubifex), and determine the extent to which hardness and sulfate modify chloride toxicity. The results indicated a significant ameliorating effect of water hardness (calcium and magnesium) on chloride toxicity for all species tested except the snail; for example, the 48-h chloride median lethal concentration (LC50) for C. dubia at 50 mg/L hardness (977 mg Cl(-) /L) was half that at 800 mg/L hardness (1,836 mg Cl(-) /L). Conversely, sulfate over the range of 25 to 600 mg/L exerted a negligible effect on chloride toxicity to C. dubia. Rank order of LC50 values for chloride at a given water hardness was in the order (lowest to highest): S. simile < C. dubia < M. transversum < G. parvus < T. tubifex. Results of the current study support the contention that the specific conductivity or TDS concentration of a water body alone is not a sufficient predictor of acute toxicity and that knowledge of the specific ion composition is critical.

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    1996-02-01

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

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

    USGS Publications Warehouse

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

    1996-01-01

    Acute toxicity tests were conducted exposingDaphnia magnaStraus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), andSelenastrum capricornutumPrintz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Chek WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC507 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC5010 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC5079 mg/liter). Un-ionized ammonia concentrations near the EC50or IC50value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

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

    SciTech Connect

    Dorn, Paige L.; Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J.

    2012-05-01

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

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

    PubMed

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

    2016-07-01

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

  17. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

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

    PubMed

    Strupp, Christian

    2011-01-01

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

  19. Beryllium Metal I. Experimental Results on Acute Oral Toxicity, Local Skin and Eye Effects, and Genotoxicity

    PubMed Central

    Strupp, Christian

    2011-01-01

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

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

    PubMed Central

    2011-01-01

    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. PMID:21466696

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

    EPA Science Inventory

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

  2. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.3

    EPA Science Inventory

    Information on the acute toxicity to multiple species is needed for the assessment of the risks to, and the protection of, individuals, populations, and ecological communities. However, toxicity data are limited for the majority of species, while standard test species are general...

  3. Acute toxicity of firefighting chemical formulations to four life stages of fathead minnow.

    PubMed

    Gaikowski, M P; Hamilton, S J; Buhl, K J; McDonald, S F; Summers, C H

    1996-08-01

    Laboratory studies were conducted with four early life stages of fathead minnow, Pimephales promelas, to determine the acute toxicity of five firefighting chemical formulations in standardized soft and hard water. Egg, fry, 30-day posthatch, and 60-day posthatch life stages were tested with three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex). Fry were generally the most sensitive life stage tested, whereas the eggs were the least sensitive life stage. Formulation toxicity was greater in hard water than in soft water for all life stages tested. Fire-suppressant foams were more toxic than the fire retardants. The 96-hr LC50s derived for fathead minnows were rank ordered from the most toxic to the least toxic formulation as follows: Phos-Chek WD-881 (13-32 mg/liter) > Silv-Ex (19-32 mg/liter) > Fire-Trol GTS-R (135-787 mg/liter) > Phos-Chek D75-F (168-2250 mg/liter) > Fire-Trol LCG-R (519-6705 mg/liter) (ranges are the lowest and highest 96-hr LC50 for each formulation).

  4. Acute toxicity of firefighting chemical formulations to four life stages of fathead minnow

    USGS Publications Warehouse

    Gaikowski, Mark P.; Hamilton, Steve J.; Buhl, Kevin J.; McDonald, Susan F.; Summers, Cliff H.

    1996-01-01

    Laboratory studies were conducted with four early life stages of fathead minnow,Pimephales promelas,to determine the acute toxicity of five firefighting chemical formulations in standardized soft and hard water. Egg, fry, 30-day posthatch, and 60-day posthatch life stages were tested with three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex). Fry were generally the most sensitive life stage tested, whereas the eggs were the least sensitive life stage. Formulation toxicity was greater in hard water than in soft water for all life stages tested. Fire-suppressant foams were more toxic than the fire retardants. The 96-hr LC50s derived for fathead minnows were rank ordered from the most toxic to the least toxic formulation as follows: Phos-Chek WD-881 (13a??32 mg/liter) > Silv-Ex (19a??32 mg/liter) > Fire-Trol GTS-R (135a??787 mg/liter) > Phos-Chek D75-F (168a??2250 mg/liter) > Fire-Trol LCG-R (519a??6705 mg/liter) (ranges are the lowest and highest 96-hr LC50for each formulation). (C) 1996 Academic Press, Inc.

  5. Evaluation of acute bioassays for assessing toxicity of polychlorinated biphenyl-contaminated soils

    SciTech Connect

    Hose, J.E.; Barlow, L.A.; Bent, S.; Elseewi, A.A.; Cliath, M.; Resketo, M.; Doyle, C.

    1986-03-01

    Proposed State of California regulations use fish toxicity information as one criterion in municipal or industrial waste hazard evaluation. Static 96-hr bioassays were performed using fathead minnows (Pimephales promelas), blacksmith (Chromis punctipinnis), and glass shrimp (Palaemonetes kadiakensis) exposed to soil experimentally contaminated with up to 500 ppm polychlorinated biphenyl (PCB) capacitor fluid added at a concentration of 500 mg liter-1. Other bioassays were conducted with a 6-day mixing period prior to the bioassay or with acetone added to solubilize the PCBs. No mortality attributable to PCB toxicity was observed in definitive bioassays using the two fish and one invertebrate species. PCB levels leached from soil containing 500 ppm Aroclor 1242 ranged from less than 0.6 to 3.4 ppb in freshwater tests to 3.5 ppb in seawater bioassays. Using these data as the basis for waste classification, soils contaminated with up to 500 ppb PCBs during capacitor spills would be designated nonhazardous. PCBs are known to be environmentally persistent and to bioaccumulate. Acute toxicity tests, therefore, do not adequately evaluate the general toxicity of PCB-contaminated soils. Hazardous waste regulations for hydrophobic compounds such as PCBs should instead be based upon chronic toxicity data and should also consider bioaccumulation potential.

  6. Evaluation of acute bioassays for assessing toxicity of polychlorinated biphenyl-contaminated soils.

    PubMed

    Hose, J E; Barlow, L A; Bent, S; Elseewi, A A; Cliath, M; Resketo, M; Doyle, C

    1986-03-01

    Proposed State of California regulations use fish toxicity information as one criterion in municipal or industrial waste hazard evaluation. Static 96-hr bioassays were performed using fathead minnows (Pimephales promelas), blacksmith (Chromis punctipinnis), and glass shrimp (Palaemonetes kadiakensis) exposed to soil experimentally contaminated with up to 500 ppm polychlorinated biphenyl (PCB) capacitor fluid added at a concentration of 500 mg liter-1. Other bioassays were conducted with a 6-day mixing period prior to the bioassay or with acetone added to solubilize the PCBs. No mortality attributable to PCB toxicity was observed in definitive bioassays using the two fish and one invertebrate species. PCB levels leached from soil containing 500 ppm Aroclor 1242 ranged from less than 0.6 to 3.4 ppb in freshwater tests to 3.5 ppb in seawater bioassays. Using these data as the basis for waste classification, soils contaminated with up to 500 ppb PCBs during capacitor spills would be designated nonhazardous. PCBs are known to be environmentally persistent and to bioaccumulate. Acute toxicity tests, therefore, do not adequately evaluate the general toxicity of PCB-contaminated soils. Hazardous waste regulations for hydrophobic compounds such as PCBs should instead be based upon chronic toxicity data and should also consider bioaccumulation potential.

  7. Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Augspurger, T.; Barnhart, M.C.; Bidwell, Joseph R.; Cope, W.G.; Dwyer, F.J.; Geis, S.; Greer, I.E.; Ingersoll, C.G.; Kane, C.M.; May, T.W.; Neves, R.J.; Newton, T.J.; Roberts, A.D.; Whites, D.W.

    2007-01-01

    The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., ???90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. ?? 2007 SETAC.

  8. Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; May, T.W.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

    2007-01-01

    The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 ??g Cu/L (except 15 ??g Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were 40 ??g/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. ?? 2007 SETAC.

  9. Acute toxicity and aqueous solubility of some condensed thiophenes and their microbial metabolites

    SciTech Connect

    Seymour, D.T.; Hrudey, S.E.; Fedorak, P.M.; Verbeek, A.G.

    1997-04-01

    Petroleum or creosote contamination of surface waters, soils, or groundwaters introduces countless aromatic compounds to these environments. Among these are condensed thiophenes that were shown to be oxidized to sulfoxides, sulfones, and 2,3-diones by microbial cultures. In this study, the acute toxicities of 12 compounds (benzothiophene, benzothiophene sulfone, benzothiophene-2,3-diones, dibenzothiophene, dibenzothiophene sulfoxide, and dibenzothiophene sulfone) were determined by the Microtox{reg_sign} and Daphnia magna bioassays. To aid in determining the toxicities, the solubilities of many of these compounds were determined, which showed that the oxidized compounds were much more water soluble than the parent thiophenes. In nearly every case, the oxidized compounds were less toxic than their parent thiophenes. The Microtox method was more sensitive than the D. magna bioassay, but in general, there was a good correlation between toxicities measured by the two tests. Samples were removed from batch cultures of a Pseudomonas strain capable of oxidizing the thiophenes, and these samples were subjected to Microtox bioassays. These experiments showed that the toxicities of the culture supernatants decreased with incubation time.

  10. Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

    SciTech Connect

    Amsbaugh, Mark J.; Grosshans, David R.; McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita

    2012-08-01

    Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

  11. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

    PubMed Central

    Farsi, Elham; Shafaei, Armaghan; Hor, Sook Yee; Khadeer Ahamed, Mohamed B.; Yam, Mun Fei; Asmawi, Mohd Z.; Ismail, Zhari

    2013-01-01

    OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg. PMID:23778480

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

    PubMed

    Bluhm, Kerstin; Seiler, Thomas-Benjamin; Anders, Nico; Klankermayer, Jürgen; Schaeffer, Andreas; Hollert, Henner

    2016-10-01

    The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC50: 83mg/L) compared to 2-MTHF (LC50: 2980mg/L), 2-MF (LC50: 405mg/L) and water accommodated fractions of the reference fuels including gasoline (LC50: 244mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels.

  13. Acute toxicity and chemistry of urban and nonurban bed material, Maricopa County, Arizona

    SciTech Connect

    Lopes, T.J.

    1995-12-31

    The acute toxicity and chemistry of bed material in the Phoenix, Arizona, area were characterized to determine if urban activities degrade bed-material quality. Samples were collected from unpaved lots and ephemeral channels in urban and undeveloped drainage basins. Samples were sieved to less than 63 microns to make comparisons between samples and were analyzed for constituent concentrations and acute toxicity using the amphipod Hyalella azteca. Analysis of variance with Tukeys` multiple comparison test indicated that bed-material samples from the undeveloped drainage basin were more toxic than samples from ephemeral channels. The toxicity of bed material was not significantly different between undeveloped and urban drainage basins and between urban drainage basins and ephemeral channels. The most toxic bed-material samples from urban drainage basins appeared to be those samples collected from areas where stormwater accumulates. Concentrations of ammonia, lead, cadmium, and zinc were significantly greater in urban bed-material samples than in samples from the undeveloped drainage basin and ephemeral channels. Zinc and cadmium were associated with organic carbon in urban bed-material samples, and trace metals were associated with iron and manganese in samples from the undeveloped drainage basin. Mortality rates in bed-material samples from the undeveloped drainage basin moderately correlated with recoverable concentrations of zinc (rank correlation of 0.71), lead (0.59), and copper (0.46). Mortality rates in bed-material samples from urban drainage basins significantly correlated with recoverable concentrations of cadmium (0.81) and zinc (0.70).The association of trace metals with iron and manganese seemed to increase trace-metal bioavailability when compared with trace metals associated with organic carbon.

  14. Acute intravenous infusion of disodium dihydrogen (1-hydroxyethylidene)diphosphonate: mechanism of toxicity.

    PubMed

    Francis, M D; Slough, C L

    1984-08-01

    The acute intravenous toxicity of disodium dihydrogen (1-hydroxyethylidene)diphosphonate (etidronate disodium; I) and the mechanism of this toxic response have been investigated in 40 beagle dogs. The intravenous toxicity of I is dependent on the total dose administered and the length of the infusion interval. The toxicity of I is directly related to the ability of the drug to bind or complex with the circulating calcium in the blood. Maximum depressions in ionized calcium coincide in time with peak blood levels of I, and at lethal doses electrocardiographic changes indicative of hypocalcemia are observed. For a 2-min infusion of 2 mg of I/kg, no effect is observed on ionized calcium levels, and the electrocardiogram remains normal. At doses of 16 and 32 mg/kg, coincident with an immediate fall in ionized calcium levels, there is a transient rise in total calcium and a fall in phosphorus levels. The ionized calcium level rises, and total calcium level falls and stabilizes at baseline levels within 30 min after the infusion. However, the phosphorus level rises and exceeds the baseline value, reaching 3-4 times normal by 72 h after the infusion. With proven lethal doses of I (60 mg/kg infused over 2 min) and the simultaneous infusion of an ionized calcium salt such as calcium gluconate (20 mg of Ca2+/kg), electrocardiograms remain normal and death is prevented. Thus, an effective antidote in the event of an overdose or too rapid an infusion of I can be employed to prevent acute toxic effects.

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

    PubMed

    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 <24h old neonates for 48h in the case of D. pulex and with 2-9 days old offspring for 96h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5-2.0mM), Na (0.5-2.0mM) and Mg (0.125-0.5mM). The effect of pH (6.5-8.0) and Suwannee River DOM 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

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

    PubMed

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

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.

  17. Effects of diiospropyl-1,3-dithiol-2-ylidene malonate (NKK-105) on acute toxicity of various drugs and heavy metals.

    PubMed

    Kitagawa, H; Saito, H; Sugimoto, T; Yanaura, S; Kitagawa, H; Hosokawa, T; Sakamoto, K

    1982-05-01

    The influence of NKK-105 on the acute toxicity of strychnine nitrate, potassium cyanide, chloral hydrate, atropine, tetrodotoxin, mercuric chloride, cadmium chloride, lead acetate and arsenic trioxide were examined in rats. NKK-105 prolonged the time of death induced by strychnine, potassium cyanide and tetrodotoxin in acute toxicity. Survival time was prolonged in rats treated with the toxic metals by pretreatment with NKK-105. NKK-105 counteracted the lethal effect of strychnine, potassium cyanide, chloral hydrate, mercuric chloride and cadmium chloride. NKK-105 significantly decreased the acute toxicity of these drugs but the inhibitory effect was not observed in the acute toxicity of atropine, tetrodotoxin, lead acetate and arsenic trioxide.

  18. Could hydroxyethyl starch be a therapeutic option in management of acute aluminum phosphide toxicity?

    PubMed

    Marashi, Sayed Mahdi; Arefi, Mohammad; Behnoush, Behnam; Nasrabad, Mahdi Ghazanfari; Nasrabadi, Zeynab Nasri

    2011-04-01

    Acute aluminum phosphide poisoning is a serious toxicity and results in high mortality rate despite the progress of critical care. After ingestion, phosphine gas is released and absorbed quickly, causing systemic poisoning and cell hypoxia. Excessive thirst, severe hypotension, arrhythmias, tachypnea, and severe metabolic acidosis are the common clinical manifestations. We think acute metabolic response which characteristically occurs in severe injury also happens in aluminum phosphide poisoning. Necropsy examinations indicate congestion in almost all vital organs because of leakage of fluids from intravascular to extravascular space. The most favorable type of fluid for intravascular volume resuscitation persists and is disputed. Colloids remain in the intravascular space rather than crystalloids, and provide more rapid hemodynamic stabilization. Furthermore, hydroxyethyl starch solution may have other benefits e.g. it can reduce the extra vascular leak of albumin and fluids from an endothelial injury site. As refractory hypotension and cardiovascular collapse, because leakage of fluids from intravascular to extravascular space are common cause of death in this toxicity, we propose that hydroxyethyl starch can dominate this refractory hypotension and consequently acute metabolic response.

  19. A QSAR study of acute toxicity of N-substituted fluoroacetamides to rats.

    PubMed

    Juranić, Ivan O; Drakulić, Branko J; Petrović, Slobodan D; Mijin, Dusan Z; Stanković, Milena V

    2006-01-01

    Acute toxicity in vivo toward rats, of nineteen N-alkyl and N-cycloalkyl fluorocetamides [F-CH(2)-C(O)-NH-R] was correlated with their structure-dependent properties. Used descriptors are: molecular weights (M(w)) and heat of formation (DeltaH(f)) of compounds; molar refractivity (CMR), lipophilicity (ClogP), Broto lipol values, virtual logP, molecular lipophilic potential (MLP), Van der Waals surfaces (VdW SAS) and hydropathicity surface (ILM) of whole molecules; Taft steric parameters (E(s)); E(s) values with Hancock corrections (E(s)(CH)) and Verloop sterimol (B(5)) and (L) parameters of alkyl and cycloalkyl residues; superdelocalizabilities and electron densities on the [NH-C(O)-CH(2)-F] fragment. Strong quantitative structure-activity relationships were assessed. Obtained correlation suggested that lipophilicity, shape and bulkiness of the alkyl and cycloalkyl substituents, particular nearest vicinity of the amide nitrogen, as well charges on the amide moiety are the main factors that influence on the acute toxicity of studied compounds toward rats. Mechanism of toxic action was proposed.

  20. Acute and subacute toxicity of Salvia scutellarioides in mice and rats.

    PubMed

    Ramírez, Jorge H; Palacios, Mauricio; Tamayo, Oscar; Jaramillo, Roberto; Gutiérrez, Oscar

    2007-01-19

    The acute and subacute toxicity of the aqueous extract of Salvia scutellarioides (Lamiaceae) was studied in mice and rats. In the acute toxicity test, oral administration of 2g/kg of Salvia scutellarioides produced neither mortality nor changes in behavior or any other physiological activities. In subacute toxicity studies, no mortality was observed when the two doses of 1 or 2g/kgday of aqueous extract of Salvia scutellarioides extract were administered orally for a period of 28 days. In the blood chemistry analysis, no significant changes occurred, including glucose, creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), alanine transaminase (ALT), potassium, sodium, chloride, calcium, phosphorus, conjugated billirrubin, total billirrubin, total cholesterol, high density lipoprotein (HDL), triglycerides, total protein, albumin, prothrombin time (PT) and thromboplastin partial time (PTT) of both sexes. Hematological analysis showed no differences in any of the parameters examined (WBC count, platelet and hemoglobin estimation) in either the control or treated group of both sexes. The urinalysis was negative for glucose, ketonic bodies, casts, red blood cells, and albumin in the control and treatment groups. There were no significant differences in the body and organ weights between controls and treated animals of both sexes. Pathologically, neither gross abnormalities nor histopathological changes were observed.

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

    PubMed Central

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A.

    2015-01-01

    Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg. PMID:27047139

  2. Hypoglycemic activity and acute oral toxicity of chromium methionine complexes in mice.

    PubMed

    Tang, Hai-yan; Xiao, Qing-gui; Xu, Hong-bin; Zhang, Yi

    2015-01-01

    The hypoglycemic activity of chromium methionine (CrMet) in alloxan-induced diabetic (AID) mice was investigated and compared with those of chromium trichloride hexahydrate (CrCl3·6H2O) and chromium nicotinate (CrNic) through a 15-day feeding experiment. The acute oral toxicity of CrMet was also investigated in ICR (Institute for Cancer Research) mice by a single oral gavage. The anti-diabetic activity of CrMet was explored in detail from the aspects of body weight (BW), blood glucose, triglyceride, total cholesterol, liver glycogen levels, aspartate transaminase (AST) and alanine transaminase (ALT) levels. The obtained results showed that CrMet had beneficial effects on glucose and lipid metabolism, and might possess hepatoprotective efficacy for diabetes. Daily treatment with 500 and 1000μg Cr/kg BW of CrMet in AID mice for 15 days indicated that this low-molecular-weight organic chromium complex had better bioavailability and more beneficial effects on diabetics than CrCl3·6H2O. CrMet also had advantage over CrNic in the control of AST and ALT activities. Acute toxicity studies revealed that CrMet had low toxicity potential and relatively high safety margins in mice with the LD50 value higher than 10.0g/kg BW. These findings suggest that CrMet might be of potential value in the therapy and protection of diabetes.

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

    PubMed

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

    2014-07-01

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

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

    USGS Publications Warehouse

    Buhl, Kevin J.; Hamilton, Steven J.

    2000-01-01

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

  5. The acute toxicity of chemically and physically dispersed crude oil to key arctic species under arctic conditions during the open water season

    PubMed Central

    Gardiner, William W; Word, Jack Q; Word, Jack D; Perkins, Robert A; McFarlin, Kelly M; Hester, Brian W; Word, Lucinda S; Ray, Collin M

    2013-01-01

    The acute toxicity of physically and chemically dispersed crude oil and the dispersant Corexit 9500 were evaluated for key Arctic species. The copepod Calanus glacialis, juvenile Arctic cod (Boreogadus saida), and larval sculpin (Myoxocephalus sp.) were tested under conditions representative of the Beaufort and Chukchi Seas during the ice-free season. The toxicity of 3 water-accommodated fractions (WAF) of Alaska North Slope crude oil was examined with spiked, declining exposures. A dispersant-only test was conducted with the copepod C. glacialis. Each preparation with oil (WAF, breaking wave WAF [BWWAF], and chemically enhanced WAF [CEWAF]) produced distinct suites of hydrocarbon constituents; the total concentrations of oil were lowest in WAF and highest in CEWAF preparations. The relative sensitivity for the different species and age classes was similar within each WAF type. Median lethal concentration values based on total petroleum hydrocarbons ranged from 1.6 mg/L to 4.0 mg/L for WAF and BWWAF treatments and from 22 mg/L to 62 mg/L for CEWAF. For Corexit 9500 exposures, median lethal concentration values ranged from 17 mg/L to 50 mg/L. The differences in the relative toxicity among the accommodated fractions indicated that the majority of petroleum hydrocarbons in the CEWAF are in less acutely toxic forms than the components that dominate the WAF or BWWAF. Further evaluation showed that the parent polycyclic aromatic hydrocarbon compounds, specifically naphthalene, were highly correlated to acute toxicity. Environ Toxicol Chem 2013;32:2284–2300. PMID:23765555

  6. Accumulation dynamics and acute toxicity of silver nanoparticles to Daphnia magna and Lumbriculus variegatus: implications for metal modeling approaches.

    PubMed

    Khan, Farhan R; Paul, Kai B; Dybowska, Agnieszka D; Valsami-Jones, Eugenia; Lead, Jamie R; Stone, Vicki; Fernandes, Teresa F

    2015-04-07

    Frameworks commonly used in trace metal ecotoxicology (e.g., biotic ligand model (BLM) and tissue residue approach (TRA)) are based on the established link between uptake, accumulation and toxicity, but similar relationships remain unverified for metal-containing nanoparticles (NPs). The present study aimed to (i) characterize the bioaccumulation dynamics of PVP-, PEG-, and citrate-AgNPs, in comparison to dissolved Ag, in Daphnia magna and Lumbriculus variegatus; and (ii) investigate whether parameters of bioavailability and accumulation predict acute toxicity. In both species, uptake rate constants for AgNPs were ∼ 2-10 times less than for dissolved Ag and showed significant rank order concordance with acute toxicity. Ag elimination by L. variegatus fitted a 1-compartment loss model, whereas elimination in D. magna was biphasic. The latter showed consistency with studies that reported daphnids ingesting NPs, whereas L. variegatus biodynamic parameters indicated that uptake and efflux were primarily determined by the bioavailability of dissolved Ag released by the AgNPs. Thus, principles of BLM and TRA frameworks are confounded by the feeding behavior of D. magna where the ingestion of AgNPs perturbs the relationship between tissue concentrations and acute toxicity, but such approaches are applicable when accumulation and acute toxicity are linked to dissolved concentrations. The uptake rate constant, as a parameter of bioavailability inclusive of all available pathways, could be a successful predictor of acute toxicity.

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

    PubMed

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

    2003-08-01

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

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

    PubMed Central

    Ravanbakhsh, Asma; Mahdavi, Majid; Jalilzade-Amin, Ghader; Javadi, Shahram; Maham, Masoud; Mohammadnejad, Daryosh; Rashidi, Mohammad Reza

    2016-01-01

    Purpose: Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p<0.05), kidney’s xanthine dehydrogenase (XDH) activity (p<0.001) and elevation of aldehyde oxidase (AO) activity (p<0.05) in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epithelium stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases. PMID:28101461

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

    PubMed

    Bianchini, Adalto; Grosell, Martin; Gregory, Sean M; Wood, Chris M

    2002-04-15

    On the basis of these facts about freshwater fish and invertebrates: (i) the Na+ turnover is a physiological process associated with the gill membranes; (ii) the key mechanism of acute silver toxicity consists of reduction in Na+ uptake by blockade of gill Na+,K+-ATPase; (iii) the mass-specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarusdiogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity and body mass of the same species was also observed. Furthermore, the whole body Na+ uptake rate was inversely related to body mass in unexposed animals. The combination of these last two results explains why the small animals in this study were more sensitive to Ag+ than the larger ones. Taken together, these results clearly point out the possibility of incorporating the Na+ uptake rate into the current version of the Biotic Ligand Model to improve the predictive capacity of this model. In the absence of information on Na+ uptake rate, then body mass may serve as a surrogate.

  10. Clinico-biochemical studies on acute toxic nephropathy in goats due to uranyl nitrate

    SciTech Connect

    Dash, P.K.; Joshi, H.C.

    1989-02-01

    Acute toxic nephropathy was produced in 6 healthy goats by injecting intravenously 1% uranyl nitrate (UN) (15 mg/kg body weight). The early painful clinical signs simulating shock progressed with subnormal temperature, slow-shallow respiration and arrhythmic pulse followed by death due to respiratory failure within 96 to 120 hr. All the affected goats had normocytic normochromic anemia, leucocytosis, neutrophilia with left shift eosinopenia, decreased monocytes and presence of 1-2% reticulocytes in the peripheral blood smears. On blood chemical analysis, a uniform and continuous rise was seen in serum creatinine with a concomitant daily increase of serum urea and uric acid. Simultaneous analysis of urine indicated polyuria leading to oliguria, acidic pH, albuminuria, glycosuria with presence of neutrophils, RBC's, epithelial and fatty casts, increase of triple phosphate, and cystine crystals reflecting acute damage of kidneys in the affected goats.

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

    USGS Publications Warehouse

    Rye, Robert P.; King, Everett Louis

    1976-01-01

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

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

    PubMed

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

    2001-07-01

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

  13. Correlation between heavy metal acute toxicity values in Daphnia magna and fish

    SciTech Connect

    Khangarot, B.S.; Ray, P.K.

    1987-04-01

    In the toxicant bioassays, invertebrates with special reference to aquatic arthropod species have been of recent interest as test models due to the need for developing nonmammalian tests system. The cladoceran Daphnia magna bioassays have several practical advantages. D. magna has been used as a useful test species and its sensitivity to environmental pollutants have been recognized as a general representative of other freshwater zooplankton species. The objectives of this study were to determine the acute toxicity of various heavy metals to Daphnia magna for 48 h of exposure and to compare these values with the existing LC50 values for rainbow trout (Salmo gairdneri); which is commonly used as a test animal in aquatic bioassay studies.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P < 0.05) 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity. PMID:26981538

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  17. Acute lethal toxicity of some reference chemicals to freshwater fishes of Scandinavia

    SciTech Connect

    Oikari, A.O.J.

    1987-07-01

    Relevance of the choice of a test organism intended to be representative for a given environment seems to be under continual debate in aquatic ecotoxicology. For instance, it is commonly argue that acute toxicity tests with rainbow trout, the species most often recommended as a standard cold water teleost, were not representative for Nordic countries because the species is an alien in local faunas. A comparative study with several freshwater species was therefore initiated to clarify the validity of this assumption. As a first approximation, standard LC 50 assays were conducted. The species used were chosen only on the basis of their local availability, i.e, they randomly represented the fish fauna of Nordic inland waters. Furthermore, inter-species variation of toxicity response was compared with certain other, quantitatively more important, intra-species sources of variability affecting the toxicity of chemicals. Use of reference toxicants has been recommended as a means of standardizing bioassays. Compounds, characteristic of effluents from the pulp and paper industry, were selected for the present study. The toxicity of organic acids such a phenols and resin acids, as well as that of pupmill effluents, strongly depends on water pH. Because of the possibility that species differences could exist in this respect, effects of water acidity on toxicity of these types of substances to a randomly selected local species was investigated. Finally, as an example of the biological source of assay variability, the effect of yolk absorption was studied with a subsequent crisis period due to moderate starvation under laboratory conditions.

  18. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation.

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

    SciTech Connect

    Vesprini, Danny; Catton, Charles; Jacks, Lindsay; Lockwood, Gina; Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig; Bristow, Robert G.

    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 study and, if validated in other large IGRT cohorts

  20. Acute toxicity, antiedematogenic activity, and chemical constituents of Palicourea rigida Kunth.

    PubMed

    Alves, Vanessa G; da Rosa, Elisa A; de Arruda, Laura L M; Rocha, Bruno A; Bersani Amado, Ciomar A; Santin, Silvana M O; Pomini, Armando M; da Silva, Cleuza C

    2016-03-01

    The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice.

  1. Hearing loss during osteosarcoma chemotherapy: when acute ifosfamide toxicity revealed unnoticed methotrexate encephalopathy.

    PubMed

    Robert, Guillaume; Chappé, Céline; Taque, Sophie; Bruneau, Bertrand; Gandemer, Virginie

    2014-03-01

    Ifosfamide and methotrexate are widely used for the treatment of pediatric osteosarcoma. However, both these chemotherapeutic drugs can cause encephalopathy. A 17-year-old girl presented with profound hearing loss and dizziness during a postoperative course of ifosfamide, 20 days after a course of methotrexate. Cerebral magnetic resonance imaging (MRI) showed bilateral white matter hypersignal in Fluid Attenuated Inversion Recovery sequences. The clinical evolution was rapidly favorable after methylene blue infusion. This is the second reported case of acute deafness, possibly associated with ifosfamide, whereas MRI data revealed unnoticed chronic methotrexate toxicity. Systematic MRI screening and hearing evaluation may be useful in such cases.

  2. Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic

    PubMed Central

    2014-01-01

    Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8

  3. Oral toxicological studies of pueraria flower extract: acute toxicity study in mice and subchronic toxicity study in rats.

    PubMed

    Takano, Akira; Kamiya, Tomoyasu; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Kinjo, Junei

    2013-11-01

    Kudzu has been widely used as an herbal medicine in China. The root of the kudzu is also well known as an antipyretic and analgesic in treatment of the common cold, while its flower has been used to treat alcohol intoxication, alcohol abuse, and dysentery. Pueraria flower extract (PFE) is a hot water extract derived from the flower of the kudzu, Pueraria thomsonii Benth. (Fabaceae), oral intake of which exhibits anti-obesity properties in mice and humans. In this study, we conducted acute and subchronic toxicity studies for an evaluation of safety. In the acute study, PFE (5 g/kg body weight) was orally administered to ddY mice. For 14 d after administration, no deaths or abnormal changes were observed in general signs, body weight (BW), or food consumption, and no abnormal findings were observed in the major organs and tissues of either males or females at necropsy. The oral LD50 of PFE was therefore estimated to be higher than 5 g/kg BW. In the subchronic study, PFE was mixed into the diet in place of powdered CRF-1 and administered at concentrations of 0% (control), 0.5%, 1.5%, and 5.0% to male and female Sprague-Dawley rats for 90 d. No mortality or toxicological changes were observed during the experimental period. Blood biochemical, hematological, and urinary parameters revealed no toxicologically significant changes. Furthermore, no anatomical or histopathological changes due to PFE were observed. The no-observed adverse-effect-level of PFE was thus estimated to be 5.0% in the diet (male: 3.0 g/kg BW/d; female: 3.5 g/kg BW/d).

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

    SciTech Connect

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

    1987-01-01

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

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

    PubMed

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

    2015-10-01

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

  6. Acute toxic effects of endosulfan sulfate on three life stages of grass shrimp, Palaemonetes pugio.

    PubMed

    Key, Peter B; Chung, Katy W; Venturella, John J; Shaddrick, Brian; Fulton, Michael H

    2010-01-01

    In this study, the toxicity of endosulfan sulfate, the primary degradation product of the insecticide endosulfan, was determined in three life stages of the grass shrimp (Palaemonetes pugio). After 96 h exposure to endosulfan sulfate, the grass shrimp adult LC50 was 0.86 microg/L (95% CI 0.56-1.31), the grass shrimp larvae LC50 was 1.64 microg/L (95% CI 1.09-2.47) and the grass shrimp embryo LC50 was 45.85 microg/L (95% CI 23.72-88.61 microg/L). This was compared to the previously published grass shrimp 96-h LC50s for endosulfan. The toxicity of the two compounds was similar for the grass shrimp life stages with adults more sensitive than larvae and embryos. The presence of sediment in 24h endosulfan sulfate-exposures raised LC50s for both adult and larval grass shrimp but not significantly. The USEPA expected environmental concentrations (EEC) for total endosulfan and endosulfan sulfate and the calculations of risk quotients (RQ) based on the more sensitive adult grass shrimp 96-h LC50 clearly show that environmental concentrations equal to acute EECs would prove detrimental to grass shrimp or other similarly sensitive aquatic organisms. These results indicate that given the persistence and toxicity of endosulfan sulfate, future risk assessments should consider the toxicity potential of the parent compound as well as this degradation product.

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

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

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

  8. Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats.

    PubMed

    Chen, Xueyan; Zhang, Yu; Zhu, Zhongning; Liu, Huanlong; Guo, Huicai; Xiong, Chen; Xie, Kerang; Zhang, Xiaofei; Su, Suwen

    2016-05-01

    Doxorubicin (DOX), a potent broad‑spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non‑target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX‑induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX‑induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX‑induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX‑induced hepatorenal toxicity in clinical practice.

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

    PubMed Central

    Kalsi, Sarbjeet S.; Wood, David M.; Dargan, Paul I.

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  10. Comprehensive mollusk acute toxicity database improves the use of Interspecies Correlation Estimation (ICE) models to predict toxicity of untested freshwater and endangered mussel species

    EPA Science Inventory

    Interspecies correlation estimation (ICE) models extrapolate acute toxicity data from surrogate test species to untested taxa. A suite of ICE models developed from a comprehensive database is available on the US Environmental Protection Agency’s web-based application, Web-I...

  11. Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I) to Daphnia magna. Part 2: toxicity results.

    PubMed

    Bianchini, Adalto; Bowles, Karl C; Brauner, Colin J; Gorsuch, Joseph W; Kramer, James R; Wood, Chris M

    2002-06-01

    The protective effect of reactive sulfide against AgNO3 toxicity to Daphnia magna neonates was studied. Acute (48-h) toxicity tests were performed in the absence (<5 nM) and presence of low (approximately 25 nM) and high (approximately 250 nM) concentrations of zinc sulfide clusters under oxic conditions. In both the presence and the absence of sulfide, lower mean lethal concentration (LC50) values were observed when measured as opposed to nominal silver concentrations were used in calculations. This reflected the fact that measured total silver concentrations were lower than nominal concentrations due to losses of silver from solution observed during the experiment. High concentration (approximately 250 nM) of sulfide completely protected against toxicity up to the highest silver concentration tested (2 microg/L [19 nM]) with measured silver data. In the presence of environmentally realistic levels of sulfide (approximately 25 nM) in receiving waters, acute silver toxicity was reduced by about 5.5-fold. However, when filtered (0.45 microm) silver concentrations alone were considered, toxicity (48-h LC50) was similar in the absence (0.22 microg/L) and presence (0.28 microg/L) of sulfide. The difference between measured total and filtered silver was attributed to chemisorption of the metal sulfide onto the membrane filter and provides evidence that the toxic fraction of silver is that which is unbound to sulfide. Accumulation of silver was greater in daphnids exposed to silver in the presence of sulfide than in its absence, even though a toxic effect was not observed under these conditions. In this case, silver appears to be incorporated by daphnids rather than merely adsorbed on the surface. Our results point out the need to incorporate sulfide into the acute biotic ligand model and to assess its potentially large role in preventing chronic toxicity.

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

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

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

  13. Vicious circle of acute radiation toxicities and weight loss predicts poor prognosis for nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

    PubMed Central

    Li, Guo; Jiang, Xiong-ying; Qiu, Bo; Shen, Lu-Jun; Chen, Chen; Xia, Yun-Fei

    2017-01-01

    Background: Weight loss during radiotherapy has been known as a negative prognostic factor for nasopharyngeal carcinoma (NPC) patients, but the factors related to weight loss during radiotherapy were not fully understood. Methods: A total of 322 newly diagnosed NPC patients receiving intensity modulated radiotherapy (IMRT) in Sun Yat-sen University Cancer Center between June 2002 and August 2006 were enrolled. Kaplan-Meier methods and log-rank test were applied for survival analysis; a multiple regression was used to identify the factors related to weight loss during radiotherapy. Results: The mean and median values of weight loss (%) during radiotherapy were 6.85% and 6.70%. NPC patients with critical weight loss (> 5.4%) have poorer overall survival (OS) and distant metastasis-free survival (DMFS) than the patients without critical weight loss (p = 0.002 and 0.021, respectively). Pre-radiotherapy weight, acute mucosal toxicity, acute pharynx and esophagus toxicity, and acute upper gastrointestinal toxicity were related to the weight loss during radiotherapy independently (p = 0.01, p < 0.001, p < 0.001, and p = 0.009, respectively). Conclusions: Acute radiation toxicities had significant and independent impact on weight loss during radiotherapy. The vicious circle of acute radiation toxicities and weight loss had bad effect on prognosis of NPC patients. PMID:28382146

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

    PubMed

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

    2011-04-01

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

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

    PubMed

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

    2016-06-01

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

  16. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  17. Anti-tumor potential and acute toxicity of Jacaranda puberula Cham. (Bignoniacea).

    PubMed

    de-Almeida, Michelle Rodrigues-Ayres; Ramos-Leal, Ivana Correa; Ruela, Halliny Siqueira; Justo-Araujo, Maria da-Graça; Martins, Thiago Martino; Pinto-Coelho, Marsen Garcia; Kuster, Ricardo Machado; Carvalho-Sabino, Kátia Costa

    2013-09-01

    Cancer chemotherapy is an important strategy to treat this leading cause of death worldwide and plants may constitute a source of new antineoplastic agents. This work fractionated the ethanolic extract of Jacaranda puberula leaves and studied the in vitro antitumoral action and some toxicological effects of the most bioactive fraction. Cell lines related to worldwide cancers were used. The Dichloromethane (DCM) and PP fractions were the most bioactive ones. The anti-tumoral action of the DCM fraction was higher than that of the crude EtOH extract while that of PP fraction was higher than the original one (DCM) for both breast (MCF-7), prostate (PC3) and lung (A549) tumor cells, chronic leukemia cells. The K562 cells were the most sensitive cell line. The PP fraction (20 μg/mL) cytotoxicity for these cells was similar to that of the ursolic acid triterpene or the antineoplastic ethoposide. The PP fraction inhibited K562 cell proliferation without cell cycle arrest in a specific phase or apoptosis. PP increased the mitochondrial reduction activity of lymphocytes. After a single dose by oral route, PP fraction did not induce intrinsic acute toxicity or animal death. This work demonstrated that the J. puberula fraction (PP) present high in vitro anti-tumoral effect with no cytotoxicity for immune system cells or oral acute toxicity, improving the Jacaranda puberula ethnopharmacology and reporting new biological effects for the genus Jacaranda.

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

    USGS Publications Warehouse

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

    2015-01-01

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

  19. Acute toxicity of interstitial and particle-bound cadmium to a marine infaunal amphipod

    SciTech Connect

    Kemp, P.F.; Swartz, R.C.

    1988-01-01

    The relative acute toxicity of particle-bound and dissolved interstitial cadmium was investigated using a new bioassay procedure. Interstitial concentration of Cd was controlled by means of peristaltic pumps, allowing separate manipulation of interstitial and particle properties. Addition of small quantities of organic-rich fine particles to sandy sediment resulted in greatly differing particle-bound Cd concentrations in sediment with similar interstitial Cd concentrations. Analysis of variance indicated no significant difference in the survival or ability to rebury in sediment of the phoxocephalid amphipod Rhepoxynius abronius (Barnard), when exposed to sediment with different total Cd concentrations but nearly equal interstitial Cd concentrations; in one case LC50 data indicated slightly increased mortality in sediment with higher total Cd concentration. At least 70.2-87.9% of mortality could be predicted from past data on mortality based on dissolved Cd concentrations. The acute toxicity of Cd to the infaunal amphipod appears to be due principally to Cd dissolved in interstitial water.

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

    PubMed Central

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

    2013-01-01

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

  1. Acute toxicity of 8 antidepressants: what are their modes of action?

    PubMed

    Minguez, Laetitia; Farcy, Emilie; Ballandonne, Céline; Lepailleur, Alban; Serpentini, Antoine; Lebel, Jean-Marc; Bureau, Ronan; Halm-Lemeille, Marie-Pierre

    2014-08-01

    Currently, the hazard posed by pharmaceutical residues is a major concern of ecotoxicology. Most of the antidepressants belong to a family named the Cationic Amphipathic Drugs known to have specific interactions with cell membranes. The present study assessed the impact of eight antidepressants belonging to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors by the combination of multi-approaches (in vivo, in vitro, in silico) and gives some insights on the mode of action for these molecules. Antidepressants were from the most to the least toxic compound for Daphnia magna: Sertraline (EC50=1.15 mg L(-1))>Clomipramine (2.74 mg L(-1))>Amitriptyline (4.82 mg L(-1))>Fluoxetine (5.91 mg L(-1))>Paroxetine (6.24 mg L(-1))>Mianserine (7.81 mg L(-1))>Citalopram (30.14 mg L(-1)) and Venlafaxine (141.28 mg L(-1)). These acute toxicities were found correlated to Log Kow coefficients (R=0.93, p<0.001) and to cytotoxicity assessed on abalone hemocytes through the neutral red uptake assay (R=0.96, p<0.001). If narcosis as mode of action is typically expected during acute ecotoxicity bioassays, we showed by molecular modeling that particular interactions can exist between antidepressants and phosphatidylcholine, a major component of cell membranes, leading to a more specific mode of action corresponding to a potential acidic hydrolysis of ester functions.

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

    SciTech Connect

    Not Available

    1986-09-01

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

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

    PubMed Central

    Alasil, Saad Musbah; Omar, Rahmat; Yusof, Mohd Yasim

    2014-01-01

    The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5 (MW 368.512), and an antibacterial agent C14H11N3O2 (MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups (P > 0.05). Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections. PMID:24790603

  4. Pediatric Craniospinal Axis Irradiation With Helical Tomotherapy: Patient Outcome and Lack of Acute Pulmonary Toxicity

    SciTech Connect

    Penagaricano, Jose; Moros, Eduardo; Corry, Peter; Saylors, Robert; Ratanatharathorn, Vaneerat

    2009-11-15

    Purpose: To present the patient outcomes and risk of symptomatic acute radiation pneumonitis (ARP) in 18 pediatric patients treated with helical tomotherapy to their craniospinal axis for a variety of neoplasms. Methods and Materials: A total of 18 patients received craniospinal axis irradiation with helical tomotherapy. The median age was 12 years (range, 2.5-21). The follow-up range was 3-48 months (median, 16.5). Of the 18 patients, 15 received chemotherapy in the neoadjuvant, adjuvant, or concomitant setting. Chemotherapy was tailored to the particular histologic diagnosis; 10 of 18 patients underwent surgical removal of the gross primary tumor. The patients were followed and evaluated for ARP starting at 3-6 months after completion of craniospinal axis irradiation. ARP was graded using the Common Toxicity Criteria, version 3. Results: At the last follow-up visit, 14, 2, and 2 patients were alive without disease, alive with disease, and dead of disease, respectively. The cause-specific survival rate was 89% (16 of 18), disease-free survival rate was 78% (14 of 18), and overall survival rate was 89% (16 of 18). No patient had treatment failure at the cribriform plate. No patient developed symptoms of ARP. Conclusion: Craniospinal axis irradiation using helical tomotherapy yielded encouraging patient outcomes and acute toxicity profiles. Although large volumes of the lung received low radiation doses, no patient developed symptoms of ARP during the follow-up period.

  5. Acute and subacute toxicity assessment of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Baskaran, Vallikannan

    2013-10-01

    Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment-related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no-observed-adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

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

    PubMed

    Burgoon, Lyle D

    2016-06-01

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

  11. Acute silver toxicity in the euryhaline copepod Acartia tonsa: influence of salinity and food.

    PubMed

    Pedroso, Mariana Saia; Bersano, José Guilherme Filho; Bianchini, Adalto

    2007-10-01

    The euryhaline copepod Acartia tonsa was exposed to silver (AgNO(3)) in either the absence or the presence of food (diatom Thalassiosira weissflogii; 2 x 10(4) cells/ml). Standard static-renewal toxicity tests that included a fixed photoperiod of 16: 8 h light:dark and temperature (20 degrees C) were run in three different salinities (5, 15, and 30 ppt) together with measurements of pH, ions (Na(+), Cl(-), K(+), SO(4)(2-), Mg(2+), and Ca(2+)), alkalinity, dissolved organic carbon, and total and dissolved (0.45 microm) silver concentrations in the experimental media. In the absence of food, the 48-h EC50 (concentration causing effect to 50% of the individuals tested) values based on total and dissolved silver concentrations were 11.6, 87.2, and 163.2 microg Ag/L and 7.1, 79.2, and 154.6 microg Ag/L at salinities 5, 15, and 30 ppt, respectively. In the presence of food, they were 62.1, 98.5, and 238.4 microg Ag/L and 48.4, 52.3, and 190.9 microg Ag/L, respectively. In all experimental conditions, most of the toxic silver fraction was in the dissolved phase, regardless of salinity or the presence of food in the water. In either the absence or the presence of food, acute silver toxicity was salinity dependent, decreasing as salinity increased. Data indicate that changes in water chemistry can account for the differences in acute silver toxicity in the absence of food, but not in the presence of food, suggesting that A. tonsa requires extra energy to cope with the stressful conditions imposed by acute silver exposure and ionoregulatory requirements in low salinities. These findings indicate the need for incorporation of both salinity and food (organic carbon) in a future biotic ligand model (BLM) version for estuarine and marine conditions, which could be validated and calibrated using the euryhaline copepod A. tonsa.

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

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

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

  13. Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Fowler, Jack; Gomellini, Sara; Arcangeli, Stefano; Saracino, Biancamaria; Petrongari, Maria Grazia; Benassi, Marcello; Strigari, Lidia

    2011-03-15

    Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

  14. Trajectories of acute low back pain: a latent class growth analysis.

    PubMed

    Downie, Aron S; Hancock, Mark J; Rzewuska, Magdalena; Williams, Christopher M; Lin, Chung-Wei Christine; Maher, Christopher G

    2016-01-01

    Characterising the clinical course of back pain by mean pain scores over time may not adequately reflect the complexity of the clinical course of acute low back pain. We analysed pain scores over 12 weeks for 1585 patients with acute low back pain presenting to primary care to identify distinct pain trajectory groups and baseline patient characteristics associated with membership of each cluster. This was a secondary analysis of the PACE trial that evaluated paracetamol for acute low back pain. Latent class growth analysis determined a 5 cluster model, which comprised 567 (35.8%) patients who recovered by week 2 (cluster 1, rapid pain recovery); 543 (34.3%) patients who recovered by week 12 (cluster 2, pain recovery by week 12); 222 (14.0%) patients whose pain reduced but did not recover (cluster 3, incomplete pain recovery); 167 (10.5%) patients whose pain initially decreased but then increased by week 12 (cluster 4, fluctuating pain); and 86 (5.4%) patients who experienced high-level pain for the whole 12 weeks (cluster 5, persistent high pain). Patients with longer pain duration were more likely to experience delayed recovery or nonrecovery. Belief in greater risk of persistence was associated with nonrecovery, but not delayed recovery. Higher pain intensity, longer duration, and workers' compensation were associated with persistent high pain, whereas older age and increased number of episodes were associated with fluctuating pain. Identification of discrete pain trajectory groups offers the potential to better manage acute low back pain.

  15. Developmental and acute toxicity of cetylpyridinium chloride in Bombina orientalis (Amphibia: Anura).

    PubMed

    Park, Chan Jin; Song, Sang Ha; Kim, Dae Han; Gye, Myung Chan

    2016-08-01

    In an effort to evaluate the toxicity of cetylpyridinium chloride (CPC), a cationic surfactant in amphibians, we examined the developmental and acute toxicity of CPC in Bombina orientalis embryos and tadpoles. Embryonic exposure to 2.0μM (0.72mg/l) CPC for 7 days significantly decreased the survival rates and increased DNA damage in the intestine of developed tadpoles. Exposure to 1.5μM (0.54mg/l) CPC significantly decreased the growth of embryos and increased developmental abnormalities. The 168-h LC50 and EC50 values of CPC were 1.95μM (0.697mg/l) and 1.48μM (0.531mg/l) in embryos, respectively. In an extended acute toxicity test using tadpoles, the 168-h LC50 value of CPC was 5.07μM (1.82mg/l). In terms of survival and growth rates, the lowest observed effective concentration of CPC was 1.5μM. At sub-lethal concentrations (1.0 and 2.0μM) CPC treatment to embryos increased lipid peroxidation in the intestine and gills of developed tadpoles, indicating that CPC can impose oxidative stress. At 2.0μM CPC, pro-apoptotic Bax and Bak mRNA levels were significantly increased together with DNA fragmentation, indicative of apoptotic cell death. CPC in freshwater system may threaten the normal development of amphibian embryos.

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

    PubMed

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

    2014-06-01

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

  17. Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia.

    PubMed

    Henry, Theodore B; Kwon, Jeong-Wook; Armbrust, Kevin L; Black, Marsha C

    2004-09-01

    Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac; fluvoxamine, Luvox; paroxetine, Paxil; citalopram, Celexa; and sertraline, Zoloft) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment.

  18. Acute effects of three isoflavone class phytoestrogens and a mycoestrogen on cerebral microcirculation.

    PubMed

    Salom, Juan B; Castelló-Ruiz, María; Pérez-Asensio, Fernando J; Burguete, María C; Torregrosa, Germán; Alborch, Enrique

    2007-08-01

    Phytoestrogens and mycoestrogens are naturally occurring plant and fungus secondary metabolites with estrogen-like structure and/or actions. We aimed to check the hypothesis that phytoestrogens and mycoestrogens, due to their ability to elicit cerebral vasodilation, can induce acute increases in brain blood perfusion. For this purpose, we continuously recorded cerebrocortical perfusion by laser-Doppler flowmetry in anesthetized rats receiving intracarotid infusions (1 mg/kg) of one of the following estrogenic compounds: biochanin A, daidzein, genistein or zearalanone. We have shown the ability of two isoflavone class phytoestrogens (daidzein and biochanin A) and the mycoestrogen zearalanone to induce acute increases in brain blood flow when locally infused into the cerebral circulation of anesthetized rats. The isoflavone genistein failed to induce a significant increase in brain perfusion. No concomitant changes in blood pressure were recorded during the cerebral effects of the estrogenic compounds. Therefore, these microcirculatory effects were due to direct actions of the estrogenic compounds on the cerebrovascular bed.

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

    SciTech Connect

    McGuire, S.A.

    1991-02-01

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

  20. Acute toxicity assessment of camphor in biopesticides by using Daphnia magna and Danio rerio

    PubMed Central

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

    2014-01-01

    Objectives An ecofriendly alternative to chemical pesticides is bio-pesticides, which are derived from natural sources. The interest in bio-pesticides is based on the disadvantages associated with chemical pesticides. Methods We conducted acute toxicity assessments of camphor, a major component of bio-pesticides, by using Daphnia magna (D. magna) as well as assessed the morphological abnormalities that occurred in Danio rerio (D. rerio) embryos. Results The median effective concentration of camphor on D. magna after 48 hours was 395.0 μM, and the median lethal concentration on D. rerio embryos after 96 hours was 838.6 μM. The no observed effect concentration and predicted no effect concentration of camphor on D. magna, which was more sensitive than D. rerio, were calculated as 55.2 μM and 3.95 μM, respectively. Morphological abnormalities in D. rerio embryos exposed to camphor increased over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation of embryos mainly appeared between 24 and 48 hours. Further, symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects and collapsed symptoms of fertilized embryonic tissue were observed after 96 hours. Conclusions The camphor toxicity results suggest that continuous observations on the ecosystem are necessary to monitor toxicity in areas where biological pesticides containing camphor are sprayed. PMID:25234414

  1. Acute toxicity and histopathology of brook trout (Salvelinus fontinalis, mitchill) exposed to aluminum in acid water

    SciTech Connect

    Tandjung, S.D.

    1982-01-01

    Fingerling brook trout were exposed to different concentrations of Al at pH 5.6. The Basic Static Acute Toxicity Test was used to determine the 96-hr LC50. The toxicity of Al varied inversely with water hardness. The 96-hr LC/sub 50/ at a hardness of 2, 18, and 40 mg/l (CaCO/sub 3/) was 0.37, 3.4, and 6.53 mg/l Al respectively. Darkening of skin color was possible due to an increase in Na ions in the water as a result of body ion loss, activating the hormone MSH which causes melanin granules to spread within the melanocytes. Histology of all tissues of surviving fish appeared normal 3 months after transfer to uncontaminated water. The lateral line canal was regenerated by the end of the second month of the recovery period. In conclusion, we found that histology was essential to the interpretation of the toxicological effects of Al. The mortality of brook trout was attributed to Al toxicity that increased cell membrane permeability and mucification. Increased permeability resulted in the loss of body salt and an influx of Al and H ions. Mucus on gill surfaces caused anoxia leading to cell degeneration. Death was due to disturbances in osmoregulation, breakdown in enzyme activity, and disruption of O/sub 2/ transport.

  2. Acute toxicity of zinc to several aquatic species native to the Rocky Mountains.

    PubMed

    Brinkman, Stephen F; Johnston, Walter D

    2012-02-01

    National water-quality criteria for the protection of aquatic life are based on toxicity tests, often using organisms that are easy to culture in the laboratory. Species native to the Rocky Mountains are poorly represented in data sets used to derive national water-quality criteria. To provide additional data on the toxicity of zinc, several laboratory acute-toxicity tests were conducted with a diverse assortment of fish, benthic invertebrates, and an amphibian native to the Rocky Mountains. Tests with fish were conducted using three subspecies of cutthroat trout (Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus, greenback cutthroat trout O. clarkii stomias, and Rio Grande cutthroat trout O. clarkii virginalis), mountain whitefish (Prosopium williamsoni), mottled sculpin (Cottus bairdi), longnose dace (Rhinichthys cataractae), and flathead chub (Platygobio gracilis). Aquatic invertebrate tests were conducted with mayflies (Baetis tricaudatus, Drunella doddsi, Cinygmula sp. and Ephemerella sp.), a stonefly (Chloroperlidae), and a caddis fly (Lepidostoma sp.). The amphibian test was conducted with tadpoles of the boreal toad (Bufo boreas). Median lethal concentrations (LC(50)s) ranged more than three orders of magnitude from 166 μg/L for Rio Grande cutthroat trout to >67,000 μg/L for several benthic invertebrates. Of the organisms tested, vertebrates were the most sensitive, and benthic invertebrates were the most tolerant.

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

    PubMed Central

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

    2015-01-01

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

  4. Impacts of hypersaline acclimation on the acute toxicity of the organophosphate chlorpyrifos to salmonids.

    PubMed

    Maryoung, Lindley A; Lavado, Ramon; Schlenk, Daniel

    2014-07-01

    Acclimation to hypersaline conditions enhances the acute toxicity of certain thioether organophosphate and carbamate pesticides in some species of euryhaline fish. As the organophosphate chlorpyrifos is commonly detected in salmonid waterways, the impacts of hypersaline conditions on its toxicity were examined. In contrast to other previously examined pesticides, time to death by chlorpyrifos was more rapid in freshwater than in hypersaline water (16ppth). The median lethal time (LT50) after 100μg/L chlorpyrifos exposure was 49h (95% CI: 31-78) and 120h (95% CI: 89-162) for rainbow trout (Oncorhynchus mykiss) in freshwater and those acclimated to hypersaline conditions, respectively. Previous studies with hypersaline acclimated fish indicated induction of xenobiotic metabolizing enzymes that may detoxify chlorpyrifos. In the current study, chlorpyrifos metabolism was unaltered in liver and gill microsomes of freshwater and hypersaline acclimated fish. Acetylcholinesterase inhibition in brain and bioavailability of chlorpyrifos from the aqueous exposure media were also unchanged. In contrast, mRNA expression of neurological targets: calcium calmodulin dependent protein kinase II delta, chloride intracellular channel 4, and G protein alpha i1 were upregulated in saltwater acclimated fish, consistent with diminished neuronal signaling which may protect animals from cholinergic overload associated with acetylcholinesterase inhibition. These results indicate targets other than acetylcholinesterase may contribute to the altered toxicity of chlorpyrifos in salmonids under hypersaline conditions.

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

    PubMed

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

    2011-01-01

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

  6. Toxic Megacolon and Acute Ischemia of the Colon due to Sigmoid Stenosis Related to Diverticulitis

    PubMed Central

    Antonopoulos, P.; Almyroudi, M.; Kolonia, V.; Kouris, S.; Troumpoukis, N.; Economou, N.

    2013-01-01

    We present a rare case of toxic megacolon accompanied by necrosis of the colon due to chronic dilation caused by stenosis of the sigmoid colon as a complication of diverticulitis. The patient presented at the emergency department with diffuse abdominal pain, fever (38.8°C) and tachycardia (120 beats/min). Physical examination revealed distension and tenderness on deep palpation on the left lower quadrant without peritoneal signs. Abdominal computed tomography showed located stenosis in the sigmoid colon and marked dilation of the descending (12 cm diameter) and transverse (7.5 cm diameter) colon. A few hours later, the patient developed severe septic shock with electrolyte abnormalities. He had a history of two prior admissions to our hospital due to crises of acute diverticulitis. Based on Jalan's criteria the diagnosis was compatible with toxic megacolon. The patient's condition deteriorated suddenly and an emergency colectomy was performed. The operative findings revealed a necrotic colon. Histology examination confirmed the diagnosis of ischemia of the colon. To our knowledge this is the first published report in the literature which refers to a rare complication of diverticulitis, namely chronic stenosis which complicated to colonic ischemia and toxic megacolon. PMID:24163654

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

    PubMed

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

    2011-05-01

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

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

    USGS Publications Warehouse

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

    2011-01-01

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

  9. Toxicities associated with NBOMe ingestion, a novel class of potent hallucinogens: A review of the literature

    PubMed Central

    Suzuki, Joji; Dekker, Michael A.; Valenti, Erin S.; Arbelo Cruz, Fabiola A.; Correa, Ady M.; Poklis, Justin L.; Poklis, Alphonse

    2014-01-01

    Objective A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion. Methods We searched the PubMed for relevant English language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted. Results Ten citations met criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analog identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Seven (35%) were discharged after a period of observation, while 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common laboratory abnormalities were elevated creatine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%). Conclusion NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens. PMID:25659919

  10. Changes in food (Chlorella) levels and the acute toxicity of cadmium to Daphnia carinata and Eschinisca triserialis

    SciTech Connect

    Chandini, T.

    1988-09-01

    Inasmuch as cadmium is known to be toxic to both fish and aquatic invertebrates due to bioaccumulation and biomagnification potential, the present study was initiated to determine the acute effects of cadmium on two cladoceran species - Daphnia carinata and Echinisca triserialis commonly found in fresh waters of Delhi. The two species in the extreme ends of the size continuum and were chosen to determine the magnitude of toxicity in relation to body size. As extraneous abiotic and biotic factors such as temperature, pH, food have been shown to greatly modify a pollutant stress, the present study was conducted with the objective of determining if differences in food levels could modify the acute toxicity effects of cadmium on these cladocerans. An attempt has also been made to compare these results with previous studies on cadmium toxicity.

  11. Development of miniaturized acute toxicity tests for Daphnia magna and Pimephales promelas

    SciTech Connect

    Powell, R.L.; Kimerle, R.A.; Moser, E.M.; McKee, M.J.

    1995-12-31

    Standard EPA methods for conducting static, 48-hour, acute toxicity tests using Daphnia magna and Pimephales promelas (fathead minnows) can be miniaturized to successfully yield accurate LC50/EC50 values. The screening procedure involves exposing the test organisms to 1 mL of test solution, in test chambers which consist of the wells on 48-well microliter plates. Toxicity of the microliter plates and solvent, DO concentration, organism biomass to test solution ratio, partitioning of the chemicals and dilution of the test solution during transfer of the test organisms were examined. Survival and exposure were not significantly altered using non-standard test chambers. Toxicity of linear alkylbenzene sulfonate (LAS), pentachlorophenol (PCP), kepone, and sodium lauryl sulfate (SLS) was determined using D. magna and fathead minnows. Serial dilutions were made and 1 mL aliquots pipetted into the wells. Daphnia magna, < 24 hours old, and newly hatched fathead minnows, were transferred into the wells, twenty individuals per concentration, one per well. Dose-response curves were established for all test compounds. LC50/EC50`s values obtained using miniaturized methods strongly correlated with those obtained using standard EPA procedures. The tests were repeated a number of times with coefficient of variances for D. magna ranging from 10% with kepone to 64% with SLS. For fathead minnows CVs ranged from 0% with PCP to 23% with kepone. It was concluded that current methods can be miniaturized, yet still provide accurate information regarding toxicity for compounds in limited supply. This method may also be amenable to effluent testing i.e. TIE fractions. Other benefits include reducing the amount of equipment and space needed to conduct a test and the time involved.

  12. Acute and chronic toxicities of zinc pyrithione alone and in combination with copper to the marine copepod Tigriopus japonicus.

    PubMed

    Bao, Vivien W W; Lui, Gilbert C S; Leung, Kenneth M Y

    2014-12-01

    Zinc pyrithione (ZnPT) is a widely used booster biocide in combination with copper (Cu) in antifouling paints as a substitute for tributyltin. The co-occurrence of ZnPT and Cu in coastal marine environments is therefore very common, and may pose a higher risk to marine organisms if they can result in synergistic toxicity. This study comprehensively investigated the combined toxicity of ZnPT and Cu, on the marine copepod Tigriopus japonicus, for the first time, based on both 96-h acute toxicity tests using adult copepods and chronic full-life cycle tests (21 d) using nauplii <24-h old. As ZnPT has been reported to be easily trans-chelated to copper pyrithione (CuPT) in the presence of Cu, the acute toxicities of CuPT alone and in combination with Cu on adult copepods were also assessed. Our results showed that ZnPT and Cu exhibited a strong synergistic toxic effect on the copepod in both acute and chronic tests. During the acute test, the mortalities of adult copepods increased dramatically even with an addition of Cu at concentrations as low as 1-2 μg/L compared with those exposed to ZnPT alone. Severe chronic toxicities were further observed in the copepods exposed to ZnPT-Cu mixtures, including a significant increase of naupliar mortality, postponing of development from naupliar to copepodid and from copepodid to adult stage, and a significant decrease of intrinsic population growth when compared with those of copepods exposed to ZnPT or Cu alone. Such synergistic effects might be partly attributable to the formation of CuPT by the trans-chelation of ZnPT and Cu, because CuPT was found to be more toxic than ZnPT based on the acute toxicity results. Mixtures of CuPT and Cu also led to synergistic toxic effects to the copepod, in particular at high Cu concentrations. A novel non-parametric response surface model was applied and it proved to be a powerful method for analysing and predicting the acute binary mixture toxicities of the booster biocides (i.e., ZnPT and

  13. The utility of QSARs in predicting acute fish toxicity of pesticide metabolites: A retrospective validation approach.

    PubMed

    Burden, Natalie; Maynard, Samuel K; Weltje, Lennart; Wheeler, James R

    2016-10-01

    The European Plant Protection Products Regulation 1107/2009 requires that registrants establish whether pesticide metabolites pose a risk to the environment. Fish acute toxicity assessments may be carried out to this end. Considering the total number of pesticide (re-) registrations, the number of metabolites can be considerable, and therefore this testing could use many vertebrates. EFSA's recent "Guidance on tiered risk assessment for plant protection products for aquatic organisms in edge-of-field surface waters" outlines opportunities to apply non-testing methods, such as Quantitative Structure Activity Relationship (QSAR) models. However, a scientific evidence base is necessary to support the use of QSARs in predicting acute fish toxicity of pesticide metabolites. Widespread application and subsequent regulatory acceptance of such an approach would reduce the numbers of animals used. The work presented here intends to provide this evidence base, by means of retrospective data analysis. Experimental fish LC50 values for 150 metabolites were extracted from the Pesticide Properties Database (http://sitem.herts.ac.uk/aeru/ppdb/en/atoz.htm). QSAR calculations were performed to predict fish acute toxicity values for these metabolites using the US EPA's ECOSAR software. The most conservative predicted LC50 values generated by ECOSAR were compared with experimental LC50 values. There was a significant correlation between predicted and experimental fish LC50 values (Spearman rs = 0.6304, p < 0.0001). For 62% of metabolites assessed, the QSAR predicted values are equal to or lower than their respective experimental values. Refined analysis, taking into account data quality and experimental variation considerations increases the proportion of sufficiently predictive estimates to 91%. For eight of the nine outliers, there are plausible explanation(s) for the disparity between measured and predicted LC50 values. Following detailed consideration of the robustness of

  14. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions

    PubMed Central

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

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

    SciTech Connect

    Sherry, J.; Scott, B.; Dutka, B.

    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.

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

    SciTech Connect

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

    1993-03-31

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

  17. Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.

    PubMed

    Li, Fang; Wu, Xiangyang; Zou, Yanmin; Zhao, Ting; Zhang, Min; Feng, Weiwei; Yang, Liuqing

    2012-05-01

    Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity.

  18. Replacement of in vivo acute oral toxicity studies by in vitro cytotoxicity methods: opportunities, limits and regulatory status.

    PubMed

    Ukelis, Ute; Kramer, Peter-Jürgen; Olejniczak, Klaus; Mueller, Stefan O

    2008-06-01

    The development of a new medicinal product is a long and costly process in particular due to the regulatory requirements for quality, safety and efficacy. There is a common interest to increase the efficiency of drug development and to provide new, better quality medicinal products much faster to the public. One possible way to economize time and costs, as well as to consider animal protection issues, is to introduce new alternative methods into non-clinical toxicity testing. Currently, animal tests are mandatory for the evaluation of acute toxicity of chemicals and new drugs. The replacement of the in vivo tests by alternative in vitro assays would offer the opportunity to screen and assess numerous compounds at the same time, to predict acute oral toxicity and thus accelerate drug development. Moreover, the substitution of in vivo tests by in vitro methods shows a proactive pursuit of ethical and animal welfare issues. Importantly, the implementation of in vitro assays for acute oral toxicity would require the establishment of common test guidelines across the EU, USA and Japan, i.e., the regions of ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use). Presently, alternative in vitro tests are being investigated internationally. Yet, in order to achieve regulatory acceptance and implementation of in vitro assays, convincing results from validation studies are required. In this review, we discuss the current regulatory status of acute oral toxicity testing and point out achievements of alternative methods. We describe the application of in vitro tests, correlating in vitro with in vivo data. The use of in vitro data to predict in vivo acute oral toxicity is analyzed using the Registry of Cytotoxicity, an official independent database. We have then analyzed opportunities and drawbacks for future implementation of in vitro test methods, with particular focus on industrial use.

  19. Acute and chronic toxic effects of chloramphenicol on Scenedesmus obliquus and Chlorella pyrenoidosa.

    PubMed

    Zhang, Wei; Sun, Wenfang; An, Shuai; Xiong, Bang; Lin, Kuangfei; Cui, Xinhong; Guo, Meijin

    2013-08-01

    The acute and chronic toxicological effects of Chloramphenicol (CAP) on Scenedesmus obliquus and Chlorella pyrenoidosa are not well understood. The indoor experiments were carried to observe and analyze the CAP induced changes. Results of the observations have showed that CAP exposure could significantly inhibit the growth of Scenedesmus obliquus in almost all the treated groups, while Chlorella pyrenoidosa exhibited less sensitivity. Chlorophyll-a syntheses of Scenedesmus obliquus were all inhibited by CAP exposure, while Chlorella pyrenoidosa displayed obvious stimulation effect. Catalase (CAT) and Superoxide dismutase (SOD) activities of both algae were promoted in all the treatments. The experimental results indicated that the growth and Chlorophyll-a syntheses of Scenedesmus obliquus were more sensitive in response to CAP exposure than that of Chlorella pyrenoidosa. While for CAT and SOD activities, Chlorella pyrenoidosa showed more susceptible. This research provides a basic understanding of CAP toxicity to aquatic organisms.

  20. Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

    PubMed

    Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

    2015-01-01

    Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile.

  1. Acute toxicity of a No. 6 fuel oil to marine organisms

    SciTech Connect

    Hollister, T.A.; Ward, G.S.; Parrish, P.R.

    1980-05-01

    The oil tanker Argo Merchant broke up in shoal waters off Nantucket, Massachusetts, in December 1976 and spilled a No. 6 fuel oil containing a No. 2 cutter stock. The US Coast Guard attempted to burn the oil slick at sea, but heavy seas contributed to an unsuccessful operation. Shortly after the spill, acute toxicity tests were performed with five test materials and three saltwater organisms - an alga, a copepod, and a fish. The test materials included a No. 6 fuel oil, a wicking agent, and lighter fluid. The materials were tested singularly and in combination. The three materials were also combined according to instructions from the US Coast Guard, ignited, and the resulting residue tested.

  2. Acute toxicity testing of some herbicides-, alkaloids-, and antibiotics-metabolizing soil bacteria in the rat.

    PubMed

    Kaiser, A; Classen, H G; Eberspächer, J; Lingens, F

    1981-01-01

    Seven strains of soil bacteria with the ability to metabolize herbicides, alkaloids or antibiotics were tested in rats for acute toxicity. 1. Upon oral administration of 9.0 x 10(8) to 6.6 x 10(10) cells daily during 7 d no adverse reactions were observed. 2. Exposure by air did not lead to specific pulmonary changes. 3. Intracutaneous injection of 7.5 x 10(6) to 1.4 x 10(8) cells did not lead to adverse skin reactions. 4. Intraperitoneal injections up to 10(8) cells per animal did not kill rats although bacteria entered blood. At higher concentrations some mortality occurred partly due to unspecific stress reactions. 5. Animal data and observations on 20 humans being exposed to these strains for 2 months up to 15 years support the view that the bacteria tested are essentially harmless for health.

  3. Acute, aquatic toxicity of selected mineral particles. Technical report, September 1985-October 1986

    SciTech Connect

    Johnson, D.W.; Landis, W.G.

    1988-11-01

    Graphite fibers, nickel-graphite fibers, polycrystalline iron whiskers, and graphite Mirco-260 (M-260) were tested to determine their toxicities to Daphnia magna. The graphite fibers and nickel-graphite fibers were ground with a mortar and pestle before testing. The M-260 had an EC50 of 80.6 mg/L for four pooled replicates. None of the other compounds caused any deaths at concentrations up to 100 mg/L. All the bioassays were 48-hr acute studies. A 96-hr growth inhibition assay using Ankistrodesmus falcatus was performed with the graphite. No inhibition of A. falcatus was observed; however, the growth of the algae was enhanced by the two lowest test concentrations.

  4. Efficacy and Toxicity of Induction Therapy with Cladribine, Idarubicin, and Cytarabine (IAC) for Acute Myeloid Leukemia.

    PubMed

    Woelich, Susan K; Braun, James T; Schoen, Martin W; Ramlal, Reshma; Freter, Carl E; Petruska, Paul J; Lionberger, Jack M

    2017-02-01

    We report our single-center experience with cytarabine and idarubicin for induction therapy for acute myeloid leukemia (AML) with an additional 5 days of cladribine (IAC therapy). From July 2012 to September 2014, 38 patients completed a full course of IAC induction. Median patient age was 61 years, 61% of patients were ≥60 years old, and 71% were male. The complete remission (CR) rate was 63% following a single induction course, three patients (8%) required a second induction course to achieve CR, for an overall response rate of 71%. The median duration of severe neutropenia was 30.5 days. Thirty-two percent of patients developed mucositis, 76% experienced diarrhea, and 61% developed a rash. Incidence of CR following IAC induction therapy for AML was comparable to historical data, but with frequent diarrhea, rash, and fungal infections. This study found IAC efficacy and toxicity was similar irrespective of age.

  5. Alpha-lipoic acid improves acute deltamethrin-induced toxicity in rats.

    PubMed

    Abdou, Rania H; Abdel-Daim, Mohamed M

    2014-09-01

    Alpha-lipoic acid (ALA) is a natural dithiol compound, with a free radical scavenger and biological antioxidant properties. The purpose of the current study was to investigate the protective effects of ALA on biochemical alteration and oxidative stress induced by acute deltamethrin intoxication in rats. Markers of liver and kidney injuries in serum of deltamethrin-intoxicated as well as ALA-pretreated rats were analyzed. Moreover, serum and (or) tissue lipid peroxidation, malondialdehyde and antioxidant markers, reduced glutathione, catalase, superoxide dismutase activity, and total antioxidant capacity were evaluated. The results showed that all parameters were altered in the intoxicated group, indicating hepatorenal oxidative damage of deltamethrin. Pre-treatment with ALA reversed the changes in most of the studied parameters in a dose-dependent manner. Histopathological and biochemical findings were parallel. It can be concluded that ALA may be a promising therapeutic option for prevention and (or) treatment of deltamethin toxicity.

  6. Behavioral consequences of chelator administration in acute cadmium toxicity (journal version)

    SciTech Connect

    Peele, D.B.; Farmer, J.D.; MacPhail, R.C.

    1988-01-01

    The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received cadmium either alone or in combination with BAL or DMSA. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete, attenuations of conditioned flavor aversions when compared to rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hrs.

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

    PubMed

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

    2011-11-01

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

  8. Role of vitamin E in mitigating methomyl induced acute toxicity in blood of male Wistar rats.

    PubMed

    Garg, Dharm Paul; Kiran, Ravi; Bansal, Anil K; Malhotra, Anshoo; Dhawan, Devinder K

    2008-01-01

    The present study was designed to evaluate the protective potential of vitamin E, if any, in attenuating the toxic effects induced by acute methomyl treatment in rats. Male Wistar rats, weighing between 230 and 250 g, received either a single oral dose of 9 mg/kg of methomyl, vitamin E alone injected intraperitoneally on alternate days (4 injections) at 50 mg/kg body for 1 week prior to methomyl treatment, or both methomyl plus vitamin E given in a similar manner. The effects of different treatments were studied on lipid peroxidation (LPO), reduced glutathione (GSH) and antioxidant enzymes, which included superoxide dismutase (SOD), glutathione-s-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSHPx) and catalase and various hematological parameters, including total leucocytes count (TLC), differential leukocyte count (DLC), hemoglobin, platelets counts, red cell counts, and scanning electron microscopy (SEM). Acute 24-h treatment to rats resulted in a significant increase in the LPO. GSH levels and the activities of catalase, GST, and GSHPx were found to be significantly decreased following methomyl treatment. A significant elevation in the activity of SOD and in TLC was also observed after 24 h of methomyl treatment. Further, a significant increase in the neutrophils and eosinophil counts was also observed. However, lymphocytes showed a significant decrease following methomyl treatment. SEMs showed significant morphological changes following methomyl treatment. Vitamin E pretreatment to methomyl-treated rats effectively normalized the levels of LPO and GSH. Vitamin E could also significantly elevate the activity of catalase, increase platelets counts and TLC, and normalized the activities of SOD and GSHPx. Vitamin E pretreatment improved the morphology of the red blood cells. The study concludes that vitamin E affords protection in methomyl-induced toxicity in the rat.

  9. Extended acute toxicity study of (188) Re-liposome in rats.

    PubMed

    Chi-Mou, Liu; Chia-Che, Tsai; Chia-Yu, Yu; Wan-Chi, Lee; Chung-Li, Ho; Tsui-Jung, Chang; Chih-Hsien, Chang; Te-Wei, Lee

    2013-09-01

    Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness as well as reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. As our previous study found that a high dosage (185 of MBq) of (188) Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposomes ((188) Re-liposome) induced a decrease in white blood cell (WBC) count in Sprague-Dawley rats 7 days postinjection, the objective of the present study was to investigate extended acute radiotoxicity of (188) Re-liposome. Rats were administered via intravenous (i.v.) injection with (188) Re-liposome (185, 55.5 and 18.5 MBq), normal saline as a blank control or non-radioactive liposome as a vehicle control. Mortality, clinical signs, food consumption, body weights, urinary, biochemical and hematological analyzes were examined. In addition, gross necropsy and histopathological examinations were also performed at the end of the follow-up period. None of the rats died and no clinical sign was observed during the 28-day study period. Only male rats receiving (188) Re-liposome at a high dosage (185 MBq) displayed a slight weight loss compared with the control rats. In both male and female rats, the WBC counts of both high-dose and medium-dose (55.5 MBq) groups reduced significantly 7 days postinjection, but recovered to the normal range on Study Day 29. There was no significant difference in urinary analyzes, biochemical parameters and histopathological assessments between the (188) Re-liposome-treated and control groups. The information generated from the present study on extended acute toxicity of (188) Re-liposome will serve as a safety reference for radiopharmaceuticals in early-phase clinical trials.

  10. Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata.

    PubMed

    Sumon, Kizar Ahmed; Saha, Sampa; van den Brink, Paul J; Peeters, Edwin T H M; Bosma, Roel H; Rashid, Harunur

    2017-02-01

    This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10 and 100 µg L(-1)) of chlorpyrifos in plastic bowls. Log-logistic regression was used to calculate LC10 and LC50 values. Results showed that embryo mortality significantly increased with increasing chlorpyrifos concentrations. The 24-h LC10 and LC50 values (with 95% confidence limits) of chlorpyrifos for embryos were 0.89 (0.50-1.58) and 11.8 (9.12-15.4) µg L(-1), respectively. Hatching success decreased and mortality of larvae significantly increased with increasing concentrations of chlorpyrifos. The 24-h LC10 and LC50 values (with 95% confidence limits) of chlorpyrifos for larvae were 0.53 (0.27-1.06) and 21.7 (15.9-29.4) µg L(-1), respectively; the 48-h LC10 and LC50 for larvae were 0.04 (0.02-0.09) and 5.47 (3.77-7.94) µg L(-1), respectively. The results of this study suggest that 1 µg L(-1) of chlorpyrifos in the aquatic environment may adversely affect the development and the reproduction of banded gourami. Our study also suggests that banded gourami fish can serve as an ideal model species for evaluating developmental toxicity of environmental contaminants.

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

    SciTech Connect

    Brown, Aaron P.; Barney, Christian L.; Grosshans, David R.; McAleer, Mary Frances; Groot, John F. de; Puduvalli, Vinay K.; Tucker, Susan L.; Crawford, Cody N.; Khan, Meena; Khatua, Soumen; Gilbert, Mark R.; Brown, Paul D.; Mahajan, Anita

    2013-06-01

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

  12. Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes.

    PubMed

    Schmiegelow, Kjeld

    2016-12-01

    Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all childhood ALL cases are due to such germline mutations, but the figure may be higher. Most of these syndromes are primarily characterized by their non-malignant phenotype, whereas ALL may be the dominating or even only striking manifestation of the syndrome in some families. Identification of such ALL patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring cancer predisposing mutations can be challenging for both the physician and the patient due to their preexisting symptoms, their reduced tolerance to radio- and/or chemotherapy with enhanced risk of life-threatening organ toxicities, and the paucity of data from ALL patients with the same or similar syndromes being treated by contemporary protocols. Recent studies clearly indicate that many of these patients stand a good chance of cure, and that they should be offered chemotherapy with the intention to cure. Some of these syndromes are characterized by reduced tolerance to radiotherapy and/or specific anticancer agents, while others are not. This review summarises our current knowledge on the risk of acute toxicities for these ALL patients and provides guidance for treatment adjustments.

  13. Acute and subchronic toxic effects of atrazine and chlorpyrifos on common carp (Cyprinus carpio L.): Immunotoxicity assessments.

    PubMed

    Xing, Houjuan; Liu, Tao; Zhang, Ziwei; Wang, Xiaolong; Xu, Shiwen

    2015-08-01

    Atrazine (ATR) and chlorpyrifos (CPF) are widely used pesticides in agricultural practices throughout world. It has resulted in a series of toxicological and environmental problems, such as impacts on many non-target aquatic species, including fish. The spleen and head kidney in the bony fish are the major hematopoietic organs, and play a crucial part in immune responses. This study evaluated the subchronic effects of ATR and CPF on the mRNA and protein levels of HSP60, HSP70 and HSP90 in the immune organs of common carp and compared the acute and subchronic effects of ATR and CPF on the swimming speed (SS) of common carp. The results of acute toxicity tests showed that the 96 h-LC50 of ATR and CPF for common carp was determined to be 2.142 and 0.582 mg/L, respectively. Meanwhile, acute and subacute toxicity of ATR and CPF in common carp resulted in hypoactivity. We also found that the mRNA and protein levels of HSP60, HSP70 and HSP90 genes were induced in the spleen and head kidney of common carp exposed to ATR and CPF in the subchronic toxicity test. Our results indicate that ATR and CPF are highly toxic to common carp, and hypoactivity in common carp by acute and subchronic toxicity of ATR and CPF may provide a useful tool for assessing the toxicity of triazine herbicide and organophosphorous pesticides to aquatic organisms. In addition, the results from the subchronic toxicity test exhibited that increasing concentration of ATR and CPF in the environment causes considerable stress for common carp, suggesting that ATR and CPF exposure cause immunotoxicity to common carp.

  14. Acute toxicity of parabens and their chlorinated by-products with Daphnia magna and Vibrio fischeri bioassays.

    PubMed

    Terasaki, Masanori; Makino, Masakazu; Tatarazako, Norihisa

    2009-04-01

    The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by means of two toxicity bioassays: Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. The median effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to 62 mg l(-1) in the D. magna test and from 0.0038 to 5.9 mg l(-1) in the V. fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and n-propylparaben, the most commonly used preservatives in cosmetics, toward D. magna was 3.9- and 2.8-fold that of their corresponding parent compounds. Toxicity toward D. magna showed a linear relationship with log P, indicating that toxicity increases with increasing hydrophobicity. On the other hand, the correlations of toxicity toward V. fischeri with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens. A complete assessment of the ecological and toxicological risks of parabens may require the examination of chlorinated parabens as well as the parent pollutants, as described in the present study.

  15. Correlation between acute toxicity for Daphnia magna, Aliivibrio fischeri and physicochemical variables of the leachate produced in landfill simulator reactors.

    PubMed

    Barrios Restrepo, José J; Flohr, Letícia; Melegari, Silvia P; da Costa, Cristina H; Fuzinatto, Cristiane F; de Castilhos, Armando B; Matias, William G

    2017-02-03

    Due to the diversified nature of municipal solid waste and the different stages of its decomposition, the formed leachates result in a complex chemical mixture with toxic potential. These chemicals can cause environmental problems, such as the contamination of surface or groundwater, thus affecting the balance of aquatic ecosystems. The aim of our study was to evaluate the acute toxicity of leachates in Daphnia magna and Aliivibrio fischeri and to identify the main physicochemical variables that influence the toxicity of the landfill leachates produced in reactors within pilot simulations. Acute toxicity tests carried out on D. magna and A. fischeri showed that the leachates produced inside the reactors are highly toxic, presenting EC5048h < 1% for D. magna and EC5015min < 12% for A. fischeri. This result indicates that microcrustaceans are more sensitive to leachates, making them more suitable to our study. Pb showed the highest correlation with EC5048h, suggesting that Pb is the main chemical variable indicative of toxicity for the conditions of the experiment. In smaller scale, phosphate (PO4(3-)) and nitrate (NO(3-)) were the macronutrients that most influenced the toxicity. Clearly, this correlation should be viewed with caution because the synergistic effects of this complex mixture are difficult to observe.

  16. Interspecies quantitative structure-activity-activity relationships (QSAARs) for prediction of acute aquatic toxicity of aromatic amines and phenols.

    PubMed

    Furuhama, A; Hasunuma, K; Aoki, Y

    2015-01-01

    We propose interspecies quantitative structure-activity-activity relationships (QSAARs), that is, QSARs with descriptors, to estimate species-specific acute aquatic toxicity. Using training datasets consisting of more than 100 aromatic amines and phenols, we found that the descriptors that predicted acute toxicities to fish (Oryzias latipes) and algae were daphnia toxicity, molecular weight (an indicator of molecular size and uptake) and selected indicator variables that discriminated between the absence or presence of various substructures. Molecular weight and the selected indicator variables improved the goodness-of-fit of the fish and algae toxicity prediction models. External validations of the QSAARs proved that algae toxicity could be predicted within 1.0 log unit and revealed structural profiles of outlier chemicals with respect to fish toxicity. In addition, applicability domains based on leverage values provided structural alerts for the predicted fish toxicity of chemicals with more than one hydroxyl or amino group attached to an aromatic ring, but not for fluoroanilines, which were not included in the training dataset. Although these simple QSAARs have limitations, their applicability is defined so clearly that they may be practical for screening chemicals with molecular weights of ≤364.9.

  17. Mammalian Toxicity of Munition Compounds. Phase 1. Acute Oral Toxicity Primary Skin and Eye Irritation, Dermal Sensitization, and Disposition and Metabolism

    DTIC Science & Technology

    1975-07-22

    and 6 days for 1,3-DNG and 1-MNG. WP caused depression, anorexia, and death in several days with enlarged yellow nutmeg livers. ^ 2,5-DNT was...several days. Animals that died were found to have large yellow nutmeg livers. Primary skin irritation and eye irritation tests were negative with a...amount of radioactivity is consistent with white phosphorus poisoning since enlarged nutmeg liver was observed in the acute oral toxicity study. The

  18. Acute toxicity to freshwater organisms of antiparasitic drugs for veterinary use.

    PubMed

    Yoshimura, Haruo; Endoh, Yuuko S

    2005-02-01

    The acute toxicity of five antiparasitic drugs used in the veterinary field-amprolium hydrochloride (APH), bithionol (BT), levamisole hydrochloride (LVH), pyrimethamine (PYM) and trichlorfon (TRC)-to the aquatic organisms Oryzias latipes, Daphnia magna, and Brachionus calyciflorus was examined. The toxicity test with O. latipes was conducted in accordance with the OECD Guidelines for the Testing of Chemicals (1993) to determine the 24-, 48-, 72-, and 96-h LC(50) values. In addition, 24- and 48-h EC(50) values for D. magna and a 24-h EC(50) for B. calyciflorus were determined with the DAPHTOXKIT F(trade mark) magna (Creasel, Belgium) and the ROTOXKIT F(trade mark) (Creasel, Belgium), respectively. High-performance liquid chromatographic analysis revealed that APH, LVH, and PYM were stable in water, but BT was unstable, decreasing by 84% on average at 24 h. TRC rapidly decomposed, with only 0.7% of the initial concentration remaining after 96 h, forming dichlorvos. The toxicity of TRC to O. latipes was determined in two ways: exposure to the same medicated water for 96 h (static test) and exposure to medicated water replaced every 24 h (semistatic test). AMP, LVM, and PYM were tested in the static condition, and BT was tested in the semistatic condition. BT was most toxic to O. latipes, with a 96-h LC(50) of 0.24 mg L(-1), followed by PYM, with a 96-h LC(50) of 5.6 mg L(-1). The 24-, 48-, 72-, and 96-h LC(50) values of TRC in the static test were 92.0, 45.2, 29.5, and 17.6 mg L(-1), respectively, which tended to be lower than those in the semistatic test, especially late in the observation period. D. magna was the most susceptible to TRC, with a 48-h EC(50) as low as 0.00026 mg L(-1). The 48-h EC(50) values of BT, PYM, and LVH for D. magna were 0.3, 5.2, and 64.0 mg L(-1), respectively. B. calyciflorus was the most susceptible to BT, with an EC(50) of 0.063 mg L(-1), followed by PYM, with an EC(50) of 15.0 mg L(-1). Among the test compounds, APH was the least toxic

  19. Acute Radiation Disease : Cutaneous Syndrome and Toxic properties of Radiomimetics -Radiation Neurotoxins and Hematotoxins.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Cutaneous injury is an important complication of a general or local acute irradiation. A type of a skin and tissues lesions depends on a type, intensity, and period of irradiation. Also, the clinical picture, signs, and manifestations of the cutaneous syndrome depend on a type of the radiation toxins circulated in lymph and blood of irradiated mammals. Radiation Toxins were isolated from lymph of the mammals that were irradiated and developed different forms of the Acute Radiation Syndromes (ARS) -Cerebrovascular, Cardiovascular, Gastrointestinal, and Hematopoietic. Radiation Toxins can be divided into the two important types of toxins (Neu-rotoxins and Hematotoxins) or four groups. The effects of Radiation Neurotoxins include severe damages and cell death of brain, heart, gastrointestinal tissues and endothelial cells of blood and lymphatic vessels. The hematotoxicity of Hematotoxic Radiation Toxins includes lym-phopenia, leukopenia, thrombocytopenia, and anemia in the blood circulation and transitory lymphocytosis and leukocytosis in the Central Lymphatic System. In all cases, administration of the Radiomimetics (Radiation Toxins) intramuscularly or intravenously to healthy, radiation naive mammals had induced and developed the typical clinical manifestations of the ARS. In all cases, administration of Radiomimetics by subtoxic doses had demonstrated development of typical clinical signs of the cutaneous syndrome such as hair loss, erythema, swelling, desqua-mation, blistering and skin necrosis. In animal-toxic models, we have activated development of the local skin and tissue injury after injection of Radiation Toxins with cytoxic properties.

  20. Acute alloxan renal toxicity in the rat initially causes degeneration of thick ascending limbs of Henle

    PubMed Central

    Terayama, Yui; Kodama, Yasushi; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2016-01-01

    Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla. These tubular lesions progressed from the outer medulla to the cortex. At day 2 after AL treatment, the lesions reached a peak, then both proximal and distal tubules also showed degeneration and necrosis, and tubular regeneration was seen in TAL. Immunohistochemically, damaged tubular epithelium included slightly enlarged prohibitin-positive granules, but it expressed no GLUT2, which is an AL transporter. Ultrastructurally, cytoplasmic and mitochondrial swelling was detected in degenerated cells of TAL. These findings suggest that AL initially causes degeneration of TAL, and induces mitochondrial and cellular damage in the tubular epithelium without involving GLUT2. PMID:28190920

  1. Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

    NASA Technical Reports Server (NTRS)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

    2007-01-01

    Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and

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

    PubMed

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

    2009-05-01

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

  3. Relative sensitivity of bull trout (Salvelinus confluentus) and rainbow trout (Oncorhynchus mykiss) to acute copper toxicity.

    PubMed

    Hansen, James A; Lipton, Josh; Welsh, Paul G

    2002-03-01

    Bull trout (Salvelinus confluentus) were recently listed as threatened in the United States under the federal Endangered Species Act. Past and present habitat for this species includes waterways contaminated with heavy metals released from mining activities. Because the sensitivity of this species to copper was previously unknown, we conducted acute copper toxicity tests with bull and rainbow trout (Oncorhynchus mykiss) in side-by-side comparison tests. Bioassays were conducted using water at two temperatures (8 degrees C and 16 degrees C) and two hardness levels (100 and 220 mg/L as CaCO3). At a water hardness of 100 mg/L, both species were less sensitive to copper when tested at 16 degrees C compared to 8 degrees C. The two species had similar sensitivity to copper in 100-mg/ L hardness water, but bull trout were 2.5 to 4 times less sensitive than rainbow trout in 220-mg/L hardness water. However, when our results were viewed in the context of the broader literature on rainbow trout sensitivity to copper, the sensitivities of the two species appeared similar. This suggests that adoption of toxicity thresholds that are protective of rainbow trout would be protective of bull trout; however, an additional safety factor may be warranted because of the additional level of protection necessary for this federally threatened species.

  4. Evaluation of the acute toxicity of Orimulsion and Fuel Oil No. 6 using standard estuarine species

    SciTech Connect

    Johnson, I.C.; Kosalwat, P.; Baldwin, L.; Kostecki, P.T.

    1995-12-31

    Fuel Oil No.6 is a typical fuel used nationwide by power plants in the generation of electricity and orimulsion is an alternative fuel also used for this purpose in facilities in Canada, Japan and the United Kingdom. Orimulsion is currently being evaluated for combustion in the US by Florida Power and Light Company. Several cute and partial life cycle toxicity tests were conducted in order to assess the potential aquatic toxicity and environmental consequences of an accidental Orimulsion spill in seawater. Environmental studies conducted using Orimulsion indicate that in the case of a spill into seawater, Orimulsion will become a bitumen particle suspension in seawater and a floating slick is not expected to form. Therefore, the typical acute effects associated with oil slicks were not anticipated for the dispersed bitumen. In the case of Orimulsion, all of the bitumen can be assumed to be in the water column following an accidental spill. Therefore, Orimulsion potential environmental impacts are expected to be observed primarily on organisms inhabiting the water column. Test species included mysid shrimp, inland silversides, polychaetes, amphipods, eastern oysters, and sheepshead minnows.

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

    PubMed Central

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

    2015-01-01

    Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm′) by 50% at concentrations ranging from 3.5 μg l−1 (ametryn) to 132 μg l−1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm′. PMID:26616444

  6. Acute inhalation toxicity of 3-methylfuran in the mouse: pathology, cell kinetics, and respiratory rate effects

    SciTech Connect

    Haschek, W.M.; Boyd, M.R.; Hakkinen, P.J.; Owenby, C.S.; Witschi, H.

    1984-01-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in male BALB/c mice by morphologic examination of animals killed at varying timepoints following a 1-hr exposure to an initial chamber concentration of 14 to 37 mumol/liter (343 to 906 ppm). In addition, respiratory rate measurements and cell kinetics were used to assess quantitatively pulmonary damage and repair. Necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen 1 day following exposure and was followed by regeneration, which was virtually complete, within 21 days. Cell kinetic studies showed peak bronchiolar cell proliferation at 3 days with a labeling index (LI) of 5.0% compared to 0.4% in controls. An increase in parenchymal cell proliferation was also noted coincident with a mild interstitial pneumonitis. This parenchymal proliferation, peaking at 10 days with an LI of 1.4% compared to 0.2% in controls, consisted primarily of type II epithelial and endothelial cell proliferation indicating possible delayed damage and repair of type I epithelial and endothelial cells. The respiratory rate showed an initial transient increase followed by a more prolonged decrease with eventual return to control levels. 3MF toxicity was also evidenced by a necrotizing suppurative rhinitis, centrilobular hepatic necrosis, lymphocyte necrosis in the thymus and spleen, sialoadenitis, and otitis media.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    Jalilzadeh-Amin, Ghader; Maham, Massoud

    2015-01-01

    Objectives: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acute toxicity evaluation, rats were orally administrated with single dose of EOML at doses ranging from 10 to 1000 mg/kg. Results: EOML caused a significant (p<0.05) and dose-dependent decrease of gastrointestinal transit, nevertheless, it could not block the inhibitory effect of atropine (0.1 mg/kg). EOML at oral doses of 20 and 80 mg/kg protected the animals against castor oil-induced diarrhea significantly (p<0.05). EOML decreased the intestinal fluid accumulation as indicated by the significantly (p<0.05 to p<0.001) decrease compared to control. The oral LD50 of EOML was found to be 470 mg/kg in rat. Conclusion: Since the inhibition of intestinal hyperactivity and hypersecretory are the bases of the treatment of diarrhea, results obtained in the present study suggest that EOML is endowed with antidiarrheal activity. EOML is moderately toxic for oral medication. PMID:25949954

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

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

    PubMed

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

    2015-11-30

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

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

    PubMed

    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.

  12. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

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

    PubMed Central

    Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

    2014-01-01

    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

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

    PubMed Central

    Li, Caixia; Li, Ping; Tan, Yee Min; Lam, Siew Hong; Chan, Eric C. Y.; Gong, Zhiyuan

    2016-01-01

    Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury. PMID:26967897

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

    PubMed Central

    Chandramouli, Kondethimmanahalli H.; Xu, Ying; Pan, Ke; Wang, Wen-Xiong; Qian, Pei-Yuan

    2011-01-01

    Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD's guideline, the predicted no effect concentration (PNEC) was 0.168 µg l−1, which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound. PMID:21897857

  16. Automated red blood cell exchange for acute drug removal in a patient with sirolimus toxicity.

    PubMed

    Galera, Pallavi; Martin, Hannah C; Welch, Linda; Sulmasy, Paula; Cerny, Jan; Greene, Mindy; Vauthrin, Michelle; Bailey, Jeffrey A; Weinstein, Robert

    2015-12-01

    Sirolimus is an immunosuppressant used to prevent graft versus host disease in allogeneic hematopoietic stem cell transplant recipients. It has a large volume of distribution (12 ± 7.5 l/kg) and within the intravascular space ∼95% of it is bound to red blood cells. Because of potential toxic effects at high trough levels, therapeutic drug monitoring is recommended for sirolimus. We present a case of severe hepatic dysfunction due to Hepatitis B and sirolimus toxicity, in a 51-year-old male stem cell transplant recipient. An automated red cell exchange decreased his blood sirolimus level from 22.6 to 10.3 ng/ml (55% reduction) and improved his liver enzymes. Re-equilibration of sirolimus from other compartments to the blood necessitated a series of four red cell exchanges, after which the sirolimus level was 4.7 ng/ml. Although the patient ultimately succumbed to multiorgan failure, red cell exchange may be considered for acute removal of sirolimus in selected patients.

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

    PubMed

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

    2007-03-21

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

  18. INTERSPECIES CORRELATION ESTIMATION (ICE) FOR ACUTE TOXICITY TO AQUATIC ORGANISMS AND WILDLIFE. II. USER MANUAL AND SOFTWARE

    EPA Science Inventory

    Asfaw, Amha, Mark R. Ellersieck and Foster L. Mayer. 2003. Interspecies Correlation Estimations (ICE) for Acute Toxicity to Aquatic Organisms and Wildlife. II. User Manual and Software. EPA/600/R-03/106. U.S. Environmental Protection Agency, National Health and Environmental Effe...

  19. PREDICTION OF THE ACUTE TOXICITY OF ORGANIC COMPOUNDS TO THE FATHEAD MINNOW (PIMEPHALES PROMALAS) USING A GROUP CONTRIBUTION METHOD

    EPA Science Inventory

    A group contribution method has been developed to correlate the acute toxicity (96 h LC50) to the fathead minnow (Pimephales promelas) for 379 organic chemicals. Multilinear regression and computational neural networks (CNNs) were used for model building. The multilinear linear m...

  20. Development of Graves’ disease after long-standing hypothyroidism on treatment, with acute toxicity to thionamides and lithium

    PubMed Central

    Gupta, Yashdeep; Singh, Sandeep; Ammini, Ariachery C

    2012-01-01

    Thyroid hyperfunction in a patient with long-standing hypothyroidism is uncommon. Here, we describe and discuss the unusual scenario of development of severe skin rash to carbimazole, with subsequent acute toxicity to lithium in clinically indicated doses, in a patient who manifested hyperthyroidism after being on treatment for hypothyroidism for 7 years. PMID:22854236

  1. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.1

    EPA Science Inventory

    Predictive toxicological models are integral to ecological risk assessment because data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ge...

  2. Acute toxicity of plant essential oils to scarab larvae (Coleoptera: Scarabaeidae) and their analysis by gas chromatography-mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larvae of scarab beetles (Coleoptera: Scarabaeidae) are important contaminant and root-herbivore pests of ornamental crops. In order to develop alternatives to conventional insecticides, 24 plant essential oils were tested for their acute toxicity against third instar larvae of the Japanese beetle P...

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

    PubMed

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

    2013-11-01

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

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

    SciTech Connect

    Cavender, R.C.; Cherry, D.S.; Yeager, M.M.; Bidwell, J.R.

    1995-12-31

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

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

    PubMed

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

    2012-11-01

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

  6. Evaluation of acute toxicity and genotoxicity of liquid products from pyrolysis of Eucalyptus grandis wood.

    PubMed

    Pimenta, A S; Bayona, J M; García, M T; Solanas, A M

    2000-02-01

    Slow pyrolysis of Eucalyptus grandis wood was performed in an oven laboratory, and smoke was trapped and condensed to yield liquid products. Polycyclic aromatic hydrocarbons (PAHs) and phenolic fractions were isolated from the former liquid products using adsorption column chromatography (ACC) and identified by GC/MS. Concentrations of PAH and phenolic fractions in total pyrolysis liquids were respectively 48.9 microg/g and 8.59% (w/w). Acute toxicity of total samples of pyrolysis liquids and the phenolic fraction was evaluated by means of two bioassays, namely, 24-h immobilization bioassay with Daphnia magna and Microtox bioassays, the latter employing the luminescent bacteria Photobacterium phosphoreum. Total pyrolysis liquids and the PAH fraction were evaluated for genotoxicity by the Microtox bioassay conducted using rehydrated freeze-dried dark mutant of the luminescent bacteria Vibrio fisheri strain M169. Total pyrolysis liquids and the phenolic fraction, respectively, in concentrations of 170 and 68 mg/L were able to immobilize 50% (EC(50)) of the D. magna population following 24-h exposure. Concentrations of 19 and 6 mg/L, respectively, for total pyrolysis liquids and phenolic fraction were the effective concentrations that resulted in a 50% (EC(50)) reduction in light produced by bacteria in the Microtox bioassay. Accordingly, the Microtox bioassay was more sensitive to toxic effects of both kind of samples than the D. magna bioassay, particularly for the phenolic fraction. Regarding to the genotoxicity evaluation, the results achieved by Microtox bioassay showed that total pyrolysis liquids had no genotoxic effects with and without exogenous metabolic activation using rat liver homogenate (S9). However, the PAH fraction showed toxic effects with rat liver activation and had a dose-response number (DRN) equal to 1.6, being in this way suspected genotoxic. The lowest detected concentration (LDC) of the PAH fraction able to cause genotoxic effects was 375

  7. Acute toxicity of six freshwater mussel species (Glochidia) to six chemicals: Implications for daphnids and Utterbackia imbecillis as surrogates for protection of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Milam, C.D.; Farris, J.L.; Dwyer, F.J.; Hardesty, D.K.

    2005-01-01

    Acute (24-h) toxicity tests were used in this study to compare lethality responses in early life stages (glochidia) of six freshwater mussel species, Leptodea fragilis, U. imbecillis, Lampsilis cardium, Lampsilis siliquoidea, Megalonaias nervosa, and Ligumia subrostrata, and two standard test organisms, Ceriodaphnia dubia and Daphnia magna. Concentrations of carbaryl, copper, 4-nonylphenol, pentachlorophenol, permethrin, and 2,4-D were used in acute exposures to represent different chemical classes and modes of action. The relative sensitivities of species were evaluated by ranking their LC 50 values for each chemical. We used these ranks to determine the extent to which U. imbecillis (one of the most commonly used unionids in toxicity tests) was representative of the tolerances of other mussels. We also calculated geometric mean LC50s for the families Unionidae and Daphnidae. Rankings of these data were used to assess the extent to which Daphnidae can be used as surrogates for freshwater mussels relative to chemical sensitivity. While no single chemical elicited consistently high or low toxicity estimates, carbaryl and 2,4-D were generally the least toxic to all species tested. No species was always the most sensitive, and Daphnidae were generally protective of Unionidae. Utterbackia imbecillis, while often proposed as a standard unionid mussel test species, did not always qualify as a sufficient surrogate (i.e., a substitute organism that often elicits similar sensitivity responses to the same contaminant exposure) for other species of mussels, since it was usually one of the more tolerant species in our rankings. U. imbecillis should be used as a surrogate species only with this caution on its relative insensitivity. ?? 2005 Springer Science+Business Media, Inc.

  8. Nanoparticular surface-bound PCBs, PCDDs, and PCDFs-a novel class of potentially higher toxic POPs.

    PubMed

    Schön, Peter; Ctistis, Georgios; Bakker, Wouter; Luthe, Gregor

    2016-03-04

    In a previous study, Env Sci Poll Res:1-7, 2015 showed that polychlorinated biphenyls (PCBs), polychlorinated dibenzo dioxins (PCDDs), and polychlorinated dibenzo furanes (PCDFs) are found in commercially available (nano) particular titanium dioxide as a result of the fabrication. Here, we give a brief perspective and reason the toxicity of these new classes of persistent organic pollutants (POPs) by reviewing also their nanoparticular properties, such as surface-to-volume ratio, photocatalytic activity, polarity shifts, and stealth effect. These insights point towards a new class of POPs and toxicologic effects, which are related to the size but not a result of nanotechnology itself. We pave the way to the understanding of until now unresolved very complex phenomena, such as the indoor exposure, formation, and transformation of POP and sick-building syndrome. This is a fundamental message for nanotoxicology and kinetics and should be taken into account when determining the toxicity of nanomaterials and POPs separately and as a combination.

  9. Acute toxicity evaluation of explosive wastewater by bacterial bioluminescence assays using a freshwater luminescent bacterium, Vibrio qinghaiensis sp. Nov.

    PubMed

    Ye, Zhengfang; Zhao, Quanlin; Zhang, Mohe; Gao, Yuchen

    2011-02-28

    The compositions of explosive wastewater generated from TNT (2,4,6-trinitrotoluene) purification stage were characterized by using UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), high performance liquid chromatograph (HPLC) and gas chromatograph/mass spectroscopy (GC/MS). The acute toxicity was evaluated by bacterium bioluminescence assay using a freshwater luminescent bacterium (Vibrio qinghaiensis sp. Nov.) and a marine luminescent bacterium (Photobacterium phosphoreum). The results showed that the wastewater's biodegradability was poor due to the high amount of chemical oxygen demand (COD). The main organic components were dinitrotoluene sulfonates (DNTS) with small amount of TNT, dinitrotoluene (DNT), mononitrotoluene (MNT) and other derivatives of nitrobenzene. It was highly toxic to luminescent bacteria P. phosphoreum and V. qinghaiensis sp. Nov. After reaction time of 15 min, the relative concentration of toxic pollutants (expressed as reciprocal of dilution ratio of wastewater) at 50% of luminescence inhibition ratio was 5.32×10(-4) for P. phosphoreu, while that was 4.34×10(-4) for V. qinghaiensis. V. qinghaiensis is more sensitive and suitable for evaluating the wastewater's acute toxicity than P. phosphoreum. After adsorption by resin, the acute toxicity can be greatly reduced, which is helpful for further treatment by biological methods.

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

    PubMed

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

    2009-09-01

    This study assessed the use of the European amphipod Corophium multisetosum Stock [Stock, J.H., 1952. Some notes on the taxonomy, the distribution and the ecology of four species of the genus Corophium (Crustacea, Malacostraca). Beaufortia 21, 1-10] in estuarine sediment acute toxicity testing. The sensitivity of adults to the reference toxicant CdCl(2) was determined in water-only 96 h exposures in salinity 2. LC(50) values ranged from 0.33mgCd(2+)L(-1) at 22 degrees C to 0.57mgCd(2+)L(-1) at 15 degrees C. Adult survival was studied in control sediment with water salinity from 0 to 36 and with fine particles content (<63 microm) from 2% to 97% of total sediment, dry weight. Experiments were conducted at 15, 18 and 22 degrees C and the results indicate that the species can be used under the full salinity range although higher mortality was observed at the lower salinity in the higher water temperature, and at the higher salinity in the lower water temperature. The species also tolerated the studied range of sediment fines content and showed the highest sensitivity at intermediate values of fines, especially at the higher temperature, thus advising that tests which have to accommodate sediments with a wide range in fines content should preferably be conducted at 15 degrees C rather than at 22 degrees C. The response in natural sediments was studied in samples collected yearly from 1997 to 2006, at a site located off the Tagus Estuary, western Portugal. A major flood event in winter 2000-2001 induced detectable alterations in sediment baseline descriptors (grain-size, redox potential and total volatile solids), organic contaminants (PAHs, PCBs, DDT metabolites and gamma-HCH) and the macrofauna benthic community. Mortality of the amphipod diminished significantly from the before to the after flood period, in close agreement with diminishing sediment contamination and increasing benthic fauna diversity, in the same time period. C. multisetosum is suitable to conduct

  11. Imazapyr+imazapic herbicide determines acute toxicity in silver catfish Rhamdia quelen.

    PubMed

    Golombieski, Jaqueline Ineu; Sutili, Fernando Jonas; Salbego, Joseânia; Seben, Débora; Gressler, Luciane Tourem; da Cunha, Jéssyka Arruda; Gressler, Leticia Trevisan; Zanella, Renato; Vaucher, Rodrigo de Almeida; Marchesan, Enio; Baldisserotto, Bernardo

    2016-06-01

    Imazapyr (IMY) and imazapic (IMI) are imidazolinone herbicides which have been associated in a commercial formulation (Kifix(®)). To date, there are no studies on the toxicity of an IMY+IMI herbicide in fish. This work aimed to assess the acute toxicity (24 and 96 h) of IMY+IMI (0, 0.488 and 4.88 µg/L) towards Rhamdia quelen through hematological, biochemical, immunological, ionoregulatory and enzymatic indexes. Red blood cell count was lower at 4.88 than at 0.488 µg/L (24 and 96 h); mean corpuscular volume was lower than control at both concentrations (24 h) and at 0.488 µg/L (96 h); lymphocytes declined at 4.88 µg/L comparing to control (96 h); and monocytes increased at 4.88 µg/L (96 h) in comparison with the respective control and with 4.88 µg/L at 24h. Aspartate aminotransferase was higher at 0.488 µg/L (96 h) than the respective control and the respective concentration at 24 h; uric acid reduced at 4.88 µg/L comparing with 0.488 µg/L (96 h); and cortisol was lower at 4.88 µg/L compared to 0.488 µg/L and control (96 h). Herbicide exposure lowered plasma bactericidal activity at both concentrations (24 h) and at 0.488 µg/L (96 h); and plasma complement activity declined at 4.88 µg/L comparing with 0.488 µg/L and control (96 h), and was lower at all concentrations at 96 h than at 24 h. Plasma K(+) levels were higher at 4.88µg/L than in the remaining groups (24 and 96h); and Na(+) levels decreased at 4.88 µg/L compared to control (96 h). Na(+)/K(+)-ATPase and H(+)-ATPase activities in gills were lower at 4.88 µg/L comparing with control (24 h) and with the respective concentration at 96 h; and AChE activity in brain was higher at 0.488 and 4.88 µg/L than control (24 h) and the respective concentrations at 96 h, while in muscle it was higher at 0.488 and 4.88 µg/L than control (96 h) and the respective concentrations at 24 h. The present findings demonstrate that, despite IMY+IMI targets the animal-absent AHAS enzyme, such formulation displayed

  12. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea).

    PubMed

    Wang, Ning; Erickson, Russell J; Ingersoll, Christopher G; Ivey, Christopher D; Brunson, Eric L; Augspurger, Tom; Barnhart, M Christopher

    2008-05-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20 degrees C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity.

  13. Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

    PubMed Central

    Ishii, Kentaro; Ogino, Ryo; Hosokawa, Yukinari; Fujioka, Chiaki; Okada, Wataru; Nakahara, Ryota; Kawamorita, Ryu; Tada, Takuhito; Hayashi, Yoshiki; Nakajima, Toshifumi

    2015-01-01

    The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients. PMID:25304328

  14. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

    USGS Publications Warehouse

    Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

    2008-01-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

  15. Acute and sub-acute oral toxicity assessment of the methanolic extract from leaves of Hibiscus rosa-sinensis L. in mice

    PubMed Central

    Nath, Purobi; Yadav, Arun K.

    2015-01-01

    Background: The leaves of Hibiscus rosa-sinensis L. (Malvaceae) are used for the treatment of dysentery and diarrhea, to promote draining of abscesses and as analgesic agent in the traditional medicine of Cook Islands, Haiti, Japan and Mexico. Aim: The present study investigated the oral acute and subacute toxicity of methanol leaf extract of H. rosa-sinensis in mice. Materials and Methods: In the acute toxicity study, a single oral dose of 2000 mg/kg of extract was given to five mice at 48 h intervals. Animals were observed individually for any clinical signs of toxicity or mortality for