Sample records for cinnabar toxicologically similar

  1. In vitro investigation on cinnabar dissolution

    Institute of Scientific and Technical Information of China (English)

    ZENG Kewu; WANG Qi; YANG Xiaoda; WANG Kui


    To study the effects of different chemical factors in the gastrointestinal tract, I.e. pH, proteins, amino acids,ionic strength and Na2S, on the dissolution of cinnabar. The content of the total mercury in various dissolutions of cinnabar was analyzed by UV/VIS Spectrophotometer. Laser Particle Size Analyzer measured the particle distributionsin the dissolution of cinnabar. The chemical species of dis-solved substance of cinnabar in the presence of Na2S were determined using ESI-MS. The results indicate that the solu-bility of cinnabar could be increased significantly in the pres-ence ofNa2S/S0, and strong acidic pH, respectively. While theinfluence of thiol amino acid on promoting dissolutionremains relatively low. Cinnabar did not dissolve in the form of nanoparticle. It is postulated that cinnabar could be dissolved in the gastrointestinal tract in various forms of sulfur-containing mercury complexes.

  2. Cinnabar Induces Renal Inflammation and Fibrogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Ying Wang


    Full Text Available The purpose of this study was to investigate whether cinnabar causes renal inflammation and fibrosis in rats. Rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks. The control rats were treated with solvent (5% carboxymethylcellulose solution over the same time periods, respectively. Renal mercury (RHg, urinary mercury (UHg, serum creatinine (SCr, urine kidney injury molecule 1 (KIM-1, renal pathology, and renal mediators were examined. At both 8 weeks and 12 weeks, RHg, UHg, and urine KIM-1 were significantly higher in the cinnabar group than in the control group, although SCr was unchanged. Kidney lesions in the cinnabar-treated rats occurred mainly in the tubules and interstitium, including vacuolization, protein casts, infiltration of inflammatory cells, and slight increase in interstitial collagen. In addition, mild mesangial proliferation was observed in glomeruli. Moreover, the expression of inflammatory and fibrogenic mediators was upregulated in the cinnabar group. In conclusion, cinnabar may cause kidney damage due to the accumulation of mercury, and renal inflammation and slight fibrogenesis may occur in rats. In the clinic, the potential risk of renal injury due to the prolonged consumption of cinnabar should be considered even though the agent is relatively nontoxic.

  3. ToxDBScan: Large-Scale Similarity Screening of Toxicological Databases for Drug Candidates

    Directory of Open Access Journals (Sweden)

    Michael Römer


    Full Text Available We present a new tool for hepatocarcinogenicity evaluation of drug candidates in rodents. ToxDBScan is a web tool offering quick and easy similarity screening of new drug candidates against two large-scale public databases, which contain expression profiles for substances with known carcinogenic profiles: TG-GATEs and DrugMatrix. ToxDBScan uses a set similarity score that computes the putative similarity based on similar expression of genes to identify chemicals with similar genotoxic and hepatocarcinogenic potential. We propose using a discretized representation of expression profiles, which use only information on up- or down-regulation of genes as relevant features. Therefore, only the deregulated genes are required as input. ToxDBScan provides an extensive report on similar compounds, which includes additional information on compounds, differential genes and pathway enrichments. We evaluated ToxDBScan with expression data from 15 chemicals with known hepatocarcinogenic potential and observed a sensitivity of 88 Based on the identified chemicals, we achieved perfect classification of the independent test set. ToxDBScan is publicly available from the ZBIT Bioinformatics Toolbox.

  4. Cinnabar and realgar in traditional chinese medicines:remedies or poisons?%含朱砂、雄黄的中成药,是药还是毒?

    Institute of Scientific and Technical Information of China (English)

    刘杰; 陆远富; 时京珍; 张锋; 吴芹


    朱砂(96% HgS)和雄黄(90% As4S4)与其它中药配伍应用于临床已有上千年历史.但由于朱砂含汞,雄黄含砷,其安全性近年来引起了越来越多的关注.一般认为把已知的金属毒物用于医药中不可取,但也有不同的意见认为朱砂和雄黄有长期用药历史,临床有效,其毒副作用可耐受.含朱砂、雄黄的中药是药还是毒?本文就含朱砂和雄黄的中成药的研究进展作一综述,并提出(1)以总砷和总汞为标准进行评价含朱砂、雄黄中药的安全性不妥,(2)朱砂和雄黄的用药量和用药时间决定其毒性反应,(3)朱砂和雄黄是中药复方中的有效成分之一,应作深入研究来决定其取舍.%Cinnabar( 96 % of HgS)and realgar( 90 % of As4S4)have been used in traditional Chinese medicines for thousands of years.Both mercury ( Hg) and arsenic ( As)are well-known toxic substances and the safety of cinnabar-and realgar-containing traditional Chinese medicines is of concern.It is presumed that any intentional use of known toxic metals in medicine is an unacceptable risk,hut an opposing opinion holds that cinnabar and realgar have a long history of clear pharmacological utility with tolerable side effects.Are cinnabar-and/or realgar-containing Chinese medicines remedies or poisons? This chapter summarizes recent progress of toxicological and pharmacological studies on this issue and highlights that( 1 ) the use of total Hg and As for risk evaluation of cinnabar and realgar is inappropriate,(2) the right dose and duration of cinnabar and realer administration differentiate a remedy from a poison,and( 3 )cinnabar and realgar are active ingredients in Chinese medicines.The well-designed studies are needed to support or to reject their existence in traditional remedies.

  5. Green toxicology. (United States)

    Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas


    Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops

  6. Cinnabar alteration in archaeological wall paintings: an experimental and theoretical approach (United States)

    Neiman, Madeleine Kegelman; Balonis, Magdalena; Kakoulli, Ioanna


    The red mineral pigment known as cinnabar (HgS) was commonly employed in Roman fresco wall paintings. Fresco artists of the period favored this pigment for its striking red color. However, upon excavation and exposure to air and light, cinnabar-pigmented surfaces recovered from archaeological contexts often proved to be unstable. Mural paintings colored with cinnabar that have been exposed in the open air frequently demonstrate a disfiguring, irreversible darkening of the surface. Traditionally, scholars have attributed this alteration to a light-induced phase change from red α-cinnabar to black β-cinnabar (meta-cinnabar). While this transformation has not been totally excluded, the prevailing view among conservation scientists is that chlorine plays a key role in the darkening process through the formation of light-sensitive mercury chloride compounds, or as a catalyst in the photochemical redox of Hg(II)S into Hg(0) and S(0). Using laboratory-based experiments and thermodynamic modeling, this paper attempts to further clarify the mechanism(s) and kinetics of cinnabar alteration in fresco applications, especially the role of light, humidity, and chlorine ions. Additionally, it explores possible pathways and preventive as well as remedial conservation treatments during or immediately following excavation, to inhibit or retard darkening of cinnabar-pigmented fresco surfaces.

  7. Phase Transition and EOS of Cinnabar (α-HgS) at High Pressure and High Temperature

    Institute of Scientific and Technical Information of China (English)

    FAN Da-Wei; ZHOU Wen-Ge; LIU Cong-Qiang; WAN Fang; XING Yin-Suo; LIU Jing; LI Yan-Chun; XIE Hong-Sen


    @@ Phase relations and equation of state (EOS) of natural cinnabar (α-HgS) are investigated by high-pressure and high-temperature synchrotron x-ray powder diffraction. The unambiguous cinnabar-rocksalt structure phase boundaries are determined to be Plower(Gpa)=15.54-0.014T(℃) and Pupper(Gpa)= 23.84 - 0.014T(℃) at 300--623K. With K' axed at 4, we obtain K0 = 37(4) Gpa, ( K/ T)p=-0.025(2) GPaK-1, and α0= 3.79(20)× 10-5 K-1 for the cinnabar phase of α-HgS. The ( K/ T)p and α0 of cinnabar phase are obtained for the first time. A nearly isotropic compression of cinnabar phase is observed by linear regressions.

  8. Similarity (United States)

    Apostol, Tom M. (Editor)


    In this 'Project Mathematics! series, sponsored by the California Institute for Technology (CalTech), the mathematical concept of similarity is presented. he history of and real life applications are discussed using actual film footage and computer animation. Terms used and various concepts of size, shape, ratio, area, and volume are demonstrated. The similarity of polygons, solids, congruent triangles, internal ratios, perimeters, and line segments using the previous mentioned concepts are shown.

  9. Evaluating the role of re-adsorption of dissolved Hg(2+) during cinnabar dissolution using isotope tracer technique. (United States)

    Jiang, Ping; Li, Yanbin; Liu, Guangliang; Yang, Guidi; Lagos, Leonel; Yin, Yongguang; Gu, Baohua; Jiang, Guibin; Cai, Yong


    Cinnabar dissolution is an important factor controlling mercury (Hg) cycling. Recent studies have suggested the co-occurrence of re-adsorption of the released Hg during the course of cinnabar dissolution. However, there is a lack of feasible techniques that can quantitatively assess the amount of Hg re-adsorbed on cinnabar when investigating cinnabar dissolution. In this study, a new method, based on isotope tracing and dilution techniques, was developed to study the role of Hg re-adsorption in cinnabar dissolution. The developed method includes two key components: (1) accurate measurement of both released and spiked Hg in aqueous phase and (2) estimation of re-adsorbed Hg on cinnabar surface via the reduction in spiked (202)Hg(2+). By adopting the developed method, it was found that the released Hg for trials purged with oxygen could reach several hundred μgL(-1), while no significant cinnabar dissolution was detected under anaerobic condition. Cinnabar dissolution rate when considering Hg re-adsorption was approximately 2 times the value calculated solely with the Hg detected in the aqueous phase. These results suggest that ignoring the Hg re-adsorption process can significantly underestimate the importance of cinnabar dissolution, highlighting the necessity of applying the developed method in future cinnabar dissolution studies.

  10. Cinnabar-Induced Subchronic Renal Injury Is Associated with Increased Apoptosis in Rats

    Directory of Open Access Journals (Sweden)

    Ying Wang


    Full Text Available The aim of this study was to explore the role of apoptosis in cinnabar-induced renal injury in rats. To test this role, rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks, and the control rats were treated with 5% carboxymethylcellulose solution. Levels of urinary mercury (UHg, renal mercury (RHg, serum creatinine (SCr, and urine kidney injury molecule 1 (KIM-1 were assessed, and renal pathology was analyzed. Apoptotic cells were identified and the apoptotic index was calculated. A rat antibody array was used to analyze expression of cytokines associated with apoptosis. Results from these analyses showed that UHg, RHg, and urine KIM-1, but not SCr, levels were significantly increased in cinnabar-treated rats. Renal pathological changes in cinnabar-treated rats included vacuolization of tubular cells, formation of protein casts, infiltration of inflammatory cells, and increase in the number of apoptotic tubular cells. In comparison to the control group, expression of FasL, Fas, TNF-α, TRAIL, activin A, and adiponectin was upregulated in the cinnabar-treated group. Collectively, our results suggest that prolonged use of cinnabar results in kidney damage due to accumulation of mercury and that the underlying mechanism involves apoptosis of tubular cells via a death receptor-mediated pathway.

  11. Quality Study on Cinnabar-analysis of Dyeing Status for Cinnabar%朱砂染色现状分析

    Institute of Scientific and Technical Information of China (English)

    邢潇; 刘治民; 徐彤彤; 谷妲; 梁玉冰; 张鑫; 杨建龙


    目的:分析朱砂药材及饮片染色现状,为朱砂药材及饮片的品质和临床安全应用提供参考依据。方法:采用薄层色谱法(TLC)对药材和饮片中苋菜红、胭脂红、赤藓红、酸性红73、808猩红、靛玉红进行定性鉴别。采用高效液相色谱-质谱联用法(HPLC-MS)检测药材及饮片中的808猩红。HPLC条件:色谱柱为Acquity UPLC BEH C18,流动相为乙腈-0.1%甲酸(70∶30,V/V),流速为0.3 ml/min,检测波长为520 nm;MS条件:离子源为电喷雾离子源,扫描方式为正离子扫描,检测方式为全扫描二级质谱,雾化器压力为30 psi,干燥气为氮气,离子喷雾电压为4000 V,碰撞能为30 V,进样量为5μl。采用容量法测定药材及饮片中硫化汞(HgS)的含量。结果:苋菜红、胭脂红、赤藓红、酸性红73、808猩红、靛玉红的TLC斑点清晰,分离良好。18批样品中有4批808猩红染色,有6批HgS含量不达标(其中3批同时为808猩红染色)。结论:目前市场中流通的朱砂药材及饮片存在染色掺杂和HgS含量不达标等质量问题,应引起重视。%OBJECTIVE:To analyze the dyeing status of cinnabar and its pieces,and provide reference for its quality clinical safetey appicaton. METHODS:TLC was used for the qualitative identification of amaranth,carmine,erythrosine,acid red 73, 808 udan and indirubin. HPLC-MS was used to detect the 808 udan :HPLC conditions were as follows,column was Acquity UPLC BEH C18 with mobile phase of cetonitrile-0.1% formic acid(70∶30,V/V)at a flow rate of 0.3 ml/min,the detection wave-length was 520 nm;MS conditions were as follows,ion source was electrospray ionization source,scanning mode was positive ion scanning with full scanning tandem mass spectrometry,nebulizer pressure was 30 psi,drying gas was nitrogen,ion spray voltage was 4 000 V,collision energy was 30 V,and the injection volume was 5 μl. The volumetric method was used

  12. [Dissolution, absorption and bioaccumulation in gastrointestinal tract of mercury in HgS-containing traditional medicines Cinnabar and Zuotai]. (United States)

    Zheng, Zhi-yuan; Li, Cen; Zhang, Ming; Yang, Hong-xia; Geng, Lu-jing; Li, Lin-shuai; Du, Yu-zhi; Wei, Li-xin


    α-HgS is the main component of traditional Chinese medicine cinnabar, while β-HgS is the main component of Tibetan medicine Zuotai. However, there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar, Zuotai, α-HgS and β-HgS. In this study, the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions. To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms, mice were orally administered with clinical equivalent doses cinnabar and Zuotai. Meanwhile, a group of mice was given α-HgS and β-HgS with the equivalent mercury with cinnabar, while another group was given β-HgS and HgCl2 with the equivalent mercury with Zuotai. The mercury absorption and bioaccumulation capacities of different medicines in mice and their mercury bioaccumulation in different tissues and organs were compared. The experimental results showed a high mercury dissolutions of Zuotai in artificial gastrointestinal fluid, which was followed by β-HgS, cinnabar and α-HgS. As for the mercury absorption and bioaccumulation in mice, HgCl2 was the highest, β-HgS was the next, and a-HgS was slightly higher than cinnabar. The organs with the mercury bioaccumulation from high to low were kidney, liver and brain. This study is close to clinical practices and can provide reference for the clinical safe medication as well as a study model for the safety evaluation on heavy metal-containing medicines by observing the mercury dissolution, absorption, distribution and accumulation of mercury-containing medicines cinnabar and zuotai.

  13. Chronic mercury exposure in Late Neolithic/Chalcolithic populations in Portugal from the cultural use of cinnabar (United States)

    Emslie, Steven D.; Brasso, Rebecka; Patterson, William P.; Carlos Valera, António; McKenzie, Ashley; Maria Silva, Ana; Gleason, James D.; Blum, Joel D.


    Cinnabar is a natural mercury sulfide (HgS) mineral of volcanic or hydrothermal origin that is found worldwide. It has been mined prehistorically and historically in China, Japan, Europe, and the Americas to extract metallic mercury (Hg0) for use in metallurgy, as a medicinal, a preservative, and as a red pigment for body paint and ceramics. Processing cinnabar via combustion releases Hg0 vapor that can be toxic if inhaled. Mercury from cinnabar can also be absorbed through the gut and skin, where it can accumulate in organs and bone. Here, we report moderate to high levels of total mercury (THg) in human bone from three Late Neolithic/Chalcolithic (5400-4100 B.P.) sites in southern Portugal that were likely caused by cultural use of cinnabar. We use light stable isotope and Hg stable isotope tracking to test three hypotheses on the origin of mercury in this prehistoric human bone. We traced Hg in two individuals to cinnabar deposits near Almadén, Spain, and conclude that use of this mineral likely caused mild to severe mercury poisoning in the prehistoric population. Our methods have applications to bioarchaeological investigations worldwide, and for tracking trade routes and mobility of prehistoric populations where cinnabar use is documented.

  14. Bacterial Influence on the Solubility of Cinnabar and Metacinnabar at New Idria, CA (United States)

    Jew, A. D.; Rytuba, J. J.; Spormann, A. M.; Brown, G. E.


    Mercury in the forms of cinnabar (α-HgS) and metacinnabar (β-HgS) is generally considered to be unreactive and of little environmental concern. To determine if this current belief is valid, a consortium of bacteria (including a Thiomonas intermedia-like bacterium) was taken from the acid mine drainage (AMD) pond at the New Idria Hg Mine, San Benito Co., CA, and inoculated into filter-sterilized AMD pond water (pH = 4) containing either ground cinnabar or metacinnabar crystals (Minteq with AMD pond water chemistry determined by ICP-MS and total mercury and total sulfide analyses. These calculations give an equilibrium solubility product for the dissolution of HgS up to 25 orders of magnitude higher than HgS under standard conditions. When compared to calculations by Paquette et al., 1997 and Benoit et al., 1999, the bacterial consortium at New Idria causes an increase in the pK for all reported reactions including H+, HS-, and H2S of 11-13 orders of magnitude. These results indicate that the biofilm consortium at the New Idria AMD pond has a profound effect on the solubility of cinnabar and metacinnabar, suggesting that a reassessment of HgS stability in aerobic AMD environments is needed.

  15. Toxicology screen (United States)

    Toxicology screening is most often done using a blood or urine sample. However, it may be done soon after the person swallowed the medication, using stomach contents taken through gastric lavage (stomach pumping) or after vomiting.

  16. Spaceflight Toxicology (United States)

    Meyers, Valerie


    This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.

  17. Exposure to Low Dose of Cinnabar (a Naturally Occurring Mercuric Sulfide (HgS Caused Neurotoxicological Effects in Offspring Mice

    Directory of Open Access Journals (Sweden)

    Chun-Fa Huang


    Full Text Available Cinnabar, a naturally occurring mercuric sulfide (HgS, has long been used in Chinese mineral medicine for more than 2000 years. Although mercury is well-known for its toxicity, whether cinnabar induces neurotoxicity, especially in infants and children, is unknown. The purpose of this study was to explore the neurotoxic effects of low-dose of cinnabar (10 mg/kg/day on developing mice. The results revealed neurobehavioral defects in F1-C-Cin group, which were associated with Hg accumulation, increased NOx levels in whole blood, and Na+/K+-ATPase activities in brain tissues. F1- and F2-Cin-V groups were found to increase brain Hg contents and prominent neurobehavioral defects compared with F1-C-V group, suggesting that the fetal brain was more susceptible to irreversible effects for cinnabar-induced damage. Moreover, F1- and F2-Cin-Cin groups had severely neurobehavioral dysfunctions, closely correlated with the further alteration of NOx levels and Na+/K+-ATPase activities than F1- and F2-C-Cin groups. Effects in F2-Cin-Cin group were more significant than those in F1-Cin-Cin group. In conclusion, this study demonstrates that exposure to low-dose of cinnabar during the perinatal and developmental stages results in irreversible and severe injuries of the neurotoxicity in offspring, and NOx and Na+/K+-ATPase activities may exist potential and useful biomarkers for neurotoxicity-induced by low-doses of mercuric compounds.

  18. Environmental Toxicology Research Facility (United States)

    Federal Laboratory Consortium — Fully-equipped facilities for environmental toxicology research The Environmental Toxicology Research Facility (ETRF) located in Vicksburg, MS provides over 8,200 ft...

  19. Space Toxicology (United States)

    James, John T.


    Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

  20. Forensic toxicology. (United States)

    Drummer, Olaf H


    Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results.

  1. Cinnabar, arsenian pyrite and thallium-enrichment in active shallow submarine hydrothermal vents at Paleochori Bay, Milos Island, Greece (United States)

    Kati, Marianna; Voudouris, Panagiotis; Valsami-Jones, Eugenia; Magganas, Andreas; Baltatzis, Emmanouil; Kanellopoulos, Christos; Mavrogonatos, Constantinos


    We herein report the discovery of active cinnabar-depositing hydrothermal vents in a submarine setting at Paleochori Bay, within the offshore southeastern extension of the Milos Island Geothermal Field, South Aegean Active Volcanic Arc. Active, low temperature (up to 115 °C) hydrothermal venting through volcaniclastic material has led to a varied assemblage of sulfide and alteration mineral phases in an area of approximately 1 km2. Our samples recovered from Paleochori Bay are hydrothermal edifices composed of volcaniclastic detrital material cemented by pyrite, or pure sulfide (mainly massive pyrite) mounts. Besides pyrite and minor marcasite, the hydrothermal minerals include cinnabar, amorphous silica, hydrous ferric oxides, carbonates (aragonite and calcite), alunite-jarosite solid solution and Sr-rich barite. Among others, growth textures, sieve-textured pyrite associated with barite, alunite-jarosite solid solution and hydrous ferric oxides rims colloform-banded pyrite layers. Overgrowths of arsenian pyrite layers (up to 3.2 wt. % As and/or up to 1.1 wt. % Mn) onto As-free pyrite indicate fluctuation in As content of the hydrothermal fluid. Mercury, in the form of cinnabar, occurs in up to 5 μm grains within arsenian pyrite layers, usually forming distinct cinnabar-enriched micro-layers. Hydrothermal Sr-rich barite (barite-celestine solid solution), pseudocubic alunite-jarosite solid solution and Mn- and Sr-enriched carbonates occur in various amounts and closely associated with pyrite and/or hydrous ferric oxides. Thallium-bearing sulfides and/or sulfosalts were not detected during our study; however, hydrous ferric oxides show thallium content of up to 0.5 wt. % Tl. The following scenarios may have played a role in pyrite precipitation at Paleochori: (a) H2S originally dissolved in the deep fluid but separated upon boiling could have reacted with oxygenated seawater under production of sulphuric acid, thus causing leaching and dissolution of primary iron

  2. Mercury emission and dispersion models from soils contaminated by cinnabar mining and metallurgy. (United States)

    Llanos, Willians; Kocman, David; Higueras, Pablo; Horvat, Milena


    The laboratory flux measurement system (LFMS) and dispersion models were used to investigate the kinetics of mercury emission flux (MEF) from contaminated soils. Representative soil samples with respect to total Hg concentration (26-9770 μg g(-1)) surrounding a decommissioned mercury-mining area (Las Cuevas Mine), and a former mercury smelter (Cerco Metalúrgico de Almadenejos), in the Almadén mercury mining district (South Central Spain), were collected. Altogether, 14 samples were analyzed to determine the variation in mercury emission flux (MEF) versus distance from the sources, regulating two major environmental parameters comprising soil temperature and solar radiation. In addition, the fraction of the water-soluble mercury in these samples was determined in order to assess how MEF from soil is related to the mercury in the aqueous soil phase. Measured MEFs ranged from less than 140 to over 10,000 ng m(-2) h(-1), with the highest emissions from contaminated soils adjacent to point sources. A significant decrease of MEF was then observed with increasing distance from these sites. Strong positive effects of both temperature and solar radiation on MEF was observed. Moreover, MEF was found to occur more easily in soils with higher proportions of soluble mercury compared to soils where cinnabar prevails. Based on the calculated Hg emission rates and with the support of geographical information system (GIS) tools and ISC AERMOD software, dispersion models for atmospheric mercury were implemented. In this way, the gaseous mercury plume generated by the soil-originated emissions at different seasons was modeled. Modeling efforts revealed that much higher emissions and larger mercury plumes are generated in dry and warm periods (summer), while the plume is smaller and associated with lower concentrations of atmospheric mercury during colder periods with higher wind activity (fall). Based on the calculated emissions and the model implementation, yearly emissions from

  3. Toxicology Education Foundation (United States)

    ... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... TEF In the Classroom Our Goal The Toxicology Education Foundation seeks to help build the public's understanding ...

  4. Environmental Toxicology Research Facility (United States)

    Federal Laboratory Consortium — Fully-equipped facilities for environmental toxicology researchThe Environmental Toxicology Research Facility (ETRF) located in Vicksburg, MS provides over 8,200 ft...

  5. National Toxicology Program (United States)

    ... to Main Navigation Skip to Site Sidebar National Toxicology Program Home Testing ... NTP Cell Phone Radiofrequency Radiation Studies The National Toxicology Program (NTP) has been conducting experiments in rats ...

  6. Sulfur isotope analysis of cinnabar from Roman wall paintings by elemental analysis/isotope ratio mass spectrometry--tracking the origin of archaeological red pigments and their authenticity. (United States)

    Spangenberg, Jorge E; Lavric, Jost V; Meisser, Nicolas; Serneels, Vincent


    The most valuable pigment of the Roman wall paintings was the red color obtained from powdered cinnabar (Minium Cinnabaris pigment), the red mercury sulfide (HgS), which was brought from mercury (Hg) deposits in the Roman Empire. To address the question of whether sulfur isotope signatures can serve as a rapid method to establish the provenance of the red pigment in Roman frescoes, we have measured the sulfur isotope composition (δ(34)S value in ‰ VCDT) in samples of wall painting from the Roman city Aventicum (Avenches, Vaud, Switzerland) and compared them with values from cinnabar from European mercury deposits (Almadén in Spain, Idria in Slovenia, Monte Amiata in Italy, Moschellandsberg in Germany, and Genepy in France). Our study shows that the δ(34)S values of cinnabar from the studied Roman wall paintings fall within or near to the composition of Almadén cinnabar; thus, the provenance of the raw material may be deduced. This approach may provide information on provenance and authenticity in archaeological, restoration and forensic studies of Roman and Greek frescoes.

  7. Genetic toxicology: web resources. (United States)

    Young, Robert R


    Genetic toxicology is the scientific discipline dealing with the effects of chemical, physical and biological agents on the heredity of living organisms. The Internet offers a wide range of online digital resources for the field of Genetic Toxicology. The history of genetic toxicology and electronic data collections are reviewed. Web-based resources at US National Library of Medicine (NLM), including MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies and Medical Subject Headings (MeSH) are reviewed in the context of genetic toxicology. The TOXNET group of databases are discussed with emphasis on those databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous Substances Data Bank, Integrated Risk Information System, and Chemical Carcinogenesis Research Information System. Location of chemical information including chemical structure and linkage to health and regulatory information using CHEMIDPLUS at NLM and other databases is reviewed. Various government agencies have active genetic toxicology research programs or use genetic toxicology data to assist fulfilling the agency's mission. Online resources at the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA), the National Institutes of Environmental Health Sciences, and the National Toxicology Program (NTP) are outlined. Much of the genetic toxicology for pharmaceuticals, industrial chemicals and pesticides that is performed in the world is regulatory-driven. Regulatory web resources are presented for the laws mandating testing, guidelines on study design, Good Laboratory Practice (GLP) regulations, and requirements for electronic data collection and reporting. The Internet provides a range of other supporting resources to the field of genetic toxicology. The web links for key professional societies and journals in genetic toxicology are listed. Distance education, educational media resources, and job placement services are also

  8. Mercury analysis of acid- and alkaline-reduced biological samples: identification of meta-cinnabar as the major biotransformed compound in algae. (United States)

    Kelly, David; Budd, Kenneth; Lefebvre, Daniel D


    The biotransformation of Hg(II) in pH-controlled and aerated algal cultures was investigated. Previous researchers have observed losses in Hg detection in vitro with the addition of cysteine under acid reduction conditions in the presence of SnCl2. They proposed that this was the effect of Hg-thiol complexing. The present study found that cysteine-Hg, protein and nonprotein thiol chelates, and nucleoside chelates of Hg were all fully detectable under acid reduction conditions without previous digestion. Furthermore, organic (R-Hg) mercury compounds could not be detected under either the acid or alkaline reduction conditions, and only beta-HgS was detected under alkaline and not under acid SnCl2 reduction conditions. The blue-green alga Limnothrix planctonica biotransformed the bulk of Hg(II) applied as HgCl2 into a form with the analytical properties of beta-HgS. Similar results were obtained for the eukaryotic alga Selenastrum minutum. No evidence for the synthesis of organomercurials such as CH3Hg+ was obtained from analysis of either airstream or biomass samples under the aerobic conditions of the study. An analytical procedure that involved both acid and alkaline reduction was developed. It provides the first selective method for the determination of beta-HgS in biological samples. Under aerobic conditions, Hg(II) is biotransformed mainly into beta-HgS (meta-cinnabar), and this occurs in both prokaryotic and eukaryotic algae. This has important implications with respect to identification of mercury species and cycling in aquatic habitats.

  9. Toxicology: then and now. (United States)

    Langman, Loralie J; Kapur, Bhushan M


    Toxicology is "the science of poisons"; more specifically the chemical and physical properties of poisons, their physiological or behavioral effects on living organisms, qualitative, and quantitative methods for their analysis and the development of procedures for the treatment of poisoning. Although the history of poisons dates to the earliest times, the study and the science of toxicology can be traced to Paracelsus (1493-1541) and Orfila (1757-1853). Modern toxicology is characterized by sophisticated scientific investigation and evaluation of toxic exposures. The 20th century is marked by an advanced level of understanding of toxicology. DNA and various biochemicals that maintain cellular functions were discovered. Our level of knowledge of toxic effects on organs and cells is now being revealed at the molecular level. This paper will review the historical progress of clinical and forensic toxicology by exploring analytical techniques in drug analysis, differing biological matrices, clinical toxicology, therapeutic drug management, workplace drug testing, and pharmacodynamic monitoring and pharmacogenetics.

  10. Occupational medicine and toxicology



    Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational ...

  11. Toxicology ontology perspectives. (United States)

    Hardy, Barry; Apic, Gordana; Carthew, Philip; Clark, Dominic; Cook, David; Dix, Ian; Escher, Sylvia; Hastings, Janna; Heard, David J; Jeliazkova, Nina; Judson, Philip; Matis-Mitchell, Sherri; Mitic, Dragana; Myatt, Glenn; Shah, Imran; Spjuth, Ola; Tcheremenskaia, Olga; Toldo, Luca; Watson, David; White, Andrew; Yang, Chihae


    The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

  12. Green Toxicology – Application of predictive toxicology

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Wedebye, Eva Bay; Taxvig, Camilla


    Humans are constantly challenged by exposure to a cocktail of chemicals that can have negative health effects, and fetuses and young children are particularly vulnerable. Therefore, we need safer chemicals in order to reduce any potential environmental and human hazards. A solid framework to design...... safer chemicals and to identify problematic compounds already in use such as industrial compounds, drugs, pesticides and cosmetics, is required. Green toxicology is the application of predictive toxicology to the production of chemicals with the specific intent of improving their design for hazard...

  13. Occupational medicine and toxicology

    Directory of Open Access Journals (Sweden)

    Fischer Axel


    Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

  14. Drug screening in clinical or forensic toxicology: are there differences? (United States)

    Gerostamoulos, Dimitri; Beyer, Jochen


    Legal and medical practitioners need to remember that, with respect to drug analysis, there are two distinct disciplines in analytical toxicology concerned with human biological matrices, namely clinical and forensic toxicology. Both fields use similar analytical techniques designed to detect and quantify drugs, chemicals and poisons in fluids or tissues. In clinical toxicology, analytical results help to specify the appropriate treatment of a poisoned or intoxicated patient. In forensic toxicology, the results often play a vital role in determining the possible impairment or behavioural changes in an individual, or the contribution of drugs or poisons to death in a medico-legal investigation. This column provides an overview of the similarities and differences inherent in clinical and forensic toxicology.

  15. Aerospace Toxicology and Microbiology (United States)

    James, John T.; Parmet, A. J.; Pierson, Duane L.


    Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

  16. Animal-free toxicology

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E


    Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk...... assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure......-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data....

  17. Shuttle Lesson Learned - Toxicology (United States)

    James, John T.


    This is a script for a video about toxicology and the space shuttle. The first segment is deals with dust in the space vehicle. The next segment will be about archival samples. Then we'll look at real time on-board analyzers that give us a lot of capability in terms of monitoring for combustion products and the ability to monitor volatile organics on the station. Finally we will look at other issues that are about setting limits and dealing with ground based lessons that pertain to toxicology.

  18. Toxicología Vegetal


    García Fernández, Antonio Juan


    Presentaciones de clase de los temas de Toxicología Vegetal de la licenciatura de Veterinaria de la Universidad de Murcia del curso 2011/12. Presentaciones de Toxicología Vegetal de la asignatura de Toxicología de la Licenciatura de Veterinaria del curso 2011/12

  19. Evidence from pharmacology and pathophysiology suggests that chemicals with dissimilar mechanisms of action could be of bigger concern in the toxicological risk assessment of chemical mixtures than chemicals with a similar mechanism of action

    DEFF Research Database (Denmark)

    Hadrup, Niels


    mechanisms of action, similar modes of action or with common target organs. In the European Union, efforts are currently being made to subgroup chemicals according to this need. However, it remains to be determined whether this is the best strategy to obtain data for risk assessment. In conditions...... such as cancer or HIV, it is generally recognised that pharmacological combination therapy targeting different mechanisms of action is more effective than a strategy where only one mechanism is targeted. Moreover, in diseases such as acute myocardial infarction and congestive heart failure, several organ systems...

  20. The pseudo-binary mercury chalcogenide alloy HgSe sub 0 sub . sub 7 S sub 0 sub . sub 3 at high pressure: a mechanism for the zinc blende to cinnabar reconstructive phase transition

    CERN Document Server

    Kozlenko, D P; Ehm, L; Hull, S; Savenko, B N; Shchennikov, V V; Voronin, V I


    The structure of the pseudo-binary mercury chalcogenide alloy HgSe sub 0 sub . sub 7 S sub 0 sub . sub 3 has been studied by x-ray and neutron powder diffraction at pressures up to 8.5 GPa. A phase transition from the cubic zinc blende structure to the hexagonal cinnabar structure was observed at P approx 1 GPa. A phenomenological model of this reconstructive phase transition based on a displacement mechanism is proposed. Analysis of the geometrical relationship between the zinc blende and the cinnabar phases has shown that the possible order parameter for the zinc blende-cinnabar structural transformation is the spontaneous strain e sub 4. This assignment agrees with the previously observed high pressure behaviour of the elastic constants of some mercury chalcogenides.

  1. Toxicology, an STS Approach. (United States)

    Wagner, Richard


    Presented are activities suggested through Project L.A.B.S. that involve the topic of toxicology. Activities include suggested research, the risk benefit seesaw, human-made compounds, legislation, a historical perspective, and health. A suggested readings list is provided. (KR)

  2. From alternative methods to a new toxicology. (United States)

    Hartung, Thomas


    Mechanistic toxicology has evolved by relying, to a large extent, on methodologies that substitute or complement traditional animal tests. The biotechnology and informatics revolutions of the last decades have made such technologies broadly available and useful, but regulatory toxicology has been slow to embrace these new approaches. Major validation efforts, however, have delivered the evidence that new approaches do not lower safety standards and can be integrated into regulatory safety assessments. Particularly in the EU, political pressures, such as the REACH legislation and the 7th Amendment to the cosmetic legislation, have prompted the need of new approaches. In the US, the NRC vision report calling for a toxicology for the 21st century (and its most recent adaptation by EPA for their toxicity testing strategy) have initiated a debate about how to create a novel approach based on human cell cultures, lower species, high-throughput testing, and modeling. Lessons learned from the development, validation, and acceptance of alternative methods support the creation of a new approach based on identified toxicity pathways. Conceptual steering and an objective assessment of current practices by evidence-based toxicology (EBT) are required. EBT is modeled on evidence-based medicine, which has demonstrated that rigorous systematic reviews of current practices and meta-analyses of studies provide powerful tools to provide health care professionals and patients with the current best scientific evidence. Similarly, a portal for high-quality reviews of toxicological approaches and tools for the quantitative meta-analyses of data promise to serve as door opener for a new regulatory toxicology.

  3. Emerging approaches in predictive toxicology. (United States)

    Zhang, Luoping; McHale, Cliona M; Greene, Nigel; Snyder, Ronald D; Rich, Ivan N; Aardema, Marilyn J; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan


    Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described.

  4. Toxicologic evaluation of ofloxacin. (United States)

    Davis, G J; McKenzie, B E


    Results of studies conducted to characterize local, systemic, reproductive, and mutagenic effects indicate that ofloxacin is well tolerated within reasonable multiples of the intended clinical dose. Quinolone-associated arthropathic effects characterized by blister, erosion, and increased synovial fluid occurred in rats and dogs and appeared to be both age- and dose-related. Maternal toxicity and embryotoxicity were noted, but there was no teratogenicity in rats or rabbits. There was no impairment of fertility, and no adverse effects on late fetal development, labor, delivery, lactation, neonatal viability, or growth of offspring occurred. Target-organ studies revealed no evidence of ocular toxicity in rats, nephrotoxicity in rabbits, or antigenicity or ototoxicity in guinea pigs. Overall, the toxicologic evaluation of ofloxacin has shown this compound to be a drug with a low toxicologic potential.

  5. Cytotoxicity of Cinnabar and Cinnabar-containing Compounds in Human Liver HL-7702 Cells%朱砂、含朱砂复方对人肝细胞的毒性对比研究

    Institute of Scientific and Technical Information of China (English)

    付中祥; 时京珍; 刘杰; 张永萍


    Objective:To study the toxicity of cinnabr,Zhusha Anshen Wan,Liaoyuan Hetang Huafeng Dan,Wansheng Huafeng Dan,HgS,HgC12 and MeHg in human liver HL-7702 cells.Method:Cultured cells were treated with cinnabar containing compounds and mercurial for 24 h,and was determined by the MTS assay,extracellular and intracellular Hg contents were determined by atomic fluoresence detector.Result:The cytotoxicity of cinnabr,Zhusha Anshen Wan,Liaoyuan Hetang Huafeng Dan,Wansheng Huafeng Dan,HgS had a obvious difference compared with HgCl2 and MeHg is same as the intracellular and extracellular mercury accumulation.Conclusion:The toxicity of cinnabr,Zhusha Anshen Wan,Liaoyuan Hetang Huafeng Dan,Wansheng Huafeng Dan,HgS with same mercury accumulation and same mercury dissolution is extremely lower than the corresponding HgCl2 and MeHg in human liver HL-7702 cells.%目的:对比研究朱砂、几种含朱砂复方与其他汞存在形式对HL-7702人肝细胞的毒性.方法:分别以朱砂、朱砂安神丸、廖元和堂化风丹、万胜化风丹、硫化汞、氯化汞、甲基汞加入已接种于96孔板的HL-7702人肝细胞后,检测各组的细胞存活率、检测各组细胞内、外的汞含量.结果:等汞含量和等汞浸出量的朱砂、朱砂安神丸、廖元和堂化风丹、万胜化风丹和硫化汞对HL-7702人肝细胞的存活率与正常组无明显差异,与等汞含量和等汞浸出量的氯化汞和甲基汞均有明显差异(P<0.05);分别以等汞含量、等汞浸出量的朱砂、朱砂安神丸、廖元和堂化风丹、万胜化风丹和硫化汞培养的HL-7702人肝细胞内、外汞含量均低于氯化汞、甲基汞(P<0.05).结论:等汞含量、等汞浸出量的朱砂、朱砂安神丸、廖元和堂化风丹和万胜化风丹对人肝HL-7702细胞的毒性远小于对应等汞含量、等汞浸出量的氯化汞、甲基汞.

  6. Assessment of food toxicology



    The interest in food toxicology is evident by the dependency of humankind on nutrition by virtue of their heterotrophic metabolism. By means of modern biochemistry, molecular and cell biology, computer science, bioinformatics as well as high-throughput and high-content screening technologies it has been possible to identify adverse effects and characterize potential toxicants in food. The mechanisms of toxicant actions are multifactorial but many toxic effects converge on the generation of ox...

  7. Information science in toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Lu, P.Y.; Wassom, J.S.


    Toxicology is an exciting and rapidly expanding scientific discipline, and the volume of literature being generated is growing at an exponential rate. This ouput reflects the current information explosion in science and technology. Generally, this large-scale increase in information began around 1960, and consequently two President's Science Advisory Committees were appointed to focus attention on the issues of information generation, compilation, and dissemination and the application of advanced computer technology in information storage and retrieval. This national policy for information development is substantiated by the fact that today online interactive retrieval of scientific and technical databases is becoming a routine process in information acquisition. Although file dispersion and lack of quality control have been major problems, new approaches are continually being devised to resolve these problems. For example, the intellectual filter as a recognized segment of the scientific information utilization cycle has naturally evolved. This function is expanding and becoming critical to the decision-making process. Future challenges to those working to make toxicology information more readily available include assessing fugitive literature and negative testing results and converting these into a new information resource for toxicology. 23 references, 1 figure, 2 tables.

  8. Assessment of food toxicology

    Directory of Open Access Journals (Sweden)

    Alexander Gosslau


    Full Text Available The interest in food toxicology is evident by the dependency of humankind on nutrition by virtue of their heterotrophic metabolism. By means of modern biochemistry, molecular and cell biology, computer science, bioinformatics as well as high-throughput and high-content screening technologies it has been possible to identify adverse effects and characterize potential toxicants in food. The mechanisms of toxicant actions are multifactorial but many toxic effects converge on the generation of oxidative stress and chronic inflammation resulting in cell death, aging and degenerative diseases. Integration of food toxicology data obtained throughout biochemical and cell-based in vitro, animal in vivo and human clinical settings has enabled the establishment of alternative, highly predictable in silico models. These systems utilize a combination of complex in vitro cell-based models with computer-based algorithms. A decrease of rodent animal testing with its limitations of high costs, low throughput readouts, inconsistent responses, ethical issues and concerns of extrapolability to humans have led to an increased use of these but also alternative lower hierarchy surrogate animal models (e.g. Drosophila melanogaster; Caenorhabditis elegans or Danio rerio and efforts to integrate organotypic systems and stem cell-based assays. Despite those achievements, there are numerous challenges in various disciplines of food toxicology.

  9. Toxicological Benchmarks for Wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E. Opresko, D.M. Suter, G.W.


    Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red

  10. Preclinical Toxicology of New Drugs. (United States)



  11. Experimental Study on the Use of Cinnabar During Pregnancy%朱砂妊娠用药的实验研究

    Institute of Scientific and Technical Information of China (English)

    陈斌; 肖敏; 李飞艳; 冯传平; 李辉; 刘杰


      目的:比较孕兔、幼兔、成年兔和新生兔(实验中孕兔所产)血汞含量,探讨不同兔对朱砂中汞的吸收情况。方法:用朱砂定时定量灌胃,用吹气富集-冷原子吸收法测定孕兔、幼兔、成年兔和新生兔血汞含量,并对实验数据进行统计学分析与比较。结果:血汞浓度:孕兔>幼兔>成年兔;新生兔血汞浓度显著高于孕兔给药前的血汞浓度。结论:实验表明朱砂中汞能透过孕兔胎盘屏障进入新生兔体内。鉴于汞的巨大毒性,提出《中国药典》在中药妊娠禁忌药中应增列朱砂。%Objectives: To investigate the absorption of the mercury in Cinnabarr by different rabbits, the blood mercury concentrations in pregnant rabbits, young rabbits, adult rabbits and newborn rabbits (the neonatal of the pregnant rabbits used in the experiment) were compared. Methods: The rabbits were given Cinnabar by intragastric administration quantitatively at regular intervals. The blood mercury concentrations in the pregnant rabbits, young rabbits, adult rabbits and newborn rabbits were measured by cold vapour atomic absorption spectrometry, and the experiment data has been analyzed. Results: Blood mercury concentrations were in the series as follows: pregnant rabbits > young rabbits > adult rabbits; The newborn rabbits had significantly higher blood mercury concentrations than that of adult rabbits. Conclusions: Experimental results indicated that the mercury in Cinnabar could through the placental barrier of pregnant rabbits to pass into the fetal rabbit. Considering the severe toxicity of mercury, Cinnabar should be added to the list of the contraindicated traditional Chinese medicines during pregnancy in Chinese Pharmacopoeia.

  12. Bioaccessibility as well as absorption and excretion of mercury in cinnabar%朱砂中汞的生物可接受性及其吸收与排泄

    Institute of Scientific and Technical Information of China (English)

    霍韬光; 王海宇; 林欣然; 畅蓓; 李维凯; 杨卉蕾; 张颖花; 姜泓


    研究了朱砂中汞的生物可接受性及其在体内的吸收与排泄.采用体外消化透析法测定了朱砂中汞的生物可按受性;计算了大鼠灌胃给予临床剂量(50 mg/kg)朱砂后汞的药动学参数;测定了给予临床剂量的朱砂后大鼠粪样中汞的排泄量.结果表明,朱砂中汞的溶出率为0.011%,生物可接受率为0.003 3%.大鼠灌胃给予临床剂量的朱砂后,汞的药动学参数为:最高血药浓度(Pmax)为(6.3±1.3)μg/L,达峰时间(tmax)为(1.3±0.4)h,半衰期(t1/2)为(4.2±0.5)h,血药浓度-时间曲线下面积(AUC)为(54.7±8.7) μg·h·L-1.给予朱砂12 h后汞在粪便中排泄量最大,96 h后在粪样中仍可检测到少量汞.朱砂中汞的生物可接受性较低,在体内吸收少,滞留时间较长,排泄缓慢,长期服用可在体内蓄积,产生毒性.%The bioaccessibility and absorption and excretion of mercury in cinnabar were studied. The bioaccessibility of mercury in cinnabar was evaluated by adopting in vitro digestion and dialysis method to simulate the conditions of gastric compartment and intestinal compartment of mercury. The pharmacokinetic parameters of mercury with respect to intragastric administration of cinnabar at a clinical dosage of 50 mg/kg for rats were calculated) and the excretion fraction of mercury in the fecal sample of the rats after intragastric administration of cinnabar at a clinical dosage was determined. Results indicate that, in the gastric compartment, the solubility of mercury from cinnabar is 0. 011%; and the bioaccessibility of mercury in the intestinal compartment is 0. 003 3%. The time-course pharmacokinetic parameters of mercury when the rats are intragastrically given cinnabar at a clinical dosage of 50 mg/kg are determined as the maximum concentration in blood Cmax(6.3 ± 1.3) μg/L, time to reach the maximum concentration tmax(l. 3 ± 0. 4) h, half-time period t1/2(4. 2 ± 0. 5) h, and area under the concentration-time curve AUC (54. 7

  13. Synthetic toxicology: where engineering meets biology and toxicology. (United States)

    Schmidt, Markus; Pei, Lei


    This article examines the implications of synthetic biology (SB) for toxicological sciences. Starting with a working definition of SB, we describe its current subfields, namely, DNA synthesis, the engineering of DNA-based biological circuits, minimal genome research, attempts to construct protocells and synthetic cells, and efforts to diversify the biochemistry of life through xenobiology. Based on the most important techniques, tools, and expected applications in SB, we describe the ramifications of SB for toxicology under the label of synthetic toxicology. We differentiate between cases where SB offers opportunities for toxicology and where SB poses challenges for toxicology. Among the opportunities, we identified the assistance of SB to construct novel toxicity testing platforms, define new toxicity-pathway assays, explore the potential of SB to improve in vivo biotransformation of toxins, present novel biosensors developed by SB for environmental toxicology, discuss cell-free protein synthesis of toxins, reflect on the contribution to toxic use reduction, and the democratization of toxicology through do-it-yourself biology. Among the identified challenges for toxicology, we identify synthetic toxins and novel xenobiotics, biosecurity and dual-use considerations, the potential bridging of toxic substances and infectious agents, and do-it-yourself toxin production.

  14. Ion channels in toxicology. (United States)

    Restrepo-Angulo, Iván; De Vizcaya-Ruiz, Andrea; Camacho, Javier


    Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

  15. [Antidotes in clinical toxicology]. (United States)

    Hruby, K


    This overview describes antidotes, and their clinical pharmacology, that have an established significance in the currently practiced clinical toxicology because of their proven effectiveness in the treatment of serious poisonings. For the proper, efficient, and targeted use of an antidote, pharmacological knowledge is required, which is a central subject of this article. Current data from the literature are used as reference along with the accumulated experiences about possible adverse effects in order to include them in therapeutic considerations. The dosage of antidotes is the subject of several other review articles and is therefore not included in this synopsis.

  16. Toxicology: Old Art, New Science. (United States)

    Timbrell, John A.


    Examines the need for a science of toxicology and training at both the undergraduate and graduate levels in response to legislation controlling drugs, food additives and toxic substances in the work environment, and concern about effects on man. Stresses need for putting toxicology on a scientific base with adequate funding. (JM)

  17. Web Similarity

    NARCIS (Netherlands)

    Cohen, A.R.; Vitányi, P.M.B.


    Normalized web distance (NWD) is a similarity or normalized semantic distance based on the World Wide Web or any other large electronic database, for instance Wikipedia, and a search engine that returns reliable aggregate page counts. For sets of search terms the NWD gives a similarity on a scale fr

  18. Mass Spectrometry Applications for Toxicology (United States)

    Mbughuni, Michael M.; Jannetto, Paul J.


    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  19. Mass Spectrometry Applications for Toxicology. (United States)

    Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J


    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS(n)) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  20. Overview: developmental toxicology: new directions. (United States)

    Shuey, Dana; Kim, James H


    Since regulatory agencies began implementing the use of standardized developmental toxicology protocols in the mid-1960s, our knowledge base of embryo-fetal development and technologies for experimentation has grown exponentially. These developmental toxicology protocols were a direct result of the thalidomide tragedy from earlier that decade, when large numbers of women were exposed to the drug and over 10,000 cases of phocomelia resulted. In preventing a recurrence of such tragedies, the testing protocols are immensely successful and the field of toxicology has been dedicated to using them to advance safety and risk assessment of chemicals and pharmaceuticals. Recently, our perspectives on toxicity testing have been challenged by a growing awareness that while we have excelled in hazard identification, we are in dire need of improved methodologies for human health risk assessment, particularly with respect to the large numbers of environmental chemicals for which we have little toxicology data and to the growing sentiment that better alternatives to whole animals tests are needed. To provide a forum for scientists, researchers, and regulators, the Developmental and Reproductive Toxicology Technical Committee of the Health and Environmental Sciences Institute organized a 2-day workshop titled "Developmental Toxicology-New Directions" to evaluate lessons learned over the past 30 years and discuss the future of toxicology testing. The following four articles describe different presentations and discussions that were held over the course of those 2 days.

  1. Diagnostic and forensic toxicology. (United States)

    Galey, F D


    In most competent veterinary diagnostic laboratories, analytical findings are interpreted by the veterinary toxicologist to determine the significance of the finding in view of historic, clinical, and pathologic findings. A veterinary toxicologist also will provide consultation about possible toxic rule-outs for a case, treatment of affected animals, and prevention of additional cases. Once all of the information is available, a complete summary of the findings can be provided to the client. When the procedures outlined are followed, including a systematic approach to collecting all the evidence (historic, clinical, pathologic, and analytic), proper sampling techniques, and good communication between the clinician and the client and laboratory, the usefulness of the toxicology investigation will be maximized.

  2. [New antidotes in toxicology]. (United States)

    Bédry, Régis


    New antidotes appeared in the French pharmacopoeia (fomepizole, Viperfav), and old drugs, usually unused in toxicology, saw their indications enlarged in an antidotic activity (glucose and insulin, L-carnitine, octreotide). Fomepizole is an antidote for toxic alcohol and glycol intoxications, which is much easier to handle than ethylic alcohol and as efficient as the classical antidote of this kind of intoxication. Octreotide improves the result of hypertonic glucose infusion in sulfonylurea derivatives intoxications, by blocking insulin release. The glucose-insulin association allows the myocardium to use the main energy substrate necessary for its action in the setting of beta-blocking and calcium channel blocking agents intoxications when they are associated to a cardiogenic shock. Viperfav is a polyvalent antivenom used in European adders envenomations, which showed its effectiveness and safety. Levocarnitine allows to correct the wrong metabolic pathway induced by a deficit in carnitine in valproïc acid intoxications.

  3. Honey bee toxicology. (United States)

    Johnson, Reed M


    Insecticides are chemicals used to kill insects, so it is unsurprising that many insecticides have the potential to harm honey bees (Apis mellifera). However, bees are exposed to a great variety of other potentially toxic chemicals, including flavonoids and alkaloids that are produced by plants; mycotoxins produced by fungi; antimicrobials and acaricides that are introduced by beekeepers; and fungicides, herbicides, and other environmental contaminants. Although often regarded as uniquely sensitive to toxic compounds, honey bees are adapted to tolerate and even thrive in the presence of toxic compounds that occur naturally in their environment. The harm caused by exposure to a particular concentration of a toxic compound may depend on the level of simultaneous exposure to other compounds, pathogen levels, nutritional status, and a host of other factors. This review takes a holistic view of bee toxicology by taking into account the spectrum of xenobiotics to which bees are exposed.

  4. 朱砂对雄性大鼠精子质量影响的研究%Effect of cinnabar on sperm quality of male rats

    Institute of Scientific and Technical Information of China (English)

    顾祖曦; 刘炯; 谷颖敏; 姜昕; 吴文斌; 米金霞; 汤家铭


    Objective To observe the effect of cinnabar on the sperm motility and related movement parameters of male rats. Methods The male rats of reproductive toxicity section I were randomized into four groups; negative control group (0.5% CMC-Na) , small close cinnabar group (100 (xg/g) , medium dose group (300 μg/g) , large dose group (1 000 μg/g) and positive group (tripterygium glycosides 10 μg/g) , corresponding interventions were given in each group with the course of 6 weeks. After administration, the epididymis of each rat was taken to prepare sperm suspensions, then transfer 10 ui of rat sperm suspensions to sperm counting chambers to examine the quantity, vitality, motility of sperm by computer assisted sperm analysis ( CASA). Histo-pathological examination of testes and epididymis was done by HE staining. Results Compared with negative control group, the living rate, vitality, effective quantity and density of sperm in three cinnabar groups were decreases, with significant differences in living rate, vitality and density of sperm between negative control group and medium dose group, and with significant difference in effective quantity of sperm between negative control group and small dose group (P 0.05). Conclusion Cinnabar has negative effect on vitality, living rate, density and motility of rats sperm, and the results prompt that long term administration of cinnabar may had some harmful effect on male fertility.%目的 观察朱砂灌胃给药对雄性大鼠精子活力及相关运动参数的影响.方法 利用生殖毒性Ⅰ段雄性大鼠,按体质量随机分为阴性对照组(0.5% CMC-Na)、朱砂低剂量组(100μg∥g)、朱砂中剂量组(300 μg/g)、朱砂高剂量组(1 000ug/g)、阳性对照组(雷公藤多苷10 μg/g),分别给予相应的干预措施,共6周.给药结束后,取大鼠一侧附睾制备精子悬液,吸取10μl精子悬液至大鼠专用精子计数池,用计算机辅助精子分析系统(CASA)进行精子数量、活

  5. Toxicology of Biodiesel Combustion products (United States)

    1. Introduction The toxicology of combusted biodiesel is an emerging field. Much of the current knowledge about biological responses and health effects stems from studies of exposures to other fuel sources (typically petroleum diesel, gasoline, and wood) incompletely combusted. ...

  6. Aggregated Computational Toxicology Online Resource (United States)

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  7. Behavioral assays in environmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.


    Environmental toxicology is too permeated by questions about how the whole organism functions to abandon intact animals as test systems. Behavior does not participate as a single entity or discipline. It ranges across the total spectrum of functional toxicity, from tenuous subjective complaints to subtle sensory and motor disturbances demanding advanced instrumentation for their evaluation. Three facets of behavioral toxicology that illustrate its breadth of interests and potential contributions are discussed.

  8. 78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods... (United States)


    ... HUMAN SERVICES National Institutes of Health National Toxicology Program Scientific Advisory Committee... (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative... . Dated: July 17, 2013. John R. Bucher, Associate Director, National Toxicology Program. BILLING CODE...

  9. Toxicology of melatonin. (United States)

    Guardiola-Lemaître, B


    Despite the fact that melatonin has been released for public use in the United States by the Food and Drug Administration and is available over the counter nationwide, there currently is a total lack of information on the toxicology of melatonin. In Europe, melatonin has a completely different status in that it is considered a "neurohormone" and cannot be sold over the counter. Even though administration of melatonin in humans, as well as in animals (even at supraphysiological doses), has not shown evidence of toxicological effects (i.e., no deaths), a drug toxicological file still would need to be prepared and approved by the regulatory authorities. Several features that are specific to this neurohormone need to be taken into consideration. Whatever the species concerned, melatonin is secreted during the night; it is the "hormone of darkness." It presents a circadian rhythm and a circannual rhythm (in photoperiodic species). The duration of these secretions could have an impact on the reproductive system, for example, showing the importance of the pharmacodynamics of melatonin. An inappropriate time schedule of melatonin administration could induce supraphysiological concentrations of the neurohormone and a desensitization of melatonin receptors. A long duration of exposure to melatonin also could mimic an "artificial darkness" condition when a circadian rhythm with a basal zero level during the day needs to be conserved for a physiological function. Furthermore, administration of large doses of melatonin could induce high concentrations of melatonin and of different metabolites that could have deleterious effects per se. Numerous books, magazines, and articles have praised melatonin as a "miraculous cure-all" for ailments ranging from sleeplessness, to aging, without any clinical evidence of efficacy (with the exception of its chronobiotic and resynchronizing effect). Very little attention has been paid to the possible side effects of melatonin. Nightmares

  10. Similarity Scaling (United States)

    Schnack, Dalton D.

    In Lecture 10, we introduced a non-dimensional parameter called the Lundquist number, denoted by S. This is just one of many non-dimensional parameters that can appear in the formulations of both hydrodynamics and MHD. These generally express the ratio of the time scale associated with some dissipative process to the time scale associated with either wave propagation or transport by flow. These are important because they define regions in parameter space that separate flows with different physical characteristics. All flows that have the same non-dimensional parameters behave in the same way. This property is called similarity scaling.

  11. Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3, In Vivo in Mice

    Directory of Open Access Journals (Sweden)

    Wen-Hao Yu


    Full Text Available Toxic heavy metals, including mercury (Hg and arsenic (As, accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice (n=10 were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH, and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p<0.05, PAH accumulations in the kidney tissues were significantly higher (p<0.05, PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3.


    Directory of Open Access Journals (Sweden)

    Madhuri Sharma


    Full Text Available A number of experiments and the use of drugs have been performed in fish. The fish may be used as model organism in various biological experiments, including environmental toxicology. Aquatic animals are being engineered to increase aquaculture production, for medical and industrial research, and for ornamental reasons. Fish have been found to play an important role in assessing potential risks associated with exposure to toxic substances in aquatic environment. Hence, it has been thought that the development of transgenic fish can enhance the use of fish in environmental toxicology. India has developed experimental transgenics of rohu fish, zebra fish, cat fish and singhi fish. Genes, promoters and vectors of indigenous origin are now available for only two species namely rohu and singhi for engineering growth. Development of fish model carrying identical transgenes to those found in rodents is beneficial and has shown that several aspects of in vivo mutagenesis are similar between the two classes of vertebrates. Fish shows the frequencies of spontaneous mutations similar to rodents and respond to mutagen exposure consistent with known mutagenic mechanisms. The feasibility of in vivo mutation analysis using transgenic fish has been demonstrated and the potential value of transgenic fish as a comparative animal model has been illustrated. Therefore, the transgenic fish can give the significant contribution to study the environmental toxicity in animals as a whole.

  13. Toxicología clínica comunitaria Community Clinical Toxicology

    Directory of Open Access Journals (Sweden)

    María Elena Leal


    Full Text Available En algunos países de América Latina las intoxicaciones agudas se manejan de manera profesional por médicos especialistas en la mate-ria. Algo similar ocurre con las intoxicaciones crónicas de origen laboral en el sector formal. No obstante, una realidad diferente ocurre en cuanto a la evaluación de las intoxicaciones crónicas de origen ambiental, dado que éstas por su naturaleza, son más difíciles de diagnosticar. Para el tratamiento de las intoxicaciones agudas se han organizado Centros de Información y Atención Toxicológica, pero para las intoxicaciones crónicas ambientales no se ha generado organismos semejantes. Por consiguiente, en este trabajo sugerimos un modelo de atención de la intoxicaciones crónicas a través de grupos multidisciplinarios bajo el esquema de una nueva disciplina: la Toxicología Clínica Comunitaria, cuyo objetivo sería la atención simultánea de las intoxicaciones agudas que generalmente se atienden en un ámbito hospitalario y de las intoxicaciones ambientales que por lo normal se presentan a nivel comunitario. El objetivo final es aprovechar la experiencia que existe en la Región en cuanto a Toxicología Clínica para organizar el trabajo comunitario.In some Latin American countries acute intoxication is professionally managed by specialized physicians qualified in the area. Something similar occurs with work-related chronic intoxication in the formal sector. However, a different reality prevails for the assessment of chronic intoxication of environmental origin, since it is by definition more difficult to diagnose. For treatment of acute intoxication, Toxicological Information and Care Centers have been set up, though similar bodies have not been created for chronic environmental intoxication. Therefore, in this study a model of chronic intoxication care is proposed, using multidisciplinary teams adopting a new approach, namely Community Clinical Toxicology, the goal of which would be the

  14. Developmental and Reproductive Toxicology Database (DART) (United States)

    U.S. Department of Health & Human Services — A bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET) with references to developmental and reproductive toxicology...

  15. IRIS Toxicological Review of Acrolein (2003 Final) (United States)

    EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

  16. 42 CFR 493.937 - Toxicology. (United States)


    ... 42 Public Health 5 2010-10-01 2010-10-01 false Toxicology. 493.937 Section 493.937 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.937 Toxicology. (a) Program content and frequency of challenge. To be approved for proficiency testing for toxicology, the annual program...

  17. 42 CFR 493.1213 - Condition: Toxicology. (United States)


    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Toxicology. 493.1213 Section 493.1213 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1213 Condition: Toxicology. If the laboratory provides services in the subspecialty of Toxicology,...

  18. Predictive toxicology of chemicals and database mining

    Institute of Scientific and Technical Information of China (English)


    The toxic chemicals from the database Registry of Toxic Effects of Chemical Substances (RTECS) were analyzed by structural similarity comparison, which shows that the structure patterns or characteristics of toxic chemicals exist in a sufficiently large database. Then, a two-step strategy was proposed to explore noncongeneric toxic chemicals in the database: the screening of structure patterns by similarity comparison and the derivation of detailed relationship between structure and activity by using comparative molecular field analysis (CoMFA) of Quantitative Structure-Activity Relationship (QSAR) technologies. From the performance of the procedure, such a stepwise scheme is demonstrated to be feasible and effective to mine a database of toxic chemicals. It can be anticipated that database mining of toxic chemicals will be a new area for predictive toxicology of chemicals.

  19. Toxicological evaluation of chemical mixtures

    NARCIS (Netherlands)

    Feron, V.J.; Groten, J.P.


    This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures

  20. Toxicological evaluation of organic residues

    Directory of Open Access Journals (Sweden)

    Eduardo de la Peña de Torres


    Full Text Available It is pointed out the importance of short term assays for the characterization of organic residues, specially some methods for toxicological, mutagenic, genotoxic and cytotoxic evaluation (Vibrio fischeri, Salmonella typhimurium and Allium cepa, used in the characterization of environmental complex mixtures lixiviates. These methods take part together with other bioassays in the evaluation by toxicological identification (VIT, which allows the evaluation of other ecotoxicological effects: a bioluminescence inhibition of Vibrio fischeri; b germination and root length of Lepidum sativum; c root length of Allium cepa and Tradescantia sp.; d inhibition of the mobility of Daphnia magna; and e abnormalities in the development of Oryzias latipes, or medaka fish. All these assays take part in the EU battery of bioassays, applied to discriminate and select between those environmental matrixes which must be subject to more complex and specific chemical characterizations.We make a review of the methods for toxicological evaluation, used for the characterization of chemical compounds or complex mixtures, as well as the use of its results for the human and environmental risk assessment. This evaluation consists, in short, of the identification of dangers, evaluation of dose-response ratio, evaluation of exposure and risk characterization, resulting in the analysis, use and communication of this risk. It is emphasized the high predictive value for carcinogenicity of some of these bioassays.It is shown the utility of short term assays for the evaluation of substances, products and complex mixtures, which would contribute to improve the toxicological knowledge of a greater number substances. This is a vital need in the EU, due to the lack of complete toxicological information of about the 70% of the 106.000 existing and used substances.It is emphasized the great value that mutagenicity assays represent inside the toxicological tests in the basic level, which

  1. Regulatory issues in accreditation of toxicology laboratories. (United States)

    Bissell, Michael G


    Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

  2. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. (United States)

    Michelot, Didier; Melendez-Howell, Leda Maria


    The fly agaric is a remarkable mushroom in many respects; these are its bearing, history, chemical components and the poisoning that it provokes when consumed. The 'pantherina' poisoning syndrome is characterized by central nervous system dysfunction. The main species responsible are Amanita muscaria and A. pantherina (Amanitaceae); however, some other species of the genus have been suspected for similar actions. Ibotenic acid and muscimol are the active components, and probably, some other substances detected in the latter species participate in the psychotropic effects. The use of the mushroom started in ancient times and is connected with mysticism. Current knowledge on the chemistry, toxicology, and biology relating to this mushroom is reviewed, together with distinctive features concerning this unique species.

  3. A medical-toxicological view of tattooing

    DEFF Research Database (Denmark)

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta;


    Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention...... of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application...... of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage...

  4. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  5. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  6. 21 CFR 862.3280 - Clinical toxicology control material. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology...

  7. Resource Guide to Careers in Toxicology, 3rd Edition. (United States)

    Society of Toxicology, Reston, VA.

    This resource guide was prepared by the Tox 90's Educational Issues Task Force of the Society of Toxicology. The introduction provides information on the Society of Toxicology and financial support for graduate students in toxicology. Other sections include career opportunities in toxicology, academic and postdoctoral programs in toxicology, and…

  8. 21 CFR 862.3200 - Clinical toxicology calibrator. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator...

  9. Toxicología General y Aplicada


    García Fernández, Antonio Juan


    Presentaciones de los temas de Toxicología General y Aplicada: clínica, alimentaria y ambiental impartidos en la asignatura de Toxicología de la licenciatura de Veterinaria en la Universidad de Murcia en el curso 2011/12. Presentaciones de los temas de Toxicología General y Aplicada: clínica, alimentaria y ambiental impartidos en la Facultad de Veterinaria en el curso 2011/12.

  10. Discussion on Improvement of Toxicological Pathology Study

    Institute of Scientific and Technical Information of China (English)



    Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation procedure (SOP) for toxico-logical pathology assessment; emphasizing on immunotoxicology evaluation; adopting a new ex-periment model of replacement, featuring high speed and reliability; introducing new techniques and new models in toxicological mechanism re-search; and establishing a new appraisal system to screen innovative drug and rapid and high pre-cision methods for early security assessment, de-tection and measurement.

  11. Graduate Training in Toxicology in Colleges of Veterinary Medicine. (United States)

    Robens, J. F.; Buck, W. B.


    Presented are an American Board of Veterinary Toxicology survey and evaluation of the training resources available in graduate programs in toxicology located in colleges of veterinary medicine. Regulatory toxicology, number of toxicologists needed, and curriculum are also discussed. (JMD)

  12. Toxicological evaluation of pure hydroxytyrosol. (United States)

    Auñon-Calles, David; Canut, Lourdes; Visioli, Francesco


    Of all the phenolic constituents of olives and extra virgin olive oil, hydroxytyrosol is currently being actively exploited as a potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and food industry. In terms of safety profile, hydroxytyrosol has only been investigated as the predominant part of raw olive mill waste water extracts, due to the previous unavailability of appropriate quantities of the pure compound. We report the toxicological evaluation of hydroxytyrosol and, based on the results, propose a No Observed Adverse Effects Level (NOAEL) of 500mg/kg/d.

  13. Toxicology for the Equine Practitioner. (United States)

    Al-Dissi, Ahmad


    A wide variety of toxins cause diseases in the horse and are investigated routinely by veterinarians and veterinary pathologists to identify the cause of illness and death. A complete investigation involves performing a thorough necropsy and requires macroscopic and microscopic examination of lesions and a variety of laboratory testing to obtain an accurate diagnosis. The identification of gross lesions by equine practitioners is often the first step in formulating a diagnostic plan. This article provides a description of selected common toxins producing detectable gross lesions in horses in North America. The article is useful to equine practitioners and veterinary pathologists investigating a toxicology-related death.

  14. Selecting the best design for nonstandard toxicology experiments. (United States)

    Webb, Jennifer M; Smucker, Byran J; Bailer, A John


    Although many experiments in environmental toxicology use standard statistical experimental designs, there are situations that arise where no such standard design is natural or applicable because of logistical constraints. For example, the layout of a laboratory may suggest that each shelf serve as a block, with the number of experimental units per shelf either greater than or less than the number of treatments in a way that precludes the use of a typical block design. In such cases, an effective and powerful alternative is to employ optimal experimental design principles, a strategy that produces designs with precise statistical estimates. Here, a D-optimal design was generated for an experiment in environmental toxicology that has 2 factors, 16 treatments, and constraints similar to those described above. After initial consideration of a randomized complete block design and an intuitive cyclic design, it was decided to compare a D-optimal design and a slightly more complicated version of the cyclic design. Simulations were conducted generating random responses under a variety of scenarios that reflect conditions motivated by a similar toxicology study, and the designs were evaluated via D-efficiency as well as by a power analysis. The cyclic design performed well compared to the D-optimal design.

  15. The Toxicology Education Summit: building the future of toxicology through education. (United States)

    Barchowsky, Aaron; Buckley, Lorrene A; Carlson, Gary P; Fitsanakis, Vanessa A; Ford, Sue M; Genter, Mary Beth; Germolec, Dori R; Leavens, Teresa L; Lehman-McKeeman, Lois D; Safe, Stephen H; Sulentic, Courtney E W; Eidemiller, Betty J


    Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collaborative approaches that require advanced and continuing education in toxicology and associated disciplines. This requires paradigm shifts in educational programs that support recruitment, development, and training of the modern toxicologist, as well as continued education and retraining of the midcareer professional to keep pace and sustain careers in industry, government, and academia. The Society of Toxicology convened the Toxicology Educational Summit to discuss the state of toxicology education and to strategically address educational needs and the sustained advancement of toxicology as a profession. The Summit focused on core issues of: building for the future of toxicology through educational programs; defining education and training needs; developing the "Total Toxicologist"; continued training and retraining toxicologists to sustain their careers; and, finally, supporting toxicology education and professional development. This report summarizes the outcomes of the Summit, presents examples of successful programs that advance toxicology education, and concludes with strategies that will insure the future of toxicology through advanced educational initiatives.

  16. Hair: a complementary source of bioanalytical information in forensic toxicology. (United States)

    Barroso, Mário; Gallardo, Eugenia; Vieira, Duarte Nuno; López-Rivadulla, Manuel; Queiroz, João António


    Hair has been used for years in the assessment and documentation of human exposure to drugs, as it presents characteristics that make it extremely valuable for this purpose, namely the fact that sample collection is performed in a noninvasive manner, under close supervision, the possibility of collecting a specimen reflecting a similar timeline in the case of claims or suspicion of a leak in the chain of custody, and the increased window of detection for the drugs. For these reasons, testing for drugs in hair provides unique and useful information in several fields of toxicology, from which the most prominent is the possibility of studying individual drug use histories by means of segmental analysis. This paper will review the unique role of hair as a complementary sample in documenting human exposure to drugs in the fields of clinical and forensic toxicology and workplace drug testing.

  17. 42 CFR 493.845 - Standard; Toxicology. (United States)


    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Toxicology. 493.845 Section 493.845 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.845 Standard; Toxicology. (a) Failure to attain a score of at least 80 percent...



    Piegorsch, Walter W.; Simmons, Susan J.; Zeiger, Errol


    We discuss use of data mining techniques to study estimators of toxic potency (activity) in toxicological databases. The methods are slight variations on the standard data mining motif, but fit fully within the larger context of knowledge discovery in databases. An example illustrates the general theme of the approach, using results from a U.S. National Toxicology Program Salmonella mutagenicity database.

  19. Toxicological management of chlorophacinone poisoning. (United States)

    Lagrange, F; Corniot, A G; Titier, K; Bedry, R; Pehourcq, F


    A 33-year-old man was admitted 8 hours after voluntary ingestion of 1875 mg of chlorophacinone (C'Operat 750 mL). The examination revealed excitation and nausea, with a normal prothrombin index (PI). Comprehensive testing for abused and therapeutic drugs in blood confirmed chlorophacinone (maximum plasma level: 27.6 mg/L), an antivitamin K (AVK) rodenticide. In a search for easy toxicological management of chlorophacinone poisoning treated by phytomenadione and a cytochrome P450 inducer (phenobarbital), PI and chlorophacinone plasma levels were monitored concomitantly during 17 days. A simple HPLC procedure for the determination of chlorophacinone in human plasma is reported for that purpose. Under phenobarbital 200 mg/day, chlorophacinone exhibited an apparent elimination half-life (3.27 days) shorter than in previously reported cases. If PI is useful for planning phytomenadione treatment and used for therapeutic monitoring of AVK, the chlorophacinone concentrations follow-up may provide a better estimation of the duration of hospitalisation. Chlorophacinone accumulation in target cells or existence of an unidentified metabolite may explain persistence of the hypocoagulability syndrome at low plasmatic concentrations of chlorophacinone. This case illustrates how toxicological management may facilitate toxicokinetics and therapeutic data acquisition.

  20. Toxicological Assessment of Noxious Inhalants

    Directory of Open Access Journals (Sweden)

    Kleinsasser, N. H.


    Full Text Available In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects.The following essay describes the main features of toxicological assessment of inhalative environmental and workplace xenobiotics. The essay also explains relevant characteristics and limit values of noxious compounds and gases and depicts modern testing methods. To this end, emphasis is given on methods characterizing the different stages of tumorigenic processes. Various test systems have been developed which can be used in vivo, ex vivo or in vitro. They are to a great part based on the evidence of changes in DNA or particular genes of cells. Among others they have highlighted the impact of interindividual variability on enzymatic activation of xenobiotics and on susceptibility of the host to tumor diseases.Unfortunately, for many inhalative environmental noxious agents no sufficient risk profiles have been developed. The completion of these profiles should be the goal of toxicological assessment in order to allow reasonable socioeconomic or individual-based risk reduction.

  1. Evolution of toxicology information systems

    Energy Technology Data Exchange (ETDEWEB)

    Wassom, J.S.; Lu, P.Y. [Oak Ridge National Laboratory, TN (United States)


    Society today is faced with new health risk situations that have been brought about by recent scientific and technical advances. Federal and state governments are required to assess the many potential health risks to exposed populations from the products (chemicals) and by-products (pollutants) of these advances. Because a sound analysis of any potential health risk should be based on the use of relevant information, it behooves those individuals responsible for making the risk assessments to know where to obtain needed information. This paper reviews the origins of toxicology information systems and explores the specialized information center concept that was proposed in 1963 as a means of providing ready access to scientific and technical information. As a means of illustrating this concept, the operation of one specialized information center (the Environmental Mutagen Information Center at Oak Ridge National Laboratory) will be discussed. Insights into how toxicological information resources came into being, their design and makeup, will be of value to those seeking to acquire information for risk assessment purposes. 7 refs., 1 fig., 4 tabs.

  2. Nutritional toxicology: basic principles and actual problems. (United States)

    Hathcock, J N


    Nutritional toxicology is a specialty that combines the backgrounds and research approaches of nutrition and toxicology. Many problems of substantial importance to health and food safety involve interactions of nutrition process and requirement with the effects of toxicological impact. Solution of these problems requires research that meets the procedural and design criteria of experimental nutrition and these of experimental toxicology. The relationships may be described in three basic categories: (1) influence of nutrition on toxicities; (2) influence of toxicants on nutrition; and (3) toxicities of nutrients. Trypsin inhibitor research, an example of diet impacting on toxicological response, illustrates the necessity of controlling nutritional composition aspects that can confound the results. Prolonged acetaminophen administration provides an example of the effects of toxicants on nutritional requirement and function which could be important for persons with marginal sulphur amino acid intake.

  3. The Toxicology Investigators Consortium Case Registry--the 2014 Experience. (United States)

    Rhyee, Sean H; Farrugia, Lynn; Campleman, Sharan L; Wax, Paul M; Brent, Jeffrey


    The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. The Registry was queried for all cases entered between January 1 and December 31, 2014. Specific data reviewed for analysis included demographics (age, gender, ethnicity), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms, clinical findings, fatalities, and treatment. In 2014, 9172 cases were entered in the Registry across 47 active member sites. Females accounted for 51.1 % of cases. The majority (65.1 %) of cases were adults between the ages of 19 and 65. Caucasians made up the largest identified ethnic group (48.9 %). Most Registry cases originated from the inpatient setting (93.5 %), with a large majority of these consultations coming from the emergency department or inpatient admission services. Intentional and unintentional pharmaceutical exposures continued to be the most frequent reasons for consultation, accounting for 61.7 % of cases. Among cases of intentional pharmaceutical exposure, 62.4 % were associated with a self-harm attempt. Non-pharmaceutical exposures accounted for 14.1 % of Registry cases. Similar to the past years, non-opioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Clinical signs or symptoms were noted in 81.9 % of cases. There were 89 recorded fatalities (0.97 %). Medical treatment (e.g., antidotes, antivenom, chelators, supportive care) was rendered in 62.3 % of cases. Patient demographics and exposure characteristics in 2014 Registry cases remain similar to prior years. The majority of consultations arose in the acute care setting (emergency department or inpatient) and involved exposures to pharmaceutical products. Among exposures, non-opioid analgesics, sedative/hypnotics, and opioids were the most frequently

  4. Toxicology (United States)

    Macewen, J. W.


    Oxygen toxicity is examined, including the effects of oxygen partial pressure variations on toxicity and oxygen effects on ozone and nitrogen dioxide toxicity. Toxicity of fuels and oxidizers, such as hydrazines, are reported. Carbon monoxide, spacecraft threshold limit values, emergency exposure limits, spacecraft contaminants, and water quality standards for space missions are briefly summarized.

  5. Toxicologic Study of Monochloroacetic Acid

    Institute of Scientific and Technical Information of China (English)

    Lu Bo; Zhan Ping


    @@ Monochloroacetic Acid (MCA) is a chlorinated analog of acetic acids. MCA and its sodium salt (SMCA) are widely used as a chemical intermediate (primarily in the manufacture of chlorophenoxy herbicides,carboxymethylcelluose, glycine and indigoid dyes).Moreover, MCA has been found as a common by-product of the chlorination of drinking water. Chloroacetates are ubiquitous in the environment, and MCA is the most abundant among chloroacetates. A background level of 0.1 - 1μg/L is expected to occur in precipitation[1]. Total world wide annual production of MCA reported was about 400 000 tons[2]. Many studies have showed that MCA not only caused acute or chronic damage to the skin , liver, kidney, heart, brain and other organs, but also caused acute death systemically under high concentration[2,3]. So this article will discuss the toxic effect of Monochloroacetic Acid in Toxicology.

  6. Defining the toxicology of aging. (United States)

    Sorrentino, Jessica A; Sanoff, Hanna K; Sharpless, Norman E


    Mammalian aging is complex and incompletely understood. Although significant effort has been spent addressing the genetics or, more recently, the pharmacology of aging, the toxicology of aging has been relatively understudied. Just as an understanding of 'carcinogens' has proven crucial to modern cancer biology, an understanding of environmental toxicants that accelerate aging ('gerontogens') will inform gerontology. In this review, we discuss the evidence for the existence of mammalian gerontogens, as well as describe the biomarkers needed to measure the age-promoting activity of a given toxicant. We focus on the effects of putative gerontogens on the in vivo accumulation of senescent cells, a characteristic feature of aging that has a causal role in some age-associated phenotypes.

  7. The snake as the symbol of medicine, toxicology and toxinology. (United States)

    Ramoutsaki, I A; Haniotakis, S; Tsatsakis, A M


    We investigated the meaning and the roots of the snake's usage as a symbol of medicine, the medical profession, toxicology and toxinology by examining mythological, archeological data and a variety of texts from the ancient Greek world. The snake figure was associated with Asclepios, the ancient Greek God of medicine, and possessed benevolent properties. It was believed to be able to cure a patient or a wounded person just by touch. The snake is also connected with pharmacology and antisepsis, as snakes possess an antivenom against their own poison. The snake is related to sciences associated with poison and death, such as toxicology and toxinology, and it also implies a metaphysical idea. It is connected with the underworld, not only because it crawls on the ground, but because it can bring death, connecting the upper with the underground world. The ability of the snake to shed its skin has been associated with the circle of life, and the renaissance spirit also, ever since early Hellenic antiquity. Consequently, as a symbol of the modern medical profession, toxicology and toxinology, the snake twisted around a stick or the snake beside a pharmapeutic cup, which also implies the use of medicines or even poison, has its roots in the ancient Mediterranean area as proven by the archeological data combined with literary references. Its benevolent as well as its poisonous properties could be paralleled by the similar properties of medicines.

  8. TOXNET: A computerized collection of toxicological and environmental health information. (United States)

    Fonger, G C; Stroup, D; Thomas, P L; Wexler, P


    The Toxicology and Environmental Health Information Program, managed by the National Library of Medicine's Division of Specialized Information Services, provides access to a number of online bibliographic and factual computer files concerned with the toxicology, safety and handling, and environmental fate of chemicals, along with other files that cover genetic toxicology, developmental and reproductive toxicology, mutagenesis, carcinogenesis and toxic chemical releases.

  9. Principles and procedures in forensic toxicology. (United States)

    Wyman, John F


    The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

  10. A medical-toxicological view of tattooing. (United States)

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta; Blume, Annegret; Al Dahouk, Sascha; Bäumler, Wolfgang; Bernstein, Eric; Bocca, Beatrice; Alimonti, Alessandro; Colebrook, Helen; de Cuyper, Christa; Dähne, Lars; Hauri, Urs; Howard, Paul C; Janssen, Paul; Katz, Linda; Klitzman, Bruce; Kluger, Nicolas; Krutak, Lars; Platzek, Thomas; Scott-Lang, Victoria; Serup, Jørgen; Teubner, Wera; Schreiver, Ines; Wilkniß, Elena; Luch, Andreas


    Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing.

  11. Review of the toxicology of styrene. (United States)

    Bond, J A


    Styrene is used in the production of plastics and resins, which include polystyrene resins, acrylonitrile-butadiene-styrene resins, styrene-acrylonitrile resins, styrene-butadiene copolymer resins, styrene-butadiene rubber, and unsaturated polyester resins. In 1985, styrene ranked in the top ten of synthetic organic chemicals produced in the U.S. This review focuses on various aspects of styrene toxicology including acute and chronic toxicity, carcinogenicity, genotoxicity, pharmacokinetics, effects on hepatic and extrahepatic xenobiotic-metabolizing enzymes, pharmacokinetic modeling, and covalent interactions with macromolecules. There appear to be many similarities between the toxicity and metabolism of styrene in rodents and humans. Needed areas of future research on styrene include studies on the molecular dosimetry of styrene in terms of both hemoglobin and DNA adducts. The results of such research should improve our ability to assess the relationship between exposure to styrene and surrogate measures of "effective dose", thereby improving our ability to estimate the effects of low-level human exposures.

  12. Multiscale Toxicology- Building the Next Generation Tools for Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Retterer, S. T. [ORNL; Holsapple, M. P. [Battelle Memorial Institute


    A Cooperative Research and Development Agreement (CRADA) was established between Battelle Memorial Institute (BMI), Pacific Northwest National Laboratory (PNNL), Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Lawrence Livermore National Laboratory (LLNL) with the goal of combining the analytical and synthetic strengths of the National Laboratories with BMI's expertise in basic and translational medical research to develop a collaborative pipeline and suite of high throughput and imaging technologies that could be used to provide a more comprehensive understanding of material and drug toxicology in humans. The Multi-Scale Toxicity Initiative (MSTI), consisting of the team members above, was established to coordinate cellular scale, high-throughput in vitro testing, computational modeling and whole animal in vivo toxicology studies between MSTI team members. Development of a common, well-characterized set of materials for testing was identified as a crucial need for the initiative. Two research tracks were established by BMI during the course of the CRADA. The first research track focused on the development of tools and techniques for understanding the toxicity of nanomaterials, specifically inorganic nanoparticles (NPs). ORNL"s work focused primarily on the synthesis, functionalization and characterization of a common set of NPs for dissemination to the participating laboratories. These particles were synthesized to retain the same surface characteristics and size, but to allow visualization using the variety of imaging technologies present across the team. Characterization included the quantitative analysis of physical and chemical properties of the materials as well as the preliminary assessment of NP toxicity using commercially available toxicity screens and emerging optical imaging strategies. Additional efforts examined the development of high-throughput microfluidic and imaging assays for measuring NP uptake, localization, and

  13. Analysis of Statistical Methods Currently used in Toxicology Journals


    Na, Jihye; Yang, Hyeri; Bae, SeungJin; Lim, Kyung-Min


    Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and in...

  14. Pulmonary toxicology of respirable particles. [Lead abstract

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, C.L.; Cross, F.T.; Dagle, G.E.; Mahaffey, J.A. (eds.)


    Separate abstracts were prepared for the 44 papers presented in these proceedings. The last paper (Stannard) in the proceedings is an historical review of the field of inhalation toxicology and is not included in the analytics. (DS)

  15. Informing mechanistic toxicology with computational molecular models. (United States)

    Goldsmith, Michael R; Peterson, Shane D; Chang, Daniel T; Transue, Thomas R; Tornero-Velez, Rogelio; Tan, Yu-Mei; Dary, Curtis C


    Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo efforts. From a molecular biophysical ansatz, we describe how 3D molecular modeling methods used to numerically evaluate the classical pair-wise potential at the chemical/biological interface can inform mechanism of action and the dose-response paradigm of modern toxicology. With an emphasis on molecular docking, 3D-QSAR and pharmacophore/toxicophore approaches, we demonstrate how these methods can be integrated with chemoinformatic and toxicogenomic efforts into a tiered computational toxicology workflow. We describe generalized protocols in which 3D computational molecular modeling is used to enhance our ability to predict and model the most relevant toxicokinetic, metabolic, and molecular toxicological endpoints, thereby accelerating the computational toxicology-driven basis of modern risk assessment while providing a starting point for rational sustainable molecular design.

  16. Systems toxicology from genes to organs. (United States)

    Jack, John; Wambaugh, John; Shah, Imran


    This unique overview of systems toxicology methods and techniques begins with a brief account of systems thinking in biology over the last century. We discuss how systems biology and toxicology continue to leverage advances in computational modeling, informatics, large-scale computing, and biotechnology. Next, we chart the genesis of systems toxicology from previous work in physiologically based models, models of early development, and more recently, molecular systems biology. For readers interested in further details this background provides useful linkages to the relevant literature. It also lays the foundations for new ideas in systems toxicology that could translate laboratory measurements of molecular responses from xenobiotic perturbations to adverse organ level effects in humans. By providing innovative solutions across disciplinary boundaries and highlighting key scientific gaps, we believe this chapter provides useful information about the current state, and valuable insight about future directions in systems toxicity.

  17. Space Toxicology: Human Health during Space Operations (United States)

    Khan-Mayberry, Noreen; James, John T.; Tyl, ROchelle; Lam, Chiu-Wing


    Space Toxicology is a unique and targeted discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion. As we begin to explore other celestial bodies in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

  18. Techniques for Investigating Molecular Toxicology of Nanomaterials. (United States)

    Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong


    Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

  19. Multiscale Toxicology - Building the Next Generation Tools for Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, Brian D.; Minard, Kevin R.; Teeguarden, Justin G.; Waters, Katrina M.


    A Cooperative Research and Development Agreement (CRADA) was sponsored by Battelle Memorial Institute (Battelle, Columbus), to initiate a collaborative research program across multiple Department of Energy (DOE) National Laboratories aimed at developing a suite of new capabilities for predictive toxicology. Predicting the potential toxicity of emerging classes of engineered nanomaterials was chosen as one of two focusing problems for this program. PNNL’s focus toward this broader goal was to refine and apply experimental and computational tools needed to provide quantitative understanding of nanoparticle dosimetry for in vitro cell culture systems, which is necessary for comparative risk estimates for different nanomaterials or biological systems. Research conducted using lung epithelial and macrophage cell models successfully adapted magnetic particle detection and fluorescent microscopy technologies to quantify uptake of various forms of engineered nanoparticles, and provided experimental constraints and test datasets for benchmark comparison against results obtained using an in vitro computational dosimetry model, termed the ISSD model. The experimental and computational approaches developed were used to demonstrate how cell dosimetry is applied to aid in interpretation of genomic studies of nanoparticle-mediated biological responses in model cell culture systems. The combined experimental and theoretical approach provides a highly quantitative framework for evaluating relationships between biocompatibility of nanoparticles and their physical form in a controlled manner.

  20. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

  1. Health environmental risks surveillance systems: toxicological surveillance

    Directory of Open Access Journals (Sweden)

    Ana Ferrer Dufol


    Full Text Available A study of the Clinical Toxicological Section, about the Epidemiological Surveillance in Emergency Services, in relation to chemical products intoxications during the 1999-2003 period, is presented. This work is a result of an agreement between the Spanish Toxicological Association (AETOX and the Spanish Ministry of Health and Consumption, and was presented in the National Congress of Environment (CONAMA within the “Health Environmental Risks Surveillance Systems” working group.

  2. Health environmental risks surveillance systems: toxicological surveillance


    Ana Ferrer Dufol; Santiago Nogué Xarau; Francisco Vargas Marcos; Olivia Castillo Soria; Pilar Gascó Alberich; Ana de la Torre Reoyo; Eduardo de la Peña de Torres


    A study of the Clinical Toxicological Section, about the Epidemiological Surveillance in Emergency Services, in relation to chemical products intoxications during the 1999-2003 period, is presented. This work is a result of an agreement between the Spanish Toxicological Association (AETOX) and the Spanish Ministry of Health and Consumption, and was presented in the National Congress of Environment (CONAMA) within the “Health Environmental Risks Surveillance Systems” working group.

  3. Modern instrumental methods in forensic toxicology. (United States)

    Smith, Michael L; Vorce, Shawn P; Holler, Justin M; Shimomura, Eric; Magluilo, Joe; Jacobs, Aaron J; Huestis, Marilyn A


    This article reviews modern analytical instrumentation in forensic toxicology for identification and quantification of drugs and toxins in biological fluids and tissues. A brief description of the theory and inherent strengths and limitations of each methodology is included. The focus is on new technologies that address current analytical limitations. A goal of this review is to encourage innovations to improve our technological capabilities and to encourage use of these analytical techniques in forensic toxicology practice.

  4. Food for thought ... A toxicology ontology roadmap. (United States)

    Hardy, Barry; Apic, Gordana; Carthew, Philip; Clark, Dominic; Cook, David; Dix, Ian; Escher, Sylvia; Hastings, Janna; Heard, David J; Jeliazkova, Nina; Judson, Philip; Matis-Mitchell, Sherri; Mitic, Dragana; Myatt, Glenn; Shah, Imran; Spjuth, Ola; Tcheremenskaia, Olga; Toldo, Luca; Watson, David; White, Andrew; Yang, Chihae


    Foreign substances can have a dramatic and unpredictable adverse effect on human health. In the development of new therapeutic agents, it is essential that the potential adverse effects of all candidates be identified as early as possible. The field of predictive toxicology strives to profile the potential for adverse effects of novel chemical substances before they occur, both with traditional in vivo experimental approaches and increasingly through the development of in vitro and computational methods which can supplement and reduce the need for animal testing. To be maximally effective, the field needs access to the largest possible knowledge base of previous toxicology findings, and such results need to be made available in such a fashion so as to be interoperable, comparable, and compatible with standard toolkits. This necessitates the development of open, public, computable, and standardized toxicology vocabularies and ontologies so as to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. Such ontology development will support data management, model building, integrated analysis, validation and reporting, including regulatory reporting and alternative testing submission requirements as required by guidelines such as the REACH legislation, leading to new scientific advances in a mechanistically-based predictive toxicology. Numerous existing ontology and standards initiatives can contribute to the creation of a toxicology ontology supporting the needs of predictive toxicology and risk assessment. Additionally, new ontologies are needed to satisfy practical use cases and scenarios where gaps currently exist. Developing and integrating these resources will require a well-coordinated and sustained effort across numerous stakeholders engaged in a public-private partnership. In this communication, we set out a roadmap for the development of an integrated toxicology ontology

  5. Toxicological assessment of Ashitaba Chalcone. (United States)

    Maronpot, Robert R


    The plant Angelica keiskei contains two main physiologically active flavonoid chalcones, 4-hydroxyderricin and xanthoangelol. Known as ashitaba in Japan, powder from the sap is widely consumed for its medicinal properties in Asia as a dietary supplement. Limited previously reported mammalian studies were without evidence of toxicity. GLP studies reported here, including a bacterial reverse mutation assay, a chromosome aberration assay, and an in vivo micronucleus assay are negative for genotoxicity. A GLP- compliant 90-day repeated oral gavage study of ashitaba yellow sap powder containing 8.45% chalcones in Sprague Dawley rats resulted in expected known physiological effects on coagulation parameters and plasma lipids at 300 and 1000 mg/kg/day. Ashitaba-related pathology included a dose-related male rat-specific alpha 2-urinary globulin nephropathy at 100, 300, and 1000 mg/kg/day and jejunal lymphangiectasia in both sexes at 1000 mg/kg/day. All other study parameters and histopathological changes were incidental or not of toxicological concern. Based on these studies ashitaba chalcone powder is not genotoxic with a NOAEL of 300 mg/kg in male and female rats.

  6. [Toxicological evaluation in the childhood]. (United States)

    Arroyo, Amparo; Rodrigo, Carlos; Marrón, M Teresa


    Intoxications in infancy require urgent medical treatment within national health systems. In our country they represent 0.3% of paediatric urgencies. Most of them are accidental intoxications but is not infrequent to find some related to child abuse or to suicidal intentions, especially in adolescence. The objectives of the study are to evaluate both clinical health care and medical legal aspects in intoxications in infancy. Medical assistance is described and it includes clinical diagnosis, typology of the more common toxics, percentages and referral to social work and emergency care equipment units of the Ministry of Social Welfare and the Department of Health or, where appropriate, directly to prosecutors and courts for their intervention. In cases of detection of alcohol, drugs or medication in infants, the importance of the correct interpretation of the results of toxicological findings is discussed. Several studies for the interpretation of results concerning the detection of these toxics are reported. Both legal aspects and the forensic medical opinion are assessed. The findings will be analysed by the judicial authority in order to circumscribe responsibilities or to take appropriate decisions concerning the protection of infants' interests. In conclusion intoxication in infancy can lead to legal proceedings requiring specific actions for their protection. Both physicians and hospitals must comply with the legal requirement of the submission to the court of judicial parties. On the other hand, this information is an interesting step toward reinforcing public health surveillance.

  7. [Cosmetic colorants. Toxicology and regulation]. (United States)

    Platzek, T; Krätke, R; Klein, G; Schulz, C


    Some recent publications raised concern over a possible link between hair dye use and the incidence of bladder tumours in a Californian population. The Scientific Committee for Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) demanded the toxicological testing of all hair dyes used in Europe to exclude any risk. The EU commission initiated corresponding measures. Only safe hair dyes will be included on a positive list while all other hair dyes will be banned. The hair dye lawsone--the dyeing ingredient of henna--was evaluated by the SCCNFP as genotoxic but the BfR came to another conclusion. The regulation of both lawsone and henna remains an open question. Furthermore, some cosmetic colorants were critically discussed. The azo dyes CI 12150, CI 26100, CI 27290 and CI 20170 are allowed for use in cosmetics. On cleavage they form the carcinogenic aromatic amines o-anisidine, 4-aminoazobenzene and 2,4-xylidine, respectively. For three of these dyes the cleavage by human skin bacteria in vitro to the respective arylamine was shown experimentally. Further problems may arise from colorants used for tattoos and permanent makeup. These products up to now are not subject to legislation and there are no regulatory stipulations with respect to health safety and purity for colorants used for these purposes.

  8. Toxicologically relevant phthalates in food. (United States)

    Kappenstein, Oliver; Vieth, Bärbel; Luch, Andreas; Pfaff, Karla


    Various phthalates have been detected in a wide range of food products such as milk, dietary products, fat-enriched food, meat, fish, sea food, beverages, grains, and vegetables as well as in breast milk. Here we present an overview on toxicologically considerable phthalate levels in food reported in the literature. The most common phthalates detected are di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP). Milk analyses demonstrate that background levels in unprocessed milk are usually low. However, during processing the phthalate contents may significantly increase due to migration from plastic materials in contact with food. Among dietary products fat-enriched food such as cheese and cream were identified with highest levels of DEHP. Plasticized PVC from tubes, conveyor belts, or disposable gloves used in food processing is an important source for contamination of food, especially of fatty food. Paper and cardboard packaging made from recycled fibers are another important source of contamination. In addition, gaskets used in metal lids for glass jars have been identified as possible source for the contamination of foodstuffs with phthalates. The highest concentrations of DEHP reported (>900 mg kg(-1)) were detected in food of high fat content stored in such glass jars. Beyond classical food, DEHP and DnBP were identified in human breast milk samples as the main phthalate contaminants. Phthalate monoesters and some oxidative metabolites were also quantified in breast milk.

  9. [Modern toxicology of magnetic nanomaterials]. (United States)

    Cywińska, Monika A; Grudziński, Ireneusz P


    Current advances in nanobiotechnology have led to the development of new field of nanomedicine, which includes many applications of nano(bio)materials for both diagnostic and therapeutic purposes (theranostics). Major expectations and challenges are on bioengineered magnetic nanoparticles when their come to delivering drug compounds, especially to targeting anticancer drugs to specific molecular endpoints in cancer therapy. The unique physicochemical properties of these nanoparticles offer great promise in modern cancer nanomedicine to provide new technological breakthroughs, such as guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cancer cell tracking and molecular magnetic resonance imaging. Along with the expanding interest in bio-engineered magnetic nanoproducts their potential toxicity has become one of the major concerns. To date, a number of recent scientific evidences suggest that certain properties of magnetic nanoparticles (e.g., enhanced reactive area, ability to cross cell membranes, resistance to biodegradation) may amplify their cytotoxic potential relative to bulk non-nanoscale counterparts. In other words, safety assessment developed for ordinary magnetic materials may be of limited use in determining the health and environmental risks of the novel bio-engineered magnetic nanoproducts. In the present paper we discuss the main directions of research conducted to assess the toxicity of magnetic nanocompounds in experimental in vitro and in vivo models, pointing to the key issues concerning the toxicological analysis of magnetic nanomaterials. In addition new research directions of nanotoxicological studies elucidating the importance of developing alternative methods for testing magnetic nano(bio)products are also presented.

  10. Introduction: biomarkers in neurodevelopment toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Needleman, H.L.


    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  11. Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology

    DEFF Research Database (Denmark)

    Grandjean, P


    existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology......A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other...... being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published...

  12. Non-precautionary aspects of toxicology. (United States)

    Grandjean, Philippe


    Empirical studies in toxicology aim at deciphering complex causal relationships, especially in regard to human disease etiologies. Several scientific traditions limit the usefulness of documentation from current toxicological research, in regard to decision-making based on the precautionary principle. Among non-precautionary aspects of toxicology are the focus on simplified model systems and the effects of single hazards, one by one. Thus, less attention is paid to sources of variability and uncertainty, including individual susceptibility, impacts of mixed and variable exposures, susceptible life-stages, and vulnerable communities. In emphasizing the need for confirmatory evidence, toxicology tends to penalize false positives more than false negatives. An important source of uncertainty is measurement error that results in misclassification, especially in regard to exposure assessment. Standard statistical analysis assumes that the exposure is measured without error, and imprecisions will usually result in an underestimation of the dose-effect relationship. In testing whether an effect could be considered a possible result of natural variability, a 5% limit for "statistical significance" is usually applied, even though it may rule out many findings of causal associations, simply because the study was too small (and thus lacked statistical power) or because some imprecision or limited sensitivity of the parameters precluded a more definitive observation. These limitations may be aggravated when toxicology is influenced by vested interests. Because current toxicology overlooks the important goal of achieving a better characterization of uncertainties and their implications, research approaches should be revised and strengthened to counteract the innate ideological biases, thereby supporting our confidence in using toxicology as a main source of documentation and in using the precautionary principle as a decision procedure in the public policy arena.

  13. Reproductive toxicological study on epristeride

    Institute of Scientific and Technical Information of China (English)

    SunZY; ZhuY


    Benign protate hyperplasia (BPH) is a common disease in older men.Epristeride is an uncompetitive inhibitor of steroid 5α-reductase,the enzyme that converts testosterone to dihydrotestosterone (DHT),and has been shown to retard the growth of hyperplastic prostates.The study included the toxicological effects of epristeride on prostate,vas deferens and sperm.The results were listed below.(1)The 180 days toxicity of epristeride (100mg·kg-1) on interstitial cells of Beagle dog tests and DNA in prostatic epithelial cells couldn't reverse during 60 days vonvalescence,and that the DHT and prostate specific antigen (PSA) level in the gland,the volume of the grland,glandular epithelial cell height and acinar luminal area could reverse to normal during the same convalescence.(2)It was demonstrated that an apoptosis of vas deferens epithelial cell of SD rat was observed at the concentration of 0.3 and 1.0nmol·L-1 epristeride in vitro.The results of PCR showed the exkpression of bcl-2 on vas deferens epithelial cells treated or untreated with epristeride,but the sequence of bcl-2 did not altered.(3)Motility and motile rate of sperm of rat,dog and human in vitro were videotaped and analyzed with computer-assisted sperm anaysis(CASA) system after 1h and 2h incubation.MOT(the percentage of motile sperm) of Beagle dog sperm were significantly reduced after treated with 0.6,6 and 60μmol·L-1 epristeride,respectively,but no significant change occurred in SD rat and human at the same concertations of epristeride.Is a word,epristeride is a better drug against BPH though there are much reproductive toxicity.

  14. Application of mass spectrometry to hair analysis for forensic toxicological investigations. (United States)

    Vincenti, Marco; Salomone, Alberto; Gerace, Enrico; Pirro, Valentina


    The increasing role of hair analysis in forensic toxicological investigations principally owes to recent improvements of mass spectrometric instrumentation. Research achievements during the last 6 years in this distinctive application area of analytical toxicology are reviewed. The earlier state of the art of hair analysis was comprehensively covered by a dedicated book (Kintz, 2007a. Analytical and practical aspects of drug testing in hair. Boca Raton: CRC Press and Taylor & Francis, 382 p) that represents key reference of the present overview. Whereas the traditional organization of analytical methods in forensic toxicology divided target substances into quite homogeneous groups of drugs, with similar structures and chemical properties, the current approach often takes advantage of the rapid expansion of multiclass and multiresidue analytical procedures; the latter is made possible by the fast operation and extreme sensitivity of modern mass spectrometers. This change in the strategy of toxicological analysis is reflected in the presentation of the recent literature material, which is mostly based on a fit-for-purpose logic. Thus, general screening of unknown substances is applied in diverse forensic contexts than drugs of abuse testing, and different instrumentation (triple quadrupoles, time-of-flight analyzers, linear and orbital traps) is utilized to optimally cope with the scope. Other key issues of modern toxicology, such as cost reduction and high sample throughput, are discussed with reference to procedural and instrumental alternatives.

  15. Clinical toxicology: clinical science to public health. (United States)

    Bateman, D N


    1. The aims of the present paper are to: (i) review progress in clinical toxicology over the past 40 years and to place it in the context of modern health care by describing its development; and (ii) illustrate the use of clinical toxicology data from Scotland, in particular, as a tool for informing clinical care and public health policy with respect to drugs. 2. A historical literature review was conducted with amalgamation and comparison of a series of published and unpublished clinical toxicology datasets from NPIS Edinburgh and other sources. 3. Clinical databases within poisons treatment centres offer an important method of collecting data on the clinical effects of drugs in overdose. These data can be used to increase knowledge on drug toxicity mechanisms that inform licensing decisions, contribute to evidence-based care and clinical management. Combination of this material with national morbidity datasets provides another valuable approach that can inform public health prevention strategies. 4. In conclusion, clinical toxicology datasets offer clinical pharmacologists a new study area. Clinical toxicology treatment units and poisons information services offer an important health resource.

  16. Lupinus mutabilis: Composition, Uses, Toxicology, and Debittering. (United States)

    Carvajal-Larenas, F E; Linnemann, A R; Nout, M J R; Koziol, M; van Boekel, M A J S


    Lupinus mutabilis has protein (32.0-52.6 g/100 g dry weight) and lipid (13.0-24.6 g/100 g dry weight) contents similar to soya bean (Glycine max). The Ω3, Ω6, and Ω9 contents are 1.9-3.0, 26.5-39.6, and 41.2-56.2 g/100 g lipid, respectively. Lupins can be used to fortify the protein content of pasta, bread, biscuits, salads, hamburgers, sausages, and can substitute milk and soya bean. Specific lupin protein concentrates or isolates display protein solubility (>90%), water-absorption capacity (4.5 g/g dry weight), oil-absorption capacity (3.98 g/g), emulsifying capacity (2000 mL of oil/g), emulsifying stability (100%, 60 hours), foaming capacity (2083%), foaming stability (78.8%, 36 hours), and least gelation concentration (6%), which are of industrial interest. Lupins contain bitter alkaloids. Preliminary studies on their toxicity suggest as lethal acute dose for infants and children 10 mg/kg bw and for adults 25 mg/kg bw. However, alkaloids can also have medical use for their hypocholesterolemic, antiarrhythmic, and immunosuppressive activity. Bitter lupins can be detoxified by biological, chemical, or aqueous processes. The shortest debittering process requires one hour. This review presents the nutritional composition of lupins, their uses (as food, medicine, and functional protein isolates), toxicology, and debittering process scenarios. It critically evaluates the data, infers conclusions, and makes suggestions for future research.

  17. Perlite toxicology and epidemiology--a review. (United States)

    Maxim, L Daniel; Niebo, Ron; McConnell, Ernest E


    Perlite is a generic name for an amorphous volcanic alumina-silicate rock that expands by a factor of 4-20 when rapidly heated to 1400-1800 °F (760-980 °C). Both the ore and the expanded product have extensive and widespread commercial applications. Limited data on the toxicology of perlite in animal studies indicate that the LD₅₀ (oral ingestion) is more than 10 g/kg and, from a chronic inhalation study in guinea pigs and rats, that the NOAEL for the inhalation pathway is 226 mg/m³. Health surveillance studies of workers in US perlite mines and expansion plants (including some workers exposed to levels greater than prevailing occupational exposure limits (OELs) conducted over 20 years indicate that the respiratory health of workers is not adversely affected. Studies in Turkish mines and expanding plants had generally similar results, but are more difficult to interpret because of high smoking rates in these populations. A recent mortality study of permanent residents of the island of Milos (Greece) exposed to various mining dusts (including perlite) resulted in non-significant increases in standard mortality ratios for pneumonia and chronic obstructive pulmonary disease (COPD), whereas a companion morbidity study revealed elevated odds ratios for allergic rhinitis, pneumonia, and COPD when compared to another industrial area of Greece. Residents were exposed to other mining dusts and other possible causes or contributing factors and no ambient monitoring data were presented so it is not possible to use this study for risk calculations of perlite-exposed populations. Perlite is regulated as a "nuisance dust" in most countries.

  18. The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21st Century (United States)

    Claxton, Larry D.; de A. Umbuzeiro, Gisela; DeMarini, David M.


    Objectives According to the 2007 National Research Council report Toxicology for the Twenty-First Century, modern methods (e.g., “omics,” in vitro assays, high-throughput testing, computational methods) will lead to the emergence of a new approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has been central to the field of genetic toxicology since the 1970s. Here we document the paradigm shifts engendered by the assay, the validation and applications of the assay, and how the assay is a model for future in vitro toxicology assays. Data sources We searched PubMed, Scopus, and Web of Knowledge using key words relevant to the Salmonella assay and additional genotoxicity assays. Data extraction We merged the citations, removing duplicates, and categorized the papers by year and topic. Data synthesis The Salmonella assay led to two paradigm shifts: that some carcinogens were mutagens and that some environmental samples (e.g., air, water, soil, food, combustion emissions) were mutagenic. Although there are > 10,000 publications on the Salmonella assay, covering tens of thousands of agents, data on even more agents probably exist in unpublished form, largely as proprietary studies by industry. The Salmonella assay is a model for the development of 21st century in vitro toxicology assays in terms of the establishment of standard procedures, ability to test various agents, transferability across laboratories, validation and testing, and structure–activity analysis. Conclusions Similar to a stethoscope as a first-line, inexpensive tool in medicine, the Salmonella assay can serve a similar, indispensable role in the foreseeable future of 21st century toxicology. PMID:20682480

  19. Prospects for applying synthetic biology to toxicology

    DEFF Research Database (Denmark)

    Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.


    The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

  20. Comparison of toxicological and radiological aspects of K basins sludge

    Energy Technology Data Exchange (ETDEWEB)



    The composition of various K Basins sludge is evaluated for its toxicological and radiological impacts downwind from accidents. It is shown that the radiological risk evaluation guidelines are always more limiting than the toxicological risk evaluation guidelines.

  1. Risk assessment and toxicology databases for health effects assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lu, P.Y.; Wassom, J.S. [Oak Ridge National Laboratory, TN (United States)


    Scientific and technological developments bring unprecedented stress to our environment. Society has to predict the results of potential health risks from technologically based actions that may have serious, far-reaching consequences. The potential for error in making such predictions or assessment is great and multiplies with the increasing size and complexity of the problem being studied. Because of this, the availability and use of reliable data is the key to any successful forecasting effort. Scientific research and development generate new data and information. Much of the scientific data being produced daily is stored in computers for subsequent analysis. This situation provides both an invaluable resource and an enormous challenge. With large amounts of government funds being devoted to health and environmental research programs and with maintenance of our living environment at stake, we must make maximum use of the resulting data to forecast and avert catastrophic effects. Along with the readily available. The most efficient means of obtaining the data necessary for assessing the health effects of chemicals is to utilize applications include the toxicology databases and information files developed at ORNL. To make most efficient use of the data/information that has already been prepared, attention and resources should be directed toward projects that meticulously evaluate the available data/information and create specialized peer-reviewed value-added databases. Such projects include the National Library of Medicine`s Hazardous Substances Data Bank, and the U.S. Air Force Installation Restoration Toxicology Guide. These and similar value-added toxicology databases were developed at ORNL and are being maintained and updated. These databases and supporting information files, as well as some data evaluation techniques are discussed in this paper with special focus on how they are used to assess potential health effects of environmental agents. 19 refs., 5 tabs.

  2. Toxicological benchmarks for wildlife: 1996 Revision

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E.; Opresko, D.M.; Suter, G.W., II


    The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets.

  3. [Forensic toxicology, a growing scientific discipline]. (United States)

    Augsburger, Marc; Staub, Christian


    Forensic toxicology has to bring evidence of substances that could have been involved directly or indirectly in the cause of death or that could influence the behaviour of somebody. The increase of the consumption of illegal and legal drugs in modern societies during last decades gave a boost to forensic toxicology. Moreover, improvement with analytical technology gave tools with high degrees of sensitivity and specificity for the screening and quantification of a large amount of substances in various biological specimens, even with very low concentration resulting of a single dose of medication.

  4. Statistical studies in genetic toxicology: a perspective from the U.S. National Toxicology Program.


    Margolin, B H


    This paper surveys recent, as yet unpublished, statistical studies arising from research in genetic toxicology within the U.S. National Toxicology Program (NTP). These studies all involve analyses of data from Ames Salmonella/microsome mutagenicity tests, but the statistical methodologies are broadly applicable. Three issues are addressed: First, what is a tenable sampling model for Ames test data, and how does one best test the adequacy of the Poisson sampling assumption? Second, given that ...

  5. The Toxicology Education Summit: Building the Future of Toxicology Through Education



    Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collabor...

  6. Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology. (United States)

    Grandjean, P


    A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication.

  7. A prospective toxicology analysis in alcoholics

    DEFF Research Database (Denmark)

    Thomsen, Jørgen Lange; Simonsen, Kirsten Wiese; Felby, Søren


    A prospective and comprehensive investigation was done on 73 medico–legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis...... than the exception in deaths in alcoholics....


    Scientists from ten countries presented papers at the Fifth International Symposium on Fish Physiology, Toxicology, and Water Quality, which was held on the campus of the city University of Hong Kong on November 10-13, 1998. These Proceedings include 23 papers presented in sessi...

  9. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.


    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  10. Toward an evidence-based toxicology. (United States)

    Hoffmann, S; Hartung, T


    The increasing demands on toxicology of large-scale risk assessment programmes for chemicals and emerging or expanding areas of chemical use suggest it is timely to review the toxicological toolbox. Like in clinical medicine, where an evidence-based medicine (EBM) is critically reviewing traditional approaches, toxicology has the opportunity to reshape and enlarge its methodology and approaches on the basis of compounded scientific knowledge. Such revision would have to be based on structured reviews of current practice, ie, assessment of test performance characteristics, mechanistic understanding, extended quality assurance, formal validation and the use of integrated testing strategies. This form of revision could optimize the balance between safety, costs and animal welfare, explicitly stating and, where possible, quantifying uncertainties. After a self-critical reassessment of current practices and evaluation of the thus generated information, such an evidence-based toxicology (EBT) promises to make better use of resources and to increase the quality of results, facilitating their interpretation. It shall open up hazard and also risk assessments to new technologies, flexibly accommodating current and future mechanistic understanding. An EBT will be better prepared to answer the continuously growing safety demands of modern societies.

  11. Research Models in Developmental Behavioral Toxicology. (United States)

    Dietrich, Kim N.; Pearson, Douglas T.

    Developmental models currently used by child behavioral toxicologists and teratologists are inadequate to address current issues in these fields. Both child behavioral teratology and toxicology scientifically study the impact of exposure to toxic agents on behavior development: teratology focuses on prenatal exposure and postnatal behavior…


    Twenty-one participants from Europe, North America and China convened in Chongqing, China, October 12-14, 2005, for the Eighth International Symposium in Fish Physiology, Toxicology and Water Quality. The subject of the meeting was "Hypoxia in vertebrates: Comparisons of terrestr...

  13. An argument for the chicken embryo as a model for the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs)

    Energy Technology Data Exchange (ETDEWEB)

    Henshel, D.S. [Indiana Univ., Bloomington, IN (United States). School of Public and Environmental Affairs


    This article will present the argument that the chicken embryo is especially appropriate as an animal model for studying the mechanism of the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs). The PHAHs are a group of toxicologically related compounds including, in part, the polychlorinated dibenzodioxins, dibenzofurans and biphenyls. The chicken (Gallus gallus) embryo is relatively sensitive to the toxicological effects of the PHAHs being approximately two orders of magnitude more sensitive than the mature bird. The chicken embryo has been used to demonstrate general toxicological teratogeneicity, hepatotoxicity and neurotoxicity. Many of these effects, or analogous effects, have also been observed in mammals and fish. Thus, most animals appear to respond to the PHAHs with a similar toxicological profile, indicating that many of the biomarkers used for the PHAHs are valid across a number of species, including the chicken. Furthermore, the chicken embryo is relatively inexpensive to use for toxicity testing. In addition, all effects detected are due to direct effects on the embryo and are not complicated by maternal interactions. In short, for sensitivity, ease of use, cost and applicability of results to other animals, the chicken embryo is an excellent animal model for evaluation of the mechanism underlying the developmental toxicological effects of the PHAHs.

  14. Comparison and Research of Cinnabar, Zhusha Anshen Wan and HgS on Rat Absorption and Distribution%朱砂、朱砂安神丸及氯化汞在小鼠体内吸收、分布对比

    Institute of Scientific and Technical Information of China (English)

    付中祥; 杨虹; 陈秀芬; 刘杰; 时京珍


    目的:对比研究朱砂、朱砂安神丸及氯化汞在小鼠体内的吸收、分布规律.方法:昆明种小鼠180只,分为正常组、朱砂临床剂量组(0.2 g·kg-1,ig)、朱砂高剂量组(11.2 g·kg-1,ig)、朱砂安神丸组(2 g·kg-1,ig)、氯化汞组(0.07 g·kg-1,ig),每组小鼠在给药1,2,4,8,16,24 h后各取6只鼠的血、脑、肝、肾,原子荧光光度法检测汞含量.结果:朱砂临床剂量组和朱砂安神丸组体内最大血药浓度及各时间点血药浓度与氯化汞组相比具有明显差异(P<0.05);朱砂临床剂量组与朱砂安神丸组各时间点肝、肾组织中汞含量与氯化汞组有显著性差异(p< 0.05);朱砂临床剂量组和朱砂高剂量组在血液和组织中汞含量亦有显著性差异(P<0.05);朱砂高剂量组脑中汞含量最高.结论:临床剂量的朱砂、朱砂安神丸的汞吸收及各组织的汞含量均明显低于高剂量的朱砂和氯化汞.%Objective: To study the regulation of Cinnabar, Zhusha Anshen wan (ZSASW) and HgS on absorption and distribution in mice. Method: Oral gavage was given to Kunming mice with cinnabar (0. 2 g · kg-1), high dose of cinnabar (11.2 g·kg-1), ZSASW (2g·kg-1) , HgS (0.07 g·kg-1) or saline daily for 1, 2, 4, 8, 16, 24 hours, mercury accumulation in blood, liver, kidney and brain was determined by atomic fluoresence detector. Result: In comparison, the maximal serum concentration and serum concentration in each time of cinnabar clinical dose group and ZSASW group have obvious difference with the HgCl2 group. The mercury accumulation in liver and kidney in each time of clinical dose group and ZSASW group have obvious difference with the HgCl2 group. The mercury accumulation in blood and organs also had obvious difference between cinnabar clinical dose group and high dose group, and the high dose has the maximal accumulation in brain. Conclusion: Both cinnabar clinical dose group and ZSASW group have obvious difference with cinnabar high

  15. Application of PCR techniques in toxicology

    Directory of Open Access Journals (Sweden)

    Maja Kazubek


    Full Text Available Molecular biology techniques have become widely used in toxicology, leading to the creation of a new science – molecular toxicology. The goal of molecular toxicology is to detect and study the changes induced by xenobiotics at the molecular level. The research scope of molecular toxicology includes examination of mutations in genomic DNA, differences in mRNA expression and study of genotype indicating individual sensitivity.The processes of activation and detoxification of xenobiotics, drugs and environmental carcinogens involve several enzymes (xenobiotic-metabolizing enzymes – XMEs. Most of the chemicals entering our bodies, regardless of whether they have medical, pathogenic or carcinogenic properties, require metabolic activation by phase I enzymes (cytochrome P-450. In the next process the phase I products are usually detoxified by phase II enzymes, mainly by epoxide hydrolase, glutathione transferase, N-acetyltransferase or sulfotransferase. PCR techniques allow precise study of the effects of xenobiotics on cells and tissues by examining the level of activation of genes coding for phase I and II enzymes, or by testing the activity of other elements of the transcriptome. Studies of sensitivity of individual cells or tissues based on examination of mutation or gene polymorphism presence are also relevant.This paper presents the possibility of using various PCR techniques in toxicology and especially in the study of genetically determined sensitivity to xenobiotics. It also covers the possibilities of applying qPCR and qRT-PCR methods in the search for exposure biomarkers with particular emphasis on individual cytochrome P450 isoforms. Furthermore, it provides information about the possibility of implementing the differential display technique in the identification of new genes activated by toxic agents.

  16. Distance learning in toxicology: Australia's RMIT program. (United States)

    Ahokas, Jorma; Donohue, Diana; Rix, Colin; Wright, Paul


    RMIT University was the first to offer a comprehensive Masters of Toxicology in Australasia 19 years ago. In 2001 the program was transformed into two stages, leading to a Graduate Diploma and Master of Applied Science in Toxicology. Now, these programs are fully online and suitable for graduates living and working anywhere in the world. The modular distance-learning courses are specifically designed to equip students with essential skills for entering fields such as chemical and drug evaluation; risk assessment of chemicals in the workplace; environmental and food toxicology. RMIT's online course delivery system has made it possible to deliver the toxicology programs, both nationally and internationally. The learning material and interactive activities (tests and quizzes, discussion boards, chat sessions) use Blackboard and WebBoard, each with a different educational function. Students log in to a Learning Hub to access their courses. The Learning Hub enables students to extend their learning beyond the classroom to the home, workplace, library and any other location with Internet access. The teaching staff log in to the Learning Hub to maintain and administer the online programs and courses which they have developed and/or which they teach. The Learning Hub is also a communication tool for students and staff, providing access to email, a diary and announcements. The early experience of delivering a full toxicology program online is very positive. However this mode of teaching continues to present many interesting technical, educational and cultural challenges, including: the design and presentation of the material; copyright issues; internationalization of content; interactive participation; and the assessment procedures.

  17. Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology. (United States)

    Gundert-Remy, U; Barth, H; Bürkle, A; Degen, G H; Landsiedel, R


    The paper describes the importance of toxicology as a discipline, its past achievements, current scientific challenges, and future development. Toxicological expertise is instrumental in the reduction of human health risks arising from chemicals and drugs. Toxicological assessment is needed to evaluate evidence and arguments, whether or not there is a scientific base for concern. The immense success already achieved by toxicological work is exemplified by reduced pollution of air, soil, water, and safer working places. Predominantly predictive toxicological testing is derived from the findings to assess risks to humans and the environment. Assessment of the adversity of molecular effects (including epigenetic effects), the effects of mixtures, and integration of exposure and biokinetics into in vitro testing are emerging challenges for toxicology. Toxicology is a translational science with its base in fundamental science. Academic institutions play an essential part by providing scientific innovation and education of young scientists.

  18. Similarity transformations of MAPs

    Directory of Open Access Journals (Sweden)

    Andersen Allan T.


    Full Text Available We introduce the notion of similar Markovian Arrival Processes (MAPs and show that the event stationary point processes related to two similar MAPs are stochastically equivalent. This holds true for the time stationary point processes too. We show that several well known stochastical equivalences as e.g. that between the H 2 renewal process and the Interrupted Poisson Process (IPP can be expressed by the similarity transformations of MAPs. In the appendix the valid region of similarity transformations for two-state MAPs is characterized.

  19. Toxicology in Asia--Past, present, and future. (United States)

    Satoh, T


    The Asian Society of Toxicology (ASIATOX), which consists of the seven national toxicology member societies of Japan, Korea, China, Taiwan, Thailand, Singapore, and Iran, now boasts of more than 3,000 members from a variety of industries, academia, and regulatory organizations. ASIATOX congresses are spaced three years apart and rotated among the member societies. In 1995, ASIATOX joined the International Union of Toxicology (IUTOX) as a regional society, and now serves as the scientific voice of toxicology in Asia under the IUTOX umbrella. Since its inauguration, the society has worked diligently to handle matters deemed essential to promoting the vision set fourth by its founders. Future perspectives of ASIATOX include the establishment of education and training programs, and the certification and accreditation of toxicologists. As the leading voice of toxicology in Asia, the society seeks to extend knowledge of toxicological issues to developing nations in Asia based on the following missions and goals: (1) to provide leadership as a worldwide scientific organization that objectively addresses global issues involving the toxicological sciences, (2) to broaden the geographical base of toxicology as a discipline and profession to all countries of the world, and (3) to pursue capacity building in toxicology, particularly in developing countries, while utilizing its global perspective and network to contribute to the enhancement of toxicology education and the career development of young toxicologists.

  20. The sensitivity of metabolomics versus classical regulatory toxicology from a NOAEL perspective. (United States)

    van Ravenzwaay, B; Montoya, G A; Fabian, E; Herold, M; Krennrich, G; Looser, R; Mellert, W; Peter, E; Strauss, V; Walk, T; Kamp, H


    The identification of the no observed adverse effect level (NOAEL) is the key regulatory outcome of toxicity studies. With the introduction of "omics" technologies into toxicological research, the question arises as to how sensitive these technologies are relative to classical regulatory toxicity parameters. BASF SE and metanomics developed the in vivo metabolome database MetaMap®Tox containing metabolome data for more than 500 reference compounds. For several years metabolome analysis has been routinely performed in regulatory toxicity studies (REACH mandated testing or new compound development), mostly in the context of 28 day studies in rats (OECD 407 guideline). For those chemicals for which a toxicological NOAEL level was obtained at either high or mid-dose level, we evaluated the associated metabolome to investigate the sensitivity of metabolomics versus classical toxicology with respect to the NOAEL. For the definition of a metabolomics NOAEL the ECETOC criteria (ECETOC, 2007) were used. In this context we evaluated 104 cases. Comparable sensitivity was noted in 75% of the cases, increased sensitivity of metabolomics in 8%, and decreased sensitivity in 18% of the cases. In conclusion, these data suggest that metabolomics profiling has a similar sensitivity to the classical toxicological study (e.g. OECD 407) design.

  1. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina


    In data science, there are important parameters that affect the accuracy of the algorithms used. Some of these parameters are: the type of data objects, the membership assignments, and distance or similarity functions. This paper discusses similarity functions as fundamental elements in membership...

  2. Clustering by Pattern Similarity

    Institute of Scientific and Technical Information of China (English)

    Hai-xun Wang; Jian Pei


    The task of clustering is to identify classes of similar objects among a set of objects. The definition of similarity varies from one clustering model to another. However, in most of these models the concept of similarity is often based on such metrics as Manhattan distance, Euclidean distance or other Lp distances. In other words, similar objects must have close values in at least a set of dimensions. In this paper, we explore a more general type of similarity. Under the pCluster model we proposed, two objects are similar if they exhibit a coherent pattern on a subset of dimensions. The new similarity concept models a wide range of applications. For instance, in DNA microarray analysis, the expression levels of two genes may rise and fall synchronously in response to a set of environmental stimuli. Although the magnitude of their expression levels may not be close, the patterns they exhibit can be very much alike. Discovery of such clusters of genes is essential in revealing significant connections in gene regulatory networks. E-commerce applications, such as collaborative filtering, can also benefit from the new model, because it is able to capture not only the closeness of values of certain leading indicators but also the closeness of (purchasing, browsing, etc.) patterns exhibited by the customers. In addition to the novel similarity model, this paper also introduces an effective and efficient algorithm to detect such clusters, and we perform tests on several real and synthetic data sets to show its performance.

  3. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS


    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the formatio

  4. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina


    In data science, there are important parameters that affect the accuracy of the algorithms used. Some of these parameters are: the type of data objects, the membership assignments, and distance or similarity functions. This paper discusses similarity functions as fundamental elements in membership...... assignments. The paper introduces Weighted Feature Distance (WFD), and Prioritized Weighted Feature Distance (PWFD), two new distance functions that take into account the diversity in feature spaces. WFD functions perform better in supervised and unsupervised methods by comparing data objects on their feature...... spaces, in addition to their similarity in the vector space. Prioritized Weighted Feature Distance (PWFD) works similarly as WFD, but provides the ability to give priorities to desirable features. The accuracy of the proposed functions are compared with other similarity functions on several data sets...

  5. Current developments in toxicological research on arsenic. (United States)

    Bolt, Hermann M


    There is a plethora of recent publications on all aspects relevant to the toxicology of arsenic (As). Over centuries exposures to arsenic continue to be a major public health problem in many countries. In particular, the occurrence of high As concentrations in groundwater of Southeast Asia receives now much attention. Therefore, arsenic is a high-priority matter for toxicological research. Key exposure to As are (traditional) medicines, combustion of As-rich coal, presence of As in groundwater, and pollution due to mining activities. As-induced cardiovascular disorders and carcinogenesis present themselves as a major research focus. The high priority of this issue is now recognized politically in a number of countries, research funds have been made available. Also experimental research on toxicokinetics and toxicodynamics and on modes of toxic action is moving very rapidly. The matter is of high regulatory concern, and effective preventive measures are required in a number of countries.

  6. Toxicology of Nanomaterials: Permanent interactive learning

    Directory of Open Access Journals (Sweden)

    Castranova Vince


    Full Text Available Abstract Particle and Fibre Toxicology wants to play a decisive role in a time where particle research is challenged and driven by the developments and applications of nanomaterials. This aim is not merely quantitative in publishing a given number of papers on nanomaterials, but also qualitatively since the field of nanotoxicology is rapidly emerging and benchmarks for good science are needed. Since then a number of things have happened that merit further analysis. The interactive learning issue is best shown by report and communications on the toxicology of multi-wall carbon nanotubes (CNT. A special workshop on the CNT has now been organized twice in Nagano (Japan and this editorial contains a summary of the most important outcomes. Finally, we take the opportunity discuss some recent reports from the nanotech literature, and more specifically a Chinese study that claims severe consequences of nanoparticle exposure.

  7. Toxicogenomic approaches in developmental toxicology testing. (United States)

    Robinson, Joshua F; Piersma, Aldert H


    The emergence of toxicogenomic applications provides new tools to characterize, classify, and potentially predict teratogens. However, due to the vast number of experimental and statistical procedural steps, toxicogenomic studies are challenging. Here, we guide researchers through the basic framework of conducting toxicogenomic investigations in the field of developmental toxicology, providing examples of biological and technical factors that may influence response and interpretation. Furthermore, we review current, diverse applications of toxicogenomic-based approaches in teratology testing, including exposure-response characterization (dose and duration), chemical classification studies, and cross-model comparisons study designs. This review is intended to guide scientists through the challenging and complex structure of conducting toxicogenomic analyses, while considering the many applications of using toxicogenomics in study designs and the future of these types of "omics" approaches in developmental toxicology.

  8. Avian models in teratology and developmental toxicology. (United States)

    Smith, Susan M; Flentke, George R; Garic, Ana


    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

  9. The toxicology expert: what is required? (United States)

    Bass, R; Vamvakas, S


    In contrast to many traditional professions, toxicologists form a group with very different backgrounds, i.e. they may have been educated to become medical doctors, veterinarians, pharmacists, chemists, biochemists or biologists. Professional competence can be gained in different ways by candidate toxicologists, and according to the European system, their training can be divided into two parts. (i) Theoretical training on several topics such as analytical methods, organ toxicity, mutagenicity, carcinogenicity can be obtained by attending courses organised by the national societies of toxicology. (ii) Spending several years on active experimental work in the fields of modern toxicology (e.g. analytical methods, toxic and genotoxic mechanisms, reproductive toxicity) is necessary to develop the capability to design and carry out experimental studies and to evaluate one's own and other people's research results. Candidate toxicologists should learn to evaluate data with a strictly scientific 'plausibility above numbers' approach.

  10. Ethical Considerations for Perinatal Toxicology Screening. (United States)

    Kohsman, Mindy G


    Neonatal nurses frequently care for babies who have been exposed in utero to potentially harmful substances, both licit and illicit. The risks to the fetus from nicotine, marijuana, alcohol, and opiates are significant. Adverse effects from environmental factors may confound pharmacologic effects of substances. Nurses are called to shift the perception of substance use disorder from that of willful harm to the fetus to that of an opportunity to provide treatment assistance that can positively affect child health and development. Concerns for unethical practices in the toxicology screening of pregnant women and their babies by risk factors that are unproven or disproven are discussed, and three goals of toxicology screening based on the ethical principles of justice and beneficence are proposed. This article will help equip neonatal nurses to fulfill their professional responsibility to advocate for just screening and referral practices in their institutions and communities.

  11. Systems Toxicology: The Future of Risk Assessment. (United States)

    Sauer, John Michael; Hartung, Thomas; Leist, Marcel; Knudsen, Thomas B; Hoeng, Julia; Hayes, A Wallace


    Risk assessment, in the context of public health, is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. With increasing public health concern regarding the potential risks associated with chemical exposure, there is a need for more predictive and accurate approaches to risk assessment. Developing such an approach requires a mechanistic understanding of the process by which xenobiotic substances perturb biological systems and lead to toxicity. Supplementing the shortfalls of traditional risk assessment with mechanistic biological data has been widely discussed but not routinely implemented in the evaluation of chemical exposure. These mechanistic approaches to risk assessment have been generally referred to as systems toxicology. This Symposium Overview article summarizes 4 talks presented at the 35th Annual Meeting of the American College of Toxicology.

  12. Regulated necrosis and its implications in toxicology. (United States)

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi


    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology.

  13. Wind of Change Challenges Toxicological Regulators


    Tralau, Tewes; Riebeling, Christian; Pirow, Ralph; OELGESCHLÄGER, MICHAEL; Seiler, Andrea; Liebsch, Manfred; Luch, Andreas


    Background: In biomedical research, the past two decades have seen the advent of in vitro model systems based on stem cells, humanized cell lines, and engineered organotypic tissues, as well as numerous cellular assays based on primarily established tumor-derived cell lines and their genetically modified derivatives. Objective: There are high hopes that these systems might replace the need for animal testing in regulatory toxicology. However, despite increasing pressure in recent years to red...

  14. Mycotoxins: occurrence, toxicology, and exposure assessment. (United States)

    Marin, S; Ramos, A J; Cano-Sancho, G; Sanchis, V


    Mycotoxins are abiotic hazards produced by certain fungi that can grow on a variety of crops. Consequently, their prevalence in plant raw materials may be relatively high. The concentration of mycotoxins in finished products is usually lower than in raw materials. In this review, occurrence and toxicology of the main mycotoxins are summarised. Furthermore, methodological approaches for exposure assessment are described. Existing exposure assessments, both through contamination and consumption data and biomarkers of exposure, for the main mycotoxins are also discussed.

  15. Modern Instrumental Methods in Forensic Toxicology*



    This article reviews modern analytical instrumentation in forensic toxicology for identification and quantification of drugs and toxins in biological fluids and tissues. A brief description of the theory and inherent strengths and limitations of each methodology is included. The focus is on new technologies that address current analytical limitations. A goal of this review is to encourage innovations to improve our technological capabilities and to encourage use of these analytical techniques...

  16. Nature's chemicals and synthetic chemicals: comparative toxicology.


    Ames, B N; Profet, M; Gold, L S


    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in brocco...

  17. In vivo models for male reproductive toxicology. (United States)

    Tyl, Rochelle W


    In Vivo Models for Male Reproductive Toxicology (Rochelle W. Tyl, Research Triangle Institute, Research Triangle Park, North Carolina). Assessment of male reproductive function requires a specific set of evaluations of the various steps in successful mating from sperm production to copulation to fertilization to production of a viable litter. This unit outlines the measurements that are standard for determining the effects of treatment with toxicant on the reproductive capacity of male mice and rats.

  18. Toxicological benchmarks for wildlife: 1994 Revision

    Energy Technology Data Exchange (ETDEWEB)

    Opresko, D.M.; Sample, B.E.; Suter, G.W. II


    The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report.

  19. Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties

    Directory of Open Access Journals (Sweden)

    Monika Batke


    Full Text Available 1.AbstractInterest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g. the European Union´s Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine structural similarity with shared mechanisms of action. Substances with similar chemical structure and toxicological profile form candidate categories suitable for read-across. We combined two databases on repeated dose toxicity, RepDose database and ELINCS database to form a common database for the identification of categories. The resulting database contained physicochemical, structural and toxicological data, which were refined and curated for cluster analyses. We applied the Predictive Clustering Tree (PCT approach for clustering chemicals based on structural and on toxicological information to detect groups of chemicals with similar toxic profiles and pathways/mechanisms of toxicity. As many of the experimental toxicity values were not available, this data was imputed by predicting them with a multi-label classification method, prior to clustering. The clustering results were evaluated by assessing chemical and toxicological similarities with the aim of identifying clusters with a concordance between structural information and toxicity profiles/mechanisms. From these chosen clusters, seven were selected for a quantitative read-across, based on a small ratio of NOAEL of the members with the highest and the lowest NOAEL in the cluster (<5. We discuss

  20. Similar component analysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; WANG Xin; LI Junwei; CAO Xianguang


    A new unsupervised feature extraction method called similar component analysis (SCA) is proposed in this paper. SCA method has a self-aggregation property that the data objects will move towards each other to form clusters through SCA theoretically,which can reveal the inherent pattern of similarity hidden in the dataset. The inputs of SCA are just the pairwise similarities of the dataset,which makes it easier for time series analysis due to the variable length of the time series. Our experimental results on many problems have verified the effectiveness of SCA on some engineering application.

  1. Gender similarities and differences. (United States)

    Hyde, Janet Shibley


    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research.

  2. Alternative methods in toxicology: pre-validated and validated methods. (United States)

    Kandárová, Helena; Letašiová, Silvia


    The development of alternative methods to animal experimentation has progressed rapidly over the last 20 years. Today, in vitro and in silico methods have an important role in the hazard identification and assessment of toxicology profile of compounds. Advanced alternative methods and their combinations are also used for safety assessment of final products. Several alternative methods, which were scientifically validated and accepted by competent regulatory bodies, can be used for regulatory toxicology purposes, thus reducing or fully replacing living animals in toxicology experimentation. The acceptance of the alternative methods as valuable tools of modern toxicology has been recognized by regulators, including OECD, FDA and EPA.This paper provides a brief overview of the topic "alternative methods in toxicology" and focuses on pre-validated and validated alternative methods and their position in the modern toxicology.

  3. [Clinical toxicology of the Academy: yesterday, today and tomorrow]. (United States)

    Sofronov, G A; Khalimov, Iu Sh; Matveev, S Iu; Kuz'mich, V G; Fomichev, A V


    National toxicology school of the Kirov Military Medical Academy, demonstrates the unity of clinical and experimental approaches related to one purpose throughout its history--saving human life and health from exposure to toxic substances of chemical nature. For more than three centuries the russian science of toxicology has been steadily developing, often ahead of the world science. It helped to create the means of protection and develop methods of treatment for chemical lesions. Currently, toxicology departments of military field therapy and military toxicology and medical protection are actively involved in the current study of military medicine, restructuring policy to provide toxicological aid in the Armed Forces, the development and introduction of Innovative methods of diagnosis and treatment of victims of toxicological etiology.

  4. In silico toxicology for the pharmaceutical sciences. (United States)

    Valerio, Luis G


    The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

  5. Gordon Research Conference on Genetic Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Project Director Penelope Jeggo


    Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotoxic agents and to assess how individual genetic differences influence the response to genotoxic damage. In recent years, the importance of maintaining genomic stability has become increasingly recognized, in part by the realization that failure of the damage response mechanisms underlies many, if not all, cancer incidence. The importance of these mechanisms is also underscored by their remarkable conservation between species, allowing the study of simple organisms to provide significant input into our understanding of the underlying mechanisms. It has also become clear that the damage response mechanisms interface closely with other aspects of cellular metabolism including replication, transcription and cell cycle regulation. Moreover, defects in many of these mechanisms, as observed for example in ataxia telangiectasia patients, confer disorders with associated developmental abnormalities demonstrating their essential roles during growth and development. In short, while a decade ago, a study of the impact of DNA damage was seen as a compartmentalized area of cellular research, it is now appreciated to lie at the centre of an array of cellular responses of crucial importance to human health. Consequently, this has become a dynamic and rapidly advancing area of research. The Genetic Toxicology Gordon Research Conference is biannual with an evolving change in the emphasis of the meetings. From evaluating the nature of genotoxic chemicals, which lay at the centre of the early

  6. La toxicología en la Universidad de Sevilla


    IM Moreno; A. Jos; Pichardo, S.; Prieto, A.; Puerto, M.; AM Cameán


    La docencia del Área de Toxicología en la Universidad de Sevilla se desarrolla en la actualidad en dos titulaciones, Farmacia y Bioquímica. En los planes de estudios actuales la carga lectiva del Área viene dada por las asignaturas de Toxicología (asignatura troncal), y Toxicología Alimentaria (asignatura optativa) en la Licenciatura de Farmacia, y de Toxicología Molecular (asignatura optativa) en la Licenciatura de Bioquímica. Una vez aprobados por la Agencia Nacional de la Evaluación de la ...

  7. Compression-based Similarity

    CERN Document Server

    Vitanyi, Paul M B


    First we consider pair-wise distances for literal objects consisting of finite binary files. These files are taken to contain all of their meaning, like genomes or books. The distances are based on compression of the objects concerned, normalized, and can be viewed as similarity distances. Second, we consider pair-wise distances between names of objects, like "red" or "christianity." In this case the distances are based on searches of the Internet. Such a search can be performed by any search engine that returns aggregate page counts. We can extract a code length from the numbers returned, use the same formula as before, and derive a similarity or relative semantics between names for objects. The theory is based on Kolmogorov complexity. We test both similarities extensively experimentally.

  8. Segmentation Similarity and Agreement

    CERN Document Server

    Fournier, Chris


    We propose a new segmentation evaluation metric, called segmentation similarity (S), that quantifies the similarity between two segmentations as the proportion of boundaries that are not transformed when comparing them using edit distance, essentially using edit distance as a penalty function and scaling penalties by segmentation size. We propose several adapted inter-annotator agreement coefficients which use S that are suitable for segmentation. We show that S is configurable enough to suit a wide variety of segmentation evaluations, and is an improvement upon the state of the art. We also propose using inter-annotator agreement coefficients to evaluate automatic segmenters in terms of human performance.

  9. Application of toxicogenomics in hepatic systems toxicology for risk assessment: Acetaminophen as a case study

    NARCIS (Netherlands)

    Kienhuis, A.S.; Bessems, J.G.M.; Pennings, J.L.A.; Driessen, M.; Luijten, M.; Delft, van J.H.M.; Ven, van der L.T.M.


    Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employ

  10. 76 FR 68461 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (United States)


    ... HUMAN SERVICES Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors AGENCY: National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National... from recognized authorities knowledgeable in fields such as toxicology, pharmacology,...

  11. 76 FR 67200 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request... (United States)


    ... HUMAN SERVICES National Institutes of Health Proposed National Toxicology Program (NTP) Review Process... the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS... Toxicology Program. BILLING CODE 4140-01-P...

  12. 77 FR 24714 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (United States)


    ... HUMAN SERVICES Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors AGENCY: National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National... fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk...

  13. 77 FR 60707 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for... (United States)


    ... HUMAN SERVICES National Institutes of Health National Toxicology Program Board of Scientific Counselors... Toxicology Program (NTP) Board of Scientific Counselors (BSC). The NTP BSC, a federally chartered, external... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry,...

  14. The placenta in toxicology. Part IV : Battery of toxicological test systems based on human placenta

    NARCIS (Netherlands)

    Göhner, Claudia; Svensson-Arvelund, Judit; Pfarrer, Christiane; Häger, Jan-Dirk; Faas, Marijke; Ernerudh, Jan; Cline, J Mark; Dixon, Darlene; Buse, Eberhard; Markert, Udo R


    This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, ves

  15. Chemical mixture toxicology: from descriptive to mechanistic, and going on to in silico toxicology. (United States)

    Yang, Raymond S H; El-Masri, Hisham A; Thomas, Russell S; Dobrev, Ivan D; Dennison, James E; Bae, Dong-Soon; Campain, Julie A; Liao, Kai H; Reisfeld, Brad; Andersen, Melvin E; Mumtaz, Moiz


    Because of the pioneering vision of certain leaders in the biomedical field, the last two decades witnessed rapid advances in the area of chemical mixture toxicology. Earlier studies utilized conventional toxicology protocol and methods, and they were mainly descriptive in nature. Two good examples might be the parallel series of studies conducted by the U.S. National Toxicology Program and TNO in The Netherlands, respectively. As a natural course of progression, more and more sophistication was incorporated into the toxicology studies of chemical mixtures. Thus, at least the following seven areas of scientific achievements in chemical mixture toxicology are evident in the literature: (a) the application of better and more robust statistical methods; (b) the exploration and incorporation of mechanistic bases for toxicological interactions; (c) the application of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling; (d) the studies on more complex chemical mixtures; (e) the use of science-based risk assessment approaches; (f) the utilization of functional genomics; and (g) the application of technology. Examples are given for the discussion of each of these areas. Two important concepts emerged from these studies and they are: (1) dose-dependent toxicologic interactions; and (2) "interaction thresholds". Looking into the future, one of the most challenging areas in chemical mixture research is finding the answer to the question "when one tries to characterize the health effects of chemical mixtures, how does one deal with the infinite number of combination of chemicals, and other possible stressors?" Undoubtedly, there will be many answers from different groups of researchers. Our answer, however, is first to focus on the finite (biological processes) rather than the infinite (combinations of chemical mixtures and multiple stressors). The idea is that once we know a normal biological process(es), all stimuli and insults from external stressors

  16. Similarity boosted quantitative structure-activity relationship--a systematic study of enhancing structural descriptors by molecular similarity. (United States)

    Girschick, Tobias; Almeida, Pedro R; Kramer, Stefan; Stålring, Jonna


    The concept of molecular similarity is one of the most central in the fields of predictive toxicology and quantitative structure-activity relationship (QSAR) research. Many toxicological responses result from a multimechanistic process and, consequently, structural diversity among the active compounds is likely. Combining this knowledge, we introduce similarity boosted QSAR modeling, where we calculate molecular descriptors using similarities with respect to representative reference compounds to aid a statistical learning algorithm in distinguishing between different structural classes. We present three approaches for the selection of reference compounds, one by literature search and two by clustering. Our experimental evaluation on seven publicly available data sets shows that the similarity descriptors used on their own perform quite well compared to structural descriptors. We show that the combination of similarity and structural descriptors enhances the performance and that a simple stacking approach is able to use the complementary information encoded by the different descriptor sets to further improve predictive results. All software necessary for our experiments is available within the cheminformatics software framework AZOrange.

  17. Collaborative development of predictive toxicology applications

    Directory of Open Access Journals (Sweden)

    Hardy Barry


    Full Text Available Abstract OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals. The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation. Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure

  18. Genetic toxicology in industrial practice: general introduction

    Energy Technology Data Exchange (ETDEWEB)

    Tassignon, J.P.


    During the past decade, important position statements on mutagenicity testing have been issued by industrial organizations such as CEFIC (the European Council of Chemical Industry Federations) and ECETOC (the European Chemical Industry Ecology and Toxicology Centre). Mutagenicity testing is of potential value as a research tool for screening new compounds, as a probe for the identification of harmful substances and as a diagnostic tool for monitoring the health of individuals exposed to certain chemicals. The problems inherent in mutagenicity testing include specificity and sensitivity, and meaningful interpretation of test data will depend on the strict maintenance of accepted quality standards.

  19. Genetic toxicology in industrial practice: general introduction. (United States)

    Tassignon, J P


    During the past decade, important position statements on mutagenicity testing have been issued by industrial organizations such as CEFIC (the European Council of Chemical Industry Federations) and ECETOC (the European Chemical Industry Ecology and Toxicology Centre). Mutagenicity testing is of potential value as a research tool for screening new compounds, as a probe for the identification of harmful substances and as a diagnostic tool for monitoring the health of individuals exposed to certain chemicals. The problems inherent in mutagenicity testing include specificity and sensitivity, and meaningful interpretation of test data will depend on the strict maintenance of accepted quality standards.

  20. The role of clinical pharmacists in the diagnosis and treatment of mercury poisoning caused by the topical use of cinnabar%临床药师在朱砂外用致汞中毒诊治中的作用

    Institute of Scientific and Technical Information of China (English)

    于丽; 轩姣; 李晋宝


    Objective:To explore the role of clinical pharmacists in the diagnosis and treatment of drug poisoning. Methods:According to the symptoms and medication history of the patient with mercury poisoning caused by topical use of cinnabar, clinical pharmacists provided some vermilion composition information for physicians and the basis for early diagnosis, and recommended to check the urinary mercury concentration and participated in the design of the treatment plan and carry out medication supervision after the clear diagnosis. Results:The concentration of acute urinary mercury in the patient exceeded the standard, however, it decreased to the normal level after the treatment of eliminating mercury and protecting liver and the condition was significantly improved. Conclusion: Clinical pharmacists can provide drug information for physicians in the treatment of drug poisoning, participate in making drug treatment plan and carry out pharmaceutical care.%目的:探讨临床药师在药物致中毒诊治中的作用。方法:在外用朱砂致汞中毒患者救治中,临床药师结合患者症状和用药史,为医师提供朱砂成分信息,并提出检查尿汞浓度的建议,为及早诊断提供依据,诊断明确后参与治疗方案的设计并开展用药监护。结果:急查患者尿汞浓度超标,经驱汞、保肝等治疗后,尿汞浓度降至正常,病情明显好转。结论:临床药师能够在药物中毒救治中提供药品信息、参与制定药物治疗方案和开展药学监护。

  1. Oxidative stress in toxicology: established mammalian and emerging piscine model systems. (United States)

    Kelly, K A; Havrilla, C M; Brady, T C; Abramo, K H; Levin, E D


    Interest in the toxicological aspects of oxidative stress has grown in recent years, and research has become increasingly focused on the mechanistic aspects of oxidative damage and cellular responses in biological systems. Toxic consequences of oxidative stress at the subcellular level include lipid peroxidation and oxidative damage to DNA and proteins. These effects are often used as end points in the study of oxidative stress. Typically, mammalian species have been used as models to study oxidative stress and to elucidate the mechanisms underlying cellular damage and response, largely because of the interest in human health issues surrounding oxidative stress. However, it is becoming apparent that oxidative stress also affects aquatic organisms exposed to environmental pollutants. Research in fish has demonstrated that mammalian and piscine systems exhibit similar toxicological and adaptive responses to oxidative stress. This suggests that piscine models, in addition to traditional mammalian models, may be useful for further understanding the mechanisms underlying the oxidative stress response.

  2. IRIS Toxicological Review of Methanol (Noncancer) (Interagency Science Discussion Draft) (United States)

    On May 3, 2013, the Toxicological Review of Methanol (noncancer) (Revised External Review Draft) was posted for public review and comment. Subsequently, the draft Toxicological Review, Appendices, and draft IRIS Summary were reviewed internally by EPA and by other federal agenci...

  3. IRIS Toxicological Review of Ammonia (Interagency Science Consultation Draft) (United States)

    On June 1, 2012, the draft Toxicological Review of Ammonia and the draft charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House ...

  4. Recent developments in analytical toxicology : for better or for worse

    NARCIS (Netherlands)

    de Zeeuw, RA


    When considering the state of the art in toxicology from an analytical perspective, the key developments relate to three major areas. (1) Forensic horizon: Today forensic analysis has broadened its scope dramatically, to include workplace toxicology, drug abuse testing, drugs and driving, doping, en

  5. 40 CFR 159.165 - Toxicological and ecological studies. (United States)


    ... inhalation or skin and eye irritation studies in which the only change in toxicity is a numerical decrease in... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicological and ecological studies... Information § 159.165 Toxicological and ecological studies. Adverse effects information must be submitted...

  6. Historical milestones and discoveries that shaped the toxicology sciences. (United States)

    Hayes, Antoinette N; Gilbert, Steven G


    Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages, toxicological science has provided information that has shaped and guided society. This chapter examines the development of the discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This chapter also examines how toxicology and the toxicologist have interacted with other scientific and cultural disciplines, including religion, politics, and the government. Toxicology has evolved to a true scientific discipline with its own dedicated scientists, educational institutes, sub-disciplines, professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, pharmacology, and molecular biology. We invite you to join us on a path of discovery and to offer our suggestions as to what are the most significant milestones and discoveries in toxicology. Additional information is available on the history section of Toxipedia (

  7. 朱砂灌胃给药后汞在孕大鼠脏器内的分布和排泄途径研究%Study on Distribution in Organs and Excretion Pathway of Mercury in Pregnant Rats after Administration of Cinnabar

    Institute of Scientific and Technical Information of China (English)

    汤家铭; 米金霞; 吴文斌; 谷颖敏; 李咏梅; 夏晶; 张甦; 曹帅; 季申


    Objective: To study the distribution and excretion pathway of mercury in pregnant rats after administration of cinnabar. Methods; Compared with the reproductive toxicity test, the female SD rats after mating were randomly divided into high (1 000 mg/kg) , medium (300 mg/kg) , and low-dose (100 mg/kg) cinnabar groups, and negative control group (0.5% CMC-Na) , with ten rats in each group. The rats in different dose cinnabar groups were administered intragastrically with cinnabar from the sixth day to the fifteenth day after pregnancy, and all the rats were sacrificed on the twentieth day of pregnancy. The main organs (including heart, liver, spleen, lung, kidney, brain and uterus) , blood, placentae, fetuses and urine of the pregnant rats were obtained to detect the mercury concentration by inductively coupled plasma mass spectrometry ( ICP-MS) ; the feces were taken at different time points to determine the mercury concentration by inductively coupled plasma optical emission spectrometer (ICP-OES) ; the distribution in different organs and the excretion pathway of mercury were analyzed. Results: The mercury concentrations of the heart, liver, kidney and uterus of the rats in different dose cinnabar groups were higher than those of the rats in negative control group, and the concentration increased with the enhanced dose; there was no statistical difference on the mercury concentrations of the brain, placentae and fetuses between different dose cinnabar groups and negative control group. There were large amount of mercury in the feces on the second day after administration, and the mercury excretion accounted for 38. 2% ~ 50.4% of HgS intake; while the mercury excretion accounted for72.2% -86.6% on the tenth day after administration; The a-mount of HgS discharged in the feces decreased rapidly on the fourth day after drug discontinuation. Only extreme trace of mercury excreted from urine with dose-dependent pattern, and the mercury excretion maintained the high

  8. Dissolution, absorption and bioaccumulation in gastrointestinal tract of mercury in HgS-containing traditional medicines Cinnabar and Zuotai%含HgS传统药物朱砂和佐太中汞的胃肠道溶出及吸收蓄积研究

    Institute of Scientific and Technical Information of China (English)

    郑植元; 李岑; 张明; 杨红霞; 耿卢婧; 李林帅; 杜玉枝; 魏立新


    中药朱砂和藏药佐太的主要成分分别为α-HgS和β-HgS,但是关于朱砂、佐太、α-HgS和β-HgS中的汞在人体胃肠道中的溶出吸收以及在器官中的分布蓄积的比较研究未见报道.该研究模拟了4种硫化汞类化合物在人体胃肠道中的溶出过程,然后测定汞溶出度,分别比较不同药物间汞溶出度差异以及不同溶液的促溶能力差异.为了探究朱砂和佐太在机体内的吸收蓄积情况,分别以其临床等效剂量灌胃小鼠,同时设置与朱砂等汞量的α-HgS和β-HgS给药组,以及与佐太等汞量的β-HgS和HgC12给药组,然后比较各组不同药物中的汞在小鼠体内吸收蓄积能力差异以及小鼠不同组织器官对汞的蓄积能力差异.实验结果表明,佐太在人工胃肠液中的汞溶出度均较大,其次是β-HgS,朱砂和α-HgS也有一定的溶出.对于小鼠汞吸收蓄积实验,HgCl2吸收蓄积能力最强,β-HgS其次,α-HgS略强于朱砂;不同器官对汞的蓄积能力大小依次是肾>肝>脑.该研究贴近临床实际,观察含汞药物朱砂和佐太在胃肠道中的溶出以及吸收分布蓄积,为临床安全用药提供参考,也希望为含重金属药物的安全性评价提供研究模式.%α-HgS is the main component of traditional Chinese medicine cinnabar,while β-HgS is the main component of Tibetan medicine Zuotai.However,there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar,Zuotai,α-HgS and β-HgS.In this study,the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions.To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms,mice were orally administered with clinical equivalent doses cinnabar and Zuotai

  9. More Similar Than Different

    DEFF Research Database (Denmark)

    Pedersen, Mogens Jin


    What role do employee features play into the success of different personnel management practices for serving high performance? Using data from a randomized survey experiment among 5,982 individuals of all ages, this article examines how gender conditions the compliance effects of different...... incentive treatments—each relating to the basic content of distinct types of personnel management practices. The findings show that males and females are more similar than different in terms of the incentive treatments’ effects: Significant average effects are found for three out of five incentive...

  10. Space Toxicology Challenges and Ethical Considerations (United States)

    James, John T.


    Before delineating specific ways that nanotechnology enterprises might contribute to better management of toxicological risks during spaceflight, I will show how ethical considerations and several theories of justice can be applied to nanotechnology strategic plans. The principles that guide an ethical technical enterprise include autonomy, beneficence, non-maleficence, veracity and justice. Veracity (truth) is the underpinning principle; however, beyond this, proponents of nanotechnology must think carefully about balancing conflicting principles. For example, autonomy must yield to beneficence when fearful individuals simply lack knowledge to appreciate nanotechnology's beneficial advances. Justice is a complex topic upon which I will place six models: utilitarian, distributive, free-exchange/choice, individual dignity (social participation), equity vs. greed, and liberation of the poor. After briefly summarizing each model, I will present what I call an iterative-hybrid model of justice to show specifically how our thinking can be applied to nanotechnology enterprises. Within that broad landscape, I will discuss a single feature: how our early effort to understand health risks of carbon nanotubes fits into the iterative model. Finally, I will suggest ways that nanotechnology might advance our management of toxicological risks during spaceflight, but always with an eye toward how such advances might result in a more just world.

  11. Confusion of concepts in mixture toxicology. (United States)

    Könemann, W H; Pieters, M N


    Regulatory limit values are generally set for single compounds. However, humans are exposed both simultaneously and sequentially to a wide variety of compounds. Some concepts on mixture toxicology are discussed in this introduction to the European Conference on Combination Toxicology. Studies on mixtures are often accompanied by statements about the type of combined action, which can be, for example, additive, synergistic or antagonistic. Unfortunately, comparison of results is hardly possible for various reasons. First, the terminology for indicating combined action is far from consistent. Bearing this in mind, researchers should be explicit in the definitions of terms. Secondly, depending on the model, different conclusions may be drawn from the same results. It is therefore important to provide clear definitions of the null hypothesis. Thirdly, adequate statistical methods should be used for testing the null hypothesis. In the past, many mixtures studies either used no statistics or used statistics incorrectly. Last, but not least, the study should be designed in such a way that it should be possible to obtain clear answers. In this introduction, it is stressed that environmental toxicologists should focus on the low-dose region of the dose-effect curves. It appears that interactions are less plausible at low doses. Dose additivity, however, cannot be excluded.

  12. Applicability of computational systems biology in toxicology. (United States)

    Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie


    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research.

  13. Toxicological Effects of Fullerenes on Caenorhabditis elegans (United States)

    Schomaker, Justin; Snook, Renee; Howell, Carina


    The nematode species Caenorhabditis elegans is a useful genetic model organism due to its simplicity and the substantial molecular, genetic, and developmental knowledge about the species. In this study, this species was used to test the toxicological effects of C60 fullerene nanoparticles. In previous studies using rats, a solution of C60 fullerenes in olive oil proved to extend the life of the subjects. The purpose of this experiment was to subject C. elegans to varying concentrations of C60 fullerenes and observe their toxicological effects. Initial findings indicate a link between fullerene exposure and enlargement of the vulva as well as the formation of a small nodule at the base of the tail in some individuals. While the fullerenes are not lethally toxic in C. elegans, results will be presented that pertain to changes in life span and progeny of the nematodes exposed to varying concentrations of fullerenes as well as the mechanisms of toxicity. High magnification imaging via SEM and/or AFM will be used to characterize the fullerene nanoparticles. Testing the toxicity of fullerenes in a wide variety of organisms will lead to a more complete understanding of the effects of fullerenes on living organisms to ultimately understand their effects in humans. This work was supported by National Science Foundation grants DUE-1058829, DMR-0923047, DUE-0806660 and Lock Haven FPDC grants.

  14. PIXE applications to the toxicological field

    Energy Technology Data Exchange (ETDEWEB)

    Santos, C.E.I. dos; Dias, J.F.; Jobim, P.F.C.; Yoneama, M.L. [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Instituto de Fisica. Laboratorio de Implantacao Ionica; Andrade, V.M. [Universidade do Extremo Sul Catarinense, Criciuma, SC (Brazil). Laboratorio de Biologia Celular e Molecular; Amaral, L.; Silva, J. da [Universidade Luterana do Brasil, Canoas, RS (Brazil). Laboratorio de Toxicologia Generica


    Full text: Several studies have been carried out in order to investigate the toxicological properties of some chemical elements in different type of biological samples. lon beam techniques, in particular PIXE, have been successfully used to analyze the elemental composition of food, beverage, plants and animal tissues. In this context, the PIXE line of the lon Implantation Laboratory (Porto Alegre, Brazil) have been used in the last few years to study food and beverage processing and biological specimens exposed to contaminated environment. The aim of this study is to present some of our results using PIXE analysis applied to toxicological research field. For instance, a recent published research [1] investigated the genotoxic and mutagenic effects in tobacco farmers exposed to metal-based formulated pesticides. Levels of Mg, AI, CI, Zn, Cr and Br, elements associated with DNA damage, were higher in the blood samples of tobacco farmers exposed to pesticide than in the non-exposed group. The occupational genotoxicity among copper smelters was also investigated [2]. The elemental content of blood samples were analyzed by PIXE. DNA damage in the peripheral blood Iymphocytes of workers exposed to copper smelter was observed. However, no clear correlation was found between the metal content and DNA damage. [1] F. R. da Silva, J. da Silva, M. C. AlIgayer, C. F. Simon, J. F. Dias, C. E. I. dos Santos, M. Salvador, C. Branco, N. B. Schneider, V. Kahl, P. Rohr, K. Kvitko, J. Hazard. Mat., 225-226 (2012) 81-90. (author)

  15. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz


    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  16. Similar dissection of sets

    CERN Document Server

    Akiyama, Shigeki; Okazaki, Ryotaro; Steiner, Wolfgang; Thuswaldner, Jörg


    In 1994, Martin Gardner stated a set of questions concerning the dissection of a square or an equilateral triangle in three similar parts. Meanwhile, Gardner's questions have been generalized and some of them are already solved. In the present paper, we solve more of his questions and treat them in a much more general context. Let $D\\subset \\mathbb{R}^d$ be a given set and let $f_1,...,f_k$ be injective continuous mappings. Does there exist a set $X$ such that $D = X \\cup f_1(X) \\cup ... \\cup f_k(X)$ is satisfied with a non-overlapping union? We prove that such a set $X$ exists for certain choices of $D$ and $\\{f_1,...,f_k\\}$. The solutions $X$ often turn out to be attractors of iterated function systems with condensation in the sense of Barnsley. Coming back to Gardner's setting, we use our theory to prove that an equilateral triangle can be dissected in three similar copies whose areas have ratio $1:1:a$ for $a \\ge (3+\\sqrt{5})/2$.

  17. The relative physiological and toxicological properties of americium and plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Carter, R.E.; Busch, E.; Johnson, O. [and others


    The relative physiological and toxicological properties of americium and plutonium have been studied following their intravenous administration to rats. The urinary and fecal excretion of americium was similar to that of plutonium administered as Pu(N0{sub 3}){sub 4}. The deposition of americium the tissues and organs of the rat was also similar to that observed for plutonium. The liver and the skeleton were the major sites of deposition. Zirconium citrate administered 15 minutes after injection of americium increased the urinary excretion of americium and decreased the amount found in the liver and the skeleton at 4 and 16 days. LD{sub 30}{sup 50} studies showed americium was slightly less toxic when given in the acute toxic range than was plutonium. The difference was, however, too slight to be important in establishing a larger tolerance does for americium. Survival studies, hematological observations, bone marrow observations, comparison of tumor incidence and the incidence of skeletal abnormalities indicated that americium and plutonium have essentially the same chronic toxicity when given on an equal {mu}c. basis. These studies support the conclusion that the tolerance values for americium should be essentially the same as those for Plutonium.

  18. Similarity transformed semiclassical dynamics (United States)

    Van Voorhis, Troy; Heller, Eric J.


    In this article, we employ a recently discovered criterion for selecting important contributions to the semiclassical coherent state propagator [T. Van Voorhis and E. J. Heller, Phys. Rev. A 66, 050501 (2002)] to study the dynamics of many dimensional problems. We show that the dynamics are governed by a similarity transformed version of the standard classical Hamiltonian. In this light, our selection criterion amounts to using trajectories generated with the untransformed Hamiltonian as approximate initial conditions for the transformed boundary value problem. We apply the new selection scheme to some multidimensional Henon-Heiles problems and compare our results to those obtained with the more sophisticated Herman-Kluk approach. We find that the present technique gives near-quantitative agreement with the the standard results, but that the amount of computational effort is less than Herman-Kluk requires even when sophisticated integral smoothing techniques are employed in the latter.

  19. Statistical studies in genetic toxicology: a perspective from the U.S. National Toxicology Program. (United States)

    Margolin, B H


    This paper surveys recent, as yet unpublished, statistical studies arising from research in genetic toxicology within the U.S. National Toxicology Program (NTP). These studies all involve analyses of data from Ames Salmonella/microsome mutagenicity tests, but the statistical methodologies are broadly applicable. Three issues are addressed: First, what is a tenable sampling model for Ames test data, and how does one best test the adequacy of the Poisson sampling assumption? Second, given that nonmonotone dose-response curves are fairly common in the Salmonella assay, what new statistical techniques or modifications of existing ones seem appropriate to accommodate to this reality? Finally, an intriguing question: How can the extensive NTP Ames test data base be used to assess the characteristics of any mutagen-nonmutagen decision rule? The last issue is illustrated with the commonly used "two-times background" rule.

  20. Toxicological consultation data management system based on experience of Pomeranian Center of Toxicology

    Directory of Open Access Journals (Sweden)

    Piotr Maciej Kabata


    Full Text Available Background: In this paper the structure of poisonings is described, based on the material collected from tele-toxicology consults by the Pomeranian Center of Toxicology in Gdańsk and harvested from its Electronic Poison Information Management System. In addition, we analyzed conclusions drawn from a 27-month operation of the system. Material and Methods: Data were harvested from the Electronic Poison Information Management System developed in 2012 and used by the Pomeranian Center of Toxicology since then. The research was based on 2550 tele-toxicology consults between January 1 and December 31, 2014. Subsequently the data were electronically cleaned and presented using R programming language. Results: The Pomeranian voivodeship was the prevalent localisation of calls (N = 1879; 73.7%. Most of the calls came from emergency rooms (N = 1495; 58.63%. In the case of 1396 (54.7% patients the time-lag between intoxication and the consult was less than 6 h. There were no differences in the age distribution between genders. Mean age was 26.3 years. Young people predominated among intoxicated individuals. The majority of intoxications were incidental (N = 888; 34.8% or suicidal (N = 814; 31.9% and the most of them took place in the patient’s home. Conclusions: Information about Poison Control Center consultations access should be better spread among medical service providers. The extent of poison information collected by Polish Poison Control Centers should be limited and unified. This should contribute to the increased percentage of properly documented consultations. Additional duties stemming from the need of digital archiving of consults provided, require the involvement of additional staff, leading to the increased operation costs incurred by Poison Control Centers. Med Pr 2015;66(5:635–644

  1. Computational chemistry, systems biology and toxicology. Harnessing the chemistry of life: revolutionizing toxicology. a commentary. (United States)

    Kimber, Ian; Humphris, Colin; Westmoreland, Carl; Alepee, Nathalie; Negro, Gianni Dal; Manou, Irene


    There is a continuing interest in, and increasing imperatives for, the development of alternative methods for toxicological evaluations that do not require the use of animals. Although a significant investment has resulted in some achievements, progress has been patchy and there remain many challenges. Among the most significant hurdles is developing non-animal methods that would permit assessment of the potential for a chemical or drug to cause adverse health effects following repeated systemic exposure. Developing approaches to address this challenge has been one of the objectives of the European Partnership for Alternative Approaches to Animal Testing (EPAA). The EPAA is a unique partnership between the European Commission and industry that has interests in all aspects of reducing, refining and replacing the use of animals (the '3Rs'). One possible strategy that emerged from a broad scientific debate sponsored by the EPAA was the opportunity for developing entirely new paradigms for toxicity testing based upon harnessing the increasing power of computational chemistry in combination with advanced systems biology. This brief commentary summarizes a workshop organized by the EPAA in 2010, that had the ambitious title of 'Harnessing the Chemistry of Life: Revolutionizing Toxicology'. At that workshop international experts in chemistry, systems biology and toxicology sought to map out how best developments in these sciences could be exploited to design new strategies for toxicity testing using adverse effects in the liver as an initial focus of attention. Here we describe the workshop design and outputs, the primary purpose being to stimulate debate about the need to align different areas of science with toxicology if new and truly innovative approaches to toxicity testing are to be developed.

  2. [Forensic medicine as the cradle of toxicology in Russia]. (United States)

    Popov, V L; Grebeniuk, A N; Pigolkin, Iu I; Tolmachev, I A; Bozhchenko, A P; Timoshevskiĭ, A A


    Modern toxicology as a science and educational subject originated from forensic medicine in the middle of the XIXth century. In the beginning, selected toxicological problems were taught in the Emperor's Medical Surgical Academy (presently S.M. Kirov Military Medical Academy, Sankt-Peterburg) and at the Medical Faculty of the Moscow University (presently I.M. Sechenov First Moscow State Medical University, Moscow). The greatest contribution to the development of toxicology was made by such outstanding scientists as professors S.A. Gromov, P.P. Pelekhin, P.P. Zablotsky-Desyatovsky, E.V. Pelikan, Ya.A. Chistovich, G.I. Blosfel'd, I.M. Sorokin, D.P. Kosorotov, A.V. Grigoriev, V.V. Andreev, A.A. Glebovich, A.N. Grigoriev, B.I. Predtechensky, V.M. Rozhkov, S.S. Vail, M.N. Lubotsky, etc. The works of these researchers predetermined the further development of toxicology in this country, its main purpose being provision of medical aid in case of poisoning and diseases of chemical etiology. Another line of toxicological research became industrial and environmental toxicology having the purpose of hygienic rating and prevention of poisoning. Nevertheless, all aspects of the multifaceted science of toxicology are related to forensic medicine as the cradle in which it originated, evolved, and turned into a self-consistent science.

  3. Public health partnerships in medical toxicology education and practice. (United States)

    Schier, Joshua G; Rubin, Carol; Schwartz, Michael D; Thomas, Jerry D; Geller, Robert J; Morgan, Brent W; McGeehin, Michael A; Frumkin, Howard


    In December 2002, the medical toxicology sub-board, which consists of representatives from emergency medicine, preventive medicine, and pediatrics, released revised core content for medical toxicology, aiming to better meet the academic challenges imposed by the continually expanding knowledge base of medical toxicology. These challenges included the addition of relatively new areas of interest in medical toxicology, including population health, while simultaneously ensuring that a structural framework existed to accommodate future areas of interest. There is no evidence readily available to assess how well the educational curricula of existing fellowship programs are meeting these needs. In an effort to address this, the authors describe a medical toxicology fellowship program that consists of a partnership among the Emory University School of Medicine, the Georgia Poison Control Center, and the CDC, as well as the results of a reorganization of its academic curriculum that occurred in 2006. To the best of the authors' knowledge, this is the first published report describing such a curriculum redesign. Suggestions and potential resources proposed as enhancements for the public health-associated education of medical toxicology fellows are discussed. The authors also seek to initiate a discussion among programs about how to optimally meet the new challenges developed by the medical toxicology sub-board.

  4. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure


    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...... be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method...

  5. Biosynthesis and toxicological effects of patulin. (United States)

    Puel, Olivier; Galtier, Pierre; Oswald, Isabelle P


    Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects.

  6. Toxicological criterion of the heroin poisoning. (United States)

    Shigeev, S


    The paper presents toxicological characteristics of 198 cases of acute parenteral heroin intoxication, analyzes the clinically encountered range of blood and urinary concentrations of its metabolites. The principal causes of death are elucidated in victims of heroin poisoning at the hospital stage. Where there is a relationship of death probability to the detection of morphine in the victims' biological fluids is considered; its blood and urinary concentrations are determined, which undoubtedly suggests the occurrence of poisoning-related death. It has been established that death from poisoning by heroin may occur in the whole range of its detectable concentrations. There is no doubt that the blood morphine concentrations of at least 2.0 microg/ml should be considered to be fatal.

  7. Toxicological benchmarks for wildlife. Environmental Restoration Program

    Energy Technology Data Exchange (ETDEWEB)

    Opresko, D.M.; Sample, B.E.; Suter, G.W.


    This report presents toxicological benchmarks for assessment of effects of 55 chemicals on six representative mammalian wildlife species (short-tailed shrew, white-footed mouse, cottontail ink, red fox, and whitetail deer) and eight avian wildlife species (American robin, woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, Cooper`s hawk, and redtailed hawk) (scientific names are presented in Appendix C). These species were chosen because they are widely distributed and provide a representative range of body sizes and diets. The chemicals are some of those that occur at United States Department of Energy (DOE) waste sites. The benchmarks presented in this report are values believed to be nonhazardous for the listed wildlife species.

  8. Handbook of toxicology of chemical warfare agents

    CERN Document Server


    This groundbreaking book covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this one-of-a-kind handbook is prepared in a very user- friendly format that can easily be followed by students, teachers and researchers, as well as lay people. Stand-alone chapters on individual chemicals and major topics allow the reader to easily access required information without searching through the entire book. This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security. Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves research...

  9. Pyridoxine in clinical toxicology: a review. (United States)

    Lheureux, Philippe; Penaloza, Andrea; Gris, Mireille


    Pyridoxine (vitamin B6) is a co-factor in many enzymatic pathways involved in amino acid metabolism: the main biologically active form is pyridoxal 5-phosphate. Pyridoxine has been used as an antidote in acute intoxications, including isoniazid overdose, Gyromitra mushroom or false morrel (monomethylhydrazine) poisoning and hydrazine exposure. It is also recommended as a co-factor to improve the conversion of glyoxylic acid into glycine in ethylene glycol poisoning. Other indications are recommended by some sources (for example crimidine poisoning, zipeprol and theophylline-induced seizures, adjunct to d-penicillamine chelation), without significant supporting data. The value of pyridoxine or its congener metadoxine as an agent for hastening ethanol metabolism or improving vigilance in acute alcohol intoxication is controversial. This paper reviews the various indications of pyridoxine in clinical toxicology and the supporting literature. The potential adverse effects of excessive pyridoxine dosage will also be summarized.

  10. 40 CFR 158.230 - Experimental use permit data requirements for toxicology. (United States)


    ... requirements for toxicology. 158.230 Section 158.230 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Experimental use permit data requirements for toxicology. All toxicology data, as described in paragraph (c) of...) Table. The following table shows the experimental use data requirements for toxicology. The test...

  11. Toxicología de metales y minerales


    García Fernández, Antonio Juan


    Presentaciones de los temas de Toxicología de metales y minerales: mercurio, cadmio, plomo, cobre, arsénico, flúor, selenio, zinc, talio, etc impartidas en la asignatura de Toxicología en el curso 2011/12. Se aborda desde las perspectivas ambiental, alimentaria y clínica, tanto sobre los animales como sobre las personas. Presentaciones de los temas de Toxicología de metales y minerales: mercurio, cadmio, plomo, cobre, arsénico, flúor, selenio, zinc, talio, etc impartidas en la asignatura d...

  12. National toxicology program chemical nomination and selection process

    Energy Technology Data Exchange (ETDEWEB)

    Selkirk, J.K. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)


    The National Toxicology Program (NTP) was organized to support national public health programs by initiating research designed to understand the physiological, metabolic, and genetic basis for chemical toxicity. The primary mandated responsibilities of NTP were in vivo and vitro toxicity testing of potentially hazardous chemicals; broadening the spectrum of toxicological information on known hazardous chemicals; validating current toxicological assay systems as well as developing new and innovative toxicity testing technology; and rapidly communicating test results to government agencies with regulatory responsibilities and to the medical and scientific communities. 2 figs.

  13. Evidence-based toxicology: a comprehensive framework for causation. (United States)

    Guzelian, Philip S; Victoroff, Michael S; Halmes, N Christine; James, Robert C; Guzelian, Christopher P


    This paper identifies deficiencies in some current practices of causation and risk evaluation by toxicologists and formulates an evidence-based solution. The practice of toxicology focuses on adverse health events caused by physical or chemical agents. Some relations between agents and events are identified risks, meaning unwanted events known to occur at some frequency. However, other relations that are only possibilities--not known to occur (and may never be realized)--also are sometimes called risks and are even expressed quantitatively. The seemingly slight differences in connotation among various uses of the word 'risk' conceal deeply philosophic differences in the epistemology of harm. We label as 'nomological possibilities' (not as risks) all predictions of harm that are known not to be physically or logically impossible. Some of these nomological possibilities are known to be causal. We term them 'epistemic'. Epistemic possibilities are risks. The remaining nomological possibilities are called 'uncertainties'. Distinguishing risks (epistemic relationships) from among all nomological possibilities requires knowledge of causation. Causality becomes knowable when scientific experiments demonstrate, in a strong, consistent (repeatable), specific, dose-dependent, coherent, temporal and predictive manner that a change in a stimulus determines an asymmetric, directional change in the effect. Many believe that a similar set of characteristics, popularly called the 'Hill Criteria', make it possible, if knowledge is robust, to infer causation from only observational (nonexperimental) studies, where allocation of test subjects or items is not under the control of the investigator. Until the 1980s, medical decisions about diagnosis, prevention, treatment or harm were often made authoritatively. Rather than employing a rigorous evaluation of causal relationships and applying these criteria to the published knowledge, the field of medicine was dominated by authority


    EPA is releasing the draft report, Toxicological Review of Tetrachloroethylene (Perchloroethylene), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment...

  15. La Toxicología en la Universidad de Sevilla

    Directory of Open Access Journals (Sweden)

    IM Moreno


    Full Text Available La docencia del Área de Toxicología en la Universidad de Sevilla se desarrolla en la actualidad en dos titulaciones, Farmacia y Bioquímica. En los planes de estudios actuales la carga lectiva del Área viene dada por las asignaturas de Toxicología (asignatura troncal, y Toxicología Alimentaria (asignatura optativa en la Licenciatura de Farmacia, y de Toxicología Molecular (asignatura optativa en la Licenciatura de Bioquímica. Una vez aprobados por la Agencia Nacional de la Evaluación de la Calidad y Acreditación (ANECA ambos títulos de Grado, la docencia no sólo se mantiene sino que se amplía gracias a la participación en la impartición de dos asignaturas pluridisciplinares de nueva creación en el Grado de Farmacia.

  16. Diversification in toxicology: man and environment. EUROTOX proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Seiler, J.P. [Intercantonal Office for the Control of Medicines (IOCM), Bern (Switzerland); Autrup, J.L.; Autrup, H. [eds.] [Aarhus Univ. (Denmark). Steno Inst. of Public Health


    This volume contains the main papers presented at the 1997 EUROTOX Congress, Aaarhus, Denmark, 24-28 June 1997. Diversification in toxicology is not seen as splitting into subfields, but as the application of basic science to such diverse areas as man and his environment. The pressing issues which have been dealt with not only include reproductive effects of environmental chemicals (`xenoestrogens`), but also receptor-mediated toxic responses, new frontiers in human and ecological toxicology, chemoprevention of cancer and molecular approaches in toxicological research. The practical and ethical facets of toxicology, e.g. ecotoxicological risk assessment, biomarkers of exposure, complex chemical mixtures as well as animal welfare and the ethics of animal experimentation, are also treated. (orig.)

  17. IRIS Toxicological Review for Acrylamide (Interagency Science Discussion Draft) (United States)

    EPA is releasing the draft report, Toxicological Review for Acrylamide, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process<...

  18. The minipig as a platform for new technologies in toxicology

    DEFF Research Database (Denmark)

    Forster, Roy; Ancian, Philippe; Fredholm, Merete;


    The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress...... pigs and humans suggest that minipigs will be useful for the testing of biotechnology products (and possibly for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology model where transgenic animals can be readily generated, and reproductive technologies are well developed...... in the pig. These properties should also make the minipig an interesting model for the testing of biotechnology products. These factors all support the idea that the minipig is well placed to meet the challenges of the emerging technologies and the toxicology of the future; it also seems likely...

  19. Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos (United States)

    Summary sentence: Comparative toxicology of Libby amphibole (LA) and site-specific naturally occurring asbestos (NOA) provides new insights on physical properties influencing health effects and mechanisms of asbestos-induced inflammation, fibrosis, and tumorigenesis.Introduction/...

  20. Toxicology and risk assessment information resources for librarians. (United States)

    Stirling, D A


    Many librarians work with toxicologists and risk assessors seeking information about chemicals and hazardous substances of concern to human health and the environment. Therefore, this article reviews reliable, accurate, readily accessible, and user-friendly sources of toxicological and risk assessment information. A summary and description of pertinent toxicological data, literature, and profile sources is presented. The majority of the resources are available online; however, descriptions of several important print sources are included.

  1. Especialización en Toxicología Ambiental

    Directory of Open Access Journals (Sweden)

    E. de la Peña de Torres


    Full Text Available Se hace una exposición de las actividades y cursos de formación en el área de toxicología ambiental tomando como partida la creación en la AETOX de la Sección de Toxicología Ambiental (STA; previamente se inició la actividad de dicha Sección en mayo de 2001, con la celebración de la primera Reunión de Toxicología Ambiental, en el Centro de Ciencias Medioambientales del CSIC; y en ese mismo año se inicia una estrecha colaboración en el Máster de Toxicología. Se remarca el interés de los cursos de especialización ya organizados y que se proyectan para un futuro, que han contado y cuentan con destacados profesionales, facultativos, científicos e investigadores, lo que complementan la labor docente de la Universidad, que no es muy extensa en esta sub-área de la Toxicología la Toxicología Ambiental. Se señala la utilidad que las redes de información tienen en la actualidad para la promoción y visibilidad, lo que contribuye en el desarrollo y difusión de la toxicología, en la que la AETOX promociona y colabora activamente donde se muestran las propuestas de actividades tanto en España como en Iberoamérica, que se difunden realizadas en la página web de la Red Iberoamericana de Toxicología y Seguridad Química (RITSQ (

  2. Systems Toxicology: From Basic Research to Risk Assessment



    Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic u...

  3. Principals Of Radiation Toxicology: Important Aspects. (United States)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    “All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al

  4. Analysis of Statistical Methods Currently used in Toxicology Journals. (United States)

    Na, Jihye; Yang, Hyeri; Bae, SeungJin; Lim, Kyung-Min


    Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and inferential statistics. One hundred thirteen endpoints were observed in those 30 papers, and most studies had sample size less than 10, with the median and the mode being 6 and 3 & 6, respectively. Mean (105/113, 93%) was dominantly used to measure central tendency, and standard error of the mean (64/113, 57%) and standard deviation (39/113, 34%) were used to measure dispersion, while few studies provide justifications regarding why the methods being selected. Inferential statistics were frequently conducted (93/113, 82%), with one-way ANOVA being most popular (52/93, 56%), yet few studies conducted either normality or equal variance test. These results suggest that more consistent and appropriate use of statistical method is necessary which may enhance the role of toxicology in public health.

  5. Toxicology as a nanoscience? – Disciplinary identities reconsidered

    Directory of Open Access Journals (Sweden)

    Maasen Sabine


    Full Text Available Abstract Toxicology is about to establish itself as a leading scientific discipline in addressing potential health effects of materials on the nanosize level. Entering into a cutting-edge field, has an impact on identity-building processes within the involved academic fields. In our study, we analyzed the ways in which the entry into the field of nanosciences impacts on the formation of disciplinary identities. Using the methods of qualitative interviews with particle toxicologists in Germany, Holland, Switzerland and the USA, we could demonstrate that currently, toxicology finds itself in a transitional phase. The development of its disciplinary identity is not yet clear. Nearly all of our interview partners stressed the necessity of repositioning toxicology. However, they each suggested different approaches. While one part is already propagandizing the establishment of a new discipline – 'nanotoxicology'- others are more reserved and are demanding a clear separation of traditional and new research areas. In phases of disciplinary new-orientation, research communities do not act consistently. Rather, they establish diverse options. By expanding its disciplinary boundaries, participating in new research fields, while continuing its previous research, and only vaguely defining its topics, toxicology is feeling its way into the new fields without giving up its present self-conception. However, the toxicological research community is also discussing a new disciplinary identity. Within this, toxicology could develop from an auxiliary into a constitutive position, and take over a basic role in the cognitive, institutional and social framing of the nanosciences.

  6. Systems toxicology: from basic research to risk assessment. (United States)

    Sturla, Shana J; Boobis, Alan R; FitzGerald, Rex E; Hoeng, Julia; Kavlock, Robert J; Schirmer, Kristin; Whelan, Maurice; Wilks, Martin F; Peitsch, Manuel C


    Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment.

  7. Estimating similarity of XML Schemas using path similarity measure

    Directory of Open Access Journals (Sweden)

    Veena Trivedi


    Full Text Available In this paper, an attempt has been made to develop an algorithm which estimates the similarity for XML Schemas using multiple similarity measures. For performing the task, the XML Schema element information has been represented in the form of string and four different similarity measure approaches have been employed. To further improve the similarity measure, an overall similarity measure has also been calculated. The approach used in this paper is a distinguished one, as it calculates the similarity between two XML schemas using four approaches and gives an integrated values for the similarity measure. Keywords-componen

  8. Nano-silicon dioxide toxicological characterization on two human kidney cell lines (United States)

    Paget, V.; Sergent, J. A.; Chevillard, S.


    Silicon dioxide nanoparticles (n-SiO2) have recently encountered a wide variety of applications in medicine or engineering but their toxicological effects are poorly understood. In this study, we have used SiO2-25 nm and SiO2-100 nm mono-dispersed nanoparticles labeled with Rhodamine B and TMPyP respectively. These two fluorophores were incorporated during synthesis in order to track nanoparticles cell incorporation. Up-to-date, no evaluation of the toxicological effects of these nanoparticles upon human kidney has been published. As kidney is one of the major traditional retention organs, the aim of our study is to evaluate the potential toxicity of these nanoparticles on two human cell lines from proximal tubule (Caki-1 and Hek293). Our results report that the two cell lines do not show similar responses after 24 hours of exposure to SiO2-nanoparticles disregarding a similar origin in the kidney. Interestingly, our results indicate that for both tested SiO2-nanoparticles, Caki-1 cells present a higher sensitivity in terms of cytotoxicity and genotoxicity than Hek293 cells. Furthermore, our results show that for similar concentration of exposure, SiO2-25 nm seems to be more cytotoxic and genotoxic than SiO2-100nm for both tested cell lines.

  9. Nano-silicon dioxide toxicological characterization on two human kidney cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Paget, V; Sergent, J A; Chevillard, S, E-mail: [Laboratory of Experimental Cancerology, Institute of Cellular and Molecular Radiobiology, CEA, Fontenay-aux-Roses (France)


    Silicon dioxide nanoparticles (n-SiO{sub 2}) have recently encountered a wide variety of applications in medicine or engineering but their toxicological effects are poorly understood. In this study, we have used SiO{sub 2}-25 nm and SiO{sub 2}-100 nm mono-dispersed nanoparticles labeled with Rhodamine B and TMPyP respectively. These two fluorophores were incorporated during synthesis in order to track nanoparticles cell incorporation. Up-to-date, no evaluation of the toxicological effects of these nanoparticles upon human kidney has been published. As kidney is one of the major traditional retention organs, the aim of our study is to evaluate the potential toxicity of these nanoparticles on two human cell lines from proximal tubule (Caki-1 and Hek293). Our results report that the two cell lines do not show similar responses after 24 hours of exposure to SiO{sub 2}-nanoparticles disregarding a similar origin in the kidney. Interestingly, our results indicate that for both tested SiO{sub 2}-nanoparticles, Caki-1 cells present a higher sensitivity in terms of cytotoxicity and genotoxicity than Hek293 cells. Furthermore, our results show that for similar concentration of exposure, SiO{sub 2}-25 nm seems to be more cytotoxic and genotoxic than SiO{sub 2}-100nm for both tested cell lines.

  10. Medical management of toxicological mass casualty events. (United States)

    Markel, Gal; Krivoy, Amir; Rotman, Eran; Schein, Ophir; Shrot, Shai; Brosh-Nissimov, Tal; Dushnitsky, Tsvika; Eisenkraft, Arik


    The relative accessibility to various chemical agents, including chemical warfare agents and toxic industrial compounds, places a toxicological mass casualty event, including chemical terrorism, among the major threats to homeland security. TMCE represents a medical and logistic challenge with potential hazardous exposure of first-response teams. In addition, TMCE poses substantial psychological and economic impact. We have created a simple response algorithm that provides practical guidelines for participating forces in TMCE. Emphasis is placed on the role of first responders, highlighting the importance of early recognition of the event as a TMCE, informing the command and control centers, and application of appropriate self-protection. The medical identification of the toxidrome is of utmost importance as it may dictate radically different approaches and life-saving modalities. Our proposed emergency management of TMCE values the "Scoop & Run" approach orchestrated by an organized evacuation plan rather than on-site decontamination. Finally, continuous preparedness of health systems - exemplified by periodic CBRN (Chemical, Biological, Radio-Nuclear) medical training of both first responders and hospital staff, mandatory placement of antidotal auto-injectors in all ambulances and CBRN emergency kits in the emergency departments - would considerably improve the emergency medical response to TMCE.

  11. applications of nanomaterials and their toxicological evaluation.

    Directory of Open Access Journals (Sweden)

    C. López-Alonso


    Full Text Available La necesidad de herramientas informáticas para procesar toda la información generada en el ámbito de la nanotecnología ha originado el desarrollo de una nueva disciplina conocida como nanoinformática. En los próximos años es esperable poder disponer de bases de datos con información, no sólo de las propiedades físico-químicas de los nanomateriales, sino también con información de sus posibles interacciones con el medio ambiente y sistemas biológicos, lo que favorecerá la investigación de nuevas aplicaciones biomédicas de los nanomateriales, sin olvidar sus aspectos toxicológicos. En este artículo se presentan diversos recursos de estandarización, ontologías, bases de datos, iniciativas y colaboraciones que ayudan a gestionar la información generada sobre nanomateriales, especialmente orientados a favorecer la Investigación biomédica y la toxicología de los nanomateriales. Además, se presentan otros recursos web complementarios que facilitarán el proceso de autoaprendizaje y el desarrollo de contenidos curriculares en escuelas superiores y facultades, útiles en la formación de esta nueva disciplina, denominada nanotecnología.

  12. Oleoresin Capsicum toxicology evaluation and hazard review

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, M.M.


    Oleoresin Capsicum (OC) is an extract of the pepper plant used for centuries as a culinary spice (hot peppers). This material has been identified as a safe and effective Less-Than- Lethal weapon for use by Law enforcement and security professionals against assault. The National Institute of Justice (NIJ) is currently also evaluating its use in conjunction with other Less-Than-Lethal agents such as aqueous foam for use in corrections applications. Therefore, a comprehensive toxicological review of the literature was performed for the National Institute of Justice Less-Than-Lethal Force program to review and update the information available on the toxicity and adverse health effects associated with OC exposure. The results of this evaluation indicate that exposure to OC can result in dermatitis, as well as adverse nasal, pulmonary, and gastrointestinal effects in humans. The primary effects of OC exposure include pain and irritation of the mucous membranes of the eyes, nose, and lining of the mouth. Blistering and rash have been shown to occur after chronic or prolonged dermal exposure. Ingestion of capsicum may cause acute stinging of the lips, tongue, and oral mucosa and may lead to vomiting and diarrhea with large doses. OC vapors may also cause significant pulmonary irritation and prolonged cough. There is no evidence of long term effects associated with an acute exposure to OC, and extensive use as a culinary additive and medicinal ointment has further provided no evidence of long term adverse effects following repeated or prolonged exposure.

  13. The new toxicology of sophisticated materials: nanotoxicology and beyond. (United States)

    Maynard, Andrew D; Warheit, David B; Philbert, Martin A


    It has long been recognized that the physical form of materials can mediate their toxicity--the health impacts of asbestiform materials, industrial aerosols, and ambient particulate matter are prime examples. Yet over the past 20 years, toxicology research has suggested complex and previously unrecognized associations between material physicochemistry at the nanoscale and biological interactions. With the rapid rise of the field of nanotechnology and the design and production of increasingly complex nanoscale materials, it has become ever more important to understand how the physical form and chemical composition of these materials interact synergistically to determine toxicity. As a result, a new field of research has emerged--nanotoxicology. Research within this field is highlighting the importance of material physicochemical properties in how dose is understood, how materials are characterized in a manner that enables quantitative data interpretation and comparison, and how materials move within, interact with, and are transformed by biological systems. Yet many of the substances that are the focus of current nanotoxicology studies are relatively simple materials that are at the vanguard of a new era of complex materials. Over the next 50 years, there will be a need to understand the toxicology of increasingly sophisticated materials that exhibit novel, dynamic and multifaceted functionality. If the toxicology community is to meet the challenge of ensuring the safe use of this new generation of substances, it will need to move beyond "nano" toxicology and toward a new toxicology of sophisticated materials. Here, we present a brief overview of the current state of the science on the toxicology of nanoscale materials and focus on three emerging toxicology-based challenges presented by sophisticated materials that will become increasingly important over the next 50 years: identifying relevant materials for study, physicochemical characterization, and

  14. Toxicological Properties of the Organophosphorus Insecticide Dimethoate (United States)

    Sanderson, D. M.; Edson, E. F.


    The results are presented of extensive toxicological studies on the systemic organophosphate insecticide dimethoate, and compared with published results from other laboratories. It behaves as a typical indirect anticholinesterase, by conversion in the liver to at least four short-lived active metabolites, whose hydrolysis products are rapidly excreted, mainly in the urine. The acute oral toxicity of dimethoate is low in mammals but higher in avians. Dermal absorption is notably slow and dermal toxicity correspondingly low. Cumulative dosing of rats and guinea-pigs gave no cholinesterase inhibition at 0·7 and 4 mg./kg./day respectively. Dietary feeding to growing rats caused no cholinesterase inhibition at 0·5 mg./kg./day and no other effect at 10 times this dose. The main plant metabolite is identical with one formed in the liver, and comparative feeding tests with normal dimethoate and that partly metabolized in vegetation showed that residue analysis determined total hazard. Tests on humans, some with 32P-labelled material, confirmed that metabolism and urinary excretion are very rapid, that skin absorption is very slow, and that at least 2·5 mg., and probably up to 18 mg., could be ingested daily for at least three weeks without cholinesterase inhibition or other effects. Vapour hazards proved negligible. Oral toxicity was not potentiated by any of 17 other insecticides. The earliest detectable effect of dimethoate poisoning was always erythrocyte cholinesterase inhibition. Symptoms of poisoning could be effectively treated by atropine but not by oxime therapy. No known cases of occupational poisoning have occurred during five years' commercial usage of dimethoate. PMID:14106136

  15. Toxicology of upper aerodigestive tract pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Holt, G.R. (Department of Otolaryngology--Head and Neck Surgery, University of Texas Health Science Center, San Antonio (United States))


    The field of environmental toxicology has become quite important to the study of environmental health in human beings. The stability of the ecosystem in which we live is threatened by the nearly 5 million chemical compounds that have been synthesized worldwide, many of which have real or potentially toxic effects on the environment and on life forms. Four major groups of chemicals--metallic elements, nonmetallic elements, organic compounds and inorganic compounds--have certain agents within them that are known toxins to human beings. Some of these agents have an as yet unknown effect, whereas others have been well characterized. They can be found in the workplace, home, and outdoors, and many are unseen and odorless. In the past, most agents have been described in terms of their carcinogenic potential or major toxic effects on organ systems. It is now likely that the important characterization of some of these agents referrable to the upper aerodigestive tract should be at their receptor sites and identify the very discrete and small effects on these sites and their cumulative effects. The concept of threshold is probably an arbitrary one because to date these discrete effects have not been studied. Susceptibility on an individual basis probably varies from low to high, depending on the patient's immunologic and defense mechanisms and the existence of congenital or acquired risk factors. New attention must be given to more subtle effects on the upper aerodigestive tract (i.e., sinusitis and laryngitis) in view of the potential effects of certain toxic agents on these tissues.

  16. 75 FR 12244 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board... (United States)


    ... HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP); Office of Liaison... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology,...

  17. Role of chronic toxicology studies in revealing new toxicities. (United States)

    Galijatovic-Idrizbegovic, Alema; Miller, Judith E; Cornell, Wendy D; Butler, James A; Wollenberg, Gordon K; Sistare, Frank D; DeGeorge, Joseph J


    Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our review shows that majority of the findings are observed in the subchronic studies since additional target organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 studies in non rodents and 6 studies in rodents yielded new findings that were not seen in studies of 3-month or shorter duration. For 3 compounds the new safety findings did contribute to termination of clinical development plans. Although the incidence of compound termination associated with chronic toxicology study observations is low (∼10%), the observations made in these studies can be important for evaluating human safety risk.

  18. Chemical mixtures: considering the evolution of toxicology and chemical assessment. (United States)

    Monosson, Emily


    The assessment of chemical mixtures is a complex topic for toxicologists, regulators, and the public. In this article the linkage between the science of toxicology and the needs of governmental regulatory agencies in the United States is explored through an overview of environmental regulations enacted over the past century and a brief history of modern toxicology. One of the goals of this overview is to encourage both regulators and scientists to consider the benefits and limitations of this science-regulatory relationship as they tackle existing issues such as chemical mixtures. It is clear that a) over the past 100 years chemical regulation and toxicologic research, have in large part, shared a common emphasis on characterization and regulation of individual chemicals. But chemical mixtures have been, and continue to be, evaluated at hazardous waste sites around the United States. For this reason the current U.S. Environmental Protection Agency guidelines for chemical mixtures assessment are also reviewed. These guidelines highlight the current practice of mixtures assessment, which relies primarily on the existing single-chemical database. It is also clear that b) the science and assessment of chemical mixtures are moving forward through the combined efforts of regulatory agencies and scientists from a broad range of disciplines, including toxicology. Because toxicology is at this exciting crossroads, particular attention should be paid to the forces (e.g., public demands, regulatory needs, funding, academic interests) that both promote and limit the growth of this expanding discipline.

  19. Computational toxicology: Its essential role in reducing drug attrition. (United States)

    Naven, R T; Louise-May, S


    Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them.

  20. The role of the toxicologic pathologist in the post-genomic era(#). (United States)

    Maronpot, Robert R


    molecular biologists. In this present era newly emerging DVM and MD scientists enter the work arena with a PhD in pathology often based on some aspect of molecular biology or molecular pathology research. In molecular biology, the almost daily technological advances require one's complete dedication to remain at the cutting edge of the science. Similarly, the practice of toxicologic pathology, like other morphological disciplines, is based largely on experience and requires dedicated daily examination of pathology material to maintain a well-trained eye capable of distilling specific information from stained tissue slides - a dedicated effort that cannot be well done as an intermezzo between other tasks. It is a rare individual that has true expertise in both molecular biology and pathology. In this genomic era, the newly emerging DVM-PhD or MD-PhD pathologist enters a marketplace without many job opportunities in contrast to the pre-genomic era. Many face an identity crisis needing to decide to become a competent pathologist or, alternatively, to become a competent molecular biologist. At the same time, more PhD molecular biologists without training in pathology are members of the research teams working in drug development and toxicology. How best can the toxicologic pathologist interact in the contemporary team approach in drug development, toxicology research and safety testing? Based on their biomedical training, toxicologic pathologists are in an ideal position to link data from the emerging technologies with their knowledge of pathobiology and toxicology. To enable this linkage and obtain the synergy it provides, the bench-level, slide-reading expert pathologist will need to have some basic understanding and appreciation of molecular biology methods and tools. On the other hand, it is not likely that the typical molecular biologist could competently evaluate and diagnose stained tissue slides from a toxicology study or a cancer bioassay. The post-genomic era: The post

  1. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper


    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformatio...

  2. Functional Similarity and Interpersonal Attraction. (United States)

    Neimeyer, Greg J.; Neimeyer, Robert A.


    Students participated in dyadic disclosure exercises over a five-week period. Results indicated members of high functional similarity dyads evidenced greater attraction to one another than did members of low functional similarity dyads. "Friendship" pairs of male undergraduates displayed greater functional similarity than did "nominal" pairs from…

  3. The added value of proteomics for toxicological studies. (United States)

    Miller, I; Serchi, T; Murk, A J; Gutleb, A C


    Proteomics has the potential to elucidate complex patterns of toxic action attributed to its unique holistic a posteriori approach. In the case of toxic compounds for which the mechanism of action is not completely understood, a proteomic approach may provide valuable mechanistic insight. This review provides an overview of currently available proteomic techniques, including examples of their application in toxicological in vivo and in vitro studies. Future perspectives for a wider application of state-of-the-art proteomic techniques in the field of toxicology are discussed. The examples concern experiments with dioxins, polychlorinated biphenyls, and polybrominated diphenyl ethers as model compounds, as they exhibit a plethora of sublethal effects, of which some mechanisms were revealed via successful proteomic studies. Generally, this review shows the added value of including proteomics in a modern tool box for toxicological studies.

  4. Radiopreservation of food: Toxicological and microbiological safety aspects; Aspetti tossicologici e microbiologici nel trattamento di alimenti con radiazioni

    Energy Technology Data Exchange (ETDEWEB)

    Leonardi, M.; Mauro, F.; Spano`, M. [ENEA, Casaccia (Italy)


    This paper reviews the findings and opinions of leading world health groups (e.g., the US Bureau of Foods - Irradiated Foods Committee, the World Health Organization, the European Communities Selected Committee, etc.) regarding the toxicological and microbiological safety aspects of food radiopreservation. For that which regards toxicology, research studies considered the practice of radiopreservation similar to that of the use of chemical preservatives, i.e., it adds to or forms new substances in the treated food, and care must be taken not to alter normal dietary balance during the performance of health effects studies. The paper notes that toxicological tests are insensitive to the effects induced by radiolysis products since the concentrations of these products are simply far too low. With regard to radiation induced mutations in radiopreserved foods, the paper notes that many study groups share the opinion that radiopreservation induced mutations are not qualitatively different from those produced in conventional treatment methods, and that the practice of radiopreservation appears to be, from a purely microbiological point of view, similar to cold pasteurization of solid foods. It is recommended that more effort be given to the dissemination of public information with regard to the possible health benefits afforded through the use of this food preservation technology.

  5. 75 FR 43918 - National Center for Toxicological Research, et al.; Notice of Consolidated Decision on... (United States)


    ... National Laboratory, Lemont, IL 60439. Instrument: Electron Microscope. Manufacturer: JEOL, Ltd., Japan... International Trade Administration National Center for Toxicological Research, et al.; Notice of Consolidated... Avenue, NW., Washington, DC. Docket Number: 10-015. Applicant: National Center for Toxicological...

  6. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request... (United States)


    ... HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens... Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS); National Institutes... (see ADDRESSES). Dated: November 8, 2011. John R. Bucher, Associate Director, National...

  7. 76 FR 2388 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative... (United States)


    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of... Director, National Toxicology Program. BILLING CODE 4140-01-P...

  8. Applications of scientific imaging in environmental toxicology (United States)

    El-Demerdash, Aref M.

    The national goals of clean air, clean water, and healthy ecosystems are a few of the primary forces that drive the need for better environmental monitoring. As we approach the end of the 1990s, the environmental questions at regional to global scales are being redefined and refined in the light of developments in environmental understanding and technological capability. Research in the use of scientific imaging data for the study of the environment is urgently needed in order to explore the possibilities of utilizing emerging new technologies. The objective of this research proposal is to demonstrate the usability of a wealth of new technology made available in the last decade to providing a better understanding of environmental problems. Research is focused in two imaging techniques macro and micro imaging. Several examples of applications of scientific imaging in research in the field of environmental toxicology were presented. This was achieved on two scales, micro and macro imaging. On the micro level four specific examples were covered. First, the effect of utilizing scanning electron microscopy as an imaging tool in enhancing taxa identification when studying diatoms was presented. Second, scanning electron microscopy combined with energy dispersive x-ray analyzer were demonstrated as a valuable and effective tool for identifying and analyzing household dust samples. Third, electronic autoradiography combined with FT-IR microscopy were used to study the distribution pattern of [14C]-Malathion in rats as a result of dermal exposure. The results of the autoradiography made on skin sections of the application site revealed the presence of [ 14C]-activity in the first region of the skin. These results were evidenced by FT-IR microscopy. The obtained results suggest that the penetration of Malathion into the skin and other tissues is vehicle and dose dependent. The results also suggest the use of FT-IR microscopy imaging for monitoring the disposition of

  9. Lewisite: its chemistry, toxicology, and biological effects. (United States)

    Goldman, M; Dacre, J C


    routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic.

  10. Toxicological evaluation of u-hEGF. (United States)

    Maraschin, R; Bussi, R; Conz, A; Orlando, L; Pirovano, R; Nyska, A


    The toxicological evaluation of urinary human epidermal growth factor (u-hEGF) included mutagenicity, single and repeated dose general toxicity, and teratogenicity studies in various animal species. The mutagenic potential of u-hEGF was tested in vitro (Ames test, chromosome aberration in human lymphocytes, unscheduled DNA synthesis in HeLa cells) and in vivo (chromosome aberration in Chinese hamster bone marrow and micronucleus test in rat bone marrow). No mutagenic or clastogenic effects were found. The acute toxicity of u-hEGF was evaluated in mice and rats, using single subcutaneous (sc) or intravenous (i.v.) injection of 15 mg/kg. No toxic effects were observed Four-week i.v. daily administration of u-hEGF at the doses of 0.3, o.9, and 3 mg/kg in the SD rat followed by 2 wk of compound withdrawal induced pronounced and generally dose-related effects (i.e., epithelial hyperplasia) in a wide range of tissues and organs, at all doses. However, these effects were not apparently detrimental to the general health of the rats. The repeated sc administration of u-hEGF to cynomolgus monkeys for 4 wk at the same doses as used in the rat study resulted in lethality after about 7 days of treatment in the 2 higher dose groups or after 14 days at the lowest dose. The main clinical signs observed were gastrointestinal effects, respiratory distress, sedation, marked loss of body weight, and cutaneous desquamation. At histology, hyperplasia of most epithelia was seen in all groups. In addition, atrophy of the ovarian follicles and necrosis of the uterine endometrium were noted. Changes considered secondary to physical distress were atrophy of the hemopoietic and lymphatic system and hepatic steatosis. The embryofetal toxicity and teratogenicity of u-hEGF was tested, using the i.v. route in the SD rat and the i.v. and sc routes in the New Zealand White rabbit. In both species, the compound was administered at the doses of 0, 0.3, 0.9, and 3 mg/kg/day, from day 6 to 15 of

  11. Toxicología de Medicamentos y Residuos en Alimentos


    García Fernández, Antonio Juan


    Presentaciones de las clases de las asignatura de Toxicología en la Licenciatura de Veterinaria del curso 2011/12. El documento se centra en, por un lado, la toxicología de los medicamentos y las reacciones adversas de éstos; y por otro lado, en la toxicologia y problemática en torno a las sustancias prohibidas en la clínica y producción animal; y que pueden generar problemas de salud pública, relacionados con inseguridad alimentaria.

  12. Henry Matthew: the father of modern clinical toxicology. (United States)

    Proudfoot, A T; Prescott, L F


    Henry Matthew was appointed a consultant in the Royal Infirmary of Edinburgh in 1955, by which time he was a highly regarded general physician with an interest in cardiology. In 1964 he agreed, almost certainly reluctantly, to head the recently designated Regional Poisoning Treatment Centre, which he did until his retirement ten years later. Matthew quickly established himself as an authority in clinical toxicology, mainly from an unrivalled experience of treating poisoned patients, day-in and day-out, but also by publishing original research, letters and books. Such were his contributions that he is regarded as the father of clinical toxicology.

  13. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) ... (United States)

    The IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) was released for external peer review in April 2017. EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) will conduct a peer review of the scientific basis supporting the ETBE assessment and release a final report of their review. Information regarding the peer review can be found on the SAB website. EPA is conducting an Integrated Risk Information System (IRIS) health assessment for Ethyl Tertiary Butyl Ether (ETBE). The outcome of this project is a Toxicological Review and IRIS Summary for ETBE that will be entered into the IRIS database.

  14. 78 FR 54476 - Availability of Draft National Toxicology Program Technical Reports; Request for Comments; Notice... (United States)


    ... HUMAN SERVICES National Institutes of Health Availability of Draft National Toxicology Program Technical Reports; Request for Comments; Notice of Meeting SUMMARY: The National Toxicology Program (NTP) announces..., 2013. John R. Bucher, Associate Director, National Toxicology Program. BILLING CODE 4140-01-P...

  15. 75 FR 37443 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative... (United States)


    ... HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of...'-deoxyuridine (BrdU) incorporation. Toxicology Letters 119(3): 203-208. Dated: June 16, 2010. John R. Bucher, Associate Director, National Toxicology Program. BILLING CODE 4140-01-P...

  16. Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference. (United States)

    Adami, Hans-Olov; Berry, Sir Colin L; Breckenridge, Charles B; Smith, Lewis L; Swenberg, James A; Trichopoulos, Dimitrios; Weiss, Noel S; Pastoor, Timothy P


    Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step "Epid-Tox" process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality.


    Directory of Open Access Journals (Sweden)

    Q. X. Xu


    Full Text Available The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  18. a Comparison of Semantic Similarity Models in Evaluating Concept Similarity (United States)

    Xu, Q. X.; Shi, W. Z.


    The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  19. Renewing the Respect for Similarity

    Directory of Open Access Journals (Sweden)

    Shimon eEdelman


    Full Text Available In psychology, the concept of similarity has traditionally evoked a mixture of respect, stemmingfrom its ubiquity and intuitive appeal, and concern, due to its dependence on the framing of the problemat hand and on its context. We argue for a renewed focus on similarity as an explanatory concept, bysurveying established results and new developments in the theory and methods of similarity-preservingassociative lookup and dimensionality reduction — critical components of many cognitive functions, aswell as of intelligent data management in computer vision. We focus in particular on the growing familyof algorithms that support associative memory by performing hashing that respects local similarity, andon the uses of similarity in representing structured objects and scenes. Insofar as these similarity-basedideas and methods are useful in cognitive modeling and in AI applications, they should be included inthe core conceptual toolkit of computational neuroscience.

  20. Similarity Learning of Manifold Data. (United States)

    Chen, Si-Bao; Ding, Chris H Q; Luo, Bin


    Without constructing adjacency graph for neighborhood, we propose a method to learn similarity among sample points of manifold in Laplacian embedding (LE) based on adding constraints of linear reconstruction and least absolute shrinkage and selection operator type minimization. Two algorithms and corresponding analyses are presented to learn similarity for mix-signed and nonnegative data respectively. The similarity learning method is further extended to kernel spaces. The experiments on both synthetic and real world benchmark data sets demonstrate that the proposed LE with new similarity has better visualization and achieves higher accuracy in classification.

  1. 3D liver models in tissue engineering and toxicology

    NARCIS (Netherlands)

    Starokozhko, Viktoriia


    In her thesis, Viktoriia Starokozhko developed new and improved existing liver models for the use in tissue engineering and toxicology. One of the models she described and used are liver slices (PCLS), a mini-organ model for the liver. PCLS are used already for many years in various fields of pharma

  2. Adverse outcome pathways (AOPs): A framework to support predictive toxicology (United States)

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  3. Solid-phase extraction procedures in systematic toxicological analysis

    NARCIS (Netherlands)

    Franke, J.P.; de Zeeuw, R.A


    In systematic toxicological analysis (STA) the substance(s) present is (are) not known at the start of the analysis. in such an undirected search the extraction procedure cannot be directed to a given substance but must be a general procedure where a compromise must be reached in that the substances

  4. Human environments: definition, scope, and the role of toxicology. (United States)

    Hodgson, Ernest


    This chapter is a brief introduction to the subject matter of the volume including the complexity and definition of human environments. Exposure to complex mixtures and the problem of interactions are considered as well as the important role of toxicology in environmental and human health, including risk analysis, risk management, and risk communication.

  5. Statistical approaches to the design of toxicology studies. (United States)

    Gad, S C


    Application of statistics to toxicological studies involves hypothesis testing, model fitting, and reduction of dimensionality. This unit reviews statistical approaches to data (i.e., descriptive statistics, experimental design, outliers and rounding of numbers, and specific applications) and includes a set of decision trees to assist in choosing the appropriate methods.

  6. Application of DNA Profiling in Resolving Aviation Forensic Toxicology Issues (United States)


    Pilot: Bone ,.muscle,.skin,.and.lung Toxicological Findings Pilot: Propoxyphene.0 .308.µg/ .341. µg/ Norpropoxyphene.0 .671...Female Passenger: Negative Male Passenger: Diazepam ,.nordiazepam,.and.zolpi- Reason for DNA Profiling

  7. [The toxicological aspects of poisonings by psilocybine-containing mushrooms]. (United States)

    Babakhanian, R V; Bushuev, E S; Kazankov, S P; Kostyrko, T A


    Cases involving the investigation of psylocybin-containing mushrooms became more frequent in forensic chemical and criminological expert evaluation in recent years. The authors present the data on the main chemical factors contained in these mushrooms, on the mechanism of their toxic effect, clinical picture of poisoning, and methods of chemical and toxicological analysis.

  8. Manpower Development in Toxicology. EURO Reports and Studies, No. 9. (United States)

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This report addresses the widely held view that currently available literature in toxicology is inadequate in that there is a need to identify manpower deficiencies in this field and to suggest means to correct these deficiencies. It contains a list of specific recommendations including the organization of a working group, sponsored by the World…

  9. Stem Cell-Derived Systems in Toxicology Assessment

    NARCIS (Netherlands)

    Suter-Dick, Laura; Alves, Paula M.; Blaauboer, Bas J.; Bremm, Klaus-Dieter; Brito, Catarina; Coecke, Sandra; Flick, Burkhard; Fowler, Paul; Hescheler, Juergen; Ingelman-Sundberg, Magnus; Jennings, Paul; Kelm, Jens M.; Manou, Irene; Mistry, Pratibha; Moretto, Angelo; Roth, Adrian; Stedman, Donald; van de Water, Bob; Beilmann, Mario


    Industrial sectors perform toxicological assessments of their potential products to ensure human safety and to fulfill regulatory requirements. These assessments often involve animal testing, but ethical, cost, and time concerns, together with a ban on it in specific sectors, make appropriate in vit

  10. Comment on " An update on toxicology of aluminum phosphide "

    Directory of Open Access Journals (Sweden)

    Omid Mehrpour


    Full Text Available I read with interest the recent published article by Dr Moghadamnia titled "An update on toxicology of aluminum phosphide". Since aluminum phosphide (AlP poisoning is an important medical concern in Iran, I have had the opportunities to work and publish many papers in this regard. I would like to comment on that paper.


    Scientists from Europe, North America and South America convened in Capri, Italy, April 24-28, 2006 for the Ninth International Symposium on Fish Physiology, Toxicology, and Water Quality. The subject of the meeting was Eutrophication: The toxic effects of ammonia, nitrite and th...

  12. IRIS Toxicological Review of Libby Amphibole Asbestos (Final Report) (United States)

    EPA has finalized the, Toxicological Review of Libby Amphibole Asbestos: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  13. Dynamic similarity in erosional processes (United States)

    Scheidegger, A.E.


    A study is made of the dynamic similarity conditions obtaining in a variety of erosional processes. The pertinent equations for each type of process are written in dimensionless form; the similarity conditions can then easily be deduced. The processes treated are: raindrop action, slope evolution and river erosion. ?? 1963 Istituto Geofisico Italiano.

  14. Occupational asphyxiation by unknown compound(s): environmental and toxicological approach. (United States)

    Poli, D; Solarino, B; Di Vella, G; Tattoli, L; Strisciullo, G; Goldoni, M; Mutti, A; Gagliano-Candela, R


    During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death. Environmental results indicated that H(2)S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks. These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H(2)S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2 mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction. This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s).

  15. Consideraciones importantes acerca de la cuarentena de perros como Biomodelos experimentales en Toxicología

    Directory of Open Access Journals (Sweden)

    Arencibia Arrebola Daniel Francisco, Pardo Acosta Balia, Gámez Menéndez Rafael


    Full Text Available Las sustancias químicas son indispensables en la vida del hombre,contribuyen al aumento de la producción de alimentos, alivian muchasenfermedades y facilitan la existencia cotidiana de nuestra sociedad. El desarrollo de la toxicología como una ciencia independiente se ha ido consolidando durante los últimos años ante la necesidad de profundizar los conocimientos para abordar y resolver los problemas que a esta ciencia competen. El uso del perro como biomodelo experimental en toxicología viene dado tras los resultados favorables obtenidos en disímiles experimentos, planteándose que en esta especie los procesos metabólicosson similares a los del humano. En este trabajo nos trazamos como objetivo debatir todo lo concerniente a la cuarentena de perros de laboratorio, así como los factores que intervienen en la misma, con una duración de 3-4 semanas desde la llegada de los animales hasta su empleo en las diferentes investigaciones. Se tuvieron en cuenta la transportación, recepción, ambiente en los locales, acciones posteriores a la recepción, frecuencias de las observaciones, local de aislamiento, limpieza y desinfección, consumo de alimento y agua, así como los criterios y métodos de eutanasia.

  16. Review of the toxicology of carbonyl sulfide, a new grain fumigant. (United States)

    Bartholomaeus, Andrew R; Haritos, Victoria S


    Carbonyl sulfide (COS) is a new grain fumigant which has been developed to replace methyl bromide, being phased out due to its ozone depletion properties, and to supplement phosphine gas which is experiencing increased insect resistance. Treatment of commodities with COS, a highly effective fumigant, results in residues that are near or indistinguishable to natural background levels of this compound. COS is a naturally occurring gas, being the predominant sulfur moiety in the atmosphere, occurs naturally in food and is a normal by-product of mammalian aerobic metabolism. COS has low acute inhalational toxicity but with a steep dose response curve; COS is neither genotoxic nor a developmental toxicant but does reversibly impair male fertility. Prolonged, repeated exposure to COS is likely to present similar neurotoxicity hazards to that of the structurally and toxicologically related compound carbon disulfide. Although the occupational risks presented by COS as a fumigant of bulk grain are significant, these are, as they have been for a considerable time for phosphine and methyl bromide, manageable by good occupational safety practices. Consideration may need to be given to scrubbing of ventilated COS and its breakdown product hydrogen sulfide, at the completion of fumigation to minimise worker and bystander exposure. In terms of classical regulatory toxicology studies, the available database for COS is deficient in many aspects and registration in most jurisdictions will depend on sound scientific argument built upon the totality of the existing scientific data as there are strong arguments supporting the registration of this compound.

  17. Distance learning and toxicology: new horizons for Paracelsus. (United States)

    Huggins, Jane; Morris, John; Peterson, C Erik


    Distance learning offers many advantages to students and teachers of almost any scientific discipline. Toxicology is no exception. For example, should Paracelsus be interested in learning more about toxicology at Drexel University, he would have the opportunity to take two courses in this subject utilizing the content management software, WebCT. The two courses would offer a website from which he could view and/or download his notes for each class. He could correspond with the instructor as well as fellow students, participate in discussions about timely topics, and make presentations to the class, all via electronic communication. Moreover, his examinations would also be computerized. Although he might have the option of attending traditional "face-to-face" lectures with other students in the class, he could also access these lectures at any time from a remote location by using the archive of taped lectures on the class website. Overall, Paracelsus would have access to many tools to enhance his understanding of toxicology, and he probably would never have to worry about parking before class (!). The two WebCT modules in toxicology that we have developed at Drexel represent the successful migration of two courses from a traditional "face-to-face" model of classroom instruction to hybrid models that combine "face-to-face" interaction with online instruction. Student and faculty evaluations of these courses have been very positive. Future plans include linking the two modules together so that students in the advanced class can do "review" or "remedial" work in the basic module. Furthermore, a library of video clips is also planned in which researchers will be discussing their work on various toxicologic topics. Students will be able to access these clips as resources from which to write research papers.

  18. [The challenges of the ethics of personalism to clinical toxicology]. (United States)

    Brusiło, Jerzy


    The fields of philosophical anthropology and the ethics of personalism overlap in the area of many difficult personal situations involving clinical toxicology. These therapeutic situations need an integral, multidimensional, and personal approach for both the patient and the toxicologist. This means that man is treated not only as a physical (biological) being but also there is an appreciation for the mental sphere, which includes rational, emotional, and spiritual elements while not forgetting that the human person is also part of the human community. Studying such an individual's personal decision as suicide, we must realize that it's not just physiological or biochemical poisons but also includes the poisoning of the psyche, as well as poisoning relationships with loved ones (family), poisoning social relations (in school or the workplace) and poisoning the spirit, in other words, there is no meaning in life itself, nor the meaning of God's existence, nor the meaning of faith, hope and love. Not only is there a greater "variety of poisons" than before, they are much more extensive and deep. For example, we can name environmental pollution, industrial poisons, chemical waste, genetic modification, powerful medications, or even the toxic social environment of evil ideas, malicious manipulation of the human mind (destructive religious sects). In approaching the challenges of clinical toxicology, the doctor must not only be a specialist in chemistry, biochemistry and pharmacology. What then is of future of toxicology because of this human dimension (anthropological, ethical and spiritual) of this teaching? As today marks the occasion of the 45th anniversary of the Clinic of Toxicology CM UJ, should we shape the ethos of young doctors who want to deal with toxicology seriously?

  19. Similarity of samples and trimming

    CERN Document Server

    Álvarez-Esteban, Pedro C; Cuesta-Albertos, Juan A; Matrán, Carlos; 10.3150/11-BEJ351


    We say that two probabilities are similar at level $\\alpha$ if they are contaminated versions (up to an $\\alpha$ fraction) of the same common probability. We show how this model is related to minimal distances between sets of trimmed probabilities. Empirical versions turn out to present an overfitting effect in the sense that trimming beyond the similarity level results in trimmed samples that are closer than expected to each other. We show how this can be combined with a bootstrap approach to assess similarity from two data samples.

  20. Opportunities and challenges of strengthening veterinary toxicology in Africa in the 21st century. (United States)

    Rumbeiha, W K


    Veterinary toxicology is the specialty of veterinary medicine dealing with the study, diagnosis and treatment of effects of natural and man-made chemicals, forms of energy, and gasses in the animal kingdom. Historically, veterinary toxicology has been narrowly defined as the diagnosis and treatment of poisoning in domesticated animals and poultry, but the profession has grown to include food safety and environmental toxicology. Veterinary toxicology is most well-developed and recognized as a specialty in North America where professional societies and specialty board certification exist. In many parts of Africa, perhaps with the exception of South Africa, veterinary toxicology has not evolved in more than 40 years. The importance of veterinary toxicology in the modern era can not be over emphasized. This report examines the status of veterinary toxicology in Africa at the beginning of the 21st century and offers arguments why it is important for African governments to devote more resources to strengthen it.

  1. Self-similar aftershock rates

    CERN Document Server

    Davidsen, Jörn


    In many important systems exhibiting crackling noise --- intermittent avalanche-like relaxation response with power-law and, thus, self-similar distributed event sizes --- the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is in particular true for the case of seismicity and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features. Comparing our theoretical predictions with high resolution earthquake data from Southern California we find excellent agreement, providing in particular clear evidence for a unified description of aftershocks and foreshocks. This may offer an improved way of time-dependent seismic hazard assessment and earthquake forecasting.

  2. Self-similar aftershock rates (United States)

    Davidsen, Jörn; Baiesi, Marco


    In many important systems exhibiting crackling noise—an intermittent avalanchelike relaxation response with power-law and, thus, self-similar distributed event sizes—the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is particularly true for the case of seismicity, and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features. Comparing our theoretical predictions with high-resolution earthquake data from Southern California we find excellent agreement, providing particularly clear evidence for a unified description of aftershocks and foreshocks. This may offer an improved framework for time-dependent seismic hazard assessment and earthquake forecasting.

  3. Contextual Bandits with Similarity Information

    CERN Document Server

    Slivkins, Aleksandrs


    In a multi-armed bandit (MAB) problem, an online algorithm makes a sequence of choices. In each round it chooses from a time-invariant set of alternatives and receives the payoff associated with this alternative. While the case of small strategy sets is by now well-understood, a lot of recent work has focused on MAB problems with exponentially or infinitely large strategy sets, where one needs to assume extra structure in order to make the problem tractable. In particular, recent literature considered information on similarity between arms. We consider similarity information in the setting of "contextual bandits", a natural extension of the basic MAB problem where before each round an algorithm is given the "context" -- a hint about the payoffs in this round. Contextual bandits are directly motivated by placing advertisements on webpages, one of the crucial problems in sponsored search. A particularly simple way to represent similarity information in the contextual bandit setting is via a "similarity distance...

  4. The National Toxicology Program Web-based nonneoplastic lesion atlas: a global toxicology and pathology resource. (United States)

    Cesta, Mark F; Malarkey, David E; Herbert, Ronald A; Brix, Amy; Hamlin, Melvin H; Singletary, Emily; Sills, Robert C; Bucher, John R; Birnbaum, Linda S


    Toxicologists and pathologists worldwide will benefit from a new, website-based, and completely searchable Nonneoplastic Lesion Atlas just released by the U.S. National Toxicology Program (NTP). The atlas is a much-needed resource with thousands of high-quality, zoomable images and diagnostic guidelines for each rodent lesion. Liver, gallbladder, nervous system, bone marrow, lower urinary tract and skin lesion images, and diagnostic strategies are available now. More organ and biological systems will be added with a total of 22 chapters planned for the completed project. The atlas will be used by the NTP and its many pathology partners to standardize lesion diagnosis, terminology, and the way lesions are recorded. The goal is to improve our understanding of nonneoplastic lesions and the consistency and accuracy of their diagnosis between pathologists and laboratories. The atlas is also a useful training tool for pathology residents and can be used to bolster any organization's own lesion databases. Researchers have free access to this online resource at

  5. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper


    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...... a synthetic example from molecular dynamics simulations. We then apply the algorithms to revisit the problem of ensemble averaging during structure determination of proteins, and find that an ensemble refinement method is able to recover the correct distribution of conformations better than standard single...

  6. Community Detection by Neighborhood Similarity

    Institute of Scientific and Technical Information of China (English)

    LIU Xu; XIE Zheng; YI Dong-Yun


    Detection of the community structure in a network is important for understanding the structure and dynamics of the network.By exploring the neighborhood of vertices,a local similarity metric is proposed,which can be quickly computed.The resulting similarity matrix retains the same support as the adjacency matrix.Based on local similarity,an agglomerative hierarchical clustering algorithm is proposed for community detection.The algorithm is implemented by an efficient max-heap data structure and runs in nearly linear time,thus is capable of dealing with large sparse networks with tens of thousands of nodes.Experiments on synthesized and real-world networks demonstrate that our method is efficient to detect community structures,and the proposed metric is the most suitable one among all the tested similarity indices.%Detection of the community structure in a network is important for understanding the structure and dynamics of the network. By exploring the neighborhood of vertices, a local similarity metric is proposed, which can be quickly computed. The resulting similarity matrix retains the same support as the adjacency matrix. Based on local similarity, an agglomerative hierarchical clustering algorithm is proposed for community detection. The algorithm is implemented by an efficient max-heap data structure and runs in nearly linear time, thus is capable of dealing with large sparse networks with tens of thousands of nodes. Experiments on synthesized and real-world networks demonstrate that our method is efficient to detect community structures, and the proposed metric is the most suitable one among all the tested similarity indices.

  7. [Specific toxicological considerations on anabolic agents; transmitted toxicity]. (United States)

    Ferrando, R; Truhaut, R


    The growth of populations and the spread of urbanization, resulting in new agricultural structures, have entailed a concentration of livestock production and recourse to new techniques. Of some importance among these techniques is the enteric or parenteral administration of substances in very low doses. These substances include anabolic agents, some of which, like many natural feeds, exhibit hormonal activity. They may be divided into two classes: --those of the DES type, synthetic compounds non-existent in the natural state, --natural agents, which are normally distributed throughout the animal and human organism, and hence in food of animal origin---milk, meat, eggs. The compounds belonging to the second class may also be synthesized and the main toxicological consideration is that they then have to meet clear-cut standards of identity and purity. A compound belonging to the first class, diethylstilbestrol (DES), administered to rats in doses as small as 60 mug/kg of feed or even smaller, causes in general lower growth rates as well as alterations in the genital system and reproductive functions. In long-term experiments (12 months) using rats and mice and applying so-called toxicity "de relais" tests, developed and described by the authors, it also appeared that meat from calves in which DES pellets were implanted under normal rearing conditions, inhibits growth and reproduction in mice and rats fed a diet containing 20% of this meat. Studies in which the livers from treated calves constituted 6% of the diet of these two rodent species also led to the conclusion that fertility was impaired in the second reproduction test. The authors also recall cases of vaginal cancer observed in young girls whose mothers had been treated with DES during pregnancy. Compounds belonging to the second class (estradiol-progesterone and estradiol-testosterone) gave no evidence of harmful effects upon rats when mixed with their rations during short and medium-term trials. Similar

  8. Similarity of atoms in molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cioslowski, J.; Nanayakkara, A. (Florida State Univ., Tallahassee, FL (United States))


    Similarity of atoms in molecules is quantitatively assessed with a measure that employs electron densities within respective atomic basins. This atomic similarity measure does not rely on arbitrary assumptions concerning basis functions or 'atomic orbitals', is relatively inexpensive to compute, and has straightforward interpretation. Inspection of similarities between pairs of carbon, hydrogen, and fluorine atoms in the CH[sub 4], CH[sub 3]F, CH[sub 2]F[sub 2], CHF[sub 3], CF[sub 4], C[sub 2]H[sub 2], C[sub 2]H[sub 4], and C[sub 2]H[sub 6] molecules, calculated at the MP2/6-311G[sup **] level of theory, reveals that the atomic similarity is greatly reduced by a change in the number or the character of ligands (i.e. the atoms with nuclei linked through bond paths to the nucleus of the atom in question). On the other hand, atoms with formally identical (i.e. having the same nuclei and numbers of ligands) ligands resemble each other to a large degree, with the similarity indices greater than 0.95 for hydrogens and 0.99 for non-hydrogens. 19 refs., 6 tabs.

  9. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico


    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  10. Metabolomics of Methylphenidate and Ethylphenidate: Implications in Pharmacological and Toxicological Effects. (United States)

    Dinis-Oliveira, Ricardo Jorge


    Methylphenidate (MPH) is primarily indicated for attention-deficit hyperactivity disorder and narcolepsy therapy. A marked individual variability in the dose-response has been observed, and therefore dosage must be titrated for optimal therapeutic effect with minimal toxicity. This variability has been claimed to be predominantly pharmacokinetic. Moreover, due to its similar pharmacodynamics to amphetamine, MPH has been abused and fatalities have been reported. This review aims to discuss metabolomics of MPH, namely by presenting all major and minor metabolites. Ritalinic acid is the main metabolite. In addition, minor pathways involving aromatic hydroxylation, microsomal oxidation and conjugation have also been reported to form the p-hydroxy-, oxo- and conjugated metabolites, respectively. MPH may undergo transesterification with ethanol producing ethylphenidate, which is also pharmacologically active. It is expected that knowing the metabolomics of MPH may provide further insights regarding individual contribution for MPH pharmacodynamics and toxicological effects, namely if ethanol is co-consumed.

  11. Distance learning for similarity estimation

    NARCIS (Netherlands)

    Yu, J.; Amores, J.; Sebe, N.; Radeva, P.; Tian, Q.


    In this paper, we present a general guideline to find a better distance measure for similarity estimation based on statistical analysis of distribution models and distance functions. A new set of distance measures are derived from the harmonic distance, the geometric distance, and their generalized

  12. Distance learning for similarity estimation. (United States)

    Yu, Jie; Amores, Jaume; Sebe, Nicu; Radeva, Petia; Tian, Qi


    In this paper, we present a general guideline to find a better distance measure for similarity estimation based on statistical analysis of distribution models and distance functions. A new set of distance measures are derived from the harmonic distance, the geometric distance, and their generalized variants according to the Maximum Likelihood theory. These measures can provide a more accurate feature model than the classical Euclidean and Manhattan distances. We also find that the feature elements are often from heterogeneous sources that may have different influence on similarity estimation. Therefore, the assumption of single isotropic distribution model is often inappropriate. To alleviate this problem, we use a boosted distance measure framework that finds multiple distance measures which fit the distribution of selected feature elements best for accurate similarity estimation. The new distance measures for similarity estimation are tested on two applications: stereo matching and motion tracking in video sequences. The performance of boosted distance measure is further evaluated on several benchmark data sets from the UCI repository and two image retrieval applications. In all the experiments, robust results are obtained based on the proposed methods.

  13. Comparison of hydrological similarity measures (United States)

    Rianna, Maura; Ridolfi, Elena; Manciola, Piergiorgio; Napolitano, Francesco; Russo, Fabio


    The use of a traditional at site approach for the statistical characterization and simulation of spatio-temporal precipitation fields has a major recognized drawback. Indeed, the weakness of the methodology is related to the estimation of rare events and it involves the uncertainty of the at-site sample statistical inference, because of the limited length of records. In order to overcome the lack of at-site observations, regional frequency approach uses the idea of substituting space for time to estimate design floods. The conventional regional frequency analysis estimates quantile values at a specific site from multi-site analysis. The main idea is that homogeneous sites, once pooled together, have similar probability distribution curves of extremes, except for a scaling factor. The method for pooling groups of sites can be based on geographical or climatological considerations. In this work the region of influence (ROI) pooling method is compared with an entropy-based one. The ROI is a flexible pooling group approach which defines for each site its own "region" formed by a unique set of similar stations. The similarity is found through the Euclidean distance metric in the attribute space. Here an alternative approach based on entropy is introduced to cluster homogeneous sites. The core idea is that homogeneous sites share a redundant (i.e. similar) amount of information. Homogeneous sites are pooled through a hierarchical selection based on the mutual information index (i.e. a measure of redundancy). The method is tested on precipitation data in Central Italy area.

  14. Toxicological mass disaster management - a hospital deployment scheme. (United States)

    Baniel, J; Ram, Z; Kami, A; Schindel, D


    Toxicological mass disasters have occurred frequently in past years and constitute a permanent threat in urban areas. From the standpoint of hospital planning, special consideration is required to treat a large number of poisoned casualties in a relatively short period. Several unique medical aspects characterize toxicological mass disasters: casualties present a single disease entity with many "borderline" cases, most medical personnel are unfamiliar with the problem and casualties present a potential contamination hazard to the hospital. A hospital deployment scheme is presented recommending Decontamination, Triage and simple Treatment Algorithms to meet the medical and organizational challenge of such a mass casualty situation. A further specific deployment scheme for treatment of organophosphorus agents poisoning is described to illustrate the principles presented.

  15. Toxicological perspectives on perfluorinated compounds in avian species

    Energy Technology Data Exchange (ETDEWEB)

    Giesy, J.; Jones, P. [Michigan State Univ., East Lansing, MI (United States)


    Perfluorinated chemicals have been widely used in commerce for the last few decades. Until recently little was known about their environmental fate and even less was known about their potential environmental effects. Since Giesy and co-workers first demonstrated the widespread occurrence of perfluorooctane sulfonic acid (PFOS) in wildlife there has been renewed interest in determining the biological and possible ecological effects of these compounds. The assessment of possible effects of these chemicals has been hampered by a limited understanding of their mode of action and by a lack of toxicological data for wildlife species. Here we summarize recently obtained toxicological studies available for perfluorinated compounds (PFCs) in two avian species and use this information and environmental concentration data to evaluate the potential for environmental risk that these compounds pose.

  16. Histo- and cytochemistry as a tool in environmental toxicology. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Graumann, W. (Tuebingen Univ. (Germany). Dept. of Anatomy); Drukker, J. (Rijksuniversiteit Limburg, Maastricht (Netherlands). Dept. of Anatomy and Embryology) (eds.)


    Toxicology is expected to play more and more a key role in the context of environmental pollution. The central question taken up by this book is whether histo- and cytochemistry, by virtue of their superior localization capabilities, can make decisive contribution to toxicology. This volume comprises lectures and reviews in different fields of research (e.g. carcinogenesis, Alzheimer's Disease, transport of mercury from silver amalgam restorations) using a spectrum of methodological techniques (e.g. enzyme histochemistry, immunocytochemistry, autometallography, microprobe analysis), presented at the 32nd symposium of the Gesellschaft fuer Histochemie (International Association of Histochemists) in Gargellen (Austria) from September 26-29, 1990. (orig.). With 207 figs., 28 tabs.

  17. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    Directory of Open Access Journals (Sweden)

    Anne Marie Ciobanu


    Full Text Available Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance in the case of an overdose, determining compliance of the treatment. The present paper aims to address the needs of healthcare professionals involved in drugs addiction treatment through systematic presentation of information regarding their toxicological analysis. Basically, it is a tool that help you to select the suitable biological sample and the right collecting time, as well as the proper analysis technique, depending on the purpose of analysis, pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise.

  18. Salvia divinorum: toxicological aspects and analysis in human biological specimens. (United States)

    Margalho, Cláudia; Corte-Real, Francisco; López-Rivadulla, Manuel; Gallardo, Eugenia


    The identification and quantitation of the main psychoactive component of Salvia divinorum (salvinorin A) in biological specimens are crucial in forensic and clinical toxicology. Despite all the efforts made, its uncontrolled abuse has increased quickly, exposing its users' health to serious risks both in the short and long term. The use of alternative biological matrices in toxicological analyzes can be advantageous as complementary postmortem samples, or in situations when neither blood nor urine can be collected; they may be useful tools in those determinations, providing important information about prior exposure. The aim of this article is to present a brief summary of legal aspects of Salvia divinorum and salvinorin A, including the methods used for the determination of the latter in biological matrices.

  19. Toxicological effects of pyrethroids on non-target aquatic insects. (United States)

    Antwi, Frank B; Reddy, Gadi V P


    The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments.

  20. Modern imaging technologies in toxicologic pathology: An overview. (United States)

    Ying, Xiaoyou; Monticello, Thomas M


    Modern imaging technology, now utilized in most biomedical research areas (bioimaging), enables the detection and visualization of biological processes at various levels of the molecule, organelle, cell, tissue, organ and/or whole body. In toxicologic pathology, the impact of modern imaging technology is becoming apparent from digital histopathology to novel molecular imaging for in vivo studies. This overview summarizes recent progresses in digital microscopy imaging and newly developed digital slide techniques. Applications of virtual microscopy imaging are discussed and compared to traditional optical microscopy reading. New generation digital pathology approaches, including automatic slide inspection, digital slide databases and image management are briefly introduced. Commonly used in vivo preclinical imaging technologies are also summarized. While most of these new imaging techniques are still undergoing rapid development, it is important that toxicologic pathologists embrace and utilize these technologies as advances occur.

  1. The adverse outcome pathway concept: a pragmatic tool in toxicology. (United States)

    Vinken, Mathieu


    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies.


    Directory of Open Access Journals (Sweden)

    Ramshankar Vijayalakshmi


    Full Text Available Recently Biopharmaceuticals are the new chemotherapeutical agents that are called as “Biosimilars” or “follow on protein products” by the European Medicines Agency (EMA and the American regulatory agencies (Food and Drug Administration respectively. Biosimilars are extremely similar to the reference molecule but not identical, however close their similarities may be. A regulatory framework is therefore in place to assess the application for marketing authorisation of biosimilars. When a biosimilar is similar to the reference biopharmaceutical in terms of safety, quality, and efficacy, it can be registered. It is important to document data from clinical trials with a view of similar safety and efficacy. If the development time for a generic medicine is around 3 years, a biosimilar takes about 6-9 years. Generic medicines need to demonstrate bioequivalence only unlike biosimilars that need to conduct phase I and Phase III clinical trials. In this review, different biosimilars that are already being used successfully in the field on Oncology is discussed. Their similarity, differences and guidelines to be followed before a clinically informed decision to be taken, is discussed. More importantly the regulatory guidelines that are operational in India with a work flow of making a biosimilar with relevant dos and dont’s are discussed. For a large populous country like India, where with improved treatments in all sectors including oncology, our ageing population is increasing. For the health care of this sector, we need more newer, cheaper and effective biosimilars in the market. It becomes therefore important to understand the regulatory guidelines and steps to come up with more biosimilars for the existing population and also more information is mandatory for the practicing clinicians to translate these effectively into clinical practice.

  3. Developments in analysis and toxicology of toxaphene compounds


    de Geus, H-J; Besselink, H.; Brouwer, A.; Klungsøyr, J; MacGovern, E.; MacHugh, B.; Nixon, E.; Rimkus, G.G.; Wester, P.G.; De Boer, J.


    Over the last 50 years toxaphene has been produced and used as a pesticide extensively. The US Environmental Protection Agency banned it in 1982. In the early 1990s the presence of toxaphene in marine fish in Europe caused concern with regard to human health in relation with consumption. This paper gives a brief overview of recent developments in the analytical and toxicological research on toxaphene.

  4. Toxicologic evaluation of analytes from Tank 241-C-103

    Energy Technology Data Exchange (ETDEWEB)

    Mahlum, D.D.; Young, J.Y.; Weller, R.E.


    Westinghouse Hanford Company requested PNL to assemble a toxicology review panel (TRP) to evaluate analytical data compiled by WHC, and provide advice concerning potential health effects associated with exposure to tank-vapor constituents. The team`s objectives would be to (1) review procedures used for sampling vapors from tanks, (2) identify constituents in tank-vapor samples that could be related to symptoms reported by workers, (3) evaluate the toxicological implications of those constituents by comparison to establish toxicological databases, (4) provide advice for additional analytical efforts, and (5) support other activities as requested by WHC. The TRP represents a wide range of expertise, including toxicology, industrial hygiene, and occupational medicine. The TRP prepared a list of target analytes that chemists at the Oregon Graduate Institute/Sandia (OGI), Oak Ridge National Laboratory (ORNL), and PNL used to establish validated methods for quantitative analysis of head-space vapors from Tank 241-C-103. this list was used by the analytical laboratories to develop appropriate analytical methods for samples from Tank 241-C-103. Target compounds on the list included acetone, acetonitrile, ammonia, benzene, 1, 3-butadiene, butanal, n-butanol, hexane, 2-hexanone, methylene chloride, nitric oxide, nitrogen dioxide, nitrous oxide, dodecane, tridecane, propane nitrile, sulfur oxide, tributyl phosphate, and vinylidene chloride. The TRP considered constituent concentrations, current exposure limits, reliability of data relative to toxicity, consistency of the analytical data, and whether the material was carcinogenic or teratogenic. A final consideration in the analyte selection process was to include representative chemicals for each class of compounds found.

  5. Progress in the toxicological researches for quantum dots

    Institute of Scientific and Technical Information of China (English)


    Quantum dots (QDs) have received more and more attention as a novel example of nanomaterials. Due to their unique fluorescent characteristics,quantum dots have been successfully applied in biotech-nology and medicine applications. Recently,the toxicity and the potential environmental effects of QDs have become a research hotspot. In this paper,toxicological effects of QDs are reviewed,and the prospects and research directions are given based on the analysis of this research field.

  6. Behavior as a common focus of toxicology and nutrition

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.


    Behavior as an index of toxicity parallels its role as an index of nutritional impairment, just as toxicology and nutrition share other common themes. Intersections among the three disciplines arise because foodstuffs serve as one of the major routes of toxic exposure and also because food elements modify toxicity. With this perspective, the safety of our food supply is examined in the contexts of essential nutrients, toxins, toxic metals, manufactured contaminants, self-administered toxicants, and food additives.

  7. Pilot in vivo toxicological investigation of boron nitride nanotubes

    Directory of Open Access Journals (Sweden)

    Ciofani G


    Full Text Available Gianni Ciofani1, Serena Danti2, Giada Graziana Genchi1,3, Delfo D'Alessandro2, Jean-Luc Pellequer4, Michaël Odorico4, Virgilio Mattoli1, Mario Giorgi51Italian Institute of Technology, Center of MicroBioRobotics co Scuola Superiore Sant'Anna, 2Department of Neuroscience, University of Pisa, 3The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy; 4Commissariat à l'Energie Atomique, Institut de Biologie Environnementale et Biotechnologie, Department of Biochemistry and Nuclear Toxicology, Bagnols-sur-Cèze, France; 5Division of Pharmacology and Toxicology, Veterinary Clinics Department, University of Pisa, Pisa, ItalyAbstract: Boron nitride nanotubes (BNNTs have attracted huge attention in many different research fields thanks to their outstanding chemical and physical properties. During recent years, our group has pioneered the use of BNNTs for biomedical applications, first of all assessing their in vitro cytocompatibility on many different cell lines. At this point, in vivo investigations are necessary before proceeding toward realistic developments of the proposed applications. In this communication, we report a pilot toxicological study of BNNTs in rabbits. Animals were injected with a 1 mg/kg BNNT solution and blood tests were performed up to 72 hours after injection. The analyses aimed at evaluating any acute alteration of hematic parameters that could represent evidence of functional impairment in blood, liver, and kidneys. Even if preliminary, the data are highly promising, as they showed no adverse effects on all the evaluated parameters, and therefore suggest the possibility of the realistic application of BNNTs in the biomedical field.Keywords: boron nitride nanotubes, in vivo testing, toxicology

  8. Toxicological evaluation of lactase derived from recombinant Pichia pastoris. (United States)

    Zou, Shiying; He, Xiaoyun; Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao


    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

  9. Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Shiying Zou

    Full Text Available A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50 based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

  10. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine


    Fenderson, Joshua L.; Stratton, Amy N; Domingo, Jennifer S.; Matthews, Gerald O.; Tan, Christopher D.


    The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substan...

  11. Current trends in safety testing and toxicological research (United States)

    Zbinden, G.


    The paper reviews current concepts of toxicological evaluation of new drugs and other chemicals. Instead of completing a predetermined check-list toxicologists now consider the potential adverse effects of the substances under actual conditions of use. They then design experimental models which have a high probability to predict the toxic effects. Moreover, the enhanced susceptibilities of special risk populations is more and more taken into consideration.

  12. 77 FR 74192 - Availability of Final Toxicological Profiles (United States)


    ... . Toxicological profile CAS No. 1. Acrylamide 79-06-1 2. 1,3-Butadiene 106-99-0 3. Cadmium 7440-43-9 4. Carbon Monoxide 630-08-0 5. Chromium 7440-47-3 6. 1,4-Dioxane 123-91-1 7. Manganese 7439-96-5 8. Phosphate Ester... substances'' under CERCLA Section 104(i)(1)(B), to respond to requests for consultation under section...

  13. Aerospace toxicology overview: aerial application and cabin air quality. (United States)

    Chaturvedi, Arvind K


    Aerospace toxicology is a rather recent development and is closely related to aerospace medicine. Aerospace toxicology can be defined as a field of study designed to address the adverse effects of medications, chemicals, and contaminants on humans who fly within or outside the atmosphere in aviation or on space flights. The environment extending above and beyond the surface of the Earth is referred to as aerospace. The term aviation is frequently used interchangeably with aerospace. The focus of the literature review performed to prepare this paper was on aerospace toxicology-related subject matters, aerial application and aircraft cabin air quality. Among the important topics addressed are the following: · Aerial applications of agricultural chemicals, pesticidal toxicity, and exposures to aerially applied mixtures of chemicals and their associated formulating solvents/surfactants The safety of aerially encountered chemicals and the bioanalytical methods used to monitor exposures to some of them · The presence of fumes and smoke, as well as other contaminants that may generally be present in aircraft/space vehicle cabin air · And importantly, the toxic effects of aerially encountered contaminants, with emphasis on the degradation products of oils, fluids, and lubricants used in aircraft, and finally · Analytical methods used for monitoring human exposure to CO and HCN are addressed in the review, as are the signs and symptoms associated with exposures to these combustion gases. Although many agricultural chemical monitoring studies have been published, few have dealt with the occurrence of such chemicals in aircraft cabin air. However, agricultural chemicals do appear in cabin air; indeed, attempts have been made to establish maximum allowable concentrations for several of the more potentially toxic ones that are found in aircraft cabin air. In this article, I emphasize the need for precautionary measures to be taken to minimize exposures to aerially

  14. Alternative methods in toxicology: pre-validated and validated methods



    The development of alternative methods to animal experimentation has progressed rapidly over the last 20 years. Today, in vitro and in silico methods have an important role in the hazard identification and assessment of toxicology profile of compounds. Advanced alternative methods and their combinations are also used for safety assessment of final products. Several alternative methods, which were scientifically validated and accepted by competent regulatory bodies, can be used for regulatory ...

  15. University Clinic of Toxicology--historical note and present work. (United States)

    Bozinovska, C


    The University Clinic of Toxicology (UCT) in Skopje was founded as the Clinic for Toxicology and Emergency Internal Medicine on January 15th 1976. Today UCT has a modern building with office space of 1,300 m2 on 4 floors, 40 hospital beds and 72 employees including 18 doctors. UCT works in accordance with the public healthcare services in the Republic of Macedonia through the use of specialist/consultative and hospital healthcare for people over the age of 14 years. The Clinic also provides services in the field of emergency internal medicine, acute poisoning with medications, pesticides, corrosives, poisonous gases and mushrooms, heavy metals and other chemicals. The Clinic takes an active part in the detoxification programme for users of opiates and psychotropic substances, protocols for enteral and parenteral nutrition and guides for home treatment. Yearly there are more than 14,000 ambulance admissions, over 1,400 hospitalized patients, over 4,000 urgent EHO checks, more than 1,000 urgent upper endoscopies and over 700 other toxicological analyses and other interventions. The educational services and activities are realized through the chair for internal medicine. The Clinic offers undergraduate and graduate level education for medical students and dentists, for medical nurses, radiology technicians, speech therapists and physiotherapists. Over 300 papers and reports have been published to date by the medical staff at the UCT in the form of abstracts and integrated projects in the Republic of Macedonia and aboard. 8 doctorates have been successfully completed by employees from the Clinic as well as 4 master's theses and 1 in-depth project. UCT employees are the authors of some textbooks and monographs. UCT have undertaken some scientific projects. Employees from the Clinic of Toxicology are members taking an active part in many domestic and international associations.

  16. Threshold of Toxicological Concern (TTC) and Mixture Effects of Chemicals


    Wennermark, Henrik


    The threshold of toxicological concern (TTC) has been proposed as a novel tool in the risk assessment of chemicals, which based on knowledge of chemical structure, can set safe-levels without the necessity of performing expensive and time consuming animal toxicity experiments. However, questions have been raised whether the TTC approach, in a sufficient manner, are capable of setting safe thresholds in the context of chemicals mixture effects. This is the subject for this project. The current...

  17. The minipig as a platform for new technologies in toxicology. (United States)

    Forster, Roy; Ancian, Philippe; Fredholm, Merete; Simianer, Henner; Whitelaw, Bruce


    The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress in these areas. There is no equivalent economic driver for progress in the dog or the monkey. As a result the available knowledge-bases are much greater for pigs (than for dogs or monkeys) in many areas (physiology, disease, genetics, immunology etc). Fundamental genomic knowledge and phenotypic characterization in regard to the pig is well in advance of the dog or the monkey and basic knowledge of the pig is therefore likely to stay ahead of the other two species. While the emerging technologies are essentially "species neutral" and can in principle be applied to all species, for all the technologies that we examined, basic knowledge and technical capabilities are greater for the pig than the dog or monkey. In concrete terms, in application to safety testing we have seen that: (i) The Göttingen minipig is well positioned for the performance of toxicogenomics studies, (ii) The close sequence homology between pigs and humans suggest that minipigs will be useful for the testing of biotechnology products (and possibly for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology model where transgenic animals can be readily generated, and reproductive technologies are well developed in the pig. These properties should also make the minipig an interesting model for the testing of biotechnology products. These factors all support the idea that the minipig is well placed to meet the challenges of the emerging technologies and the toxicology of the future; it also seems likely that the minipig can be an advantageous model for the testing of biotechnology products.

  18. Progress in the toxicological researches for quantum dots

    Institute of Scientific and Technical Information of China (English)

    LI HongCheng; ZHOU QunFang; LIU Wei; YAN Bing; ZHAO Yibing; JIANG GuiBin


    Quantum dots (QDs) have Received more and more attention as a novel example of nanomaterials. Due to their unique fluorescent characteristics, quantum dots have been successfully applied in biotech-nology and medicine applications. Recently, the toxicity and the potential environmental effects of QDs have become a research hotspot. In this paper, toxicological effects of QDs are reviewed, and the prospects and research directions are given based on the analysis of this research field.

  19. Toxicology profiles of chemical and radiological contaminants at Hanford

    Energy Technology Data Exchange (ETDEWEB)

    Harper, B.L.; Strenge, D.L.; Stenner, R.D.; Maughan, A.D.; Jarvis, M.K.


    This document summarizes toxicology information required under Section 3.3 (Toxicity Assessment) of HSRAM, and can also be used to develop the short toxicology profiles required in site assessments (described in HSRAM, Section 3.3.5). Toxicology information is used in the dose-response step of the risk assessment process. The dose-response assessment describes the quantitative relationship between the amount of exposure to a substance and the extent of toxic injury or disease. Data are derived from animal studies or, less frequently, from studies in exposed human populations. The risks of a substance cannot be ascertained with any degree of confidence unless dose-response relations are quantified. This document summarizes dose-response information available from the US Environmental Protection Agency (EPA). The contaminants selected for inclusion in this document represent most of the contaminants found at Hanford (both radiological and chemical), based on sampling and analysis performed during site investigations, and historical information on waste disposal practices at the Hanford Site.

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

    Directory of Open Access Journals (Sweden)

    Brandon David Gaytán


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

  1. What is toxicology and how does toxicity occur? (United States)

    Mückter, Harald


    Toxicology has matured since it was defined as the 'science of poisons'. Modern toxicology is no longer anthropocentric but takes on different views at various biological systems, including ecosystems. Each will interact specifically when exposed to defined chemical agents, including drugs. Adverse effects during drug therapy or after (accidental) poisoning are the result of some negative interactions between the agent and the exposed biological system. Toxicity is no longer a specific property of drugs and chemicals but an operative term to describe the adverse outcome of a specific drugs-host interaction. Newer developments in toxicology have focused on the host. Toxicogenetics continues to provide answers to variations of host response to xenobiotics, including drugs. Clinically relevant genetic polymorphisms and gene defects have been detected, and their number is rapidly growing. The key to understanding is in the host proteins that interact with the drug and mediate the cellular response. Hence, the proteom, i.e. the complete set of proteins of a cell, an individual or a species, determines how an exposed biological system may interact with the manifold of different xenobiotics. Structure-activity studies try to find out useful predictive parameters for risk and toxicity assessment.

  2. Pharmacology and toxicology of chaconine and tomatine. (United States)

    Nishie, K; Norred, W P; Swain, A P


    The pharmacological responses produced by alpha chaconine and tomatine on guinea pig ileum, on the isolated electrically stimulated frog ventricle, and recordings of EEG, ECG, respiration and blood pressure in the rabbit showed no essential differences from those produced by alpha solanine. The LD50 values of chaconine and solanine in the mouse and rabbit are also similar and suggest that compounds other than these are probably responsible for the predominant toxic effects of certain hybrid potatoes in man and animals. The failure of the three glycoalkaloids to produce a significant teratological effect in the chick embryo lends no support to the hypothesis that they may be the teratogens responsible for certain congenital malformations in man.

  3. Sparse Similarity-Based Fisherfaces

    DEFF Research Database (Denmark)

    Fagertun, Jens; Gomez, David Delgado; Hansen, Mads Fogtmann;


    In this work, the effect of introducing Sparse Principal Component Analysis within the Similarity-based Fisherfaces algorithm is examined. The technique aims at mimicking the human ability to discriminate faces by projecting the faces in a highly discriminative and easy interpretative way. Pixel...... obtain the same recognition results as the technique in a dense version using only a fraction of the input data. Furthermore, the presented results suggest that using SPCA in the technique offers robustness to occlusions....

  4. Self-similarity Driven Demosaicking

    Directory of Open Access Journals (Sweden)

    Antoni Buades


    Full Text Available Digital cameras record only one color component per pixel, red, green or blue. Demosaicking is the process by which one can infer a whole color matrix from such a matrix of values, thus interpolating the two missing color values per pixel. In this article we propose a demosaicking method based on the property of non-local self-similarity of images.

  5. Active browsing using similarity pyramids (United States)

    Chen, Jau-Yuen; Bouman, Charles A.; Dalton, John C.


    In this paper, we describe a new approach to managing large image databases, which we call active browsing. Active browsing integrates relevance feedback into the browsing environment, so that users can modify the database's organization to suit the desired task. Our method is based on a similarity pyramid data structure, which hierarchically organizes the database, so that it can be efficiently browsed. At coarse levels, the similarity pyramid allows users to view the database as large clusters of similar images. Alternatively, users can 'zoom into' finer levels to view individual images. We discuss relevance feedback for the browsing process, and argue that it is fundamentally different from relevance feedback for more traditional search-by-query tasks. We propose two fundamental operations for active browsing: pruning and reorganization. Both of these operations depend on a user-defined relevance set, which represents the image or set of images desired by the user. We present statistical methods for accurately pruning the database, and we propose a new 'worm hole' distance metric for reorganizing the database, so that members of the relevance set are grouped together.

  6. Self-Similar Collisionless Shocks

    CERN Document Server

    Katz, B; Waxman, E; Katz, Boaz; Keshet, Uri; Waxman, Eli


    Observations of gamma-ray burst afterglows suggest that the correlation length of magnetic field fluctuations downstream of relativistic non-magnetized collisionless shocks grows with distance from the shock to scales much larger than the plasma skin depth. We argue that this indicates that the plasma properties are described by a self-similar solution, and derive constraints on the scaling properties of the solution. For example, we find that the scaling of the characteristic magnetic field amplitude with distance from the shock is B \\propto D^{s_B} with -1 \\propto x^{2s_B} (for x>>D). We show that the plasma may be approximated as a combination of two self-similar components: a kinetic component of energetic particles and an MHD-like component representing "thermal" particles. We argue that the latter may be considered as infinitely conducting, in which case s_B=0 and the scalings are completely determined (e.g. dn/dE \\propto E^{-2} and B \\propto D^0). Similar claims apply to non- relativistic shocks such a...

  7. Roget's Thesaurus and Semantic Similarity

    CERN Document Server

    Jarmasz, Mario


    We have implemented a system that measures semantic similarity using a computerized 1987 Roget's Thesaurus, and evaluated it by performing a few typical tests. We compare the results of these tests with those produced by WordNet-based similarity measures. One of the benchmarks is Miller and Charles' list of 30 noun pairs to which human judges had assigned similarity measures. We correlate these measures with those computed by several NLP systems. The 30 pairs can be traced back to Rubenstein and Goodenough's 65 pairs, which we have also studied. Our Roget's-based system gets correlations of .878 for the smaller and .818 for the larger list of noun pairs; this is quite close to the .885 that Resnik obtained when he employed humans to replicate the Miller and Charles experiment. We further evaluate our measure by using Roget's and WordNet to answer 80 TOEFL, 50 ESL and 300 Reader's Digest questions: the correct synonym must be selected amongst a group of four words. Our system gets 78.75%, 82.00% and 74.33% of ...

  8. Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC). (United States)

    Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S


    Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

  9. Toxicological evaluation of clay minerals and derived nanocomposites: a review. (United States)

    Maisanaba, Sara; Pichardo, Silvia; Puerto, María; Gutiérrez-Praena, Daniel; Cameán, Ana M; Jos, Angeles


    Clays and clay minerals are widely used in many facets of our society. This review addresses the main clays of each phyllosilicate groups, namely, kaolinite, montmorillonite (Mt) and sepiolite, placing special emphasis on Mt and kaolinite, which are the clays that are more frequently used in food packaging, one of the applications that are currently exhibiting higher development. The improvements in the composite materials obtained from clays and polymeric matrices are remarkable and well known, but the potential toxicological effects of unmodified or modified clay minerals and derived nanocomposites are currently being investigated with increased interest. In this sense, this work focused on a review of the published reports related to the analysis of the toxicological profile of commercial and novel modified clays and derived nanocomposites. An exhaustive review of the main in vitro and in vivo toxicological studies, antimicrobial activity assessments, and the human and environmental impacts of clays and derived nanocomposites was performed. From the analysis of the scientific literature different conclusions can be derived. Thus, in vitro studies suggest that clays in general induce cytotoxicity (with dependence on the clay, concentration, experimental system, etc.) with different underlying mechanisms such as necrosis/apoptosis, oxidative stress or genotoxicity. However, most of in vivo experiments performed in rodents showed no clear evidences of systemic toxicity even at doses of 5000mg/kg. Regarding to humans, pulmonary exposure is the most frequent, and although clays are usually mixed with other minerals, they have been reported to induce pneumoconiosis per se. Oral exposure is also common both intentionally and unintentionally. Although they do not show a high toxicity through this pathway, toxic effects could be induced due to the increased or reduced exposure to mineral elements. Finally, there are few studies about the effects of clay minerals on

  10. Toxicologic disease of the digestive tract. (United States)

    Garland, T


    There is a diverse and long list of toxicants that can affect the digestive system of food-producing animals. The plants and other natural toxicants discussed in this article are those primarily affecting the GI system. A number of other plants may also affect the digestive tract, but the effects from these are considered secondary and less pronounced. Often, plant poisonings affecting the digestive tract present with similar clinical signs, and a good thorough history is necessary to help differentiate between them. Moreover, a careful walk through the pasture with a keen eye to note plants that have been browsed or grazed may greatly assist the history. In cases where toxins are suspected as the cause of a GI disorder, consultation with a veterinary toxicologist at a diagnostic laboratory may be indicated. These professionals are knowledgeable about a wide variety of natural and other toxicants that may be present in your area. They can help with developing a differential diagnosis and the selection of appropriate samples to confirm the diagnosis.

  11. Toxicology of sorbic acid and sorbates. (United States)

    Walker, R


    Sorbic acid and its salts have been subjected to an extensive battery of tests, including acute, short-term and chronic toxicity/carcinogenicity tests, two-generation reproduction and teratogenicity studies. These studies show that sorbic acid and sorbates have a very low level of mammalian toxicity, even in chronic studies at up to 10% of the diet, and are devoid of carcinogenic activity. They are non-mutagenic and non-clastogenic in vitro and in vivo. The low toxicity is explicable by the fact that sorbic acid is metabolized rapidly by similar pathways to other fatty acids. In humans, a few cases of idiosyncratic intolerances have been reported (non-immunological contact urticaria and pseudo-allergy). The frequency appears low but there are too few reported data for an accurate assessment of the true incidence. In extreme conditions (high concentrations and temperature) sorbic acid may react with nitrite to form mutagenic products but these mutagens are not detectable under normal conditions of use, even in curing brines.

  12. The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21st Century



    Objectives: According to the 2007 National Research Council report Toxicology for the Twenty-First Century, modern methods (e.g., "omics," in vitro assays, high-throughput testing, computational methods) will lead to the emergence of a new approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has been central to the field of genetic toxicology since the 1970s. Here we document the paradigm shifts engendered by the assay, the validation and applications of the assay, an...

  13. "You Can't Always Get What You Want" - Linearity as the Golden Ratio of Toxicology. (United States)

    Bast, Aalt; Hanekamp, Jaap C


    Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity. The latter seems imposed on pharmaco-toxicological processes that in fact show far more complexity than simple linearity could hope to elucidate. Understanding physiological and pharmaco-toxicological processes as primarily linear is challenged in this contribution based on very straightforward principles and examples.

  14. Assessing protein kinase target similarity

    DEFF Research Database (Denmark)

    Gani, Osman A; Thakkar, Balmukund; Narayanan, Dilip


    : focussed chemical libraries, drug repurposing, polypharmacological design, to name a few. Protein kinase target similarity is easily quantified by sequence, and its relevance to ligand design includes broad classification by key binding sites, evaluation of resistance mutations, and the use of surrogate......" of sequence and crystal structure information, with statistical methods able to identify key correlates to activity but also here, "the devil is in the details." Examples from specific repurposing and polypharmacology applications illustrate these points. This article is part of a Special Issue entitled...

  15. Aqueous foam toxicology evaluation and hazard review

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, M.M.


    Aqueous foams are aggregates of bubbles mechanically generated by passing air or other gases through a net, screen, or other porous medium that is wetted by an aqueous solution of surface-active foaming agents (surfactants). Aqueous foams are important in modem fire-fighting technology, as well as for military uses for area denial and riot or crowd control. An aqueous foam is currently being developed and evaluated by Sandia National Laboratories (SNL) as a Less-Than-Lethal Weapon for the National Institute of Justice (NIJ). The purpose of this study is to evaluate the toxicity of the aqueous foam developed for the NIJ and to determine whether there are any significant adverse health effects associated with completely immersing individuals without protective equipment in the foam. The toxicity of the aqueous foam formulation developed for NIJ is determined by evaluating the toxicity of the individual components of the foam. The foam is made from a 2--5% solution of Steol CA-330 surfactant in water generated at expansion ratios ranging from 500:1 to 1000:1. SteoI CA-330 is a 35% ammonium laureth sulfate in water and is produced by Stepan Chemical Company and containing trace amounts (<0.1%) of 1,4-dioxane. The results of this study indicate that Steol CA-330 is a non-toxic, mildly irritating, surfactant that is used extensively in the cosmetics industry for hair care and bath products. Inhalation or dermal exposure to this material in aqueous foam is not expected to produce significant irritation or systemic toxicity to exposed individuals, even after prolonged exposure. The amount of 1,4-dioxane in the surfactant, and subsequently in the foam, is negligible and therefore, the toxicity associated with dioxane exposure is not significant. In general, immersion in similar aqueous foams has not resulted in acute, immediately life-threatening effects, or chronic, long-term, non-reversible effects following exposure.

  16. Advancing alternatives analysis: The role of predictive toxicology in selecting safer chemical products and processes. (United States)

    Malloy, Timothy; Zaunbrecher, Virginia; Beryt, Elizabeth; Judson, Richard; Tice, Raymond; Allard, Patrick; Blake, Ann; Cote, Ila; Godwin, Hilary; Heine, Lauren; Kerzic, Patrick; Kostal, Jakub; Marchant, Gary; McPartland, Jennifer; Moran, Kelly; Nel, Andre; Oguseitan, Oladele; Rossi, Mark; Thayer, Kristina; Tickner, Joel; Whittaker, Margaret; Zarker, Ken


    Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in more cost-effective manner than traditional approaches. This article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents four recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA; adopting a stepwise process to employing predicative toxicology in AA beginning with prioritization of chemicals of concern; leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting trans-disciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. This article is protected by copyright. All rights reserved.

  17. Mechanisms for similarity based cooperation (United States)

    Traulsen, A.


    Cooperation based on similarity has been discussed since Richard Dawkins introduced the term “green beard” effect. In these models, individuals cooperate based on an aribtrary signal (or tag) such as the famous green beard. Here, two different models for such tag based cooperation are analysed. As neutral drift is important in both models, a finite population framework is applied. The first model, which we term “cooperative tags” considers a situation in which groups of cooperators are formed by some joint signal. Defectors adopting the signal and exploiting the group can lead to a breakdown of cooperation. In this case, conditions are derived under which the average abundance of the more cooperative strategy exceeds 50%. The second model considers a situation in which individuals start defecting towards others that are not similar to them. This situation is termed “defective tags”. It is shown that in this case, individuals using tags to cooperate exclusively with their own kind dominate over unconditional cooperators.

  18. Predictive Toxicology: Modeling Chemical Induced Toxicological Response Combining Circular Fingerprints with Random Forest and Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Alexios eKoutsoukas


    Full Text Available Modern drug discovery and toxicological research are under pressure, as the cost of developing and testing new chemicals for potential toxicological risk is rising. Extensive evaluation of chemical products for potential adverse effects is a challenging task, due to the large number of chemicals and the possible hazardous effects on human health. Safety regulatory agencies around the world are dealing with two major challenges. First, the growth of chemicals introduced every year in household products and medicines that need to be tested, and second the need to protect public welfare. Hence, alternative and more efficient toxicological risk assessment methods are in high demand. The Toxicology in the 21st Century (Tox21 consortium a collaborative effort was formed to develop and investigate alternative assessment methods. A collection of 10,000 compounds composed of environmental chemicals and approved drugs were screened for interference in biochemical pathways and released for crowdsourcing data analysis. The physicochemical space covered by Tox21 library was explored, measured by Molecular Weight (MW and the octanol/water partition coefficient (cLogP. It was found that on average chemical structures had MW of 272.6 Daltons. In case of cLogP the average value was 2.476. Next relationships between assays were examined based on compounds activity profiles across the assays utilizing the Pearson correlation coefficient r. A cluster was observed between the Androgen and Estrogen Receptors and their ligand bind domains accordingly indicating presence of cross talks among the receptors. The highest correlations observed were between NR.AR and NR.AR_LBD, where it was r=0.66 and between NR.ER and NR.ER_LBD, where it was r=0.5.Our approach to model the Tox21 data consisted of utilizing circular molecular fingerprints combined with Random Forest and Support Vector Machine by modeling each assay independently. In all of the 12 sub-challenges our modeling

  19. Interneurons targeting similar layers receive synaptic inputs with similar kinetics. (United States)

    Cossart, Rosa; Petanjek, Zdravko; Dumitriu, Dani; Hirsch, June C; Ben-Ari, Yehezkel; Esclapez, Monique; Bernard, Christophe


    GABAergic interneurons play diverse and important roles in controlling neuronal network dynamics. They are characterized by an extreme heterogeneity morphologically, neurochemically, and physiologically, but a functionally relevant classification is still lacking. Present taxonomy is essentially based on their postsynaptic targets, but a physiological counterpart to this classification has not yet been determined. Using a quantitative analysis based on multidimensional clustering of morphological and physiological variables, we now demonstrate a strong correlation between the kinetics of glutamate and GABA miniature synaptic currents received by CA1 hippocampal interneurons and the laminar distribution of their axons: neurons that project to the same layer(s) receive synaptic inputs with similar kinetics distributions. In contrast, the kinetics distributions of GABAergic and glutamatergic synaptic events received by a given interneuron do not depend upon its somatic location or dendritic arborization. Although the mechanisms responsible for this unexpected observation are still unclear, our results suggest that interneurons may be programmed to receive synaptic currents with specific temporal dynamics depending on their targets and the local networks in which they operate.

  20. Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. (United States)

    Munro, I C; Berndt, W O; Borzelleca, J F; Flamm, G; Lynch, B S; Kennepohl, E; Bär, E A; Modderman, J; Bernt, W O


    A critical and comprehensive review of the safety information on erythritol was undertaken. Numerous toxicity and metabolic studies have been conducted on erythritol in rats, mice and dogs. The toxicity studies consist of long-term feeding studies conducted to determine carcinogenic potential, intravenous and oral teratogenicity studies to determine the potential for effects on the foetus, oral studies in which erythritol was administered over one or two generations to determine the potential for reproductive effects, and studies in bacterial and mammalian systems to determine mutagenic potential. The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%. The metabolic studies in animals have shown that erythritol is almost completely absorbed, not metabolized systemically and is excreted unchanged in the urine. The safety studies have demonstrated that erythritol is well tolerated and elicits no toxicological effects. The clinical program for erythritol involved a series of single-dose and repeat-dose, short-duration studies which have been used to investigate the human correlates to the physiological responses seen in the preclinical studies. The clinical studies showed erythritol to be well tolerated and not to cause any toxicologically relevant effects, even following high-dose exposure. Erythritol administered orally to humans was rapidly absorbed from the gastrointestinal tract and quantitatively excreted in the urine without undergoing metabolic change. At high oral doses, urinary excretion accounted for approximately 90% of the administered dose with minimal amounts appearing in the faeces. A comparison of the human and animal data indicated a high degree of similarity in the metabolism of erythritol and this finding supports the use of the animal species used to evaluate the safety of erythritol for human consumption. It can be concluded, based on the available studies

  1. Performance Indexes: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    André Machado Caldeira


    Full Text Available The investor of today is more rigorous on monitoring a financial assets portfolio. He no longer thinks only in terms of the expected return (one dimension, but in terms of risk-return (two dimensions. Thus new perception is more complex, since the risk measurement can vary according to anyone’s perception; some use the standard deviation for that, others disagree with this measure by proposing others. In addition to this difficulty, there is the problem of how to consider these two dimensions. The objective of this essay is to study the main performance indexes through an empirical study in order to verify the differences and similarities for some of the selected assets. One performance index proposed in Caldeira (2005 shall be included in this analysis.

  2. Semantically enabled image similarity search (United States)

    Casterline, May V.; Emerick, Timothy; Sadeghi, Kolia; Gosse, C. A.; Bartlett, Brent; Casey, Jason


    Georeferenced data of various modalities are increasingly available for intelligence and commercial use, however effectively exploiting these sources demands a unified data space capable of capturing the unique contribution of each input. This work presents a suite of software tools for representing geospatial vector data and overhead imagery in a shared high-dimension vector or embedding" space that supports fused learning and similarity search across dissimilar modalities. While the approach is suitable for fusing arbitrary input types, including free text, the present work exploits the obvious but computationally difficult relationship between GIS and overhead imagery. GIS is comprised of temporally-smoothed but information-limited content of a GIS, while overhead imagery provides an information-rich but temporally-limited perspective. This processing framework includes some important extensions of concepts in literature but, more critically, presents a means to accomplish them as a unified framework at scale on commodity cloud architectures.


    Directory of Open Access Journals (Sweden)



    Full Text Available act: Similarities between the accounting of companies and territorial administrative units accounting are the following: organizing double entry accounting; accounting method both in terms of fundamental theoretical principles and specific practical tools. The differences between the accounting of companies and of territorial administrative units refer to: the accounting of territorial administrative units includes besides general accounting (financial also budgetary accounting, and the accounts system of the budgetary accounting is completely different from that of companies; financial statements of territorial administrative units to which leaders are not main authorizing officers are submitted to the hierarchically superior body (not at MPF; the accounts of territorial administrative units are opened at treasury and financial institutions, accounts at commercial banks being prohibited; equity accounts in territorial administrative units are structured into groups of funds; long term debts have a specific structure in territorial administrative units (internal local public debt and external local public debt.

  4. Features Based Text Similarity Detection

    CERN Document Server

    Kent, Chow Kok


    As the Internet help us cross cultural border by providing different information, plagiarism issue is bound to arise. As a result, plagiarism detection becomes more demanding in overcoming this issue. Different plagiarism detection tools have been developed based on various detection techniques. Nowadays, fingerprint matching technique plays an important role in those detection tools. However, in handling some large content articles, there are some weaknesses in fingerprint matching technique especially in space and time consumption issue. In this paper, we propose a new approach to detect plagiarism which integrates the use of fingerprint matching technique with four key features to assist in the detection process. These proposed features are capable to choose the main point or key sentence in the articles to be compared. Those selected sentence will be undergo the fingerprint matching process in order to detect the similarity between the sentences. Hence, time and space usage for the comparison process is r...

  5. Tasks of regulatory toxicology; Aufgaben der regulatorischen Toxikologie

    Energy Technology Data Exchange (ETDEWEB)

    Schwenk, M. [Landesgesundheitsamt Stuttgart (Germany)


    Regulatory toxicology aims at protecting the population and environment from toxic effects of chemicals, pesticides, food additives, cosmetics, drugs, medical products, genetic engineering products, natural toxins, etc. by establishing and applying safety standards. Different institutions are involved: authorities (regulation), industry (characterization of toxicity), universities (mechanisms of action), and contract institutes (compilation, testing). Toxicologists are involved in the regulation processes primarily at the levels of risk assessment and risk estimation. As a result of the progress in molecular and cell biology, new and innovative test methods evolve at high speed (in vitro systems, ''omics,'' knock out mice). At the same time there is political compulsion to employ alternative methods. Therefore, the validation of new test systems is a major scientific challenge for regulatory toxicology. Moreover, there is need for harmonization in many areas, including evaluation paradigms (adversity, safety factors, low-dose extrapolation). A study group in the German Society for Toxicology works on these tasks. (orig.) [German] Die regulatorische Toxikologie hat das Ziel, durch Festlegung von sicheren Standards und Normen die Bevoelkerung und Umwelt vor Gefaehrdungen durch Chemikalien in allen Anwendungsbereichen sicher zu schuetzen. Verschiedene Institutionen sind mit unterschiedlichen Arbeitsschwerpunkten beteiligt: Behoerden (Regulierung), Industrie (toxikologische Stoffcharakterisierung), Universitaet (Wirkmechanismen) und Vertragsinstitute (Aufarbeitung, Versuchsdurchfuehrung). Der Toxikologe bearbeitet im Risikoregulierungsprozess vor allem die Schritte der Risikoabschaetzung und Risikobewertung. Durch die rapiden Entwicklungen in der Molekular- und Zellbiologie werden staendig neue, innovative Testsysteme verfuegbar (In-vitro-Systeme, ''omics'', Knock-out-Maeuse). Gleichzeitig besteht ein Zwang zur Nutzung von

  6. Meta-analysis of ionic liquid literature and toxicology. (United States)

    Heckenbach, Mary E; Romero, Felicia N; Green, Matthew D; Halden, Rolf U


    A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213) with the goal of establishing the state of knowledge and existing information gaps. Additionally, patent literature pertaining to issued patents utilizing ILs (n = 3358) or dealing with IL toxicity (n = 112) were analyzed. Total publishing activity and patent count served to gauge research activity, industrial usage and toxicology knowledge of ILs. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 0.55% ± 0.27% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemical. Toxicity studies on ILs were dominated by the use of in vitro models (18%) and marine bacteria (15%) as studied biological systems. Whole animal studies (n = 87) comprised 31% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need to fill crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies.

  7. The utility of the small rodent electrocardiogram in toxicology. (United States)

    Farraj, Aimen K; Hazari, Mehdi S; Cascio, Wayne E


    Extensive research has lead to a growing appreciation that the heart is acutely sensitive to a broad array of toxicants via multiple routes of exposure. These agents are as diverse as the antineoplastic drug doxorubicin and environmental agents including ambient air pollution. Adverse effects in the heart often manifest as a change in the electrocardiogram (ECG). The ECG has long been used in the clinic to assess human cardiovascular health. Surface electrocardiographic recordings (i.e., those made from the skin) in humans often help to detect abnormal myocardial impulse formation, conduction, cardiac rhythm disturbances, and altered autonomic regulation of the heart. In toxicology, the ECG provides a collection of end points that may be used to assess both the quality and magnitude of cardiac toxicity. Increasingly over the last two decades, the cardiotoxicity of agents have been characterized using small rodent electrocardiography. Additionally, tremendous insight into possible mechanisms of action of known human cardiotoxicants has been gained. Rat and mouse models offer a number of advantages relative to larger animals including lower cost, less variability, the availability of transgenic models, and a plethora of research tools. Modern day advances in small rodent electrocardiography have enabled assessments in conscious unrestrained animals and improved ECG interpretation. Thus, the incorporation of small rodent electrocardiographic assessments into toxicology studies may facilitate the screening of cardiotoxic potential and the elucidation of mechanisms of action. This review will discuss the utility of the small rodent ECG, various methodologies used to derive ECG data in rats and mice, and various applications in toxicology.

  8. Toxicological assessment of Ricinus communis Linn root extracts. (United States)

    Ilavarasan, Raju; Mallika, Moni; Venkataraman, Subramanian


    Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

  9. Toxicological study of plant extracts on termite and laboratory animals. (United States)

    Rahman, I; Gogoi, Inee; Dolui, A K; Handique, Ruma


    Toxic activity of leaf extracts of Polygonum hydropiper L. and Pogostemon parviflorus Benth. were tested in the laboratory against tea termite, Odontotermes assamensis Holm. Both the tested extracts caused mortality of the termite. The highest toxic activity (100%) was found in the 2.0% chloroform extracts of P. hydropiper. The chloroform extract of P. hydropiper was explored for possible mammalian toxicological effects. The LD50 was 758.58 mg/kg in male albino mice. Subcutaneous injection of sub-lethal dose of extract into male mice once a week for 6 weeks failed to express any significant influence on WBC, RBC count and blood cholesterol.

  10. Toxicología aguda del D-004 en conejos


    Ariadne Gutiérrez Martínez; Rafael Gámez Menéndez; Rosa Más Ferreiro; Miriam Noa Puig; Balia Pardo Acosta; Eddy Goicochea Carrero; Dayisell Curveco Sánchez; Haydée García Cambián


    El D-004 es un extracto lipídico obtenido del fruto de la palma real (Roystonea regia) (Arecaceae) que consiste en una mezcla reproducible de ácidos grasos, en la cual el ácido oleico, el láurico y el palmítico son los más abundantes. El tratamiento oral con D-004 inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. La toxicología preclínica de un nuevo compuesto incluye la evaluación aguda en una especie no roedora. Con este objetivo se realizó el ensayo...

  11. Data mining and knowledge discovery in predictive toxicology. (United States)

    Helma, C


    This article describes the knowledge discovery process in predictive toxicology. This process consists of five major steps (i) feature calculation, (ii) feature selection, (iii) model induction, (iv) model validation and (v) interpretation of predictions and models. Data mining is a part of the knowledge discovery process and consists of the application of data analysis and discovery algorithms, which can be useful in all of the above steps. A brief review of suitable algorithms and their advantages and disadvantages is given for each knowledge discovery step, followed by a more detailed description of a problem-specific implementation of the lazar prediction system.

  12. Towards a Fuzzy Expert System on Toxicological Data Quality Assessment. (United States)

    Yang, Longzhi; Neagu, Daniel; Cronin, Mark T D; Hewitt, Mark; Enoch, Steven J; Madden, Judith C; Przybylak, Katarzyna


    Quality assessment (QA) requires high levels of domain-specific experience and knowledge. QA tasks for toxicological data are usually performed by human experts manually, although a number of quality evaluation schemes have been proposed in the literature. For instance, the most widely utilised Klimisch scheme1 defines four data quality categories in order to tag data instances with respect to their qualities; ToxRTool2 is an extension of the Klimisch approach aiming to increase the transparency and harmonisation of the approach. Note that the processes of QA in many other areas have been automatised by employing expert systems. Briefly, an expert system is a computer program that uses a knowledge base built upon human expertise, and an inference engine that mimics the reasoning processes of human experts to infer new statements from incoming data. In particular, expert systems have been extended to deal with the uncertainty of information by representing uncertain information (such as linguistic terms) as fuzzy sets under the framework of fuzzy set theory and performing inferences upon fuzzy sets according to fuzzy arithmetic. This paper presents an experimental fuzzy expert system for toxicological data QA which is developed on the basis of the Klimisch approach and the ToxRTool in an effort to illustrate the power of expert systems to toxicologists, and to examine if fuzzy expert systems are a viable solution for QA of toxicological data. Such direction still faces great difficulties due to the well-known common challenge of toxicological data QA that "five toxicologists may have six opinions". In the meantime, this challenge may offer an opportunity for expert systems because the construction and refinement of the knowledge base could be a converging process of different opinions which is of significant importance for regulatory policy making under the regulation of REACH, though a consensus may never be reached. Also, in order to facilitate the implementation

  13. Review of Toxicology of Atrazine and Chlorpyrifos on Fish

    Institute of Scientific and Technical Information of China (English)

    WANG Xu; LI Jilong; XING Houjuan; XU Shiwen


    Atrazine (ATR) and chlorpyrifos (CPF) are widely used in agriculture, but have resulted in a series of toxicological and environmental problems. They were heavily used which have potential threat to fish and rodents. Several recent laboratory studies have shown ATR and CPF could lead to oxidative damage, immunocyte reduced and inhibit acetylcholinesterase (ACHE). In order to clarify the toxicity of ATR and CPF, this paper summarized the adverse effects of ATR and CPF on reproduction, nerve and immune systems in fish.

  14. Application of radioreceptor assay of benzodiazepines for toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, L.; Scheinin, M. (Department of Pharmacology and the Department of Internal Medicine, University of Turku, Finland)


    A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum samples from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra-assay variation < 8%, inter-assay variation < 10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas-liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affinities.

  15. Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium. (United States)

    Hoenerhoff, Mark J; Hartke, James


    The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies.

  16. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.


    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and dru

  17. 78 FR 13347 - Clinical Chemistry and Clinical Toxicology Devices Panel of the Medical Devices Advisory... (United States)


    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Clinical Chemistry and Clinical Toxicology Devices Panel of... Chemistry and Clinical Toxicology Devices Panel of the Medical Devices Advisory Committee. General...

  18. Toxicological interactions of silver nanoparticles and non-essential metals in human hepatocarcinoma cell line

    DEFF Research Database (Denmark)

    Miranda, Renata Rank; Bezerra, Arandi Ginane; Ribeiro, Ciro Alberto Oliveira;


    Toxicological interaction represents a challenge to toxicology, particularly for novel contaminants. There are no data whether silver nanoparticles (AgNPs), present in a wide variety of products, can interact and modulate the toxicity of ubiquitous contaminants, such as nonessential metals. In th...

  19. 77 FR 6800 - Notice of Development of Set 25 Toxicological Profiles (United States)


    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Notice of Development of Set 25... and Human Services (DHHS). ACTION: Notice. SUMMARY: This notice announces the development of Set . Set 25 Toxicological Profiles The following toxicological profiles...

  20. 78 FR 4147 - Notice of Development of Set 26 Toxicological Profiles (United States)


    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Notice of Development of Set 26... and Human Services (HHS). ACTION: Notice. SUMMARY: This notice announces the development of Set 26.../toxprofiles/index.asp . Set 26 Toxicological Profiles The following toxicological profiles are now...

  1. The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21 st Century (United States)

    OBJECTIVES: According to the 2007 National Research Council report Toxicology for the Twenty-first Century, modem methods ("omics," in vitro assays, high-throughput testing, computational methods, etc.) will lead to the emergence of a new approach to toxicology. The Salmonella ma...

  2. TOXNET and Beyond - Using the NLMs Environmental Health and Toxicology Portal-February

    Energy Technology Data Exchange (ETDEWEB)

    Templin-Branner, W.


    The purpose of this training is to familiarize participants with reliable online environmental health and toxicology information, from the National Library of Medicine and other reliable sources. Skills and knowledge acquired in this training class will enable participants to access, utilize, and refer others to environmental health and toxicology information.

  3. 76 FR 10906 - Proposed Substances To Be Evaluated for Set 25 Toxicological Profiles (United States)


    ... Environmental Medicine is soliciting public nominations from the list of proposed substances to be evaluated for... toxicological profiles (CERCLA Set 25). This notice announces the list of proposed substances that will be... toxicological profiles for substances not found at sites on the National Priorities List. The agency will do...


    Energy Technology Data Exchange (ETDEWEB)



    This report presents the atmospheric dispersion coefficients used in Tank Farms safety analysis. The basis equations for calculating radiological and toxicological exposures are also included. In this revision, the time averaging for toxicological consequence evaluations is clarified based on a review of DOE complex guidance and a review of tank farm chemicals.

  5. 78 FR 24762 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for... (United States)


    ... HUMAN SERVICES National Institutes of Health National Toxicology Program Board of Scientific Counselors... Toxicology Program (NTP) Board of Scientific Counselors (BSC). The NTP BSC, a federally chartered, external... quality. Its members are selected from recognized authorities knowledgeable in fields such as...

  6. 75 FR 25866 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative... (United States)


    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP); NTP Interagency Center.... John R. Bucher, Associate Director, National Toxicology Program. BILLING CODE 4140-01-P...

  7. Methods for the Compilation of a Core List of Journals in Toxicology. (United States)

    Kuch, T. D. C.

    Previously reported methods for the compilation of core lists of journals in multidisciplinary areas are first examined, with toxicology used as an example of such an area. Three approaches to the compilation of a core list of journals in toxicology were undertaken and the results analyzed with the aid of models. Analysis of the results of the…

  8. A Directory of Information Resources in the United States, General Toxicology. (United States)

    Library of Congress, Washington, DC. National Referral Center for Science and Technology.

    Listed are institutions and organizations which can serve as information sources on toxicology. Each entry gives the toxicology-related interests of the institution, holdings (of publications), publications of the institution, and information services provided. Poison control centers are listed separately as an appendix. Other appendices list some…

  9. Patty's toxicology. Volume 1: toxicology issues, inorganic particulates, dusts, products of biological origin and pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, E.; Cohrssen, B; Powell, C.H. (eds.) [University of Cincinnati, Cincinnati, OH (US). Kettering Laboratory


    This book discusses toxic agents and pathogens in the workplace and its adverse health effects on workers. This volume includes discussions on industrial toxicology, measuring exposure to toxic substances, occupational chemical carcinogenesis, non-cancer risk assessment, gene-environment interaction, regulations and guidelines in the workplace, toxic chemical information sources, chemical safety, silica and silica compounds, asbestos, talc, rock wool and refractory ceramic fibres, fibreglass, coal, wood dust, cotton and other textile dusts, bioaerosols and disease, bloodborne pathogens in the workplace, tuberculosis and other mycobacteria and petroleum, coal tar and its related products.

  10. TOXNET and Beyond: Using the National Library of Medicine's Environmental Health and Toxicology Portal

    Energy Technology Data Exchange (ETDEWEB)

    Templin-Branner, W.


    The National Library of Medicine's Environmental Health and Toxicology Portal provides access to numerous databases that can help you explore environmental chemicals and risks. TOXNET and Beyond: Using NLM's Environmental Health and Toxicology Portal conveys the fundamentals of searching the NLM's TOXNET system of databases in chemistry, toxicology, environmental health, and related fields. In addition to TOXNET, the course will highlight various resources available through the Environmental Health and Toxicology Portal.

  11. Pharmacology and Toxicology of Extract from Arcangelisia gusanlung

    Institute of Scientific and Technical Information of China (English)

    HU Hai-zhen; DONG Zhi; ZHU Yi; CHEN Guo-biao


    Objective To study the pharmacology and toxicology of the extracts from Arcangelisia gusanlung (EAG).Methods The anti-inflammatory activities were investigated using various inflammatory models including ear edema induced by xylene in mice,paw edema induced by carrageenan,and cotton pellet granuloma in rats.The analgesic effect was observed in hot-plate test and writhing test in mice and the antipyretic effect was observed in rat fever model induced by yeast.The antitussive action was tested in mice by sequential method and expectorant action was evaluated by tracheal excretion of phenol red.The antidiarrhea function was observed on normal intestinal propulsion of mouse model of diarrhea induced by decoction of Sennae Folium.The toxicity was measured by toxicological experiment.Results Each dose of EAG could significantly inhibit the paw edema,cotton pellet granuloma,and intestinal propulsion.EAG significantly reduced writhing times and amount of wet manure.Obvious antipyretic action to fevered rat was observed.EAG obviously increased the tracheal excretion of phenol red and prolonged the latency of cough.No toxic reaction was shown in the observed period,and the maximum tolerance dose of mice was equivalent to 1360 times of common-used dose in human.Conclusion The clinical dosage of EAG is safe,and its anti-inflammatory,analgesia,antipyresis,antitussive,expectorant,and antidiarrhea effects are significant.

  12. Environmental Sciences Division Toxicology Laboratory standard operating procedures

    Energy Technology Data Exchange (ETDEWEB)

    Kszos, L.A.; Stewart, A.J.; Wicker, L.F.; Logsdon, G.M.


    This document was developed to provide the personnel working in the Environmental Sciences Division's Toxicology Laboratory with documented methods for conducting toxicity tests. The document consists of two parts. The first part includes the standard operating procedures (SOPs) that are used by the laboratory in conducting toxicity tests. The second part includes reference procedures from the US Environmental Protection Agency document entitled Short-Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to Freshwater Organisms, upon which the Toxicology Laboratory's SOPs are based. Five of the SOPs include procedures for preparing Ceriodaphnia survival and reproduction test. These SOPs include procedures for preparing Ceriodaphnia food (SOP-3), maintaining Ceriodaphnia cultures (SOP-4), conducting the toxicity test (SOP-13), analyzing the test data (SOP-13), and conducting a Ceriodaphnia reference test (SOP-15). Five additional SOPs relate specifically to the fathead minnow (Pimephales promelas) larval survival and growth test: methods for preparing fathead minnow larvae food (SOP-5), maintaining fathead minnow cultures (SOP-6), conducting the toxicity test (SOP-9), analyzing the test data (SOP-12), and conducting a fathead minnow reference test (DOP-14). The six remaining SOPs describe methods that are used with either or both tests: preparation of control/dilution water (SOP-1), washing of glassware (SOP-2), collection and handling of samples (SOP-7), preparation of samples (SOP-8), performance of chemical analyses (SOP-11), and data logging and care of technical notebooks (SOP-16).

  13. CEBS: a comprehensive annotated database of toxicological data (United States)

    Lea, Isabel A.; Gong, Hui; Paleja, Anand; Rashid, Asif; Fostel, Jennifer


    The Chemical Effects in Biological Systems database (CEBS) is a comprehensive and unique toxicology resource that compiles individual and summary animal data from the National Toxicology Program (NTP) testing program and other depositors into a single electronic repository. CEBS has undergone significant updates in recent years and currently contains over 11 000 test articles (exposure agents) and over 8000 studies including all available NTP carcinogenicity, short-term toxicity and genetic toxicity studies. Study data provided to CEBS are manually curated, accessioned and subject to quality assurance review prior to release to ensure high quality. The CEBS database has two main components: data collection and data delivery. To accommodate the breadth of data produced by NTP, the CEBS data collection component is an integrated relational design that allows the flexibility to capture any type of electronic data (to date). The data delivery component of the database comprises a series of dedicated user interface tables containing pre-processed data that support each component of the user interface. The user interface has been updated to include a series of nine Guided Search tools that allow access to NTP summary and conclusion data and larger non-NTP datasets. The CEBS database can be accessed online at PMID:27899660

  14. Aquatic toxicology of fluoxetine: understanding the knowns and the unknowns. (United States)

    Stewart, Adam Michael; Grossman, Leah; Nguyen, Michael; Maximino, Caio; Rosemberg, Denis Broock; Echevarria, David J; Kalueff, Allan V


    Fluoxetine is one of the most prescribed psychotropic medications, and is an agent of increasing interest for environmental toxicology. Fish and other aquatic organisms are excellent models to study neuroactive small molecules like fluoxetine. However, prone to variance due to experimental factors, data obtained in these models need to be interpreted with caution, using proper experimental protocols, study designs, validated endpoints as well as well-established models and tests. Choosing the treatment protocol and dose range for fluoxetine and other serotonergic drugs is critical for obtaining valid test results and correct data interpretation. Here we discuss the value of aquatic models to study fluoxetine effects, based on prior high-quality research, and outline the directions of future translational studies in the field. We review fluoxetine-evoked phenotypes in acute vs. chronic protocols, discussing them in the contact of complex role of serotonin in behavioral regulation. We conclude that zebrafish and other aquatic models represent a useful in-vivo tool for fluoxetine pharmacology and (eco)toxicology research.

  15. Using Pareto points for model identification in predictive toxicology. (United States)

    Palczewska, Anna; Neagu, Daniel; Ridley, Mick


    : Predictive toxicology is concerned with the development of models that are able to predict the toxicity of chemicals. A reliable prediction of toxic effects of chemicals in living systems is highly desirable in cosmetics, drug design or food protection to speed up the process of chemical compound discovery while reducing the need for lab tests. There is an extensive literature associated with the best practice of model generation and data integration but management and automated identification of relevant models from available collections of models is still an open problem. Currently, the decision on which model should be used for a new chemical compound is left to users. This paper intends to initiate the discussion on automated model identification. We present an algorithm, based on Pareto optimality, which mines model collections and identifies a model that offers a reliable prediction for a new chemical compound. The performance of this new approach is verified for two endpoints: IGC50 and LogP. The results show a great potential for automated model identification methods in predictive toxicology.

  16. Issues in qualitative and quantitative risk analysis for developmental toxicology. (United States)

    Kimmel, C A; Gaylor, D W


    The qualitative and quantitative evaluation of risk in developmental toxicology has been discussed in several recent publications. A number of issues still are to be resolved in this area. The qualitative evaluation and interpretation of end points in developmental toxicology depends on an understanding of the biological events leading to the end points observed, the relationships among end points, and their relationship to dose and to maternal toxicity. The interpretation of these end points is also affected by the statistical power of the experiments used for detecting the various end points observed. The quantitative risk assessment attempts to estimate human risk for developmental toxicity as a function of dose. The current approach is to apply safety (uncertainty) factors to the no observed effect level (NOEL). An alternative presented and discussed here is to model the experimental data and apply a safety factor to an estimated risk level to achieve an "acceptable" level of risk. In cases where the dose-response curves upward, this approach provides a conservative estimate of risk. This procedure does not preclude the existence of a threshold dose. More research is needed to develop appropriate dose-response models that can provide better estimates for low-dose extrapolation of developmental effects.

  17. An animal protection perspective on 21st century toxicology. (United States)

    Stephens, Martin L


    The Humane Society of the United States (HSUS) strongly endorses the vision for the future of toxicity testing proposed in the 2007 National Research Council report Toxicity Testing in the 21st Century. Although crafted primarily with the aim of better assessing the public health risks from chemical exposures, the vision would have a major impact on advancing both alternative testing methods and animal welfare. Consequently, The HSUS seeks to have the vision implemented expeditiously. The HSUS is pleased that the report has elicited considerable discussion and debate and garnered a certain level of approval and applaud current implementation efforts. However, these efforts do not fully capture the vision and strategy outlined by the NRC. The HSUS believes that the timely implementation of the NRC vision warrants a large-scale "Human Toxicology Project" akin to the Human Genome Project of the late 20th century. The HSUS spearheaded the formation of the Human Toxicology Project Consortium to help marshal the necessary will, funding, and research for this effort. Our sister organization, the Humane Society International, is embarking on a related effort with European partners. The HSUS cofounded a website,, devoted exclusively to the scientific and policy issues central to advancing nonanimal methods of toxicity testing. The NRC report has provided a unified framework by which to systematically incorporate the fruits of modern biology and technology into hazard identification and risk assessment, to the betterment not only of toxicity testing and public health, but also of animal protection.

  18. Toxicological risk assessment of complex mixtures through the Wtox model

    Directory of Open Access Journals (Sweden)

    William Gerson Matias


    Full Text Available Mathematical models are important tools for environmental management and risk assessment. Predictions about the toxicity of chemical mixtures must be enhanced due to the complexity of eects that can be caused to the living species. In this work, the environmental risk was accessed addressing the need to study the relationship between the organism and xenobiotics. Therefore, ve toxicological endpoints were applied through the WTox Model, and with this methodology we obtained the risk classication of potentially toxic substances. Acute and chronic toxicity, citotoxicity and genotoxicity were observed in the organisms Daphnia magna, Vibrio scheri and Oreochromis niloticus. A case study was conducted with solid wastes from textile, metal-mechanic and pulp and paper industries. The results have shown that several industrial wastes induced mortality, reproductive eects, micronucleus formation and increases in the rate of lipid peroxidation and DNA methylation of the organisms tested. These results, analyzed together through the WTox Model, allowed the classication of the environmental risk of industrial wastes. The evaluation showed that the toxicological environmental risk of the samples analyzed can be classied as signicant or critical.

  19. 78 FR 26029 - Toxicological Review of Methanol (Non-Cancer): In Support of Summary Information on the... (United States)


    ... AGENCY Toxicological Review of Methanol (Non-Cancer): In Support of Summary Information on the Integrated... public comment period and peer review on the draft non-cancer toxicological review of methanol. SUMMARY... titled ``Toxicological Review of Methanol (Non-Cancer): In Support of Summary Information on...

  20. 77 FR 1707 - National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC) (United States)


    ... HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC) AGENCY: Division of the National Toxicology Program (DNTP...: December 21, 2011. John R. Bucher, Associate Director, National Toxicology Program. BILLING CODE 4140-01-P...

  1. 75 FR 21003 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board... (United States)


    ... HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the... ``Request for Comments'' below). The NTP welcomes toxicology study information from completed, ongoing, or... concept may also encompass larger public health issues or topics in toxicology that could be...

  2. Toxicological Assessment of the Cochleate Derived from Neisseria meningitidis Proteoliposome in Sprague Dawley Rats (United States)

    Infante-Bourzac, Juan Francisco; Sifontes-Rodríguez, Sergio; Arencibia-Arrebola, Daniel Francisco; Hernández-Salazar, Tamara; Fariñas-Medina, Mildrey; Pérez, Oliver


    Background: The AFCo1 cochleate is a potential novel adjuvant derived from Neisseria meningitidis B proteoliposome. Aim: The aim was to assessing the safety of AFCo1 by single and repeated doses in Sprague Dawley rats. Materials and Methods: Rats were grouped for treatment with AFCo1, placebo formulation or control. The first study was a single intranasal dose of 100 μl and monitoring body weight, water, and food intakes as well as clinical symptoms. Fourteen days later the rats were killed and anatomopathological studies were conducted. In a second study, four similar doses of the test substance were instilled every 5 days. Clinical observations were carried out as for the single dose study and a number of rats from each group were killed 3 and 14 days after the last dose in order to conduct hematological, hemochemical, and anatomopathological studies. Results: No variable showed differences of toxicological relevance; the histological changes found were mild and similarly frequently in the three groups. According to the irritability index calculated form histology of the nasal region, AFCo1 was also classified as nonirritating. Conclusion: AFCo1 is potentially safe for human use by nasal route as evidenced by the absence of local and systemic signs of toxicity in Sprague Dawley rats. PMID:22454827

  3. In situ mass spectrometry imaging and ex vivo characterization of renal crystalline deposits induced in multiple preclinical drug toxicology studies.

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    Full Text Available Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition, an un-targeted analysis revealed molecular changes in the kidney that were specifically associated with the area of the tissue defined as pathologically damaged. In the presented study, we show the usefulness of combining mass spectrometry imaging with an array of powerful analytical tools to solve complex toxicological problems occurring during drug development.

  4. NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis

    Energy Technology Data Exchange (ETDEWEB)

    Wu Huifeng [Section of Marine Ecology and Biotechnology, Division of Life Science, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong); Wang Wenxiong, E-mail: [Section of Marine Ecology and Biotechnology, Division of Life Science, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong)


    Traditional toxicology studies have focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. In this study, a system biology tool, metabolomics, was applied to the marine mussel Perna viridis to investigate changes in the metabolic profiles of soft tissue as a response to copper (Cu) and cadmium (Cd), both as single metal and as a mixture. The major metabolite changes corresponding to metal exposure are related to amino acids, osmolytes, and energy metabolites. Following metal exposure for 1 week, there was a significant increase in the levels of branched chain amino acids, histidine, glutamate, glutamine, hypotaurine, dimethylglycine, arginine and ATP/ADP. For the Cu + Cd co-exposed mussels, the levels of lactate, branched chain amino acid, succinate, and NAD increased, whereas the levels of glucose, glycogen, and ATP/ADP decreased, indicating a different metabolic profile for the single metal exposure groups. After 2 weeks of exposure, the mussels showed acclimatization to Cd exposure based on the recovery of some metabolites. However, the metabolic profile induced by the metal mixture was very similar to that from Cu exposure, suggesting that Cu dominantly induced the metabolic disturbances. Both Cu and Cd may lead to neurotoxicity, disturbances in energy metabolism, and osmoregulation changes. These results demonstrate the high applicability and reliability of NMR-based metabolomics in interpreting the toxicological mechanisms of metals using global metabolic biomarkers.

  5. Occupational cancer in France: epidemiology, toxicology, prevention, and compensation. (United States)

    Aubrun, J C; Binet, S; Bozec, C; Brochard, P; Dimerman, S; Fontaine, B; Guénel, P; Luce, D; Martinet, Y; Moulin, J J; Mur, J M; Pietruszynski, M; Vallayer, C


    This article is a description of the current situation in France with regard to occupational cancer: research, prevention, and occupation. Toxicologic experiments are carried out using (italic)in vitro(/italic) and (italic)in vivo(/italic) tests, particularly using transgenic mice. Several epidemiologic studies have been conducted over the last decades: population-based case-control studies; mortality studies and cancer incidence studies carried out in historical cohorts of workers employed in the industry; and case-control studies nested in occupational cohorts. French ethical aspects of toxicologic and epidemiologic studies are described. The results thus obtained are used to establish regulations for the prevention and the compensation of cancers attributable to occupational exposure. This French regulation for prevention of occupational cancer involves several partners: (italic)a(/italic)) the states authorities, including labor inspectors, responsible for preparing and implementing the labor legislation and for supervising its application, particularly in the fields of occupational health and safety and working conditions; (italic)b(/italic)) the Social Security Organisation for the analysis of present or potential occupational risks based on tests, visits in plants, complaints or requests from various sources, and statistics. These activities are performed within the framework of the general French policy for the prevention of occupational cancer. This organization includes the National Institute for Research and Safety, particularly involved in research in the various fields of occupational risks--animal toxicology, biologic monitoring, exposure measurements epidemiology, psychology, ergonomy, electronic systems and machineries, exposure to chemicals, noise, heat, vibration, and lighting; and (italic)c(/italic)) companies where the regulation defines the role of the plant manager, the occupational physician, and the Health, Safety and Working Conditions

  6. Predictive toxicology: the paths of the future; Toxicologie predictive: les voies du futur

    Energy Technology Data Exchange (ETDEWEB)

    Detilleux, Ph.; Vallier, L.; Legallais, C.; Leclerc, E.; Prot, J.M.; Choucha, L.; Baudoin, R.; Dufresne, M.; Gautier, A.; Carpentier, B.; Mansuy, D.; Pery, A.; Brochot, C.; Manivet, Ph.; Rabilloud, Th.; Spire, C.; Coumoul, X.; Junot, Ch.; Laprevote, O.; Le pape, A.; Le Guevel, R.; Tourneur, E.; Ben Mkaddem, S.; Chassin, C.; Aloulou, M.; Goujon, J.M.; Hertif, A.; Ouali, N.; Vimont, S.; Monteiro, R.; Rondeau, E.; Elbim, C.; Werts, C.; Vandewalle, A.; Ben Mkaddem, S.; Pedruzzi, E.; Coant, N.; Bens, M.; Cluzeaud, F.; Ogier-Denis, E.; Pongnimitprasert, N.; Babin-Chevaye, C.; Fay, M.; Bernard, M.; Dupuy, C.; Ei Benna, J.; Gougerot-Pocidale, M.A.; Braut-Boucher, F.; Pinton, Ph.; Lucioli, J.; Tsybulskyy, D.; Joly, B.; Laffitte, J.; Bourges-Abella, N.; Oswald, I.P.; Kolf-Clauw, M.; Pierre, St.; Bats, A.S.; Chevallier, A.; Bui, L.Ch.; Ambolet-Camoit, A.; Garlatti, M.; Aggerbeck, M.; Barouki, R.; Al Khansa, I.; Blanck, O.; Guillouzo, A.; Bars, R.; Rouas, C.; Bensoussan, H.; Suhard, D.; Tessier, C.; Grandcolas, L.; Pallardy, M.; Gueguen, Y.; Sparfel, L.; Pinel-Marie, M.L.; Boize, M.; Koscielny, S.; Desmots, S.; Pery, A.; Fardel, O.; Alvergnas, M.; Rouleau, A.; Lucchi, G.; Mantion, G.; Heyd, B.; Richert, L.; Ducoroy, P.; Martin, H.; Val, St.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A.; Martin-Chouly, C.; Bonvallet, M.; Morzadec, C.; Fardel, O.; Vernhet, L.; Baverel, G.; El Hage, M.; Nazaret, R.; Conjard-Duplany, A.; Ferrier, B.; Martin, G.; Legendre, A.; Desmots, S.; Lecomte, A.; Froment, P.; Habert, R.; Lemazurier, E.; Robinel, F.; Dupont, O.; Sanfins, E.; Dairou, J.; Chaffotte, A.F.; Busi, F.; Rodrigues Lima, F.; Dupret, J.M.; Mayati, A.; Le Ferrec, E.; Levoin, N.; Paris, H.; Uriac, Ph.; N' Diaye, M.; Lagadic-Gossmann, D.; Fardel, O.; Assemat, E.; Boublil, L.; Borot, M.C.; Marano, F.; Baeza-Squiban, A.; Martiny, V.Y.; Moroy, G.; Badel, A.; Miteva, M.A.; Hussain, S.; Ferecatu, I.; Borot, C.; Andreau, K.; Baeza-Squiban, A. [and others


    Prevention of possible noxious effects in relation with the exposure to one or several chemical, physical or biological agents present in our domestic or professional environment is one of today's big public health stakes. Another stake is the better assessment of the risks linked with the use of health-care products. The efficacy and predictiveness of toxicology studies are directly related to the combination of alternate complementary methods and animal experiments (obtaining data from different species and with different models: in vitro, ex vivo and in vivo). Despite important efforts, the toxicological evaluation remains perfectible. The proceedings of this 2010 congress of the French Society of cell pharmaco-toxicology deal with recent advances, both scientific and technological, in 'predictive toxicology'. Four main topics are approached: cell and organ models, 'omics', in silico modeling, and new technologies (imaging, cell ships, high-speed processing). Among the different presentations, 3 abstracts present some recent advances in imaging techniques applied to toxicology studies. These are: 1 - first uses in toxicology of TOF-SIMS mass spectroscopy imaging (O. Laprevote, Paris-Descartes Univ. (FR)); 2 - Small animal imaging, a tool for predictive toxicology (A. Le Pape, CNRS Orleans (FR)); 3 - uranium localization at cell level using SIMS imaging technique (C. Rouas et al., IRSN Fontenay-aux-Roses (FR)). (J.S.)

  7. Pharmacologic and toxicologic evaluation of C. novyi-NT spores. (United States)

    Diaz, Luis A; Cheong, Ian; Foss, Catherine A; Zhang, Xiaosong; Peters, Brock A; Agrawal, Nishant; Bettegowda, Chetan; Karim, Baktiar; Liu, Guosheng; Khan, Khalid; Huang, Xin; Kohli, Manu; Dang, Long H; Hwang, Paul; Vogelstein, Ahava; Garrett-Mayer, Elizabeth; Kobrin, Barry; Pomper, Martin; Zhou, Shibin; Kinzler, Kenneth W; Vogelstein, Bert; Huso, David L


    Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration.

  8. Pollutants bioavailability and toxicological risk from microplastics to marine mussels. (United States)

    Avio, Carlo Giacomo; Gorbi, Stefania; Milan, Massimo; Benedetti, Maura; Fattorini, Daniele; d'Errico, Giuseppe; Pauletto, Marianna; Bargelloni, Luca; Regoli, Francesco


    Microplastics represent a growing environmental concern for the oceans due to their potential of adsorbing chemical pollutants, thus representing a still unexplored source of exposure for aquatic organisms. In this study polyethylene (PE) and polystyrene (PS) microplastics were shown to adsorb pyrene with a time and dose-dependent relationship. Results also indicated a marked capability of contaminated microplastics to transfer this model PAH to exposed mussels Mytilus galloprovincialis; tissue localization of microplastics occurred in haemolymph, gills and especially digestive tissues where a marked accumulation of pyrene was also observed. Cellular effects included alterations of immunological responses, lysosomal compartment, peroxisomal proliferation, antioxidant system, neurotoxic effects, onset of genotoxicity; changes in gene expression profile was also demonstrated through a new DNA microarray platform. The study provided the evidence that microplastics adsorb PAHs, emphasizing an elevated bioavailability of these chemicals after the ingestion, and the toxicological implications due to responsiveness of several molecular and cellular pathways to microplastics.

  9. Phytochemistry, Pharmacology and Toxicology of Spilanthes acmella: A Review

    Directory of Open Access Journals (Sweden)

    Suchita Dubey


    Full Text Available Spilanthes acmella is an important medicinal plant, found in tropical and subtropical countries mainly India and South America. Popularly, it is known as toothache plant which reduces the pain associated with toothaches and can induce saliva secretion. Various extracts and active metabolites from various parts of this plant possess useful pharmacological activities. Literature survey proposed that it has multiple pharmacological actions, which include antifungal, antipyretic, local anaesthetic, bioinsecticide, anticonvulsant, antioxidant, aphrodisiac, analgesic, pancreatic lipase inhibitor, antimicrobial, antinociception, diuretic, vasorelaxant, anti-human immunodeficiency virus, toothache relieve and anti-inflammatory effects. This review is elaborately describing the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. This review would assist researchers to search scientific information in the future.

  10. Review of the Pharmacological and Toxicological Effects of Salvia leriifolia

    Directory of Open Access Journals (Sweden)

    Hossein Hosseinzadeh


    Full Text Available Salvia leriifolia Benth. (vernacular names such as Nuruozak and Jobleh is a perennial herbaceous plant that grows exclusively in south and tropical regions of Khorasan and Semnan provinces, I. R. Iran. Unlike other species of Salvia genus, the chemical constituents of S. leriifolia are not well recognized. The stem oil of the plant consisted mainly both monoterpenes and sesquiterpenes, while in leaf and flower oils monoterpenes predominated over sesquiterpenes. In recent years, the different properties of this plant such as the attenuation of morphine dependence, hypoglycemic, antinociceptive and antiinflammatory, antioxidant, anti-ischemia, anticonvulsant, antiulcer effects, antibacterial activities and antimutagenic effects were evaluated. These effects introduce this plant for more toxicological and clinical trials evaluations as a herbal medicine.

  11. Efficient Experimental Design Strategies in Toxicology and Bioassay

    Directory of Open Access Journals (Sweden)

    Timothy E. O'Brien


    Full Text Available Modelling in bioassay often uses linear or nonlinear logistic regression models, and relative potency is often the focus when two or more compounds are to be compared.  Estimation in these settings is typically based on likelihood methods.  Here, we focus on the 3-parameter model representation given in Finney (1978 in which the relative potency is a model parameter.  Using key matrix results and the general equivalence theorem of Kiefer & Wolfowitz (1960, this paper establishes key design properties of the optimal design for relative potency using this model.  We also highlight aspects of subset designs for the relative potency parameter and extend geometric designs to efficient design settings of bioassay.  These latter designs are thus useful for both parameter estimation and checking for goodness-of-fit.  A typical yet insightful example is provided from the field of toxicology to illustrate our findings.

  12. Poisonings and clinical toxicology: a template for Ireland.

    LENUS (Irish Health Repository)

    Tormey, W P


    Poisons information is accessed around the clock in the British Isles from six centres of which two are in Ireland at Dublin and Belfast accompanied by consultant toxicologist advisory service. The numbers of calls in Ireland are down to about 40 per day due to easy access to online data bases. Access to Toxbase, the clinical toxicology database of the National Poisons Information Service is available to National Health Service (NHS) health professionals and to Emergency Departments and Intensive Care units in the Republic of Ireland. There are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates in Emergency Departments. All United States Poison Control Centres primarily use Poisindex which is a commercial database from Thomson Reuters.

  13. Long-term toxicological effects of paracetamol in rats

    Directory of Open Access Journals (Sweden)

    S.K. Majeed,


    Full Text Available The analgesic and antipyretic properties of paracetamol were first described in 1893, then it has been widely available as a non-prescription drug, with a therapeutic profile that reflects widespread safety and efficacy as well as paracetamol became the most widely used analgesic and antipyretic in children. It is the most frequently used over-the counter medicine in young children and is nearly universally used in infants. The drug is used by millions of children every day. The study was designed to study the toxicological effect of therapeutic dose of paracetamol after oral administration for three months in laboratory rats (Rattus norvegicous on the heart, kidney and liver. Results showed oral administration of the paracetamol for three months in laboratory rats showed that this drug has a severe damaging effect on most of the vital organs in the body like kidney, liver and heart.

  14. Inhalation Toxicology Research Institute Site Environmental report, 1994

    Energy Technology Data Exchange (ETDEWEB)



    The Inhalation Toxicology Research Institute (ITRI) was constructed in 1960 with the initial purpose of studying human health hazards of inhaling airborne radioactive fission products; its scope was broadened to cover other airborne materials. ITRI has in place an extensive radiological and nonradiological environmental monitoring program which monitors air emissions, groundwater, soil and ambient air around the facility. ITRI is in compliance with air quality and hazardous waste regulations; however, sewage lagoons remain from previous operations. Remediation activities have been begun or are scheduled to begin on these lagoons and on low-level radioactive liquid waste evaporation ponds. Except for the issues mentioned, ITRI is in compliance with all other federal, state, and local regulations.

  15. That's a Phat Antidote: Intravenous Fat Emulsions and Toxicological Emergencies. (United States)

    Schultz, Amy E; Lewis, Temeka; Reed, Brittany S; Weant, Kyle A; Justice, Stephanie Baker


    Health care providers in the emergency department (ED) frequently find themselves caring for patients who may have overdosed on a medication(s) or other toxic substance. These patients can prove to be a challenge, as providers must try to determine the substance(s) involved so that the appropriate treatment can be initiated. For those patients who are hemodynamically unstable upon presentation, it is important to note that supportive care is of the utmost importance, as there are few substances that have antidotes available. In these situations, lipid emulsion can be considered. This is especially true in the setting of the following toxicities: local anesthetics, β-blockers, calcium channel blockers, and the tricyclic antidepressants. Even though lipid emulsion may not be used that frequently in the ED, it is important to be aware of its role in the setting of toxicological emergencies, how it should be dosed and administered, and the necessary safety precautions.

  16. Characterisation of nanoparticle size and concentration for toxicological studies. (United States)

    Bendre, V; Gautam, M; Carr, R; Smith, J; Malloy, A


    The assessment of the complete distribution of nanoparticle sizes within a suspension is notoriously difficult to carry out. We demonstrate the Nanoparticle Tracking Analysis (NTA) technique that sizes nanoparticles in suspension, based on their Brownian motion. This technique has found significant use in the field of nano- and eco-toxicology, in several research groups showing of the technique to assess a range of engineered nanoparticles including gold, SiO2, TiO2 and polystyrene. This capability shares many features in common with conventional flow cytometry but is unique in this deeply sub-micron size range. NTA is a direct and fast technique by which nanoparticles in their natural solvated state in a liquid can be rapidly detected, sized and counted. The technique can be used to complement existing techniques for the sizing of nanoparticles (e.g., DLS, PCS) allowing data obtained from these methods to be validated by direct microscopical observation of the sample.

  17. Toxicological Concerns of Engineered Nanosize Drug Delivery Systems. (United States)

    Mukherjee, Biswajit; Maji, Ruma; Roychowdhury, Samrat; Ghosh, Saikat


    Matters when converted into nanosize provide some unique surface properties, which are different from those of the bulk materials. Nanomaterials show some extraordinary behavioral patterns because of those properties, such as supermagnetism, quantum confinement, etc. A great deal of implication of nanomaterials in nanomedicine has already been realized. Utility of nanomaterials as drug nanocarrier projects many potential advantages of them in drug delivery. Despite many such advantages, the potential risk of health and environmental hazards related to them cannot be ignored. Here various physicochemical factors, such as chemical nature, degradability, surface properties, surface charge, particle size, and shape, have been shown to play a crucial role in toxicity related to drug nanocarriers. Evidence-based findings of some drug nanocarriers have been incorporated to provide distinct knowledge to the readers in the field. A glimpse of current regulatory controls and measures required to combat the challenges of toxicological aspects of drug nanocarriers have been described.

  18. Toxicological Studies of Mycotoxins Using Enzymatic and Histochemical Methods

    Energy Technology Data Exchange (ETDEWEB)

    Badea, Mihaela, E-mail:; Taus, Nicoleta [Transilvania University of Brasov, Faculty of Medicine (Romania); Potrovita, Monica [Sanitary-Veterinary and Food Safety Direction of Brasov (Romania); Moarcas, Monica [Transilvania University of Brasov, Faculty of Medicine (Romania)


    Studies concerning mycotoxins involve activities of relevant potential for furthering knowledge in the fields of toxicology and environmental analysis. Using bioanalytical methods (biosensors, histochemistry), the conducted research aims at contributing to raising the awareness of local, national, and international media in relation to the safety of obtaining and processing vegetal and animal foods, by analyzing the possible effects of aflatoxins and ochratoxins, promoting animal health, food hygiene, in view of ensuring animal and human health. The study using laboratory animals (mice) while being part of one of the current national research directions, also holds international priority, by its contribution to a better understanding of several fundamental mechanisms of life at molecular level and to the characterization of certain biological processes that appear in mycotoxicosis.

  19. Systematic toxicological analysis revealing a rare case of captan ingestion. (United States)

    Gottzein, Anne K; Musshoff, Frank; Madea, Burkhard


    This article presents a case of suicide by intoxication with various pharmaceuticals, particularly anticonvulsants, combined with the fungicide captan. A cause of death could not be ascertained at autopsy. However, systematic toxicological analysis (STA) including a screening via solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) for (semi) volatile organic compounds revealed results suggesting a possible cause of death. The effects of captan on the human organism, its metabolism, and distribution will be discussed. Macroscopically, the cause of death was unascertained. STA revealed clonazepam, citalopram, and its metabolites, lamotrigine, levetiracetam, lacosamide, clonazepam, captan, and its metabolite tetrahydrophthalimide (THPI). For the first time, it was detected in human viscera. A quantification of THPI was performed to obtain distribution in the organs. The significance of a complete STA must be emphasized. The presence of THPI would have been missed without previous detection of captan. Consequently, this fatality would not have been investigated satisfactorily.

  20. Integrating zebrafish toxicology and nanoscience for safer product development. (United States)

    Kim, Ki-Tae; Tanguay, Robert L


    The design, manufacture and application of safer products and manufacturing processes have been important goals over the last decade and will advance in the future under the umbrella of "Green Chemistry". In this review, we focus on the burgeoning diversity of new engineered nanomaterials (ENMs) and the prescient need for a nanotoxicology paradigm that quickly identifies potentially hazardous nanochemistries. Advances in predictive toxicological modeling in the developing zebrafish offer the most immediate translation to human hazard that is practically achievable with high throughput approaches. Translation in a vertebrate model that is also a low cost alternative to rodents for hazard prediction has been a desirable but elusive testing paradigm. The utility of zebrafish, if applied early in the ENM discovery pipeline, could greatly enhance efforts toward greener and more efficient nanoscience. Early pipeline detection of human and environmental health impacts will quickly inform decisions in the design and production of safer commercial ENMs.

  1. Toxicology effects of saffron and its constituents: a review (United States)

    Bostan, Hasan Badie; Mehri, Soghra; Hosseinzadeh, Hossein


    Saffron (Crocus sativus L.) has been considered as a medicinal plant since ancient times and also widely used as food additive for its color, taste and odor. The pharmacological properties of saffron and its main constituents, crocin and safranal have been evaluated using different in vivo and in vitro models. Additionally, other lines of studies have found toxicological effects of saffron. However, a comprehensive review that covers all aspects of its toxicity has not been published yet. The current study provides classified information about the toxic effects of saffron and its constituents in various exposure conditions including acute, sub-acute, sub-chronic and chronic studies. Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations. PMID:28293386

  2. A review on Ipomoea carnea: pharmacology, toxicology and phytochemistry. (United States)

    Fatima, Nusrat; Rahman, Mohammad Mijanur; Khan, Md Asaduzzaman; Fu, Junjiang


    Phytomedicines are increasingly being established in modern medical science. The shrub Ipomoea carnea has been used traditionally for thousands of years. However, there are few scientific studies on this medicinal plant, and most of the information are scattered. In this review, we have summarized the existing knowledge and recent progress on the medicinal importance of I. carnea. Different extracts of I. carnea plant possess anti-bacterial, anti-fungal, anti-oxidant, anti-cancer, anti-convulsant, immunomodulatory, anti-diabetic, hepatoprotective, anti-inflammatory, anxiolytic, sedative and wound healing activities. However, some toxicological effects have been also reported. Some of the major phytochemicals associated with the bioactivity of I. carnea have been characterized, which have been discussed in this study too. This review article might be beneficial for phytotherapy research, as I. carnea can be a good source for drug development.

  3. Risks, risk assessment and risk competence in toxicology. (United States)

    Stahlmann, Ralf; Horvath, Aniko


    Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  4. Climate change and ocean acidification-interactions with aquatic toxicology. (United States)

    Nikinmaa, Mikko


    The possibilities for interactions between toxicants and ocean acidification are reviewed from two angles. First, it is considered how toxicant responses may affect ocean acidification by influencing the carbon dioxide balance. Second, it is introduced, how the possible changes in environmental conditions (temperature, pH and oxygenation), expected to be associated with climate change and ocean acidification, may interact with the toxicant responses of organisms, especially fish. One significant weakness in available data is that toxicological research has seldom been connected with ecological and physiological/biochemical research evaluating the responses of organisms to temperature, pH or oxygenation changes occurring in the natural environment. As a result, although there are significant potential interactions between toxicants and natural environmental responses pertaining to climate change and ocean acidification, it is very poorly known if such interactions actually occur, and can be behind the observed disturbances in the function and distribution of organisms in our seas.

  5. Risks, risk assessment and risk competence in toxicology

    Directory of Open Access Journals (Sweden)

    Stahlmann, Ralf


    Full Text Available Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  6. Inequalities between similarities for numerical data

    NARCIS (Netherlands)

    Warrens, Matthijs J.


    Similarity measures are entities that can be used to quantify the similarity between two vectors with real numbers. We present inequalities between seven well known similarities. The inequalities are valid if the vectors contain non-negative real numbers.

  7. Managing Toxicological Risks: The Legacy of Shuttle Operations (United States)

    James, John T.


    Space toxicology greatly matured as a result of research and operations associated with the Shuttle. Materials offgassing had been a manageable concern since the Apollo days, but we learned to pay careful attention to compounds that could escape containment, to combustion events, to toxic propellants, to overuse of utility compounds, and to microbial and human metabolites. We also learned that flying real-time hardware to monitor air pollutants was a pathway with unanticipated speed bumps. Each new orbiter was tested for any excess offgassing products that could pollute the air during flight. In the late 1990s toxicologists and safety experts developed a 5-level toxicity rating system to guide containment of toxic compounds. This system is now in use aboard the International Space Station (ISS). Several combustion events during Shuttle Mir and also during Shuttle free-flight impelled toxicologists to identify hardware capable of monitoring toxic products; however, rapid adaptation of the hardware for the unique conditions of spaceflight caused unexpected missteps. Current and planned combustion analyzers would be useful to commercial partners that wish to manage the risk of health effects from thermal events. Propellants received special attention during the Shuttle program because of the possibility of bringing them into the habitable volume on extravehicular activity suits. Monitors for the airlocks were developed to mitigate this risk. Utility materials, such as lubricants, posed limited toxicological problems because water was not recovered. One clearly documented case of microbial metabolites polluting the Shuttle atmosphere was noted, and this has implications for commercial flights and control of microbes. Finally, carbon dioxide, the major human metabolite, episodically presented air quality problems aboard Shuttle, especially when nominal air flows were obstructed. Commercial vehicles must maintain robust air circulation given the anticipated high density

  8. Pesticide Chemical Research in Toxicology: Lessons from Nature. (United States)

    Casida, John E; Durkin, Kathleen A


    Pesticide researchers are students of nature, and each new compound and mechanism turns a page in the ever-expanding encyclopedia of life. Pesticides are both probes to learn about life processes and tools for pest management to facilitate food production and enhance health. In contrast to some household and industrial chemicals, pesticides are assumed to be hazardous to health and the environment until proven otherwise. About a thousand current pesticides working by more than 100 different mechanisms have helped understand many processes and coupled events. Pesticide chemical research is a major source of toxicology information on new natural products, novel targets or modes of action, resistance mechanisms, xenobiotic metabolism, selective toxicity, safety evaluations, and recommendations for safe and effective pest management. Target binding site models help define the effect of substituent changes and predict modifications for enhanced potency and safety and circumvention of resistance. The contribution of pesticide chemical research in toxicology is illustrated here with two each of the newer or most important insecticides, herbicides, and fungicides. The insecticides are imidacloprid and chlorantraniliprole acting on the nicotinic acetylcholine receptor and the ryanodine receptor Ca(2+) channel, respectively. The herbicides are glyphosate that inhibits aromatic amino acid biosynthesis and mesotrione that prevents plastoquinone and carotenoid formation. The fungicides are azoxystrobin inhibiting the Qo site of the cytochrome bc1 complex and prothioconazole inhibiting the 14α-demethylase in ergosterol biosynthesis. The two target sites involved for each type of pesticide account for 27-40% of worldwide sales for all insecticides, herbicides, and fungicides. In each case, selection for resistance involving a single amino acid change in the binding site or detoxifying enzyme circumvents the pesticide chemists's structure optimization and guarantees survival of

  9. Advice on Degradation Products in Pharmaceuticals: A Toxicological Evaluation. (United States)

    Melo, Sâmia Rocha de Oliveira; Homem-de-Mello, Maurício; Silveira, Dâmaris; Simeoni, Luiz Alberto

    Degradation products are unwanted chemicals that can develop during the manufacturing, transportation, and storage of drug products and can affect the efficacy of pharmaceutical products. Moreover, even small amounts of degradation products can affect pharmaceutical safety because of the potential to cause adverse effects in patients. Consequently, it is crucial to focus on mechanistic understanding, formulation, storage conditions, and packaging to prevent the formation of degradation products that can negatively affect the quality and safety of the drug product. In this sense, databases and software that help predict the reactions involving the pharmaceutically active substance in the presence of degradation conditions can be used to obtain information on major degradation routes and the main degradation products formed during pharmaceutical product storage. In some cases, when the presence of a genotoxic degradation product is verified, it is necessary to conduct more thorough assessments. It is important to consider the chemical structure to distinguish between compounds with toxicologically alerting structures with associated toxic/genotoxic risks and compounds without active structures that can be treated as ordinary impurities. Evaluating the levels of degradation products based on a risk/benefit analysis is mandatory. Controlling critical variables during early development of drug products and conducting a follow-up study of these impurities can prevent degradation impurities present at concentrations greater than threshold values to ensure product quality. The definition of the impurity profile has become essential per various regulatory requirements. Therefore, this review includes the international regulatory perspective on impurity documents and the toxicological evaluation of degradation products. Additionally, some techniquesused in the investigation of degradation products and stability-indicating assay methods are highlighted.

  10. The toxicology of ion-shedding zinc oxide nanoparticles. (United States)

    Liu, Jia; Feng, Xiaoli; Wei, Limin; Chen, Liangjiao; Song, Bin; Shao, Longquan


    Zinc oxide nanoparticles (ZnO NPs) are nanomaterials that are widely used in many fields. ZnO NPs are ion-shedding particles, and zinc ions produce important and potent effects that differ from those of other metal or metal oxide NPs. Several studies have reported the toxicological effects of ZnO NPs administered via several different routes, including orally, dermally, by pulmonary absorption, intraperitoneally, and intravenously. Some potential routes for human exposure have produced various toxic effects in animal models. Moreover, several in vitro studies using a range of cell lines have reported the mechanisms underlying ZnO NP toxicity. Zinc ions play a very important role in ZnO NP toxicity, although the effects of the particulate form cannot be excluded. A crucial determinant of toxicity is the solubility of ZnO NPs, which is influenced by various factors, including the pH of the environment in tissues, cells, and organelles. In addition to the inflammatory responses and oxidative stress known to be induced by ZnO NPs, these NPs also exhibit some positive anti-inflammatory, anti-diabetic, and pro-coagulant effects at sub-toxic doses; these effects are probably induced by zinc ions, which are an essential element in cell homeostasis. It is highly likely that there are additional distinct mechanisms at sub-toxic doses and concentrations, which may be concealed or altered by the toxic effects observed at higher levels of ZnO NPs. Furthermore, many signaling pathway molecules associated with necrosis and apoptosis can be activated, leading to cell death. This review presents the status of ZnO NP toxicology and highlights areas requiring further investigation.

  11. Toxicology from the Perspective of Iranian Traditional Medicine (United States)

    Rahimi, Roja; Mehriardestani, Mozhgan


    Background: The science of toxicology has a long history and been highly valued in Islamic countries. Numerous scientists were the expert in this field, particularly during the third and fourth centuries. Through reading such literature and gaining the experience of the scientists, one can use such valuable information to promote this science. Methods: In this article, different sources of traditional medicine from the first to the fourteenth century were evaluated. Results: The first toxicologist during the Islamic era was Ibn Uthal. Jāber ibn Hayyān offered interesting ideas about the pharmacokinetics of toxins. Ibn Wahshia, along with translating books, described his personal experiences in a book called Al-Somum va al-Tary aghat. The most important bites, poisons, and related treatments were specifically viewed by Rhazi. Then, Ibn Sīnā explained different aspects of poisons, including their identity and constituents, diagnoses of poison types, methods of detoxification, and treatment of poisoning. Jorjāni suggested some drugs for poisoning prevention. He recommended these drugs to be consumed before an individual enters a place that has poisoning potential. An important achievement of Imad al-Din is the innovation of new methods for detoxification of some poisons. Aghili described the symptoms of poisoning and special methods of detoxification by which toxicity is greatly reduced. Finally, Abdolhossein Zonouzi Tabrizi in Marefat-al-Somum mentioned the identification of natural and synthetic poisons. In fact, this book is a bridge between the traditional and modern toxicology. Conclusion: It seems that the study of these manuscripts would provide valuable clinical experiences from medieval Islamic toxicologists on different types of poisoning. Therefore, it helps to gain new ideas for the prevention and treatment of poisoning. PMID:27516702

  12. The Annapolis Accords on the use of toxicology in decision-making. Annapolis Center Workshop Report.

    Energy Technology Data Exchange (ETDEWEB)

    Gray, G.M.; Baskin, S.I.; Charnley, G.; Cohen, J.T.; Gold, L.S.; Kerkvliet, N.I.; Koenig, H.M.; Lewis, S.C.; McClain, R.M.; Rhomberg, L.R.; Snyder, J.W.; Weekley, L.B.


    The science of toxicology plays an important role in identifying safe conditions of use or exposure for many different kinds of environmental agents. The use of toxicologic information in risk assessment requires careful analysis, evaluation of data, and scientific judgment. These Annapolis Accords are intended to guide appropriate use in risk assessment of the scientific information from toxicology. We believe that application of these principles will improve the scientific credibility of risk assessment and the quality of decisions aimed at reducing and eliminating risks to human health and the environment.

  13. Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. (United States)

    Lindon, John C; Nicholson, Jeremy K; Holmes, Elaine; Antti, Henrik; Bollard, Mary E; Keun, Hector; Beckonert, Olaf; Ebbels, Timothy M; Reily, Michael D; Robertson, Donald; Stevens, Gregory J; Luke, Peter; Breau, Alan P; Cantor, Glenn H; Bible, Roy H; Niederhauser, Urs; Senn, Hans; Schlotterbeck, Goetz; Sidelmann, Ulla G; Laursen, Steen M; Tymiak, Adrienne; Car, Bruce D; Lehman-McKeeman, Lois; Colet, Jean Marie; Loukaci, Ali; Thomas, Craig


    The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here together with a brief summary of published studies. To provide a comprehensive assessment of this approach, the Consortium for Metabonomic Toxicology (COMET) has been formed between six pharmaceutical companies and Imperial College of Science, Technology and Medicine (IC), London, UK. The objective of this group is to define methodologies and to apply metabonomic data generated using (1)H NMR spectroscopy of urine and blood serum for preclinical toxicological screening of candidate drugs. This is being achieved by generating databases of results for a wide range of model toxins which serve as the raw material for computer-based expert systems for toxicity prediction. The project progress on the generation of comprehensive metabonomic databases and multivariate statistical models for prediction of toxicity, initially for liver and kidney toxicity in the rat and mouse, is reported. Additionally, both the analytical and biological variation which might arise through the use of metabonomics has been evaluated. An evaluation of intersite NMR analytical reproducibility has revealed a high degree of robustness. Second, a detailed comparison has been made of the ability of the six companies to provide consistent urine and serum samples using a study of the toxicity of hydrazine at two doses in the male rat, this study showing a high degree of consistency between samples from the various companies in terms of spectral patterns and biochemical composition. Differences between samples from the various companies were small compared to the biochemical effects of the toxin. A metabonomic model has been constructed for urine from control rats, enabling identification of outlier samples and the metabolic reasons for the deviation. Building on this success, and with the completion of studies on approximately 80 model toxins, first expert systems for prediction of liver and kidney

  14. Physiology and toxicology of hormone-disrupting chemicals in higher plants. (United States)

    Couée, Ivan; Serra, Anne-Antonella; Ramel, Fanny; Gouesbet, Gwenola; Sulmon, Cécile


    Higher plants are exposed to natural environmental organic chemicals, associated with plant-environment interactions, and xenobiotic environmental organic chemicals, associated with anthropogenic activities. The effects of these chemicals result not only from interaction with metabolic targets, but also from interaction with the complex regulatory networks of hormone signaling. Purpose-designed plant hormone analogues thus show extensive signaling effects on gene regulation and are as such important for understanding plant hormone mechanisms and for manipulating plant growth and development. Some natural environmental chemicals also act on plants through interference with the perception and transduction of endogenous hormone signals. In a number of cases, bioactive xenobiotics, including herbicides that have been designed to affect specific metabolic targets, show extensive gene regulation effects, which are more in accordance with signaling effects than with consequences of metabolic effects. Some of these effects could be due to structural analogies with plant hormones or to interference with hormone metabolism, thus resulting in situations of hormone disruption similar to animal cell endocrine disruption by xenobiotics. These hormone-disrupting effects can be superimposed on parallel metabolic effects, thus indicating that toxicological characterisation of xenobiotics must take into consideration the whole range of signaling and metabolic effects. Hormone-disruptive signaling effects probably predominate when xenobiotic concentrations are low, as occurs in situations of residual low-level pollutions. These hormone-disruptive effects in plants may thus be of importance for understanding cryptic effects of low-dosage xenobiotics, as well as the interactive effects of mixtures of xenobiotic pollutants.

  15. Toxicologic evaluation of DHA-rich algal oil: Genotoxicity, acute and subchronic toxicity in rats. (United States)

    Schmitt, D; Tran, N; Peach, J; Bauter, M; Marone, P


    DHA-rich algal oil ONC-T18, tested in a battery of in vitro and in vivo genotoxicity tests, did not show mutagenic or genotoxic potential. The acute oral LD50 in rats has been estimated to be greater than 5000 mg/kg of body weight. In a 90-day subchronic dietary study, administration of DHA-rich algal oil at concentrations of 0, 10,000, 25,000, and 50,000 ppm in the diet for 13 weeks did not produce any significant toxicologic manifestations. The algal oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The no observed adverse effect level (NOAEL) was the highest level fed of 50,000 ppm which is equivalent to 3,305 and 3,679 mg/kg bw/day, for male and female rats, respectively. The studies were conducted as part of an investigation to examine the safety of DHA-rich algal oil. The results confirm that it possesses a toxicity profile similar to other currently marketed algal oils and support the safety of DHA-rich algal oil for its proposed use in food.

  16. The EPA Comptox Chemistry Dashboard: A Web-Based Data Integration Hub for Toxicology Data (SOT) (United States)

    The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

  17. IRIS Toxicological Review of Halogenated Platinum Salts and Platinum Compounds (External Review Draft) (United States)

    EPA released the draft toxicological review for public comment under the Integrated Risk Information System (IRIS) Program. The original draft assessment (January 2009) has been archived but is available on this web page for the sake of transparency.

  18. Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System

    DEFF Research Database (Denmark)

    Autrup, Herman; Barile, Frank A; Blaauboer, Bas J


    The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can...

  19. Waste tank safety program annual status report for FY 1993, Task 5: Toxicology and epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Mahlum, D.D.; Young, J.Y.


    A toxicology team independently reviewed analytical data and provided advice concerning potential health effects associated with exposure to tank-vapor constituents at the Hanford site. Most of the emphasis was directed toward Tank 241-C-103, but a preliminary assessment was also made of the toxicologic implication of the cyanide levels in the headspace of Tank 241-C-108. The objectives of this program are to (1) review procedures used for sampling vapors from various tanks, (2) identify constituents in tank-vapor samples that could be related to symptoms reported by waste-tank workers, (3) evaluate the toxicologic implications of those constituents by comparison to established toxicologic data bases, (4) provide advice for additional analytical efforts, and (5) support other activities as requested by the project manager and the cognizant Westinghouse Hanford Company Tank Vapor Issues Safety Resolution Manager.

  20. Historia de la Asociación Española de Toxicología

    Directory of Open Access Journals (Sweden)

    E. de la Peña de Torres


    Full Text Available Se detalla la creación y constitución de la Asociación Española de Toxicología y una descripcion pormenorizada de cada una de las actividades y elementos que la constituyen: Información, Secciones, Junta Directiva, Revista de Toxicología, Congresos, Registro Español de Toxicólogos, Comité Español de Toxicología CeTox, Glosario toxicológico; se concluye con la vocación de la AETOX de promover el desarrollo y formación de la Toxicología tanto en España como en Iberoamérica

  1. Opinions expressed by Italian National Advisory Toxicological Committee on some active ingredients of pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Camoni, I. [Ist. Superiore di Sanita`, Rome (Italy). Lab. di Tossicologia Applicata


    The opinions expressed by the Italian National Advisory Toxicological Committee (CCTN) on some active ingredients of pesticides are presented. Carcinogenic and mutagenic effects of these substances have been examined and, on this basis, an evaluation and relative classification were expressed.

  2. Inhalation Toxicology Research Institute. Annual report, October 1, 1992--September 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Nikula, K.J.; Belinsky, S.A.; Bradley, P.L. [eds.


    This annual report for the Inhalation Toxicology Research Institute for 1992-1993 consists of 60 individual reports prepared separately by investigators describing progress in their own projects. Most papers are 2-5 pages long.

  3. Exposure Science and the US EPA National Center for Computational Toxicology (United States)

    The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. The...

  4. Historia de la Asociación Española de Toxicología


    E. de la Peña de Torres


    Se detalla la creación y constitución de la Asociación Española de Toxicología y una descripcion pormenorizada de cada una de las actividades y elementos que la constituyen: Información, Secciones, Junta Directiva, Revista de Toxicología, Congresos, Registro Español de Toxicólogos, Comité Español de Toxicología CeTox, Glosario toxicológico; se concluye con la vocación de la AETOX de promover el desarrollo y formación de la Toxicología tanto en España como en Iberoamérica

  5. Advances in the use of mass spectral libraries for forensic toxicology. (United States)

    Aebi, Beat; Bernhard, Werner


    Gas chromatography in combination with mass spectrometry (GC-MS) plays an important role in the field of analytical toxicology. The identification of unknown compounds is very frequently undertaken with GC-MS and utilizing mass spectral libraries. Currently available libraries for analytical toxicology were compared for overlapping and uniqueness of their entries. Furthermore, the widely known Pfleger-Maurer-Weber-Drugs-and-Pesticides-Library for toxicology (PMW_tox2) was used to compare the search algorithms PBM (Probability Based Matching, Agilent Technologies), INCOS (Finnigan/Thermoquest), and MassLib (Max Planck Institute). To our knowledge, direct comparisons of mass spectral libraries and search programs for analytical toxicology have not been published previously. The capabilities and necessities of modern MS technology in the field of general unknown analysis are revealed, and some of the potential pitfalls are described.

  6. Decavanadate toxicology and pharmacological activities: V10 or V1, both or none?



    This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mi...

  7. Toxicology in the use, misuse and abuse of food, drugs and chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, P.L.; Chambers, C.M.; Gitter, S.


    The present proceedings containing 77 papers were presented at a meeting of the European Society of Toxicology held in Tel Aviv, March 21-24, 1982. The topics were: Effects of foreign substances on blood, drugs of abuse with special reference to marijuana and phencyclidine, toxic agents in food, xenobiotics, novel and new techniques in toxicology and miscellaneous toxic effects. Individual abstracts are prepared of 11 papers.

  8. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research


    Mark T. Mc Auley; Hyunok Choi; Kathleen Mooney; Emily Paul; Miller, Veronica M.


    Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditiona...

  9. Multimodal Molecular Mass Spectrometry Imaging : Development and Applications in Plant Biology and Forensic Toxicology


    Porta, Tiffany


    This thesis focuses on the development of new analytical platforms for molecular mass spectrometry imaging and their applications in plant biology and forensic toxicology. So far, in drug metabolism or forensic toxicology, liquid chromatography with mass spectrometric detection is the technique of choice for analyzing drugs and metabolites in complex biological samples. LC-MS remains however challenging, because the development of appropriate sample preparation requires complex and time-consu...

  10. The Toxicology Investigators Consortium Case Registry--the 2012 experience. (United States)

    Wiegand, Timothy; Wax, Paul; Smith, Eric; Hart, Katherine; Brent, Jeffrey


    In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab

  11. Metabolomic application in toxicity evaluation and toxicological biomarker identification of natural product. (United States)

    Chen, Dan-Qian; Chen, Hua; Chen, Lin; Tang, Dan-Dan; Miao, Hua; Zhao, Ying-Yong


    Natural product plays a vital role in disease prevention and treatment since the appearance of civilization, but the toxicity severely hinders its wide use. In order to avoid toxic effect as far as possible and use natural product safely, more comprehensive understandings of toxicity are urgently required. Since the metabolome represents the physiological or pathological status of organisms, metabolomics-based toxicology is of significance to observe potential injury before toxins have caused physiological or pathological damages. Metabolomics-based toxicology can evaluate toxicity and identify toxicological biomarker of natural product, which is helpful to guide clinical medication and reduce adverse drug reactions. In the past decades, dozens of metabolomic researches have been implemented on toxicity evaluation, toxicological biomarker identification and potential mechanism exploration of nephrotoxicity, hepatotoxicity, cardiotoxicity and central nervous system toxicity induced by pure compounds, extracts and compound prescriptions. In this paper, metabolomic technology, sample preparation, data process and analysis, and metabolomics-based toxicological research of natural product are reviewed, and finally, the potential problems and further perspectives in toxicological metabolomic investigations of natural product are discussed.

  12. The current state and future directions of marine turtle toxicology research. (United States)

    Finlayson, Kimberly A; Leusch, Frederic D L; van de Merwe, Jason P


    Chemical contamination of marine turtles has been well documented in the literature, although information on the toxicological effects of these contaminants is poorly understood. This paper systematically and quantitatively presents the available marine turtle toxicological research (excluding oil chemicals and natural toxins) and the related fields of cell line establishment and biomarkers as indicators of exposure. Examination of the published literature identified a total of 49 papers on marine turtle toxicology, which were split into three categories: toxicity studies (n=33, 67%), cell line establishment (n=7, 14%), and publications using biomarkers (n=13, 27%). Toxicity studies were further broken down into four subcategories: those correlating contaminants with toxicological endpoints (n=16, 48%); in vitro exposure experiments (n=11, 33%); in vivo exposure experiments (n=5, 15%); and screening risk assessments using hazard quotients (n=3, 9%). In quantitatively assessing the literature, trends and gaps in this field of research were identified. This paper highlights the need for more marine turtle toxicology research on all species, particularly using high throughput and non-invasive in vitro assays developed for marine turtle cells, including investigations into further toxicological endpoints and mixture effects. This will provide more comprehensive species-specific assessment of the impacts of chemical contaminants on these threatened animals, and improve conservation and management strategies globally.

  13. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    Directory of Open Access Journals (Sweden)

    Mark T. Mc Auley


    Full Text Available Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs and their effects on adverse birth outcomes as an illustrative example. We introduce how systems toxicology (and their subdisciplines, genomic, proteomic, and metabolomic toxicology will help to overcome such limitations. In particular, we discuss the advantages and disadvantages of mathematical frameworks that computationally represent biological systems. Finally, we discuss the nascent discipline of synthetic biology and highlight relevant toxicological centred applications of this technique, including improvements in personalised medicine. We conclude this review by presenting a number of opportunities and challenges that could shape the future of these rapidly evolving disciplines.

  14. Reflections on the origins and evolution of genetic toxicology and the Environmental Mutagen Society. (United States)

    Wassom, John S; Malling, Heinrich V; Sankaranarayanan, K; Lu, Po-Yung


    This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969, this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to "encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health." As the mutagenesis field unfolded and expanded, new wording appeared to better describe this evolving area of research. The term "genetic toxicology" was coined and became an important subspecialty of the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society's main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society's major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references in this article is unintentional.

  15. Reconstructing propagation networks with temporal similarity metrics

    CERN Document Server

    Liao, Hao


    Node similarity is a significant property driving the growth of real networks. In this paper, based on the observed spreading results we apply the node similarity metrics to reconstruct propagation networks. We find that the reconstruction accuracy of the similarity metrics is strongly influenced by the infection rate of the spreading process. Moreover, there is a range of infection rate in which the reconstruction accuracy of some similarity metrics drops to nearly zero. In order to improve the similarity-based reconstruction method, we finally propose a temporal similarity metric to take into account the time information of the spreading. The reconstruction results are remarkably improved with the new method.


    Energy Technology Data Exchange (ETDEWEB)

    Annette Rohr


    This report documents progress made on the subject project during the period of March 1, 2004 through August 31, 2004. The TERESA Study is designed to investigate the role played by specific emissions sources and components in the induction of adverse health effects by examining the relative toxicity of coal combustion and mobile source (gasoline and/or diesel engine) emissions and their oxidative products. The study involves on-site sampling, dilution, and aging of coal combustion emissions at three coal-fired power plants, as well as mobile source emissions, followed by animal exposures incorporating a number of toxicological endpoints. The DOE-EPRI Cooperative Agreement (henceforth referred to as ''the Agreement'') for which this technical progress report has been prepared covers the analysis and interpretation of the field data collected at the first power plant (henceforth referred to as Plant 0, and located in the Upper Midwest), followed by the performance and analysis of similar field experiments at two additional coal-fired power plants (Plants 1 and 2) utilizing different coal types and with different plant configurations. Significant progress was made on the Project during this reporting period, with field work being initiated at Plant 0. Initial testing of the stack sampling system and reaction apparatus revealed that primary particle concentrations were lower than expected in the emissions entering the mobile chemical laboratory. Initial animal exposures to primary emissions were carried out (Scenario 1) to ensure successful implementation of all study methodologies and toxicological assessments. Results indicated no significant toxicological effects in response to primary emissions exposures. Exposures were then carried out to diluted, oxidized, neutralized emissions with the addition of secondary organic aerosol (Scenario 5), both during the day and also at night when primary particle concentrations in the sampled stack emissions

  17. Toxicological risks to humans of toxaphene residues in fish. (United States)

    Leonards, Pim E G; Besselink, Harrie; Klungsøyr, Jarle; McHugh, Brendan; Nixon, Eugene; Rimkus, Gerhard G; Brouwer, Abraham; de Boer, Jacob


    A revised risk assessment for toxaphene was developed, based on the assumption that fish consumers are only exposed to toxaphene residues that differ substantially from technical toxaphene due to environmental degradation and metabolism. In vitro studies confirmed that both technical toxaphene and degraded toxaphene inhibit gap junctional intercellular communication that correlates with the mechanistic potential to cause tumor promotion. In vivo rat studies established the NOAEL for degraded and technical toxaphene at the highest dose tested in the bioassay. Toxaphene residue intakes from European fishery products were estimated and compared to the provisional tolerable daily intakes (TDIs) from various regulatory agencies including Canada, the United States, and Germany. The estimated intake was also compared to a new calculated provisional MATT pTDI. The MATT pTDI is based on new toxicological information (in vivo rat studies) developed on a model for environmental toxaphene residues rather than technical toxaphene. A MATT pTDI (1.08 mg total toxaphene for a person of 60 kg) for tumor promotion potency was adopted for use in Europe and is referred to here as the MATT pTDI. These new data result in a better estimate of safety and a higher TDI than previously used. Based on realistic fish consumption data and recent baseline concentration data of toxaphene in European fishery products, the toxaphene intake for the consumers of Germany, Ireland, Norway, and the Netherlands was estimated. For an average adult fish consumer, the average daily intake of toxaphene was estimated to be 1.2, 0.4, 0.5, and 0.2 µg for the consumers of Norway, Germany, Ireland, and the Netherlands, respectively. The toxaphene intake of these average fish consumers was far below the MATT pTDI of 1.08 mg/60 kg bw. In conclusion, based on the most relevant toxicological studies and the most realistic estimates of fish consumption and recent concentrations of toxaphene in European fishery

  18. Genetic toxicology of lysergic acid diethylamide (LSD-25). (United States)

    Cohen, M M; Shiloh, Y

    The acute and the chronic psychotomimetic potentials of the hallucinogen lysergic acid diethylamide (LSD-25) have been recognized for almost 40 years. That additional types of the biological effects should have come under scrutiny was directly attributable to widespread use and abuse of this drug on a world-wide basis. Although "genetic toxicology" encompasses a broad spectrum of disciplines, including many areas of highly specialized research, perhaps the most germane, and those on which this review has concentrated, are Clastogenicity, Mutagenicity, Teratogenicity and Oncogenicity. Based on our current understanding and interpretation of the available data, the genetic toxicology of LSD provides an excellent example of Newton's "third law of motion", e.g., to every force there is an equal and opposite reaction force. From the published material it is impossible to draw clear cut conclusions regarding any of the above "problem areas" in spite of the considerable scientific effort invested. Most of the in vitro studies performed on the clastogenicity of LSD indicate either suppression of mitosis or enhanced chromosome damage. However, extrapolation of such results to the in vivo situation is very difficult. With regard to in vivo human use of the drug, no concensus is attainable as to chromosome breakage and the inconsistencies within and between studies remain inexplicable. However, several of the "controlled" investigations assessing the in vivo effect of chemically pure LSD suggest a transient increase in lymphocyte chromosome breakage. On the other hand, the results of cytogenetic studies on experimental animals are contradictory. Although human studies are nonexistent, in those experimental organisms tested, using accepted techniques, LSD proved to be, at best, a weak mutagen, if mutagenic at all. Teratogenicity studies in animals are confusing due to the multitude of organisms and plethora of discriminant parameters studied. However, with regard to man there

  19. [Plants' materials and synthetic agonists of cannabinoid receptors use as a substitute of Marihuana, appearing in a current forensic toxicology practice of evidence materials]. (United States)

    Geppert, Bogna; Tezyk, Artur; Florek, Ewa; Zaba, Czesław


    Cannabis sativa species Indica (Marihuana) is nowadays one of the most common plant drug, with psychoactive activity, presently appearing on the illegal market in Poland. It is reported that frequency of securing evidential materials so called substitute of Marihuana, is growing rapidly during the last few years. The substitutes of Marihuana occurring on the market are of natural or synthetic origins, for example different species of raw plants' materials having action similar to Cannabis or raw plants' materials with no psychoactive properities but with an addition of components so called synthetic cannabinoids. The review presents recent developments in drug market and current problems of forensic toxicology on the example of Marihuana.

  20. Conditional Similarity Solutions of the Boussinesq Equation

    Institute of Scientific and Technical Information of China (English)

    TANG Xiao-Yan; LIN Ji; LOU Sen-Yue


    The direct method proposed by Clarkson and Kruskal is modified to obtain some conditional similarity solutions of a nonlinear physics model. Taking the (1+ 1 )-dimensional Boussinesq equation as a simple example, six types of conditional similarity reductions are obtained.

  1. Shape Similarity Measures of Linear Entities

    Institute of Scientific and Technical Information of China (English)


    The essential of feature matching technology lies in how to measure the similarity of spatial entities.Among all the possible similarity measures,the shape similarity measure is one of the most important measures because it is easy to collect the necessary parameters and it is also well matched with the human intuition.In this paper a new shape similarity measure of linear entities based on the differences of direction change along each line is presented and its effectiveness is illustrated.

  2. Alternaria in Food: Ecophysiology, Mycotoxin Production and Toxicology. (United States)

    Lee, Hyang Burm; Patriarca, Andrea; Magan, Naresh


    Alternaria species are common saprophytes or pathogens of a wide range of plants pre- and post-harvest. This review considers the relative importance of Alternaria species, their ecology, competitiveness, production of mycotoxins and the prevalence of the predominant mycotoxins in different food products. The available toxicity data on these toxins and the potential future impacts of Alternaria species and their toxicity in food products pre- and post-harvest are discussed. The growth of Alternaria species is influenced by interacting abiotic factors, especially water activity (aw), temperature and pH. The boundary conditions which allow growth and toxin production have been identified in relation to different matrices including cereal grain, sorghum, cottonseed, tomato, and soya beans. The competitiveness of Alternaria species is related to their water stress tolerance, hydrolytic enzyme production and ability to produce mycotoxins. The relationship between A. tenuissima and other phyllosphere fungi has been examined and the relative competitiveness determined using both an Index of Dominance (ID) and the Niche Overlap Index (NOI) based on carbon-utilisation patterns. The toxicology of some of the Alternaria mycotoxins have been studied; however, some data are still lacking. The isolation of Alternaria toxins in different food products including processed products is reviewed. The future implications of Alternaria colonization/infection and the role of their mycotoxins in food production chains pre- and post-harvest are discussed.

  3. Mineralogical, chemical and toxicological characterization of urban air particles. (United States)

    Čupr, Pavel; Flegrová, Zuzana; Franců, Juraj; Landlová, Linda; Klánová, Jana


    Systematic characterization of morphological, mineralogical, chemical and toxicological properties of various size fractions of the atmospheric particulate matter was a main focus of this study together with an assessment of the human health risks they pose. Even though near-ground atmospheric aerosols have been a subject of intensive research in recent years, data integrating chemical composition of particles and health risks are still scarce and the particle size aspect has not been properly addressed yet. Filling this gap, however, is necessary for reliable risk assessment. A high volume ambient air sampler equipped with a multi-stage cascade impactor was used for size specific particle collection, and all 6 fractions were a subject of detailed characterization of chemical (PAHs) and mineralogical composition of the particles, their mass size distribution and genotoxic potential of organic extracts. Finally, the risk level for inhalation exposure associated to the carcinogenic character of the studied PAHs has been assessed. The finest fraction (<0.45 μm) exhibited the highest mass, highest active surface, highest amount of associated PAHs and also highest direct and indirect genotoxic potentials in our model air sample. Risk assessment of inhalation scenario indicates the significant cancer risk values in PM 1.5 size fraction. This presented new approach proved to be a useful tool for human health risk assessment in the areas with significant levels of air dust concentration.

  4. Pharmacokinetics and toxicology of therapeutic proteins:Advances and challenges

    Institute of Scientific and Technical Information of China (English)

    Yulia; Vugmeyster; Frank-Peter; Theil; Leslie; A; Khawli; Michael; W; Leach


    Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins.

  5. General and Genetic Toxicology of Guayusa Concentrate (Ilex guayusa). (United States)

    Kapp, Robert W; Mendes, Odete; Roy, Shambhu; McQuate, Robert S; Kraska, Richard


    Tea from the leaves of guayusa (Ilex guayusa) has a long history of consumption by Ecuadorian natives in regions where the plant is indigenous. The tea contains the methylxanthines caffeine and theobromine as well as chlorogenic acids, flavonoids, and sugars. Various studies were performed to evaluate the general and genetic toxicology of a standardized liquid concentrate of guayusa (GC). Guayusa concentrate was found to be negative in in vitro genotoxicity tests including the Ames test and a chromosome aberration study in human lymphocytes. The oral median lethal dose (LD50) of GC was >5,000 mg/kg for female rats. Guayusa concentrate was administered to male and female rats in a 90-day subchronic study at 1,200, 2,500, and 5,000 mg/kg/d of GC and a caffeine-positive control at 150 mg/kg/d corresponding to the amount of caffeine in the high-dose GC group. Effects observed in the GC-treated groups were comparable to those in the caffeine control group and included reductions in body weights, food efficiency, triglycerides values, and fat pad weights and increases in blood chemistry values for serum aspartate aminotransferase, serum alanine aminotransferase, and cholesterol and adaptive salivary gland hypertrophy. No signs of incremental toxicity due to any other components of guayusa were observed. The studies indicate no harmful effects of GC in these test systems.

  6. Emerging pattern mining to aid toxicological knowledge discovery. (United States)

    Sherhod, Richard; Judson, Philip N; Hanser, Thierry; Vessey, Jonathan D; Webb, Samuel J; Gillet, Valerie J


    Knowledge-based systems for toxicity prediction are typically based on rules, known as structural alerts, that describe relationships between structural features and different toxic effects. The identification of structural features associated with toxicological activity can be a time-consuming process and often requires significant input from domain experts. Here, we describe an emerging pattern mining method for the automated identification of activating structural features in toxicity data sets that is designed to help expedite the process of alert development. We apply the contrast pattern tree mining algorithm to generate a set of emerging patterns of structural fragment descriptors. Using the emerging patterns it is possible to form hierarchical clusters of compounds that are defined by the presence of common structural features and represent distinct chemical classes. The method has been tested on a large public in vitro mutagenicity data set and a public hERG channel inhibition data set and is shown to be effective at identifying common toxic features and recognizable classes of toxicants. We also describe how knowledge developers can use emerging patterns to improve the specificity and sensitivity of an existing expert system.

  7. “New designer drugs” in aspects of forensic toxicology

    Directory of Open Access Journals (Sweden)

    Martyna Maciów-Głąb


    Full Text Available Aim of the study : In autumn of 2010, in response to an ever-increasing market of “new designer drugs” and in view of new legal regulations, the Sanitary Inspection inspected numerous so-called “smart shops” where such products were sold. In the course of mass inspections, 3545 packages of various preparations were secured on the market in the Malopolska province. A total of 942 preparations were collected for analysis; of this number, 539 were sold as tablets and pills and 403 as plant-derived substances. The objective of the study was to determine potentially psychoactive components of the investigated preparations. Material and methods : The prepared samples were identified by employing an analytical procedure where the analytes were investigated by gas chromatography-electron impact mass spectrometry (GC-EI-MS and thus a library of mass spectra was created. Results: The analysis revealed the following substances in the investigated products: piperazine derivatives (BZP, MPMP, TFMPP, cathinone derivatives (N-ethylcathinone, buthylone, ethylone, methylone, buphedrone, flephedrone, pyrovalerone derivatives (MDPV, naphyrone, and synthetic cannabinoids (AM-694, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-250. Conclusions : An unlimited source, i.e. the Internet, continues to provide the worldwide market with preparations of this type and their composition is constantly modified. The scale and complexity of the problem pose a challenge to forensic and clinical toxicology in the field of new designer drugs.

  8. Acute arsenic poisoning: clinical, toxicological, histopathological, and forensic features. (United States)

    Tournel, Gilles; Houssaye, Cédric; Humbert, Luc; Dhorne, Christine; Gnemmi, Viviane; Bécart-Robert, Anne; Nisse, Patrick; Hédouin, Valéry; Gosset, Didier; Lhermitte, Michel


    This report describes a suicide case by acute arsenic intoxication via intravenous injection. A 30-year-old woman injected arsenic As (V) (sodium arseniate disodique: Disodium Hydrogena Arsenik RP) in a successful suicide attempt. Three hours following administration, the woman developed severe digestive symptoms. She was admitted to a hospital and transferred to the intensive care unit within 12 h of the massive administration of arsenic. Despite therapeutic efforts, over the next 2 h she developed multiorgan failure and died. A postmortem examination was performed. Pulmonary edema and congestion of liver were apparent. As (V) and As (III) were determined by high performance liquid chromatography and inductively coupled plasma mass spectrometry after mineralization of samples by concentrated nitric acid. Toxicological analysis revealed high concentrations of arsenic in biological fluids as well as in organs. Histopathological examination showed a typical indication of myocarditis. These findings were in agreement with acute arsenic poisoning. The symptoms developed by this young woman (intoxication by intravenous administration) were comparable to oral intoxication. The clinical signs, survival time, and administration type are discussed in light of the literature on acute and chronic arsenic poisoning.

  9. NCTR computer systems designed for toxicologic experimentation. I. Overview. (United States)

    Cranmer, M F; Lawrence, L R; Konvicka, A J; Herrick, S S


    Established in 1971 by the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA), the National Center for Toxicological Research is committed to the study of long-term, low-dose effects of potentially toxic substances, including carcinogens. The Scientific Information Systems Division (SISD) facility provides logistic support for complex experiments involving large numbers of test animals. Animal population at the Center, including the breeding colony and animals on experiment, can be as high as 80,000. Each animal must be accounted for, fed and watered under strict control, and continually observed. From birth to final examination, an individual animal might have as many as 3,000 individual elements of information associated with it. This paper introduces a series of reports dealing with an integrated and comprehensive system of experiment planning and implementation (including information gathering, classification, analyses and reporting), employing state-of-the-art data processing techniques. This extensive use of computer technology has permitted the collection, proper classification, and rapid retrieval of virtually error-free data, resulting in cost-sensitive experiment planning.

  10. In vitro toxicological characterisation of three arsenic-containing hydrocarbons. (United States)

    Meyer, S; Matissek, M; Müller, S M; Taleshi, M S; Ebert, F; Francesconi, K A; Schwerdtle, T


    Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.

  11. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    Directory of Open Access Journals (Sweden)

    Joshua L. Fenderson


    Full Text Available The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS. She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  12. Amphetamine positive urine toxicology screen secondary to atomoxetine. (United States)

    Fenderson, Joshua L; Stratton, Amy N; Domingo, Jennifer S; Matthews, Gerald O; Tan, Christopher D


    The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS). She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  13. Comparative toxicology of laboratory organisms for assessing hazardous waste sites

    Energy Technology Data Exchange (ETDEWEB)

    Miller, W.E.; Peterson, S.A.; Greene, J.C.; Callahan, C.A.


    Multi-media/multi-trophic level bioassays have been proposed to determine the extent and severity of environmental contamination at hazardous waste sites. Comparative toxicological profiles for algae (Selenastrum capricornutum), daphnia (Daphnia magna), earthworms (Eisenia foetida), microbes (Photobacterium fisherii, mixed sewage microorganisms) and plants; wheat Stephens, (Triticum aestivum), lettuce, butter crunch, (Lactuca sativa L.) radish, Cherry Belle, (Raphanus sativa L.), red clover, Kenland, (Trifolium pratense L.) and cucumber, Spartan Valor, (Cucumis sativa L.) are presented for selected heavy metals, herbicides and insecticides. Specific chemical EC/sub 50/ values are presented for each test organism. Differences in standard deviations were compared between each individual test organism, as well as for the chemical subgroup assayed. Algae and daphnia are the most sensitive test organisms to heavy metals and insecticides followed in order of decreasing sensitivity by Microtox (Photobacterium fisherii), DO depletion rate, seed germination and earthworms. Higher plants were most sensitive to 2,4-D, (2,4-Dichlorophenoxy acetic acid) followed by algae, Microtox, daphnia and earthworms. Differences in toxicity of 2,4-D chemical formulations and commercial sources of insecticides were observed with algae and daphia tests.

  14. Aldehydic acids in frying oils: formation, toxicological significance and analysis

    Directory of Open Access Journals (Sweden)

    Kamal-Eldin, Afaf


    Full Text Available Aldehydic acids are generated in oxidized lipids as a result of decomposition of hydroperoxides by (β-scission reactions. Aldehydes are known to interact with proteins and DNA and to impair enzymatic functions. Aldehydic esters from oxidized lipids were reabsorbed to a significant extent in rats. This paper reviews the mechanism of formation of esterified aldehydic acids in frying oils and their physiological/toxicological effects. The paper also gives an overview of relevant basic analytical techniques that needs to be improved to establish reliable quantitative method (s.

    Ácidos aldehídicos son producidos en lípidos oxidados como resultado de la descomposición de hidroperóxidos por reacciones de (β-escición. Es conocido que los aldehídos interaccionan con las proteínas y el ADN y debilitan las funciones enzimáticas. Los esteres aldehídicos de lípidos oxidados fueron reabsorbidos en una cantidad significativa en ratas. Este artículo revisa los mecanismos de formación de ácidos aldehídicos esterificados en aceites de fritura y sus efectos fisiológicos/toxicológicos. El artículo también ofrece una visión de conjunto de las técnicas analíticas básicas que necesitan ser mejoradas para establecer métodos cuantitativos fiables.

  15. Silver nanoparticles: synthesis, properties, toxicology, applications and perspectives (United States)

    Tran, Quang Huy; Quy Nguyen, Van; Le, Anh-Tuan


    In recent years the outbreak of re-emerging and emerging infectious diseases has been a significant burden on global economies and public health. The growth of population and urbanization along with poor water supply and environmental hygiene are the main reasons for the increase in outbreak of infectious pathogens. Transmission of infectious pathogens to the community has caused outbreaks of diseases such as influenza (A/H5N1), diarrhea (Escherichia coli), cholera (Vibrio cholera), etc throughout the world. The comprehensive treatments of environments containing infectious pathogens using advanced disinfectant nanomaterials have been proposed for prevention of the outbreaks. Among these nanomaterials, silver nanoparticles (Ag-NPs) with unique properties of high antimicrobial activity have attracted much interest from scientists and technologists to develop nanosilver-based disinfectant products. This article aims to review the synthesis routes and antimicrobial effects of Ag-NPs against various pathogens including bacteria, fungi and virus. Toxicology considerations of Ag-NPs to humans and ecology are discussed in detail. Some current applications of Ag-NPs in water-, air- and surface- disinfection are described. Finally, future prospects of Ag-NPs for treatment and prevention of currently emerging infections are discussed.

  16. Basis for the toxicological evaluation of engineered nanomaterials

    Directory of Open Access Journals (Sweden)

    C. Porredon Guarch


    Full Text Available El aumento de producción anual de nanomateriales eleva la exposición humana y ambiental, y tiene un posible impacto en la opinión pública. Con el fin de reglamentar esta producción, organizaciones internacionales como la Organización para la Cooperación y Desarrollo Económico (OECD y la Comisión Europea a través de la reglamentación REACH han establecido algunas medidas para evaluar la seguridad para la salud y el medio ambiente de los nanomateriales. Esta revisión intenta analizar las medidas propuestas por estas instituciones de acuerdo con las pruebas estándar usadas en toxicología, las distintas clasificaciones de los nanomateriales y los principales mecanismos de toxicidad conocidos de los nanomateriales. Como resultado de este análisis se cree conveniente continuar desarrollando tests específicos para la evaluación de nanomateriales, ya que las medidas establecidas por las organizaciones de referencia no son suficientes para conseguir unas bases estándares para testar nanomateriales. En gran parte esto es debido a la gran diversidad de nanomateriales existentes y la importancia de la manipulación, técnicas y sistemas experimentales escogidos en los resultados de toxicidad.

  17. The advent of system toxicology: aims and aspect of toxicogenomics

    Directory of Open Access Journals (Sweden)

    S. M. Neaz Mahmud


    Full Text Available Last fifty years a significant advancement has been established in biological science. It happened due to the discovery of gene, genome and genetic code, function of genes and mutation of genes. Through this, the scientists have discovered that genetic code is the building block and fundamental of all molecular activity in biological system. According to this, several molecular techniques have been established to prove molecular events, effects of chemical exposure within individuals and environment. For this evaluation, the necessary of toxicogenomics is crucial, that deals with the effects of chemical in changing the genetic pattern along with mutation into gene. Toxicogenomics also deals with transcription of proteins and metabolite profiling to investigate the interaction of genes and environment stress in disease. Toxicogenomics also described the altered expression of genes caused by mutation and chemical exposure that cause several disease and show toxicant functions in cell. The main objective of toxicogenomics is to remove this exposure and provide remedy of these toxical diseases. The use, application, correlation, combination and collaboration of different significant, major, modern biological fields like proteomics, transcriptomics, bioinformatics, microarray and several other molecular process is carried out by toxicogenomics that gradually evolving in systems toxicology. This review recovered the evolution and significant application of the different fields of toxicogenomics. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1164-1174

  18. Engineering epithelial-stromal interactions in vitro for toxicology assessment. (United States)

    Belair, David G; Abbott, Barbara D


    Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues.

  19. [New toxicological patterns of nanomaterials, nanostructures and nanoparticles]. (United States)

    Mazzotta, M; Mazzotta, A D; Fernández, M; Tamborino, B; De Filippis, G


    Nanomaterials engineered as nanotubes, quantum-dots, dendrimers or hybrid systems are increasing themselves by an annual mean rate of 4-5%, with rapid spread in various sectors e.g. biomedical. The liposolubility through membranes and the hydrosolubility through active transport do not interfere with nanoparticles below a certain size, which without activation processes and carrier, transport through thanks to capillaries, to intracellular pores (60 - 70 nm) and fissures (4 - 6 nm) in the same membranes. Conversely, in the processes of pinocytosis/endocytosis energy and carrier are required and endocytosis clathrin/caveolae mediated,is respectively for nanoparticles higher or lower than 200 nm. In occupational hazard nanostructures ranging from a few nm up to 100 - 150 nm have the ability to affect several organs through inhalation, intestinal, parental or dermal route of access. New toxicological aspects are associated to the capacity of nanomaterials of being more or less biocompatible or hydrosoluble, of creating bonds with proteins or to determine accumulation in the cells due to an incomplete elimination process.

  20. Applying evolutionary genetics to developmental toxicology and risk assessment. (United States)

    Leung, Maxwell C K; Procter, Andrew C; Goldstone, Jared V; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J; Siddall, Mark E; Timme-Laragy, Alicia R


    Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease.

  1. Stability of similarity measurements for bipartite networks

    CERN Document Server

    Liu, Jian-Guo; Pan, Xue; Guo, Qiang; Zhou, Tao


    Similarity is a fundamental measure in network analyses and machine learning algorithms, with wide applications ranging from personalized recommendation to socio-economic dynamics. We argue that an effective similarity measurement should guarantee the stability even under some information loss. With six bipartite networks, we investigate the stabilities of fifteen similarity measurements by comparing the similarity matrixes of two data samples which are randomly divided from original data sets. Results show that, the fifteen measurements can be well classified into three clusters according to their stabilities, and measurements in the same cluster have similar mathematical definitions. In addition, we develop a top-$n$-stability method for personalized recommendation, and find that the unstable similarities would recommend false information to users, and the performance of recommendation would be largely improved by using stable similarity measurements. This work provides a novel dimension to analyze and eval...

  2. “You Can’t Always Get What You Want” – Linearity as the Golden Ratio of Toxicology (United States)

    Bast, Aalt; Hanekamp, Jaap C.


    Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity. The latter seems imposed on pharmaco-toxicological processes that in fact show far more complexity than simple linearity could hope to elucidate. Understanding physiological and pharmaco-toxicological processes as primarily linear is challenged in this contribution based on very straightforward principles and examples. PMID:25552963

  3. “You Can’t Always Get What You Want” – Linearity as the Golden Ratio of Toxicology


    Bast, Aalt; Hanekamp, Jaap C.


    Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity. The latter seems imposed on pharmaco-toxicological processes that in fact show far more complexity than simple linearity could hope to elucidate. Understanding physiological and pharmaco-toxicological processes as primarily linear is challenged in this contribution based on very straightforward principles and examples.

  4. Structural improvement of higher education in environmental toxicology in Latin America and Europe. (United States)

    Albores, A; Cebrián, M E; Dekant, W; De Matteis, F; Diaz-Barriga, F; Barril-Antuña, J; Fowler, J; Gil, L; Jaramillo-Juárez, F; King, L J; Olarte, G; Ostrosky-Wegman, P; Patño, R I; Torres-Alanís, O; Manno, M


    Industrial development has resulted in an increased release of chemicals and other agents into the environment, resulting in damage to the environment as well as increasing the risk of adverse effects on human health. Environmental toxicology (ET) is the discipline responsible for assessing the risks to human health and the environment from the effects of new chemicals and those already present in the environment. The development of human resources in toxicology is therefore a priority in both Latin America (LA) and the European Union (EU), although LA professionals are more involved in risk evaluation than in risk assessment compared to their EU colleagues. A solid background in general toxicology will enable those interested in environmental issues to tackle local problems. Moreover, the increasing globalization of markets and, therefore, of the necessary regulations, requires harmonisation of postgraduate programmes to ensure that risk assessment and management related to the environment are dealt with uniformly and by highly qualified scientists. The Inaugural Meeting of the ALFA-OMET Toxicology', a 2-year programme supported by the European Commission, offered the opportunity to discuss a number of these issues. The present status of existing ET courses in the EU and LA and the corresponding professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate course in environmental toxicology was developed. Finally, a course programme for toxicology and a specialization in environmental toxicology designed by a panel of experts was discussed, and its relevance as a model for other specialisation programmes was analysed. Exercises such as those performed by ALFA-OMET may be useful not only in promoting discussion for the implementation of national and international professional registers in LA, but also in

  5. In vitro toxicity of carbon nanotubes, nano-graphite and carbon black, similar impacts of acid functionalization. (United States)

    Figarol, Agathe; Pourchez, Jérémie; Boudard, Delphine; Forest, Valérie; Akono, Céline; Tulliani, Jean-Marc; Lecompte, Jean-Pierre; Cottier, Michèle; Bernache-Assollant, Didier; Grosseau, Philippe


    Carbon nanotubes (CNT) and nano-graphite (NG) are graphene-based nanomaterials which share exceptional physicochemical properties, but whose health impacts are unfortunately still not well understood. On the other hand, carbon black (CB) is a conventional and widely studied material. The comparison of these three carbon-based nanomaterials is thus of great interest to improve our understanding of their toxicity. An acid functionalization was carried out on CNT, NG and CB so that, after a thorough characterization, their impacts on RAW 264.7 macrophages could be compared for a similar surface chemistry (15 to 120 μg·mL(-1) nanomaterials, 90-min to 24-h contact). Functionalized nanomaterials triggered a weak cytotoxicity similar to the pristine nanomaterials. Acid functionalization increased the pro-inflammatory response except for CB which did not trigger any TNF-α production before or after functionalization, and seemed to strongly decrease the oxidative stress. The toxicological impact of acid functionalization appeared thus to follow a similar trend whatever the carbon-based nanomaterial. At equivalent dose expressed in surface and equivalent surface chemistry, the toxicological responses from murine macrophages to NG were higher than for CNT and CB. It seemed to correspond to the hypothesis of a platelet and fiber paradigm.

  6. La docencia del área de Toxicología de la Universidad de La Laguna


    A. J. Gutiérrez Fernández; C Rubio Armendáriz; G. Luis González; C Hernández Sánchez; D. González- Weller; J. M. Caballero Mesa; A. Hardisson de la Torre


    La docencia de Toxicología en la Universidad de La Laguna (ULL) se integra en diversas Licenciaturas y Grados tales como Farmacia, Ciencia y Tecnología de los Alimentos (CTA), Medicina, Náutica y Transporte Marítimo y el Máster Oficial de Seguridad y Calidad de los Alimentos. En la Licenciatura de Farmacia en la ULL, el Área de Toxicología imparte la asignatura troncal Toxicología de 7 créditos y dos asignaturas optativas, Drogodependencias y Toxicología Clínica y Laboral, de 4,5 créditos...

  7. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji


    Self-similar processes have been widely used in modeling real-world phenomena occurring in environmetrics, network traffic, image processing, and stock pricing, to name but a few. The estimation of the degree of self-similarity has been studied extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi-self-similarity for a random field indexed in higher dimensions. If self-similarity is not rejected, our test provides a set of estimated self-similarity indexes. The key is to test stationarity of the inverse Lamperti transformations of the process. The inverse Lamperti transformation of a self-similar process is a strongly stationary process, revealing a theoretical connection between the two processes. To demonstrate the capability of our test, we test self-similarity of fractional Brownian motions and sheets, their time deformations and mixtures with Gaussian white noise, and the generalized Cauchy family. We also apply the self-similarity test to real data: annual minimum water levels of the Nile River, network traffic records, and surface heights of food wrappings. © 2016, International Biometric Society.

  8. Molecular quantum similarity using conceptual DFT descriptors

    Indian Academy of Sciences (India)

    Patrick Bultinck; Ramon carbó-dorca


    This paper reports a Molecular Quantum Similarity study for a set of congeneric steroid molecules, using as basic similarity descriptors electron density ρ (r), shape function (r), the Fukui functions +(r) and -(r) and local softness +(r) and -(r). Correlations are investigated between similarity indices for each couple of descriptors used and compared to assess whether these different descriptors sample different information and to investigate what information is revealed by each descriptor.

  9. Similarity effects in visual working memory. (United States)

    Jiang, Yuhong V; Lee, Hyejin J; Asaad, Anthony; Remington, Roger


    Perceptual similarity is an important property of multiple stimuli. Its computation supports a wide range of cognitive functions, including reasoning, categorization, and memory recognition. It is important, therefore, to determine why previous research has found conflicting effects of inter-item similarity on visual working memory. Studies reporting a similarity advantage have used simple stimuli whose similarity varied along a featural continuum. Studies reporting a similarity disadvantage have used complex stimuli from either a single or multiple categories. To elucidate stimulus conditions for similarity effects in visual working memory, we tested memory for complex stimuli (faces) whose similarity varied along a morph continuum. Participants encoded 3 morphs generated from a single face identity in the similar condition, or 3 morphs generated from different face identities in the dissimilar condition. After a brief delay, a test face appeared at one of the encoding locations for participants to make a same/different judgment. Two experiments showed that similarity enhanced memory accuracy without changing the response criterion. These findings support previous computational models that incorporate featural variance as a component of working memory load. They delineate limitations of models that emphasize cortical resources or response decisions.

  10. Cluster Tree Based Hybrid Document Similarity Measure

    Directory of Open Access Journals (Sweden)

    M. Varshana Devi


    Full Text Available similarity measure is established to measure the hybrid similarity. In cluster tree, the hybrid similarity measure can be calculated for the random data even it may not be the co-occurred and generate different views. Different views of tree can be combined and choose the one which is significant in cost. A method is proposed to combine the multiple views. Multiple views are represented by different distance measures into a single cluster. Comparing the cluster tree based hybrid similarity with the traditional statistical methods it gives the better feasibility for intelligent based search. It helps in improving the dimensionality reduction and semantic analysis.

  11. Toxicological studies of aqueous extract of Acacia nilotica root

    Directory of Open Access Journals (Sweden)

    Alli Lukman Adewale


    Full Text Available Acacia nilotica is a widely used plant in traditional medical practice in Northern Nigeria and many African countries. The aim of this study was to determine the toxicological effects of a single dose (acute and of repeated doses (sub-acute administration of aqueous extract of A. nilotica root in rodents, following our earlier study on antiplasmodial activity. In the acute toxicity test, three groups of Swiss albino mice were orally administered aqueous extract of A. nilotica (50, 300 and 2000 mg/kg body weight and signs of toxicity were observed daily for 14 days. In the sub-acute toxicity study, four groups of 12 rats (6 male and 6 female were used. Group 1 received 10 ml/kg b.w distilled water (control, while groups 2, 3 and 4 received 125, 250 and 500 mg/kg b.w of the extract, respectively, for 28 consecutive days by oral gavage. Signs of toxicity/mortality, food and water intake and body weight changes were observed. Biochemical parameters were analysed in both plasma and liver homogenate. In the acute and sub-acute toxicity studies, the extract did not cause mortality. A significant reduction in the activity of lactate dehydrogenase was observed at 250 and 500 mg/kg b.w, while alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities were significantly higher than control values at 500 mg/kg b.w. The aqueous extract of A. nilotica was found to be safe in single dose administration in mice but repeated administration of doses higher than 250 mg/kg b.w of the extract for 28 days in rats may cause hepatotoxicity.

  12. Profiles of pregabalin and gabapentin abuse by postmortem toxicology. (United States)

    Häkkinen, Margareeta; Vuori, Erkki; Kalso, Eija; Gergov, Merja; Ojanperä, Ilkka


    Pregabalin (PRG) and gabapentin (GBP) are used in the treatment of neuropathic pain and epilepsy, and PRG also in generalized anxiety disorder. There is increasing evidence that PRG possesses considerable abuse potential. PRG may have a higher addiction potential than GBP due to its rapid absorption and faster onset of action. Our objective is to estimate the proportion of all PRG- and GBP-related fatalities attributable to PRG and GBP abuse. We investigated all medico-legal death cases in Finland in which PRG or GBP was found in postmortem toxicology during 2010-2011. PRG was found in 316 cases and GBP in 43 cases. Drug abuse was associated with 48.1% of the PRG and 18.6% of the GBP findings. PRG poisoning accounted for 10.1% of all PRG cases and GBP poisoning for 4.7% of all GBP cases. In the drug abuser cases, PRG poisoning represented 19.1%, and GBP poisoning 12.5%. The median blood concentration of PRG was 15 mg/L in the abuser group and 5.8 mg/L in the other cases. For GBP, these concentrations were 12 mg/L and 8.3mg/L, respectively. In the PRG abuser group, 91.4% of cases showed concomitant opioid use, while in the rest of these cases neither alcohol nor opioids were detected, but other central nervous system acting drugs were found in each abuser case. In the GBP abuser group, 87.5% of cases showed concomitant opioid use. PRG abuse with high doses is increasingly common and can be fatal when combined with opioids.

  13. Position of immunological techniques in screening in clinical toxicology. (United States)

    George, Steve


    There is a continuing increase in the use of immunological techniques in the field of clinical toxicology. This is primarily due to the rapidity by which analytical results are now required, and can be obtained, following the testing of individuals for drug use. There has recently been an increase in the repertoire of assays now available to testing laboratories (e.g., buprenorphine and heroin metabolite assays), with the techniques themselves becoming increasingly more specific for the drugs and/or metabolites being monitored (e.g., methadone metabolite assays). The near patient testing (NPT), or point-of-care testing (POCT), devices are now several generations forward from their inception, with some tests now approaching the sensitivity and specificity of automated laboratory-based methods. This review has been collated from the literature to illustrate some of the possible reasons for the move towards the increasing use of immunological techniques, and to highlight some of the advantages and disadvantages associated with such drug screening methods. In particular, it has been shown that it is important to determine, monitor and review the knowledge and training of the individual using the technique. In addition, quality control and quality assessment are paramount to ensure the validity of any drug testing being performed. It has also been shown that it is vital to maintain and develop the relationships between the staff performing the testing, the laboratory (if the testing is performed using NPT devices), and the clinicians utilising the results obtained from drug testing. Without these links, interpretive errors could arise which could adversely affect the diagnosis and management of patients.

  14. A critical review on toxicological safety of 2-alkylcyclobutanones (United States)

    Song, Beom-Seok; Choi, Soo-Jeong; Jin, Young-Bae; Park, Jong-Heum; Kim, Jae-Kyung; Byun, Eui-Baek; Kim, Jae-Hun; Lee, Ju-Woon; Kim, Gang-Sung; Marchioni, Eric


    2-Alkylcyclobutanones (2-ACBs) are known as unique radiolytic products generated from the major fatty acids and triglycerides in food through only irradiation. Since 1990, studies on the toxicological safety of 2-ACBs have been conducted extensively with synthetic compounds. Mutagenicity tests of 2-ACBs on the microorganisms reviewed in this study clearly indicate that no evidence was observed, while several in vitro studies demonstrated the cytotoxicity of 2-ACBs through cell death. Moreover, the genotoxicity of 2-ACBs was suggested as DNA strand breaks were observed. However, these findings should be interpreted with caution because genotoxicity may result from cytotoxicity, which causes DNA damage or from cell membrane destruction and indirect oxidative DNA damage. Therefore, elucidation of the mechanism of genotoxic effects is needed. With regards to the suggestion of Raul et al. (2002) who showed the promoting effect of colon cancer by the administration of 2-ACBs, further studies are needed to correct some experimental design errors. Moreover, an in-vivo experiment that evaluated the metabolism of 2-ACBs has revealed that 2-dDCB was metabolized into cyclic alcohol and excreted through fecal discharge. In conclusion, it is considered that the ingestion of 2-ACBs through irradiated foods is unlikely to affect the human health. However, more specific studies are required to identify the fate of 2-ACBs in body and the LD50 values. The determination of chronic toxicity by long-term exposure to low concentrations of 2-ACBs has to be evaluated more clearly to determine if these compounds are safe to human.

  15. Characterization and toxicological evaluation of leachate from closed sanitary landfill. (United States)

    Emenike, Chijioke U; Fauziah, Shahul H; Agamuthu, P


    Landfilling is a major option in waste management hierarchy in developing nations. It generates leachate, which has the potential of polluting watercourses. This study analysed the physico-chemical components of leachate from a closed sanitary landfill in Malaysia, in relation to evaluating the toxicological impact on fish species namely Pangasius sutchi S., 1878 and Clarias batrachus L., 1758. The leachate samples were taken from Air Hitam Sanitary Landfill (AHSL) and the static method of acute toxicity testing was experimented on both fish species at different leachate concentrations. Each fish had an average of 1.3 ± 0.2 g wet weight and length of 5.0 ± 0.1 cm. Histology of the fishes was examined by analysing the gills of the response (dead) group, using the Harris haemtoxylin and eosin (H&E) method. Finneys' Probit method was utilized as a statistical tool to evaluate the data from the fish test. The physico-chemical analysis of the leachate recorded pH 8.2 ± 0.3, biochemical oxygen demand 3500 ± 125 mg L(-1), COD 10 234 ± 175 mg L(-1), ammonical nitrogen of 880 ± 74 mg L(-1), benzene 0.22 ± 0.1 mg L(-1) and toluene 1.2 ± 0.4 mg L(-1). The 50% lethality concentration (LC(50)) values calculated after 96 h exposure were 3.2% (v/v) and 5.9% (v/v) of raw leachate on P. sutchi and C. batrachus, respectively. The H&E staining showed denaturation of the nucleus and cytoplasm of the gills of the response groups. Leachate from the sanitary landfill was toxic to both fish species. The P. sutchi and C. batrachus may be used as indicator organisms for leachate pollution in water.

  16. A Review of Liver Perfusion Method in Toxicology Studies

    Directory of Open Access Journals (Sweden)

    M karami


    Full Text Available Introduction: The isolated perfused rat liver is an accepted method in toxicology studies. The isolated perfused rat liver (IPRL is a useful experimental system for evaluating hepatic function without the influence of other organ systems, undefined plasma constituents, and neural-hormonal effects. Methods: The untreated male rats (180-220gr body weight were anesthetised with ether and then surgery with proper method. The abdomen was opened through a midline and one transversal incision and the bile duct was cannulated. Heparin sodium solution (0.5 ml; 500 U/ml in 0.9% NaCl was injected via the abdominal vena cava to prevent blood clotting. The liver inferior venacava was cannulated with PE-10 tubing and secured. The portal vein was immediately cannulated with an 23gr catheter which was secured and then liver was perfused in situ by Krebs- Henseleit buffer (pH 7.4; saturated with 95% O2 and 5% CO2; 37°C at a flow rate of 20 ml/min for 3hr. Temperature, perfusion pressure, flow rate and perfusion fluid pH were closely monitored during the perfusion. Results: Transferase enzymes (ALT, AST alterations can be widely used as a measure of biochemical alterations in order to assess liver damage due to use of drugs such as isoniazid (INH and animal and plant toxins. Accumulated material in gallbladder are valuable samples to assess the level of Glutathione (GSH. Sections of perfused liver tissue can also be effectively analyzed for pathological aspects such as necrosis, fibrosis, cellularity. Conclusion: The isolated perfused rat liver (IPRL is a useful and Sutible experimental system for evaluating hepatic function. In this system, the effects of adjacent organs, on the liver is minimized

  17. Toxicological findings in a fatal multidrug intoxication involving mephedrone. (United States)

    Gerace, Enrico; Petrarulo, Michele; Bison, Fabrizio; Salomone, Alberto; Vincenti, Marco


    The distribution of mephedrone in the body fluids and tissues of a subject found dead after the concomitant intake of cocaine and mephedrone is reported. Mephedrone (4-methylmethcathinone) is a designer drug of the phenethylamine family that is able to cause central nervous system stimulation, psychoactivity and hallucinations and that is becoming popular among youth as a recreational drug. Mephedrone has been available in Europe since 2007, and it is sold through the internet and by local shops as bath salt or plant food. In the case reported here, a 25-year-old man was found dead in the apartment of a friend after a night spent in several local clubs. A fragment of a blue diamond-shaped pill was found in the pocket of the trousers worn by the decedent. During the autopsy, no evidence of natural disease or trauma was found to account for this death. Blood, urine and gastric content samples were collected and submitted for toxicological analysis. Moreover, bile, brain, lung and hair samples were collected as additional matrices. The content of the pill was submitted to a general screening analysis in order to determine its composition. Mephedrone was detected in the blood, urine, gastric contents and in the additional matrices using an expressly validated GC/MS method. The blood and urine concentrations were 1.33mg/L and 144mg/L, respectively. Contextually, cocaine and cocaethylene were found in the blood and urine specimens. The distribution of mephedrone in the body organs was evaluated by analyzing the brain, bile and lung specimens. Hair analysis revealed a past exposure to mephedrone, ketamine, MDMA and cocaine. Sildenafil was identified as the main component of the blue, diamond-shaped pill. The quantitative determination of mephedrone in several body fluids and tissues provides significant knowledge about the distribution of this new drug of abuse in the human body after massive ingestion.

  18. Mephedrone (methylmethcathinone) in toxicology casework: a Northern Ireland perspective. (United States)

    Cosbey, Simon H; Peters, K Laota; Quinn, Amy; Bentley, Alastair


    Mephedrone (4-methylmethcathinone) is the beta-keto analogue of 4-methylmethylamphetamine. Before its control in April 2010, it became popular as a legal high in the United Kingdom, displacing methylenedioxymethylamphetamine as the stimulant drug of choice. The drug has stimulant and psychoactive properties, and therefore has forensic significance in criminal and morbid toxicology. The purpose of this study was to survey casework involving the drug (impaired driving and sudden death). The cases were received in the laboratory for analysis between late 2009 and the end of 2010. Analysis of blood samples for mephedrone was conducted by liquid chromatography-mass spectrometry (LC-MS). Routine screening for alcohol and a range of other pharmaceuticals and drugs of abuse was conducted using a combination of enzyme-linked immunoassay, gas chromatography (GC) headspace, GC-MS and high-performance liquid chromatography with diode array detection. Mephedrone was detected in a total of 12 fatal cases. Most of these cases involved death by mechanical means; in two cases, death was attributed directly to mephedrone intoxication (blood concentrations of 2.1 and 1.94 mg/L). Mephedrone was detected in a total of 32 impaired driving cases. Blood concentrations ranged up to 0.74 mg/L (mean 0.21, median 0.10). The casework evidence in this study indicated that recreational use of the drug can produce to blood levels as high as 0.74 mg/L, although the most common value encountered is likely to lie between 0.2 and 0.3 mg/L.

  19. Allergological and Toxicological Aspects in a Multiple Chemical Sensitivity Cohort

    Directory of Open Access Journals (Sweden)

    Paolo D. Pigatto


    Full Text Available Background. Multiple chemical sensitivity (MCS is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. Methods. We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n=21 for dental series and did lymphocyte transformation test (n=18 for metals. We measured mercury in samples of blood (n=19, urine (n=19, saliva (n=20, and scalp hair (n=17 to investigate the association between mercury levels and cases of MCS. Results. The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32. The mean (±SD in blood concentrations of mercury was 7.6±13.6 μg/L; mean in urine was 1.9±2.5 μg/L; mean in scalp hair was 2.2±2.5 μg/g; mean in saliva was 38.1±52.1 μg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients, compared with controls (8 patients (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P=0.023. Conclusions. Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.

  20. Toxicological implications of modulation of gene expression by microRNAs. (United States)

    Yokoi, Tsuyoshi; Nakajima, Miki


    MicroRNAs (miRNAs) are a large family of non-coding RNAs that are evolutionarily conserved, endogenous, and 21-23 nucleotides in length. miRNAs regulate gene expression by targeting messenger RNAs (mRNAs) by binding to complementary regions of transcripts to repress their translation or mRNA degradation. miRNAs are encoded by the genome, and more than 1000 human miRNAs have been identified so far. miRNAs are predicted to target ∼60% of human mRNAs and are expressed in all animal cells and have fundamental roles in cellular responses to xenobiotic stresses, which affect a large range of physiological processes such as development, immune responses, metabolism, tumor formation as well as toxicological outcomes. Recently, many reports concerning miRNAs related to cancer have been published; however, the miRNA research in the metabolism of xenobiotics and endobiotics and in toxicology has only recently been established. This review describes the current knowledge on the miRNA-dependent regulation of drug-metabolizing enzymes and nuclear receptors and its potential toxicological implications. In this review, miRNAs with reference to target prediction, potential modulation of toxicology-related changes of miRNA expression, role of miRNA in immune-mediated drug-induced liver injury, miRNA in plasma as potential toxicological biomarkers, and relevance of miRNA-related genetic polymorphisms are discussed.