WorldWideScience

Sample records for tetrodotoxin ttx toxicity

  1. The Chemical and Evolutionary Ecology of Tetrodotoxin (TTX) Toxicity in Terrestrial Vertebrates

    Science.gov (United States)

    Hanifin, Charles T.

    2010-01-01

    Tetrodotoxin (TTX) is widely distributed in marine taxa, however in terrestrial taxa it is limited to a single class of vertebrates (Amphibia). Tetrodotoxin present in the skin and eggs of TTX-bearing amphibians primarily serves as an antipredator defense and these taxa have provided excellent models for the study of the evolution and chemical ecology of TTX toxicity. The origin of TTX present in terrestrial vertebrates is controversial. In marine organisms the accepted hypothesis is that the TTX present in metazoans results from either dietary uptake of bacterially produced TTX or symbiosis with TTX producing bacteria, but this hypothesis may not be applicable to TTX-bearing amphibians. Here I review the taxonomic distribution and evolutionary ecology of TTX in amphibians with some attention to the origin of TTX present in these taxa. PMID:20411116

  2. Bibliographic Studies on the Tetrodotoxin(TTX

    Directory of Open Access Journals (Sweden)

    Hwang, Tae-Joon

    2000-12-01

    Full Text Available We were trying to study the validity of Puffer fish's poison(Tetrodotoxin- TTX to make a traditional Korean Medical treatment. The following conclusions were made after literary studies. 1. The first record of the puffer fish dates back 2000 years ago in the Chinese text Book of Mountain and Sea and other texts from the similar period. 2. Puffer fish's poison IS known as tetrodotoxin which is an amino perhydroquinazoline compound. It has a chemical formula of C11H17N3O8 in the hemiacetal structure and has the molecular weight of 319. 3. Tetrodotoxin (TTX plays a role as potent neurotransmitter blocker by blocking the Na+-gate channel which hinders the influx of Na+ ion into the cell. 4. Symptoms of the puffer fish poisoning ranges from blunted sense in the lips and tongue, occasional vomiting in the first degree to sudden descending of the blood pressure, apnea, and other critical conditions in the fourth degree. Intoxication of the puffer fish poison progresses at a rapid pace as death may occur after an hour and half up to eight hours in maximum. Typical death occurs after four to six hours. 5. Ways to treat the puffer fish poisoning include gastric irrigation, induce vomiting, purgation, intravenous fluid injection, and correcting electrolytic imbalance and acidosis. In cases of dyspnea, apply oxygen inhalation and conduct artificial respiration. 6. Tetrodotoxin (TTX may be applied in treating brain disorders, ocular pain, excess pain in the large intestine and ileum, and relieving tension of the skeletal museles, neuralgia, rheumatism, arthritis, and etc. 7. In terms of Oriental medicine, the puffer fish poison has characteristics of sweet, warm, and poisonous. It's known efficacies are to tonify weakness, dispel damp, benefit the lower back, relieve hemorrhoid, kills parasites, remove edema, and so forth. And the puffer fish eggs processed with ginger are said to be effective against tuberculosis and lung cancer, thus, it's validity must be

  3. Tetrodotoxin (TTX as a Therapeutic Agent for Pain

    Directory of Open Access Journals (Sweden)

    Cruz Miguel Cendán

    2012-01-01

    Full Text Available Tetrodotoxin (TTX is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs. VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.

  4. High-resolution mass spectrometry analysis of tetrodotoxin (TTX) and its analogues in puffer fish and shellfish.

    Science.gov (United States)

    Bane, Vaishali; Brosnan, Brid; Barnes, Paul; Lehane, Mary; Furey, Ambrose

    2016-09-01

    Tetrodotoxin (TTX) is an emerging toxin in the European marine environment. It has various known structural analogues. It acts as a sodium channel blocker; the ability of each analogue to bind to the sodium channel varies with the particular structure of each analogue. Thus, each analogue will vary in its toxic potential. TTX analogues co-occur in food samples at variable concentrations. An LC-MS method was developed for the identification and quantitation of several analogues of TTX using an LTQ-Orbitrap XL mass spectrometer. The LTQ-Orbitrap XL mass spectrometer facilitates high mass accuracy measurement up to 100,000 full width at half maximum (FWHM). Using high resolution at 100,000 FWHM allows for the identification of TTX and its analogues in various matrices, including puffer fish and molluscan shellfish samples (Δ ppm = 0.28-3.38). The confirmation of characteristic fragment ions of TTX and its analogues was achieved by determining their elemental formulae via high mass accuracy. A quantitative method was then developed and optimised using these characteristic fragment ions. The limit of quantitation (LOQ) of the method was 0.136 µg g(-1) (S/N = 10) and the limit of detection (LOD) was 0.041 µg g(-1) (S/N = 3) spiking TTX standard into TTX-free mackerel fish extracts. The method was applied to naturally contaminated puffer fish and molluscan shellfish samples to confirm the presence of TTX and its analogues.

  5. Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection

    Directory of Open Access Journals (Sweden)

    Vaishali Bane

    2014-02-01

    Full Text Available Tetrodotoxin (TTX is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined to regions of South East Asia, but recent studies have demonstrated that the toxin has spread to regions in the Pacific and the Mediterranean. There is no known antidote to TTX which is a powerful sodium channel inhibitor. This review aims to collect pertinent information available to date on TTX and its analogues with a special emphasis on the structure, aetiology, distribution, effects and the analytical methods employed for its detection.

  6. Shewanella putrefaciens, a major microbial species related to tetrodotoxin (TTX)-accumulation of puffer fish Lagocephalus lunaris.

    Science.gov (United States)

    Auawithoothij, W; Noomhorm, A

    2012-08-01

    To investigate the major micro-organisms, which were isolated from internal organs, related to tetrodotoxin (TTX)-accumulation of puffer fish Lagocephalus lunaris. Puffer fish Lagocephalus lunaris around Chang Island in the Gulf of Thailand were collected to examine TTX-accumulation and microbial load in internal organs. The nine predominant micro-organisms isolated from the internal organs were determined TTX and studied in relation to the TTX-accumulation of the puffer fish. Shewanella putrefaciens, a predominant bacterium and related to the TTX-accumulation of the puffer fish, was examined growth and TTX-production after culture in modified Zobell medium. The results revealed that the average TTX-accumulation of the puffer fish directly varied to the bacterium load periodically, year-round. Furthermore, it coincided with the growth and the TTX-production of the bacterium, which grew slowly but produced high TTX at low temperature. Shewanella putrefaciens was a major bacterium relating to TTX-accumulation of puffer fish L. lunaris. It resulted in high TTX-accumulation of the puffer fish at low temperatures of seawater. Temperature affected growth and TTX-production of S. putrefaciens that resulted in TTX accumulated in puffer fish L. lunaris. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  7. Scientific opinion on the risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

    DEFF Research Database (Denmark)

    Petersen, Annette

    Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine...... bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 μg/kg body......, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC–MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 0.1 and 25 μg/kg....

  8. 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs.

    Science.gov (United States)

    Chang, F C; Spriggs, D L; Benton, B J; Keller, S A; Capacio, B R

    1997-07-01

    The extent to which cardiorespiratory infirmity and other sublethal effects of saxitoxin (STX) and tetrodotoxin (TTX) can be reversed by 4-aminopyridine (4-AP) was investigated in guinea pigs chronically instrumented for the concurrent electrophysiological recordings of electrocorticogram (ECoG), diaphragmatic electromyogram (DEMG), Lead II electrocardiogram, and neck skeletal muscle electromyogram. Animals were intoxicated with either STX or TTX (2 and 3 microg/kg, im) to produce a state of progressive cardiorespiratory depression (depicted by decreasing DEMG amplitude, bradypnea, and bradycardia). At the point where cardiorespiratory performance was most seriously compromised (approximately 30 min posttoxin), 4-AP (1 or 2 mg/kg, im) was administered. The therapeutic effect of 4-AP was striking in that, within minutes, the toxin-induced diaphragmatic blockade, bradypnea, bradycardia, and depressed cortical activity were all restored to a level either comparable to, or surpassing, that of control. The optimal 4-AP dose level was determined to be 2 mg/kg (im) based on analyses of cardiorespiratory activity profiles throughout the course of intoxication and 4-AP treatment. At the dose levels (either 1 or 2 mg/kg) used to restore ventilatory function and cardiovascular performance, 4-AP produced no sign of seizures and convulsions. Although less serious secondary effects such as cortical excitant/arousal effect (indicated by ECoG power spectral analysis) and transient periods of skeletal muscle fasciculation were observed, these events were of minor concern particularly in view of the remarkable therapeutic effects of 4-AP.

  9. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

    Directory of Open Access Journals (Sweden)

    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  10. Toxic marine puffer fish in Thailand seas and tetrodotoxin they contained.

    Science.gov (United States)

    Chulanetra, Monrat; Sookrung, Nitat; Srimanote, Potjanee; Indrawattana, Nitaya; Thanongsaksrikul, Jeeraphong; Sakolvaree, Yuwaporn; Chongsa-Nguan, Manas; Kurazono, Hisao; Chaicumpa, Wanpen

    2011-10-01

    A total of 155 puffers caught from two of Thailand's seas, the Gulf of Siam and the Andaman seas, during April to July 2010 were included in this study. Among 125 puffers from the Gulf of Siam, 18 were Lagocephalus lunaris and 107 were L. spadiceus which were the same two species found previously in 2000-2001. Thirty puffers were collected from the Andaman seas, 28 Tetraodon nigroviridis and two juvenile Arothron reticularis; the two new species totally replaced the nine species found previously in 1992-1993. Conventional mouse bioassay was used to determine the toxicity in all fish tissue extracts, i.e., liver, reproductive tissue, digestive tissue and muscle. One of each of the species L. lunaris and L. spadiceus (5.56 and 0.93%, respectively) were toxic. All 28 T. nigroviridis and 2 A. reticularis (100%) from the Andaman seas were toxic. The toxicity scores in T. nigroviridis tissues were much higher than in the respective tissues of the other three fish species. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) revealed that the main toxic principle was tetrodotoxin (TTX). This study is the first to report TTX in L. spadiceus. Our findings raised a concern for people, not only Thais but also inhabitants of other countries situated on the Andaman coast; consuming puffers of the Andaman seas is risky due to potential TTX intoxication.

  11. Toxic Marine Puffer Fish in Thailand Seas and Tetrodotoxin They Contained

    Directory of Open Access Journals (Sweden)

    Hisao Kurazono

    2011-10-01

    Full Text Available A total of 155 puffers caught from two of Thailand’s seas, the Gulf of Siam and the Andaman seas, during April to July 2010 were included in this study. Among 125 puffers from the Gulf of Siam, 18 were Lagocephalus lunaris and 107 were L. spadiceus which were the same two species found previously in 2000–2001. Thirty puffers were collected from the Andaman seas, 28 Tetraodon nigroviridis and two juvenile Arothron reticularis; the two new species totally replaced the nine species found previously in 1992–1993. Conventional mouse bioassay was used to determine the toxicity in all fish tissue extracts, i.e., liver, reproductive tissue, digestive tissue and muscle. One of each of the species L. lunaris and L. spadiceus (5.56 and 0.93%, respectively were toxic. All 28 T. nigroviridis and 2 A. reticularis (100% from the Andaman seas were toxic. The toxicity scores in T. nigroviridis tissues were much higher than in the respective tissues of the other three fish species. Liquid chromatography/tandem mass spectrometry (LC-MS/MS revealed that the main toxic principle was tetrodotoxin (TTX. This study is the first to report TTX in L. spadiceus. Our findings raised a concern for people, not only Thais but also inhabitants of other countries situated on the Andaman coast; consuming puffers of the Andaman seas is risky due to potential TTX intoxication.

  12. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses

    Directory of Open Access Journals (Sweden)

    Jorge Lago

    2015-10-01

    Full Text Available Tetrodotoxin (TTX is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of “fugu” is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains.

  13. The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder.

    Science.gov (United States)

    Lepiarczyk, Ewa; Bossowska, Agnieszka; Kaleczyc, Jerzy; Majewska, Marta; Gonkowski, Sławomir; Majewski, Mariusz

    2017-03-30

    The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine urinary bladder after intravesical instillation of tetrodotoxin (TTX). The CaMG neurons were visualized with retrograde tracer Fast blue (FB) and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), calbindin (CB), galanin (GAL) and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 6) and TTX-treated pigs (n = 6), the vast majority (92.6% ± 3.4% and 88.8% ± 2%, respectively) of FB-positive (FB+) nerve cells were TH+. TTX instillation caused a decrease in the number of FB+/TH+ neurons immunopositive to NPY (88.9% ± 5.3% in the control animals vs. 10.6% ± 5.3% in TTX-treated pigs) or VIP (1.7% ± 0.6% vs. 0%), and an increase in the number of FB+/TH+ neurons immunoreactive to SOM (8.8% ± 1.6% vs. 39% ± 12.8%), CB (1.8% ± 0.7% vs. 12.6% ± 2.7%), GAL (1.7% ± 0.8% vs. 10.9% ± 2.6%) or nNOS (0% vs. 1.1% ± 0.3%). The present study is the first to suggest that TTX modifies the chemical coding of CaMG neurons supplying the porcine urinary bladder.

  14. The Influence of Tetrodotoxin (TTX on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG Neurons Supplying the Porcine Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Ewa Lepiarczyk

    2017-03-01

    Full Text Available The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG neurons supplying the porcine urinary bladder after intravesical instillation of tetrodotoxin (TTX. The CaMG neurons were visualized with retrograde tracer Fast blue (FB and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against tyrosine hydroxylase (TH, neuropeptide Y (NPY, vasoactive intestinal polypeptide (VIP, somatostatin (SOM, calbindin (CB, galanin (GAL and neuronal nitric oxide synthase (nNOS. It was found that in both the control (n = 6 and TTX-treated pigs (n = 6, the vast majority (92.6% ± 3.4% and 88.8% ± 2%, respectively of FB-positive (FB+ nerve cells were TH+. TTX instillation caused a decrease in the number of FB+/TH+ neurons immunopositive to NPY (88.9% ± 5.3% in the control animals vs. 10.6% ± 5.3% in TTX-treated pigs or VIP (1.7% ± 0.6% vs. 0%, and an increase in the number of FB+/TH+ neurons immunoreactive to SOM (8.8% ± 1.6% vs. 39% ± 12.8%, CB (1.8% ± 0.7% vs. 12.6% ± 2.7%, GAL (1.7% ± 0.8% vs. 10.9% ± 2.6% or nNOS (0% vs. 1.1% ± 0.3%. The present study is the first to suggest that TTX modifies the chemical coding of CaMG neurons supplying the porcine urinary bladder.

  15. Highly Toxic Ribbon Worm Cephalothrix simula Containing Tetrodotoxin in Hiroshima Bay, Hiroshima Prefecture, Japan

    Directory of Open Access Journals (Sweden)

    Manabu Asakawa

    2013-02-01

    Full Text Available In 1998, during a toxicological surveillance of various marine fouling organisms in Hiroshima Bay, Japan, specimens of the ribbon worm, Cephalothrix simula (Nemertea: Palaeonemertea were found. These ribbon worms contained toxins with extremely strong paralytic activity. The maximum toxicity in terms of tetrodotoxin (TTX was 25,590 mouse units (MU per gram for the whole worm throughout the monitoring period. The main toxic component was isolated and recrystallized from an acidified methanolic solution. The crystalline with a specific toxicity of 3520 MU/mg was obtained and identified as TTX by high performance liquid chromatography (HPLC-fluorescent detection (FLD (HPLC-FLD, electrospray ionization-mass spectrometry (ESI-MS, infrared (IR, nuclear magnetic resonance (NMR and gas chromatography–mass spectrometry (GC-MS. The highest toxicity of C. simula exceeded the human lethal dose per a single worm. A toxicological surveillance of C. simula from 1998 to 2005 indicated approximately 80% of the individuals were ranked as “strongly toxic” (≥1000 MU/g. Forty-eight percent of the specimens possessed toxicity scores of more than 2000 MU/g. Seasonal variations were observed in the lethal potency of C. simula. Specimens collected on January 13, 2000 to December 26, 2000 showed mean toxicities of 665–5300 MU/g (n = 10. These data prompted a toxicological surveillance of ribbon worms from other localities with different habitats in Japan, including Akkeshi Bay (Hokkaido under stones on rocky intertidal beaches, as well as Otsuchi (Iwate among calcareous tubes of serpulid polychaetes on rocky shores. Within twelve species of ribbon worms examined, only C. simula possessed extremely high toxicity. Therefore, C. simula appears to show generally high toxicity irrespective of their locality and habitat.

  16. Plasma protein binding of tetrodotoxin in the marine puffer fish Takifugu rubripes.

    Science.gov (United States)

    Matsumoto, Takuya; Tanuma, Daisuke; Tsutsumi, Kazuma; Jeon, Joong-Kyun; Ishizaki, Shoichiro; Nagashima, Yuji

    2010-01-01

    To elucidate the involvement of plasma protein binding in the disposition of tetrodotoxin (TTX) in puffer fish, we used equilibrium dialysis to measure protein binding of TTX in the plasma of the marine puffer fish Takifugu rubripes and the non-toxic greenling Hexagrammos otakii, and in solutions of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AGP). TTX (100-1000 microg/mL) bound to protein in T. rubripes plasma with low affinity in a non-saturable manner. The amount of bound TTX increased linearly with the TTX concentration, reaching 3.92+/-0.42 microg TTX/mg protein at 1000 microg TTX/mL. Approximately 80% of the TTX in the plasma of T. rubripes was unbound in the concentration range of TTX examined, indicating that TTX exists predominantly in the unbound form in the circulating blood of T. rubripes at a wide range of TTX concentrations. TTX also bound non-specifically to H. otakii plasma proteins, BSA, and bovine AGP. The amount of the bound TTX in the plasma of H. otakii and BSA, respectively, was 1.86+/-0.36 and 4.65+/-0.70 microg TTX/mg protein at 1000 microg TTX/mL, and that in the bovine AGP was 8.78+/-0.25 microg TTX/mg protein at 200 microg TTX/mL. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Examination of transformation among tetrodotoxin and its analogs in the living cultured juvenile puffer fish, kusafugu, Fugu niphobles by intramuscular administration.

    Science.gov (United States)

    Kono, Michiko; Matsui, Takashi; Furukawa, Kiyoshi; Takase, Takuhiko; Yamamori, Kunio; Kaneda, Hideko; Aoki, Daisuke; Jang, Jun-Ho; Yotsu-Yamashita, Mari

    2008-11-01

    In puffer fish, tetrodotoxin (TTX) exists as the major toxin with chemically equilibrium analogs (4-epiTTX, 4,9-anhydroTTX) and chemically non-equilibrium analogs (deoxy analogs, 11-oxoTTX, 4-S-cysteinylTTX). There are two purposes to this study: 1) to search for the reason why TTX is the most major analog in puffer fish, even 4,9-anhydroTTX is chemically more stable, 2) to investigate whether or not chemically non-equilibrium analogs are transformed in puffer fish, because these were predicted to be biosynthetic intermediates. Pure TTX, 4-epiTTX, 4,9-anhydroTTX, and 11-oxoTTX were separately administrated to the cultured non-toxic juvenile puffer fish kusafugu, Fugu niphobles by intramuscular injection. Sixteen days after administration, TTX analogs in the whole fish were analyzed by LC-fluorescent detection and LC/MS. By the administration of TTX, 4-epiTTX, and 4,9-anhydroTTX, 34-40% of the administrated doses of the toxins were accumulated, and 4,9-anhydroTTX has become the major toxin after inter-conversion. This result indicates discrepancy from the previous ones wherein TTX was predominantly accumulated when TTXs were administrated through diets; this suggests that dietary administration might be necessary to accumulate TTX as the major toxin, and not 4,9-anhydroTTX. Transformations from TTX to deoxy analogs or 11-oxoTTX, or from 11-oxoTTX to TTX were not detected in this study.

  18. Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication

    Directory of Open Access Journals (Sweden)

    Osamu Arakawa

    2008-05-01

    Full Text Available Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX. In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue.

  19. Comparison of the localization of tetrodotoxin between wild pufferfish Takifugu rubripes juveniles and hatchery-reared juveniles with tetrodotoxin administration.

    Science.gov (United States)

    Okita, Kogen; Takatani, Tomohiro; Nakayasu, Junichi; Yamazaki, Hideki; Sakiyama, Kazutaka; Ikeda, Koichi; Arakawa, Osamu; Sakakura, Yoshitaka

    2013-09-01

    To reveal the accumulation profile of tetrodotoxin (TTX) in pufferfish Takifugu rubripes juveniles, we compared the localization of TTX in various tissues among wild juveniles and hatchery-reared juveniles with or without TTX administration using immunohistochemical technique with anti-TTX monoclonal antibody. Immuno-positive reaction was observed in hepatic tissue, basal cell of skin and olfactory, olfactory epithelium, optic nerve and brain (optic tectum, cerebellum, medulla oblongata) of wild juveniles (body length: BL, 4.7-9.4 cm). TTX was detected in the same tissues as wild juveniles and epithelial cell layer of intestine of hatchery-reared juveniles (BL, 5.0-5.3 cm) to which TTX was orally administrated. No positive reaction was observed from the tissues of hatchery-reared juveniles without TTX administration. These results suggest that orally administrated TTX to the non-toxic cultured juveniles is accumulated in the same manner of wild juveniles. In addition, our study revealed that pufferfish accumulates TTX in the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the Toxin in Aquatic Systems

    Directory of Open Access Journals (Sweden)

    Timur Yu. Magarlamov

    2017-05-01

    Full Text Available This review is devoted to the marine bacterial producers of tetrodotoxin (TTX, a potent non-protein neuroparalytic toxin. In addition to the issues of the ecology and distribution of TTX-producing bacteria, this review examines issues relating to toxin migration from bacteria to TTX-bearing animals. It is shown that the mechanism of TTX extraction from toxin-producing bacteria to the environment occur through cell death, passive/active toxin excretion, or spore germination of spore-forming bacteria. Data on TTX microdistribution in toxic organs of TTX-bearing animals indicate toxin migration from the digestive system to target organs through the transport system of the organism. The role of symbiotic microflora in animal toxicity is also discussed: despite low toxin production by bacterial strains in laboratory conditions, even minimal amounts of TTX produced by intestinal microflora of an animal can contribute to its toxicity. Special attention is paid to methods of TTX detection applicable to bacteria. Due to the complexity of toxin detection in TTX-producing bacteria, it is necessary to use several methods based on different methodological approaches. Issues crucial for further progress in detecting natural sources of TTX investigation are also considered.

  1. [Study on tetrodotoxin detection and toxic puffer fish identification of roasted fish fillet at the retail in Beijing and Qingdao].

    Science.gov (United States)

    Shen, Qing; Jiang, Tao; Li, Nan; Wang, Jiahui; Han, Chunhui; Zhang, Jing; Xu, Jin; Zhang, Dongfeng; Li, Fengqin

    2014-11-01

    The roasted fish fillet sample at the retail collected in Beijing and Qingdao were detected for TTX, and the TTX positive samples was analyzed for fish species identification. TTX was tested by EUSA method and the cytochrome c oxidase I (COI) genome of TTX-positive samples was extracted and identified by DNA barcode. Totally, 90 samples were tested by EUSA and 58 (64.4%) samples were positive for TTX with the levels ranging from 0.10 mg/kg to 63.81 mg/kg. Among the TTX positive samples, 24 (41.3%) were identified containing toxic puffer fish and 21 (87.5%) were Lagocephalus lunaris, the highly toxic puffer fish. Some roasted fish fillet samples obtained from the retail in two cities were positive for TTX and contained toxic puffer fish. Based on these results, we suggest that roasted fish fillet producers should prevent toxic puffer fish from mixing in the raw material and the I regulators should strengthen the TTX surveillance and product labeling supervision of roasted fish fillet.

  2. Tetrodotoxin Poisoning Due to Pufferfish and Gastropods, and Their Intoxication Mechanism

    Science.gov (United States)

    Noguchi, Tamao; Onuki, Kazue; Arakawa, Osamu

    2011-01-01

    Marine pufferfish generally contain a large amount of tetrodotoxin (TTX) in their skin and viscera, and have caused many incidences of food poisoning, especially in Japan. Edible species and body tissues of pufferfish, as well as their allowable fishing areas, are therefore clearly stipulated in Japan, but still 2 to 3 people die every year due to pufferfish poisoning. TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. Pufferfish become nontoxic when fed TTX-free diets in a closed environment in which there is no possible invasion of TTX-bearing organisms. On the other hand, TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe. In addition, TTX poisoning of dogs due to the ingestion of sea slugs was recently reported in New Zealand. TTX in these gastropods also seems to be exogenous; carnivorous large snails are intoxicated by eating toxic starfish, and necrophagous small-to-medium snails, the viscera of dead pufferfish after spawning. Close attention must be paid to the geographic expansion and/or diversification of TTX-bearing organisms, and to the sudden occurrence of other forms of TTX poisoning due to their ingestion. PMID:23724281

  3. An in silico perspective on the toxicodynamic of tetrodotoxin and analogues - A tool for supporting the hazard identification.

    Science.gov (United States)

    Dellafiora, Luca; Galaverna, Gianni; Dall'Asta, Chiara

    2017-11-01

    Tetrodotoxin (TTX) is a potent neurotoxin naturally found in terrestrial and marine animals targeting the voltage-gated sodium channels. Historically, TTX has raised food safety concerns mainly in the Asian countries due to the consumption of the typical pufferfish-derived delicacy fugu. However, the diffusion of TTX is getting wider today, reasonably threating in a close future a broader number of consumers than before. The understanding of TTX group toxicity is still incomplete as most of the analogues and metabolites found together with TTX are largely understudied. This prevents the establishment of a solid background for risk assessment and additional data have been claimed to timely foster the assessment of TTX toward a group-based approach. However, the high costs in sourcing TTX analogues make practically unfeasible the wide-scale assessment using experimental trials. The toxicological assessment in silico may succeed in extending data on compounds poorly affordable, hierarchizing compound to focus experiments and supporting the hazard identification. Therefore, the present work investigated the toxicodynamic of TTX, analogues and metabolites by using a molecular modeling approach. In the framework of the hazard identification, the model analyzed TTX analogues never tested before assessing qualitatively their potential toxicity in comparison to TTX. While the analogues from TTX bearing species appeared to be less toxic than TTX, some human metabolites showed a better interaction with the toxin binding site. Such results suggest that human metabolism may partially fail in preventing the interaction with the biological target. Therefore, the identification and assessment of human metabolites should be done to support the decision making process from a more informed perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Determination of tetrodotoxin and its analogs in the puffer fish Takifugu oblongus from Bangladesh by hydrophilic interaction chromatography and mass-spectrometric detection.

    Science.gov (United States)

    Diener, Marc; Christian, Bernd; Ahmed, M Sagir; Luckas, Bernd

    2007-11-01

    Tetrodotoxin (TTX) and its analogs (TTXs), widely distributed among marine as well as terrestrial animals, induce dangerous intoxications. These highly potential toxins are also known as the causative agent of puffer fish poisoning. A newly developed highly sensitive method for determination of TTXs based on hydrophilic interaction chromatography and mass-spectrometric detection is presented. TTX, anhydrotetrodotoxin, 11-deoxytetrodotoxin and trideoxytetrodotoxin were determined in separated tissues of Bangladeshi marine puffers, Takifugu oblongus. TTX was predominant in skin, muscle and liver, whereas trideoxytetrodotoxin preponderated in the ovary. The toxicity of the various tissues was determined by a mouse bioassay.

  5. Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1

    Directory of Open Access Journals (Sweden)

    Takuya Matsumoto

    2017-07-01

    Full Text Available This study examined the urinary excretion of tetrodotoxin (TTX modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK1. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA, l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH, and unaffected by 1-methyl-4-phenylpyridinium (MPP+, oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs and organic cation/carnitine transporters (OCTNs, partially transported by organic anion transporters (OATs and multidrug resistance-associated proteins (MRPs, and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs.

  6. Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates.

    Science.gov (United States)

    Calhoun, Dana M; Bucciarelli, Gary M; Kats, Lee B; Zimmer, Richard K; Johnson, Pieter T J

    2017-10-01

    The dermal glands of many amphibian species secrete toxins or other noxious substances as a defense strategy against natural enemies. Newts in particular possess the potent neurotoxin tetrodotoxin (TTX), for which the highest concentrations are found in species within the genus Taricha. Adult Taricha are hypothesized to use TTX as a chemical defense against vertebrate predators such as garter snakes (Thamnophis spp.). However, less is known about how TTX functions to defend aquatic-developing newt larvae against natural enemies, including trematode parasites and aquatic macroinvertebrates. Here we experimentally investigated the effects of exogenous TTX exposure on survivorship of the infectious stages (cercariae) of five species of trematode parasites that infect larval amphibians. Specifically, we used dose-response curves to test the sensitivity of trematode cercariae to progressively increasing concentrations of TTX (0.0 [control], 0.63, 3.13, 6.26, 31.32, and 62.64 nmol L-1) and how this differed among parasite species. We further compared these results to the effects of TTX exposure (0 and 1000 nmolL-1) over 24 h on seven macroinvertebrate taxa commonly found in aquatic habitats with newt larvae. TTX significantly reduced the survivorship of trematode cercariae for all species, but the magnitude of such effects varied among species. Ribeiroia ondatrae - which causes mortality and limb malformations in amphibians - was the least sensitive to TTX, whereas the kidney-encysting Echinostoma trivolvis was the most sensitive. Among the macroinvertebrate taxa, only mayflies (Ephemeroptera) showed a significant increase in mortality following exogenous TTX exposure, despite the use of a concentration 16x higher than the maximum used for trematodes. Our results suggest that maternal investment of TTX into larval newts may provide protection against certain trematode infections and highlight the importance of future work assessing the effects of newt toxicity on

  7. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes.

    Science.gov (United States)

    Nguyen, Tu Hoang Khue; Nguyen, Huu Ngoc; Nghe, Dat Van; Nguyen, Kim Hoang

    2015-01-01

    Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds.

  8. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes

    Directory of Open Access Journals (Sweden)

    Tu Hoang Khue Nguyen

    2015-01-01

    Full Text Available Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX. Thin layer chromatography (TLC and high performance lipid chromatography (HPLC were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp. and sea fish (Auxis thazard, respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds.

  9. Development of competitive indirect ELISA for the detection of tetrodotoxin and a survey of the distribution of tetrodotoxin in the tissues of wild puffer fish in the waters of south-east China.

    Science.gov (United States)

    Tao, J; Wei, W J; Nan, L; Lei, L H; Hui, H C; Fen, G X; Jun, L Y; Jing, Z; Rong, J

    2010-11-01

    A monoclonal antibody against tetrodotoxin (TTX) was produced from the hybridoma cell line T6D9, which was established by the fusion of Sp2/0 myeloma cells with spleen cells isolated from a Balb/c mouse immunized with the TTX-keyhole limpet hemocyanin (KLH) conjugate. This monoclonal antibody belongs to the IgG1 subclass; the affinity constant of the antibody is 2.4 × 10(-8) mol l(-1). The relative cross-reactivity of the antibody with TTX was 100%, but with saxitoxin, KLH and bovine serum albumin (BSA) it was less than 1%, respectively. The titre of the antibody in ascites was 6.4 × 10(6); the reference working concentration was 1:1.2 × 10(5). By using this monoclonal antibody, a competitive indirect enzyme-linked immunoabsorbant assay (ELISA) for the analysis of TTX was developed. The linear portion of the dose-response curve of TTX concentration was in range 5-500 ng ml(-1). The limit of detection was 5 ng ml(-1) according 10% inhibition with TTX to anti-TTX monoclonal antibody. The concentration of TTX inhibiting 50% of antibody binding was about 50 ng ml(-1). The recoveries from TTX spiked samples were 79.5-109.5%. In addition, the toxicity of some wild puffer fish specimens captured from south-east China and the Yangzi River in Jiangsu province was determined. The results indicate that the toxicity and toxin tissue distribution vary in different species of wild puffer fish.

  10. EVOLUTIONARY RESPONSE OF PREDATORS TO DANGEROUS PREY: PREADAPTATION AND THE EVOLUTION OF TETRODOTOXIN RESISTANCE IN GARTER SNAKES.

    Science.gov (United States)

    Motychak, Jeffrey E; Brodie, Edmund D; Iii, Edmund D Brodie

    1999-10-01

    Coevolutionary interactions typically involve only a few specialized taxa. The factors that cause some taxa and not others to respond evolutionarily to selection by another species are poorly understood. Preadaptation may render some species predisposed for evolutionary response to new pressures, whereas a lack of genetic variation may limit the evolutionary potential of other taxa. We evaluate these factors in the predator-prey interaction between toxic newts (Taricha granulosa) and their resistant garter snake predators (Thamnophis sirtalis). Using a bioassay of resistance to tetrodotoxin (TTX), the primary toxin in the prey, we examined phenotypic evolution in the genus Thamnophis. Reconstruction of ancestral character states suggests that the entire genus Thamnophis, and possibly natricine snakes in general, has slightly elevated TTX resistance compared to other lineages of snakes. While this suggests that T. sirtalis is indeed predisposed to evolving TTX resistance, it also indicates that the potential exists in sympatric congeners not expressing elevated levels of TTX resistance. We also detected significant family level variation for TTX resistance in a species of Thamnophis that does not exhibit elaborated levels of the trait. This finding suggests that evolutionary response in other taxa is not limited by genetic variability. In this predator-prey system, species and population differences in resistance appear to be largely determined by variation in the selective environment rather than preadaptation or constraint. © 1999 The Society for the Study of Evolution.

  11. Development of standardized methodology for identifying toxins in clinical samples and fish species associated with tetrodotoxin-borne poisoning incidents

    Directory of Open Access Journals (Sweden)

    Tai-Yuan Chen

    2016-01-01

    Full Text Available Tetrodotoxin (TTX is a naturally occurring toxin in food, especially in puffer fish. TTX poisoning is observed frequently in South East Asian regions. In TTX-derived food poisoning outbreaks, the amount of TTX recovered from suspicious fish samples or leftovers, and residual levels from biological fluids of victims are typically trace. However, liquid chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry methods have been demonstrated to qualitatively and quantitatively determine TTX in clinical samples from victims. Identification and validation of the TTX-originating seafood species responsible for a food poisoning incident is needed. A polymerase chain reaction-based method on mitochondrial DNA analysis is useful for identification of fish species. This review aims to collect pertinent information available on TTX-borne food poisoning incidents with a special emphasis on the analytical methods employed for TTX detection in clinical laboratories as well as for the identification of TTX-bearing species.

  12. Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.

    Science.gov (United States)

    Qiao, Guo-Fen; Li, Bai-Yan; Zhou, Yu-Hong; Lu, Yan-Jie; Schild, John H

    2009-01-01

    Persistent tetrodotoxin-resistant (TTX-R) Na(+) (Na(v)1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na(+) although the functional expression of this current was observed in the presence of PGE(2) or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na(+)). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na(+) currents were expressed in 9 out of 38 VANs bathed in 150 mM Na(+). The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV). This indicates that persistent TTX-R Na(+) channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

  13. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    Directory of Open Access Journals (Sweden)

    Christina Bognet

    2011-12-01

    Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

  14. Tetrodotoxin-Medicated Delay in Aconitine Toxicity: A Murder in Okinawa.

    Science.gov (United States)

    Ohno, Y

    2014-07-01

    Aconite (wolfsbane) plants, which belong to the genus Aconitum (Ranunculaceae family), contain highly toxic alkaloids, including aconitine, mesaconitine, hypaconitine, and jesaconitine, in all of their parts. The relevance of this plant material is illustrated by the case of a Japanese female who died suddenly in 1986 and was autopsied in Okinawa by the author. The detection in 1987 of Aconitum alkaloids in her blood using gas chromatography/selected ion monitoring (GC/SIM), which was newly developed for this case, demonstrated that she had died from aconite poisoning. Copyright © 2014 Central Police University.

  15. Rapid in vivo determination of tetrodotoxin in pufferfish (Fugu) muscle by solid-phase microextraction coupled to high-performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chen, Le; Qiu, Junlang; Tang, Yijia; Xu, Jianqiao; Huang, Shuyao; Liu, Yuan; Ouyang, Gangfeng

    2017-08-15

    Tetrodotoxin (TTX) is one of the most toxic substances of non-protein in nature. In present study, a rapid and sensitive method based on in vivo solid-phase microextraction (SPME) coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to detect the endogenous TTX in pufferfish (Fugu). Fiber evaluation experiments demonstrated that, compared with the commercial PDMS and PA fibers, the home-made electrospun PS@PDA-GA fibers exhibited much better extraction performance towards to TTX in water (120 times and 20 times, respectively), under the optimized conditions. Then, the home-made SPME fibers were employed to extract TTX in spiked homogeneous fish muscle samples, and a LC-MS-MS was used for the analysis. The reproducibilities (RSDs of inter and intra fiber were 12.1%, and 7.9% respectively), linear range (10-1000ngg-1, R2=0.9963) and sensitivity (the LOD was 2.3ngg-1) of the method were found to be excellent and satisfactory for further in vivo experiments. Especially the LOD of the established method is lower than the National Standard Method of China (GB/T 23217-2008, LOD 50ngg-1). Subsequently, the method was successfully applied to detect the TTX in the dorsal muscle of living pufferfish, and the accuracy was verified with traditional liquid extraction (LE) method. In general, this is the first study to detect TTX in pufferfish by in vivo sampling method, which provided a promising alternative method for the studies of TTX, and also advanced the implementation of SPME for more in vivo studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

    Directory of Open Access Journals (Sweden)

    Jaakko Haverinen

    2011-11-01

    Full Text Available Evolutionary origin and physiological significance of the tetrodotoxin (TTX resistance of the vertebrate cardiac Na+ current (INa is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey, three teleost fishes (crucian carp, burbot and rainbow trout, a clawed frog, a snake (viper and a bird (quail. In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L−1. In the snake heart, about 80% of the INa was TTX-resistant with EC50 value of 0.65 μmol·L−1, the rest being TTX-sensitive (EC50 = 0.5 nmol·L−1. Although TTX-resistance of the cardiac INa appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

  17. TETRODOTOXIN RESISTANCE IN GARTER SNAKES: AN EVOLUTIONARY RESPONSE OF PREDATORS TO DANGEROUS PREY.

    Science.gov (United States)

    Brodie, Edmund D; Brodie, Edmund D

    1990-05-01

    The use of the "arms race" analogy as a conceptualization of evolutionary predator-prey interactions has been criticized because of the lack of evidence that predators can and do adapt to increased antipredator ability of prey. We present evidence that the garter snake Thamnophis sirtalis has evolved resistance to tetrodotoxin (TTX) in response to the toxicity of the newt Taricha granulosa on which the snake feeds. A bioassay (locomotor performance before and after injection of TTX) was used to obtain repeated measures of resistance for individual snakes. We studied interpopulation and interspecific variation by comparing resistance in Thamnophis sirtalis from populations occurring sympatrically and allopatrically with Taricha granulosa, and in Thamnophis ordinoides (which does not feed on the newt) occurring sympatrically with Taricha granulosa. We also examined intrapopulation variation in TTX resistance using snakes from a population known to feed on Taricha granulosa. Resistance differed significantly among individuals and litters; repeatability and heritability estimates of the assay were significantly different from zero, demonstrating the potential for response to selection. The population of Thamnophis sirtalis that occurs with Taricha granulosa exhibited levels of resistance much greater than either of the other groups. These results suggest that the predator-prey arms race analogy may be applicable to this system. © 1990 The Society for the Study of Evolution.

  18. Gustatory Detection of Tetrodotoxin and Saxitoxin, and Its Competitive Inhibition by Quinine and Strychnine in Freshwater Fishes

    Directory of Open Access Journals (Sweden)

    Toshiaki J. Hara

    2011-11-01

    Full Text Available Fish detect extremely low levels of marine toxins tetrodotoxin (TTX and saxitoxin (STX via the specialized gustatory receptor(s. Physiological and pharmacological studies show that receptor(s for TTX and STX are distinct from those which detect feeding stimulant amino acids and bile acids, and that TTX and STX do not share the same receptor populations, while interacting with quinine and strychnine in a competitive fashion suggestive of an antidotal relationship.

  19. Marine Biotoxins: Occurrence, Toxicity, and Detection Methods

    Science.gov (United States)

    Asakawa, M.

    2017-04-01

    This review summarizes the role of marine organisms as vectors of marine biotoxins, and discusses the need for surveillance to protect public health and ensure the quality of seafood. I Paralytic shellfish poison (PSP) and PSP-bearing organisms-PSP is produced by toxic dinoflagellates species belonging to the genera Alexandrium, Gymnodinium, and Pyrodinium. Traditionally, PSP monitoring programs have only considered filter-feeding molluscs that concentrate these toxic algae, however, increasing attention is now being paid to higher-order predators that carry PSP, such as carnivorous gastropods and crustaceans. II. Tetrodotoxin (TTX) and TTX-bearing organisms - TTX is the most common natural marine toxin that causes food poisonings in Japan, and poses a serious public health risk. TTX was long believed to be present only in pufferfish. However, TTX was detected in the eggs of California newt Taricha torosa in 1964, and since then it has been detected in a wide variety of species belonging to several different phyla. In this study, the main toxic components in the highly toxic ribbon worm Cephalothrix simula and the greater blue-ringed octopus Hapalochlaena lunulata from Japan were purified and analysed.

  20. Isolation and structural determination of the first 8-epi-type tetrodotoxin analogs from the newt, Cynops ensicauda popei, and comparison of tetrodotoxin analogs profiles of this newt and the puffer fish, Fugu poecilonotus.

    Science.gov (United States)

    Kudo, Yuta; Yasumoto, Takeshi; Konoki, Keiichi; Cho, Yuko; Yotsu-Yamashita, Mari

    2012-03-01

    Identification of new tetrodotoxin (TTX) analogs from TTX-possessing animals might provide insight into its biosynthesis and metabolism. In this study, four new analogs, 8-epi-5,6,11-trideoxyTTX, 4,9-anhydro-8-epi-5,6,11-trideoxyTTX, 1-hydroxy-8-epi-5,6,11-trideoxyTTX, and 1-hydroxy-4,4a-anhydro-8-epi-5,6,11-trideoxyTTX, were isolated from the newt, Cynops ensicauda popei, and their structures were determined using spectroscopic methods. These are the first 8-epi-type analogs of TTX that have been found in a natural source. Furthermore, we examined the composition of the TTX analogs in this newt and in the ovary of the puffer fish, Fugu poecilonotus, using LC/MS. The results indicate that TTX and 11-deoxyTTX were present in both sources. However, 6-epiTTX and 8-epi-type analogs were detected only in the newt, while 5,6,11-trideoxyTTX was a specific and major analog in the puffer fish. Such considerable differences among analog compositions might reflect differences in the biosynthesis or metabolism of TTX between these animals.

  1. Isolation and Structural Determination of the First 8-epi-type Tetrodotoxin Analogs from the Newt, Cynops ensicauda popei, and Comparison of Tetrodotoxin Analogs Profiles of This Newt and the Puffer Fish, Fugu poecilonotus

    Directory of Open Access Journals (Sweden)

    Mari Yotsu-Yamashita

    2012-03-01

    Full Text Available Identification of new tetrodotoxin (TTX analogs from TTX-possessing animals might provide insight into its biosynthesis and metabolism. In this study, four new analogs, 8-epi-5,6,11-trideoxyTTX, 4,9-anhydro-8-epi-5,6,11-trideoxyTTX, 1-hydroxy-8-epi-5,6,11-trideoxyTTX, and 1-hydroxy-4,4a-anhydro-8-epi-5,6,11-trideoxyTTX, were isolated from the newt, Cynops ensicauda popei, and their structures were determined using spectroscopic methods. These are the first 8-epi-type analogs of TTX that have been found in a natural source. Furthermore, we examined the composition of the TTX analogs in this newt and in the ovary of the puffer fish, Fugu poecilonotus, using LC/MS. The results indicate that TTX and 11-deoxyTTX were present in both sources. However, 6-epiTTX and 8-epi-type analogs were detected only in the newt, while 5,6,11-trideoxyTTX was a specific and major analog in the puffer fish. Such considerable differences among analog compositions might reflect differences in the biosynthesis or metabolism of TTX between these animals.

  2. Toxin and species identification of toxic octopus implicated into food poisoning in Taiwan.

    Science.gov (United States)

    Wu, Ya-Jung; Lin, Chun-Lan; Chen, Chien-Hung; Hsieh, Cheng-Hong; Jen, Hsiao-Chin; Jian, Shi-Jie; Hwang, Deng-Fwu

    2014-12-01

    A food poisoning incident due to ingestion of unknown octopus occurred in Taipei in December, 2010. The serum and urine from victims (male 38 and 43 years old) were collected, determined the toxicity, and identified tetrodotoxin (TTX) by high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). It was found that only urine contained the trace of TTX. Then, two retained specimen (one without blue ring in the skin and another with small blue ring in the skin) were collected from victims and examined for the toxicity and toxin. Meanwhile, 6 specimens of octopus without blue ring in the skin and 4 specimens of octopus with blue ring in the skin were re-collected from the market. Both retained octopus samples were found to contain TTX. However, re-collected market's octopus without blue ring in the skin did not show to contain TTX the and was identified as Octopus aegina by using the analysis of cytochrome b gene (Cyt b) and cytochrome c oxidase subunit I gene (COI). Only octopus with blue ring in the skin contained TTX and was identified as Hapalochlaena fasciata by using the analysis of Cyt b and COI. Therefore, this octopus food poisoning was caused by toxic octopus H. fasciata and the causative agent was TTX. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Development and Single-Laboratory Validation of a Liquid Chromatography Tandem Mass Spectrometry Method for Quantitation of Tetrodotoxin in Mussels and Oysters.

    Science.gov (United States)

    Turner, Andrew D; Boundy, Michael J; Rapkova, Monika Dhanji

    2017-09-01

    In recent years, evidence has grown for the presence of tetrodotoxin (TTX) in bivalve mollusks, leading to the potential for consumers of contaminated products to be affected by Tetrodotoxin Shellfish Poisoning (TSP). A single-laboratory validation was conducted for the hydrophilic interaction LC (HILIC) tandem MS (MS/MS) analysis of TTX in common mussels and Pacific oysters-the bivalve species that have been found to contain TTXs in the United Kingdom in recent years. The method consists of a single-step dispersive extraction in 1% acetic acid, followed by a carbon SPE cleanup step before dilution and instrumental analysis. The full method was developed as a rapid tool for the quantitation of TTX, as well as for the associated analogs 4-epi-TTX; 5,6,11-trideoxy TTX; 11-nor TTX-6-ol; 5-deoxy TTX; and 4,9-anhydro TTX. The method can also be run as the acquisition of TTX together with paralytic shellfish toxins. Results demonstrated acceptable method performance characteristics for specificity, linearity, recovery, ruggedness, repeatability, matrix variability, and within-laboratory reproducibility for the analysis of TTX. The LOD and LOQ were fit-for-purpose in comparison to the current action limit for TTX enforced in The Netherlands. In addition, aspects of method performance (LOD, LOQ, and within-laboratory reproducibility) were found to be satisfactory for three other TTX analogs (11-nor TTX-6-ol, 5-deoxy TTX, and 4,9-anhydro TTX). The method was found to be practical and suitable for use in regulatory testing, providing rapid turnaround of sample analysis. Plans currently underway on a full collaborative study to validate a HILIC-MS/MS method for paralytic shellfish poisoning toxins will be extended to include TTX in order to generate international acceptance, ultimately for use as an alternative official control testing method should regulatory controls be adopted.

  4. Removal of toxin (tetrodotoxin) from puffer ovary by traditional fermentation.

    Science.gov (United States)

    Anraku, Kensaku; Nonaka, Kiku; Yamaga, Toshitaka; Yamamoto, Takatoshi; Shin, Min-Chul; Wakita, Masahito; Hamamoto, Ayaka; Akaike, Norio

    2013-01-18

    The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented "Nukazuke" and "Kasuzuke" ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I(Na)) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in "Nukazuke" and "Kasuzuke" ovaries decreased to 1/50-1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes" fresh muscle that is normally eaten. It was concluded that the fermented "Nukazuke" and "Kasuzuke" ovaries of puffer fish T. Stictonotus are safe and harmless as food.

  5. Removal of Toxin (Tetrodotoxin from Puffer Ovary by Traditional Fermentation

    Directory of Open Access Journals (Sweden)

    Norio Akaike

    2013-01-01

    Full Text Available The amounts of puffer toxin (tetrodotoxin, TTX extracted from the fresh and the traditional Japanese salted and fermented “Nukazuke” and “Kasuzuke” ovaries of Takifugu stictonotus (T. stictonotus were quantitatively analyzed in the voltage-dependent sodium current (INa recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in “Nukazuke” and “Kasuzuke” ovaries decreased to 1/50–1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes” fresh muscle that is normally eaten. It was concluded that the fermented “Nukazuke” and “Kasuzuke” ovaries of puffer fish T. Stictonotus are safe and harmless as food.

  6. Rapid screening of tetrodotoxin in urine and plasma of patients with puffer fish poisoning by HPLC with creatinine correction.

    Science.gov (United States)

    Yu, Chung-Him; Yu, Chun-Fai; Tam, Sidney; Yu, Peter Hoi-Fu

    2010-01-01

    A rapid and simple detection method for tetrodotoxin (TTX) in urine and plasma of patients with puffer fish poisoning was developed using commercially pre-packed solid-phase extraction (SPE) cartridges (C18 and weak cation exchange columns) and subsequent analyses by HPLC with UV detection. The detection limit of the standard TTX, TTX-spiked urine and plasma samples were all 10 ng/ml and the average TTX recovery in urine and plasma samples after SPE were 90.3 +/- 4.0 and 87.1 +/- 2.9%, respectively. It was noticed that the creatinine-adjusted urinary TTX levels obtained within the first 24 h of presentation apparently correlated much better with the severity of poisoning than the urinary TTX concentration without adjusting for variations in concomitant creatinine excretion.

  7. Effects of Tetrodotoxin on the Mammalian Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Thomas Zimmer

    2010-03-01

    Full Text Available The human genome encodes nine functional voltage-gated Na+ channels. Three of them, namely Nav1.5, Nav1.8, and Nav1.9, are resistant to nanomolar concentrations of tetrodotoxin (TTX; IC50 ≥ 1 μM. The other isoforms, which are predominantly expressed in the skeletal muscle and nervous system, are highly sensitive to TTX (IC50 ~ 10 nM. During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of those TTX sensitive isoforms are expressed in the mammalian heart. Whereas immunohistochemical and electrophysiological methods demonstrated functional expression in various heart regions, the physiological importance of those isoforms for cardiac excitation in higher mammals is still debated. This review summarizes our knowledge on the systemic cardiovascular effects of TTX in animals and humans, with a special focus on cardiac excitation and performance at lower concentrations of this marine drug. Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals.

  8. Changes in tetrodotoxin-resistant C-fibre activity during fatiguing isometric contractions in the rat.

    Directory of Open Access Journals (Sweden)

    Ivana Kalezic

    Full Text Available It is by now well established that tetrodotoxin-resistant (TTX-R afferent fibres from muscle in the rat exhibit a multisensitive profile, including nociception. TTX-R afferent fibres play an important role in motor control, via spinal and supraspinal loops, but their activation and function during muscle exercise and fatigue are still unknown. Therefore, the specific effect of isometric fatiguing muscle contraction on the responsiveness of TTX-R C-fibres has been investigated in this study. To quantify the TTX-R afferent input we recorded the cord dorsum potential (CDP, which is the result of the electrical fields set up within the spinal cord by the depolarisation of the interneurons located in the dorsal horn, activated by an incoming volley of TTX-R muscle afferents. The changes in TTX-R CDP size before, during and after fatiguing electrical stimulation of the gastrocnemius-soleus (GS muscle have been taken as a measure of TTX-R C-unit activation. At the end of the fatiguing protocol, following an exponential drop in force, TTX-R CDP area decreased in the majority of trials (9/14 to 0.75 ± 0.03% (mean ± SEM of the pre-fatigue value. Recovery to the control size of the TTX-R CDP was incomplete after 10 min. Furthermore, fatiguing trials could sensitise a fraction of the TTX-R C-fibres responding to muscle pinch. The results suggest a long-lasting activation of the TTX-R muscle afferents after fatiguing stimulation. The role of this behaviour in chronic muscle fatigue in connection with pain development is discussed. Accumulation of metabolites released into the interstitium during fatiguing stimulation might be one of the reasons underlying the C-fibres' long-lasting activation.

  9. Tetrodotoxin and paralytic shellfish poisons in gastropod species from Vietnam analyzed by high-performance liquid chromatography and liquid chromatography–tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Hsiao-Chin Jen

    2014-06-01

    Full Text Available Among marine toxins, tetrodotoxin (TTX and paralytic shellfish poisons (PSPs are known as notorious neurotoxins that induce serious food poisoning incidents in the Southeast Asia region. The aim of this study was to investigate whether TTX and PSP toxins are important issues of seafood safety. Paralytic toxicity was observed in mice exposed to 34 specimens from five species of gastropods using a PSP bioassay. Five species of gastropods, Natica vitellus, Natica tumidus, Oliva hirasei, Oliva lignaria, and Oliva annulata, were collected from the coastal seawaters in Nha Trang City, Vietnam, between August 2007 and October 2007. The average lethal potency of gastropod specimens was 90 ± 40 (mean ± standard deviation mouse units (MU for N. vitellus, 64 ± 19 MU for N. tumidus, 42 ± 28 MU for O. hirasei, 51 ± 17 MU for O. lignaria, and 39 ± 18 MU for O. annulata. All toxic extracts from the sample species were clarified using a C18 Sep-Pak solid-phase extraction column and a microcentrifuge filter prior to analysis. High-performance liquid chromatography coupled with fluorescence detection indicated that the toxins of the olive shell (O. hirasei, O. lignaria, and O. annulata were mainly composed of saxitoxin (STX (73–82%, gonyautoxin (GTX 2, 3 (12–22%, and minor levels of TTX (5–6%. The toxins of N. vitellus and N. tumidus were mainly composed of STX (76–81% and GTX 1, 4 (19–24%. Furthermore, liquid chromatography–tandem mass spectrometry analysis was used to verify the identity of the PSPs and TTX. Our evidence shows that these gastropods have novel toxin profiles.

  10. Selective suppression of in vitro electrographic seizures by low-dose tetrodotoxin: a novel anticonvulsant effect.

    Science.gov (United States)

    Burack, M A; Stasheff, S F; Wilson, W A

    1995-10-01

    Localized injections of 50 microM tetrodotoxin (TTX) in rat hippocampal slices blocked stimulus train-evoked electrographic seizures (EGSs) for several hours. Responses to single stimuli were minimally altered during TTX block of the EGSs. This selective reduction of epileptiform activity could result from general blockade of action potentials in an anatomically distinct group of neurons in the slice. To test this hypothesis, we systematically mapped TTX injection sites in the hippocampal slice, and found that TTX injections that blocked EGSs were nearly always located in or invaded CA2/3 stratum radiatum and/or stratum lacunosum-moleculare. A high degree of recurrent activity in this region contributes to both epileptiform activity and responses to single stimuli; hence our selective inhibition of EGSs suggests a more pharmacologically specific anticonvulsant effect of TTX. Consistent with this hypothesis, we found that low concentrations of TTX (5, 10, or 20 nM) in the perfusion medium blocked EGSs without decreasing the amplitude of extracellular responses to single stimuli. Polysynaptic activity and/or antidromic firing may be particularly vulnerable to TTX action on voltage-gated sodium channels, due to their lower the safety factor for action potential propagation. Selective reduction of this activity may disrupt the abnormal neuronal activity underlying EGSs.

  11. Isolation and identification of a new tetrodotoxin-producing bacterial species, Raoultella terrigena, from Hong Kong marine puffer fish Takifugu niphobles.

    Science.gov (United States)

    Yu, Vincent Chung-Him; Yu, Peter Hoi-Fu; Ho, Kin-Chung; Lee, Fred Wang-Fat

    2011-01-01

    Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01) was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX). Based on the Microbial Identification (MIDI) and 16S-23S rDNA internal transcribed spacer (ITS) phylogenetic analysis, the strain was identified as Raoultella terrigena. The TTX production ability of the strain was confirmed by mouse bioassay, ELISA and mass spectrometry (MALDI-TOF). Our results reiterate that the TTX found in puffer fish was likely produced by the associated bacteria and TTX are widely produced amongst a diversity of bacterial species.

  12. Isolation and Identification of a New Tetrodotoxin-Producing Bacterial Species, Raoultella terrigena, from Hong Kong Marine Puffer Fish Takifugu niphobles

    Directory of Open Access Journals (Sweden)

    Fred Wang-Fat Lee

    2011-11-01

    Full Text Available Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01 was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX. Based on the Microbial Identification (MIDI and 16S-23S rDNA internal transcribed spacer (ITS phylogenetic analysis, the strain was identified as Raoultella terrigena. The TTX production ability of the strain was confirmed by mouse bioassay, ELISA and mass spectrometry (MALDI-TOF. Our results reiterate that the TTX found in puffer fish was likely produced by the associated bacteria and TTX are widely produced amongst a diversity of bacterial species.

  13. Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and morphine-induced hyperalgesia

    Directory of Open Access Journals (Sweden)

    Chen J

    2012-11-01

    Full Text Available Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2 DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated. Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage

  14. No Evidence for a Culturable Bacterial Tetrodotoxin Producer in Pleurobranchaea maculata (Gastropoda: Pleurobranchidae and Stylochoplana sp. (Platyhelminthes: Polycladida

    Directory of Open Access Journals (Sweden)

    Lauren R. Salvitti

    2015-01-01

    Full Text Available Tetrodotoxin (TTX is a potent neurotoxin found in the tissues of many taxonomically diverse organisms. Its origin has been the topic of much debate, with suggestions including endogenous production, acquisition through diet, and symbiotic bacterial synthesis. Bacterial production of TTX has been reported in isolates from marine biota, but at lower than expected concentrations. In this study, 102 strains were isolated from Pleurobranchaea maculata (Opisthobranchia and Stylochoplana sp. (Platyhelminthes. Tetrodotoxin production was tested utilizing a recently developed sensitive method to detect the C9 base of TTX via liquid chromatography—mass spectrometry. Bacterial strains were characterized by sequencing a region of the 16S ribosomal RNA gene. To account for the possibility that TTX is produced by a consortium of bacteria, a series of experiments using marine broth spiked with various P. maculata tissues were undertaken. Sixteen unique strains from P. maculata and one from Stylochoplana sp. were isolated, representing eight different genera; Pseudomonadales, Actinomycetales, Oceanospirillales, Thiotrichales, Rhodobacterales, Sphingomonadales, Bacillales, and Vibrionales. Molecular fingerprinting of bacterial communities from broth experiments showed little change over the first four days. No C9 base or TTX was detected in isolates or broth experiments (past day 0, suggesting a culturable microbial source of TTX in P. maculata and Stylochoplana sp. is unlikely.

  15. Contactin regulates the current density and axonal expression of tetrodotoxin-resistant but not tetrodotoxin-sensitive sodium channels in DRG neurons.

    Science.gov (United States)

    Rush, Anthony M; Craner, Matthew J; Kageyama, Takashi; Dib-Hajj, Sulayman D; Waxman, Stephen G; Ranscht, Barbara

    2005-07-01

    Contactin, a glycosyl-phosphatidylinositol (GPI)-anchored predominantly neuronal cell surface glycoprotein, associates with sodium channels Nav1.2, Nav1.3 and Nav1.9, and enhances the density of these channels on the plasma membrane in mammalian expression systems. However, a detailed functional analysis of these interactions and of untested putative interactions with other sodium channel isoforms in mammalian neuronal cells has not been carried out. We examined the expression and function of sodium channels in small-diameter dorsal root ganglion (DRG) neurons from contactin-deficient (CNTN-/-) mice, compared to CNTN+/+ litter mates. Nav1.9 is preferentially expressed in isolectin B4 (IB4)-positive neurons and thus we used this marker to subdivide small-diameter DRG neurons. Using whole-cell patch-clamp recording, we observed a greater than two-fold reduction of tetrodotoxin-resistant (TTX-R) Nav1.8 and Nav1.9 current densities in IB4+ DRG neurons cultured from CNTN-/- vs. CNTN+/+ mice. Current densities for TTX-sensitive (TTX-S) sodium channels were unaffected. Contactin's effect was selective for IB4+ neurons as current densities for both TTX-R and TTX-S channels were not significantly different in IB4- DRG neurons from the two genotypes. Consistent with these results, we have demonstrated a reduction in Nav1.8 and Nav1.9 immunostaining on peripherin-positive unmyelinated axons in sciatic nerves from CNTN-/- mice but detected no changes in the expression for the two major TTX-S channels Nav1.6 and Nav1.7. These data provide evidence of a role for contactin in selectively regulating the cell surface expression and current densities of TTX-R but not TTX-S Na+ channel isoforms in nociceptive DRG neurons; this regulation could modulate the membrane properties and excitability of these neurons.

  16. Pyramidal cells of rodent presubiculum express a tetrodotoxin-insensitive Na+ current.

    Science.gov (United States)

    Fricker, Desdemona; Dinocourt, Céline; Eugène, Emmanuel; Wood, John N; Wood, John; Miles, Richard

    2009-09-01

    Presubicular neurons are activated physiologically by a specific preferred head direction. Here we show that firing in these neurones is characterized by action potentials with a large overshoot and a reduced firing frequency adaptation during repetitive firing. We found that a component of the sodium current of presubicular cells was not abolished by tetrodotoxin (TTX, 10 mum) and was activated at more depolarized voltages than TTX-sensitive currents. This inward current was completely abolished by the removal of external sodium, suggesting that sodium is the charge carrier of this TTX-insensitive (TTX-I) current. The channels responsible for the TTX-I sodium current seemed to be expressed at sites distant from the soma, giving rise to a voltage-dependent delay in current activation. The voltage required for half-maximal activation was 21 mV, and 36 mV for inactivation, which is similar to that reported for Na(V)1.8 sodium channels. However, the kinetics were considerably slower, with a time constant of current decay of 1.4 s. The current was not abolished in pyramidal cells from animals lacking either the Na(V)1.8 or the Na(V)1.9 subunit. This, possibly novel, TTX-I sodium current could contribute to the coding functions of presubicular neurons, specifically the maintained firing associated with signalling of a stable head position.

  17. Analytical Challenges: Determination of Tetrodotoxin in Human Urine and Plasma by LC-MS/MS

    Science.gov (United States)

    Leung, Kelvin Sze-Yin; Fong, Bonnie Mei-Wah; Tsoi, Yeuk-Ki

    2011-01-01

    Tetrodotoxin (TTX) is a powerful sodium channel blocker found in puffer fish and some marine animals. Cases of TTX poisoning most often result from puffer fish ingestion. Diagnosis is mainly from patient’s signs and symptoms or the detection of TTX in the leftover food. If leftover food is unavailable, the determination of TTX in the patient’s urine and/or plasma is essential to confirm the diagnosis. Although various methods for the determination of TTX have been published, most of them are for food tissue samples. Dealing with human urine and blood samples is much more challenging. Unlike in food, the amount of toxin in the urine and blood of a patient is generally extremely low; therefore a very sensitive method is required to detect it. In this regard, mass spectrometry (MS) methods are the best choice. Since TTX is a very polar compound, there will be lack of retention on conventional reverse-phase columns; use of ion pair reagent or hydrophilic interaction liquid chromatography (HILIC) can help solve this problem. The problem of ion suppression is another challenge in analyzing polar compound in biological samples. This review will discuss different MS methods and their pros and cons. PMID:22163187

  18. Analytical Challenges: Determination of Tetrodotoxin in Human Urine and Plasma by LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Yeuk-Ki Tsoi

    2011-11-01

    Full Text Available Tetrodotoxin (TTX is a powerful sodium channel blocker found in puffer fish and some marine animals. Cases of TTX poisoning most often result from puffer fish ingestion. Diagnosis is mainly from patient’s signs and symptoms or the detection of TTX in the leftover food. If leftover food is unavailable, the determination of TTX in the patient’s urine and/or plasma is essential to confirm the diagnosis. Although various methods for the determination of TTX have been published, most of them are for food tissue samples. Dealing with human urine and blood samples is much more challenging. Unlike in food, the amount of toxin in the urine and blood of a patient is generally extremely low; therefore a very sensitive method is required to detect it. In this regard, mass spectrometry (MS methods are the best choice. Since TTX is a very polar compound, there will be lack of retention on conventional reverse-phase columns; use of ion pair reagent or hydrophilic interaction liquid chromatography (HILIC can help solve this problem. The problem of ion suppression is another challenge in analyzing polar compound in biological samples. This review will discuss different MS methods and their pros and cons.

  19. Rapid screening and multi-toxin profile confirmation of tetrodotoxins and analogues in human body fluids derived from a puffer fish poisoning incident in New Caledonia.

    Science.gov (United States)

    Rambla-Alegre, Maria; Leonardo, Sandra; Barguil, Yann; Flores, Cintia; Caixach, Josep; Campbell, Katrina; Elliott, Christopher T; Maillaud, Claude; Boundy, Michael J; Harwood, D Tim; Campàs, Mònica; Diogène, Jorge

    2018-02-01

    In August 2014, a puffer fish poisoning incidence resulting in one fatality was reported in New Caledonia. Although tetrodotoxin (TTX) intoxication was established from the patients' signs and symptoms, the determination of TTX in the patient's urine, serum or plasma is essential to confirm the clinical diagnosis. To provide a simple cost-effective rapid screening tool for clinical analysis, a maleimide-based enzyme-linked immunosorbent assay (mELISA) adapted for the determination of TTX contents in human body fluids was assessed. The mELISA was applied to the analysis of urine samples from two patients and a response for the presence of TTX and/or structurally similar analogues was detected in all samples. The analysis by LC-MS/MS confirmed the presence of TTX but also TTX analogues (4-epiTTX, 4,9-anhydroTTX and 5,6,11-trideoxyTTX) in the urine. A change in the multi-toxin profile in the urine based on time following consumption was observed. LC-MS/MS analysis of serum and plasma samples also revealed the presence of TTX (32.9 ng/mL) and 5,6,11-trideoxyTTX (374.6 ng/mL) in the post-mortem plasma. The results provide for the first time the TTX multi-toxin profile of human samples from a puffer fish intoxication and clearly demonstrate the implication of TTX as the causative agent of the reported intoxication case. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Two critical residues in p-loop regions of puffer fish Na+ channels on TTX sensitivity.

    Science.gov (United States)

    Maruta, Satoshi; Yamaoka, Kaoru; Yotsu-Yamashita, Mari

    2008-03-01

    We previously showed that Asn-383 and Thr-1569 residues of p-loop regions in domains I and IV, respectively, of the puffer fish, Fugu pardialis, skeletal muscle Na(v) (fNa(v)1.4a), are anomalous to those of other species of TTX-sensitive Na(+) channels, where the aromatic residues of Phe or Tyr, and Gly are the counterparts [Yotsu-Yamashita, M., Nishimori, K., Nitanai, Y., Isemura, M., Sugimoto, A., Yasumoto, T., 2000. Binding properties of (3)H-PbTx-3 and (3)H-saxitoxin to brain membranes and to skeletal muscle membranes of puffer fish Fugu pardalis and the primary structure of a voltage-gated Na(+) channel alpha-subunit (fMNa1) from skeletal muscle of F. pardalis. Biochem. Biophys. Res. Commun. 267, 403-412]. The former was suggested to confer TTX resistance by using Y401N mutant of rNa(v)1.4 [Venkatesh, V., Lu, S.Q., Dandona, N., See, S.L., Benner, S., Soong, T.W., 2005. Genetic basis of tetrodotoxin resistance in pufferfishes. Curr. Biol. 15, 2069-2072]. The latter function remained to be elucidated. Thus, we further explored the function of these two residues, electrophysiologically, by evaluating the K(d) (dissociation constants) values of TTX for F385N, F385A, F385Q, G1718T, and F385N/G1718T mutants of rNa(v)1.2a, transiently expressed in HEK-293 cells. F385N caused 3000-fold increase of the K(d), while G1718T and F385N/G1718T caused 2- and 3-fold increases compared with those of WT and F385N, respectively, suggesting that G1718T further enhanced TTX resistivity caused by F385N. The K(d) for F385A and F385Q were 2- and 11-fold larger than that of F385N, respectively, suggesting that the longer side chain in the non-aromatic amino acid residue causes the larger decrease of TTX sensitivity. Despite drastic changes in the K(d), the mutations at F385 caused only small changes in the k(off) from that of WT, suggesting that the K(d) for TTX receptors are mainly determined by the k(on).

  1. New Gastropod Vectors and Tetrodotoxin Potential Expansion in Temperate Waters of the Atlantic Ocean

    Directory of Open Access Journals (Sweden)

    Vítor Vasconcelos

    2012-03-01

    Full Text Available Tetrodotoxin is a potent low weight marine toxin found in warm waters, especially of the Indian and Pacific Oceans. Intoxications are usually linked to the consumption of the puffer fish, although TTX was already detected in several different edible taxa. Benthic organisms such as mollusks and echinoderms, with different feeding habits, were collected monthly along the Portuguese coast from the summer of 2009 until the end of 2010. The extraction and analysis techniques were optimized and TTX and some analogues were detected for the first time in two intertidal gastropod species—Gibbula umbilicalis and Monodonta lineata by LC-MS/MS and UPLC-MS/MS. Although the levels are low, these findings suggest that monitoring of TTX and analogues in North Atlantic species should be implemented so as to detect potentially new toxin vectors and seasonal and/or geographical patterns.

  2. Development and validation of a maleimide-based enzyme-linked immunosorbent assay for the detection of tetrodotoxin in oysters and mussels

    NARCIS (Netherlands)

    Reverté, Laia; Rambla-Alegre, Maria; Leonardo, Sandra; Bellés, Carlos; Campbell, Katrina; Elliott, Christopher T.; Gerssen, Arjen; Klijnstra, Mirjam D.; Diogène, Jorge; Campàs, Mònica

    2018-01-01

    The recent detection of tetrodotoxins (TTXs) in puffer fish and shellfish in Europe highlights the necessity to monitor the levels of TTXs in seafood by rapid, specific, sensitive and reliable methods in order to protect human consumers. A previous immunoassay for TTX detection in puffer fish,

  3. Toxicity assessment for the horseshoe crab Carcinoscorpius rotundicauda collected from Cambodia.

    Science.gov (United States)

    Ngy, Laymithuna; Yu, Chun-Fai; Takatani, Tomohiro; Arakawa, Osamu

    2007-05-01

    In this study, we assessed the toxicity of the horseshoe crab Carcinoscorpius rotundicauda collected from Cambodia within two successive months during rainy (April-May) and dry (December-January) seasons, respectively. Toxicity assessments of the collected specimens by standard mouse bioassay showed marked individual variation, and their toxin profiles by liquid chromatography/mass spectrometry (LC/MS) revealed tetrodotoxin (TTX) was the main toxin while no paralytic shellfish toxins (PSTs) were detected. All specimens were toxic and the highest toxicity values were 315, 113, 60, 47, 44 and 38 mouse units (MU)/g in the tissues of hepatic caecum, egg, viscera, muscle, intestine and testis, respectively. Although the current findings showed that the Cambodian C. rotundicauda was a moderately toxic species, they are not suitable for human consumption due to their toxicity. To the best of our knowledge, this is the first scientific study on toxic marine seafood ever investigated in Cambodian territorial waters.

  4. Toxicity Assessment of the Xanthid Crab Demania cultripes from Cebu Island, Philippines

    Directory of Open Access Journals (Sweden)

    Manabu Asakawa

    2010-01-01

    Full Text Available Several cases of poisoning resulting in human fatalities and stemming from the ingestion of coral reef crabs have been reported from the Indo-Pacific region. We assessed the toxicity of the unidentified xanthid crab collected from the Camotes Sea off the eastern coast of Cebu Island, central Visayas region of Philippines from the food hygienic point of view. All seven specimens, which were identified with Demania cultripes, collected in 2006 were toxic to mice irrespective of the season of collection and induced paralytic symptoms typical of tetrodotoxin (TTX and paralytic shellfish poison (PSP. The activity was expressed in mouse unit (MU being defined as the amount of TTX to kill a 20 g ddY male mice in 30 min after i.p. injection. Toxicity scores for viscera and appendages of specimens were 18.2±16.0 (mean ± S.D. and 4.4±2.6 MU/g, respectively. The highest individual toxicity scores observed for viscera and appendages were 52.1 and 7.7 MU/g, respectively. The frequency of toxic samples was 100%. Toxin profiles as determined by high-performance liquid chromatography-fluorescent detection analysis (HPLC-FLD revealed that TTX was the main toxic principle accounting for about 90% of the total toxicity along with 4-epi TTX and 4,9-anhydroTTX. Furthermore, gas chromatography-mass spectrometry (GC-MS analysis revealed mass fragment ion peaks at m/z 376, 392 and 407, which were characteristic of the quinazoline skeleton (C9-base specific to TTX. In addition, only a small amount of PSP containing gonyautoxins1–4 and hydroxysaxitoxin was detected. To our knowledge, this is the first report presenting evidence of occurrence of TTX and PSP in the xanthid crab D. cultripes inhabiting waters surrounding Cebu Island. From food hygienic point of view, people in coastal areas should be warned of the potential hazard of this crab in order to prevent its intentional or accidental consumption.

  5. Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons.

    Science.gov (United States)

    Ramachandra, Renuka; McGrew, Stephanie Y; Baxter, James C; Kiveric, Esad; Elmslie, Keith S

    2012-10-01

    Muscle afferents are critical regulators of motor function (Group I and II) and cardiovascular responses to exercise (Group III and IV). However, little is known regarding the expressed voltage-dependent ion channels. We identified muscle afferent neurons in dorsal root ganglia (DRGs), using retrograde labeling to examine voltage-dependent sodium (Na(V)) channels. In patch-clamp recordings, we found that the dominant Na(V) current in the majority of identified neurons was insensitive to tetrodotoxin (TTX-R), with Na(V) current in only a few (14%) neurons showing substantial (>50%) TTX sensitivity (TTX-S). The TTX-R current was sensitive to a Na(V)1.8 channel blocker, A803467. Immunocytochemistry demonstrated labeling of muscle afferent neurons by a Na(V)1.8 antibody, which further supported expression of these channels. A portion of the TTX-R Na(V) current appeared to be noninactivating during our 25-ms voltage steps, which suggested activity of Na(V)1.9 channels. The majority of the noninactivating current was insensitive to A803467 but sensitive to extracellular sodium. Immunocytochemistry showed labeling of muscle afferent neurons by a Na(V)1.9 channel antibody, which supports expression of these channels. Further examination of the muscle afferent neurons showed that functional TTX-S channels were expressed, but were largely inactivated at physiological membrane potentials. Immunocytochemistry showed expression of the TTX-S channels Na(V)1.6 and Na(V)1.7 but not Na(V)1.1. Na(V)1.8 and Na(V)1.9 appear to be the dominant functional sodium channels in small- to medium-diameter muscle afferent neurons. The expression of these channels is consistent with the identification of these neurons as Group III and IV, which mediate the exercise pressor reflex.

  6. Diversity and Biosynthetic Potential of Culturable Microbes Associated with Toxic Marine Animals

    Directory of Open Access Journals (Sweden)

    Brett A. Neilan

    2013-08-01

    Full Text Available Tetrodotoxin (TTX is a neurotoxin that has been reported from taxonomically diverse organisms across 14 different phyla. The biogenic origin of tetrodotoxin is still disputed, however, TTX biosynthesis by host-associated bacteria has been reported. An investigation into the culturable microbial populations from the TTX-associated blue-ringed octopus Hapalochlaena sp. and sea slug Pleurobranchaea maculata revealed a surprisingly high microbial diversity. Although TTX was not detected among the cultured isolates, PCR screening identifiedsome natural product biosynthesis genes putatively involved in its assembly. This study is the first to report on the microbial diversity of culturable communities from H. maculosa and P. maculata and common natural product biosynthesis genes from their microbiota. We also reassess the production of TTX reported from three bacterial strains isolated from the TTX-containing gastropod Nassarius semiplicatus.

  7. LC/MS Analysis of Tetrodotoxin and Its Deoxy Analogs in the Marine Puffer Fish Fugu niphobles from the Southern Coast of Korea, and in the Brackishwater Puffer Fishes Tetraodon nigroviridis and Tetraodon biocellatus from Southeast Asia

    Directory of Open Access Journals (Sweden)

    Jun-Ho Jang

    2010-03-01

    Full Text Available Tetrodotoxin (TTX and its deoxy analogs, 5-deoxyTTX, 11-deoxyTTX, 6,11-dideoxyTTX, and 5,6,11-trideoxyTTX, were quantified in the tissues of three female and three male specimens of the marine puffer fish, Fugu niphobles, from the southern coast of Korea, and in the whole body of the brackishwater puffer fishes, Tetraodon nigroviridis (12 specimens and Tetrodon biocellatus (three specimens from Southeast Asia using LC/MS in single ion mode (SIM. Identification of these four deoxy analogs in the ovarian tissue of F. niphobles were further confirmed by LC/MS/MS. TTX and 5,6,11-trideoxyTTX were detected in all three puffer fish species as the major TTX analogs, similar to Japanese Fugu pardalis. While 6,11-dideoxyTTX was also found to be a major analog in almost all tissues of Korean F. niphobles, this analog was minor in the two Tetraodon species and Japanese F. pardalis. Among the tissues of F. niphobles, the concentrations of TTXs were highest in the ovaries (female and skin (female and male.

  8. LC/MS analysis of tetrodotoxin and its deoxy analogs in the marine puffer fish Fugu niphobles from the southern coast of Korea, and in the brackishwater puffer fishes Tetraodon nigroviridis and Tetraodon biocellatus from Southeast Asia.

    Science.gov (United States)

    Jang, Jun-Ho; Lee, Jong-Soo; Yotsu-Yamashita, Mari

    2010-03-31

    Tetrodotoxin (TTX) and its deoxy analogs, 5-deoxyTTX, 11-deoxyTTX, 6,11-dideoxyTTX, and 5,6,11-trideoxyTTX, were quantified in the tissues of three female and three male specimens of the marine puffer fish, Fugu niphobles, from the southern coast of Korea, and in the whole body of the brackishwater puffer fishes, Tetraodon nigroviridis (12 specimens) and Tetrodon biocellatus (three specimens) from Southeast Asia using LC/MS in single ion mode (SIM). Identification of these four deoxy analogs in the ovarian tissue of F. niphobles were further confirmed by LC/MS/MS. TTX and 5,6,11-trideoxyTTX were detected in all three puffer fish species as the major TTX analogs, similar to Japanese Fugu pardalis. While 6,11-dideoxyTTX was also found to be a major analog in almost all tissues of Korean F. niphobles, this analog was minor in the two Tetraodon species and Japanese F. pardalis. Among the tissues of F. niphobles, the concentrations of TTXs were highest in the ovaries (female) and skin (female and male).

  9. Extracted tetrodotoxin from puffer fish Lagocephalus lagocephalus ...

    African Journals Online (AJOL)

    Jane

    2011-08-03

    Aug 3, 2011 ... 2Marine Biotechnology and Biodiversity Laboratory, INSTM of Sfax, Tunisia. 3Animal Ecophysiology Laboratory ... The production of TTX in microbes such as Vibrio sp. from the xanthid crab Amphicteis floridus ... 2006) infers that TTX originates from marine bacteria and accumulates in TTX-bearing animals ...

  10. Detection of Tetrodotoxins in Puffer Fish by a Self-Assembled Monolayer-Based Immunoassay and Comparison with Surface Plasmon Resonance, LC-MS/MS, and Mouse Bioassay.

    Science.gov (United States)

    Reverté, Laia; de la Iglesia, Pablo; del Río, Vanessa; Campbell, Katrina; Elliott, Christopher T; Kawatsu, Kentaro; Katikou, Panagiota; Diogène, Jorge; Campàs, Mònica

    2015-11-03

    The increasing occurrence of puffer fish containing tetrodotoxin (TTX) in the Mediterranean could represent a major food safety risk for European consumers and threaten the fishing industry. The work presented herein describes the development of a new enzyme linked immunosorbent assay (mELISA) based on the immobilization of TTX through dithiol monolayers self-assembled on maleimide plates, which provides an ordered and oriented antigen immobilization and favors the antigen-antibody affinity interaction. The mELISA was found to have a limit of detection (LOD) of TTX of 0.23 mg/kg of puffer fish matrix. The mELISA and a surface plasmon resonance (SPR) immunosensor previously developed were employed to establish the cross-reactivity factors (CRFs) of 5,6,11-trideoxy-TTX, 5,11-deoxy-TTX, 11-nor-TTX-6-ol, and 5,6,11-trideoxy-4-anhydro-TTX, as well as to determine TTX equivalent contents in puffer fish samples. Results obtained by both immunochemical tools were correlated (R(2) = 0.977). The puffer fish samples were also analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the corresponding CRFs were applied to the individual TTX contents. Results provided by the immunochemical tools, when compared with those obtained by LC-MS/MS, showed a good degree of correlation (R(2) = 0.991 and 0.979 for mELISA and SPR, respectively). The mouse bioassay (MBA) slightly overestimated the CRF adjusted TTX content of samples when compared with the data obtained from the other techniques. The mELISA has been demonstrated to be fit for the purpose for screening samples in monitoring programs and in research activities.

  11. Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons

    OpenAIRE

    Liang, Jingyao; Liu, Xiaoyan; Zheng, Jianquan; Yu, Shengyuan

    2013-01-01

    Background Amitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present. Results Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manne...

  12. Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

    Science.gov (United States)

    Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

    2017-05-17

    Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve

  13. Differential gene expression profile in the liver of the marine puffer fish Takifugu rubripes induced by intramuscular administration of tetrodotoxin.

    Science.gov (United States)

    Matsumoto, Takuya; Ishizaki, Shoichiro; Nagashima, Yuji

    2011-02-01

    Marine puffer fish accumulate a high level of tetrodotoxin (TTX) in the liver and ovary, but the underlying mechanism of this toxification is unclear. To elucidate the genes related to toxification of the marine puffer fish, we examined the hepatic gene expression profile of the marine puffer fish Takifugu rubripes by suppression subtractive hybridization in response to the intramuscular administration of 0.50 mg TTX/kg body weight into the caudal muscle. The accumulation of TTX in the liver reached 68 ± 4% that of the administered dose within 12 h of administration. A total of 1048 clones from the subtracted cDNA libraries were successfully sequenced. The nucleotide sequence of 92 of the 1048 clones was identified as a hepcidin precursor. Reverse transcription-polymerase chain reaction experiments revealed that hepcidin precursors were highly expressed in the TTX-administered group. In addition, complement C3 (31 clones), serotransferrin (30 clones), apolipoprotein A-1 (14 clones), high temperature adaptation protein Wap65-2 (14 clones), complement C7 (12 clones), fibrinogen beta chain (12 clones), and 70 kDa heat-shock protein 4 (11 clones) were obtained. This study confirmed that the intramuscular administration of TTX increases the gene expression of the acute-phase response proteins in the liver of puffer fish T. rubripes. Copyright © 2010. Published by Elsevier Ltd.

  14. Effects of dragon's blood resin and its component loureirin B on tetrodotoxin-sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons.

    Science.gov (United States)

    Xiangming, Liu; Su, Chen; Shijin, Yin; Zhinan, Mei

    2004-08-01

    Using whole-cell patch clamp technique on the membrane of freshly isolated dorsal root ganglion (DRG) neurons, the effects of dragon's blood resin and its important component loureirin B on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium currents were observed. The results show that both blood resin and loureirin B could suppress TTX-S voltage-gated sodium currents in a dose-dependent way. The peak current amplitudes and the steady-state activation and inactivation curves are also made to shift by 0.05% blood resin and 0.2 mmol/L loureirin B. These results demonstrate that the effects of blood resin on TTX-S sodium current may contribute to loureirin B in blood resin. Perhaps the analgesic effect of blood resin is caused partly by loureirin B directly interfering with the nociceptive transmission of primary sensory neurons.

  15. Modulation of dragon's blood on tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and identification of its material basis for efficacy.

    Science.gov (United States)

    Liu, Xiangming; Chen, Su; Zhang, Yuxia; Zhang, Fan

    2006-06-01

    To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.

  16. Liquid Chromatography with a Fluorimetric Detection Method for Analysis of Paralytic Shellfish Toxins and Tetrodotoxin Based on a Porous Graphitic Carbon Column

    Directory of Open Access Journals (Sweden)

    Veronica Rey

    2016-06-01

    Full Text Available Paralytic shellfish toxins (PST traditionally have been analyzed by liquid chromatography with either pre- or post-column derivatization and always with a silica-based stationary phase. This technique resulted in different methods that need more than one run to analyze the toxins. Furthermore, tetrodotoxin (TTX was recently found in bivalves of northward locations in Europe due to climate change, so it is important to analyze it along with PST because their signs of toxicity are similar in the bioassay. The methods described here detail a new approach to eliminate different runs, by using a new porous graphitic carbon stationary phase. Firstly we describe the separation of 13 PST that belong to different groups, taking into account the side-chains of substituents, in one single run of less than 30 min with good reproducibility. The method was assayed in four shellfish matrices: mussel (Mytillus galloprovincialis, clam (Pecten maximus, scallop (Ruditapes decussatus and oyster (Ostrea edulis. The results for all of the parameters studied are provided, and the detection limits for the majority of toxins were improved with regard to previous liquid chromatography methods: the lowest values were those for decarbamoyl-gonyautoxin 2 (dcGTX2 and gonyautoxin 2 (GTX2 in mussel (0.0001 mg saxitoxin (STX·diHCl kg−1 for each toxin, decarbamoyl-saxitoxin (dcSTX in clam (0.0003 mg STX·diHCl kg−1, N-sulfocarbamoyl-gonyautoxins 2 and 3 (C1 and C2 in scallop (0.0001 mg STX·diHCl kg−1 for each toxin and dcSTX (0.0003 mg STX·diHCl kg−1 in oyster; gonyautoxin 2 (GTX2 showed the highest limit of detection in oyster (0.0366 mg STX·diHCl kg−1. Secondly, we propose a modification of the method for the simultaneous analysis of PST and TTX, with some minor changes in the solvent gradient, although the detection limit for TTX does not allow its use nowadays for regulatory purposes.

  17. Aptameric Recognition-Modulated Electroactivity of Poly(4-Styrenesolfonic Acid-Doped Polyaniline Films for Single-Shot Detection of Tetrodotoxin

    Directory of Open Access Journals (Sweden)

    Gertrude Fomo

    2015-09-01

    Full Text Available The work being reported is the first electrochemical sensor for tetrodotoxin (TTX. It was developed on a glassy carbon electrodes (C that was modified with poly(4-styrenesolfonic acid-doped polyaniline film (PANI/PSSA. An amine-end functionalized TTX-binding aptamer, 5′-NH2-AAAAATTTCACACGGGTGCCTCGGCTGTCC-3′ (NH2-Apt, was grafted via covalent glutaraldehyde (glu cross-linking. The resulting aptasensor (C//PANI+/PSSA-glu-NH2-Apt was interrogated by cyclic voltammetry (CV and electrochemical impedance spectroscopy (EIS in sodium acetate buffer (NaOAc, pH 4.8 before and after 30 min incubation in standard TTX solutions. Both CV and EIS results confirmed that the binding of the analyte to the immobilized aptamer modulated the electrochemical properties of the sensor: particularly the charge transfer resistance (Rct of the PANI+/PSSA film, which served as a signal reporter. Based on the Rct calibration curve of the TTX aptasensor, the values of the dynamic linear range (DLR, sensitivity and limit of detection (LOD of the sensor were determined to be 0.23–1.07 ng·mL−1 TTX, 134.88 ± 11.42 Ω·ng·mL−1 and 0.199 ng·mL−1, respectively. Further studies are being planned to improve the DLR as well as to evaluate selectivity and matrix effects in real samples.

  18. Toxicity of puffer fish: two species (Lagocephalus laevigatus, linaeus 1766 and Sphoeroides spengleri, Bloch 1785 from the Southeastern Brazilian coast

    Directory of Open Access Journals (Sweden)

    J. S. Oliveira

    2003-01-01

    Full Text Available In Brazil, where puffer fish are considered poisonous, there are few documented cases on human consumption and consequent poisoning. In this study, toxicity of two puffer fish species from the Brazilian coast was examined. Specimens of Sphoeroides spengleri and Lagocephalus laevigatus were caught in São Sebastião Channel (North coast of São Paulo State, Brazil between January 1996 and May 1997. Acidic ethanol extracts from muscle and skin plus viscera were tested for mice acute toxicity using the standard method of Kawabata. Polar extracts of S. spengleri showed high toxicity up to 946 MU/g. Extracts from L. laevigatus showed very low levels of toxicity, never exceeding 1.7 MU/g. All extracts from both species blocked amielinic nerve fiber evoked impulses of crustacean legs; this effect reverted on washing similar to the standard tetrodotoxin TTX. The aqueous extract solutions were partially purified using an ionic exchange column (Amberlit GC-50 followed by treatment with activated charcoal (Norit-A. The presence of TTX and their analogs in the semi-purified extracts were confirmed by HPLC and mass spectrometry (MALDI-TOF.

  19. Immunosensor array platforms based on self-assembled dithiols for the electrochemical detection of tetrodotoxins in puffer fish.

    Science.gov (United States)

    Reverté, Laia; Campbell, Katrina; Rambla-Alegre, Maria; Elliott, Christopher T; Diogène, Jorge; Campàs, Mònica

    2017-10-09

    The recent detection of tetrodotoxins (TTXs) in European fish and shellfish has emphasized the urgent need to develop specific, selective, rapid and easy-to-use methods for their detection to assess the potential risk posed to human health. For this purpose, a dithiol self-assembled monolayer (SAM)-based immunoassay previously performed on maleimide plates (mELISA) has been adapted to gold electrode arrays for the development of an electrochemical immunosensor for TTX. The electrochemical SAM-based immunosensor designed herein, provided an oriented, stable and spaced sensing platform for the determination of TTX, attaining a limit of detection of 2.6 ng mL -1 . The applicability of the biosensor array was demonstrated by the accurate quantifications obtained in the analysis of different tissues of several puffer fish species (Lagocephalus lagocephalus, L. sceleratus and Sphoeroides pachygaster) caught along the Mediterranean coast of Spain. The good agreements found between the TTX concentrations determined by the immunosensor array platforms and those determined by mELISA, surface Plasmon resonance (SPR) immunosensor and liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis, proved the feasibility of the approach. The electrochemical immunosensor enables the determination of TTXs at levels as low as 0.07 mg TTX equiv. kg -1 tissue, thus, well below the Japanese value of 2 mg TTX equiv. kg -1 tissue used as a criterion to consider puffer fish safe for consumption. Compared to the colorimetric SAM-based approach, the immunosensor array described herein shows promise towards the development of disposable, portable and compact analysis tools applicable in monitoring programs for the surveillance of fishery products. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A new lateral-flow immunochromatographic strip combined with quantum dot nanobeads and gold nanoflowers for rapid detection of tetrodotoxin.

    Science.gov (United States)

    Shen, Haicong; Xu, Fei; Xiao, Meng; Fu, Qiangqiang; Cheng, Zhenzhu; Zhang, Shiwei; Huang, Caihong; Tang, Yong

    2017-11-20

    Tetrodotoxin (TTX) is a potent, low molecular weight analyte that can lead to fatal poisoning and requires a sensitive, rapid detection method. Here, we have developed a competitive, lateral-flow immunochromatographic strip combined with quantum dot nanobeads (QDNBs) and gold nanoflowers (AuNFs). This approach is called turn-on C-LFICS and it meets all testing requirements. Subsequent analysis revealed that this turn-on C-LFICS was rapid (8 min), sensitive (LOD = 0.2 ng mL -1 ), and quantitative (DLR = 1.56-100 ng mL -1 ), and had a positive signal readout (based on fluorescence quenching effects) for TTX detection. Moreover, it had superior signal brightness and a low background interference signal when compared with previous methods. Finally, it can function free of interference from the sample matrix and has a demonstrated recovery range of 85.5% to 119.7% in spiked samples. Taken together, these results show that our turn-on C-LFICS is an effective detection tool for TTX or other small molecules.

  1. Simultaneous identification and quantification of tetrodotoxin in fresh pufferfish and pufferfish-based products using immunoaffinity columns and liquid chromatography/quadrupole-linear ion trap mass spectrometry

    Science.gov (United States)

    Guo, Mengmeng; Wu, Haiyan; Jiang, Tao; Tan, Zhijun; Zhao, Chunxia; Zheng, Guanchao; Li, Zhaoxin; Zhai, Yuxiu

    2017-07-01

    In this study, we established a comprehensive method for simultaneous identification and quantification of tetrodotoxin (TTX) in fresh pufferfish tissues and pufferfish-based products using liquid chromatography/quadrupole-linear ion trap mass spectrometry (LC-QqLIT-MS). TTX was extracted by 1% acetic acid-methanol, and most of the lipids were then removed by freezing lipid precipitation, followed by purification and concentration using immunoaffinity columns (IACs). Matrix effects were substantially reduced due to the high specificity of the IACs, and thus, background interference was avoided. Quantitation analysis was therefore performed using an external calibration curve with standards prepared in mobile phase. The method was evaluated by fortifying samples at 1, 10, and 100 ng/g, respectively, and the recoveries ranged from 75.8%-107%, with a relative standard deviation of less than 15%. The TTX calibration curves were linear over the range of 1-1 000 μg/L, with a detection limit of 0.3 ng/g and a quantification limit of 1 ng/g. Using this method, samples can be further analyzed using an information-dependent acquisition (IDA) experiment, in the positive mode, from a single liquid chromatography-tandem mass spectrometry injection, which can provide an extra level of confirmation by matching the full product ion spectra acquired for a standard sample with those from an enhanced product ion (EPI) library. The scheduled multiple reaction monitoring method enabled TTX to be screened for, and TTX was positively identified using the IDA and EPI spectra. This method was successfully applied to analyze a total of 206 samples of fresh pufferfish tissues and pufferfish-based products. The results from this study show that the proposed method can be used to quantify and identify TTX in a single run with excellent sensitivity and reproducibility, and is suitable for the analysis of complex matrix pufferfish samples.

  2. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    Science.gov (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  3. Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins.

    Science.gov (United States)

    Zhang, Min-Min; Wilson, Michael J; Gajewiak, Joanna; Rivier, Jean E; Bulaj, Grzegorz; Olivera, Baldomero M; Yoshikami, Doju

    2013-05-01

    Adult rat dorsal root ganglion (DRG) neurons normally express transcripts for five isoforms of the α-subunit of voltage-gated sodium channels: NaV 1.1, 1.6, 1.7, 1.8 and 1.9. Tetrodotoxin (TTX) readily blocks all but NaV 1.8 and 1.9, and pharmacological agents that discriminate among the TTX-sensitive NaV 1-isoforms are scarce. Recently, we used the activity profile of a panel of μ-conotoxins in blocking cloned rodent NaV 1-isoforms expressed in Xenopus laevis oocytes to conclude that action potentials of A- and C-fibres in rat sciatic nerve were, respectively, mediated primarily by NaV 1.6 and NaV 1.7. We used three μ-conotoxins, μ-TIIIA, μ-PIIIA and μ-SmIIIA, applied individually and in combinations, to pharmacologically differentiate the TTX-sensitive INa of voltage-clamped neurons acutely dissociated from adult rat DRG. We examined only small and large neurons whose respective INa were >50% and >80% TTX-sensitive. In both small and large neurons, the ability of the toxins to block TTX-sensitive INa was μ-TIIIA NaV 1-isoforms, co-expressed with various NaV β-subunits in X. laevis oocytes, were consistent: NaV 1.1, 1.6 and 1.7 could account for all of the TTX-sensitive INa , with NaV 1.1 NaV 1.6 NaV 1.7 for small neurons and NaV 1.7 NaV 1.1 NaV 1.6 for large neurons. Combinations of μ-conotoxins can be used to determine the probable NaV 1-isoforms underlying the INa in DRG neurons. Preliminary experiments with sympathetic neurons suggest that this approach is extendable to other neurons. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  4. Tetrodotoxin-sensitive α-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics.

    Science.gov (United States)

    Stoetzer, C; Doll, T; Stueber, T; Herzog, C; Echtermeyer, F; Greulich, F; Rudat, C; Kispert, A; Wegner, F; Leffler, A

    2016-06-01

    The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs.

  5. Activation of tetrodotoxin-resistant sodium channel NaV1.9 in rat primary sensory neurons contributes to melittin-induced pain behavior.

    Science.gov (United States)

    Yu, Yao-Qing; Zhao, Zhen-Yu; Chen, Xue-Feng; Xie, Fang; Yang, Yan; Chen, Jun

    2013-03-01

    Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in dorsal root ganglion (DRG) neurons play important roles in pathological pain. We recently reported that melittin, the major toxin of whole bee venom, induced action potential firings in DRG neurons even in the presence of a high concentration (500 nM) of TTX, indicating the contribution of TTX-R sodium channels. This hypothesis is fully investigated in the present study. After subcutaneous injection of melittin, NaV1.8 and NaV1.9 significantly upregulate mRNA and protein expressions, and related sodium currents also increase. Double immunohistochemical results show that NaV1.8-positive neurons are mainly medium- and small-sized, whereas NaV1.9-positive ones are only small-sized. Antisense oligodeoxynucleotides (AS ODNs) targeting NaV1.8 and NaV1.9 are used to evaluate functional significance of the increased expressions of TTX-R sodium channels. Behavioral tests demonstrate that AS ODN targeting NaV1.9, but not NaV1.8, reverses melittin-induced heat hypersensitivity. Neither NaV1.8 AS ODN nor NaV1.9 AS ODN affects melittin-induced mechanical hypersensitivity. These results provide previously unknown evidence that upregulation of NaV1.9, but not NaV1.8, in small-sized DRG neurons contributes to melittin-induced heat hypersensitivity. Furthermore, melittin-induced biological effect indicates a potential strategy to study properties of TTX-R sodium channels.

  6. Inhibition of tetrodotoxin-resistant sodium current in dorsal root ganglia neurons mediated by D1/D5 dopamine receptors.

    Science.gov (United States)

    Galbavy, William; Safaie, Elham; Rebecchi, Mario J; Puopolo, Michelino

    2013-11-28

    Dopaminergic fibers originating from area A11 of the hypothalamus project to different levels of the spinal cord and represent the major source of dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of catecholamines, is expressed in 8-10% of dorsal root ganglia (DRG) neurons, suggesting that dopamine may be released in the dorsal root ganglia. Dopamine has been shown to modulate calcium current in DRG neurons, but the effects of dopamine on sodium current and on the firing properties of small DRG neurons are poorly understood. The effects of dopamine and dopamine receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium current recorded from acutely dissociated small (diameter ≤ 25 μm) DRG neurons. Dopamine (20 μM) and SKF 81297 (10 μM) caused inhibition of TTX-R sodium current in small DRG neurons by 23% and 37%, respectively. In contrast, quinpirole (20 μM) had no effects on the TTX-R sodium current. Inhibition by SKF 81297 of the TTX-R sodium current was not affected when the protein kinase A (PKA) activity was blocked with the PKA inhibitory peptide (6-22), but was greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC inhibitory peptide (19-36), suggesting that activation of D1/D5 dopamine receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in small DRG neurons, but not D2 dopamine receptors, was confirmed by Western blotting and immunofluorescence analysis. In current clamp experiments, the number of action potentials elicited in small DRG neurons by current injection was reduced by ~ 30% by SKF 81297. We conclude that activation of D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated nociceptive neurons and dampens their intrinsic excitability by reducing the number of action potentials in response to stimulus. Increasing or decreasing levels of dopamine in the dorsal root ganglia may serve to adjust the sensitivity of

  7. Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis

    Directory of Open Access Journals (Sweden)

    Jie You

    2015-01-01

    Full Text Available OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future.

  8. Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons.

    Science.gov (United States)

    Szulczyk, Bartlomiej; Nurowska, Ewa

    2017-09-16

    Valproic acid is frequently prescribed and used to treat epilepsy, bipolar disorder and other conditions. However, the mechanism of action of valproic acid has not been fully elucidated. The aim of this study was to assess the influence of valproic acid (200 μM) on TTX-resistant sodium currents in mPFC pyramidal neurons. Valproic acid inhibited the maximal amplitude and did not change the activation parameters of TTX-resistant sodium currents. Moreover, valproic acid (2 μM and 200 μM) shifted the TTX-resistant sodium channel inactivation curve towards hyperpolarisation. In the presence of valproic acid, TTX-resistant sodium currents recovered from inactivation more slowly. Valproic acid did not influence the use-dependent blockade of TTX-resistant sodium currents. This study suggests that a potential new mechanism of the antiepileptic action of valproic acid is, among others, inhibition of TTX-resistant sodium currents. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum.

    Science.gov (United States)

    Campos, Rafael; Mónica, Fabíola Z; Rodrigues, Renata Lopes; Rojas-Moscoso, Julio Alejandro; Moreno, Ronilson Agnaldo; Cogo, José Carlos; de Oliveira, Marco Antonio; Antunes, Edson; De Nucci, Gilberto

    2017-01-01

    Reptiles are the first amniotes to develop an intromitent penis, however until now the mechanisms involved in the electrical field stimulation-induced contraction on corpora cavernosa isolated from Crotalus durissus terrificus were not investigated. Crotalus and rabbit corpora cavernosa were mounted in 10 mL organ baths for isometric tension recording. Electrical field stimulation (EFS)-induced contractions were performed in presence/absence of phentolamine (10 μM), guanethidine (30 μM), tetrodotoxin (1 μM and 1mM), A-803467 (10 μM), 3-iodo-L-Tyrosine (1 mM), salsolinol (3 μM) and a modified Krebs solution (equimolar substitution of NaCl by N-methyl-D-glucamine). Immuno-histochemistry for tyrosine hydroxylase was also performed. Electrical field stimulation (EFS; 8 Hz and 16 Hz) caused contractions in both Crotalus and rabbit corpora cavernosa. The contractions were abolished by previous incubation with either phentolamine or guanethidine. Tetrodotoxin (1 μM) also abolished the EFS-induced contractions of rabbit CC, but did not affect EFS-induced contractions of Crotalus CC. Addition of A-803467 (10 μM) did not change the EFS-induced contractions of Crotalus CC but abolished rabbit CC contractions. 3-iodo-L-Tyrosine and salsolinol had no effect on EFS-induced contractions of Crotalus CC and Rabbit CC. Replacement of NaCl by N- Methyl-D-glucamine (NMDG) abolished EFS-induced contractions of rabbit CC, but did not affect Crotalus CC. The presence of tyrosine hydroxylase was identified in endothelial cells only of Crotalus CC. Since the EFS-induced contractions of Crotalus CC is dependent on catecholamine release, insensitive to TTX, insensitive to A803467 and to NaCl replacement, it indicates that the source of cathecolamine is unlikely to be from adrenergic terminals. The finding that tyrosine hydroxylase is present in endothelial cells suggests that these cells can modulate Crotalus CC tone.

  10. Differential effects of Tityus bahiensis scorpion venom on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents.

    Science.gov (United States)

    Moraes, Eder R; Kalapothakis, Evanguedes; Naves, Lígia A; Kushmerick, Christopher

    2011-01-01

    We examined modification of sodium channel gating by Tityus bahiensis scorpion venom (TbScV), and compared effects on native tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents from rat dorsal root ganglion neurons and cardiac myocytes. In neurons, TbScV dramatically reduced the rate of sodium current inactivation, increased current amplitude, and caused a negative shift in the voltage-dependence of activation and inactivation of tetrodotoxin-sensitive channels. Enhanced activation of modified sodium channels was independent of a depolarizing prepulse. We identified two components of neuronal tetrodotoxin-resistant current with biophysical properties similar to those described for NaV1.8 and NaV1.9. In contrast to its effects on neuronal tetrodotoxin-sensitive current, TbScV caused a small decrease in neuronal tetrodotoxin-resistant sodium current amplitude and the gating modifications described above were absent. A third tetrodotoxin-resistant current, NaV1.5 recorded in rat cardiac ventricular myocytes, was inhibited approximately 50% by TbScV, and the remaining current exhibited markedly slowed activation and inactivation. In conclusion, TbScV has very different effects on different sodium channel isoforms. Among the neuronal types, currents resistant to tetrodotoxin are also resistant to gating modification by TbScV. The cardiac tetrodotoxin-resistant current has complex sensitivity that includes both inhibition of current amplitude and slowing of activation and inactivation.

  11. Effect of Tetrodotoxin from Crude Puffer Fish (Tetraodon fluviatilis Liver Extract on Intracellular Calcium Level and Apoptosis of HeLa Cell Culture

    Directory of Open Access Journals (Sweden)

    Natanael Untario

    2017-01-01

    Full Text Available Cervical cancer is the third most commonly diagnosed cancer and fourth leading cause of women death with 8% of total death caused by cancer in women in 2008. Tetrodotoxin (TTX is a potent neurotoxin found in inner organs puffer fish, with the specific mechanism of sodium channel blocking, and widely used for research purposes. Previous reports claimed that TTX has the capability of inhibiting the metastatic process of cancer and apoptotic effect. Studies also show that apoptosis is a process involving the increase of intracellular calcium level, yet the connection between TTX and increase of intracellular calcium level, therefore triggering apoptosis, has not been established. This is an experimental study with post test only control group design, carried out by exposing HeLa cell culture to a crude liver extract of a puffer fish species, Tetraodon fluviatilis. Crude puffer fish liver extract is administered into HeLa cell culture well in different concentrations 10-4, 10-2, and 10-1. Intracellular calcium level and apoptosis were then measured after 18 hours of incubation. Measurements of intracellular calcium level were done by using CLSM with Fura-2AM staining, and apoptosis by using flowcytometry with Annexin V/PI.  The result shows that there is a significant difference between samples both in intracellular calcium (p < 0.05 and apoptosis (p < 0,05. Both intracellular calcium and apoptosis levels are proportional to liver fish extract concentration. Pearson’s correlation test shows correlation between treatment and intracellular calcium levels (p = 0.000, between treatment and apoptosis (p = 0.002, but not between intracellular calcium and apoptosis (p = 0.05. These results suggest that TTX induces an increase in intracellular calcium level and apoptosis, but calcium pathway is not the sole cause of the apoptosis.

  12. Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons.

    Science.gov (United States)

    Liang, Jingyao; Liu, Xiaoyan; Zheng, Jianquan; Yu, Shengyuan

    2013-06-22

    Amitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present. Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manner and had an IC50 of 15.16 μM in acute isolated trigeminal ganglion (TG) neurons of the rats. 10 μM AMI significantly shifted the steady-state inactivation of Nav1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 μM AMI caused a use-dependent blockade of Nav1.9 currents elicited by 60 pulses at 1 Hz. These data suggest that AMI is a state-selective blocker of Nav1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines.

  13. Development and validation of a maleimide-based enzyme-linked immunosorbent assay for the detection of tetrodotoxin in oysters and mussels.

    Science.gov (United States)

    Reverté, Laia; Rambla-Alegre, Maria; Leonardo, Sandra; Bellés, Carlos; Campbell, Katrina; Elliott, Christopher T; Gerssen, Arjen; Klijnstra, Mirjam D; Diogène, Jorge; Campàs, Mònica

    2018-01-01

    The recent detection of tetrodotoxins (TTXs) in puffer fish and shellfish in Europe highlights the necessity to monitor the levels of TTXs in seafood by rapid, specific, sensitive and reliable methods in order to protect human consumers. A previous immunoassay for TTX detection in puffer fish, based on the use of self-assembled monolayers (SAMs) for the immobilization of TTX on maleimide plates (mELISA), has been modified and adapted to the analysis of oyster and mussel samples. Changing dithiol for cysteamine-based SAMs enabled reductions in the assay time and cost, while maintaining the sensitivity of the assay. The mELISA showed high selectivity for TTX since the antibody did not cross-react with co-occurring paralytic shellfish poisoning (PSP) toxins and no interferences were observed from arginine (Arg). Moreover, TTX-coated maleimide plates stored for 3 months at -20°C and 4°C were stable, thus when pre-prepared, the time to perform the assay is reduced. When analyzing shellfish samples, matrix effects and toxin recovery values strongly depended on the shellfish type and the sample treatment. Blank oyster extracts could be directly analyzed without solid-phase extraction (SPE) clean-up, whereas blank mussel extracts showed strong matrix effects and SPE and subsequent solvent evaporation were required for removal. However, the SPE clean-up and evaporation resulted in toxin loss. Toxin recovery values were taken as correction factors (CFs) and were applied to the quantification of TTX contents in the analysis of naturally-contaminated shellfish samples by mELISA. The lowest effective limits of detection (eLODs) were about 20 and 50µg/kg for oyster extracts without and with SPE clean-up, respectively, and about 30µg/kg for mussel extracts with both protocols, all of them substantially below the eLOD attained in the previous mELISA for puffer fish (230µg/kg). Analysis of naturally-contaminated samples by mELISA and comparison with LC-MS/MS quantifications

  14. Paralytic complications of puffer fish (tetrodotoxin) poisoning.

    Science.gov (United States)

    Ahasan, H A M N; Mamun, A A; Karim, S R; Bakar, M A; Gazi, E A; Bala, C S

    2004-02-01

    Puffer fish is available in Bangladesh and is occasionally eaten by some people. Ignorance regarding its proper cooking process may lead to serious health hazards, including fatality. An unusual catastrophic event happened recently in Khulna, Bangladesh that drew nationwide attention. Eight families were affected. Thirty-seven patients were admitted with a history of consumption of puffer fish. Peri-oral paraesthesia (24), weakness of both lower limbs (22), paraesthesia all over the body (18), headache (15), difficulty in respiration (14), nausea and vomiting (8), blurring of vision (7), and vertigo (6) were common clinical presentations. Twenty-two patients developed ascending paralysis of limbs and involved the respiratory muscles in 17 patients. Eight patients died due to respiratory failure while the rest improved. Health personnel should have sufficient knowledge regarding the clinical manifestations, complications and management of puffer fish poisoning. During its preparation, organs that contain the highest level of tetrodotoxin should be removed. Since there is no specific treatment, people should be made aware of the potential risk of eating puffer fish, about the warning symptoms and signs of puffer fish poisoning, and when to seek medical help.

  15. Tetrodotoxin-resistant voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 are expressed in the retina.

    Science.gov (United States)

    O'Brien, Brendan J; Caldwell, John H; Ehring, George R; Bumsted O'Brien, Keely M; Luo, Songjiang; Levinson, S Rock

    2008-06-20

    Voltage-gated sodium channels (VGSCs) are one of the fundamental building blocks of electrically excitable cells in the nervous system. These channels are responsible for the generation of action potentials that are required for the communication of neuronal signals over long distances within a cell. VGSCs are encoded by a family of nine genes whose products have widely varying biophysical properties. In this study, we have detected the expression of two atypical VGSCs (Na(v)1.8 and Na(v)1.9) in the retina. Compared with more common VGSCs, Na(v)1.8 and Na(v)1.9 have unusual biophysical and pharmacological properties, including persistent sodium currents and resistance to the canonical sodium channel blocker tetrodotoxin (TTX). Our molecular biological and immunohistochemical data derived from mouse (Mus musculus) retina demonstrate expression of Na(v)1.8 by retinal amacrine and ganglion cells, whereas Na(v)1.9 is expressed by photoreceptors and Müller glia. The fact that these channels exist in the central nervous system (CNS) and exhibit robust TTX resistance requires a re-evaluation of prior physiological, pharmacological, and developmental data in the visual system, in which the diversity of VGSCs has been previously underestimated. (c) 2008 Wiley-Liss, Inc.

  16. Association between tetrodotoxin resistant channels and lipid rafts regulates sensory neuron excitability.

    Directory of Open Access Journals (Sweden)

    Alessandro Pristerà

    Full Text Available Voltage-gated sodium channels (VGSCs play a key role in the initiation and propagation of action potentials in neurons. Na(V1.8 is a tetrodotoxin (TTX resistant VGSC expressed in nociceptors, peripheral small-diameter neurons able to detect noxious stimuli. Na(V1.8 underlies the vast majority of sodium currents during action potentials. Many studies have highlighted a key role for Na(V1.8 in inflammatory and chronic pain models. Lipid rafts are microdomains of the plasma membrane highly enriched in cholesterol and sphingolipids. Lipid rafts tune the spatial and temporal organisation of proteins and lipids on the plasma membrane. They are thought to act as platforms on the membrane where proteins and lipids can be trafficked, compartmentalised and functionally clustered. In the present study we investigated Na(V1.8 sub-cellular localisation and explored the idea that it is associated with lipid rafts in nociceptors. We found that Na(V1.8 is distributed in clusters along the axons of DRG neurons in vitro and ex vivo. We also demonstrated, by biochemical and imaging studies, that Na(V1.8 is associated with lipid rafts along the sciatic nerve ex vivo and in DRG neurons in vitro. Moreover, treatments with methyl-β-cyclodextrin (MβCD and 7-ketocholesterol (7KC led to the dissociation between rafts and Na(V1.8. By calcium imaging we demonstrated that the lack of association between rafts and Na(V1.8 correlated with impaired neuronal excitability, highlighted by a reduction in the number of neurons able to conduct mechanically- and chemically-evoked depolarisations. These findings reveal the sub-cellular localisation of Na(V1.8 in nociceptors and highlight the importance of the association between Na(V1.8 and lipid rafts in the control of nociceptor excitability.

  17. A Competitive Displacement Assay to Detect Saxitoxin and Tetrodotoxin

    Science.gov (United States)

    1983-12-09

    TTX, found in the ovaries, eggs, and liver of the puffer fish , is a public health concern only in Japan where puffer fish is regarded as a delicacy...B. (1977) J. Fish . Res. Boird Can. 314, 559-563. 18. MoFarren, E. F., Schantz, E. J., Campbell, J. E., and Lewis, K. H. (1959) J. Anr7ioc- Off. Acr

  18. Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats.

    Science.gov (United States)

    Black, Joel A; Cummins, Theodore R; Yoshimura, Naoki; de Groat, William C; Waxman, Stephen G

    2003-02-14

    Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) neurons. The urinary bladder is innervated by small afferent neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder afferent neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder afferent neurons, while Na(v)1.9 is expressed in non-bladder afferent neurons but is rarely observed in bladder afferent neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder afferents, but no change in the expression of Na(v)1.8 in non-bladder afferent neurons. Both bladder and non-bladder afferent neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder afferent neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these neurons following spinal cord injury.

  19. Antinociceptive Effects of AGAP, a Recombinant Neurotoxic Polypeptide: Possible Involvement of the Tetrodotoxin-Resistant Sodium Channels in Small Dorsal Root Ganglia Neurons

    Science.gov (United States)

    Li, Chun-Li; Liu, Xi-Fang; Li, Gui-Xia; Ban, Meng-qi; Chen, Jian-Zhao; Cui, Yong; Zhang, Jing-Hai; Wu, Chun-Fu

    2016-01-01

    Antitumor-analgesic peptide (AGAP) is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG) neurons. The results showed that AGAP (3–1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R) sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide. PMID:28066245

  20. Antinociceptive effects of AGAP, a recombinant neurotoxic polypeptide: Possible involvement of the tetrodotoxin-resistant sodium channels in small dorsal root ganglia neurons

    Directory of Open Access Journals (Sweden)

    Li Chunli

    2016-12-01

    Full Text Available Antitumor-analgesic peptide(AGAP)is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG neurons. The results showed that AGAP (3-1000 nM inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide.

  1. Efficiency of a rapid test for detection of tetrodotoxin in puffer fish.

    Science.gov (United States)

    Thattiyaphong, Aree; Unahalekhaka, Jirapa; Mekha, Nanthawan; Nispa, Wansatip; Kluengklangdon, Panawan; Rojanapantip, Laddawan

    2014-01-01

    The selling and importing of puffer fish species and their products was banned in Thailand in 2002, because of possible neurotoxic effects. However, the sale of their flesh is still happening in Thai markets. Standard methods for toxin quantification (HPLC and LC-MS) have significant limitations, therefore a lateral flow, immuno-chromatographic test (TTX-IC) was developed as a tool for rapid detection of toxin. A total of 750 puffer fishes (387 Lagocephalus lunaris(LL), and 363 Lagocephalus spadiceus (LS)) and 100 edible fishes were caught in Thailand from June 2011-February 2012. Screening of TTX from their flesh by TTX-IC revealed that 69 samples (17.8%) of LL possessed TTX at dangerous levels but LS and edible fishes did not. A selected 339 samples were quantified by LC-MS/MS, showing 50 LL possessed TTX at dangerous levels. Comparison of results with LC-MS/MS showed the TTX-IC to have 94.0% sensitivity and 92.4% specificity. The TTX-IC will be a useful tool for TTX screening of a large number of samples, reducing the testing required by LC-MS/MS, thus reducing costs. All positive cases found should be confirmed by standard methods.

  2. PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins.

    Science.gov (United States)

    Rush, Anthony M; Waxman, Stephen G

    2004-10-15

    Inflammation caused by tissue damage results in pain, reflecting an increase in excitability of the primary afferent neurons innervating the area. There is some evidence to suggest that altered function of voltage-gated sodium channels is responsible for the hyperexcitability produced by inflammatory agents, possibly acting through G-proteins, but the role of different channel subtypes has not been fully explored. The tetrodotoxin-resistant (TTX-R) sodium channel Na(v)1.9 is expressed selectively in C- and A-fibre nociceptive-type units and is upregulated by G-protein activation. In this study, we examined the effects of the inflammatory agent prostaglandin-E(2) (PGE(2)) on Na(v)1.9 current in both Na(v)1.8-null and wild-type (WT) mice and explored the role of specific G-proteins in modulation. PGE(2) caused a twofold increase in Na(v)1.9 current (pchannels by 12 mV. No differences in the activation and inactivation kinetics could be detected. The increase in current was blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of G(i/o) but not G(s) subunits. Our data indicate that Na(v)1.9 current can be increased during inflammation via a G-protein dependent mechanism and suggest that this could contribute to the regulation of electrogenesis in dorsal root ganglia (DRG) neurons.

  3. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    Directory of Open Access Journals (Sweden)

    Nélida María Conejo

    Full Text Available Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions.

  4. Co-occurrence of tetrodotoxin and saxitoxin in Cambodian marine ...

    African Journals Online (AJOL)

    The toxicity and toxin profiles of the marine pufferfish Takifugu oblongus were investigated from fish collected from Sihanouk Ville, one of the main regions where pufferfish poisonings (PFP) have occurred in Cambodia. Standard mouse bioassay revealed that all specimens collected were toxic, and their toxicities were ...

  5. [Investigating the toxicity characteristics of Nassarius Sp. in Ningbo City].

    Science.gov (United States)

    Xu, Jingye; Xu, Guozhang; Ye, Luming; Qin, Pinzhang; Hu, Danbiao; Yan, Peng; Jin, Chunguang; Yu, Mei

    2010-07-01

    To study the type, distribution, the growth and decline of toxins in Nassarius Sp. and the source of toxins to acquire the basis for the control of Nassarius Sp. poisonings. The toxicity of Nassarius Sp. was detected by mouse bioassay. The saxitoxin (STX), gonyau toxin (GTX), and tetrodo toxin (TTX) were detected by ELISA and HPLC. Sixty-three poisonous Nassarius Sp. were identified in 127 samples collected from long-term monitoring sites. The detection rate was 49.6%. The detection rate of poisonous Nassarius Sp. was different in varies habitats (P Nassa succincta A. Adams and Niotha livescens were high. The toxins of Nassarius Sp. in Ningbo City were composed of TTX, STX or GTX, or both TTX and STX. The surveillance proved that some toxins present in Nassarius Sp. in Ningbo City. Poisoning could be caused by eating Nassarius Sp.

  6. Toxicity and toxin identification in Colomesus asellus, an Amazonian (Brazil) freshwater puffer fish.

    Science.gov (United States)

    Oliveira, Joacir Stolarz; Fernandes, Solange Cristina Rego; Schwartz, Carlos Alberto; Bloch, Carlos; Melo, Jorge Alex Taquita; Rodrigues Pires, Osmindo; de Freitas, José Carlos

    2006-07-01

    Toxicity and toxin identification in Colomesus asellus, an Amazonian (Brazil) freshwater puffer fish. By using four different techniques--mouse bioassay, ELISA, HPLC and mass spectrometry-we evaluated the toxicity in the extracts of C. asellus, a freshwater puffer fish from the rivers of the Amazon, and identified for the first time the components responsible for its toxicity. The T20G10 monoclonal antibody raised against TTX, and employed in an indirect competitive enzyme immunoassay, showed very low affinity for the C. asellus extracts, indicating that TTX and its analogs are not the main toxic components of the extracts. This antibody was efficient in detecting presence of TTX in a total extract of Sphoeroides spengleri, which is one of the most toxic puffer fish found in the Atlantic coast. Extracts of C. asellus were toxic when administered intraperitonially into mice with an average toxicity of 38.6+/-12 mouse unit (MU)/g, while HPLC analysis indicated a lower toxin content (7.6+/-0 5MU/g). The HPLC profile showed no traces of TTX, but only the presence of PSPs (STX, GTX 2 and GTX 3). These toxins were also confirmed by electrospray ionization mass spectrometry.

  7. Potential Threats Posed by Tetrodotoxins in UK Waters: Examination of Detection Methodology Used in Their Control

    Directory of Open Access Journals (Sweden)

    Andrew D. Turner

    2015-12-01

    Full Text Available Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are well studied in fish and gastropods, in recent years, there have been a number of reports of tetrodotoxin occurring in bivalve shellfish, including those harvested from the UK and other parts of Europe. This paper reviews evidence concerning the prevalence of tetrodotoxins in the UK together with methodologies currently available for testing. Biological, biomolecular and chemical methods are reviewed, including recommendations for further work. With the recent development of quantitative chromatographic methods for these and other hydrophilic toxins, as well as the commercial availability of rapid testing kits, there are a number of options available to ensure consumers are protected against this threat.

  8. Potential Threats Posed by Tetrodotoxins in UK Waters: Examination of Detection Methodology Used in Their Control

    Science.gov (United States)

    Turner, Andrew D.; Higgins, Cowan; Higman, Wendy; Hungerford, James

    2015-01-01

    Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are well studied in fish and gastropods, in recent years, there have been a number of reports of tetrodotoxin occurring in bivalve shellfish, including those harvested from the UK and other parts of Europe. This paper reviews evidence concerning the prevalence of tetrodotoxins in the UK together with methodologies currently available for testing. Biological, biomolecular and chemical methods are reviewed, including recommendations for further work. With the recent development of quantitative chromatographic methods for these and other hydrophilic toxins, as well as the commercial availability of rapid testing kits, there are a number of options available to ensure consumers are protected against this threat. PMID:26690455

  9. Public health response to puffer fish (Tetrodotoxin) poisoning from mislabeled product.

    Science.gov (United States)

    Cohen, Nicole J; Deeds, Jonathan R; Wong, Eugene S; Hanner, Robert H; Yancy, Haile F; White, Kevin D; Thompson, Trevonne M; Wahl, Michael; Pham, Tu D; Guichard, Frances M; Huh, In; Austin, Connie; Dizikes, George; Gerber, Susan I

    2009-04-01

    Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However, genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation of puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption, and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies.

  10. Anti-tumor activity of tetrodotoxin extracted from the Masked Puffer ...

    African Journals Online (AJOL)

    of tumor cells. - There was also an obvious cytotoxic effect of tetrodotoxins on cells, leading to apoptosis and a decrease in the volume of the peritoneal fluid. - The negative effects of tumor cells on the ..... degradation of cell contents and loss of nucleus integrity, which left the cell as an unrecognizeable mass. During the last ...

  11. Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles.

    Science.gov (United States)

    Carrasco, Dario I; Vincent, Jacob A; Cope, Timothy C

    2017-04-01

    Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV 1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV 1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV 1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV 1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV 1.1 , predominantly in sensory terminals together with NaV 1.6 and for NaV 1.7 , mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles. NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site

  12. Tetrodotoxin poisoning outbreak from imported dried puffer fish--Minneapolis, Minnesota, 2014.

    Science.gov (United States)

    Cole, Jon B; Heegaard, William G; Deeds, Jonathan R; McGrath, Sara C; Handy, Sara M

    2015-01-02

    On June 13, 2014, two patients went to the Hennepin County Medical Center Emergency Department in Minneapolis, Minnesota, with symptoms suggestive of tetrodotoxin poisoning (i.e., oral paresthesias, weakness, and dyspnea) after consuming dried puffer fish (also known as globefish) purchased during a recent visit to New York City. The patients said two friends who consumed the same fish had similar, although less pronounced, symptoms and had not sought care. The Minnesota Department of Health conducted an investigation to determine the source of the product and samples were sent to the Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition for chemical and genetic analysis. Genetic analysis identified the product as puffer fish (Lagocephalus lunaris) and chemical analysis determined it was contaminated with high levels of tetrodotoxin. A traceback investigation was unable to determine the original source of the product. Tetrodotoxin is a deadly, potent poison; the minimum lethal dose in an adult human is estimated to be 2-3 mg. Tetrodotoxin is a heat-stable and acid-stable, nonprotein, alkaloid toxin found in many species of the fish family Tetraodontidae (puffer fish) as well as in certain gobies, amphibians, invertebrates, and the blue-ringed octopus. Tetrodotoxin exerts its effects by blocking voltage-activated sodium channels, terminating nerve conduction and muscle action potentials, leading to progressive paralysis and, in extreme cases, to death from respiratory failure. Because these fish were reportedly purchased in the United States, they pose a substantial U.S. public health hazard given the potency of the toxin and the high levels of toxin found in the fish.

  13. Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing.

    Science.gov (United States)

    Yamada-Hanff, Jason; Bean, Bruce P

    2015-10-01

    We used dynamic clamp and action potential clamp techniques to explore how currents carried by tetrodotoxin-sensitive sodium channels and HCN channels (Ih) regulate the behavior of CA1 pyramidal neurons at resting and subthreshold voltages. Recording from rat CA1 pyramidal neurons in hippocampal slices, we found that the apparent input resistance and membrane time constant were strongly affected by both conductances, with Ih acting to decrease apparent input resistance and time constant and sodium current acting to increase both. We found that both Ih and sodium current were active during subthreshold summation of artificial excitatory postsynaptic potentials (EPSPs) generated by dynamic clamp, with Ih dominating at less depolarized voltages and sodium current at more depolarized voltages. Subthreshold sodium current-which amplifies EPSPs-was most effectively recruited by rapid voltage changes, while Ih-which blunts EPSPs-was maximal for slow voltage changes. The combined effect is to selectively amplify rapid EPSPs. We did similar experiments in mouse CA1 pyramidal neurons, doing voltage-clamp experiments using experimental records of action potential firing of CA1 neurons previously recorded in awake, behaving animals as command voltages to quantify flow of Ih and sodium current at subthreshold voltages. Subthreshold sodium current was larger and subthreshold Ih was smaller in mouse neurons than in rat neurons. Overall, the results show opposing effects of subthreshold sodium current and Ih in regulating subthreshold behavior of CA1 neurons, with subthreshold sodium current prominent in both rat and mouse CA1 pyramidal neurons and additional regulation by Ih in rat neurons. Copyright © 2015 the American Physiological Society.

  14. First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.

    Science.gov (United States)

    Kirchhof, Paulus; Tal, Tzachy; Fabritz, Larissa; Klimas, Jan; Nesher, Nir; Schulte, Jan S; Ehling, Petra; Kanyshkova, Tatayana; Budde, Thomas; Nikol, Sigrid; Fortmueller, Lisa; Stallmeyer, Birgit; Müller, Frank U; Schulze-Bahr, Eric; Schmitz, Wilhelm; Zlotkin, Eliahu; Kirchhefer, Uwe

    2015-01-01

    New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents. © 2014 American Heart Association, Inc.

  15. Tetrodotoxin-resistant non-cholinergic neurogenic contraction evoked by capsaicinoids and piperine on the guinea-pig trachea.

    Science.gov (United States)

    Szolcsányi, J

    1983-11-21

    Contraction of the isolated tracheal strip to capsaicin was prevented by chronic denervation of the tissue. Tetrodotoxin, hyoscine and hexamethonium caused no inhibition of the response, suggesting that tetrodotoxin-resistant terminal portions of non-cholinergic nerves were activated in this way. There was a strong correlation between the pain-producing and tracheoconstrictor effects of piperine, pungent and non-pungent capsaicin congeners. Common site of action was evidenced by crossed tachyphylaxis. It is concluded that the capsaicin-sensitive sensory nerve endings have a dual sensory-efferent function. Excitation-secretion coupling in this system could operate without an axon reflex.

  16. 4-Aminopyridine antagonizes saxitoxin-and tetrodotoxin-induced cardiorespiratory depression.

    Science.gov (United States)

    Chang, F C; Bauer, R M; Benton, B J; Keller, S A; Capacio, B R

    1996-06-01

    Antagonism of saxitoxin-and tetrodotoxin-induced lethality by 4-aminopyridine was studied in urethane-anesthetized guinea pigs instrumented for the concurrent recordings of medullary respiratory-related unit activities (Bötzinger complex and Nu. para-Ambiguus), diaphragmatic electromyogram, electrocorticogram, Lead II electrocardiogram, blood pressure, end-tidal CO2 and arterial O2/CO2/pH. The toxin (either saxitoxin or tetrodotoxin) was infused at a dose rate of 0.3 microgram/kg/min (i.v.) to produce a state of progressive cardiorespiratory depression. The animals were artificially ventilated when the magnitude of integrated diaphragm activities was reduced to 50% of control. Immediately after the disappearance of the diaphragm electromyogram, the toxin infusion was terminated, and 4-aminopyridine (2 mg/kg, i.v.) was administered. The therapeutic effect of 4-aminopyridine was striking in that the toxin-induced blockade of diaphragmatic neurotransmission, vascular hypotension, myocardial anomalies, bradycardia and aberrant discharge patterns of medullary respiratory-related neurons could all be promptly restored to a level comparable to that of control condition. The animals were typically able to breathe spontaneously within minutes after 4-aminopyridine. At the dose level used to achieve the desired therapeutic responses, 4-aminopyridine produced no sign of seizure and convulsion. Although less serious side-effects such as cortical excitant/arousal and transient periods of fascicular twitch could be observed, these events were of minor concern, in our opinion, particularly in view of the remarkable therapeutic effects of 4-aminopyridine.

  17. Effects of (−-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Jian-Min Jiang

    2013-05-01

    Full Text Available The (−-gallocatechin-3-gallate (GCG concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent.

  18. Selective expression of a persistent tetrodotoxin-resistant Na+ current and NaV1.9 subunit in myenteric sensory neurons.

    Science.gov (United States)

    Rugiero, François; Mistry, Mohini; Sage, Dominique; Black, Joel A; Waxman, Stephen G; Crest, Marcel; Clerc, Nadine; Delmas, Patrick; Gola, Maurice

    2003-04-01

    Voltage-gated Na(+) currents play critical roles in shaping electrogenesis in neurons. Here, we have identified a TTX-resistant Na(+) current (TTX-R I(Na)) in duodenum myenteric neurons of guinea pig and rat and have sought evidence regarding the molecular identity of the channel producing this current from the expression of Na(+) channel alpha subunits and the biophysical and pharmacological properties of TTX-R I(Na). Whole-cell patch-clamp recording from in situ neurons revealed the presence of a voltage-gated Na(+) current that was highly resistant to TTX (IC(50), approximately 200 microm) and selectively distributed in myenteric sensory neurons but not in interneurons and motor neurons. TTX-R I(Na) activated slowly in response to depolarization and exhibited a threshold for activation at -50 mV. V(1/2) values of activation and steady-state inactivation were -32 and -31 mV in the absence of fluoride, respectively, which, as predicted from the window current, generated persistent currents. TTX-R I(Na) also had prominent ultraslow inactivation, which turns off 50% of the conductance at rest (-60 mV). Substituting CsF for CsCl in the intracellular solution shifted the voltage-dependent parameters of TTX-R I(Na) leftward by approximately 20 mV. Under these conditions, TTX-R I(Na) had voltage-dependent properties similar to those reported previously for NaN/Na(V)1.9 in dorsal root ganglion neurons. Consistent with this, reverse transcription-PCR, single-cell profiling, and immunostaining experiments indicated that Na(V)1.9 transcripts and subunits, but not Na(V)1.8, were expressed in the enteric nervous system and restricted to myenteric sensory neurons. TTX-R I(Na) may play an important role in regulating subthreshold electrogenesis and boosting synaptic stimuli, thereby conferring distinct integrative properties to myenteric sensory neurons.

  19. Use dependence of peripheral nociceptive conduction in the absence of tetrodotoxin-resistant sodium channel subtypes.

    Science.gov (United States)

    Hoffmann, Tal; Kistner, Katrin; Nassar, Mohammed; Reeh, Peter W; Weidner, Christian

    2016-10-01

    This study examines conduction in peripheral nerves and its use dependence in tetrodotoxin-resistant (TTXr) sodium channel (Nav 1.8, Nav 1.9) knockout and wildtype animals. We observed use-dependent decreases of single fibre and compound action potential amplitude in peripheral mouse C-fibres (wildtype). This matches the previously published hypothesis that increased Na/K-pump activity is not the underlying mechanism for use-dependent changes of neural conduction. Knocking out TTXr sodium channels influences use-dependent changes of conductive properties (action potential amplitude, latency, conduction safety) in the order Nav 1.8 KO > Nav 1.9KO > wildtype. This is most likely explained by different subsets of presumably (relatively) Nav 1.7-rich conducting fibres in knockout animals as compared to wildtypes, in combination with reduced per-pulse sodium influx. Use dependency of peripheral nerves, especially of nociceptors, correlates with receptive properties. Slow inactivation of voltage-gated sodium channels has been discussed to be the underlying mechanism - pointing to a receptive class-related difference of sodium channel equipment. Using electrophysiological recordings of single unmyelinated cutaneous fibres and their compound action potential (AP), we evaluated use-dependent changes in mouse peripheral nerves, and the contribution of the tetrodotoxin-resistant (TTXr) sodium channels Nav 1.8 and Nav 1.9 to these changes. Nerve fibres were electrically stimulated using single or double pulses at 2 Hz. Use-dependent changes of latency, AP amplitude, and duration as well as the fibres' ability to follow the stimulus were evaluated. AP amplitudes substantially diminished in used fibres from C57BL/6 but increased in Nav 1.8 knockout (KO) mice, with Nav 1.9 KO in between. Activity-induced latency slowing was in contrast the most pronounced in Nav 1.8 KOs and the least in wildtype mice. The genotype was also predictive of how long fibres could follow the

  20. Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons.

    Science.gov (United States)

    Benn, S C; Costigan, M; Tate, S; Fitzgerald, M; Woolf, C J

    2001-08-15

    The development of neuronal excitability involves the coordinated expression of different voltage-gated ion channels. We have characterized the expression of two sensory neuron-specific tetrodotoxin-resistant sodium channel alpha subunits, Na(v)1. (SNS/PN3) and Na(v)1.9 (SNS2/NaN), in developing rat lumbar dorsal root ganglia (DRGs). Expression of both Na(v)1.8 and Na(v)1.9 increases with age, beginning at embryonic day (E) 15 and E17, respectively, and reaching adult levels by postnatal day 7. Their distribution is restricted mainly to those subpopulations of primary sensory neurons in developing and adult DRGs that give rise to unmyelinated C-fibers (neurofilament 200 negative). Na(v)1.8 is expressed in a higher proportion of neuronal profiles than Na(v)1.9 at all stages during development, as in the adult. At E17, almost all Na(v)1.8-expressing neurons also express the high-affinity NGF receptor TrkA, and only a small proportion bind to IB4, a marker for c-ret-expressing (glial-derived neurotrophic factor-responsive) neurons. Because IB4 binding neurons differentiate from TrkA neurons in the postnatal period, the proportion of Na(v)1.8 cells that bind to IB4 increases, in parallel with a decrease in the proportion of Na(v)1.8-TrkA co-expressing cells. In contrast, an equal number of Na(v)1.9 cells bind IB4 and TrkA in embryonic life. The differential expression of Na(v)1.8 and Na(v)1.9 in late embryonic development, with their distinctive kinetic properties, may contribute to the development of spontaneous and stimulus-evoked excitability in small diameter primary sensory neurons in the perinatal period and the activity-dependent changes in differentiation they produce.

  1. [Determination of tetrodotoxin in puffer-fish tissues, and in serum and urine of intoxicated humans by liquid chromatography with tandem mass spectrometry].

    Science.gov (United States)

    Akaki, Kouichi; Hatano, Kazuhiro

    2006-04-01

    A simple and rapid method was developed for the analysis of tetrodotoxin in puffer-fish tissues, and in serum and urine of humans poisoned after consuming puffer-fish, by means of high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS). Tetrodotoxin was extracted with 2% acetic acid. The extracted solution from puffer-fish tissues was diluted with water, and the extracted solution from human serum and urine was cleaned up by LC/MS/MS with a methacrylate-styrenedivinylbenzene cartridge. The LC separation was performed on a C18 column (50 mm x 2.1 mm i.d.) using 10 mmol/L IPCC-MS7-methanol (65 : 35) as the mobile phase at a flow rate of 0.2 mL/min. The mass spectral acquisition was done in the positive ion mode by applying selected reaction monitoring (SRM). The recoveries of tetrodotoxin were 79-90% from puffer-fish tissues fortified at 0.1 microg/g and 1 microg/g, and 93-101% from human serum and urine fortified at 0.5 ng/mL and 5 ng/mL. The detection limits of tetrodotoxin were 0.01 microg/g in puffer-fish tissues and 0.1 ng/mL in human serum and urine. Thirty samples of puffer-fish from wholesale markets, and 7 serum and 5 urine samples of humans poisoned after consuming puffer-fish were analyzed by this method. Tetrodotoxin was detected in all puffer-fish tissues, and all serum and urine samples at the levels of 0.04-140 microg/g, 0.9-1.8 ng/mL and 15-150 ng/mL, respectively.

  2. Puffer fish (Tetrodotoxin) poisoning: an analysis and outcome of six cases.

    Science.gov (United States)

    Chowdhury, Fazle Rabbi; Ahasan, H A M Nazmul; Al Mamun, Abdullah; Rashid, A K M Mamunur; Al Mahboob, Abdullah

    2007-10-01

    On 24 July 2005, six members of a single family were admitted to the Medicine and Pediatrics Department of Khulna Medical College Hospital, Khulna, Bangladesh, with a history of ingestion of puffer fish. All patients developed toxic manifestations. The cases were clinically analysed with successful outcomes.

  3. The role of tetrodotoxin-resistant sodium channels in pain states: are they the next target for analgesic drugs?

    Science.gov (United States)

    Silos-Santiago, Inmaculada

    2008-01-01

    Neuropathic pain, a persistent chronic pain resulting from damage to the central or peripheral nervous system, is a condition that severely affects the quality-of-life of millions of individuals worldwide. The treatment of neuropathic pain is still an unmet medical need; however, recent advances in our understanding of mechanisms underlying the perception and transmission of painful stimuli offer significant potential for improvement of therapies directed to neuropathic pain. Ectopic activity in damaged and dysfunctional sensory afferents is believed to have a role in the generation and maintenance of neuropathic pain. One of the mechanisms underlying this ectopic firing involves abnormal modulation of voltage-gated sodium channels (NaVs) in the soma and axonal membranes of dorsal root ganglion (DRG) sensory neurons. In fact, NaV blockers have been clinically validated as treatments for neuropathic pain. However, current drugs are weak, non-selective inhibitors of NaVs with dose-limiting CNS and cardiovascular side effects that prevent their use in long-term therapy. Selective NaV tetrodotoxin-resistant channels (NaV 1.8 and NaV 1.9) are expressed exclusively in nociceptive neurons in the DRGs where they play a key role in normal and/or pathological pain sensation, providing an opportunity for the development of novel peripheral analgesics with a better safety profile.

  4. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors...... to human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  5. Degradation photocatalysis of tetrodotoxin as a poison by gold doped PdO nanoparticles supported on reduced graphene oxide nanocomposites and evaluation of its antibacterial activity.

    Science.gov (United States)

    Fakhri, Ali; Naji, Mahsa

    2017-02-01

    In this project, synthesis of pure and gold doped PdO-reduced graphene oxide nanocomposites by sonochemical and deposition-precipitation process was performed and characterized using X-ray diffraction (XRD), transmission electronic microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The specific surface area of synthesized un-doped and Au doped PdO-RGO nanocomposites is 83.2, 109.1m(2)g(-1) and total pore volume is 0.31, 0.40cm(3)g(-1), respectively. With Tetrodotoxin as a target pollutant, photocatalytic system of UV+photocatalyst+H2O2 was set up. Some influencing parameters, including H2O2 dosage and initial pH value were investigated and the stability of the photocatalyst was also studied during the photocatalysis. The optimum values of operating parameters were found at an initial pH value of 5.0, a H2O2 dosage of 0.15mmol/L(-1) and photocatalyst dosage of 0.08g. Under the optimal conditions, the highest removal rate of Tetrodotoxin achieved 95%. Compared with the traditional photo-Fenton system, the UV+photocatalyst+H2O2 system can not only improve the degradation efficiency of Tetrodotoxin, but also reduce the dosage of H2O2 and thus reduce the processing cost. Antibacterial properties of un-doped and Au doped PdO-RGO nanocomposites were investigated by gram negative bacteria Escherichia coli and gram positive Staphylococcus aureus. The results showed that the antibacterial activity enhanced by Au PdO-RGO nanocomposites. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Antimony toxicity

    National Research Council Canada - National Science Library

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms...

  7. Antimony Toxicity

    Science.gov (United States)

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  8. [Toxic megacolon].

    Science.gov (United States)

    Leppkes, M; Ganslmayer, M; Strauß, R; Neurath, M F

    2015-10-01

    Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.

  9. Chemical Compound, Phytochemical and Toxicity on Green Rough-backed Puffer from Cirebon District

    Directory of Open Access Journals (Sweden)

    Ginanjar Pratama

    2014-11-01

    Full Text Available This aims of study was to assess yield, nutrient content and in vitro assay of extract on green rough-backed puffer from Cirebon district. The method used in this study was the proximate analysis, phytochemicals, and BSLT test of extracts on three parts of puffer fish (meat, viscera and skin. Puffer fish used measure around 10-13 cm. The yield obtained was meat 37.80%, bone 45.71%, viscera 7.25% and skin 9.23%. Protein content showed greatest potential, protein in the fish meat was 18.54% while the skin was 25.31%. Phytochemical test showed the entire extract has a positive value for alkaloids and have a negative value on the other reagents, except meat extract on molisch test. Phytochemical test results indicated that the meat of green rough-backed puffer contain tetrodotoxin, but the amount was unknown. LC50 values in meat extract was 104.3498μg/mL, extract the viscera of 105.4564μg/mL, and the skin extract was 104.9637μg/mL. These results showed that the extract of meat, viscera and skin of the puffer fish is not toxic, although there are indications of tetrodotoxin in the flesh.Keywords: extracts, phytochemical, green rough-backed puffer, nutrient content

  10. CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav 1.8 sodium channels in dorsal root ganglion neurons

    National Research Council Canada - National Science Library

    Der-Jang Kao; Allen H Li; Jin-Chung Chen; Ro-Sun Luo; Ying-Ling Chen; Juu-Chin Lu; Hung-Li Wang

    2012-01-01

    .... Transient receptor potential vanilloid receptor 1 (TRPV1) and tetrodotoxin (TTX)-resistant Na v 1.8 sodium channels play an essential role in regulating the excitability and pain transmission of DRG nociceptive neurons...

  11. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  12. Studying toxicity

    Science.gov (United States)

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  13. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  14. Expression of 5-HT3 receptors and TTX resistant sodium channels (NaV1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders

    Science.gov (United States)

    2014-01-01

    Background Previous studies have shown that 5-HT3-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Methods Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. Results A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly

  15. Expression of 5-HT3 receptors and TTX resistant sodium channels (Na(V)1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders.

    Science.gov (United States)

    Christidis, Nikolaos; Kang, Isabell; Cairns, Brian E; Kumar, Ujendra; Dong, Xudong; Rosén, Annika; Kopp, Sigvard; Ernberg, Malin

    2014-09-26

    Previous studies have shown that 5-HT3-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42

  16. Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior.

    Science.gov (United States)

    Priest, Birgit T; Murphy, Beth A; Lindia, Jill A; Diaz, Carmen; Abbadie, Catherine; Ritter, Amy M; Liberator, Paul; Iyer, Leslie M; Kash, Shera F; Kohler, Martin G; Kaczorowski, Gregory J; MacIntyre, D Euan; Martin, William J

    2005-06-28

    The transmission of pain signals after injury or inflammation depends in part on increased excitability of primary sensory neurons. Nociceptive neurons express multiple subtypes of voltage-gated sodium channels (NaV1s), each of which possesses unique features that may influence primary afferent excitability. Here, we examined the contribution of NaV1.9 to nociceptive signaling by studying the electrophysiological and behavioral phenotypes of mice with a disruption of the SCN11A gene, which encodes NaV1.9. Our results confirm that NaV1.9 underlies the persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion neurons but suggest that this current contributes little to mechanical thermal responsiveness in the absence of injury or to mechanical hypersensitivity after nerve injury or inflammation. However, the expression of NaV1.9 contributes to the persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation. These results suggest that inflammatory mediators modify the function of NaV1.9 to maintain inflammation-induced hyperalgesia.

  17. Differential expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 in normal and inflamed rats.

    Science.gov (United States)

    Coggeshall, Richard E; Tate, Simon; Carlton, Susan M

    2004-01-23

    In an attempt to understand mechanisms underlying peripheral sensitization of primary afferent fibers, we investigated the presence of the tetrodotoxin-resistant Na+ channel subunits Nav1.8 (SNS) and Nav1.9 (SNS2) on axons in digital nerves of normal and inflamed rat hindpaws. In normal animals, 14.3% of the unmyelinated and 10.7% of the myelinated axons labeled for the Nav1.8 subunit. These percentages significantly increased in 48 h inflamed animals to 22.0% (1.5-fold increase) and 57.5% (6-fold increase) for unmyelinated and myelinated axons, respectively. In normal animals, Nav1.9 labeled 9.9% of the unmyelinated and 2.1% of the myelinated axons and following inflammation, the proportion of Nav1.9-labeled unmyelinated axons significantly decreased to 3.0% with no change in the proportion of labeled myelinated axons. These data indicate that Nav1.8 and Nav1.9 subunits are transported to the periphery in normal animals and are differentially regulated during inflammation. The massive increase in Nav1.8 expression in myelinated axons suggests that these may contribute to peripheral sensitization and inflammatory hyperalgesia.

  18. [Toxic methemoglobinemia].

    Science.gov (United States)

    Bender, P; Neuhaus, H

    2011-04-01

    A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Biomedical and pharmacological potential of tetrodotoxin-producing bacteria isolated from marine pufferfish Arothron hispidus (Muller, 1841

    Directory of Open Access Journals (Sweden)

    S Bragadeeswaran

    2010-01-01

    Full Text Available Specimens of the pufferfish Arothron hispidus collected at Parangipettai, on the southeast coast of India, were subjected to bacterial isolation and identification. Three species were identified, namely Bacillus sp., Kytococcus sedentarius and Cellulomonas fimi. Partially-purified microbial filtrates exhibited hemolytic activity on chicken and human erythrocytes of O, B and AB blood groups, with maximum activity of 32 HU. The microbial filtrates also presented ATPase, Mg2+-ATPase, Na+K+-ATPase and AchE enzymatic activities of positive neuromodulation in Kytococcus sedentarius with 1300, 300.1, 1549.98 and 140.55%, in Cellulomonas fimi with 620, 300, 10 and 128.42%, and in Bacillus species with 40, 200, 849.98 and 158.69%, respectively. Toxicity symptoms were observed when the bacterial filtrate was intraperitoneally injected into mice. The bacterial filtrate caused adverse effects on viability of the mouse muscle cell line (L929 and leukemia cell line (P388. Maximum level of inhibition was observed on the growth of L929 cell line. Bacillus lentimorbus inhibited the cell line from 84.03 to 94.43% whereas Bacillus species inhibited the growth in a range between 77.25 and 86.16% at the lowest dilution.

  20. The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons.

    Science.gov (United States)

    Fang, Xin; Djouhri, Laiche; Black, Joel A; Dib-Hajj, Sulayman D; Waxman, Stephen G; Lawson, Sally N

    2002-09-01

    This is the first examination of sensory receptive properties and associated electrophysiological properties in vivo of dorsal root ganglion (DRG) neurons that express the TTX-resistant sodium channel Na(v)1.9 (NaN). Intracellular recordings in lumbar DRGs in Wistar rats enabled units with dorsal root C-, Adelta-, or Aalpha/beta-fibers to be classified as nociceptive, low-threshold mechanoreceptive (LTM), or unresponsive. Intracellular dye injection enabled subsequent immunocytochemistry for Na(v)1.9-like immunoreactivity (Na(v)1.9-LI). Na(v)1.9-LI was expressed selectively in nociceptive-type (C- and A-fiber nociceptive and C-unresponsive) units. Of the nociceptive units, 64, 54, and 31% of C-, Adelta-, and Aalpha/beta-fiber units, respectively, were positive for Na(v)1.9-LI. C-unresponsive units were included in the nociceptive-type group on the basis of their nociceptor-like membrane properties; 91% were positive. Na(v)1.9-LI was undetectable in Adelta- or Aalpha/beta-fiber LTM units and in one C-LTM unit. Na(v)1.9-LI intensity was correlated negatively with soma size and conduction velocity in nociceptive units and with conduction velocity in C-fiber units. There was a positive correlation with action potential rise time in nociceptive-type units with membrane potentials equal to or more negative than -50 mV. The data provide direct evidence that Na(v)1.9 is expressed selectively in (but not in all) C- and A-fiber nociceptive-type units and suggest that Na(v)1.9 contributes to membrane properties that are typical of nociceptive neurons.

  1. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  2. Toxic hemolytic anemias.

    OpenAIRE

    ZEMANOVÁ, Vendula

    2014-01-01

    This thesis deals with toxic hemolytic anemias which are often unheeded. There are described laboratory signs of hemolytic anemias, their dividing into the various groups and it focuses mainly to toxic and drug-related hemolytic anemias and their causations.

  3. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    than uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt...uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt.”5...FEMALES AND TOXIC LEADERSHIP A thesis presented to the Faculty of the U.S. Army Command and General Staff College in

  4. CHEMICAL TOXICITY OF URANIUM

    Directory of Open Access Journals (Sweden)

    Sermin Cam

    2007-06-01

    Full Text Available Uranium, occurs naturally in the earth’s crust, is an alpha emitter radioactive element from the actinide group. For this reason, U-235 and U-238, are uranium isotopes with long half lives, have got radiological toxicity. But, for natural-isotopic-composition uranium (NatU, there is greater risk from chemical toxicity than radiological toxicity. When uranium is get into the body with anyway, also its chemical toxicity must be thought. [TAF Prev Med Bull 2007; 6(3.000: 215-220

  5. Toxic proteins in plants.

    Science.gov (United States)

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  7. Effects of free fatty acids on sodium currents in rat dorsal root ganglion neurons.

    Science.gov (United States)

    Hong, Min-Pyo; Kim, Hong Im; Shin, Yong Kyoo; Lee, Chung Soo; Park, Mijung; Song, Jin-Ho

    2004-05-15

    Free fatty acids (FFAs), especially polyunsaturated fatty acids (PUFAs), are potent modulators of muscle-type sodium channels. It is not known if they also modulate sodium channels of sensory neurons. In this study, we investigated the effects of FFAs on the fast tetrodotoxin-sensitive (fTTX-S) and the slow tetrodotoxin-resistant (sTTX-R) sodium currents in rat dorsal root ganglion neurons. At a holding potential of -80 mV, PUFAs potently inhibited fTTX-S current, but monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) to a lesser extent. All FFAs initially increased sTTX-R current, and then decreased it slightly. PUFAs and MUFAs produced a hyperpolarizing shift of the steady-state inactivation voltage for both types of sodium currents. The shift generally increased with the number of unsaturated bonds. FFAs did not change the maximum amplitude of fTTX-S current, but increased that of sTTX-R current. Most FFAs shifted the activation voltage for fTTX-S current in the hyperpolarizing direction, which was not dependent on the degree of unsaturation. MUFAs and SFAs shifted the activation voltage for sTTX-R current in the hyperpolarizing direction, but PUFAs were without effect. The modulation of sodium currents by FFAs, especially PUFAs, may have considerable impact on the excitability of sensory neurons.

  8. Pediatric Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer Yee

    2017-09-01

    Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

  9. Electronic Cigarette Toxicity.

    Science.gov (United States)

    Payne, J Drew; Michaels, David; Orellana-Barrios, Menfil; Nugent, Kenneth

    2017-04-01

    Electronic cigarettes (e-cigarettes) are often advertised as a healthier product when compared with traditional cigarettes. Currently, there are limited data to support this and only a threat of federal regulation from the US Food and Drug Administration. Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years. This research letter reports the frequency of hazardous exposures to e-cigarettes and characterizes the reported adverse health effects associated with e-cigarette toxicity.

  10. Assessing Nanoparticle Toxicity

    Science.gov (United States)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  11. Liquid Nicotine Toxicity.

    Science.gov (United States)

    Kim, Ji Won; Baum, Carl R

    2015-07-01

    E-cigarettes, also known as electronic nicotine delivery systems and electronic cigarettes, are advertised as a healthier alternative product to tobacco cigarettes despite limited data on the consequences of e-cigarette use. Currently, there are no US Food and Drug Administration or other federal regulations of e-cigarettes, and calls to poison control centers regarding liquid nicotine toxicity, especially in children, are on the rise. This article presents the background and mechanism of action of e-cigarettes as well as up-to-date details of the toxicity of liquid nicotine. We also present management strategies in the setting of liquid nicotine toxicity.

  12. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  13. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  14. Local anaesthetic toxicity

    African Journals Online (AJOL)

    treatment strategies. Introduction ... depression and central nervous system and cardiovascular toxicity increased .... requiring analgesic therapy beyond that of surgery. ..... Progress in Biophysics and Molecular Biology 2006;91:1 –82. 32.

  15. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

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

    1980-01-01

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

  16. Recurrent amiodarone pulmonary toxicity.

    Science.gov (United States)

    Chendrasekhar, A; Barke, R A; Druck, P

    1996-01-01

    Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

  17. [Toxic alcohol poisonings].

    Science.gov (United States)

    Kulicki, Paweł; Głogowski, Tomasz

    Accidental or intentional poisonings with ethylene glycol or methanol constitute a serious toxicological problem in many countries. Both alcohols are quickly metabolized by alcohol dehydrogenase to toxic metabolites responsible for high anion gap severe metabolic acidosis and profound neurological, cardiopulmonary, renal disturbances and death. In the early period, the competing inhibition the alcohol dehydrogenase with ethanol or fomepizol may successfully prevent the formation of the toxic metabolites. Once severe acidosis develops an emergency hemodialysis is required.

  18. Distribution of homologous proteins to puffer fish saxitoxin and tetrodotoxin binding protein in the plasma of puffer fish and among the tissues of Fugu pardalis examined by Western blot analysis.

    Science.gov (United States)

    Yotsu-Yamashita, Mari; Yamaki, Hiroe; Okoshi, Natsumi; Araki, Nao

    2010-06-01

    Puffer fish saxitoxin and tetrodotoxin binding protein (PSTBP) is a glycoprotein (200 kDa as a dimer) that we previously isolated from the plasma of Fugu pardalis (Yotsu-Yamashita et al., 2001). For the study on functions of PSTBP, here we examined distribution of homologous proteins to PSTBP in the plasma of seven species of puffer fish, and among the tissues of F. pardalis by Western blot analysis probed with a polyclonal IgG against unglycosylated PSTBP1 expressed in Echelichia coli. One or two major positive broad bands were detected at 105-140 kDa molecular weight range in the plasma (0.5 microg protein) of all species of puffer fish tested, while no band was detected in the plasma (5 microg protein) of fish other than puffer fish. Glycopeptidase F treated plasma of all species of puffer fish tested commonly showed the bands at approximately 42 kDa that was consistent to the molecular weight of unglycosylated PSTBP. These data suggest that puffer fish commonly possess glycoproteins homologous to PSTBP, but the sizes of N-glycan are specific to the species. Among soluble protein extracts (5 microg protein) from the tissues of F. pardalis, PSTBP was detected in all tissues examined, most prominently in heart, skin, and gall. Copyright 2009 Elsevier Ltd. All rights reserved.

  19. Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain.

    Science.gov (United States)

    Qiu, Fang; Jiang, Yuge; Zhang, Hong; Liu, Yanhong; Mi, Weidong

    2012-03-23

    In attempt to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two tetrodotoxin-resistant sodium channels, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN), in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain. Thirty-six female Sprague-Dawley rats were randomized into three groups: Sham operation group (Sham), cancer-bearing animals killed after 7 days (C7) and cancer-bearing animals killed after 14 days group (C14). After establishment of bone cancer pain model, behavioral tests were carried out to determine the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia, respectively. Real-time RT-PCR, Western bolt and Immunofluorescence were used to determine the mRNA and protein expression of Nav1.8 and Nav1.9 in ipsilateral lumbar 4-5 DRG. Compared to Sham group, PWT of mechanical and thermal hyperalgesia in C14 group displayed a significant decrease (PNav1.9 exhibited a significant up-regulation in C14 group (8.9 times and 9 times, respectively, PNav1.9 (PNav1.9 suggested their potential involvement in the development and maintenance of bone cancer pain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. [Toxicity of puffer fish fins].

    Science.gov (United States)

    Honda, Shunichi; Ichimaru, Shunichi; Arakawa, Osamu; Takatani, Tomohiro; Noguchi, Tamao; Ishizaki, Shoichiro; Nagashima, Yuji

    2007-10-01

    Puffer fish is prized as a Japanese traditional food and its fin is also used in the cuisine. However, whether the fin is edible or not is determined for convenience from the toxicity of skin, since little information is available about the toxicity of puffer fish fins. In the present study, we examined the toxicity of fins and skin of three toxic species, Takifugu vermicularis, T. snyderi, and T. porphyreus. The toxicity of T. vermicularis fins (puffer fish with toxic skin also have toxic fins.

  1. Acute Toxicity of Vildagliptin.

    Science.gov (United States)

    Hoffmann, Peter; Martin, Lori; Keselica, Michael; Gunson, Diane; Skuba, Elizabeth; Lapadula, Dan; Hayes, Michael; Bentley, Phil; Busch, Steve

    2017-01-01

    This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances. In surviving animals, symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius appear more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data, and it is concluded that acute toxicity following vildagliptin treatment is a monkey-specific phenomenon without relevance for humans.

  2. The toxicity of refrigerants

    Energy Technology Data Exchange (ETDEWEB)

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  3. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund’s Adjuvant Models of Pain

    Science.gov (United States)

    Matson, David J.; Hamamoto, Darryl T.; Bregman, Howard; Cooke, Melanie; DiMauro, Erin F.; Huang, Liyue; Johnson, Danielle; Li, Xingwen; McDermott, Jeff; Morgan, Carrie; Wilenkin, Ben; Malmberg, Annika B.; McDonough, Stefan I.; Simone, Donald A.

    2015-01-01

    While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported “compound 52” aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund’s adjuvant (CFA) model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors. PMID:26379236

  4. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain.

    Directory of Open Access Journals (Sweden)

    David J Matson

    Full Text Available While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported "compound 52" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors.

  5. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  6. Respiratory Toxicity Biomarkers

    Science.gov (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  7. ANTIRETROVIRAl TOXICITY IN CHILDREN

    African Journals Online (AJOL)

    vertical transmission prophylaxis (VrP), and the other is treatment for symptomatic HIV infection. Fig. 7. Disease profile ofHN-positivechildren in the Italian. Collaborative Multicentric Study. Antiretroviral (ARV) toxicity is an important issue that must be fully appreciated by prescribing doctors. While the benefits of therapy are ...

  8. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    on the brain, it is used as a major taste enhancer in most eateries and cafeteria in Nigeria. However, information is scanty on the potential of Sida acuta leaf ethanolic extract. (SALEE) to mitigate MSG-induced effect on the brain. This study aimed to investigate the possible toxic effect of MSG, a natural constituent of many ...

  9. [Toxicity study of realgar].

    Science.gov (United States)

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

    2011-07-01

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

  10. Animal Toxicity of Phytopathogenic Fungi

    Science.gov (United States)

    Main, C. E.; Hamilton, P. B.

    1972-01-01

    Twelve genera of phytopathogenic fungi comprising 27 species previously reported to produce phytotoxins were tested concurrently for animal and plant toxicity. There appeared to be no direct relationship between plant and animal toxicity. PMID:5059620

  11. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  12. Kombucha--toxicity alert.

    Science.gov (United States)

    The Kombucha mushroom, also known as Manchurian mushroom, is a mail-order product touted to lower blood pressure and raise T-cell counts. No controlled trials have been conducted to test these claims. Aspergillus, a mold that may grow on the Kombucha mushroom, attacks the brain and may be fatal to persons with weakened immune systems. Reported toxicity reactions have included stomach problems and yeast infections. Taking Kombucha in combination with other drugs may affect the drugs potency.

  13. Toxicity of Depleted Uranium

    Science.gov (United States)

    1997-02-01

    cancer in dogs and humans1 and mice and humans.2 The information for inert metal toxicity in humans is foreign-body carcinogenesis data related to...high dose of Thorotrast® (> 0.4 Bq/g) developed fibrosarcomas from perivascular leakage of some injections.19 Plutonium fragments have been injected...into the footpads of dogs to simulate the plutonium-contaminated wounds of plutonium machinists.2" The plutonium was translocated to the local lymph

  14. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  15. Toxicity of nanomaterials.

    Science.gov (United States)

    Sharifi, Shahriar; Behzadi, Shahed; Laurent, Sophie; Forrest, M Laird; Stroeve, Pieter; Mahmoudi, Morteza

    2012-03-21

    Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

  16. Amiodarone Pulmonary Toxicity

    Directory of Open Access Journals (Sweden)

    Norman Wolkove

    2009-01-01

    Full Text Available Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.

  17. Amiodarone pulmonary toxicity

    Science.gov (United States)

    Wolkove, Norman; Baltzan, Marc

    2009-01-01

    Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects. PMID:19399307

  18. Modern toxic antipersonnel projectiles.

    Science.gov (United States)

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

    2014-12-01

    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  19. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-02-01

    LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Toxic metals and autophagy.

    Science.gov (United States)

    Chatterjee, Sarmishtha; Sarkar, Shuvasree; Bhattacharya, Shelley

    2014-11-17

    The earth's resources are finite, and it can no longer be considered a source of inexhaustible bounty for the human population. However, this realization has not been able to contain the human desire for rapid industrialization. The collateral to overusing environmental resources is the high-level contamination of undesirable toxic metals, leading to bioaccumulation and cellular damage. Cytopathological features of biological systems represent a key variable in several diseases. A review of the literature revealed that autophagy (PCDII), a high-capacity process, may consist of selective elimination of vital organelles and/or proteins that intiate mechanisms of cytoprotection and homeostasis in different biological systems under normal physiological and stress conditions. However, the biological system does survive under various environmental stressors. Currently, there is no consensus that specifies a particular response as being a dependable biomarker of toxicology. Autophagy has been recorded as the initial response of a cell to a toxic metal in a concentration- and time-dependent manner. Various signaling pathways are triggered through cellular proteins and/or protein kinases that can lead to autophagy, apoptosis (or necroptosis), and necrosis. Although the role of autophagy in tumorigenesis is associated with promoting tumor cell survival and/or acting as a tumor suppressive mechanism, PCDII in metal-induced toxicity has not been extensively studied. The aim of this review is to analyze the comparative cytotoxicity of metals/metalloids and nanoparticles (As, Cd, Cr, Hg, Fe, and metal-NP) in cells enduring autophagy. It is noted that metals/metalloids and nanoparticles prefer ATG8/LC3 as a potent inducer of autophagy in several cell lines or animal cells. MAP kinases, death protein kinases, PI3K, AKT, mTOR, and AMP kinase have been found to be the major components of autophagy induction or inhibition in the context of cellular responses to metals/metalloids and

  1. Nanoparticle toxicity and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Prevenslik, T, E-mail: nanoqed@gmail.com [QED Radiations, Discovery Bay, Hong Kong (Hong Kong)

    2011-07-06

    Nanoparticles (NPs) have provided significant advancements in cancer treatment. But as in any technology, there is a darkside. Experiments have shown NPs in body fluids pose a health risk by causing DNA damage that in of itself may lead to cancer. To avoid the dilemma that NPs are toxic to both cancer cells and DNA alike, the mechanism of NP toxicity must be understood so that the safe use of NPs may go forward. Reactive oxidative species (ROS) of peroxide and hydroxyl radicals damage the DNA by chemical reaction, but require NPs provide energies of about 5 eV not possible by surface effects. Only electromagnetic (EM) radiations beyond ultraviolet (UV) levels may explain the toxicity of NPs. Indeed, experiments show DNA damage from <100 nm NPs mimic the same reaction pathways of conventional sources of ionizing radiation, Hence, it is reasonable to hypothesize that NPs produce their own source of UV radiation, albeit at low intensity. Ionizing radiation from NPs at UV levels is consistent with the theory of QED induced EM radiation. QED stands for quantum electrodynamics. By this theory, fine < 100 nm NPs absorb low frequency thermal energy in the far infrared (FIR) from collisions with the water molecules in body fluids. Since quantum mechanics (QM) precludes NPs from having specific heat, absorbed EM collision energy cannot be conserved by an increase in temperature. But total internal reflection (TIR) momentarily confines the absorbed EM energy within the NP. Conservation proceeds by the creation of QED photons by frequency up-conversion of the absorbed EM energy to the TIR confinement frequency, typically beyond the UV. Subsequently, the QED photons upon scattering from atoms within the NP avoid TIR confinement and leak UV to the surroundings, thereby explaining the remarkable toxicity of NPs. But QED radiation need not be limited to natural or man-made NPs. Extensions suggest UV radiation is produced from biological NPs within the body, e.g., enzyme induced

  2. Neurological oxygen toxicity.

    Science.gov (United States)

    Farmery, Scott; Sykes, Oliver

    2012-10-01

    SCUBA diving has several risks associated with it from breathing air under pressure--nitrogen narcosis, barotrauma and decompression sickness (the bends). Trimix SCUBA diving involves regulating mixtures of nitrogen, oxygen and helium in an attempt to overcome the risks of narcosis and decompression sickness during deep dives, but introduces other potential hazards such as hypoxia and oxygen toxicity convulsions. This study reports on a seizure during the ascent phase, its potential causes and management and discusses the hazards posed to the diver and his rescuer by an emergency ascent to the surface.

  3. Steady-state properties of sodium channels from healthy and tumorous human brain

    NARCIS (Netherlands)

    Frenkel, C.; Wartenberg, H. C.; Duch, D. S.; Urban, B. W.

    1998-01-01

    This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and

  4. Conditional intrinsic voltage oscillations in mature vertebrate neurons undergo specific changes in culture

    DEFF Research Database (Denmark)

    Guertin, Pierre A; Hounsgaard, Jørn

    2006-01-01

    cord of adult turtles maintainable for several weeks in culture conditions. N-methyl-D-aspartate (NMDA)-induced-tetrodotoxin (TTX)-resistant voltage oscillations in motoneurons were approximately 10 times faster in culture than in acute preparations. Oscillations in culture were abolished by NMDA...... to understanding further the potential for plasticity of mature vertebrate neurons....

  5. Molecular toxicity of nanomaterials.

    Science.gov (United States)

    Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

    2014-10-01

    With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

  6. Biological control of toxic cyanobacteria

    CSIR Research Space (South Africa)

    Ndlela, L

    2016-04-01

    Full Text Available • If successful, the biocontrol agent may produce conformational changes to the cyanobacterial toxins or reduced eco-toxicity effects • The laboratory study may give insight into the factors inhibiting the natural balance of predatory bacteria... studies have been done on the eco-toxicity resulting from biocontrol as well as the changes to cyanotoxins, if any. Research Plan The study will be conducted at whole cell level and with specific metabolites and toxins, with eco-toxicity studied...

  7. Tapentadol toxicity in children.

    Science.gov (United States)

    Borys, Douglas; Stanton, Matthew; Gummin, David; Drott, Tracy

    2015-02-01

    Tapentadol (Nucynta) is indicated for the treatment of moderate to severe pain in adults. Tapentadol's mechanism of action consists of acting as an agonist on the μ-opioid receptor and by inhibiting the reuptake of norepinephrine. There are no published reports on the toxicity of tapentadol in pediatric patients. The goals of this study are to describe the incidence, medical outcomes, clinical effects, and treatment secondary to tapentadol exposure. This retrospective observational study used data from the National Poison Data System. Inclusion criteria were exposure to tapentadol from November 1, 2008 to December 31, 2013; age 0 to 17 years; single ingestion; and followed to a known outcome. There were 104 patients who met the inclusion criteria. Eighty patients were aged ≤ 6, 2-year-olds the most common age group (60.6%). There were 52 male and 52 female patients. Of the 104 patients, 93 had unintentional exposures. No deaths were reported. Sixty-two of the patients had no effect, 34 had minor effects, 6 had moderate and 2 had major effects. Thirty patients reported drowsiness and lethargy. Other effects reported included nausea, vomiting, miosis, tachycardia, respiratory depression, dizziness/vertigo, coma, dyspnea, pallor, vomiting, edema, hives/welts, slurred speech, pruritus, and hallucinations/delusions. Fifty-three patients were reported to have no medical intervention. This is the first study examining the toxic effects of tapentadol in a pediatric population. Although a majority of the patients in this review developed no effect from their exposure, two had life-threatening events. The most common effects reported were opioidlike. Copyright © 2015 by the American Academy of Pediatrics.

  8. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  9. Children's Ability to Recognise Toxic and Non-Toxic Fruits

    Science.gov (United States)

    Fancovicova, Jana; Prokop, Pavol

    2011-01-01

    Children's ability to identify common plants is a necessary prerequisite for learning botany. However, recent work has shown that children lack positive attitudes toward plants and are unable to identify them. We examined children's (aged 10-17) ability to discriminate between common toxic and non-toxic plants and their mature fruits presented in…

  10. Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant.

    Science.gov (United States)

    Naddy, Rami B; Tapp, Kelly; Rehner, Anita B; Pillard, David A; Schrage, Laura

    2011-10-01

    Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC=50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism.

    Science.gov (United States)

    Feldman, C R; Durso, A M; Hanifin, C T; Pfrender, M E; Ducey, P K; Stokes, A N; Barnett, K E; Brodie, E D; Brodie, E D

    2016-01-01

    Convergent evolution of tetrodotoxin (TTX) resistance, at both the phenotypic and genetic levels, characterizes coevolutionary arms races between amphibians and their snake predators around the world, and reveals remarkable predictability in the process of adaptation. Here we examine the repeatability of the evolution of TTX resistance in an undescribed predator-prey relationship between TTX-bearing Eastern Newts (Notophthalmus viridescens) and Eastern Hog-nosed Snakes (Heterodon platirhinos). We found that that local newts contain levels of TTX dangerous enough to dissuade most predators, and that Eastern Hog-nosed Snakes within newt range are highly resistant to TTX. In fact, these populations of Eastern Hog-nosed Snakes are so resistant to TTX that the potential for current reciprocal selection might be limited. Unlike all other cases of TTX resistance in vertebrates, H. platirhinos lacks the adaptive amino acid substitutions in the skeletal muscle sodium channel that reduce TTX binding, suggesting that physiological resistance in Eastern Hog-nosed Snakes is conferred by an alternate genetic mechanism. Thus, phenotypic convergence in this case is not due to parallel molecular evolution, indicating that there may be more than one way for this adaptation to arise, even among closely related species.

  12. Externalization of the Toxic Introject

    Science.gov (United States)

    Beck, Michael

    1975-01-01

    The therapist encounters patients who have incorporated toxic introjects. Therapy helps them to provide room for incorporation of a healthy object by externalizing the toxic introject. This technique is illustrated with several cases and comparison is made between the use of this technique in the treatment of adults and children. (Author)

  13. Toxic Leadership in Educational Organizations

    Science.gov (United States)

    Green, James E.

    2014-01-01

    While research on the traits and skills of effective leaders is plentiful, only recently has the phenomenon of toxic leadership begun to be investigated. This research report focuses on toxic leadership in educational organizations--its prevalence, as well as the characteristics and early indicators. Using mixed methods, the study found four…

  14. One Health and Toxic Cyanobacteria

    Science.gov (United States)

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving...

  15. The toxicity of X material

    Energy Technology Data Exchange (ETDEWEB)

    Ferry, J.L.

    1943-12-31

    This report addresses toxicity (largely chemical) of Manhattan Project materials from the point of worker protection. Known chemical toxicities of X material (uranium), nitrous fumes, fluorine, vanadium, magnesium, and lime are described followed by safe exposure levels, symptoms of exposure, and treatment recommendations. The report closes with an overview of general policy in a question and answer format.

  16. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-04-01

    Full Text Available Toxic currency options are defined on the basis of the opposition to the nature (essence of an option contract, which is justified in terms of norms founded on the general law clause of characteristics (nature of a relation (which represents an independent premise for imposing restrictions on the freedom of contracts. So-understood toxic currency options are unlawful. Indeed they contravene iuris cogentis regulations. These include for instance option contracts, which are concluded with a bank, if the bank has not informed about option risk before concluding the contract; or the barrier options, which focus only on the protection of banks interests. Therefore, such options may appear to be invalid. Therefore, performing contracts for toxic currency options may be qualified as a criminal mismanagement. For the sake of security, the manager should then take into consideration filing a claim for stating invalidity (which can be made in a court verdict. At the same time, if the supervisory board member in a commercial company, who can also be a subject to mismanagement offences, commits an omission involving lack of reaction (for example, if he/she fails to notify of the suspected offence committed by the management board members acting to the companys detriment when the management board makes the company conclude option contracts which are charged with absolute invalidity the supervisory board member so acting may be considered to act to the companys detriment. In the most recent Polish jurisprudence and judicature the standard of a good host is treated to be the last resort for determining whether the managers powers resulting from criminal regulations were performed. The manager of the exporter should not, as a rule, issue any options. Issuing options always means assuming an obligation. In the case of currency put options it is an absolute obligation to purchase a given amount in euro at exchange rate set in advance. On the other hand issuing

  17. VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, F

    2008-05-13

    Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

  18. Hydrocarbon toxicity: A review.

    Science.gov (United States)

    Tormoehlen, L M; Tekulve, K J; Nañagas, K A

    2014-06-01

    Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia

  19. Toxicity of energy drinks.

    Science.gov (United States)

    Wolk, Brian J; Ganetsky, Michael; Babu, Kavita M

    2012-04-01

    'Energy drinks', 'energy shots' and other energy products have exploded in popularity in the past several years; however, their use is not without risk. Caffeine is the main active ingredient in energy drinks, and excessive consumption may acutely cause caffeine intoxication, resulting in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The effects of chronic high-dose caffeine intake in children and adolescents are unknown. Caffeine may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors, harm to adolescent users, impaired driving, and increased use of other illicit substances. The toxicity of ingredients often present in energy drinks, such as taurine, niacin, and pyridoxine, is less well defined. Recent and significant literature describing adverse events associated with energy drink use are reviewed. Although prior studies have examined the effects of caffeine in adolescents, energy drinks should be considered a novel exposure. The high doses of caffeine, often in combination with ingredients with unknown safety profiles, mandates urgent research on the safety of energy drink use in children and adolescents. Regulation of pediatric energy drink use may be a necessary step once the health effects are further characterized.

  20. Overcoming ammonium toxicity.

    Science.gov (United States)

    Bittsánszky, András; Pilinszky, Katalin; Gyulai, Gábor; Komives, Tamas

    2015-02-01

    Ammonia (ammonium ion under physiological conditions) is one of the key nitrogen sources in cellular amino acid biosynthesis. It is continuously produced in living organisms by a number of biochemical processes, but its accumulation in cells leads to tissue damage. Current knowledge suggests that a few enzymes and transporters are responsible for maintaining the delicate balance of ammonium fluxes in plant tissues. In this study we analyze the data in the scientific literature and the publicly available information on the dozens of biochemical reactions in which endogenous ammonium is produced or consumed, the enzymes that catalyze them, and the enzyme and transporter mutants listed in plant metabolic and genetic databases (Plant Metabolic Network, TAIR, and Genevestigator). Our compiled data show a surprisingly high number of little-studied reactions that might influence cellular ammonium concentrations. The role of ammonium in apoptosis, its relation to oxidative stress, and alterations in ammonium metabolism induced by environmental stress need to be explored in order to develop methods to manage ammonium toxicity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. The future of toxicity testing.

    Science.gov (United States)

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

    2010-02-01

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

  2. A COMPREHENSIVE REVIEW OF TOXIC LEADERSHIP

    Science.gov (United States)

    2016-02-05

    Definitions of Toxic Leadership ...3 Table 1: Definitions of Toxic Leadership ... leadership . However, there are differing explanations as to the cause, solution, and even the definition of toxic leadership . This research contains

  3. National Air Toxic Assessments (NATA) Results

    Data.gov (United States)

    U.S. Environmental Protection Agency — The National Air Toxics Assessment was conducted by EPA in 2002 to assess air toxics emissions in order to identify and prioritize air toxics, emission source types...

  4. Biological control of toxic cyanobacteri

    CSIR Research Space (South Africa)

    Ndlela, Luyanda L

    2017-05-01

    Full Text Available and applications • If successful, the biocontrol agents may produce conformational changes to the cyanobacterial toxins or reduced eco-toxicity effects • The laboratory study may give insight into the factors inhibiting the natural balance of predatory... on the eco-toxicity resulting from biocontrol as well as the changes to cyanotoxins, if any. Research Plan The study will be conducted at whole cell level and with specific metabolites and toxins, with eco-toxicity studied at three trophic levels...

  5. Developmental Exposure to Environmental Toxicants.

    Science.gov (United States)

    Falck, Alison J; Mooney, Sandra; Kapoor, Shiv S; White, Kimberly M R; Bearer, Cynthia; El Metwally, Dina

    2015-10-01

    Children interact with the physical environment differently than adults, and are uniquely susceptible to environmental toxicants. Routes of absorption, distribution, metabolism, and target organ toxicities vary as children grow and develop. This article summarizes the sources of exposure and known adverse effects of toxicants that are ubiquitous in our environment, including tobacco smoke, ethanol, solvents, heavy metals, volatile organic compounds, persistent organic pollutants, and pesticides. Preventive strategies that may be used in counseling children and their families are highlighted. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. [Imatinib-induced pulmonary toxicity].

    Science.gov (United States)

    Carrillo-Esper, Raúd; Morales-Victorino, Neisser

    2009-01-01

    Antineoplasic agent-induced pulmonary toxicity is an important cause of respiratory failure. These novel antineoplastic agents include imatinib mesylate, a protein tyrosine kinase inhibitor that is encoded by the Bcr-Abl gen created by the Philadelphia chromosome abnormality in chronic myeloid leukemia. Pulmonary toxicity of imatinib is directly related to the dose used. The more severe pulmonary manifestations include pleural effusion by water retention and interstitial pneumonitis. We report the first case published in Mexico ofimatinib-induced pulmonary toxicity and its management in the intensive care unit of the Medica Sur Clinic Foundation.

  7. Toxicity of staphylococcal toxic shock syndrome toxin 1 in rabbits.

    OpenAIRE

    de Azavedo, J C; Arbuthnott, J P

    1984-01-01

    Strains of Staphylococcus aureus associated with toxic shock syndrome produce toxic shock syndrome toxin 1 (TSST 1), which is lethal to conventional rabbits and acts synergistically with gram-negative lipopolysaccharide. The lethal effect of TSST 1 was examined in specific-pathogen-free rabbits on the basis that these rabbits, being less colonized by gram-negative bacteria, would be less susceptible than conventional animals. Although there was no significant difference in mortality between s...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-01

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

  9. Determination of leachate toxicity through acute toxicity using Daphnia pulex and anaerobic toxicity assays

    Directory of Open Access Journals (Sweden)

    Patricia Torres Lozada

    2017-01-01

    Full Text Available The municipal solid waste (MSW of large cities, in particular in developing countries, is mainly disposed of in landfills (LFs, whose inadequate management generates the emission of greenhouse gases and the production of leachates with high concentrations of organic and inorganic matter and occasionally heavy metals. In this study, the toxicity of the leachates from an intermediate-age municipal landfill was evaluated by ecotoxicity and anaerobic digestion tests. The acute toxicity assays with Daphnia pulex presented a toxic unit (TU value of 49.5%, which indicates that these leachates should not be directly discharged into water sources or percolate into the soil because they would affect the ecosystems served by these waters. According to statistical analyses, the leachate toxicity is mainly associated with the inorganic fraction, with chlorides, calcium hardness and calcium having the greatest influence on the toxicity. The anaerobic toxicity assays showed that in the exposure stage, the methanogenic activity exceeded that of the control, which suggests that the anaerobic bacteria easily adapted to the leachate. Therefore, this treatment could be an alternative to mitigate the toxicity of the studied leachates. The inhibition presented in the recovery stage, represented by a reduction of the methanogenic activity, could arise because the amount of supplied substrate was not enough to fulfill the carbon and nutrient requirements of the bacterial population present.

  10. Determination of leachate toxicity through acute toxicity using Daphnia pulex and Anaerobic Toxicity Assays

    Directory of Open Access Journals (Sweden)

    Patricia Torres Lozada

    2017-01-01

    Full Text Available The municipal solid waste (MSW of large cities, in particular in developing countries, is mainly disposed of in landfills (LFs, whose inadequate management generates the emission of greenhouse gases and the production of leachates with high concentrations of organic and inorganic matter and occasionally heavy metals. In this study, the toxicity of the leachates from an intermediate-age municipal landfill was evaluated by ecotoxicity and anaerobic digestion tests. The acute toxicity assays with Daphnia pulex presented a toxic unit (TU value of 49.5%, which indicates that these leachates should not be directly discharged into water sources or percolate into the soil because they would affect the ecosystems served by these waters. According to statistical analyses, the leachate toxicity is mainly associated with the inorganic fraction, with chlorides, calcium hardness and calcium having the greatest influence on the toxicity. The anaerobic toxicity assays showed that in the exposure stage, the methanogenic activity exceeded that of the control, which suggests that the anaerobic bacteria easily adapted to the leachate. Therefore, this treatment could be an alternative to mitigate the toxicity of the studied leachates. The inhibition presented in the recovery stage, represented by a reduction of the methanogenic activity, could arise because the amount of supplied substrate was not enough to fulfill the carbon and nutrient requirements of the bacterial population present.

  11. Non-Toxic HAN Monopropellant Propulsion Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Non-toxic monopropellants have been developed that provide better performance than toxic hydrazine. Formulations based on hydroxylammonium nitrate (HAN) have...

  12. Campylobacter colitis: Rare cause of toxic megacolon

    Directory of Open Access Journals (Sweden)

    Michael Kwok, MBBS

    2016-01-01

    Conclusion: Toxic megacolon should be considered in a patient with Campylobacter colitis who becomes critically unwell. Despite treatment, toxic megacolon is associated with a significant risk of mortality.

  13. 2011 NATA - Air Toxics Monitors

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset includes annual (2005 - 2013) statistics of measured ambient air toxics concentrations (in micrograms per cubic meter) and associated risk estimates for...

  14. Methylmercury toxicity and functional programming

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2007-01-01

    PURPOSE: Adverse health effects of developmental toxicants may induce abnormal functional programming that leads to lasting functional deficits. This notion is considered from epidemiological evidence using developmental methylmercury neurotoxicity as an example. MOST IMPORTANT FINDINGS: Accumula...

  15. TOXIC AND DRUG INDUCED MYOPATHIES

    OpenAIRE

    2009-01-01

    Abstract Although the ?do no harm? dogma of Hippocrates is faithfully followed by all practitioners, drugs used for therapeutic interventions either alone or in combination, may sometimes cause unexpected toxicity to the muscles, resulting in a varying degree of symptomatology, from mild discomfort and inconvenience to permanent damage and disability. The clinician should suspect a toxic myopathy when a patient without a pre-existing muscle disease develops myalgia, fatigue, weakn...

  16. Toxic stress and child refugees.

    Science.gov (United States)

    Murray, John S

    2018-01-01

    The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life

  17. Baclofen Toxicity in Kidney Disease.

    Science.gov (United States)

    Wolf, Erin; Kothari, Niraj R; Roberts, John K; Sparks, Matthew A

    2018-02-01

    Baclofen, a commonly prescribed muscle relaxant, is primarily excreted via the kidneys; toxicity is a potentially serious adverse outcome in patients with decreased kidney function. We describe a patient with end-stage kidney disease receiving hemodialysis who developed neurotoxicity and hemodynamic instability after receiving baclofen for muscle spasms. In this case, prompt recognition of baclofen toxicity and urgent hemodialysis were effective in reversing this toxicity. This case is used to examine the pharmacokinetics and pathophysiology of baclofen toxicity and discuss appropriate diagnosis and management of baclofen toxicity. We recommend reducing the baclofen dose in patients who have moderately reduced kidney function (estimated glomerular filtration rate, 30-60mL/min/1.73m 2 ) and avoiding use in patients with severely reduced kidney function (estimated glomerular filtration rate < 30mL/min/1.73m 2 ) or on renal replacement therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Jatropha toxicity--a review.

    Science.gov (United States)

    Devappa, Rakshit K; Makkar, Harinder P S; Becker, Klaus

    2010-08-01

    Jatropha is a nonedible oil seed plant belonging to Euphorbiaceae family. Global awareness of sustainable and alternative energy resources has propelled research on Jatropha oil as a feedstock for biodiesel production. During the past two decades, several cultivation projects were undertaken to produce Jatropha oil. In future, the increased cultivation of toxic Jatropha plants and utilization of its agro-industrial by-products may raise the frequency of contact with humans, animals, and other organisms. An attempt was thus made to present known information on toxicity of Jatropha plants. The toxicity of Jatropha plant extracts from fruit, seed, oil, roots, latex, bark, and leaf to a number of species, from microorganisms to higher animals, is well established. Broadly, these extracts possess moluscicidal, piscicidal, insecticidal, rodenticidal, antimicrobial, and cytotoxic properties, and exert adverse effects on animals including rats, poultry, and ruminants. The toxicity attributed to these seeds due to their accidental consumption by children is also well documented. An attempt was also made to identify areas that need further study. The information provided in this review may aid in enhancing awareness in agroindustries involved in the cultivation, harvesting, and utilization of Jatropha plants and its products with respect to the potential toxicity of Jatropha, and consequently in application and enforcement of occupational safety measures. Data on the wide range of bioactivities of Jatropha and its products were collated and it is hoped will create new avenues for exploiting these chemicals by the phamaceutical industry to develop chemotherapeutic agents.

  19. Emerging exposures of developmental toxicants.

    Science.gov (United States)

    Wolff, Mary S; Buckley, Jessie P; Engel, Stephanie M; McConnell, Rob S; Barr, Dana B

    2017-04-01

    The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air. We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990-2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation. A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated.

  20. Predicting the toxicity of neat and weathered crude oil: toxic potential and the toxicity of saturated mixtures.

    Science.gov (United States)

    Di Toro, Dominic M; McGrath, Joy A; Stubblefield, William A

    2007-01-01

    The toxicity of oils can be understood using the concept of toxic potential, or the toxicity of each individual component of the oil at the water solubility of that component. Using the target lipid model to describe the toxicity and the observed relationship of the solubility of oil components to log (Kow), it is demonstrated that components with lower log (Kow) have greater toxic potential than those with higher log (Kow). Weathering removes the lower-log (Kow) chemicals with greater toxic potential, leaving the higher-log (Kow) chemicals with lower toxic potential. The replacement of more toxically potent compounds with less toxically potent compounds lowers the toxicity of the aqueous phase in equilibrium with the oil. Observations confirm that weathering lowers the toxicity of oil. The idea that weathering increases toxicity is based on the erroneous use of the total petroleum hydrocarbons or the total polycyclic aromatic hydrocarbons (PAHs) concentration as if either were a single chemical that can be used to gauge the toxicity of a mixture, regardless of its makeup. The toxicity of the individual PAHs that comprise the mixture varies. Converting the concentrations to toxic units (TUs) normalizes the differences in toxicity. A concentration of one TU resulting from the PAHs in the mixture implies toxicity regardless of the specific PAHs that are present. However, it is impossible to judge whether 1 microg/L of total PAHs is toxic without knowing the PAHs in the mixture. The use of toxic potential and TUs eliminates this confusion, puts the chemicals on the same footing, and allows an intuitive understanding of the effects of weathering.

  1. Gulf of Mexico mud toxicity limitations

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, H.E.; Beardmore, D.H. (Phillips Petroleum Co., Bartlesville, OK (USA)); Stewart, W.S. (Drilling Specialties Co. (US))

    1989-10-01

    Because of the Environmental Protection Agency's recent toxicity limits on drilling mud discharges for offshore Gulf of Mexico, Phillips Petroleum conducted a mud toxicity study based on both field and lab tests. The study, discussed in this article, found the polyanionic cellulose-sulfomethylated quebracho-chrome lignosulfonate mud Phillips had been using would comfortably pass the toxicity limitations. The study also found barite and thinners were of low toxicity, and hydrocarbons and surfactants were highly toxic.

  2. The Danger of Toxic Substances

    Directory of Open Access Journals (Sweden)

    M. V. Jokl

    2002-01-01

    Full Text Available Toxic (harmful gases enter building interiors partly from outdoors (sulfur oxides, nitrogen oxides, carbon monoxide, ozone, smog and acid rains, partly originate indoors - as a result of human activity (carbon monoxide, tobacco smoke, nitrogen oxides, ozone, hydrocarbons and also emanate from building materials (formaldehyde, volatile organic compounds. The human organism is most often exposed to cigarette smoke (especially nonsmokers are endangered, as cigarette smoke devastes the pulmonary and cardiovasculary system and to smog entering from outdoors, paradoxically during sunny weather. Preventing toxic production is the most effective measure, e.g., by coaxing to coax smokers out of "civilized" areas, by using energy rationally (i.e., conserving energy, to turn to pure fuels and to increase energy production by non-combustion technologies. Besides ventilation and air filtration, the toxic gases can be removed to a remarkable extent by plants (by which decay the substances into nontoxic gases, and by air ionization. Review article.

  3. Aluminium Toxicity Targets in Plants

    Directory of Open Access Journals (Sweden)

    Sónia Silva

    2012-01-01

    Full Text Available Aluminium (Al is the third most abundant metallic element in soil but becomes available to plants only when the soil pH drops below 5.5. At those conditions, plants present several signals of Al toxicity. As reported by literature, major consequences of Al exposure are the decrease of plant production and the inhibition of root growth. The root growth inhibition may be directly/indirectly responsible for the loss of plant production. In this paper the most remarkable symptoms of Al toxicity in plants and the latest findings in this area are addressed. Root growth inhibition, ROS production, alterations on root cell wall and plasma membrane, nutrient unbalances, callose accumulation, and disturbance of cytoplasmic Ca2+ homeostasis, among other signals of Al toxicity are discussed, and, when possible, the behavior of Al-tolerant versus Al-sensitive genotypes under Al is compared.

  4. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  5. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate (CuSO4) and lead nitrate (Pb[NO3]2) against the fish species. On the basis of daily mortality assessment, O. niloticus was found to be unable to survive in media with salinity ...

  6. [Amiodarone-induced pulmonary toxicity].

    Science.gov (United States)

    Heisel, A; Berg, M; Stopp, M; Ukena, D; Schieffer, H

    1997-12-01

    Amiodarone is highly effective in suppressing ventricular and supraventricular tachyarrhythmias. The most serious adverse reaction is pulmonary toxicity. The mechanisms involved in amiodarone-induced pulmonary injury are incompletely understood. Several forms of pulmonary disease occur including interstitial pneumonitis, fibrosis or organizing pneumonia. The incidence is generally lower with lower maintenance doses (amiodarone. The diagnosis of amiodarone-induced pulmonary toxicity is one of exclusion. Treatment consists primarily of stopping amiodarone application. Corticosteroid therapy can be life-saving for severe cases and for patients in whom withdrawl of amiodarone is not possible.

  7. Subacute toxicity of propyl gallate

    NARCIS (Netherlands)

    Strik JJTWA; Danse LHJC; Helleman PW; van Leeuwen FXR; Speijers GJA; Vaessen HAMG

    1986-01-01

    The 4 week oral toxicity of propyl gallate in rats, exposed to 0, 1000, 5000 and 25000 mg/kg feed, was investigated. Parameters studied comprised growth, food and water intake, biochemistry, hematology, organ weights and histopathology. In the highest dose group both females and males gained less

  8. Borocaptate sodium (BSH) toxicity issues

    Energy Technology Data Exchange (ETDEWEB)

    LaHann, T.

    1995-11-01

    ISU`s Center for Toxicology Research has been conducting toxicity testing of borocaptate sodium (BSH) to aid in assessing if proposed human studies of BSH are likely to be acceptably safe. This report describes BSH interactions with other biological agents.

  9. Gossypol Toxicity from Cottonseed Products

    Directory of Open Access Journals (Sweden)

    Ivana Cristina N. Gadelha

    2014-01-01

    Full Text Available Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.. Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal’s resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

  10. Niagara River Toxics Management Plan

    Science.gov (United States)

    This 2007 Progress Report of the Niagara River Toxics Management Plan (NRTMP) summarizes progress made by the four parties in dealing with the 18 “Priority Toxics” through reductions in point and non-point sources to the Niagara River.

  11. The Biochemistry of Alcohol Toxicity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 10. The Biochemistry of Alochol Toxicity. B Ramachandra Murty. General Article Volume 9 Issue 10 October 2004 pp 41-47. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/009/10/0041-0047 ...

  12. Holiday Plants with Toxic Misconceptions

    Directory of Open Access Journals (Sweden)

    Zabrina N. Evens

    2012-12-01

    Full Text Available Several plants are used for their decorative effect during winter holidays. This review explores the toxic reputation and proposed management for exposures to several of those, namely poinsettia (Euphorbia pulcherrima, English holly (Ilex aquifolium, American holly (Ilex opaca,bittersweet (Solanum dulcamara, Jerusalem cherry (Solanum pseudocapsicum, Americanmistletoe (Phoradendron serotinum, and European mistletoe (Viscum album.

  13. Effects of sea-anemone toxin (ATX-II) on the frequency of miniature endplate potentials at rat neuromuscular junctions.

    Science.gov (United States)

    Harris, J. B.; Tesseraux, I.

    1984-01-01

    Soleus and extensor digitorum longus muscles were isolated from rats. The muscles were exposed to ATX-II, a toxin isolated from extracts of the sea-anemone Anemonia sulcata . The toxin caused a dose-dependent increase in the frequency of miniature endplate potentials in both types of muscle. The increase in frequency could be reversed by the application of tetrodotoxin (TTX), and could be prevented by prior exposure of the muscles to TTX. It is concluded that ATX-II causes a sodium-dependent depolarization of the nerve-terminal membrane. PMID:6144341

  14. Oleander toxicity: an examination of human and animal toxic exposures.

    Science.gov (United States)

    Langford, S D; Boor, P J

    1996-05-03

    The oleander is an attractive and hardy shrub that thrives in tropical and subtropical regions. The common pink oleander, Nerium oleander, and the yellow oleander, Thevetia peruviana, are the principle oleander representatives of the family Apocynaceae. Oleanders contain within their tissues cardenolides that are capable of exerting positive inotropic effects on the hearts of animals and humans. The cardiotonic properties of oleanders have been exploited therapeutically and as an instrument of suicide since antiquity. The basis for the physiological action of the oleander cardenolides is similar to that of the classic digitalis glycosides, i.e. inhibition of plasmalemma Na+,K+ ATPase. Differences in toxicity and extracardiac effects exist between the oleander and digitalis cardenolides, however. Toxic exposures of humans and wildlife to oleander cardenolides occur with regularity throughout geographic regions where these plants grow. The human mortality associated with oleander ingestion is generally very low, even in cases of intentional consumption (suicide attempts). Experimental animal models have been successfully utilized to evaluate various treatment protocols designed to manage toxic oleander exposures. The data reviewed here indicate that small children and domestic livestock are at increased risk of oleander poisoning. Both experimental and established therapeutic measures involved in detoxification are discussed.

  15. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    ... on the actual toxicity of chemicals currently in use, discusses variables that contribute to the relative toxicity of a substance, compares alternate emphases in existing programs for reducing environmental...

  16. Boron toxicity in oil palm (Elaeis guineensis)

    Energy Technology Data Exchange (ETDEWEB)

    Rajaratnam, J.A.

    1973-01-01

    Potted oil palms were treated with fertilizer of borate-46 at several concentrations and the plants were observed for boron toxicity effects. Toxicity symptoms were apparent at high rates but not at rates equivalent to typical Malaysian soils.

  17. Toxicity and Phototoxicity of Chemical Sun Filters

    Energy Technology Data Exchange (ETDEWEB)

    Butt, S.T.; Christensen, T

    2000-07-01

    Two chemical sun filters that are ingredients in sunscreen products have been tested for their dark toxicity and possible toxicity to mouse cells after UV irradiation. Increased toxicity as a result of breakdown of a UVB filter, octyl methoxycinnamate, was observed. UV radiation absorbed by the pure chemical sunscreen may lead to breakdown to more reactive chemical compounds than the unexposed sunscreen filter. The UVA filter included in our tests, butyl methoxydibenzoylmethane, was also toxic in the dark, however, it was the more photostable of the two and no additional significant toxicity was induced by UV irradiation. It can be concluded that the two sun filters are toxic to cells in the dark, but the biological role of this dark toxicity in the skin is not clear. Unstable sun filters may be broken down by UV to form photoproducts that are potentially toxic. (author)

  18. Toxic Release Inventory Chemicals by Groupings

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released...

  19. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  20. Toxicity evaluation and hazard review Cold Smoke

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, M.M.; Stocum, W.E.

    1993-12-01

    Cold Smoke is a dense white smoke produced by the reaction of titanium tetrachloride and aqueous ammonia aerosols. Early studies on the toxicity of this nonpyrotechnically generated smoke indicated that the smoke itself is essentially non-toxic (i.e. exhibits to systemic toxicity or organ damage due to exposure) under normal deployment conditions. The purpose of this evaluation was to review and summarize the recent literature data available on the toxicity of Cold Smoke, its chemical constituents, and its starting materials.

  1. Cetuximab-associated pulmonary toxicity.

    Science.gov (United States)

    Chua, Wei; Peters, Matthew; Loneragan, Robert; Clarke, Stephen

    2009-04-01

    There is increasing evidence for the use of epidermal growth factor receptor (EGFR) inhibitors in head and neck, non-small-cell lung, and colorectal cancers. We report the case of a 78-year-old man with metastatic colorectal cancer (CRC) involving liver and lung who received cetuximab plus irinotecan as third-line treatment. Two months later, he presented with signs and symptoms consistent with bronchiolotis obliterans organizing pneumonia secondary to cetuximab. Reports of cetuximab-associated pulmonary toxicity are rare, although there have been extensive reports of interstitial fibrosis with the use of other EGFR inhibitors such as gefitinib and erlotinib. There are many causes of pulmonary infiltrates in patients treated for advanced CRC, and this case highlights the importance of considering drug toxicity.

  2. A Miniscale Algal Toxicity Test

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  3. Salicylate toxicity model of tinnitus

    Directory of Open Access Journals (Sweden)

    Daniel eStolzberg

    2012-04-01

    Full Text Available Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs or aging which affects ~14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed.

  4. Engineered Nanoparticle (Eco)Toxicity

    DEFF Research Database (Denmark)

    Cupi, Denisa

    dispersion protocol development. This may serve as a basis for the development of a harmonized dispersion protocol for ENPs. Natural organic matter (NOM) and aging of suspensions prior to testing were employed in an attempt to stabilize aqueous suspensions of three different ENPs. While NOM helped...... in stabilizing ZnO ENPs suspensions, it caused agglomeration in TiO2 ENP stock suspensions and an underestimation of toxicity for Ag ENPs. Likewise, aging only aided in the stability of ZnO ENPs. It was concluded that NOM can mitigate or eliminate toxicity of Ag ENPs and is not recommended for use. The ratio...... of NOM to ENP proved to be important in stabilizing non-capped ENPs. Another attempt towards stable suspensions involved adjusting different standard testing parameters, such as the pH and ionic strength of the test media. It was found that point of zero charge measurements should be conducted prior...

  5. Toxicity of ethion in goats.

    Science.gov (United States)

    Mosha, R D; Gyrd-Hansen, N

    1990-02-01

    Cholinesterase activities were measured in plasma and in red blood cells from 6 goats after iv injection of the organophosphorus insecticide ethion at 3 different dose levels--2 mg/kg, 5 mg/kg and 10 mg/kg. Plasma levels of ethion after injection were established. At 2 mg/kg no signs of toxicity were observed and the blood cholinesterase activity remained above 65% of the control value. After administration of the higher doses the goats showed signs of severe toxicity corresponding to increased parasympathetic stimulation. Cholinesterase activities in blood were reduced to approximately 10% of the control value for the 5 mg/kg group and to approximately 5% for the 10 mg/kg group. Reactivation of cholinesterase activity in blood cells and plasma by means of pralidoxime was very efficient during the first 24 hr after administration of ethion, but was insignificant after 72 hours.

  6. Toxicity of weight loss agents.

    Science.gov (United States)

    Yen, May; Ewald, Michele Burns

    2012-06-01

    With the rise of the obesity epidemic in the United States over the last several decades and the medical complications seen with it, weight loss and dieting have become a national public health concern. Because of their increased use and availability through internet sales, several different dieting agents were reviewed for potential toxicity. These included: syrup of ipecac, cathartics, human chorionic gonadotropin hormone, 2,4 Dinitrophenol, guar gum, phenylpropanolamine, ma huang/ ephedra, caffeine, clenbuterol, fenfluramine, sibutramine, thyroid hormone, orlistat and cannabinoid antagonists. With the internet making even banned products readily accessible, healthcare providers need to be aware of the potential toxicities of a wide range of weight loss agents. Our review covered topics we thought to be most historically significant as well as pertinent to the practice of medical toxicology today.

  7. The Effect of Toxic Leadership

    Science.gov (United States)

    2012-03-15

    leaders are a product of their environment, unlike corporations that hire mid-level and senior level managers to guide their organizations; the...01674544. 5 Tomas Giberson and others, "Leadership and Organizational Culture: Linking Ceo Characteristics to Cultural Values," Journal of Business...Craig; Lim. 23 David Lease, "From Great to Ghastly: How Toxic Organizational Cultures Poison Companies the Rise and Fall of Enron , Worldcom, Healthsouth

  8. Dietary zinc and its toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lantzsch, H.J.

    1973-01-01

    First signs of Zn-toxicity in rats appeared at 1000 to 2000 ppm Zn in food. They were characterized by growth inhibition by the appearance of a microcytic hypochromic anemia by a reversible impairment of the ability to reproduce by disturbances in fat metabolism and by Zn-accumulation especially in the liver and the skeleton. Available results in the literature concerning alimentary Zn-toxicity in horses are few. At a daily doses of 8000 mg Zn during gestation there were no noticeable adverse effects either in the mare or the foal. While with young lambs addition of Zn of up to 1000 ppm enhanced growth, food intake and feed efficiency, with older lambs it gave rise to depressions. Available results of experiments with milk cows are equally insufficient. At Zn-concentration of 40 to 80 ppm, which may be reached in normal foodstuff, there appears to be a disturbance in the metabolism of cellulose in the rumen. In spite of this fact and notwithstanding the insufficiently examined influence of high Zn-concentrations in food on the Cu-metabolism, the limit of Zn-tolerance can be given at 1000 mg per kg of food. If dissolved, Zn is far more toxic. With calves there wre no signs of clinical toxicity up to Zn-concentrations in the food of 3000 ppm. Above 900 ppm there appeared depression in growth and deterioration in the feed efficiency. Ae 1700 ppm there was a decrease infood intake. Increased Zn-intake lead to a growing Zn-accumulation in several organs and tissues, with the accumulation in the liver, bones, kidneys, pancreas and the gastrointestinal tract being of special significance. With cessation of Zn-intake in food, Zn-accumulation slowly disappeared. As a result of high Zn-intake there appears to be synergistic and antagonistic interdependent effects with the metabolism of other trace elements (Cu, Fe) and minerals (Ca, Na, P).

  9. Allergy and "toxic mold syndrome".

    Science.gov (United States)

    Edmondson, David A; Nordness, Mark E; Zacharisen, Michael C; Kurup, Viswanath P; Fink, Jordan N

    2005-02-01

    "Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

  10. Toxicity of 56 substances to trees

    DEFF Research Database (Denmark)

    Clausen, Lauge Peter Westergaard; Trapp, Stefan

    2017-01-01

    Toxicity data of substances to higher plants is needed for the purpose of risk assessment, site evaluation, phytoremediation, and plant protection. However, the results from the most common phytotoxicity tests, like the OECD algae and Lemna test, are not necessarily valid for higher terrestrial...... toxicity test is a robust method for relating uptake, accumulation, and metabolism of substances to the toxicity to trees....

  11. Joint toxic effects on Caenorhabditis elegans

    NARCIS (Netherlands)

    Jonker, M.J.

    2003-01-01

    In polluted areas organisms are generally exposed to mixtures of toxic chemicals rather than a single toxicant only. Since the number of mixture toxicity studies with regard to soil systems is limited, the research in this thesis was focused on investigating ecotoxicological consequences of combined

  12. CAESAR models for developmental toxicity

    Directory of Open Access Journals (Sweden)

    Piclin Nadège

    2010-07-01

    Full Text Available Abstract Background The new REACH legislation requires assessment of a large number of chemicals in the European market for several endpoints. Developmental toxicity is one of the most difficult endpoints to assess, on account of the complexity, length and costs of experiments. Following the encouragement of QSAR (in silico methods provided in the REACH itself, the CAESAR project has developed several models. Results Two QSAR models for developmental toxicity have been developed, using different statistical/mathematical methods. Both models performed well. The first makes a classification based on a random forest algorithm, while the second is based on an adaptive fuzzy partition algorithm. The first model has been implemented and inserted into the CAESAR on-line application, which is java-based software that allows everyone to freely use the models. Conclusions The CAESAR QSAR models have been developed with the aim to minimize false negatives in order to make them more usable for REACH. The CAESAR on-line application ensures that both industry and regulators can easily access and use the developmental toxicity model (as well as the models for the other four endpoints.

  13. Determinants of carbon nanotube toxicity.

    Science.gov (United States)

    Lanone, Sophie; Andujar, Pascal; Kermanizadeh, Ali; Boczkowski, Jorge

    2013-12-01

    In the last few years questions have been raised regarding the potential toxicity of carbon nanotubes (CNTs) to humans and environment. It is believed that the physico-chemical characteristics of these materials are key determinants of CNT interaction with living organisms, and hence determine their toxicity. As for other nanomaterials, the most important of these characteristics are the length, diameter, surface area, tendency to agglomerate, bio-durability, presence and nature of catalyst residues as well as chemical functionalization of the CNT. This review highlights the recent advancements in the understanding of the CNT properties which are essential in determining CNT toxicity. Hence the focus is on CNT dimensions, surface properties, bio-durability and corona formation as these fields have evolved greatly in recent years. A deeper understanding of these events and their underlying mechanisms could provide a molecular explanation of the biological and physiological responses following CNT administration and therefore help in the development of safe by design materials. © 2013 Elsevier B.V. All rights reserved.

  14. Pulmonary toxicity of manufactured nanoparticles

    Science.gov (United States)

    Peebles, Brian Christopher

    Manufactured nanomaterials have become ubiquitous in science, industry, and medicine. Although electron microscopy and surface probe techniques have improved understanding of the physicochemical properties of nanomaterials, much less is known about what makes nanomaterials toxic. Particulate matter less than 2.5 mum in effective aerodynamic diameter is easily inhaled and taken deep into the lungs. The toxicity of inhaled particulate matter is related to its size and surface chemistry; for instance, the smaller the size of particles, the greater their specific surface area. The chemistry and toxicity of insoluble particles depends on their surface area, since chemical reactions may happen with the environment on the surface. Oxidation and reduction may occur on the surfaces of particles after they are produced. For instance, it is known that carbonaceous particles from vehicle exhaust and industrial emission may interact with reactive species like ozone in their ambient environment, altering the surface chemistry of the particles. Reaction with species in the environment may cause changes in the chemical functionality of the surface and change the toxic properties of the particles when they are inhaled. Furthermore, metals on the surface of inhalable particles can contribute to their toxicity. Much attention has been given to the presence of iron on the surfaces of inhalable particles in the environment. After particle inhalation, particles are endocytosed by alveolar macrophages in the immune response to foreign matter. They are exposed to hydrogen peroxide in the oxidative burst, which can cause the iron-mediated production of hydroxyl free radicals via the Fenton reaction, causing oxidative stress that leads to inflammation and cell death. The toxicity of particles that contain metals depends on the redox activity and bioavailability of the metals, the causes of thich have not yet been adequately explored. In this thesis, electron paramagnetic spectroscopy showed

  15. Toxic photoproducts of phenanthrene in sunlight

    Energy Technology Data Exchange (ETDEWEB)

    McConkey, B.L.; Duxbury, C.L.; El-Alawi, Y.S.; Dixon, D.G.; Greenberg, B.M. [Univ. of Waterloo, Ontario (Canada). Dept. of Biology

    1995-12-31

    Phenanthrene, one of the most prevalent PAHs, undergoes a significant increase in toxicity on exposure to sunlight. Over a period of several days exposure to light, the toxicity of an aqueous phenanthrene solution increased dramatically. This increase in toxicity is largely due to the primary photoproduct, 9,10-phenanthrenequinone. This compound is more toxic than phenanthrene at equimolar concentrations, and is more water soluble than phenanthrene, increasing its bioavailability. Although many PAHs are potent photosensitizers, phenanthrene did not exhibit a significant increase in toxicity due to photosensitization. Photo-oxidation was the principal cause of photoinduced toxicity, with 9,10-phenanthrenequinone being formed via an unstable intermediate. In addition, mixtures of phenanthrene and 9,10-phenanthrenequinone exhibited potentially synergistic effects, as shown by joint toxicity testing using Photobacterium phosphoreum. Thus, mixtures of oxidized PAHs produced by photoaction in the environment create a significant risk to the biosphere.

  16. Genetic Toxicity Assessment of Chloropentafluorobenzene

    Science.gov (United States)

    1990-12-01

    involved in the production of the different types of aberrations which were observed, i.e., complex aberrations may have more significance than simple...used in cell cultures due to its low toxicity and ability to lower surface tension. When a preparation of lOmg /mL of CPFB in 9% w/v Pluronic® F-68 in...chemical carcinogenic potential. In: M.D. Waters, et al., eds. Short term Bioassays in the Analysis of Complex Environmental Mixtures II.. NY: Plenum

  17. Loureirin B: An Effective Component in Dragon's Blood Modulating Sodium Currents in TG Neurons.

    Science.gov (United States)

    Liu, Xiangming; Yin, Shijin; Chen, Su; Ma, Quanshun

    2005-01-01

    To test, analyze and express the relationship between the pharmacological effect of Traditional Chinese Medicine (TCM) dragon's blood and that of its component loureirin B, specify an operational definition for effective component from raw drug of TCM. Using the whole-cell patch-clamp technique, the effects of dragon's blood and its component loureirin B on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in trigeminal ganglion (TG) neurons were observed. The results show that both dragon's blood and loureirin B suppressed two types of peak sodium currents in a dose-dependent way. 0.1% dragon's blood and 0.2mmol/L loureirin B affected the activation and inactivation of sodium channels. The results further prove the analgetic mechanism of dragon's blood interfering with the nociceptive transmission. According to the above definition, loureirin B is the effective component in dragon's blood modulating sodium currents in TG neurons.

  18. Oral Chromium Exposure and Toxicity

    Science.gov (United States)

    Sun, Hong; Brocato, Jason

    2015-01-01

    Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

  19. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  20. Photoinduced toxicity of engineered nanomaterials

    Science.gov (United States)

    Jones, Philip Scott

    Engineered nanomaterials including metal, metal oxide and carbon based nanomaterials are extensively used in a wide variety of applications to the extent that their presence in the environment is expected to increase dramatically over the next century. These nanomaterials may be photodegraded by solar radiation and thereby release metal ions into the environment that can produce cytotoxic and genotoxic effects. Photoinduced toxicity experiments are performed exposing human lung epithelial carcinoma cells [H1650] to engineered semiconductor nanoparticles such as CdSe quantum dots and ZnO nanoparticles after exposure to 3, 6, and 9 hours of solar simulated radiation. Cytotoxicity and genotoxicity of the metal ions are evaluated using ZnSO4 and CdCl2 solutions for the MTT assay and Comet assay respectively. The objective of the dissertation is to obtain quantitative information about the environmental transformation of engineered nanomaterials and their mechanism of toxicity. This information is critical for addressing the environmental health and safety risks of engineered nanomaterials to workers, consumers and the environment.

  1. Mercury toxicity and neurodegenerative effects.

    Science.gov (United States)

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  2. Na+ Channel Scn1b Gene Regulates Dorsal Root Ganglion Nociceptor Excitability in Vivo*

    Science.gov (United States)

    Lopez-Santiago, Luis F.; Brackenbury, William J.; Chen, Chunling; Isom, Lori L.

    2011-01-01

    Nociceptive dorsal root ganglion (DRG) neurons express tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ current (INa) mediated by voltage-gated Na+ channels (VGSCs). In nociceptive DRG neurons, VGSC β2 subunits, encoded by Scn2b, selectively regulate TTX-S α subunit mRNA and protein expression, ultimately resulting in changes in pain sensitivity. We hypothesized that VGSCs in nociceptive DRG neurons may also be regulated by β1 subunits, encoded by Scn1b. Scn1b null mice are models of Dravet Syndrome, a severe pediatric encephalopathy. Many physiological effects of Scn1b deletion on CNS neurons have been described. In contrast, little is known about the role of Scn1b in peripheral neurons in vivo. Here we demonstrate that Scn1b null DRG neurons exhibit a depolarizing shift in the voltage dependence of TTX-S INa inactivation, reduced persistent TTX-R INa, a prolonged rate of recovery of TTX-R INa from inactivation, and reduced cell surface expression of Nav1.9 compared with their WT littermates. Investigation of action potential firing shows that Scn1b null DRG neurons are hyperexcitable compared with WT. Consistent with this, transient outward K+ current (Ito) is significantly reduced in null DRG neurons. We conclude that Scn1b regulates the electrical excitability of nociceptive DRG neurons in vivo by modulating both INa and IK. PMID:21555511

  3. Sarcoplasmic-reticulum biogenesis in contraction-inhibited skeletal-muscle cultures.

    OpenAIRE

    Charuk, J H; Guerin, C.; Holland, P.C.

    1992-01-01

    We have previously shown that inhibition of the spontaneous contractile activity of cultured embryonic-chick skeletal-muscle fibres with tetrodotoxin (TTX) leads to decreased sarcoplasmic-reticulum Ca(2+)-transport rates and steady-state concentrations of the high-energy Ca(2+)-ATPase phosphoenzyme intermediate [Charuk & Holland (1983) Exp. Cell Res. 144, 143-157]. In the present study we used a monoclonal antibody to the Ca(2+)-ATPase to show that there is a decreased amount of enzyme accumu...

  4. A Case Report of Puffer Fish Poisoning in Singapore

    OpenAIRE

    Yong, Y. S.; Quek, L. S.; Lim, E. K.; Ngo, A.

    2013-01-01

    Although many Asians regard puffer fish as a delicacy since ancient times, puffer fish (Lageocephalus scitalleratus) is also a well-known source of possibly lethal food poisoning. The fish is gaining popularity in Singapore and can be found in quite a few restaurants now. Puffer fish contains tetrodotoxin (TTX), a potent poison affecting the neural pathway. Puffer fish poisoning may cause a constellation of symptoms, such as giddiness, numbness and tingling sensation of the mouth, paresthesia...

  5. Clinical and epidemiological study of 27 poisonings caused by ingesting puffer fish (Tetrodontidae) in the states of Santa Catarina and Bahia, Brazil.

    Science.gov (United States)

    Silva, Claudia Carvalho Pestana; Zannin, Marlene; Rodrigues, Daisy Schwab; Santos, Claudia Regina dos; Correa, Ieda Ana; Haddad Junior, Vidal

    2010-01-01

    Puffer fish can be poisonous due to the presence of the potent neurotoxins such as Tetrodotoxin (TTX) and Saxitoxin (STX) found in its tissues. The authors report 27 human poisonings from ingestion of puffer fish in patients treated at Toxicology Centers in the states of Santa Catarina and Bahia, Brazil, between 1984 and January 2009. Poisonings were classified as moderate (52%) and severe (33%), two deaths were observed. Early diagnosis is very important to ensure respiratory support.

  6. Trichothecenes: structure-toxic activity relationships.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Kuca, Kamil; Yuan, Zonghui

    2013-07-01

    Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genus Fusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to address structure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecene mycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ring are essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxyl group at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or an acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. The toxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position. The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attached to this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, an oxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change from isovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidation at C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursors after hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucial information for a better understanding of trichothecene chemical and biological properties in food contamination.

  7. In silico prediction of drug toxicity

    Science.gov (United States)

    Dearden, John C.

    2003-02-01

    It is essential, in order to minimise expensive drug failures due to toxicity being found in late development or even in clinical trials, to determine potential toxicity problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening, identification of putative toxicity is advisable even before synthesis. Thus the use of predictive toxicology is called for. A number of in silico approaches to toxicity prediction are discussed. Quantitative structure-activity relationships (QSARs), relating mostly to specific chemical classes, have long been used for this purpose, and exist for a wide range of toxicity endpoints. However, QSARs also exist for the prediction of toxicity of very diverse libraries, although often such QSARs are of the classification type; that is, they predict simply whether or not a compound is toxic, and do not give an indication of the level of toxicity. Examples are given of all of these. A number of expert systems are available for toxicity prediction, most of them covering a range of toxicity endpoints. Those discussed include TOPKAT, CASE, DEREK, HazardExpert, OncoLogic and COMPACT. Comparative tests of the ability of these systems to predict carcinogenicity show that improvement is still needed. The consensus approach is recommended, whereby the results from several prediction systems are pooled. It is simply amazing that we can formulate any kind of QSAR. The (desired activity) is only the starting point. The truly formidable problem is that of toxicity, especially the difficult long-term toxicities resulting from chronic usage''. (Hansch & Leo [1])

  8. In vivo toxicity study of Lantana camara

    OpenAIRE

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions: Methanolic...

  9. Bridging environmental mixtures and toxic effects.

    Science.gov (United States)

    Allan, Sarah E; Smith, Brian W; Tanguay, Robert L; Anderson, Kim A

    2012-12-01

    Biological Response Indicator Devices Gauging Environmental Stressors (BRIDGES) is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, OR, USA. Six sampling events were conducted in the summer and fall of 2009 and 2010. Passive sampling device extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1,201 chemicals of concern using deconvolution-reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. The BRIDGES tool provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry-toxicity associations. Modeling elucidated spatial and temporal trends in PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although the present study highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples. Copyright © 2012 SETAC.

  10. Tier 3 Toxicity Value White Paper

    Science.gov (United States)

    The purpose of this white paper is to articulate the issues pertaining to Tier 3 toxicity values and provide recommendations on processes that will improve the transparency and consistency of identifying, evaluating, selecting, and documenting Tier 3 toxicity values for use in the Superfund and Resource Conservation and Recovery Act (RCRA) programs. This white paper will be used to assist regional risk assessors in selecting Tier 3 toxicity values as well as provide the foundation for future regional and national efforts to improve guidance and policy on Tier 3 toxicity values.

  11. Toxicity evaluation of PAH mixtures using Microtox

    Energy Technology Data Exchange (ETDEWEB)

    Thompkins, J.; Guthrie, E.; Pfaender, F. [Univ. of North Carolina, Chapel Hill, NC (United States)

    1995-12-31

    Polycyclic aromatic hydrocarbons (PAH) are produced from both natural and anthropogenic combustion processes. PAHs are known to be toxic and carcinogenic, are prevalent at many hazardous waste sites, and pose a potential risk to both ecological and human health. To date, few researchers have assessed the toxicity of polycyclic aromatic hydrocarbon (PAH) mixtures. The toxicity of chrysene, anthracene, pyrene, phenanthrene, fluoranthrene, acenaphthene, fluorene, and naphthalene were evaluated using Microtox, and acute toxicity assay that uses bioluminescent bacteria, Photobacterium phosphoreum, to measure toxicity. In this study, the toxicities of 2, 3, and 4 ring PAHs were determined for individual compounds. Synergistic or additive effects of PAH mixtures was assessed by comparing the toxicity of mixtures with that of pure compounds. Each PAH or mixture was evaluated at their respective water solubility concentrations, For individual PAHs tested, the toxicity of PAHs is inversely related to water solubility. Mixtures of two and three PAHs with disparate water solubilities resulted in synergistic interactions. Antagonistic interactions, a decrease in toxicity, were observed for mixtures of similar water solubilities.

  12. Distributed Structure-Searchable Toxicity Database Network

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure-Searchable Toxicity (DSSTox) Database Network provides a public forum for search and publishing downloadable, structure-searchable,...

  13. Toxic shock syndrome responsive to steroids

    Directory of Open Access Journals (Sweden)

    Vergis Nikhil

    2007-02-01

    Full Text Available Abstract Background Toxic Shock Syndrome is a dangerous disease with clinical features mimicking bacterial sepsis. The best management of Toxic Shock Syndrome is not determined. Case presentation A 28 year-old woman presenting with high fever, tachycardia and widespread erythroderma is described. She failed to respond to intravenous antibiotics and required ITU admission. High dose corticosteroids dramatically improved her clinical condition. Conclusion Toxic Shock Syndrome should be considered in the differential diagnosis of unexplained fever, rash and features resembling septic shock. Corticosteroids should be considered in the treatment of Toxic Shock Syndrome.

  14. Estimation of inorganic species aquatic toxicity

    Science.gov (United States)

    Hickey, James P.; Ostrander, Gary K.

    2005-01-01

    The acute aquatic toxicities (narcoses) for a range of organism types may be estimated with LSER for a large number of inorganic and organometal species, many with an accuracy at or within an order of magnitude. Optimum estimations make use of a bioavailable metal fraction and a more accurate structure(s) for the toxic solution species. The estimated toxicities for a number of salts were quite different from the observed values, likely due to a dominant specific toxicity mechanism other than baseline narcosis. The tool still requires fine-tuning.

  15. Toxic hazards of underground excavation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R.; Chitnis, V.; Damasian, M.; Lemm, M.; Popplesdorf, N.; Ryan, T.; Saban, C.; Cohen, J.; Smith, C.; Ciminesi, F.

    1982-09-01

    Inadvertent intrusion into natural or man-made toxic or hazardous material deposits as a consequence of activities such as mining, excavation or tunnelling has resulted in numerous deaths and injuries in this country. This study is a preliminary investigation to identify and document instances of such fatal or injurious intrusion. An objective is to provide useful insights and information related to potential hazards due to future intrusion into underground radioactive-waste-disposal facilities. The methodology used in this study includes literature review and correspondence with appropriate government agencies and organizations. Key categories of intrusion hazards are asphyxiation, methane, hydrogen sulfide, silica and asbestos, naturally occurring radionuclides, and various mine or waste dump related hazards.

  16. Toxic Shock Syndrome following Tattooing

    Directory of Open Access Journals (Sweden)

    Ki Young Jeong

    2015-08-01

    Full Text Available Toxic shock syndrome (TSS is a rare but life-threatening illness that is mainly caused by toxigenic strains of Staphylococcus aureus. Although TSS is classically known to be associated with tampon use, the number of TSS cases with non-menstrual causes such as skin and soft tissue infection has been increasing. Tattooing can result in several complications such as localized and systemic infections, inflammatory skin eruptions and neoplasms. We recently experienced a 26-year-old man diagnosed with typical TSS following tattooing. He complained of fever, chills and erythematous rash at tattoo site. Subsequently, the patient developed sign of shock. The skin cultures on the tattoo site were positive for methicillin-sensitive Staphylococcus aureus. The patient was successfully treated with vasopressor infusion and intravenous antibiotics and was discharged without complications. On discharge from the hospital 7 days later, desquamations on the tattoo site, fingers and toes were observed.

  17. Labetalol-induced toxic myopathy.

    Science.gov (United States)

    Teicher, A; Rosenthal, T; Kissin, E; Sarova, I

    1981-01-01

    Labetalol has been successful in treating hypertension, and few side effects have been reported, although there have been cases of muscle pain during treatment. A patient with essential hypertension treated with labetalol 600 mg daily complained of muscle pains, particularly in the legs. No neurological abnormality was found, but the activity of muscle enzymes in the blood was high. Findings on electromyography were compatible with myositis and electron microscopical findings suggested toxic myopathy. Labetalol was stopped for 10 days, and the muscle pain disappeared and enzyme activity returned to normal. When labetalol was restarted the pain returned and enzyme activities rose. Myopathy should be considered in patients experiencing muscle pain after treatment with labetalol. Images FIG 1 PMID:6786636

  18. Endogenous thiols enhance thallium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Sergio; Rios, Camilo [Instituto Nacional de Neurologia y Neurocirugia, ' ' Manuel Velasco Suarez' ' , Departamento de Neuroquimica, Mexico, D.F (Mexico); Soriano, Luz; Monroy-Noyola, Antonio [Universidad Autonoma del Estado de Morelos, Laboratorio de Neuroproteccion, Facultad de Farmacia, Cuernavaca, Morelos (Mexico)

    2007-10-15

    Either L-methionine (L-met) or L-cysteine (L-cys), given alone and in combination with Prussian blue (PB) was characterized as treatment against acute thallium (Tl) toxicity in rats. Animals were intoxicated with 32 mg/kg Tl acetate corresponding to rat LD{sub 50}. Antidotal treatments were administered during 4 days, as follows: (1) vehicle, (2) L-met 100 mg/kg i.p. twice a day, (3) L-cys 100 mg/kg i.p. twice a day, (4) PB 50 mg/kg oral, twice a day, (5) L-met + PB and (6) L-cys + PB. Mortality was as follows: control 50%; L-met 80%; L-cys 80%; PB 20%; L-met + PB 90% and L-cys + PB 100%. In a different experiment, using 16 mg/kg of Tl, tissue levels of this metal were analyzed. PB treatment statistically diminished Tl content in body organs and brain regions (P < 0.01). Whereas, separate treatments of L-met and L-cys failed to decrease Tl content in organs and brain regions; while its administration in combination with PB (L-met + PB and L-cys + PB groups) lowered Tl levels in body organs in the same extent as PB group. Results indicate that L-met and L-cys administered alone or in combination with PB should not be considered suitable treatments against acute Tl toxic effects because this strategy failed to prevent mortality and Tl accumulation in brain. (orig.)

  19. Amiodarone pulmonary toxicity: Case report

    Directory of Open Access Journals (Sweden)

    Vasić Nada

    2014-01-01

    Full Text Available Introduction. Amiodarone, an antiarrhythmic drug, which contains iodine compound, has a tendency to accumulate in some organs including the lungs. This is age, drug dosage and therapy duration dependent. Case Outline. We present a case of a 73-year-old man, a smoker, who was admitted as emergency case due to severe dyspnea, tachypnea with signs of cyanosis and respiratory insufficiency. Chest x-ray revealed bilateral diffuse pulmonary shadows in the middle and upper parts of the lungs, similar to those in tuberculosis. His illness history showed chronic obstructive pulmonary disease, arterial hypertension, and atrial fibrillation which has been treated with amiodarone for six years. Sputum smears were negative for mycobacteria, and by the diagnostic elimination method for specific, non-specific and malignant disease the diagnosis of amiodarone pulmonary toxicity was made. Fiberoptic bronchoscopy and pathohistological findings of bronchiolitis obliterans organizing pneumonia confirmed the diagnosis. As the first therapeutic approach, amiodarone therapy was stopped. Then, systemic therapy with methylprednisolone 21 (sodium succinate 40 mg i.v. daily during the first two weeks was initiated and continued with daily dose of methylprednisolone 30 mg orally during the next three months. The patient showed a marked subjective improvement during the first week, which was followed by the improvement of respiratory function and withdrawal of pulmonary changes with complete radiographic and CT resolution after eight months. Conclusion. Amiodarone pulmonary toxicity should be taken into consideration, especially in elderly patients with respiratory symptoms and pulmonary changes, even if only a low dose of amiodarone is administred over a longer time period.

  20. Electrocardiographic Manifestations of Benzodiazepine Toxicity

    Directory of Open Access Journals (Sweden)

    Nahid Kazemzadeh

    2014-11-01

    Full Text Available Background: The aim of this study was to evaluate and compare the clinical and electrocardiographic (ECG manifestations of benzodiazepines (BZs. Methods: In this retrospective study, all BZ-poisoned patients hospitalized at Loghman Hakim Hospital between September 2010 and March 2011 were evaluated. Patients’ information including age, sex, time elapsed between the ingestion and presentation, and type of the BZ used were extracted from the patients' charts and recorded. ECGs on presentation to the emergency department (ED were evaluated and parameters such as PR interval, QRS duration, corrected QT, amplitude of S wave in lead I, height of R wave and R/S ratio in the lead aVR were also measured and recorded. Results: Oxazepam, chlordiazepoxide, lorazepam, alprazolam, diazepam, and clonazepam were ingested by 9 (3%, 13 (4.4%, 29 (9.9%, 105 (35.8%, 65 (22.2%, and 72 (24.6% patients, respectively. Mean PR interval was reported to be 0.16 ± 0.03 sec and PR interval of greater than 200 msec was detected in 12 (4.5% patients. Mean QRS duration was 0.07 ± 0.01sec and QRS≥120 msec was observed in 7 (2.6% cases. Conclusion: Diazepam is the only BZ that does not cause QRS widening and oxazepam is the only one not causing PR prolongation. It can be concluded that if a patient refers with a decreased level of consciousness and accompanying signs of BZ toxicity, QRS widening in ECG rules out diazepam, whereas PR prolongation rules out oxazepam toxicity.

  1. How much do PCB toxic equivalents account for PHAH toxicity in predatory birds?

    NARCIS (Netherlands)

    Pereira, M.G.; Murk, A.J.; Berg, van den H.; Walker, L.A.; Shore, R.F.

    2014-01-01

    Various diffuse polyhalogenated aromatic hydrocarbons (PHAHs) exert common toxicity through the aryl hydrocarbon receptor (AhR). Apex predators spatially and temporally integrate diffuse contamination and simultaneous exposure can cause additive toxicity. We investigated the extent to which PCBs,

  2. A model for which toxic and non-toxic phytoplankton are indistinguishable by the zooplantkon

    Science.gov (United States)

    Sen, Moitri; Venturino, Ezio

    2012-09-01

    Using Haldane-Monod functions, we study the response of zooplankton avoiding to feed on phytoplankton when the latter releases toxines, but assuming that the zooplankton does not distinguish between toxic and non-toxic phytoplankton.

  3. 40 CFR 80.915 - How are the baseline toxics value and baseline toxics volume determined?

    Science.gov (United States)

    2010-07-01

    ... the statutory baseline defined in 40 CFR 80.45(b) and volumes are in gallons. (2) The toxics value, Ti... 40 Protection of Environment 16 2010-07-01 2010-07-01 false How are the baseline toxics value and... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Toxics...

  4. Enzyme inhibitors and other bioactive compounds from marine actinomycetes.

    Science.gov (United States)

    Imada, Chiaki

    2005-01-01

    Several enzyme-inhibitor-producing actinomycetes were isolated from various samples collected from the marine environment and characterized. Most of them produced novel compounds that are useful in medicine and agriculture. Actinomycete strain no. 18, which produces antibiotics against Gram-positive bacteria only in the presence of seawater, was isolated from sediment sampled from neritic sea water and characterized. The production of antibiotics was observed at seawater concentrations ranging from 60 to 110% (v/v). Thus, the production was seawater-dependent. The production of tetrodotoxin (TTX), known otherwise as puffer fish toxin, was investigated in various actinomycetes collected from the marine environment. Of 10 isolates from various sea areas, 9 produced TTX as judged by their retention times on high-performance liquid chromatography (HPLC). To our knowledge, this is the first report of actinomycetes from the marine environment that produce TTX.

  5. National Toxic Substance Incidents Program (NTSIP)

    Centers for Disease Control (CDC) Podcasts

    2011-02-03

    This podcast gives an overview of the three components of the National Toxic Substance Incidents Program: state surveillance, national database, and response teams.  Created: 2/3/2011 by Agency for Toxic Substances and Disease Registry.   Date Released: 2/3/2011.

  6. Copper toxicity in aquaculture: A practical approach

    Science.gov (United States)

    Copper sulfate is used as a therapeutant for various applications in aquaculture. There is a great deal of information on the toxicity of copper, especially in low-alkalinity waters; however, much of this information is fragmented, and a comprehensive guide of copper toxicity and safe concentration...

  7. Cadmium Toxicity to Ringed Seals (Phoca hispida)

    DEFF Research Database (Denmark)

    Sonne, Christian; Dietz, R.; Riget, F. F.

    Cadmium concentrations in kidneys from ringed seals (Phoca hispida) from North West Greenland (Qaanaaq) are high. Concentrations range at level known to induce renal toxic effects (mainly tubulopathy) and demineralisation (osteopenia) of the skeletal system (Fanconi's Syndrome) in humans as well...... the absence of toxic effects of cadmium in ringed seal...

  8. CORRELATION AMONG PHENOLIC, TOXIC METALS AND ...

    African Journals Online (AJOL)

    Preferred Customer

    toxic metals (Zn, Fe, Cu, Mn), the high content of phenolic compounds and high antioxidant activity. KEY WORDS: Toxic .... all metals). For the preparation of standard solutions high purity Milli-Q water was used. The glassware and polyethylene containers used for analysis were washed with tap water, then soaked over the ...

  9. Predictive Model of Systemic Toxicity (SOT)

    Science.gov (United States)

    In an effort to ensure chemical safety in light of regulatory advances away from reliance on animal testing, USEPA and L’Oréal have collaborated to develop a quantitative systemic toxicity prediction model. Prediction of human systemic toxicity has proved difficult and remains a ...

  10. Preliminary Phytochemical Screening, Acute Oral Toxicity and ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. ... PTZ-induced seizure mice in at the dose of 300 mg/kg p.o. The extract also reduced the frequency of convulsion and provided up to .... Oral acute toxicity test. Acute toxicity of the plant extract was carried out.

  11. BIOEQUIVALENCE APPROACH FOR WHOLE EFFLUENT TOXICITY TESTING

    Science.gov (United States)

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

  12. Chapter 6: Selenium Toxicity to Aquatic Organisms

    Science.gov (United States)

    This chapter addresses the characteristics and nature of organic selenium (Se) toxicity to aquatic organisms, based on the most current state of scientific knowledge. As such, the information contained in this chapter relates to the 'toxicity assessment' phase of aquatic ecologi...

  13. Preliminary Phytochemical Screening, Acute Oral Toxicity and ...

    African Journals Online (AJOL)

    Purpose: To investigate the preliminary phytochemical properties, acute oral toxicity and anticonvulsant activity of the berries of Solanum nigrum Linn (S. nigrum) Methods: Phytochemicals from the ethanol berry extract were screened by standard methods. Acute oral toxicity study was conducted as per Organisation for ...

  14. America's Poisoned Playgrounds: Children and Toxic Chemicals.

    Science.gov (United States)

    Freedberg, Louis

    Next to chemical and farm workers, today's children are at the greatest risk from toxic chemicals. Through their normal play activities, children are exposed to a frightening array of toxic hazards, including lead, pesticides, arsenic, and unknown dangers from abandoned landfills and warehouses. Through a series of documented examples, the author…

  15. The facts about sunn hemp toxicity

    Science.gov (United States)

    Sunn hemp (Crotalaria juncea L.) is an annual plant widely grown in the tropics. The genus Crotalaria includes some species known to be toxic to animals. Development of seed producing cultivars for the continental USA at Auburn University, AL, has raised the question if its seed and forage are toxic...

  16. ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ...

    African Journals Online (AJOL)

    In spite of the myriad of ethno medical uses and agro-feed potential of Jatropha curcas (JC) seeds and the potential for production of biodiesel, toxic properties have been adduced to the plant, especially the seeds. Thus, the current study was done with the aim of investigating the toxicity of the ethanol seed extract of JC in ...

  17. Streptococcus pyogenes toxic-shock syndrome

    OpenAIRE

    Antunes, R.; Diogo, M; Carvalho, A.; Pimentel, T; Oliveira, J.

    2011-01-01

    Recently there has been an exponential increase in invasive infections caused by Streptococcus ß hemolyticcus group A. In about one third of cases they are complicated by toxic shock syndrome, characterized by septic shock and multiorgan failure. The authors, by their rarity, report a case of bacteraemia caused by Streptococcus pyogenes complicated by toxic shock syndrome.

  18. In vitro toxicity screening of colored smokes

    NARCIS (Netherlands)

    Langenberg, J.P.; Alblas, M.J.; Makkus, J.C.; Meer, J.A. van der; Mars-Groenendijk, R.H.; Groeneveld, F.R.; Norbert, M.; Lingen, J.N.J. van

    2009-01-01

    Data on the acute and/or long-term toxicity of colored smokes appear to be scarce and inconsistent. Therefore, the objective of this study is to obtain more insight on this matter. For this purpose, existing platforms for in vitro toxicity screening are evaluated with respect to their applicability

  19. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    This article is focused on ascertaining the toxic potentials of heavy metals and the levels of PAHs and cPAHs in crude oil samples from Gokana area and using the data to determine the carcinogenicity (toxicity) of the cPAHs in the crude oil. All the cPAHs namely; benzo (a) pyrene, benzo (a) Anthracene, benzo (b) ...

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

    Science.gov (United States)

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

    2017-01-01

    The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton 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 limit test 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 toxicity study by using this adaptation.

  1. The toxicity of inhaled methanol vapors.

    Science.gov (United States)

    Kavet, R; Nauss, K M

    1990-01-01

    Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor.

  2. Harmonizing human exposure and toxicity characterization

    DEFF Research Database (Denmark)

    Fantke, Peter; Jolliet, O.; McKone, T.E.

    2017-01-01

    The UNEP-SETAC Life Cycle Initiative has launched a project to provide global guidance and build consensus on environmental life cycle impact assessment (LCIA) indicators. Human health effects from exposure to toxic chemicals was selected as impact category due to high relevance of human toxicity...... impacts, past and present efforts in human toxicity assessment, and the need for further harmonization and global guidance. To address this need, an expert workshop was implemented in Utrecht in October 2016 with the aim of building a roadmap for a reliable and consistent approach for improving...... and use of impact factors for toxic chemicals. We propose to couple fate processes in consumer and occupational environments with existing environmental compartments and processes via a consistent and mass balance-based set of transfer fractions to quantify overall aggregated exposure to toxic substances...

  3. Toxicities of selected substances to freshwater biota

    Energy Technology Data Exchange (ETDEWEB)

    Hohreiter, D.W.

    1980-05-01

    The amount of data available concerning the toxicity of various substances to freshwater biota is so large that it is difficult to use in a practical situation, such as environmental impact assessment. In this document, summary tables are presented showing acute and/or chronic toxicity of selected substances for various groups of aquatic biota. Each entry is referenced to its original source so that details concerning experimental conditions may be consulted. In addition, general information concerning factors modifying toxicity, synergisms, evidence of bioaccumulation, and water quality standards and criteria for the selected substances is given. The final table is a general toxicity table designed to provide an easily accessible and general indication of toxicity of selected substances in aquatic systems.

  4. Aluminium toxicity in winter wheat

    Directory of Open Access Journals (Sweden)

    Szabó A.

    2015-01-01

    Full Text Available Aluminium is the most frequent metal of the earth crust; it occurs mainly as biologically inactive, insoluble deposit. Environmental problems, industrial contaminations and acid rains increase the soil acidity, leading to the mobilization of Al. Half of the world’s potential arable lands are acidic; therefore, Al-toxicity decreases crop productivity. Wheat is a staple food for 35% of the world population. The effects of Al-stress (0.1 mM were studied on winter wheat; seedlings were grown hydroponically, at acidic pH. After two weeks, the root weight was decreased; a significant difference was found in the P- and Ca-content. The shoot weight and element content changed slightly; Al-content in the root was one magnitude higher than in the shoot, while Al-translocation was limited. The root plasma membrane H+-ATPase has central role in the uptake processes; Al-stress increased the Mg2+-ATPase activity of the microsomal fraction.

  5. Lead toxicity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Van der Heggen, Maarten; Martins, Sara; Flores, Gisela; Soares, Eduardo V

    2010-12-01

    The effect of Pb on Saccharomyces cerevisiae cell structure and function was examined. Membrane integrity was assessed by the release of UV-absorbing compounds and by the intracellular K(+) efflux. No leakage of UV(260)-absorbing compounds or loss of K(+) were observed in Pb (until 1,000 μmol/l) treated cells up to 30 min; these results suggest that plasma membrane seems not to be the immediate and primary target of Pb toxicity. The effect of Pb on yeast metabolism was examined using the fluorescent probe FUN-1 and compared with the ability to reproduce, evaluated by colony-forming units counting. The exposition of yeast cells, during 60 min to 1,000 μmol/l Pb, induces a decrease in the ability to process FUN-1 although the cells retain its proliferation capacity. A more prolonged contact time (120 min) of yeast cells with Pb induces a marked (> 50%) loss of yeast cells metabolic activity and replication competence through a mechanism which most likely requires protein synthesis.

  6. Topical absorption and systemic toxicity.

    Science.gov (United States)

    Alikhan, Fatima Sasha; Maibach, Howard

    2011-09-01

    Dermal absorption of some chemicals and drugs can cause systemic toxicity. We evaluated several case reports from the past decade, which discuss the dermal absorption of a specific chemical and potential local and systemic effects. We focused on herbicide and pesticide exposure along with exposure to cutaneous medication, occupational contact, and cosmeceutical exposure. Although causality cannot be established in most cases, it is critical to be aware of the possible effects of topical absorption that may not be immediately apparent. We recommended further studies on specific chemicals to ascertain causality and determine the highest exposure level with no observed adverse affect level (NOAEL) and the reference dose (RfD). Post-marketing epidemiology data in most geographical areas are markedly limited. A weak link in public health resides in the inadequate reporting and workup of alleged chemically related adverse effects. This arena mandates a re-thinking of how to increase this reporting, and workup, as a backup to our preclinical and clinical studies. Public awareness and funding will be rewarded by increased evidence to backup pre-approval pre-marketing studies.

  7. Review of Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Victoria Harris

    2016-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α, and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese.

  8. Rapidly Developing Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Viktoria Oline Barrios Poulsen

    2013-01-01

    Full Text Available Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA. SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG. The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19.

  9. Toxic material advisory report - 2-mercaptoethanol

    Energy Technology Data Exchange (ETDEWEB)

    Bernholc, N. M.; White, O. Jr.; Baloyi, R. S.; Silverstein, B. D.

    1983-03-01

    A review of the animal toxicity data for 2-ME is presented. The results revealed that chronic inhalation exposures at a concentration of 6 mg/m/sup 3/ produced decreased oxygen consumption, lymphopenia, and neutrophilia. Comparison of acute toxicity data for 2-ME with data of structurally similar compounds suggests that 2-ME may be 2.3 times more toxic than butanethiol (TLV = 0.5 ppM), 6.5 times more toxic than ethanethiol, and 6 times more toxic than propanethiol (TLV = 0.5 ppM) via oral administration but may be comparable to propanethiol and less toxic than butanethiol and ethanethiol by the inhalation route of exposure. The TLVs for ethanethiol, methanethiol, and butanethiol were based on discomfort to human volunteers rather than toxicity. Since 2-ME has many effects similar to those of the thiols discussed and its odor threshold falls in the range of other thiols, by analogy the exposure limit for 2-ME should be comparable to the TLVs for butanethiol and ethanethiol. An interim exposure limit (IEL) of 0.5 ppM for a time-weighted average concentration during an 8-hour work shift is recommended. As with other thiols, a nuisance problem due to 2-ME odors and complaints of odor may serve as a primary reason for controlling workplace concentrations.

  10. The Venom of the Spider Selenocosmia Jiafu Contains Various Neurotoxins Acting on Voltage-Gated Ion Channels in Rat Dorsal Root Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Zhaotun Hu

    2014-03-01

    Full Text Available Selenocosmia jiafu is a medium-sized theraphosid spider and an attractive source of venom, because it can be bred in captivity and it produces large amounts of venom. We performed reversed-phase high-performance liquid chromatography (RP-HPLC and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS analyses and showed that S. jiafu venom contains hundreds of peptides with a predominant mass of 3000–4500 Da. Patch clamp analyses indicated that the venom could inhibit voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglion (DRG neurons. The venom exhibited inhibitory effects on tetrodotoxin-resistant (TTX-R Na+ currents and T-type Ca2+ currents, suggesting the presence of antagonists to both channel types and providing a valuable tool for the investigation of these channels and for drug development. Intra-abdominal injection of the venom had severe toxic effects on cockroaches and caused death at higher concentrations. The LD50 was 84.24 μg/g of body weight in the cockroach. However, no visible symptoms or behavioral changes were detected after intraperitoneal injection of the venom into mice even at doses up to 10 mg/kg body weight. Our results provide a basis for further case-by-case investigations of peptide toxins from this venom.

  11. TOXIC SUBSTANCES FROM COAL COMBUSTION

    Energy Technology Data Exchange (ETDEWEB)

    A KOLKER; AF SAROFIM; CL SENIOR; FE HUGGINS; GP HUFFMAN; I OLMEZ; J LIGHTY; JOL WENDT; JOSEPH J HELBLE; MR AMES; N YAP; R FINKELMAN; T PANAGIOTOU; W SEAMES

    1998-12-08

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the Federal Energy Technology Center (FETC), the Electric Power Research Institute, the Lignite Research Council, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, MIT, the University of Arizona (UA), the University of Kentucky (UK), the University of Connecticut (UC), the University of Utah (UU) and the University of North Dakota Energy and Environmental Research Center (EERC) to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NO combustion systems, and new power generation x plants. Development of ToPEM will be based on PSI's existing Engineering Model for Ash Formation (EMAF). This report covers the reporting period from 1 July 1998 through 30 September 1998. During this period distribution of all three Phase II coals was completed. Standard analyses for the whole coal samples were also completed. Mössbauer analysis of all project coals and fractions received to date has been completed in order to obtain details of the iron mineralogy. The analyses of arsenic XAFS data for two of the project coals and for some high arsenic coals have been completed. Duplicate splits of the Ohio 5,6,7 and North Dakota lignite samples were taken through all four steps of the selective leaching procedure. Leaching analysis of the Wyodak coal has recently commenced. Preparation of polished coal/epoxy pellets for probe/SEM studies is underway. Some exploratory mercury LIII XAFS work was

  12. Anticholinesterase Toxicity and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Dejan Milatovic

    2006-01-01

    Full Text Available Anticholinesterase compounds, organophosphates (OPs and carbamates (CMs are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS, and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents.

  13. Enhanced toxic cloud knockdown spray system for decontamination applications

    Science.gov (United States)

    Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

    2011-09-06

    Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

  14. Bioremediation of toxic substances by mercury resistant marine bacteria

    Digital Repository Service at National Institute of Oceanography (India)

    De, J.; Sarkar, A.; Ramaiah, N.

    Bioremediation of toxic substances includes microbe-mediated enzymatic transformation of toxicants to non-toxic, often assimilable, forms. Mercury-resistant marine bacteria are found to be very promising in dealing with mercury, and a host of other...

  15. Toxicity evaluations of various carbon nanomaterials.

    Science.gov (United States)

    Uo, Motohiro; Akasaka, Tsukasa; Watari, Fumio; Sato, Yoshinori; Tohji, Kazuyuki

    2011-01-01

    After the discovery of fullerene and carbon nanotubes, various carbon nanomaterials were discovered or synthesized. The carbon nanomaterials have remarkable properties, different from bulk materials with the same chemical composition, and are therefore useful for industrial applications. However, the toxicity of nanomaterials may also differ from that of the bulk materials; this difference poses a concern. The physical similarity of nanomaterials to asbestos has led to evaluations for toxicity by many researchers using various methods. In this review, we compile and compare the toxicity evaluations of each carbon nanomaterial.

  16. Subacute toxicity assessment of annatto in rat

    OpenAIRE

    Bautista, Ana Rita Pedreira Lapa; E.L.T. Moreira; Batista, Márcio Santos; Miranda, M.S.; Gomes, I. C. S.

    2004-01-01

    Texto completo:acesso restrito. p. 625-629 Increased human use of annatto (Bixa orellana L), a red yellow food colorant, demands generation of toxicity data. The toxic effects of annatto powder (bixin 27%) have been assessed following administration of a subacute regimen (4 weeks, 20 doses) in Wistar male and female rats. A full study with three dose levels was considered unnecessary since no sign of toxicity had been noted in a preliminary experiment with 1000 mg/kg body weight/day as ...

  17. Applicability of early indicators of iron toxicity.

    Science.gov (United States)

    Knasel, A L; Collins-Barrow, M D

    1986-11-01

    Leukocytosis, blood glucose, vomiting, diarrhea, and abdominal radiograph have been reported as early indicators of toxic serum iron levels. To test the applicability of this battery of five variables, the charts of 64 patients admitted for toxic iron ingestion were reviewed. When these variables were subjected to tests of sensitivity, specificity, and predictive negative and positive values in 42 patients meeting study criteria, they failed to reach statistical significance. Only vomiting was found to approach statistical significance and, therefore, may serve as an early indicator of toxicity. In addition, several epidemiological issues relevant to the study population are discussed.

  18. In vivo toxicity study of Lantana camara.

    Science.gov (United States)

    Pour, Badakhshan Mahdi; Sasidharan, Sreenivasan

    2011-06-01

    To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Methanolic extract of L. camara is relatively safe on short-term exposure.

  19. The taste of toxicity: A quantitative analysis of bitter and toxic molecules.

    Science.gov (United States)

    Nissim, Ido; Dagan-Wiener, Ayana; Niv, Masha Y

    2017-12-01

    The role of bitter taste-one of the few basic taste modalities-is commonly assumed to signal toxicity and alert animals against consuming harmful compounds. However, it is known that some toxic compounds are not bitter and that many bitter compounds have negligible toxicity while having important health benefits. Here we apply a quantitative analysis of the chemical space to shed light on the bitterness-toxicity relationship. Using the BitterDB dataset of bitter molecules, The BitterPredict prediction tool, and datasets of toxic compounds, we quantify the identity and similarity between bitter and toxic compounds. About 60% of the bitter compounds have documented toxicity and only 56% of the toxic compounds are known or predicted to be bitter. The LD50 value distributions suggest that most of the bitter compounds are not very toxic, but there is a somewhat higher chance of toxicity for known bitter compounds compared to known nonbitter ones. Flavonoids and alpha acids are more common in the bitter dataset compared with the toxic dataset. In contrast, alkaloids are more common in the toxic datasets compared to the bitter dataset. Interestingly, no trend linking LD50 values with the number of activated bitter taste receptors (TAS2Rs) subtypes is apparent in the currently available data. This is in accord with the newly discovered expression of TAS2Rs in several extra-oral tissues, in which they might be activated by yet unknown endogenous ligands and play non-gustatory physiological roles. These results suggest that bitter taste is not a very reliable marker for toxicity, and is likely to have other physiological roles. © 2017 IUBMB Life, 69(12):938-946, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

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

    Directory of Open Access Journals (Sweden)

    Nivedita Chatterjee

    2015-07-01

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

  1. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  2. Simvastatin-induced Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Emmanouil Petrou

    2014-01-01

    Full Text Available Toxic epidermal necrolysis comprises a severe immune-complex mediated hypersensitivity reaction that typically involves the skin and mucous membranes. Herein, we describe a 68-year -old man who presented with the condition after simvastatin administration.

  3. Isocyano compounds as non-toxic antifoulants.

    Science.gov (United States)

    Nogata, Y; Kitano, Y

    2006-01-01

    The marine sponge Acanthella cavernosa and nudibranchs of the family Phyllidiidae contain isocyanoterpenoids and their related compounds that show potent antifouling activity against cypris larvae of the barnacle Balanus amphitrite, while their toxicity to cyprids is weak. To develop non-toxic antifoulants based on isocyanoterpenoids, especially 3-isocyanotheonellin, a total of 36 isocyano compounds have been synthesized. They were evaluated by both antifouling activity and toxicity toward B. amphitrite cyprids, which led some insight into the structure-activity relationships. Since linear alkyl isocyanides showed antifouling activity at nontoxic concentrations, a large amount of 1,1-dimethyl-10-undecyl isocyanide was synthesized, incorporated into paints, and tested for antifouling activity in the field with promising results. Therefore, isocyano compounds were considered as candidate non-toxic antifouling agents.

  4. [Arsine: an unknown industrial chemical toxic].

    Science.gov (United States)

    Plantamura, J; Dorandeu, F; Burnat, P; Renard, C

    2011-07-01

    Arsines family includes many compounds with various toxicities. Arsenic trihydride or arsine is the most toxic form of arsenic. Powerful haemolytic gas, it has never been used as a chemical weapon because its toxicity is not immediate and it is non persistent. However, cases of industrial poisoning with arsine are still identified in spite of a strict regulation at work. It is also identified as a potential toxic of chemical terrorism. This agent, of which the mechanism of action is still not well defined, is badly recognized because of intoxications rarity. However, fast detection means are available. Health professionals and especially those who are involved in piratox plan need to learn to recognize arsine intoxication (hematuria, oliguria, haemolytic anemia) in order to provide early, specific treatment and avoid damages. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. Special Consolidated Checklists for Toxicity Characteristics Revisions

    Science.gov (United States)

    This checklist consolidates the changes to the Federal code addressed by the Toxicity Characteristic (TC) Rule [55 FR 11798; March 29, 1990; Revision Checklist 74] and subsequent revisions which have occurred through December 31, 2002.

  6. Reducing toxicity chemicals plant protection products

    OpenAIRE

    Litvishko, Valery; Myaskovskaya, Tatiana

    2014-01-01

    The samples of microencapsulated pesticide have been investigated in acute experiments on laboratory animals. The results of the research have determined that microencapsulation can reduce toxicity of plant protection chemicals.

  7. Toxicity Assessment for EPA's Hydraulic Fracturing Study

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset contains data used to develop multiple manuscripts on the toxicity of chemicals associated with the hydraulic fracturing industry. These manuscripts...

  8. Understanding Genetic Toxicity Through Data Mining: The ...

    Science.gov (United States)

    This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies.

  9. Mixture toxicity of PBT-like chemicals

    DEFF Research Database (Denmark)

    Syberg, Kristian; Dai, Lina; Ramskov, Tina

    addition is a suitable model for default estimations of mixture effects. One of the major challenges is therefore how to select specific chemicals for actual mixture toxicity assessments. Persistant chemicals are likely to be present in the environment for an extended period of time, thus increasing......Even though most chemicals regulation is still conducted on a chemical by chemical basis, mixture toxicity is achieving increasing attention. The scientific understanding has increased substantially in the last decades, and a general consensus now seems to have been acieved that concentration...... the likelihood of them being present in environmentally found mixtures. Persistant, bioaccumulative and toxic (PBT) chemicals are therefore a highly relevant group of chemicals to consider for mixture toxicity regulation. The present study evaluates to what extent a number of PBT-like chemicals posess concern...

  10. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    "Catastrophic events such as the Bhopal, India tragedy and rising incidences of cancer in areas neighboring industrial facilities have heightened concern over the use of toxic chemicals in manufacturing and industry...

  11. Unknown toxic exposures. Arts and crafts materials.

    Science.gov (United States)

    Grabo, T N

    1997-03-01

    1. Arts and crafts material containing toxic chemicals have been found to be hazardous to human health. 2. Artists/craftspersons, who also may be employed in industry, often are unaware or not adequately informed about the toxic nature of many art products. 3. The occupational health nurse is in a critical position to identify and monitor the worker exposed to toxic chemicals both in the workplace and at home/art studio. 4. Education about hazardous substances can prevent illness or injury. With expertise in public health, occupational health nurses are in a key position to provide community education about the dangers of toxic art materials to the general public and the health care community.

  12. 40 CFR 798.2450 - Inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... only when there is an indication based on expected and/or observed toxicity. (12) Gross pathology. (i...; duodenum; jejunum; ileum; cecum; colon; rectum; urinary bladder; representative lymph node; (mammary gland...

  13. Anaerobic Toxicity of Cationic Silver Nanoparticles

    Data.gov (United States)

    U.S. Environmental Protection Agency — Toxicity data for the impact of nano-silver on anaerobic degradation. This dataset is associated with the following publication: Gitipour, A., S. Thiel, K. Scheckel,...

  14. Corneal Toxicity Following Exposure to Asclepias Tuberosa

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas

    2017-01-01

    PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small...... that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity...... caused by exposure to latex from Asclepias tuberosa. Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity....

  15. THERMOREGULATION AND ITS INFLUENCE ON TOXICITY ASSESSMENT

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Christopher J.; Spencer, Pamela J.; Hotchkiss, Jon; Miller, Diane B.; Hinderliter, Paul M.; Pauluhn, Jeurgen

    2008-02-28

    The thermoregulatory system of laboratory rodents is susceptible to a variety of chemical toxicants. Because temperature directly affects the reaction of virtually all biological processes, it is critical to consider how changes in the thermoregulatory response to a toxicant may affect physiological, behavioral, and pathological endpoints. Researchers in industry and government laboratories are often faced with addressing how changes in body temperature of their experimental subjects may affect the outcome of a particular toxicity test and/or screening panel. However, many toxicologists are either unaware of the importance or ignore the potential impact of a toxic-induced change in body temperature. This paper endeavors to summarize the importance of thermoregulation in the study of toxicology and propose recommendations for thermometry that researchers may utilize in their toxicological studies.

  16. GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB).

    Science.gov (United States)

    Bide, R W; Armour, S J; Yee, E

    2005-01-01

    Estimated human inhalation toxicity values for Sarin (GB) were calculated using a new two independent (concentration, exposure time), one dependent (toxic response), non-linear dose response (toxicity) model combined with re-evaluated allometric equations relating to animal and human respiration. Historical animal studies of GB toxicity containing both exposure and fractional animal response data were used to test the new process. The final data set contained 6621 animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg m(-3)) and exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2 Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between exposure times of 0.17 and 30 min, the average value for n in seven species was 1.35 +/- 0.15. The near parallel toxic load equations for each species and the linear relationship between minute volume/body weight ratio and the inhalation toxicity (LCt50) for GB were used to create a pseudo-human data set and then an exposure time/toxicity surface for the human. The calculated n for the human was 1.40. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt50 but did result in lower variability. Raising the lower value to 2 min was counterproductive. Based on the toxic load model for 1-30 min exposures, the human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15 l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34, 79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These values are recommended for general use for the total human population. The empirical relationships employed in the calculations may not be valid for exposure times >30 min. 2005 John Wiley & Sons, Ltd.

  17. Toxic hepatitis in occupational exposure to solvents

    OpenAIRE

    Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

    2012-01-01

    The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic facto...

  18. Toxicant-induced oxidative stress in cancer.

    Science.gov (United States)

    Upham, B L; Wagner, J G

    2001-11-01

    The article highlighted in this issue is "The Role of Oxidative Stress in Indium Phosphide-Induced Lung Carcinogenesis in Rats" by Barbara C. Gottschling, Robert R. Maronpot, James R. Hailey, Shyamal Peddada, Cindy R. Moomaw, James E. Klaunig, and Abraham Nyska (pp. 28-40). The article integrates a traditional pathologic study of toxicant-induced pulmonary carcinogenesis with an immunohistologic assessment of oxidative stress, thereby determining a potential mechanism of action of a toxicant, specifically indium phosphide.

  19. Toxic Keratopathy Secondary to Topical Proparacaine

    OpenAIRE

    Anıl Kubaloğlu; Esin Söğütlü Sarı; Pınar Sorgun Evcili; Sibel Akyol; Arif Koytak; Yusuf Özertürk

    2012-01-01

    Pur po se: To evaluate the clinical findings of toxic keratopathies secondary to topical proparacaine (Alcaine, Alcon) abuse and the results of medical and/or surgical treatment options. Ma te ri al and Met hod: We retrospectively analyzed twenty-two eyes of 25 patients who developed toxic keratopathy secondary to topical anesthetic abuse between March 2005 and December 2009. Severe pain unresponsive to medical treatment with persistent epithelial defects (PED) and stromal ulcers wer...

  20. Role of Bioadsorbents in Reducing Toxic Metals

    OpenAIRE

    Mathew, Blessy Baby; Jaishankar, Monisha; Biju, Vinai George; Krishnamurthy Nideghatta Beeregowda

    2016-01-01

    Industrialization and urbanization have led to the release of increasing amounts of heavy metals into the environment. Metal ion contamination of drinking water and waste water is a serious ongoing problem especially with high toxic metals such as lead and cadmium and less toxic metals such as copper and zinc. Several biological materials have attracted many researchers and scientists as they offer both cheap and effective removal of heavy metals from waste water. Therefore it is urgent to st...

  1. Nanomaterials and nanoparticles: Sources and toxicity

    OpenAIRE

    Buzea, Cristina; Pacheco, Ivan I.; Robbie, Kevin

    2008-01-01

    This review is written with the goal of informing public health concerns related to nanoscience, while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to nanoparticles and dust from natural sources and human activities, the recent development of industry and combustion-based engine transportation profoundly increasing anthropogenic nanoparticulate pollution. The key to understanding the toxicity of nano...

  2. Toxicity of Pyrolysis Gases from Elastomers

    Science.gov (United States)

    Hilado, Carlos J.; Kosola, Kay L.; Solis, Alida N.; Kourtides, Demetrius A.; Parker, John A.

    1977-01-01

    The toxicity of the pyrolysis gases from six elastomers was investigated. The elastomers were polyisoprene (natural rubber), styrene-butadiene rubber (SBR), ethylene propylene diene terpolymer (EPDM), acrylonitrile rubber, chlorosulfonated polyethylene rubber, and polychloroprene. The rising temperature and fixed temperature programs produced exactly the same rank order of materials based on time to death. Acryltonitrile rubber exhibited the greatest toxicity under these test conditions; carbon monoxide was not found in sufficient concentrations to be the primary cause of death.

  3. Preventing Toxic Behaviour through Game Mechanics

    OpenAIRE

    Fahlström, Josefine; Matson, Emma

    2014-01-01

    Toxic Behaviour, the phenomena where a person behaves in a way meant to intimidate or belittle another person, is an influential issue spreading across the virtual spaces that is online gaming communities. In this thesis we explore the possible correlations between Toxic Behaviour and game mechanics in online multi-player games by analyzing League of Legends (Riot Games, 2009), one of the most prominent online games currently dominating the market (Statista, 2014). We have analysed the game u...

  4. Toxicity test of a dental commercial composite

    OpenAIRE

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

    2015-01-01

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

  5. Military Dog Training Aids: Toxicity and Treatment

    Science.gov (United States)

    1989-11-10

    history and description, the symptoms, the toxicities and the treatments. The references used are supplied at the end of each section. II. DISCUSSION A...stat., acute poisoning with large amounts of chlorate, death may ezcur suddenly without obvious symptoms. In such cases, the history of sudden death...5 to 10 mg doses of diazepam ( Valium ) administered orally. A patient with a classic toxic psychosis 16 will be disoriented and hallucinating

  6. Relative toxicity of gossypol enantiomers in broilers

    OpenAIRE

    Lordelo, M.M.; Davis, A.J.; Calhoun, M.C.; Dowd, M.K.; Dale, N.M.

    2005-01-01

    Use of cottonseed meal in poultry diets has been avoided in large part because of fear of gossypol toxicity. Gossypol exists naturally as a mixture of 2 enantiomers that exhibit different biological activities. Two experiments were conducted to determine the relative toxicity of gossypol enantiomers on broilers. In the first experiment, 3-d-old broilers were fed a standard diet containing 0, 100, 200, 300, or 400 mg of gossypol from gossypol acetic acid per kilogram of...

  7. Toxicity of trifluoroacetate to aquatic organisms

    Energy Technology Data Exchange (ETDEWEB)

    Berends, A.G.; Rooij, C.G. de [Solvay S.A., Brussels (Belgium); Boutonnet, J.C. [Elf Atochem, Levallois-Perret (France); Thompson, R.S. [Zeneca Ltd., Devon (United Kingdom). Brixham Environmental Lab.

    1999-05-01

    As a result of the atmospheric degradation of several hydrofluorocarbons and hydrochlorofluorocarbons, trifluoroacetate (TFA) will be formed. Through precipitation, TFA will enter aquatic ecosystems. To evaluate the impact on the aquatic environment, an aquatic toxicity testing program was carried out with sodium trifluoroacetate (NaTFA). During acute toxicity tests, no effects of NaTFA on water fleas (Daphnia magna) and zebra fish (Danio retrio) were found at a concentration of 1,200 mg/L. A 7-d study with duckweed (Lemna gibba Ge) revealed a NOEC of 300 mg/L. On the basis of the results of five toxicity tests with Selenastrum capricornutum, they determined a NOEC of 0.12 mg/L. However, algal toxicity tests with NaTFA and Chlorella vulgaris, Scenedesmus subspicatus, Chlamydomonas reinhardtii, Dunaliella tertiolecta, Eugelan gracilis, Phaeodactylum tricornutum, Navicula pelliculosa, Skeletonema costatum, Anabaena flos-aquae, and Microcystis aeruginosa resulted in EC50 values that were all higher than 100 mg/L. The toxicity of TFA to S. capricornutum could be due to metabolic defluorination to monofluoroacetate (MFA), which is known to inhibit the citric acid cycle. A toxicity test with MFA and S. capricornutum revealed it to be about three orders of magnitude more toxic than TFA. However, a bioactivation study revealed that defluorination of TFA was less than 4%. On the other hand, S. capricornutum exposed to a toxic concentration of NaTFA showed a recovery of growth when citric acid was added, suggesting that TFA (or a metabolite of TFA) interferes with the citric acid cycle. A recovery of the growth of S. capricornutum was also found when TFA was removed from the test solutions. Therefore, TFA should be considered algistatic and not algicidic for S. capricornutum. On the basis of the combined results of the laboratory tests and a previously reported semi-field study, they can consider a TFA concentration of 0.10 mg/L as safe for the aquatic ecosystem.

  8. Mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna

    DEFF Research Database (Denmark)

    Syberg, K.; Engell-Kofoed, Anders Elleby; Pedersen, H.

    2008-01-01

    of similar- and dissimilar-acting toxicants equally well. CA and IA also equally predicted the ternary mixture consisting of both similar- and dissimilar-acting chemicals. The paper discusses the concept of mode of action and the implications the definition of mode of action has on the choice of reference......Mixture toxicity of similar- and dissimilar-acting toxicants can be predicted by the models concentration addition (CA) and independent action (IA) using single substance toxicity data. Knowledge of the toxicants mode of action is thus required in order to use the models. In order to test...... the predictive capability of the models, we conducted Daphnia magna 48 h immobilization experiments with three toxicants with known modes of action (dimethoate, pirimicarb and linear alkyl benzene sulfonate) singly, and in binary and ternary mixtures. Our results indicate that CA and IA predict binary mixtures...

  9. Relating nanomaterial properties and microbial toxicity

    Science.gov (United States)

    Suresh, Anil K.; Pelletier, Dale A.; Doktycz, Mitchel J.

    2012-12-01

    Metal and metal oxide nanoparticles are among the most commonly used nanomaterials and their potential for adversely affecting environmental systems raises concern. Complex microbial consortia underlie environmental processes, and the potential toxicity of nanoparticles to microbial systems, and the consequent impacts on trophic balances, is particularly worrisome. The diverse array of metal and metal oxides, the different sizes and shapes that can be prepared and the variety of possible surface coatings complicate assessments of toxicity. Further muddling biocidal interpretations are the diversity of microbes and their intrinsic tolerances to stresses. Here, we review a range of studies focused on nanoparticle-microbial interactions in an effort to correlate the physical-chemical properties of engineered metal and metal oxide nanoparticles to their biological response. General conclusions regarding the parent material of the nanoparticle and the nanoparticle's size and shape on potential toxicity can be made. However, the surface coating of the material, which can be altered significantly by environmental conditions, can ameliorate or promote microbial toxicity. Understanding nanoparticle transformations and how the nanoparticle surface can be designed to control toxicity represents a key area for further study. Additionally, the vast array of microbial species and the structuring of these species within communities complicate extrapolations of nanoparticle toxicity in real world settings. Ultimately, to interpret the effect and eventual fate of engineered materials in the environment, an understanding of the relationship between nanoparticle properties and responses at the molecular, cellular and community levels will be essential.

  10. Assessing sediment contamination using six toxicity assays

    Directory of Open Access Journals (Sweden)

    Allen G. BURTON Jr.

    2001-08-01

    Full Text Available An evaluation of sediment toxicity at Lake Orta, Italy was conducted to compare a toxicity test battery of 6 assays and to evaluate the extent of sediment contamination at various sediment depths. Lake Orta received excessive loadings of copper and ammonia during the 1900’s until a large remediation effort was conducted in 1989-90 using lime addition. Since that time, the lake has shown signs of a steady recovery of biological communities. The study results showed acute toxicity still exists in sediments at a depth of 5 cm and greater. Assays that detected the highest levels of toxicity were two whole sediment exposures (7 d using Hyalella azteca and Ceriodaphnia dubia. The MicrotoxR assay using pore water was the third most sensitive assay. The Thamnotox, Rototox, Microtox solid phase, and Seed Germination-Root Elongation (pore and solid phase assays showed occasional to no toxicity. Based on similarity of responses and assay sensitivity, the two most useful assays were the C. dubia (or H. azteca and Microtox pore water. These assays were effective at describing sediment toxicity in a weight-of-evidence approach.

  11. The C. elegans model in toxicity testing.

    Science.gov (United States)

    Hunt, Piper Reid

    2017-01-01

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

  12. Review of toxicity studies of carbon nanotubes.

    Science.gov (United States)

    Kobayashi, Norihiro; Izumi, Hiroto; Morimoto, Yasuo

    2017-09-28

    We reviewed studies on pulmonary, reproductive, and developmental toxicity caused by carbon nanotubes (CNTs). In paricular, we analyzed how CNT exposure affects the several processes of pulmonary toxicity, including inflammation, injury, fibrosis, and pulmonary tumors. In pulmonary toxicity, there are various processes, including inflammation, injury, fibrosis, respiratory tumor in the lungs, and biopersistence of CNTs and genotoxicity as tumor-related factors, to develop the respiratory tumor. We evaluated the evidence for the carcinogenicity of CNTs in each process. In the fields of reproductive and developmental toxicity, studies of CNTs have been conducted mainly with mice. We summarized the findings of reproductive and developmental toxicity studies of CNTs. In animal studies, exposure to CNTs induced sustained inflammation, fibrosis, lung cancer following long-term inhalation, and gene damage in the lung. CNTs also showed high biopersistence in animal studies. Fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offsprings after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported in mice-administered multi-walled carbon nanotubes (MWCNTs). Single-walled carbon nanotubes (SWCNTs) appeared to be embryolethal and teratogenic in mice when given by intravenous injection; moreover, the tubes induced death and growth retardation in chicken embryos. CNTs are considered to have carcinogenicity and can cause lung tumors. However, the carcinogenicity of CNTs may attenuate if the fiber length is shorter. The available data provide initial information on the potential reproductive and developmental toxicity of CNTs.

  13. Toxicity of Single and Mixed Contaminants in Seawater Measured with Acute Toxicity Bioassays

    Directory of Open Access Journals (Sweden)

    A.R. Fernandez-Alba

    2002-01-01

    Full Text Available Different types of organic pollutants commonly detected in seawater have been evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and Selenastrum capricornotum were selected to test toxic effects of individual compounds and mixtures of these compounds, obtaining EC50 values in the range of 0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were seen for a clear majority of the cases (>60%. Mixtures containing methyl-tertiary-butyl ether (MTBE exhibit accelerated processes that result in a change in concentration required to produce a toxic effect; for example, in the case of mixtures containing MTBE and Diuron and Dichlofluanid.

  14. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models.

    Science.gov (United States)

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds. Copyright © 2010. Published by Elsevier Inc.

  15. Taxation’s Troubling Toxicity

    Directory of Open Access Journals (Sweden)

    Janet E. Milne

    2015-03-01

    Full Text Available Occupy Wall Street spurred cries of indignation, including calls to reform the tax code. This article examines the difficulty of raising taxes in the United States at a time when the federal government faces many needs and new taxes could help address the growing income disparity. In Part 1, it looks at several trends—the substantial federal deficit and rising debt, the lack of funding for infrastructure, and increasing income disparity among US residents—to establish the premise that resistance to higher taxes is troublesome. The article then turns to the question why taxes are viewed negatively. It surveys literature about the general public’s attitudes toward taxation (Part 2 and the intensely political views of taxation on and surrounding Capitol Hill (Part 3. Parts 2 and 3 confirm the challenges of raising federal taxes and find a range of forces at work with varying levels of intensity. Part 4 looks forward and considers mechanisms that might help overcome the perception of taxes as politically poisonous and increase their acceptance. The article draws on research from numerous disciplines, but its analysis of potential paths forward looks through the lens of the law at ways in which various legal procedures and legally oriented approaches might help overcome resistance. It concludes that taxation is politically toxic, which is troublesome given the important roles that taxation plays in society, but that there are some glimmers of hope that the structure and details of the law may help create some opportunities for change. Occupy Wall Street impulsó gritos de indignación, incluyendo una llamada a reformar el código tributario. Este artículo analiza la dificultad de aumentar los impuestos en Estados Unidos, en un momento en el que el gobierno federal se enfrenta a muchas necesidades, y la creación de nuevos impuestos podría ayudar a abordar la creciente disparidad de ingresos. En la Parte 1, se tratan diversas tendencias

  16. A review of reproductive toxicity of microcystins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-01-15

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  17. Contact toxicity of twenty insecticides applied to Symmerista canicosta

    Science.gov (United States)

    Jacqueline L. Robertson; Robert L. Lyon; Fay L. Shon; Nancy L. Gillette

    1972-01-01

    Twenty insecticides were tested by topical application on mixed groups of 4th- and 5th -stage larvae of Symmerista canicosta Franclemont. Four exceeded DDT in toxicity at LD50 but only resmethrin was significantly mor toxic. Most of the compounds showed unusually high toxicities. Twelve, listed in decreasing order of toxicity...

  18. Simulation of heavy metal contamination of fresh water bodies: Toxic ...

    African Journals Online (AJOL)

    The results show that ZnSO4 was significantly toxic to the fish only after 96 hours. Co-contamination of the water with both toxicants was found to ameliorate the toxic effects of ZnSO4 significantly. The metal chelating property of glyphosate may be responsible for the observed attenuation of toxicity in the fish in Group ...

  19. Behavior as a sentry of metal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.

    1978-01-01

    Many of the toxic properties of metals are expressed as behavioral aberrations. Some of these arise from direct actions on the central nervous system. Others arise from primary events elsewhere, but still influence behavior. Toxicity may be expressed either as objectively measurable phenomena, such as ataxia, or as subjective complaints, such as depression. In neither instance is clinical medicine equipped to provide assessments of subtle, early indices of toxicity. Reviewers of visual disturbances, paresthesia, and mental retardation exemplify the potential contribution of psychology to the toxicology of metals. Behavior and nervous system functions act as sensitive mirrors of metal toxicity. Sensitivity is the prime aim in environmental health assessments. Early detection of adverse effects, before they progress to irreversibility, underlies the strategy for optimal health protection. Some of the toxic actions of metals originate in direct nervous system dysfunction. Others may reflect disturbances of systems less directly linked to behavior than the central nervous system. But behavior, because it expresses the integrated functioning of the organism, can indicate flaws in states and processes outside the nervous system.

  20. Toxicity of atmospheric aerosols on marine phytoplankton.

    Science.gov (United States)

    Paytan, Adina; Mackey, Katherine R M; Chen, Ying; Lima, Ivan D; Doney, Scott C; Mahowald, Natalie; Labiosa, Rochelle; Post, Anton F

    2009-03-24

    Atmospheric aerosol deposition is an important source of nutrients and trace metals to the open ocean that can enhance ocean productivity and carbon sequestration and thus influence atmospheric carbon dioxide concentrations and climate. Using aerosol samples from different back trajectories in incubation experiments with natural communities, we demonstrate that the response of phytoplankton growth to aerosol additions depends on specific components in aerosols and differs across phytoplankton species. Aerosol additions enhanced growth by releasing nitrogen and phosphorus, but not all aerosols stimulated growth. Toxic effects were observed with some aerosols, where the toxicity affected picoeukaryotes and Synechococcus but not Prochlorococcus. We suggest that the toxicity could be due to high copper concentrations in these aerosols and support this by laboratory copper toxicity tests preformed with Synechococcus cultures. However, it is possible that other elements present in the aerosols or unknown synergistic effects between these elements could have also contributed to the toxic effect. Anthropogenic emissions are increasing atmospheric copper deposition sharply, and based on coupled atmosphere-ocean calculations, we show that this deposition can potentially alter patterns of marine primary production and community structure in high aerosol, low chlorophyll areas, particularly in the Bay of Bengal and downwind of South and East Asia.

  1. Toxicity and antinociceptive effects of Hamelia patens

    Directory of Open Access Journals (Sweden)

    Angel Josabad Alonso-Castro

    Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

  2. Toxic trace elements at gastrointestinal level.

    Science.gov (United States)

    Vázquez, M; Calatayud, M; Jadán Piedra, C; Chiocchetti, G M; Vélez, D; Devesa, V

    2015-12-01

    Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

  4. CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

    Science.gov (United States)

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

  5. Food plant toxicants and safety: risk assessment and regulation of inherent toxicants in plant foods.

    NARCIS (Netherlands)

    Essers, A.J.; Alink, G.M.; Speijers, G.J.A.; Alexander, J.; Bouwmeister, P.J.; Brandt, van den P.A.; Ciere, S.; Gry, J.; Herrman, J.; Kuiper, H.A.; Mortby, E.; Renwickn, A.G.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI

  6. Novel view on predicting acute toxicity: Decomposing toxicity data in species vulnerability and chemical potency.

    NARCIS (Netherlands)

    Jager, D.T.; Posthuma, L.; Zwart, D.D.; van de Meent, D.

    2007-01-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We

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

    Science.gov (United States)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-05-01

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

  9. Relative parameter sensitivity in prenatal toxicity studies with substances classified as developmental toxicants

    NARCIS (Netherlands)

    Rorije, E.; van Hienen, F.J.W.; Dang, Z.C.; Hakkert, B.H.; Vermeire, T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    Developmental toxicity testing according to the globally standardized OECD 414 protocol is an important basis for decisions on classification and labeling of developmental toxicants in the European Union (EU). This test requires relatively large animal numbers, given that parental and offspring

  10. Active prey selection in two pelagic copepods feeding on potentially toxic and non-toxic dinoflagellates

    DEFF Research Database (Denmark)

    Schultz, Mette; Kiørboe, Thomas

    2009-01-01

    Grazing on two red tide dinoflagellates, the potentially toxic Karenia mikimotoi and the non-toxic Gyrodinium instriatum, was examined in two species of marine copepods, Pseudocalanus elongatus and Temora longicornis. Both copepods cleared K. mikimotoi at rates that were a little lower...

  11. Levels of Some Selected (Essential-Mn, Zn and Toxic-Al, Sb) Metals in

    African Journals Online (AJOL)

    ... as certain trace and toxic elements have been implicated with such tarpaulin materials which are made from polyvinyl chloride stabilized with additives. This present study is aimed at evaluating the levels of some trace/toxic elements in African Catfish (Clariasgariepinus) and the health risk associated with these elements.

  12. Exploring the Impact of Toxic Attitudes and a Toxic Environment on the Veterinary Healthcare Team.

    Science.gov (United States)

    Moore, Irene C; Coe, Jason B; Adams, Cindy L; Conlon, Peter D; Sargeant, Jan M

    2015-01-01

    The objective of this qualitative study was to compare veterinarians' and Registered Veterinary Technicians' (RVT's) perceptions of the veterinary healthcare team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with four veterinarian groups (23 companion animal veterinarians) and four Registered Veterinary Technician groups (26 RVTs). Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with manifestations of toxic attitudes negatively impacted veterinary team function. These manifestations included people being disrespectful, being resistant to change, always wanting to be the "go to person," avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when "broken communication and tension between staff members" occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands. The presence of people manifesting a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment.

  13. Exploring the impact of toxic attitudes and a toxic environment on the veterinary healthcare team

    Directory of Open Access Journals (Sweden)

    Irene eMoore

    2015-12-01

    Full Text Available AbstractThe objective of this qualitative study was to compare veterinarians’ and Registered Veterinary Technicians’ (RVT’s perceptions of the veterinary health care team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with 4 veterinarian groups (23 companion animal veterinarians and 4 Registered Veterinary Technician groups (26 RVTs. Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with toxic attitudes negatively impacted veterinary team function. These attitudes included people being disrespectful, being resistant to change, always wanting to be the go to person, avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when broken communication and tension between staff members occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands.The presence of people with a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment.

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

    Science.gov (United States)

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

  15. Isolation and Identification of Cytotoxic and Biological Active Toxin from the Puffer Fish Arothron stellatus.

    Science.gov (United States)

    Veeruraj, Anguchamy; Pugazhvendan, Sampath Renuga; Ajithkumar, Thipramalai Thankappan; Arumugam, Muthuvel

    2016-07-01

    This study is to investigate the biological, biochemical and cytotoxic effects of puffer fish (Arothron stellatus) toxin extracts under in-vitro condition. Extracted toxins from various organs of puffer fish were purified by using active charcoal column, and Bio-gel-P2 column chromatography. The lethality of toxin was tested in crabs, which consists of neurotoxic compounds. The degree of the brine shrimp lethality assay was found directly proportional to the concentration of the toxin extracts, which was well supported by hemolytic assay. The experimental results suggested that the gonad was found higher toxins than the liver and muscles. The mortality rate of brine shrimp nauplii was increased with the raise of concentrations of toxin level. Among the different doses and time dependent cytotoxic effect of human cervical carcinoma (HeLa) cells were showed 4.0 μg/mL of toxin, which was effectively inhibited cancer cell proliferation. HPLC and TLC analysis was revealed that the A. stellatus toxin contains tetrodotoxin (TTX), related compounds 4-epi TTX and anhydro-TTX. The present results suggested that the A. stellatus contain TTX as a major and anh-TTX as a minor toxin. It could be the potential candidate in the field of anticancer drug discovery against human cervical cancer cells. The present data is confirming that the puffer fish toxin as an interesting source of novel bioactive natural compounds with potent applications in pharmacology.

  16. Voltage-gated sodium channels in nociceptive versus non-nociceptive nodose vagal sensory neurons innervating guinea pig lungs

    Science.gov (United States)

    Kwong, Kevin; Carr, Michael J; Gibbard, Anna; Savage, Tony J; Singh, Kuljit; Jing, Junping; Meeker, Sonya; Undem, Bradley J

    2008-01-01

    Lung vagal sensory fibres are broadly categorized as C fibres (nociceptors) and A fibres (non-nociceptive; rapidly and slowly adapting low-threshold stretch receptors). These afferent fibre types differ in degree of myelination, conduction velocity, neuropeptide content, sensitivity to chemical and mechanical stimuli, as well as evoked reflex responses. Recent studies in nociceptive fibres of the somatosensory system indicated that the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSC) are preferentially expressed in the nociceptive fibres of the somatosensory system (dorsal root ganglia). Whereas TTX-R sodium currents have been documented in lung vagal sensory nerves fibres, a rigorous comparison of their expression in nociceptive versus non-nociceptive vagal sensory neurons has not been carried out. Using multiple approaches including patch clamp electrophysiology, immunohistochemistry, and single-cell gene expression analysis in the guinea pig, we obtained data supporting the hypothesis that the TTX-R sodium currents are similarly distributed between nodose ganglion A-fibres and C-fibres innervating the lung. Moreover, mRNA and immunoreactivity for the TTX-R VGSC molecules NaV1.8 and NaV1.9 were present in nearly all neurons. We conclude that contrary to findings in the somatosensory neurons, TTX-R VGSCs are not preferentially expressed in the nociceptive C-fibre population innervating the lungs. PMID:18187475

  17. Sediment toxicity in Boston Harbor: Magnitude, extent, and relationships with chemical toxicants. Technical memo

    Energy Technology Data Exchange (ETDEWEB)

    Long, E.R.; Sloane, G.M.; Carr, R.S.; Scott, K.J.; Thursby, G.B.

    1996-06-01

    A survey of the toxicity of sediments throughout Boston Harbor and vicinity was conducted by NOAA`s National Status and Trends (NS&T) Program. The objectives of the survey were to determine the magnitude and spatial extent of toxicity and the relationship between measures of toxicity and the concentrations of chemical toxicants in the sediments. Multiple toxicity tests were performed including: an amphipod survival test performed with whole sediments, a microbial bioluminescence test performed with organic solvent extracts of the sediments, and sea urchin fertilization and embryological development tests performed with the pore waters extracted from the sediments. Chemical analyses were performed on selected samples for trace metals, polynuclear aromatic hydrcarbons, chlorinated pesticides, PCBs, and butyltins.

  18. Novel view on predicting acute toxicity: decomposing toxicity data in species vulnerability and chemical potency.

    Science.gov (United States)

    Jager, Tjalling; Posthuma, Leo; de Zwart, Dick; van de Meent, Dik

    2007-07-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We use a database for acute aquatic toxicity, and focus on some well-defined chemical classes. Potency is strongly related to hydrophobicity and vulnerability differences between species are small for narcotic compounds. Potencies show less relation with hydrophobicity and interspecies differences are larger for organophosphate- and carbamate insecticides. Photosynthesis inhibitors generally act narcotic to animals, but were more potent for algae. Using these potencies and vulnerabilities, acute toxicity values were well predicted by the proposed approach (within a factor of 3-6). The proposed approach has potential for predicting toxicity for untested species-compound combinations; however, there is a need for a better definition of 'mode of action' in ecotoxicology.

  19. Toxicity of Engineered Nanoparticles to Aquatic Invertebrates

    DEFF Research Database (Denmark)

    Cupi, Denisa; Sørensen, Sara Nørgaard; Skjolding, Lars Michael

    2016-01-01

    This chapter provides a targeted description of some of the most important processes that influence toxicity and uptake of nanoparticles in aquatic invertebrates. It discusses silver nanoparticles (Ag NPs), on how aspects of dissolution and chemical species obtained from this process can influenc...... on bioaccumulation focusing on the effect of nanoparticle coating, uptake, and depuration in aquatic invertebrates.......This chapter provides a targeted description of some of the most important processes that influence toxicity and uptake of nanoparticles in aquatic invertebrates. It discusses silver nanoparticles (Ag NPs), on how aspects of dissolution and chemical species obtained from this process can influence...... ecotoxicity of aquatic invertebrates. The chapter focuses on how fullerenes affect the toxicity of other pollutants, but also reflect on the fate and behavior of C60 in the aquatic environment, as well as ecotoxicity to aquatic invertebrates. It presents the case of titanium dioxide nanoparticles (TiO2 NPs...

  20. Aluminum toxicity symptoms in peach seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, J.H.; Horton, B.D.; Kirkpatrick, H.C.

    1976-03-01

    Elberta (Prunus persica (L.) Batsch) peach seedlings were grown in nutrient solutions for 27 days with aluminum concentrations of 0, 222, 666 and 2000 ..mu..m concentration induced Al toxicity symptoms in leaves and severely restricted root growth. The early stage of Al toxicity was characterized by marginal chlorosis that later developed into necrotic areas that extended along the veins toward the midrib. Advanced stages of toxicity were characterized by collapse of the midrib, terminal dieback and defoliation of the seedlings which are typical symptoms of calcium deficiency in peaches. At high Al concentrations roots died back and new roots developed as irregularly shaped cylinders with constrictions and enlargements at the root apex.

  1. Traumatic white matter injury and toxic leukoencephalopathies.

    Science.gov (United States)

    Al-Hasani, Omer Hussain; Smith, Colin

    2011-09-01

    White matter injury may be secondary to a range of neurodegenerative disorders, such as the common dementing disorders of the elderly, or may be a consequence of specific white matter disorders, such as multiple sclerosis and the rare leukodystrophies. This article will focus on two relatively common primary groups of disorders of the white matter, traumatic white matter injury and toxic leukoencephalopathies. Traumatic axonal injury may be focal or diffuse, and is associated with a clinical spectrum ranging from concussion through to coma and death. The molecular mechanisms underlying axonal degeneration secondary to traumatic axonal degeneration are being elucidated and may give an insight into potential therapeutic targets. Toxic leukoencephalopathy may be secondary to exposure to a wide range of compounds, including chemotherapeutic drugs. These toxins may produce white matter injury through a range of mechanisms, and the potential toxic effects of compounds need to be considered when assessing a patient with a nonspecific leukoencephalopathy.

  2. Hazard index for underground toxic material

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C.F.; Cohen, J.J.; McKone, T.E.

    1980-06-01

    To adequately define the problem of waste management, quantitative measures of hazard must be used. This study reviews past work in the area of hazard indices and proposes a geotoxicity hazard index for use in characterizing the hazard of toxic material buried underground. Factors included in this index are: an intrinsic toxicity factor, formulated as the volume of water required for dilution to public drinking-water levels; a persistence factor to characterize the longevity of the material, ranging from unity for stable materials to smaller values for shorter-lived materials; an availability factor that relates the transport potential for the particular material to a reference value for its naturally occurring analog; and a correction factor to accommodate the buildup of decay progeny, resulting in increased toxicity.

  3. [Modern elucidative strategies for scientific connotation of controlling toxic reactions while toxic herbs are used to the indication syndrome].

    Science.gov (United States)

    Tan, Yong; Li, Jian; Lu, Cheng; He, Xiao-Juan; Jiang, Miao; Lu, Ai-Ping

    2013-10-01

    One of effective measures for controlling toxic reactions is to use toxic herbs according to corresponding indication syndrome. It is important to develop toxicity theory of Chinese medicine in a sound and international way using modern language to elucidate its scientific connotation. We expect to explain scientific connotation of controlling toxic reaction while toxic herbs are used to the indication syndrome by using holistic research ideas and methods capable of reflecting governing exterior to infer interior, establish appropriate corresponding syndrome animal models by cutting into dose-effect/toxicity of toxic Chinese herbs, construct and analyze multi-layer molecular network using theories and technologies of metabonomics, network biology, and bioinformatics.

  4. Aluminium toxicity in chronic renal insufficiency.

    Science.gov (United States)

    Savory, J; Bertholf, R L; Wills, M R

    1985-08-01

    Aluminium is a ubiquitous element in the environment and has been demonstrated to be toxic, especially in individuals with impaired renal function. Not much is known about the biochemistry of aluminium and the mechanisms of its toxic effects. Most of the interest in aluminium has been in the clinical setting of the haemodialysis unit. Here aluminium toxicity occurs due to contamination of dialysis solutions, and treatment of the patients with aluminium-containing phosphate binding gels. Aluminium has been shown to be the major contributor to the dialysis encephalopathy syndrome and an osteomalacic component of dialysis osteodystrophy. Other clinical disturbances associated with aluminium toxicity are a microcytic anaemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and haemodialysis. Aluminium is readily transferred from the dialysate to the patient's bloodstream during haemodialysis. Once transferred, the aluminium is tightly bound to non-dialysable plasma constituents. Very low concentrations of dialysate aluminium in the range of 10-15 micrograms/l are recommended to guard against toxic effects. Very few studies have been directed towards the separation of the various plasma species which bind aluminium. Gel filtration chromatography has been used to identify five major fractions, one of which is of low molecular weight and the others appear to be protein-aluminium complexes. Recommendations on aluminium monitoring have been published and provide 'safe' and toxic concentrations. Also, the frequency of monitoring has been addressed. Major problems exist with the analytical methods for measuring aluminium which result from inaccurate techniques and contamination difficulties. The most widely used analytical technique is electrothermal atomic absorption spectrometry which can provide reliable measurements in the hands of a careful analyst.

  5. Aquatic Toxicity Assessment of Phosphate Compounds

    Science.gov (United States)

    Kim, Eunju; Yoo, Sunkyoung; Ro, Hee-Young; Han, Hye-Jin; Baek, Yong-Wook; Eom, Ig-Chun; Kim, Pilje; Choi, Kyunghee

    2013-01-01

    Objectives Tricalcium phosphate and calcium hydrogenorthophosphate are high production volume chemicals, mainly used as foodstuff additives, pharmaceuticals, lubricants, synthetic resin, and disinfectants. Phosphate has the potential to cause increased algal growth leading to eutrophication in the aquatic environment. However, there is no adequate information available on risk assessment or acute and chronic toxicity. The aim of this research is to evaluate the toxic potential of phosphate compounds in the aquatic environment. Methods An aquatic toxicity test of phosphate was conducted, and its physico-chemical properties were obtained from a database recommended in the Organization for Economic Cooperation and Development (OECD) guidance manual. An ecotoxicity test using fish, Daphnia, and algae was conducted by the good laboratory practice facility according to the OECD TG guidelines for testing of chemicals, to secure reliable data. Results The results of the ecotoxicity tests of tricalcium phosphate and calcium hydrogenorthophosphate are as follows: In an acute toxicity test with Oryzias latipes, 96 hr 50% lethal concentration (LC50) was >100 (measured:>2.14) mg/L and >100 (measured: >13.5) mg/L, respectively. In the Daphnia test, 48 hr 50% effective concentration (EC50) was >100 (measured: >5.35) mg/L and >100 (measured: >2.9) mg/L, respectively. In a growth inhibition test with Pseudokirchneriella subcapitata, 72 hr EC50 was >100 (measured: >1.56) mg/L and >100 (measured: >4.4) mg/L, respectively. Conclusions Based on the results of the ecotoxicity test of phosphate using fish, Daphnia, and algae, L(E)C50 was above 100 mg/L (nominal), indicating no toxicity. In general, the total phosphorus concentration including phosphate in rivers and lakes reaches levels of several ppm, suggesting that phosphate has no toxic effects. However, excessive inflow of phosphate into aquatic ecosystems has the potential to cause eutrophication due to algal growth. PMID:23440935

  6. VORICONAZOLE TOXICITY IN MULTIPLE PENGUIN SPECIES.

    Science.gov (United States)

    Hyatt, Michael W; Georoff, Timothy A; Nollens, Hendrik H; Wells, Rebecca L; Clauss, Tonya M; Ialeggio, Donna M; Harms, Craig A; Wack, Allison N

    2015-12-01

    Aspergillosis is a common respiratory fungal disease in penguins managed under human care. Triazole antifungal drugs, including itraconazole, are most commonly used for treatment; however, itraconazole treatment failures from drug resistance are becoming more common, requiring newer treatment options. Voriconazole, a newer triazole, is being used more often. Until recently, no voriconazole pharmacokinetic studies had been performed in penguins, leading to empiric dosing based on other avian studies. This has led to increased anecdotal reporting of apparent voriconazole toxicity in penguins. This report describes 18 probable and 6 suspected cases of voriconazole toxicity in six penguin species from nine institutions: 12 African penguins (Spheniscus demersus), 5 Humboldt penguins (Spheniscus humboldti), 3 Magellanic penguins (Spheniscus magellanicus), 2 gentoo penguins (Pygoscelis papua papua), 1 macaroni penguin (Eudyptes chrysolophus), and 1 emperor penguin (Aptenodytes forsteri). Observed clinical signs of toxicity included anorexia, lethargy, weakness, ataxia, paresis, apparent vision changes, seizure-like activity, and generalized seizures. Similar signs of toxicity have also been reported in humans, in whom voriconazole therapeutic plasma concentration for Aspergillus spp. infections is 2-6 μg/ml. Plasma voriconazole concentrations were measured in 18 samples from penguins showing clinical signs suggestive of voriconazole toxicity. The concentrations ranged from 8.12 to 64.17 μg/ml, with penguins having plasma concentrations above 30 μg/ml exhibiting moderate to severe neurologic signs, including ataxia, paresis, and seizures. These concentrations were well above those known to result in central nervous system toxicity, including encephalopathy, in humans. This case series highlights the importance of species-specific dosing of voriconazole in penguins and plasma therapeutic drug monitoring. Further investigation, including pharmacokinetic studies, is

  7. Metabolism and toxicity of arsenicals in mammals.

    Science.gov (United States)

    Sattar, Adeel; Xie, Shuyu; Hafeez, Mian Abdul; Wang, Xu; Hussain, Hafiz Iftikhar; Iqbal, Zahid; Pan, Yuanhu; Iqbal, Mujahid; Shabbir, Muhammad Abubakr; Yuan, Zonghui

    2016-12-01

    Arsenic (As) is a metalloid usually found in organic and inorganic forms with different oxidation states, while inorganic form (arsenite As-III and arsenate As-v) is considered to be more hazardous as compared to organic form (methylarsonate and dimethylarsinate), with mild or no toxicity in mammals. Due to an increasing trend to using arsenicals as growth promoters or for treatment purposes, the understanding of metabolism and toxicity of As gets vital importance. Its toxicity is mainly depends on oxi-reduction states (As-III or As-v) and the level of methylation during the metabolism process. Currently, the exact metabolic pathways of As have yet to be confirmed in humans and food producing animals. Oxidative methylation and glutathione conjugation is believed to be major pathways of As metabolism. Oxidative methylation is based on conversion of Arsenite in to mono-methylarsonic acid and di-methylarsenic acid in mammals. It has been confirmed that As is only methylated in the presence of glutathione or thiol compounds, suggesting that As is being methylated in trivalent states. Subsequently, non-conjugated trivalent arsenicals are highly reactive with thiol which converts the trivalent arsenicals in to less toxic pentavalent forms. The glutathione conjugate stability of As is the most important factor for determining the toxicity. It can lead to DNA damage by alerting enzyme profile and production of reactive oxygen and nitrogen species which causes the oxidative stress. Moreover, As causes immune-dysfunction by hindering cellular and humeral immune response. The present review discussed different metabolic pathways and toxic outcomes of arsenicals in mammals which will be helpful in health risk assessment and its impact on biological world. Copyright © 2016. Published by Elsevier B.V.

  8. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  9. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  10. Lisuride toxicity in a pediatric patient

    Directory of Open Access Journals (Sweden)

    Tahani A Alahmadi

    2013-01-01

    Full Text Available Lisuride Maleate (Dopergin is semi synthetic ergot alkaloid used for a variety of medical conditions. It is licensed for use in Canada, EU and Middle East countries and is marketed by various drug companies. There are no reported cases of lisuride toxicity in the literature on Google Search or Pub med Search.Herein, we present a case of accidental overdose of lisuride maleate in a 21-month-old Saudi male and further clinical course and management. The aim of this report was to document the unusual features of lisuride toxicity in pediatric patients and to guide physicians for its management.

  11. Reproductive toxicity of carbon nanomaterials: a review

    Science.gov (United States)

    Vasyukova, I.; Gusev, A.; Tkachev, A.

    2015-11-01

    In the current review, we assembled the experimental evidences of an association between carbon nanomaterials including carbon black, graphite nanoplatelets, graphene, single- and multi-walled carbon nanotubes, and fullerene exposure and adverse reproductive and developmental effects, in vitro and in vivo studies. It is shown that carbon nanomaterials reveal toxic effect on reproductive system and offspring development of the animals of various system groups to a certain degree depending on carbon crystal structure. Although this paper provides initial information about the potential male and female reproductive toxicity of carbon nanomaterials, further studies, using characterized nanoparticles, relevant routes of administration, and doses closely reflecting all the expected levels of exposure are needed.

  12. Toxicity of chlorinated benzenes to marine algae

    Science.gov (United States)

    Ma, Yan-Jun; Wang, Xiu-Lin; Yu, Wei-Jun; Zhang, Li-Jun; Sun, Han-Zhang

    1997-12-01

    Growth of Chlorella marine, Nannochloropsis oculata, Pyramidomonas sp., Platymonas subcordiformis and Phaeodactylum tricornutum exposed to monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DCB), 1, 2, 3, 4-tetrachlorobenzene (1, 2, 3, 4-TeCB) and pentachlorobenzene (PeCB) was tested. Tests of 72 h- EC 50 values showed that the toxicity ranged in the order: MCBNannochloropsis oculata < Chlorella marine < Phaeodactylum tricomutum. Study of the QSAR (Quantitative Structure-Activity Relationship) between K OW and toxicity of CBs to marine algae showed good relationships between -log EC 50 and log K OW.

  13. Mechanistic Understanding of Toxicity from Nanocatalysts

    Directory of Open Access Journals (Sweden)

    Cuijuan Jiang

    2014-08-01

    Full Text Available Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst.

  14. A rare presentation of methanol toxicity

    Directory of Open Access Journals (Sweden)

    Nikhil Gupta

    2013-01-01

    Full Text Available Methanol is a highly toxic alcohol resembling ethanol in smell and taste. Methanol poisoning is a lethal form of poisoning that can cause severe metabolic acidosis, visual disturbances, and neurological deficit. Brain lesions typically described in methanol toxicity are in the form of hemorrhagic and non-hemorrhagic necrosis of the basal ganglia and sub-cortical white matter. To our knowledge, lesions in the parietal, temporal, or frontal areas of cerebrum and cerebellar hemispheres have been rarely reported so far. We herewith report this rare presentation.

  15. Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

    Directory of Open Access Journals (Sweden)

    Lisa H. Mason

    2014-01-01

    Full Text Available Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

  16. Acute inhalation toxicity of carbonyl sulfide

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

  17. Introduction to the concept of signal toxicity.

    Science.gov (United States)

    Kanno, Jun

    2016-01-01

    Silent Spring by Rachel Carson (1962) established a role for environmental chemicals in cancer and Our Stolen Future by Theo Colbone, Dianne Dumanoski and John Peterson Myers (1996) coined the concept of "Endocrine Disrupting Chemicals (EDCs)" with its mechanistic plausibility for all the living organisms. For basic biologists, seeing a non-monotonic dose-response curve was a matter of course. In contrast, for the toxicologists at that time, the dose-response curves should be monotonic. It took some time for toxicologists to accept the plausibility that animals and humans are subject to the effects of EDCs act in a way that is explained by the new paradigm of receptor-mediated toxicity or in other words "signal toxicity." In classical toxicology, a toxic substance reaches a cellular target and induces malfunction. The target molecules are proteins including enzymes, lipid membranes, DNA, and other components of the cell which are damaged by the toxic substances. On the other hand, in the case of signal toxicity, a chemical binds to a specific receptor - after that, the chemical itself is not important. The signal from the receptor initiates a cascade of molecular events that leads to various changes in the cells and organs. When the signal is abnormal for a cell or an organ in terms of quality, intensity and timing, then the signal will induce adverse effects to the target. An extreme example of signal toxicity is the 1981 Nobel Prize in Physiology or Medicine work by Drs. Hubel and Wiesel. They blocked the signal of sharp images from the retina to the brain and found that the visual cortex needed this signal at the correct time for its proper development. In humans, such signal disruption is well known to induce "form-deprivation amblyopia" in infants. The concept of signal toxicity widens the range of systems vulnerable to EDCs and facilitates the understanding of their biological characteristics. For example, compared with intrinsic ligands, xenobiotic chemicals

  18. Microbial fuel-cell-based toxicity sensor for fast monitoring of acidic toxicity.

    Science.gov (United States)

    Shen, Yu J; Lefebvre, Olivier; Tan, Zi; Ng, How Y

    2012-01-01

    Wastewater may contain various potential toxicants. A microbial fuel cell (MFC) is a device in which bacteria convert the chemical energy into electricity. If a toxic event occurs, microbial activity is inhibited and thus the power output of the MFC decreases. Therefore, an MFC could serve as an early toxicity warning device. A real-time biomonitoring system was developed using MFCs to detect the inflow of toxic substances into wastewater treatment systems. After the MFCs reached steady state, a toxic incident was created by adding HCl into the wastewater to alter its pH. Consequently, a rapid decrease in voltage was observed immediately, followed by a subsequent recovery. The optimal MFC design was a single-chamber air cathode MFC, where the anode and cathode were separated by a Selemion proton exchange membrane. Under an external resistance of 5 Ω, the maximum power averaged 0.23 ± 0.023 mW with domestic wastewater. The optimized MFC showed high sensitivity and fast recovery when exposed to the acidic toxic event. When the hydraulic retention time was decreased from 22 to 3.5 min, sensitivity of the MFC increased substantially. Finally, the extent of inhibition observed was found to be related to the toxicity level, suggesting that a dosage-response relationship exists.

  19. Toxicity assessment of sediment cores from Santa Monica Bay, California.

    Science.gov (United States)

    Greenstein, Darrin; Bay, Steven; Jirik, Andrew; Brown, Jeffrey; Alexander, Clark

    2003-01-01

    During the summer of 1997, sediment core samples were taken at 25 stations in Santa Monica Bay. Toxicity testing was performed on 4-cm sections of the entire length of each core using purple sea urchin fertilization and amphipod survival tests. The sea urchin test identified sections as being toxic at six stations, all located near current or former Hyperion Treatment Plant (HTP) wastewater outfall locations. The amphipod test identified sections from 17 stations as having toxic sediments. The stations having toxic sediments were scattered throughout the bay and toxicity was identified at numerous core depths. Spatial and temporal patterns indicated that toxicity was most strongly associated with the historical disposal of municipal wastewater sludge. Many of the sections toxic to the amphipods did not have chemical levels expected to cause toxicity and were in locations where a source of toxicity was not apparent.

  20. Local anaesthetics: Characteris tics, uses and toxicities

    African Journals Online (AJOL)

    neuronal cell membranes so that action potentials cannot arise and signal conduction is inhibited. ... The toxicity of LAs relates to plasma concentration. The more free. LA in the body ... LAs are membrane-stabilising drugs that reversibly decrease the rate of depolarisation and repolarisation of excitable membranes. 398 ...

  1. Benzodiazepine Synthesis and Rapid Toxicity Assay

    Science.gov (United States)

    Fletcher, James T.; Boriraj, Grit

    2010-01-01

    A second-year organic chemistry laboratory experiment to introduce students to general concepts of medicinal chemistry is described. Within a single three-hour time window, students experience the synthesis of a biologically active small molecule and the assaying of its biological toxicity. Benzodiazepine rings are commonly found in antidepressant…

  2. Physical conditions affecting pyrethroid toxicity in arthropods

    NARCIS (Netherlands)

    Jagers op Akkerhuis, G.

    1993-01-01

    The aim of this thesis was to obtain mechanistic information about how the toxicity of pesticides in the field is affected by physical factors, pesticide bioavailability and arthropod behaviour. The pyrethroid insecticide deltamethrin and linyphiid spiders were selected as pesticide-effect

  3. The toxicity of aluminium in humans.

    Science.gov (United States)

    Exley, C

    2016-06-01

    We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Raising Children in a Socially Toxic Environment.

    Science.gov (United States)

    Garbarino, James

    1998-01-01

    Examines current social issues and the challenge of raising children under such conditions. Discusses elements of a socially toxic environment such as violence, poverty, disruption of family relationships, trauma, and alienation, and their effects on child development. Encourages a commitment to improve the quality of the social environment to…

  5. Toxicity studies of fullerenes and derivatives.

    Science.gov (United States)

    Kolosnjaj, Jelena; Szwarc, Henri; Moussa, Fathi

    2007-01-01

    Due to their unique properties, fullerenes, a model of carbon-based nanoparticles, have attracted considerable interest in many fields of research including material science and biomedical applications. The potential and the growing use of fullerenes and their mass production have raised several questions about their safety and environmental impact. Available data clearly shows that pristine C60 has no acute or sub-acute toxicity in a large variety of living organisms, from bacteria and fungal to human leukocytes, and also in drosophila, mice, rats and guinea pigs. In contrast to chemically--either covalently or noncovalently--modified fullerenes, some C60 derivatives can be highly toxic. Furthermore, under light exposure, C60 is an efficient singlet oxygen sensitizer. Therefore, if pristine C60 is absolutely nontoxic under dark conditions, this is not the case under UV-Visible irradiation and in the presence of O2 where ffullerene solutions can be highly toxic through 1O2 formation. This chapter offers a general review of the studies on the toxicity of [60]fullerene or C60, the most abundant fullerene, and its derivatives.

  6. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Purpose: To assess Alchornea cordifolia, a medicinal plant with numerous biological actions and uses in traditional medicine, for possible toxicity in rats. Methods: The probable effect of the ethanol extract of Alchornea cordifolia (250 - 2000 mg/kg, p.o.) by gavage was evaluated on blood cellular elements and chemistry, ...

  7. Modeling Respiratory Toxicity of Authentic Lunar Dust

    Science.gov (United States)

    Santana, Patricia A.; James, John T.; Lam, Chiu-Wing

    2010-01-01

    The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

  8. Nanomaterial Toxicity Screening in Developing Zebrafish Embryos

    Science.gov (United States)

    To assess nanomaterial vertebrate toxicity, a high-content screening assay was created using developing zebrafish, Danio rerio. This included a diverse group of nanomaterials (n=42 total) ranging from metallic (Ag, Au) and metal oxide (CeO2, CuO, TiO2, ZnO) nanoparticles, to non...

  9. The environmental toxicity of Dicerothamnus rhinocerotis and ...

    African Journals Online (AJOL)

    The environmental toxicity of Dicerothamnus rhinocerotis and Galenia africana. E.J Pool, J.A Klaasen, Y.P Shoko. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers ...

  10. Determinants of Toxicity of Environmental Asbestos Fibers

    Science.gov (United States)

    Recent EPA-led studies have addressed the comparative toxicity and pathological mechanisms of environmental asbestos samples from Libby, Montana and other communities in the United States. Longer amosite fibers induce a 4-10 fold greater induction of pro-inflammatory mediators C...

  11. A conceptual DFT approach towards analysing toxicity

    Indian Academy of Sciences (India)

    First, two benzidine derivatives, which act as electron-donating agents in their interactions with biomolecules are considered. Overall toxicity in general and the most probable site of reactivity in particular are effectively described by the global and local electrophilicity parameters respectively. Interaction of two benzidine ...

  12. [Release of toxic agents from ceramic utensils].

    Science.gov (United States)

    Herrmann, H J

    1978-01-01

    Under the influence of acidic agents, ceramic glazes and decorations for ceramics may release certain toxicants, especially lead and cadmium. Both elements are essential constituents of ceramic colours and glazes; their release to acidic foods is technologically unavoidable, but it may be minimized by the utilization of appropriate decoration agents and techniques. In most industrial countries, the release of toxicants from utensils is severely limited, the maximum permissible values and the methods of test and analysis being in part very different and not always in agreement with the demands and conditions of practice. The problems related to the release of toxicants from ceramic utensils are treated from the aspects of ceramics, test techniques, analytics, toxicology and food law, with special regard to the necessity for a well-balanced compromise between the justified hygienic demands of health protection and the actual technological possibilities. The endeavours of the ceramic industry of the GDF to produce ceramic utensils releasing as little toxicants as possible are outlined.

  13. REPELLENCY AND FUMIGANT TOXICITY OF CLOVE AND

    African Journals Online (AJOL)

    DELL

    2013-02-27

    Feb 27, 2013 ... 3Biotechnology Research Centre, Suez Canal University, Egypt. Accepted 15 August, 2012. Repellency and ... Appel et al. (2001) evaluated the repellency and toxicity of mint oil to. American cockroach; mint oil-based formulations could provide good integrated pest management tool for cockroach control.

  14. Toxic Waste in Grand Banks. Lesson Plan.

    Science.gov (United States)

    Litchka, Peter

    "Toxic Waste in Grand Banks" is an assessment task in which students from a high school economics class investigate the issues of economic prosperity, environmental concerns, government intervention in the market economy, and responsible civic participation in solving community problems. Students will demonstrate an ability--both individually and…

  15. Subacute toxicity assessment of annatto in rat.

    Science.gov (United States)

    Bautista, A R P L; Moreira, E L T; Batista, M S; Miranda, M S; Gomes, I C S

    2004-04-01

    Increased human use of annatto (Bixa orellana L), a red yellow food colorant, demands generation of toxicity data. The toxic effects of annatto powder (bixin 27%) have been assessed following administration of a subacute regimen (4 weeks, 20 doses) in Wistar male and female rats. A full study with three dose levels was considered unnecessary since no sign of toxicity had been noted in a preliminary experiment with 1000 mg/kg body weight/day as was recommended by the OECD guideline. In this study, annatto administered by gavage at a dose level of 2000 mg/kg/day decreased male body weight gain, but had no effect on either food intake or food conversion efficiency. Haematological and plasma biochemical examination as well necropsy performed at the end of administration (29th day) and observation (43rd day) periods revealed no alterations related with annatto administration. Kidney apoptosis occurred in 20% treated female rats in restricted areas without proliferation or tubular segments modification. The precise nature of apoptosis was not investigated in the present study. These findings suggest that annatto was no toxic to the rat.

  16. Regional Models for Sediment Toxicity Assessment

    Science.gov (United States)

    This paper investigates the use of empirical models to predict the toxicity of sediment samples within a region to laboratory test organisms based on sediment chemistry. In earlier work, we used a large nationwide database of matching sediment chemistry and marine amphipod sedim...

  17. Silica binding and toxicity in alveolar macrophages.

    Science.gov (United States)

    Hamilton, Raymond F; Thakur, Sheetal A; Holian, Andrij

    2008-04-01

    Inhalation of the crystalline form of silica is associated with a variety of pathologies, from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science investigators looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage interacts with the inhaled silica particle and the consequences of silica-induced toxicity on the cellular level. Based on experimental results, several rationales have been developed for exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica), triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, by which silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis are described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

  18. Toxicity of contrast media: an update.

    NARCIS (Netherlands)

    Dam, MA ten; Wetzels, J.F.M.

    2008-01-01

    Renal toxicity of iodinated radiocontrast media (contrastinduced nephropathy; CIN) is a major cause of acute renal failure in hospitalised patients. Magnetic resonance imaging (MRI) is applied as an alternative technique but the use of gadolinium (Gd) containing contrast media carries the risk of

  19. Biological toxicity of lanthanide elements on algae.

    Science.gov (United States)

    Tai, Peidong; Zhao, Qing; Su, Dan; Li, Peijun; Stagnitti, Frank

    2010-08-01

    The biological toxicity of lanthanides on marine monocellular algae was investigated. The specific objective of this research was to establish the relationship between the abundance in the seawater of lanthanides and their biological toxicities on marine monocellular algae. The results showed that all single lanthanides had similar toxic effects on Skeletonema costatum. High concentrations of lanthanides (29.04+/-0.61 micromol L(-1)) resulted in 50% reduction in growth of algae compared to the controls (0 micromol L(-1)) after 96 h (96 h-EC50). The biological toxicity of 13 lanthanides on marine monocellular algae was unrelated with the abundance of different lanthanide elements in nature, and the "Harkins rule" was not appropriate for the lanthanides. A mixed solution that contained equivalent concentrations of each lanthanide element had the same inhibition effect on algae cells as each individual lanthanide element at the same total concentration. This phenomenon is unique compared to the groups of other elements in the periodic table. Hence, we speculate that the monocellular organisms might not be able to sufficiently differentiate between the almost chemically identical lanthanide elements. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  20. In Vitro Toxicity Assessment Technique for Volatile ...

    Science.gov (United States)

    The U.S. Environmental Protection Agency is tasked with evaluating the human health, environmental, and wildlife effects of over 80,000 chemicals registered for use in the environment and commerce. The challenge is that sparse chemical data exists; traditional toxicity testing methods are slow, costly, involve animal studies, and cannot keep up with a chemical registry that typically grows by at least 1000 chemicals every year. In recent years, High Throughput Screening (HTS) has been used in order to prioritize chemicals for traditional toxicity screening or to complement traditional toxicity studies. HTS is an in vitro approach of rapidly assaying a large number of chemicals for biochemical activity using robotics and automation. However, no method currently exists for screening volatile chemicals such as air pollutants in a HTS fashion. Additionally, significant uncertainty regarding in vitro to in in vivo extrapolation (IVIVE) remains. An approach to bridge the IVIVE gap and the current lack of ability to screen volatile chemicals in a HTS fashion is by using a probe molecule (PrM) technique. The proposed technique uses chemicals with empirical human pharmacokinetic data as PrMs to study toxicity of molecules with no known data for gas-phase analysis. We are currently studying the xenobiotic-metabolizing enzyme CYP2A6 using transfected BEAS-2B bronchial epithelial cell line. The CYP2A6 pathway activity is studied by the formation of cotinine from nicot

  1. Toxicity of Nanomaterials-Physicochemical Effects

    Directory of Open Access Journals (Sweden)

    A Rahi

    2015-02-01

    Full Text Available Nanomaterials involve the structures with at least one dimension of <100 nm. Recently, development in nanotechnology has led to the use of nanomaterials in many different fields. On the other hand, increasing use of nanomaterials has resulted in release of these materials to the environment. Therefore, before employing these materials in biological and living systems, they should be evaluated in terms of biocompatibility and distribution. Although the toxic effects of nanomaterials on living organisms, human health and the environment have been studied by some researchers, there are too much uncertainty regarding the effects and mechanisms of toxicity of nanomaterials. Therefore, understanding the toxicity effects of nanomaterials is highly desirable. Cellular uptake mechanisms and dispersion of nanomaterials in biological environments depend on their physicochemical properties. Therefore, knowledge of the unique characteristics of nanomaterials and the interactions of nanomaterials with biological systems, are important criteria for the safe use of nanomaterials. Properties of nanomaterials such as size, shape, aspect ratio, density, surface and structural defects and dissolving rate are the main causes of cytotoxicity and side effects of these materials in the body. Exposure to nanomaterials may cause a range of acute and chronic effects, including inflammation, exacerbation of asthma, metal fume fever, fibrosis, chronic inflammatory diseases and cancer. The present paper, reviews the previous studies aiming at the investigation of the relation between the physiochemical properties of nanomaterials and their toxicity.

  2. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    DR. GODSON

    Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Heavy. Metal in Crude Oil from Gokana Area, Rivers State, Nigeria. *1. IWUOHA, G;. 1. ORUBITE, O;. 1. OKITE I. 1Department of Pure and Industrial Chemistry, Faculty of Sciences, University of Port Harcourt. ABSTRACT: This article is focused ...

  3. 40 CFR 261.24 - Toxicity characteristic.

    Science.gov (United States)

    2010-07-01

    ... Toxicity characteristic. (a) A solid waste (except manufactured gas plant waste) exhibits the... Contaminant CAS No. 2 Regulatory Level (mg/L) D004 Arsenic 7440-38-2 5.0 D005 Barium 7440-39-3 100.0 D018...

  4. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Science.gov (United States)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  5. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Erah

    2010-10-21

    Oct 21, 2010 ... Purpose: To assess Alchornea cordifolia, a medicinal plant with numerous biological actions and uses in traditional medicine, for possible toxicity in rats. Methods: The probable effect of the ethanol extract of Alchornea cordifolia (250 - 2000 mg/kg, p.o.) by gavage was evaluated on blood cellular elements ...

  6. ORIGINAL ARTICLES Nevirapine toxicity- implications for ...

    African Journals Online (AJOL)

    of mother-to-child HIV transmission (MTCT) in resource-poor settings. Early in nevirapine development, ... of serious liver toxicity in patients with preserved CD4 cell counts commencing nevirapine. This article will review ... efavirenz and 2.1% for nevirapine, and liver failure rates of 0.4 and 0.3 cases per 100 person-years, ...

  7. Acute Amiodarone Pulmonary Toxicity After Surgical Procedures.

    Science.gov (United States)

    Teerakanok, Jirapat; Tantrachoti, Pakpoom; Chariyawong, Phumpattra; Nugent, Kenneth

    2016-12-01

    Amiodarone can cause toxicity in several organs, including amiodarone-induced pulmonary toxicity which is a subacute or chronic complication. Amiodarone-induced acute respiratory distress syndrome (ARDS) in postoperative patients is a rare acute complication. The PubMed and Google Scholar databases were searched. Seven retrospective and prospective case series and 10 case reports of amiodarone-induced postoperative ARDS were reviewed. All patients received amiodarone chronically or during the perioperative period. Forty-three out of 285 patients (15%) reported in the retrospective and prospective studies developed amiodarone-induced ARDS. Most of the patients were men in age group 60-80 who had undergone cardiothoracic surgery. All patients had general anesthesia and exposure to high concentrations of oxygen. The onset of symptoms ranged from 2 hours to 2 weeks after surgery. The mortality rate of amiodarone-induced ARDS after surgery was approximately 10%. Ten case reports were evaluated using Naranjo criteria. Two cases had definite amiodarone toxicity, and 8 had probable toxicity based on these criteria. The incidence of amiodarone-induced postoperative ARDS was approximately 15% in these studies. Most operations involved cardiothoracic surgery. Elderly patients on high-dose and long-term amiodarone treatment were at increased risk. This diagnosis is challenging owing to the lack of definite diagnostic criteria; careful clinical evaluation and early drug withdrawal may reduce the severity of this complication. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

  9. Anaerobic Toxicity of Cationic Silver Nanoparticles

    Science.gov (United States)

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

  10. Glycopyrrolate in toxic exposure to ammonia gas

    Directory of Open Access Journals (Sweden)

    Bhalla A

    2011-01-01

    Full Text Available Ammonia (NH 3 is a highly water-soluble, colorless, irritant gas with a unique pungent odor. Liquid ammonia stored under high pressure is still widely used for refrigeration in cold stores used for storing grains. Severe toxicity may occur following accidental exposure. We report an interesting case of accidental exposure to ammonia treated with glycopyrrolate along with other supportive measures.

  11. 35__200 - 204__Musa - Toxicity

    African Journals Online (AJOL)

    User

    ABSTRACT. Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on ...

  12. Toxicity of Brass Particulate to Daphnia magna.

    Science.gov (United States)

    1985-11-01

    adults, were used as the experimental animals. The culture techniques used were described by Goulden et al. 2 Ten neonates were placed in each 250-mi...Density on the Acute Toxicities of Surfactants , Copper, and Phenol to Daphnia magna Straus. Arch. Environ. Contam. Toxicol. 12, 51-53T9T3). 7. Berglind

  13. Cellular Metabolomics for Exposure and Toxicity Assessment

    Science.gov (United States)

    We have developed NMR automation and cell quench methods for cell culture-based metabolomics to study chemical exposure and toxicity. Our flow automation method is robust and free of cross contamination. The direct cell quench method is rapid and effective. Cell culture-based met...

  14. antioxidants, cadmium-induced toxicity, serum biochemical

    African Journals Online (AJOL)

    Daniel Owu

    (1.51/gm) and selenium (0.25mg) which on their own had little or no effects on the serum basal phosphatases, hormonal and histological stability caused a reversal of the cadmium-induced biochemical, hormonal and histological toxicities of the ..... accessory sex tissues atrophy such as the prostate. (Waalkes et al 1997a).

  15. Epigenetic mechanisms in nanomaterial-induced toxicity.

    Science.gov (United States)

    Shyamasundar, Sukanya; Ng, Cheng Teng; Yung, Lin Yue Lanry; Dheen, Shaikali Thameem; Bay, Boon Huat

    2015-01-01

    With the growing advent of nanotechnology in medicine (therapeutic, diagnostic and imaging applications), cosmetics, electronics, clothing and food industries, exposure to nanomaterials (NMs) is on the rise and therefore exploring their toxic biological effects have gained great significance. In vitro and in vivo studies over the last decade have revealed that NMs have the potential to cause cytotoxicity and genotoxicity although some contradictory reports exist. However, there are only few studies which have explored the epigenetic mechanisms (changes to DNA methylation, histone modification and miRNA expression) of NM-induced toxicity, and there is a scarcity of information and many questions in this area remain unexplored and unaddressed. This review comprehensively describes the epigenetic mechanisms involved in the induction of toxicity of engineered NMs, and provides comparisons between similar effects observed upon exposure to small or nanometer-sized particles. Lastly, gaps in existing literature and scope for future studies that improve our understanding of NM-induced epigenetic toxicity are discussed.

  16. Toxic Imports and the African Environment

    African Journals Online (AJOL)

    Administrator

    1. African Journal of Environmental Science and Technology Vol. 1 (5), December, 2007. Available online at http://www.academicjournals.org/AJest. ISSN 1996-0786. Editorial. Toxic Imports and the African Environment. December is the quintessential gifting season. Children in particular look forward to real and imagined ...

  17. Anaerobic Toxicity of Cationic Silver Nanoparticles | Science ...

    Science.gov (United States)

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNps) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10-15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L-1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L-1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L-1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. The current

  18. Toxicity of ionic liquids prepared from biomaterials.

    Science.gov (United States)

    Gouveia, W; Jorge, T F; Martins, S; Meireles, M; Carolino, M; Cruz, C; Almeida, T V; Araújo, M E M

    2014-06-01

    In search of environmentally-friendly ionic liquids (ILs), 14 were prepared based on the imidazolium, pyridinium and choline cations, with bromide and several amino acids as anions. Good yields were obtained in the synthesis of pyridinium ILs and those prepared from choline and amino acids. Four of the ILs synthesized from choline and the amino acids arginine, glutamine, glutamic acid and cystine are described here for the first time. The toxicity of the synthesized ILs was checked against organisms of various levels of organization: the crustacean Artemia salina; Human cell HeLa (cervical carcinoma); and bacteria with different types of cell wall, Bacillus subtilis and Escherichia coli. The toxicity was observed to depend on both the cation and anion. Choline-amino acid ILs showed a remarkable low toxicity to A. salina and HeLa cell culture, ten times less than imidazolium and pyridinium ILs. None of ionic liquids exhibited marked toxicity to bacteria, and the effect was 2-3 orders of magnitude smaller than that of the antibiotic chloramphenicol. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The global variability of diatomaceous earth toxicity

    DEFF Research Database (Denmark)

    Nattrass, C; Horwell, C J; Damby, D E

    2015-01-01

    BACKGROUND: Diatomaceous earth (DE) is mined globally and is potentially of occupational respiratory health concern due to the high crystalline silica content in processed material. DE toxicity, in terms of variability related to global source and processing technique, is poorly understood...

  20. Possible toxicity of boron on sugar cane

    Energy Technology Data Exchange (ETDEWEB)

    Bravo C., M.

    Analyses of necrotic and green leaf tissues from sugar cane grown in the Tambo Valley (Arequipa, Peru) have shown that the boron concentration in necrotic tissue (average 657.7 ppm) is several times higher than that in the green tissue (average 55.7 ppm). This suggests that the necrosis may be due to boron toxicity.

  1. Understanding the toxicity of carbon nanotubes.

    Science.gov (United States)

    Liu, Ying; Zhao, Yuliang; Sun, Baoyun; Chen, Chunying

    2013-03-19

    Because of their unique physical, chemical, electrical, and mechanical properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale production and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable experimental data related to CNT toxicity at the molecular, cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed. In this Account, we highlight recent investigations into the basis of CNT toxicity carried out by our team and by other laboratories. We focus on several important factors that explain the disparities in the experimental results of nanotoxicity, such as impurities, amorphous carbon, surface charge, shape, length, agglomeration, and layer numbers. The exposure routes, including inhalation, intravenous injection, or dermal or oral exposure, can also influence the in vivo behavior and fate of CNTs. The underlying mechanisms of CNT toxicity include oxidative stress, inflammatory responses, malignant transformation, DNA damage and mutation (errors in chromosome number as well as disruption of the mitotic spindle), the formation of granulomas, and interstitial fibrosis. These findings provide useful insights for de novo design and safe application of carbon nanotubes and their risk assessment to human health. To obtain reproducible and accurate results, researchers must establish standards and reliable detection methods, use standard CNT samples as a reference control, and study the impact of various factors systematically. In addition, researchers need to examine multiple types of CNTs, different cell lines and animal species, multidimensional evaluation methods, and

  2. Altered expression of sodium channel distribution in the dorsal root ganglion after gradual elongation of rat sciatic nerves.

    Science.gov (United States)

    Ohno, Katsunori; Yokota, Atsushi; Hirofuji, Shinji; Kanbara, Kiyoto; Ohtsuka, Hisashi; Kinoshita, Mitsuo

    2010-04-01

    To elucidate the pathophysiological mechanisms underlying chronic nerve-stretch injury, we gradually lengthened rat femurs by 15 mm at the rate of 0.5 mm/day (group L, n = 13). The control groups comprised sham-operated (group S, n = 10) and naive (group N, n = 8) rats. Immediately after the lengthening, we performed a conduction study on their sciatic nerves and harvested samples. Electrophysiological and histological analyses showed mild conduction slowing and axonal degeneration of unmyelinated fibers in group L rats. Altered mRNA expression of the voltage-gated sodium channels in the dorsal root ganglion was also observed. Tetrodotoxin-resistant (TTX-R) sodium-channel Nav1.8 mRNA expression was significantly decreased and TTX-R sodium-channel Nav1.9 mRNA expression showed a tendency to decrease when compared with the mRNA expressions in the control groups. However, tetrodotoxin-sensitive (TTX-S) sodium-channel Nav1.3 mRNA expression remained unaltered. The immunohistochemical alteration of Nav1.8 protein expression was parallel to the results of the mRNA expression. Previous studies involving neuropathic states have suggested that pain/paresthesia is modulated by a subset of sodium channels, including downregulation and/or upregulation of TTX-R and TTX-S sodium channels, respectively. Our findings indicate that Nav1.8 downregulation may be one of the pathophysiological mechanisms involved in limb lengthening-induced neuropathy.

  3. Toxicity of chlorine to zebrafish embryos

    Science.gov (United States)

    Kent, Michael L.; Buchner, Cari; Barton, Carrie; Tanguay, Robert L.

    2014-01-01

    Surface disinfection of fertilized fish eggs is widely used in aquaculture to reduce extraovum pathogens that may be released from brood fish during spawning, and this is routinely used in zebrafish (Danio rerio) research laboratories. Most laboratories use approximately 25 – 50 ppm unbuffered chlorine solution for 5 – 10 min. Treatment of embryos with chlorine has significant germicidal effects for many Gram-negative bacteria, viruses, and trophozoite stages of protozoa, it has reduced efficacy against cyst or spore stages of protozoa and certain Mycobacterium spp. Therefore, we evaluated the toxicity of unbufferred and buffered chlorine solution to embryos exposed at 6 or 24 hours post-fertilization (hpf) to determine if higher concentrations can be used for treating zebrafish embryos. Most of our experiments entailed using an outbred line (5D), with both mortality and malformations as endpoints. We found that 6 hpf embryos consistently were more resistant than 24 hpf embryos to the toxic effects of chlorine. Chlorine is more toxic and germicidal at lower pHs, and chlorine causes elevated pH. Consistent with this, we found that unbufferred chlorine solutions (pH ca 8–9) were less toxic at corresponding concentrations than solutions buffered to pH 7. Based on our findings here, we recommend treating 6 hpf embryos for 10 min and 24 hpf for 5 min with unbuffered chlorine solution at 100 ppm. One trial indicated that AB fish, a popular outbred line, are more susceptible to toxicity than 5Ds. This suggests that variability between zebrafish lines occurs, and researchers should evaluate each line or strain under their particular laboratory conditions for selection of the optimum chlorine treatment procedure. PMID:24429474

  4. Medical Applications and Toxicities of Gallium Compounds

    Science.gov (United States)

    Chitambar, Christopher R.

    2010-01-01

    Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use. PMID:20623028

  5. Medical Applications and Toxicities of Gallium Compounds

    Directory of Open Access Journals (Sweden)

    Christopher R. Chitambar

    2010-05-01

    Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

  6. Endothelial toxicity of unusual nucleotide metabolites.

    Science.gov (United States)

    Pelikant-Malecka, Iwona; Sielicka, Alicja; Kaniewska, Ewa; Smolenski, Ryszard T; Slominska, Ewa M

    2015-08-01

    Endothelium plays a pivotal role in the vascular tone regulation, platelet aggregation, regulation of immune response, inflammation and angiogenesis and its dysfunction is an earliest event in the development of cardiovascular disease. All these processes are affected by endothelial dysfunction. Endothelial toxicity induced by metabolites present in blood is a common scenario in pathology. This involves physiological metabolites such as asymmetric dimethylarginine or homocysteine that are normally excreted by kidneys, but accumulate in pathological conditions, adversely affecting function of endothelium. Our group identified new molecule with potential endothelial toxicity: 4-pirydone-3-carboxamide-1-β-d-ribonucleoside (4PYR). This nucleoside is most likely produced by oxidation of nicotinamide containing precursor by aldehyde oxidase. 4PYR easy crosses cell membrane and become phosphorylated inside the cell giving rise to mono-, di- and triphospates (4PYMP, 4PYDP and 4PYTP). There is considerable evidence that 4PYR is toxic in endothelium and other cell types by disrupting cell energetics evident as ATP depletion. Endothelial dysfunction in the in vitro and in vivo experiments is, however, evident only after prolonged exposure to 4PYR while acute cardiovascular effects are minor. 4PYR endothelial toxicity could be particularly important in patients with chronic renal disease where accumulation of 4PYR and its metabolites is particularly prominent. 4PYR metabolism and toxicity could be blocked by application of nucleoside transport inhibitors and we have proven efficiency of such intervention. We believe that blocking metabolism of endothelial nucleoside toxins such as 4PYR could become important strategy for endothelial targeted therapy. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

  7. The Acute Toxicity of Major Ion Salts to Ceriodaphnia dubia. III. Mathematical models for mixture toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset concerns the development of models for describing the acute toxicity of major ions to Ceriodaphnia dubia using data from single salt tests and binary...

  8. Food plant toxicants and safety - Risk assessment and regulation of inherent toxicants in plant foods

    DEFF Research Database (Denmark)

    Essers, A.J.A.; Alink, G.M.; Speijers, G.J.A.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI...... values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human...... health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial...

  9. Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

    Science.gov (United States)

    Myers, Todd M; Langston, Jeffrey L

    2011-06-01

    To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Čolović Mirjana B.

    2013-01-01

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

  11. Predicting molybdenum toxicity to higher plants: Estimation of toxicity threshold values

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C.; Zhao, F.J.; Stroud, J.L. [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhang, H.; Fozard, S. [Division of Environmental Science, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

    2010-10-15

    Four plant species (oilseed rape, Brassica napus L.; red clover, Trifolium pratense L.; ryegrass, Lolium perenne L.; and tomato, Lycopersicon esculentum L.) were tested on ten soils varying widely in soil properties to assess molybdenum (Mo) toxicity. A larger range (66-fold-609-fold) of added Mo concentrations resulting in 50% inhibition of yield (ED{sub 50}) was found among soils than among plant species (2-fold-38-fold), which illustrated that the soils differed widely in the expression of Mo toxicity. Toxicity thresholds based on soil solution Mo narrowed the variation among soils compared to thresholds based on added Mo concentrations. We conclude that plant bioavailability of Mo in soil depends on Mo solubility, but this alone did not decrease the variability in observed toxicity enough to be used in risk assessment and that other soil properties influencing Mo toxicity to plants need to be considered. - Mo toxicity thresholds varied widely in different soils and therefore soil properties need to be taken into account in order to assess the risk of Mo exposure.

  12. Anaerobic toxicity of cationic silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gitipour, Alireza; Thiel, Stephen W. [Biomedical, Chemical, and Environmental Engineering, University of Cincinnati, Cincinnati, OH (United States); Scheckel, Kirk G. [USEPA, Office of Research and Development, Cincinnati, OH (United States); Tolaymat, Thabet, E-mail: tolaymat.thabet@epa.gov [USEPA, Office of Research and Development, Cincinnati, OH (United States)

    2016-07-01

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag{sup +} under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10–15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L{sup −1}, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L{sup −1} as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag{sup +}. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L{sup −1} as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. - Highlights: • At concentrations -1 the anaerobic decomposition process was not impacted. • An impact on the microbial community at concentrations -1 were observed. • At high concentrations (100 mg L{sup −1}), the cationic BPEI-AgNPs demonstrated toxicity. • Toxicity was demonstrated without the presence of oxidative dissolution of silver. • A one size fits all approach for the evaluation of NPs may not be accurate.

  13. Toxicity of substituted benzene derivatives to four chemolithotrophic ...

    African Journals Online (AJOL)

    The toxicity of benzene, hydroxylbenzene (phenol), chlorobenzene, methylbenzene (toluene) and dimethylbenzene (xylene) to four chemolithotrophic bacteria (Nitrosomonas, Nitrobacter, Thiobacillus and Leptothrix isolated from the New Calabar River water was investigated. The static method for acute toxicity assessment ...

  14. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  15. Contaminated marine sediments: Water column and interstitial toxic effects

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, R.M.; Schweitzer, K.A.; McKinney, R.A.; Phelps, D.K.

    1993-01-01

    The toxicity that contaminated sediments may introduce into the water column has not been measured extensively. In order to quantify this potential toxicity, the seawater overlying two uncontaminated and three contaminated marine sediments was evaluated in the laboratory with the sea urchin Arbacia punctulata fertilization test. Concentrations of polychlorinated biphenyls (PCBs) and copper, as representative contaminants, were also measured. To characterize sources of toxicity, samples were chemically manipulated using reversed-phase chromatography, cation exchange, and chelation. Water column toxicity and contaminant concentrations were higher in the suspended exposures than in bedded exposures. Interstitial water toxicity and contaminant concentrations were generally greater than either bedded or suspended exposures. Chemical manipulation indicated that the observed toxicity in water column exposures was probably caused by metallic and/or nonionic organic contaminants. Conversely, manipulation of interstitial waters did not result in significantly reduced toxicity, suggesting that other toxicants such as ammonia and hydrogen sulfide may be active.

  16. Contaminated marine sediments: Water column and interstitial toxic effects

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, R.M.; McKinney, R.A. (Science Applications International Corp., Narragansett, RI (United States)); Schweitzer, K.A. (Chemical Waste Management, Inc., Dartmouth, MA (United States)); Phelps, D.K. (Environmental Protection Agency, Narragansett, RI (United States))

    1993-01-01

    The toxicity that contaminated sediments may introduce into the water column has not been measured extensively. In order to quantify this potential toxicity, the seawater overlying two uncontaminated and three contaminated marine sediments was evaluated in the laboratory with the sea urchin Arbacia punctulata fertilization test. Concentration of polychlorinated biphenyls (PCBs) and copper, as representative contaminants, were also measured. To characterize sources of toxicity, samples were chemically manipulated using reversed-phase chromatography, cation exchange, and chelation. Water column toxicity and contaminant concentrations were higher in the suspended exposures than in bedded exposures. Interstitial water toxicity and contaminant concentrations were generally greater than either bedded or suspended exposures. Chemical manipulation indicated that the observed toxicity in water column exposures was probably caused by metallic and/or nonionic organic contaminants. Conversely, manipulation of interstitial water did not result in significantly reduced toxicity, suggesting that other toxicants such as ammonia and hydrogen sulfide may be active.

  17. Non-Toxic Ionic Liquid Fuels for Exploration Applications Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop and test new, non-toxic ionic liquid fuels for propulsion applications. Vintage propulsion systems frequently use highly toxic...

  18. Microcystis aeruginosa : source of toxic microcystins in drinking water

    African Journals Online (AJOL)

    , which is the most common toxic cyanobacterium in eutrophic freshwater. The association of environmental parameters with cyanobacterial blooms and the toxicity of microcystin are discussed. Also, the synthesis of the microcystins, as well as ...

  19. Population Suppression of Subterranean Termites by Slow-Acting Toxicants

    Science.gov (United States)

    Nan-Yao Su; Rudolf H. Scheffrahn

    1991-01-01

    Historic background and the concept of slow-acting toxicants for population suppression of subterranean termites are reviewed. Information needed for development of bait-toxicants and studies needed to generate such information are summarized.

  20. Vitamin D Toxicity: What If You Get Too Much?

    Science.gov (United States)

    Healthy Lifestyle Nutrition and healthy eating What is vitamin D toxicity, and should I worry about it ... Answers from Katherine Zeratsky, R.D., L.D. Vitamin D toxicity, also called hypervitaminosis D, is a ...

  1. Recovery of anaerobic digestion after exposure to toxicants. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J.; Parkin, G.F.; Speece, R.E.

    1979-12-01

    The concept that methane fermentation cannot tolerate chronic or slug doses of toxicants has almost totally precluded methane fermentation as a viable contender for the treatment of industrial wastewaters. This study assayed a wide variety of toxicants, heavy metals, inorganic salts, organic chemicals, solvents, and antibiotics which are used in industrial processes and, therefore, appear in the industrial wastewaters therefrom. Toxicity was related to the reduction in methane production of a control containing no toxicant. The response of methane fermentation after exposure to a toxicant was assayed with unacclimated cultures as well as cultures which had been acclimated to increasing concentrations of the toxicant over long periods of time. The reversible nature of the toxicants was assayed by adding slug doses to plug flow anaerobic filters and recording gas production prior to, during, and after toxicant addition.

  2. Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

    Science.gov (United States)

    Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

    2005-04-01

    The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

  3. Fetal Toxicity and Cytotoxicity of Lannea kerstingii Engl and Krause ...

    African Journals Online (AJOL)

    is toxic to the fetus. Keywords: Lannea kerstingii, Fetal toxicity, Cytotoxicity, Mortality, Oxidative stress, Anorexia. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Toxic Leadership in the U.S. Army

    Science.gov (United States)

    2005-01-10

    characteristics attributable to toxic leaders. The following compilation of traits provides a starting point for better understanding of toxic leadership ...serve as a departure point for study. In most cases of toxic leadership the leader will present not just one, but a combination of traits ... leadership . A review of some of the toxic leadership types reflect some desired qualities of military leadership . Unlike some of the milder traits and

  6. Statistical analysis of joint toxicity in biological growth experiments

    DEFF Research Database (Denmark)

    Spliid, Henrik; Tørslev, J.

    1994-01-01

    The authors formulate a model for the analysis of designed biological growth experiments where a mixture of toxicants is applied to biological target organisms. The purpose of such experiments is to assess the toxicity of the mixture in comparison with the toxicity observed when the toxicants are...... is applied on data from an experiment where inhibition of the growth of the bacteria Pseudomonas fluorescens caused by different mixtures of pentachlorophenol and aniline was studied....

  7. Nanomaterials and nanoparticles : Sources and toxicity

    CERN Document Server

    Buzea, Cristina; Robbie, Kevin

    2008-01-01

    This review is written with the goal of informing public health concerns related to nanoscience, while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to nanoparticles and dust from natural sources and human activities, the recent development of industry and combustion-based engine transportation profoundly increasing anthropogenic nanoparticulate pollution. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Among diseases associated with nanoparticles are asthma, bronchitis, lung cancer, neurodegenerative diseases (such as Parkinson`s and Alzheimer`s diseases), Crohn`s disease, colon cancer. Nanoparticles that enter the circulatory system are related to occurrence of arteriosclerosis, and blood clots, arrhythmia, heart diseases, and ultimately cardiac d...

  8. Toxicity of calcium salts to aqueous microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Lakhina, K.G.; Dolganova, A.V.; Yakobi, L.K.

    1983-03-01

    This article investigates the toxicity of calcium to aqueous microogranisms by means of a procedure developed by VNII VODGEO (All-Union Scientific-Research Institute of Water Supply, Sewer Systems, Hydrotechnical Facilities, and Engineering Hydrogeology), with certain changes in the preparation of the culture water. Proposes that with this method, calcium toxicity can be determined for groups of microorganisms that are among the most important in biochemical wastewater treatment and self-purification of water bodies (saprophytes, phase I and II nitrifiers). Finds that calcium in the form of the hydroxide and chloride is nontoxic under the following conditions: for protozoa in concentrations up to 2 g/liter, for saprophytic bacteria up to 3 g/liter, for phase I nitrifiers up to 1 g/liter, and for phase II nitrifiers up to 0.1 g/liter.

  9. [Can nitrates lead to indirect toxicity?].

    Science.gov (United States)

    Hamon, M

    2007-09-01

    For many years, nitrates have been used, at low dosages, as an additive in salted food. New laws have been promulgated to limit their concentration in water due to increased levels found in soils, rivers and even the aquifer. Although nitrate ions themselves have not toxic properties, bacterial reduction into nitrite ions (occurring even in aqueous medium) can lead to nitrous anhydride, which in turn generates nitrosonium ions. Nitrosium ions react with secondary amine to give nitrosamines, many of which are cancer-inducing agents at very low doses. Opinions on this toxicity are clear-cut and difficult to reconcile. In fact, increased levels are due, in a large part, to the use of nitrates as fertiliéers but also to bacterial transformation of human and animal nitrogenous wastes such as urea.

  10. Protection against Radiotherapy-Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Susan Hall

    2016-07-01

    Full Text Available Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.

  11. Vitamin A and Retinoids as Mitochondrial Toxicants

    Directory of Open Access Journals (Sweden)

    Marcos Roberto de Oliveira

    2015-01-01

    Full Text Available Vitamin A and its derivatives, the retinoids, are micronutrient necessary for the human diet in order to maintain several cellular functions from human development to adulthood and also through aging. Furthermore, vitamin A and retinoids are utilized pharmacologically in the treatment of some diseases, as, for instance, dermatological disturbances and some types of cancer. In spite of being an essential micronutrient with clinical application, vitamin A exerts several toxic effects regarding redox environment and mitochondrial function. Moreover, decreased life quality and increased mortality rates among vitamin A supplements users have been reported. However, the exact mechanism by which vitamin A elicits its deleterious effects is not clear yet. In this review, the role of mitochondrial dysfunction in the mechanism of vitamin A-induced toxicity is discussed.

  12. Toxicity of inorganic nanomaterials in biomedical imaging.

    Science.gov (United States)

    Li, Jinxia; Chang, Xueling; Chen, Xiaoxia; Gu, Zhanjun; Zhao, Feng; Chai, Zhifang; Zhao, Yuliang

    2014-01-01

    Inorganic nanoparticles have shown promising potentials as novel biomedical imaging agents with high sensitivity, high spatial and temporal resolution. To translate the laboratory innovations into clinical applications, their potential toxicities are highly concerned and have to be evaluated comprehensively both in vitro and in vivo before their clinical applications. In this review, we first summarized the in vivo and in vitro toxicities of the representative inorganic nanoparticles used in biomedical imagings. Then we further discuss the origin of nanotoxicity of inorganic nanomaterials, including ROS generation and oxidative stress, chemical instability, chemical composition, the surface modification, dissolution of nanoparticles to release excess free ions of metals, metal redox state, and left-over chemicals from synthesis, etc. We intend to provide the readers a better understanding of the toxicology aspects of inorganic nanomaterials and knowledge for achieving optimized designs of safer inorganic nanomaterials for clinical applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Alcohol metabolism: role in toxicity and carcinogenesis.

    Science.gov (United States)

    Badger, Thomas M; Ronis, Martin J J; Seitz, Helmut K; Albano, Emanuele; Ingelman-Sundberg, Magnus; Lieber, Charles S

    2003-02-01

    This article contains the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, organized and co-chaired by Thomas M. Badger, Paul Shih-Jiun Yin, and Helmut Seitz. The presentations were (1) First-pass metabolism of ethanol: Basic and clinical aspects, by Charles Lieber; (2) Intracellular CYP2E1 transport, oxidative stress, cytokine release, and ALD, by Magnus Ingelman-Sundberg; (3) Pulsatile ethanol metabolism in intragastric infusion models: Potential role in toxic outcomes, by Thomas M. Badger and Martin J.J. Ronis; (4) Free radicals, adducts, and autoantibodies resulting from ethanol metabolism: Role in ethanol-associated toxicity, by Emanuele Albano; and (5) Gastrointestinal metabolism of ethanol and its possible role in carcinogenesis, by Helmut Seitz.

  14. Phenol and Its Toxicity: A Case Report

    Directory of Open Access Journals (Sweden)

    Mahesh Chand Meena

    2014-12-01

    Full Text Available Background: Phenol and its derivatives like dinitrophenol and pentachlorophenol (carbolic acid are widely used as insecticides, but they are very toxic substances. Phenol is a general protoplasmic poison with corrosive local effects that denature proteins. Poisoning with phenol compounds may occur by ingestion, inhalation, and absorption through skin. In this report we presented the toxicity effects of Phenol and its derivatives like dinitrophenol and pentachlorophenol on humans. Case report: A 27-year-old married female was found unconscious at her residence in September 2013. She was expired after hospitalization in Lady Hardinge Medical College and its associated hospital on the same day after six hours. On examination, corrosion of skin, at angel of mouth and chin, and brown discoloration in mucosa of the esophagus were seen. Histological examination showed exfoliation of esophageal mucosa and coagulative necrosis of gastric mucosa. In toxicological analyses, carbolic acid was detected. Conclusion: Strict precautionary measures are advised when using this compound.

  15. Tougher rules for mercury and other toxics

    Science.gov (United States)

    Showstack, Randy

    A new rule on mercury and air toxics standards, issued by the U.S. Environmental Protection Agency (EPA) on 21 December, will reduce emissions of heavy metals and acid gases from power plants. The rule, which gives existing sources of pollution up to 4 years to comply with the new standards, will affect about 1400 existing "units," including 1100 coal-fired units and 300 oilfired units, at about 600 power plants. EPA notes that more than half of all coal-fired plants already deploy pollution-control technologies. Power plants are the largest U.S. source of several pollutants—accounting for about 50% of mercury emissions and 77% of acid gas emissions—and emit the largest amounts of arsenic and other toxics, according to EPA.

  16. [Toxic hepatitis induced by Polygonum multiflorum].

    Science.gov (United States)

    Banarova, A; Koller, T; Payer, J

    2012-12-01

    Toxic liver injury is a common cause of acute hepatitis. Here we report a case of 33-year old female with toxic hepatitis caused by unusual agent- extract of chinese plant Polygonum multiflorum. The patient presented with clinical signs of nausea and icterus and laboratory signs of hepatocellular damage following 2 months of readministration of Polygonum mulltiflorum pills. All other causes of hepatocellular damage were excluded. The causality between hepatocellular damage and Polygonum multiflorum ingestion was supported by early recovery after discontinuation, by international scoring system of causality between drug and hepatotoxicity as well as by similarities with other reports from the literature. Considering the growing popularity of herbal products as nutrition supplements we appeal to caution in using these preparations.

  17. Toxic economy - interferences with recent Romanian experience

    Directory of Open Access Journals (Sweden)

    Cristian Gheorghe Iacob

    2015-05-01

    Full Text Available What is the toxic economy? Economy through which the legislation and control in place, fails to provide a standard of living with sustainable uptrend, getting to transform assets into cash whose value is consumed unproductively. Why we do not live well? Good life is in fact the standard of living of the economic and political offered by the laws of a state or groups of states, citizens living on a certain territory. The standard of living is a result of variety of factors, difficult to quantify both separately and in particular unit. In this article we will try to define the fractal complexity of how the toxic economy is affecting the standard of leaving

  18. Prenatal Programming and Toxicity (PPTOX) Introduction.

    Science.gov (United States)

    Birnbaum, Linda S; Miller, Mark F

    2015-10-01

    The developmental origin of health and disease hypothesis posits that early-life exposures, including prenatal, can influence disease outcomes throughout the entire lifespan of an organism. Over the past 30 years, scientific researchers have compiled robust epidemiological and mechanistic data showing the effects of early-life nutrition, chemical exposures, and stress on prenatal programing and toxicity. Using novel techniques in genomics and epigenetics, science is now establishing strong links between low-level early-life environmental exposures and the later development of noncommunicable diseases, such as cardiovascular disease, obesity, diabetes, neurodevelopmental and neurodegenerative disease, reproductive effects, immune system function and cancer. Now scientists must engage with communities, industry, policy makers, and clinicians to leverage our newfound understanding of prenatal programing and toxicity into better health outcomes across the lifespan.

  19. Glutathione attenuates uranyl toxicity in Lactococcus lactis

    Energy Technology Data Exchange (ETDEWEB)

    Fahmy, Karim; Oertel, Jana [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Obeid, M. [Technische Univ. Dresden (Germany); Solioz, M. [Bern Univ. (Switzerland)

    2017-06-01

    We investigated the role of intracellular glutathione (GSH), which in a large number of taxa plays a role in the protection against the toxicity of heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism allowing the study of GSH-dependent uranyl detoxification without interference from additional reactive oxygen species. Microcalorimetric measurements of the metabolic heat showed that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10-150 μM. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH.

  20. Reversal of opioid-induced toxicity

    Directory of Open Access Journals (Sweden)

    Shrenik P Ostwal

    2017-01-01

    Full Text Available Opioids are commonly used for pain control in palliative care setting. Accumulation of active metabolites of opioids can cause a well-recognized toxidrome including respiratory depression (RD, decreased conscious level, pinpoint pupils, and drop in blood pressure. Opioid toxicity is often associated with amount ingested and its speed of absorption in the body. This can have life-threatening effects on various body systems. Naloxone is an opioid antagonist that competitively binds to opioid receptors and reverses all their effects. The indication for use is RD because of known or suspected opioid overdose. This article presents a case report of 61-year-old female, a case of advanced pancreatic cancer, progressed on disease-modifying treatments and referred to palliative care for best supportive care. She developed features of morphine toxicity that was promptly identified and managed with use of naloxone and other supportive measures.

  1. Acute toxicity from baking soda ingestion.

    Science.gov (United States)

    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.

  2. Relative toxicity of benzodiazepines in overdose.

    OpenAIRE

    Buckley, N A; Dawson, A. H.; Whyte, I. M.; O'Connell, D. L.

    1995-01-01

    OBJECTIVE--To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN--Cohort study of patients admitted with benzodiazepine poisoning. SETTING--Newcastle, Australia. SUBJECTS--303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES--Degree of...

  3. Toxic Epidermal Necrolysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Seher Erdogan

    2016-09-01

    Full Text Available Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are severe, acute reactions of the skin and mucosa that can result in serious clinical outcomes and morbidity. We report a case of TEN resulting in mortality, following the use of tablets containing paracetamol, codeine phosphate, and chlorpheniramine for an upper respiratory tract infection. Conditions such as SJS and TEN that can lead to serious clinical outcomes should be considered in juvenile patients, and unnecessary drug use should be avoided.

  4. Toxicity Data to Determine Refrigerant Concentration Limits

    Energy Technology Data Exchange (ETDEWEB)

    Calm, James M.

    2000-09-30

    This report reviews toxicity data, identifies sources for them, and presents resulting exposure limits for refrigerants for consideration by qualified parties in developing safety guides, standards, codes, and regulations. It outlines a method to calculate an acute toxicity exposure limit (ATEL) and from it a recommended refrigerant concentration limit (RCL) for emergency exposures. The report focuses on acute toxicity with particular attention to lethality, cardiac sensitization, anesthetic and central nervous system effects, and other escape-impairing effects. It addresses R-11, R-12, R-22, R-23, R-113, R-114, R-116, R-123, R-124, R-125, R-134, R-134a, R-E134, R-141b, R-142b, R-143a, R-152a, R-218, R-227ea, R-236fa, R-245ca, R-245fa, R-290, R-500, R-502, R-600a, R-717, and R-744. It summarizes additional data for R-14, R-115, R-170 (ethane), R-C318, R-600 (n-butane), and R-1270 (propylene) to enable calculation of limits for blends incorporating them. The report summarizes the data a nd related safety information, including classifications and flammability data. It also presents a series of tables with proposed ATEL and RCL concentrations-in dimensionless form and the latter also in both metric (SI) and inch-pound (IP) units of measure-for both the cited refrigerants and 66 zerotropic and azeotropic blends. They include common refrigerants, such as R-404A, R-407C, R-410A, and R-507A, as well as others in commercial or developmental status. Appendices provide profiles for the cited single-compound refrigerants and for R-500 and R-502 as well as narrative toxicity summaries for common refrigerants. The report includes an extensive set of references.

  5. Aluminium toxicity in plants: a review

    OpenAIRE

    Rout, G.; SAMANTARAY, S.; Das, P

    2001-01-01

    International audience; Aluminium toxicity and problems concerning tolerance and ecological performance are discussed briefly. Differential tolerance of plant genotypes to aluminium stress is a more promising approach to increase our understanding of aluminium tolerance in plants. Induction of Al tolerance and its characterization are also reviewed. The cytogenetic effects of aluminium on plants are discussed in depth. Efforts have been made to compare the relative sensitivity of various plan...

  6. Bilateral putaminal necrosis and bronopol toxicity

    OpenAIRE

    Trivisano, Marina; Carapelle, Elena; Martino, Tommaso; Specchio, Luigi Maria

    2015-01-01

    Among alcohols, methanol intoxication is the most frequently associated with cerebral toxicity, causing retinal damage and putaminal necrosis. This consequence is believed to be due to the transformation of methanol into formic acid. We describe the case of a patient who presented with acute impairment of consciousness and tetraparesis after she had been drinking several bottles of a topical antiseptic solution (Lysoform Medical) containing 2-bromo-2-nitro-1,3-propandiol (bronopol) among exci...

  7. Respiratory Toxicity of Lunar Highland Dust

    Science.gov (United States)

    James, John T.; Lam, Chiu-wing; Wallace, William T.

    2009-01-01

    Lunar dust exposures occurred during the Apollo missions while the crew was on the lunar surface and especially when microgravity conditions were attained during rendezvous in lunar orbit. Crews reported that the dust was irritating to the eyes and in some cases respiratory symptoms were elicited. NASA s vision for lunar exploration includes stays of 6 months on the lunar surface hence the health effects of periodic exposure to lunar dust need to be assessed. NASA has performed this assessment with a series of in vitro and in vivo tests on authentic lunar dust. Our approach is to "calibrate" the intrinsic toxicity of lunar dust by comparison to a nontoxic dust (TiO2) and a highly toxic dust (quartz) using intratrachael instillation of the dusts in mice. A battery of indices of toxicity is assessed at various time points after the instillations. Cultures of selected cells are exposed to test dusts to assess the adverse effects on the cells. Finally, chemical systems are used to assess the nature of the reactivity of various dusts and to determine the persistence of reactivity under various environmental conditions that are relevant to a space habitat. Similar systems are used to assess the dissolution of the dust. From these studies we will be able to set a defensible inhalation exposure standard for aged dust and predict whether we need a separate standard for reactive dust. Presently-available data suggest that aged lunar highland dust is slightly toxic, that it can adversely affect cultured cells, and that the surface reactivity induced by grinding the dust persists for a few hours after activation.

  8. Silica binding and toxicity in alveolar macrophages

    OpenAIRE

    Hamilton, Raymond F.; Thakur, Sheetal A.; Holian, Andrij

    2007-01-01

    Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silica-induced toxicity on the cellular level. Based on experimental results, several rationales have...

  9. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening, proximate analysis and acute toxicity studies were carried out on the leaf extract of Cola lepidota, in accordance with established standard procedures. The proximate analysis reveals a moisture content of 27.43 ± 3.11 % w/w, total ash value 9.32 ± 0.27 % w/w, acid insoluble ash 3.12 ± 1.05 % w/w ...

  10. Diagnosis and Treatment of Cyanide Toxicity

    Science.gov (United States)

    2009-02-01

    15 ppm), From the Department of Surgery , University Health Science Center, San Antonio; and United States Army Institute of Surgical Research, Fort...editors. Fire protection hand- book . 17th ed. Quincy, MA: National Fire Protection Association; 1991:3.3–3.14. 50. Buchwald A. Cyanide toxicity [Letter...cyanide intoxication and death from an acetonitrile-containing cosmetic . JAMA 1988; 260:3470–2. 53. Berlin C. Cyanide poisoning—a challenge [Editorial

  11. Selenium deficiency and toxicity in the environment

    OpenAIRE

    Fordyce, Fiona

    2005-01-01

    Selenium (Se) is a naturally occurring metalloid element, which is essential to human and other animal health in trace amounts but is harmful in excess. Of all the elements, selenium has one of the narrowest ranges between dietary deficiency (40 gday1) and toxic levels (400gday1) (WHO, 1996), which makes it necessary to carefully control intakes by humans and other animals, hence, the importance of understanding the relationships between environmental exposure and health. Geology exerts...

  12. Menthol toxicity: an unusual cause of coma.

    Science.gov (United States)

    Baibars, Motaz; Eng, Simona; Shaheen, Khaldoon; Alraiyes, Abdul Hamid; Alraies, M Chadi

    2012-01-01

    The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  13. Menthol Toxicity: An Unusual Cause of Coma

    Directory of Open Access Journals (Sweden)

    Motaz Baibars

    2012-01-01

    Full Text Available The US Food and Drug Administration (FDA consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  14. Menthol Toxicity: An Unusual Cause of Coma

    OpenAIRE

    Motaz Baibars; Simona Eng; Khaldoon Shaheen; Abdul Hamid Alraiyes; Chadi Alraies, M.

    2012-01-01

    The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  15. Computational approaches to predicting drug induced toxicity

    OpenAIRE

    Marchese Robinson, Richard Liam

    2013-01-01

    Errors and issues requiring clarification are included as a separate document (January 2016). Novel approaches and models for predicting drug induced toxicity in silico are presented. Typically, these were based on Quantitative Structure-Activity Relationships (QSAR). The following endpoints were modelled: mutagenicity, carcinogenicity, inhibition of the hERG ion channel and the associated arrhythmia - Torsades de Pointes. A consensus model was developed based on Derek for Window...

  16. Hydrogen and Gaseous Fuel Safety and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lee C. Cadwallader; J. Sephen Herring

    2007-06-01

    Non-traditional motor fuels are receiving increased attention and use. This paper examines the safety of three alternative gaseous fuels plus gasoline and the advantages and disadvantages of each. The gaseous fuels are hydrogen, methane (natural gas), and propane. Qualitatively, the overall risks of the four fuels should be close. Gasoline is the most toxic. For small leaks, hydrogen has the highest ignition probability and the gaseous fuels have the highest risk of a burning jet or cloud.

  17. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

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

  18. Toxicity of oxidized phospholipids in cultured macrophages

    Directory of Open Access Journals (Sweden)

    Stemmer Ute

    2012-09-01

    Full Text Available Abstract Background The interactions of oxidized low-density lipoprotein (LDL and macrophages are hallmarks in the development of atherosclerosis. The biological activities of the modified particle in these cells are due to the content of lipid oxidation products and apolipoprotein modification by oxidized phospholipids. Results It was the aim of this study to determine the role of short-chain oxidized phospholipids as components of modified LDL in cultured macrophages. For this purpose we investigated the effects of the following oxidized phospholipids on cell viability and apoptosis: 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC, 1-palmitoyl-2-(5-oxovaleroyl-sn-glycero-3-phosphocholine (POVPC and oxidized alkylacyl phospholipids including 1-O-hexadecyl-2-glutaroyl-sn-glycero-3-phosphocholine (E-PGPC and 1-O-hexadecyl-2-(5-oxovaleroyl-sn-glycero-3-phosphocholine (E-POVPC. We found that these compounds induced apoptosis in RAW264.7 and bone marrow-derived macrophages. The sn-2 carboxyacyl lipid PGPC was more toxic than POVPC which carries a reactive aldehyde function in position sn-2 of glycerol. The alkylacyl phospholipids (E-PGPC and E-POVPC and the respective diacyl analogs show similar activities. Apoptosis induced by POVPC and its alkylether derivative could be causally linked to the fast activation of an acid sphingomyelinase, generating the apoptotic second messenger ceramide. In contrast, PGPC and its ether analog only negligibly affected this enzyme pointing to an entirely different mechanism of lipid toxicity. The higher toxicity of PGPC is underscored by more efficient membrane blebbing from apoptotic cells. In addition, the protein pattern of PGPC-induced microparticles is different from the vesicles generated by POPVC. Conclusions In summary, our data reveal that oxidized phospholipids induce apoptosis in cultured macrophages. The mechanism of lipid toxicity, however, largely depends on the structural features of the

  19. A Comparative Analysis of Toxicity Models

    Science.gov (United States)

    2008-04-01

    personnel by their casualty status (no effects/ miosis , casualty, fatality) as well as by These three toxicity models only consider the external...GB dosages for which an individual was expected to experience no effects/ miosis (casualty category #1), become a casualty requiring medical...Limit (mg-min./m3) Category Description 1 0.00 3.09 No effect/ miosis 2 3.09 28.54 Casualty 3 28.54 >28.54 Fatality Table 4. Dosage Ranges

  20. 78 FR 52860 - Electronic Reporting of Toxics Release Inventory Data

    Science.gov (United States)

    2013-08-27

    ... AGENCY 40 CFR Part 372 RIN 2025-AA30 Electronic Reporting of Toxics Release Inventory Data AGENCY... to report non- trade-secret Toxics Release Inventory (TRI) forms to EPA using electronic software..., Toxics Release Inventory Program Division, Mailcode 2844T, OEI, Environmental Protection Agency, 1200...