Sample records for acid toxicologic pathology

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. A brief overview of the 33rd Annual STP Symposium on the translational pathology: relevance of toxicologic pathology to human health. (United States)

    Hoenerhoff, Mark J; Silverman, Lee; Francke, Sabine


    The 33rd Society of Toxicologic Pathology's Annual Symposium focused on translational science and the relevance of toxicologic pathology to human health. Toxicologic pathologists work in diverse settings studying changes elicited by pharmacological, chemical, and environmental agents and factors that modify these responses. Regardless of the work setting, society members are dedicated to the integration of toxicologic pathology into hazard identification, risk assessment, and risk communication regarding human and animal exposure to potentially toxic substances. Toxicologic pathologists routinely face not only questions regarding pathological changes related to compound exposure but also questions concerning what translational relevance those lesions and exposures have to a human population or organ system. This symposium provided a basis for the membership to understand the variety of roles the toxicologic pathologist plays in translational science, where our gaps in translational science are, and how we can move forward to better address the challenges in the field translational science in order to continue to positively impact human health.

  8. Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries. (United States)

    Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I


    The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

  9. Aldehydic acids in frying oils: formation, toxicological significance and analysis


    Kamal-Eldin, Afaf; Appelqvist, Lars-Åke


    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...

  10. 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.

  11. Current Understanding of Perfluoroalkyl Acid Toxicology (United States)

    The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-14 carbons in length) and an anionic head group (sulfonate, carboxylate or phosphonate). These compounds have excellent surface-tension reducing properties and hav...

  12. [Folic acid in physiology and pathology]. (United States)

    Czeczot, Hanna


    This paper presents current knowledge of the biological functions of folic acid, the effects of its deficiency in the organism, as well as the possibilities of its therapeutic use. Folic acid (folate, B9) is a vitamin of special importance in normal cellular functions. Tetrahydrofolate (TH4-folate) is the biologically active form of folic acid. The main role of folic acid in biochemistry is the single-carbon transfer reaction (e.g. transfer of a methyl, methylene, or formyl group). Folic acid is involved in the transformation of certain amino acids as well as in the synthesis of purines and dTMP (2'-deoxythymidine-5'-phosphate) needed for the synthesis of nucleic acid (DNA), required by all rapidly growing cells. In humans, folate deficiency results in serious pathologies, the most important of which are neural tube defects, megablastic anemia, acceleration of the arteriosclerotic process, changes in the central nervous system, and the development of certain types of cancer. To increase the intake of folic acid, preventive actions include dietary education, the main objectives of which are to increase the intake of natural folate in the daily diet, add folic acid to selected dietary products (e.g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals.

  13. 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.

  14. Clinical and anatomic pathology effects of serial blood sampling in rat toxicology studies, using conventional or microsampling methods. (United States)

    Caron, Alexis; Lelong, Christine; Bartels, T; Dorchies, O; Gury, T; Chalier, Catherine; Benning, Véronique


    As a general practice in rodent toxicology studies, satellite animals are used for toxicokinetic determinations, because of the potential impact of serial blood sampling on toxicological endpoints. Besides toxicological and toxicokinetic determinations, blood samples obtained longitudinally from a same animal may be used for the assessment of additional parameters (e.g., metabolism, pharmacodynamics, safety biomarkers) to maximize information that can be deduced from rodents. We investigated whether removal of up to 6 × 200 μL of blood over 24h can be applied in GLP rat toxicology studies without affecting the scientific outcome. 8 week-old female rats (200-300 g) were dosed for up to 1 month with a standard vehicle and subjected or not (controls) to serial blood sampling for sham toxicokinetic/ancillary determinations, using miniaturized methods allowing collection of 6 × 50, 100 or 200 μL over 24h. In-life endpoints, clinical pathology parameters and histopathology of organs sensitive to blood volume reduction were evaluated at several time points after completion of sampling. In sampled rats, minimal and reversible changes in red blood cell mass (maximally 15%) and subtle variations in liver enzymes, fibrinogen and neutrophils were not associated with any organ/tissue macroscopic or microscopic correlate. Serial blood sampling (up to 6 × 200 μL over 24h) is compatible with the assessment of standard toxicity endpoints in adult rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Clinicopathologic, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid. (United States)

    Cianciolo, Rachel E; Bischoff, Karyn; Ebel, Joseph G; Van Winkle, Thomas J; Goldstein, Richard E; Serfilippi, Laurie M


    To document clinicopathologic, histologic, and toxicologic findings in cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid. Case series. 70 cats from a single cattery inadvertently fed contaminated food that was the subject of a March 2007 recall. Clinical signs, clinicopathologic and histopathologic findings, and results of toxicologic analyses were recorded. Clinical signs were identified in 43 cats and included inappetence, vomiting, polyuria, polydipsia, and lethargy. Azotemia was documented in 38 of the 68 cats for which serum biochemical analyses were performed 7 to 11 days after consumption of the contaminated food. One cat died, and 13 were euthanized. Histologic examination of kidney specimens from 13 cats revealed intratubular crystalluria, tubular necrosis with regeneration, and subcapsular perivascular inflammation characterized by perivascular fibroplasia or fibrosis and inflammation with intravascular fibrin thrombi. Toxicologic analyses revealed melamine and cyanuric acid in samples of cat food, vomitus, urine, and kidneys. In cats unintentionally fed pet food contaminated with melamine and cyanuric acid, the most consistent clinical and pathologic abnormalities were associated with the urinary tract, specifically tubular necrosis and crystalluria.

  16. 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

  17. Frequency of Pathological Changes in Lungs of Bodies with Positive Postmortem Toxicology Results for Narcotics and Psychotropic Substances

    Directory of Open Access Journals (Sweden)

    Babak Mostafazadeh


    Full Text Available Background: The pattern of drug abuse in Iran has dramatically changed in recent years, turning from the traditional opioids [opium, opium dross, and refined opium dross (Shireh] into drugs with newer forms. The present study is aimed at investigating the frequency of pathological changes in the lungs of bodies with positive postmortem toxicology results for narcotics and psychotropic substances autopsied in the forensic dissection hall of Tehran, Iran [the Iranian Legal Medicine Organization (LMO]. Methods: The present study is a cross-sectional descriptive study. The sample consisted of 153 bodies, which had been referred to the LMO with positive results in postmortem toxicology for narcotics and psychotropic substances. Results: We found that narcotic drugs and psychotropic substances were used more in men than women. Moreover, the average age of death due to drug use was 36 years old. In addition, methamphetamine was the mostly-used type of substances, and smoking was the most widely used method to use the drugs. Besides, the dominant consistency and color of the lungs of half of the bodies investigated were elastic brown-gray. Moreover, the most common pathologic changes observed in the lungs of the bodies investigated were congestion and edema. Conclusion: Given the prevalence of pathological changes in the lungs of the examined bodies and congestion, edema, and pulmonary hemorrhage, the results of the present study can be particularly effective in determining the drug use and the resultant death in the absence of any previous records and/or a negative result of toxicology.

  18. The ICH S8 immunotoxicity guidance. Immune function assessment and toxicological pathology: autonomous or synergistic methods to predict immunotoxicity? (United States)

    Spanhaak, Steven


    The new ICH S8 guideline on Immunotoxicology Studies for Human Pharmaceuticals indicates that additional, functional testing of pharmaceuticals is not mandatory to screen for unintended immunotoxicity. The usefulness of conventional parameters like clinical pathology, organ weights and histopathology as measured in Standard Toxicity Studies (STS) to screen for potential unintended immunotoxicity was investigated in an ICH survey. Data of this survey appear to support the notion that properly evaluated STS endpoints would be sufficient for the detection of the majority of unintended immunosuppression by investigational pharmaceutical compounds. Thus the ICH S8 guideline was based on a cause for concern approach using a weight of evidence review of various factors like: findings from STS, pharmacological properties of the drug, intended patient population, structural similarities to known immunomodulators, drug disposition and/or clinical information. Overall the S8 guideline allows for more flexible approaches, and requires a weight of evidence review for which there is no given set of rules. For a proper use this asks for a sensible, realistic and above all a responsible approach both from Industry and Regulators. Some examples regarding the use of clinical pathology parameters like immunoglobulin levels and lymphocyte phenotyping have been included to illustrate this. In conclusion, to detect and evaluate potential immunotoxic effects of human pharmaceuticals the ICH S8 guideline allows for a more flexible, scientifically sound approach. For a proper evaluation of potential immunotoxic effects integration of data from standard toxicological parameters like clinical pathology, histopathology and functional assays are important.

  19. Acid stress in the pathology of asthma. (United States)

    Ricciardolo, Fabio L M; Gaston, Benjamin; Hunt, John


    Although alteration of airway pH may serve an innate host defense capacity, it also is implicated in the pathophysiology of obstructive airway diseases. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays. The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins (major mediators of this pathway) that, in conjunction with kinins, nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis.

  20. Review of approaches to the recording of background lesions in toxicologic pathology studies in rats. (United States)

    McInnes, E F; Scudamore, C L


    Pathological evaluation of lesions caused directly by xenobiotic treatment must always take into account the recognition of background (incidental) findings. Background lesions can be congenital or hereditary, histological variations, changes related to trauma or normal aging and physiologic or hormonal changes. This review focuses on the importance and correct approach to recording of background changes and includes discussion on sources of variability in background changes, the correct use of terminology, the concept of thresholds, historical control data, diagnostic drift, blind reading of slides, scoring and artifacts. The review is illustrated with background lesions in Sprague Dawley and Wistar rats.

  1. Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food. (United States)

    Bakhiya, Nadiya; Abraham, Klaus; Gürtler, Rainer; Appel, Klaus Erich; Lampen, Alfonso


    Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 μg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs.


    Institute of Scientific and Technical Information of China (English)

    胡渝华; 李寿祺; 董奇男


    In order to draw up the permit limit value of Formic Acid in air of work place in China, the literatures published during the last 20 years were reviewed to understand it's physic and chemic property, kinetics, mechanism of toxic action, gen-eral toxicity, reproductive and developmental toxicity, mutagenicity, work hygienics, the cases of accidents, the concentration in ertvironmental air and the threshold limit values in different countries.

  3. Toxicological and histopathological effects of boric acid on Atta sexdens rubropilosa (Hymenoptera: Formicidae) workers. (United States)

    Sumida, Simone; Silva-Zacarin, Elaine C M; Decio, Pâmela; Malaspina, Osmar; Bueno, Fabiana C; Bueno, Odair C


    The current study compared the toxicity of different concentrations of boric acid in adult workers of Atta sexdens rubropilosa Forel (Hymenoptera: Formicidae), with toxicological bioassays, and examining the dose-dependent and time-dependent histopathological changes, of the midgut, Malpighian tubules, and postpharyngeal glands. Our results revealed the importance of conducting toxicological bioassays combined with morphological analyses of the organs of ants chronically exposed to insecticides used in commercial ant baits. In vitro bioassays showed that boric acid significantly decreases the survivorship of workers regardless of concentration, whereas the morphological data suggested progressive dose-dependent and time-dependent changes in the organs examined, which were evident in the midgut. The midgut is the first organ to be affected, followed by the postpharyngeal gland and Malpighian tubules. This sequence is in agreement with the absorption pathway of this chemical compound in the midgut, its transference to the hemolymph, possibly reaching the postpharyngeal glands, and excretion by the Malpighian tubules. These progressive changes might be due to the cumulative and delayed effect of boric acid. Our findings provide important information for the understanding of the action of boric acid in ant baits in direct and indirect target organs.

  4. A comprehensive evaluation of the toxicology of cigarette ingredients: aliphatic and aromatic carboxylic acids. (United States)

    Coggins, Christopher R E; Liu, Jianmin; Merski, Jerome A; Werley, Michael S; Oldham, Michael J


    Aromatic and aliphatic carboxylic acids are present in tobacco and tobacco smoke. A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic carboxylic acids and the salt of one acid that were added individually at three different levels (lowest and highest target inclusions were 100 and 90,000 ppm, respectively). Mainstream smoke from cigarettes containing each of the test ingredients was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For four of the compounds (citric, lactic, benzoic acids, and sodium benzoate), 90-day rodent inhalation studies were also performed. Although sporadic statistically significant differences in some experimental cigarette smoke constituents occurred, none resulted in significant changes in mutagenicity or cytotoxicity responses, nor in responses measured in the inhalation studies, except for lactic acid (LA). Inclusion of LA resulted in dose-dependent increase in water and caused a dose-dependent decrease in cytotoxicity. Incorporation of LA into cigarettes resulted in several dose-related reductions in histopathology, which were largely restricted to the nasal passages. Incorporation of LA also ameliorated some of the typical decrease in body weight gain seen in cigarette smoke-exposed rats. Inclusion of these ingredients at exaggerated use levels resulted in sporadic dose-related and treatment effects for some smoke constituents, but no toxicological response was noted in the in vitro and in vivo tests performed.

  5. Assessment of toxicologic interactions resulting from acute inhalation exposure to sulfuric acid and ozone mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Schlesinger, R.B.; Zelikoff, J.T.; Chen, L.C.; Kinney, P.L. (Department of Environmental Medicine, New York University Medical Center, NY (United States))


    Studies examining effects of air pollutants often use single compounds, while real world' exposures are to more than one chemical. Thus, it is necessary to assess responses following inhalation of chemical mixtures. Rabbits were exposed for 3 hr to sulfuric acid aerosol at 0, 50, 75, or 125 micrograms/m3 in conjunction with ozone at 0, 0.1, 0.3, or 0.6 ppm, following which broncho-pulmonary lavage was performed. Various pulmonary response endpoints related to general cytotoxicity and macrophage function were examined. In addition, a goal of the study was to define an improved approach to the analysis of data sets involving binary pollutant mixtures. Results were evaluated using analysis of variance with multiple linear contrasts to determine the significance of any effect in the pollutant-exposed groups compared to sham control animals and to assess the type, and extent, of any toxicological interaction between acid and ozone. Interaction was considered to occur when the effects of combined exposure were either significantly greater or less than additive. Pollutant exposures had no effect on lavage fluid levels of lactate dehydrogenase, prostaglandins E2 and F2 alpha, nor on the numbers, viability, or types of immune cells recovered by lavage. Phagocytic activity of macrophages was depressed at the two highest acid levels and at all levels of ozone. Superoxide production by stimulated macrophages was depressed by acid exposure at the two highest concentrations, while ozone alone had no effect. Significant antagonistic interaction was observed following exposure to mixtures of 75 or 125 micrograms/m3 acid with 0.1 or 0.3 ppm ozone. The activity of tumor necrosis factor elicited from stimulated macrophages was depressed by acid at 75 and 125 micrograms/m3 while ozone had no effect. Exposure to mixtures of 125 micrograms/m3 acid with 0.3 or 0.6 ppm ozone resulted in synergistic interaction.

  6. Toxicologic Evaluation of Trichloroacetic Acid: Effects on Rat Liver Peroxisomes and Enzyme Altered Foci. (United States)


    submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY WASHINGTON STATE UNIVERSITY Program in Pharmacology /Toxicology May...Protection Agency for their financial support of my research. The faculty and staff of the Pharmacology /Toxicology program at WSU and Veterinary...chemical carcinogens. Nature. 283:397-398 (1980). 91. Blane, G.F. and Pinaroli, F. Fenofibrate : animal toxic- ology in relatin to side effects in man. Nour

  7. Essential fatty acid requirements of cats: pathology of essential fatty acid deficiency. (United States)

    MacDonald, M L; Anderson, B C; Rogers, Q R; Buffington, C A; Morris, J G


    The pathologic changes of essential fatty acid (EFA) deficiency were studied in specific-pathogen-free, domestic shorthair cats which were fed purified diets for 1.5 to 2.5 years. Cats fed an EFA-deficient diet exhibited signs of deficiency: severe fatty degeneration of the liver, excessive fat in the kidneys, dystrophic mineralization of the adrenal glands, degeneration of the testes, and hyperkeratosis of the skin. Minor clinical pathologic changes were consistent with liver damage. Fatty acid analyses of plasma lipids revealed low concentrations of linoleate and other n6-fatty acids, and high concentrations of n7- and n9-fatty acids, consistent with EFA deficiency. These signs of deficiency were prevented by including safflower seed oil in the diet at a concentration to supply linoleate at 6.7% of dietary energy. Therefore, linoleate is an EFA for the cat, despite negligible conversion of linoleate to arachidonate in cat liver. However, in cats fed a diet containing linoleate, but lacking arachidonate, there was mild mineralization of the kidneys, and the neutral fat content of the liver was slightly higher than that of cats fed a diet containing arachidonate and other long-chain polyunsaturated fatty acids. Also, 2 of the 19 cats fed arachidonate-deficient diets developed unusual inflammatory skin lesions. In cats fed a diet containing hydrogenated coconut oil, safflower seed oil, and chicken fat, fatty livers developed despite the presence of high levels of linoleate. The fatty livers appeared to result from a specific deleterious effect of the medium-chain triglycerides in hydrogenated coconut oil. Most of the organ pathologic changes of EFA deficiency in the cat can be prevented by feeding dietary linoleate. Linoleate meets the EFA requirement for functions which depend on proper membrane structure: growth, lipid transport, normal skin and coat condition, and maintenance of the epidermal permeability barrier. However, dietary arachidonate is required by the

  8. Evaluation of the toxicological effects of perfluorooctane sulfonic acid in the common carp (Cyprinus carpio)

    Energy Technology Data Exchange (ETDEWEB)

    Hoff, P.T.; Dongen, W. van; Esmans, E.L.; Blust, R.; Coen, W.M. de


    In the present study we evaluated the toxicological effects of a scarcely documented environmental pollutant, perfluorooctane sulfonic acid (PFOS), on selected biochemical endpoints in the common carp, Cyprinus carpio. Juvenile organisms were exposed to PFOS through a single intraperitoneal injection (liver concentrations ranging from 16 to 864 ng/g after 5 days of exposure) and after 1 and 5 days effects were assessed in liver and serum of the exposed organisms. The investigation of the hepatotoxicity of PFOS included the determination of the peroxisome proliferating potential (peroxisomal palmitoyl CoA oxidase and catalase activity) and the compounds influence on the average DNA basepair length (ABPL) by agarose gel electrophoresis. Total antioxidant activity (TAA), cholesterol and triglyceride levels were monitored in the serum. After 1 day of exposure the ABPL was significantly increased in the 270 and 864 ng/g treatment groups. After 5 days of exposure significant increases relative to the control were observed for the 16, 270 and 864 ng/g treatment groups. Enzyme leakage from the liver was investigated by measurement of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the serum. At 561, 670 and 864 ng/g PFOS a significant increase in serum ALT activity became apparent after 5 days of exposure with values ranging from 159 to 407% relative to the control. For serum AST activity a significant increase for the 864 ng/g treatment group was observed with a value of 112% relative to the control. Determination of the polymorphonuclear leukocyte migration into liver tissue as assessed through myeloperoxidase (MPO) activity in liver, was used as an indicator for inflammation. It appeared that inflammation was not involved in the observed membranous enzyme leakage for the 561, 670 and 864 ng/g PFOS treatment groups. The results of this study suggest that PFOS induces inflammation-independent enzyme leakage through liver cell membranes

  9. Research of Toxicological Pathology on Animals' Arsenicalism%动物慢性砷中毒的毒理病理学研究进展

    Institute of Scientific and Technical Information of China (English)

    崔连成; 孙永学; 宁章勇


    砷制剂由于在提高增重和改进饲料利用率方面的作用而被广泛应用于畜禽生产,长期使用或剂量不当,会导致动物砷的慢性中毒,通过食物链的富集作用,导致人类相应疾病的发生.慢性砷中毒可以导致皮肤损伤、心血管疾病、泌尿系统及神经系统损伤、糖尿病等,砷还是一种确定的致癌物.文章对动物慢性砷中毒的毒理病理学进行了综述,并对慢性砷中毒可能的研究方向进行了展望.%Arsenic preparations has been widely used in the production of livestock just because its effect on increasing weight and improving the feed efficiency,however,long-term use or improper dosage can cause chronic poisoning of arsenic in animals. Then it can lead to the corresponding disease of human through the enrichment of food chain. Chronic arsenic poisoning can cause skin damage,cardiovascular disease,urinary system and neurological damage and diabetes, what's more,arsenic is also a certain carcinogens. The article summarizes on the poisoning toxicological pathology of animal's arsenicalism and outlooks the possible research directions of arsenicalism.

  10. 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...

  11. 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,...

  12. Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis. (United States)

    Browne, Elisse C; Parakh, Sonam; Duncan, Luke F; Langford, Steven J; Atkin, Julie D; Abbott, Belinda M


    Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.

  13. Expression patterns of glial fibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies

    NARCIS (Netherlands)

    L. Martinian; K. Boer; J. Middeldorp; E.M. Hol; S.M. Sisodiya; W. Squier; E.M.A. Aronica; M. Thom


    Aims: Glial fibrillary acidic protein (GFAP)-delta is a novel isoform that differs in its C-terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological co

  14. 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

  15. Evaluation of Bioequivalency and Toxicological Effects of Three Sources of Arachidonic Acid (ARA) in Domestic Piglets



    Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are routinely added to infant formula to support growth and development. We evaluated the bioequivalence and safety of three ARA-rich oils for potential use in infant formula using the neonatal pig model. The primary outcome for bioequivalence was brain accretion of ARA and DHA. Days 3 to 22 of age, domestic pigs fed one of three formulas, each containing ARA at ~0.64% and DHA at ~0.34% total fatty acids (FA). Control diet ARA was provided...

  16. 全氟烷酸类化合物的毒理学研究%Toxicological study on perfluoroalkyl acids

    Institute of Scientific and Technical Information of China (English)

    陈思怀; 石志敏


    全氟烷酸类化合物是一类新型的持久性有机污染物,已被广泛应用于工业生产以及生活用品中,在全球各地的环境介质和人群中均检测到了该化合物的存在,该类化合物的环境健康效应已经引起了广泛的关注。本文对该化合物的特征、来源、毒代动力学特征、毒性效应以及相关的机制进行了总结,以进一步了解该化合物毒理学方面的研究进展。%Perfluoroalkyl acids (PFAAs) are an emerging persistent organic pollutant. With the wide application in industrial and general products, these compounds have been detected in the environmental matris and human population. The concerns about the effects of PFAAs on environment and health have been generated. This review summarizes the characteristics, source, toxicokinetics, toxic effects of PFAAs and related mechanisms for further understanding PFAAs progress in toxicology.

  17. Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells. (United States)

    Ebert, Franziska; Leffers, Larissa; Weber, Till; Berndt, Svenia; Mangerich, Aswin; Beneke, Sascha; Bürkle, Alexander; Schwerdtle, Tanja


    Thio-dimethylarsinic acid (thio-DMA(V)) has recently been identified as human metabolite after exposure toward both the human carcinogen inorganic arsenic and arsenosugars, which are the major arsenical constituents of marine algae. This study aims to get further insight in the toxic modes of action of thio-DMA(V) in cultured human urothelial cells. Among others effects of thio-DMA(V) on eight cell death related endpoints, cell cycle distribution, genotoxicity, cellular bioavailability as well as for the first time its impact on DNA damage induced poly(ADP-ribosyl)ation were investigated and compared to effects induced by arsenite. The data indicate that thio-DMA(V) exerts its cellular toxicity in a similar or even lower concentration range, however most likely via different mechanisms, than arsenite. Most interestingly, thio-DMA(V) decreased damage-induced cellular poly(ADP-ribosyl)ation by 35,000-fold lower concentrations than arsenite. The inhibition of this essential DNA-damage induced and DNA-repair related signaling reaction might contribute to inorganic arsenic induced toxicity, at least in the bladder. Therefore, and also because thio-DMA(V) is to date by far the most toxic human metabolite identified after arsenosugar intake, thio-DMA(V) should contemporary be fully (also in vivo) toxicologically characterized, to assess risks to human health related to inorganic arsenic but especially arsenosugar dietary intake. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. 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.

  19. 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.

  20. 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,...

  1. Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models. (United States)

    Anekonda, Thimmappa S; Wadsworth, Teri L; Sabin, Robert; Frahler, Kate; Harris, Christopher; Petriko, Babett; Ralle, Martina; Woltjer, Randy; Quinn, Joseph F


    Alzheimer's disease (AD) causes progressive, age-dependent cortical and hippocampal dysfunction leading to abnormal intellectual capacity and memory. We propose a novel protective treatment for AD pathology with phytic acid (inositol hexakisphosphate), a phytochemical found in food grains and a key signaling molecule in mammalian cells. We evaluated the protective and beneficial effects of phytic acid against amyloid-β (Aβ) pathology in MC65 cells and the Tg2576 mouse model. In MC65 cells, 48-72-hour treatment with phytic acid provided complete protection against amyloid precursor protein-C-terminal fragment-induced cytotoxicity by attenuating levels of increased intracellular calcium, hydrogen peroxide, superoxide, Aβ oligomers, and moderately upregulated the expression of autophagy (beclin-1) protein. In a tolerance paradigm, wild type mice were treated with 2% phytic acid in drinking water for 70 days. Phytic acid was well tolerated. Ceruloplasmin activity, brain copper and iron levels, and brain superoxide dismutase and ATP levels were unaffected by the treatment. There was a significant increase in brain levels of cytochrome oxidase and a decrease in lipid peroxidation with phytic acid administration. In a treatment paradigm, 12-month old Tg2576 and wild type mice were treated with 2% phytic acid or vehicle for 6 months. Brain levels of copper, iron, and zinc were unaffected. The effects of phytic acid were modest on the expression of AβPP trafficking-associated protein AP180, autophagy-associated proteins (beclin-1, LC3B), sirtuin 1, the ratio of phosphorylated AMP-activated protein kinase (PAMPK) to AMPK, soluble Aβ1-40, and insoluble Aβ1-42. These results suggest that phytic acid may provide a viable treatment option for AD.

  2. Protective role of metallothionein (Ⅰ/Ⅱ) against pathological damage and apoptosis induced by dimethylarsinic acid

    Institute of Scientific and Technical Information of China (English)

    Guang Jia; Yi-Qun Gu; Kung-Tung Chen; You-Yong Lu; Lei Yan; Jian-Ling Wang; Ya-Ping Su; J. C. Gaston Wu


    AIM: To better clarify the main target organs of dimethylarsinic acid toxicity and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA) toxicity.METHODS: MT-Ⅰ/Ⅱ null (MT-/-) mice and the corresponding wild-type mice (MT+/+), six in each group, were exposed to DMAA (0-750 mg/kg body weight) by a single oral injection.Twenty four hours later, the lungs, livers and kidneys were collected and undergone pathological analysis, induction of apoptotic cells as determined by TUNEL and MT concentration was detected by radio-immunoassay.RESULTS: Remarkable pathological lesions were observed at the doses ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and MT+/+ mice exhibited a relatively slight destruction when compared with that in dose matched MT-/- mice. The number of apoptotic cells was increased in a dose dependent manner in the lungs and livers in both types of mice. DMAA produced more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg,however, no significant increase was observed in the kidney.Hepatic MT level in MT+/+ mice was significantly increased by DMAA in a dose-dependent manner and there was nodetectable amount of hepatic MT in untreated MT-/- mice.CONCLUSION: DMAA treatment can lead to the induction of apoptosis and pathological damage in both types of mice.MT exhibits a protective effect against DMAA toxicity.

  3. Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach. (United States)

    Ball, Gwendolyn L; McLellan, Clifton J; Bhat, Virunya S


    Polyethylene terephthalate, a copolymer of terephthalic acid (TPA) or dimethyl terephthalate (DMT) with ethylene glycol, has food, beverage, and drinking water contact applications. Di-2-ethylhexyl terephthalate (DEHT) is a plasticizer in food and drinking water contact materials. Oral reference doses (RfDs) and total allowable concentrations (TACs) in drinking water were derived for TPA, DMT, and DEHT. Category RfD and TAC levels were also established for nine C(1)-C(8) terephthalate esters. The mode of action of TPA, and of DMT, which is metabolized to TPA, involves urinary acidosis, altered electrolyte elimination and hypercalciuria, urinary supersaturation with calcium terephthalate or calcium hydrogen terephthalate, and crystallization into bladder calculi. Weanling rats were more sensitive to calculus formation than dams. Calculi-induced irritation led to bladder hyperplasia and tumors in rats fed 1000 mg/kg-day TPA. The lack of effects at 142 mg/kg-day supports a threshold for urine saturation with calcium terephthalate, a key event for calculus formation. Chronic dietary DMT exposure in rodents caused kidney inflammation, but not calculi. Chronic dietary DEHT exposure caused general toxicity unrelated to calculi, although urine pH was reduced suggesting the TPA metabolite was biologically-active, but of insufficient concentration to induce calculi. Respective oral reference doses of 0.5, 0.5, and 0.2 mg/kg-day and total allowable drinking water concentrations of 3, 3, and 1 mg/L were derived for TPA, DMT, and DEHT. An oral RfD of 0.2 mg/kg-day for the terephthalate category chemicals corresponded to a drinking water TAC of 1 mg/L.

  4. Nontraditional applications in clinical pathology. (United States)

    Jordan, Holly L; Register, Thomas C; Tripathi, Niraj K; Bolliger, Anne Provencher; Everds, Nancy; Zelmanovic, David; Poitout, Florence; Bounous, Denise I; Wescott, Debra; Ramaiah, Shashi K


    Most published reviews of preclinical toxicological clinical pathology focus on the fundamental aspects of hematology, clinical chemistry, coagulation, and urinalysis in routine toxicology animal species, for example, rats, mice, dogs, and nonhuman primates. The objective of this continuing education course was to present and discuss contemporary examples of nonroutine applications of clinical pathology endpoints used in the drug development setting. Area experts discussed bone turnover markers of laboratory animal species, clinical pathology of pregnant and growing laboratory animals, clinical pathology of nonroutine laboratory animal species, and unique applications of the Siemens Advia(®) hematology analyzer. This article is a summary based on a presentation given at the 31st Annual Symposium of the Society of Toxicologic Pathology, during the Continuing Education Course titled "Nontraditional Applications of Clinical Pathology in Drug Discovery and Preclinical Toxicology."

  5. Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Jesús Avila


    Full Text Available Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA, has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed.

  6. The Pathological Effects of Melamine and Cyanuric Acid in the Diet of Walking Catfish (Clarius batrachus). (United States)

    Pirarat, N; Katagiri, T; Chansue, N; Ponpornpisit, A; Endo, M; Maita, M


    The toxicity of melamine and its analogue in man and animals has been reported widely. The aim of the present study was to examine the pathological effects of feeding melamine and cyanuric acid, separately or in combination, to walking catfish (Clarius batrachus). The catfish developed darkening of the skin as early as 3 days post feeding. Melamine-related crystals were distributed multifocally throughout the liver, kidney, heart, spleen and corpuscle of Stannius of fish fed melamine and cyanuric acid in combination. Oil red O staining and electron microscopy revealed that the melamine-related crystals had structure resembling that of plastic polymer crystals. Elevations in the serum concentrations of alanine transaminase, aspartate transaminase, creatinine and uric acid were related to the crystal-associated granulomatous inflammation in the liver and kidney of affected fish. None of the catfish died during the 2-week experiment. Melamine and cyanuric acid are therefore systemically toxic to fish in addition to causing renal crystal formation and renal damage as seen in man and animals. The finding of extrarenal crystals implies that the metabolism and biotransformation of these toxic compounds should be further investigated in aquatic animals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. (United States)

    Petzold, Axel


    This review on the role of glial fibrillary acidic protein (GFAP) as a biomarker for astroglial pathology in neurological diseases provides background to protein synthesis, assembly, function and degeneration. Qualitative and quantitative analytical techniques for the investigation of human tissue and biological fluid samples are discussed including partial lack of parallelism and multiplexing capabilities. Pathological implications are reviewed in view of immunocytochemical, cell-culture and genetic findings. Particular emphasis is given to neurodegeneration related to autoimmune astrocytopathies and to genetic gain of function mutations. The current literature on body fluid levels of GFAP in human disease is summarised and illustrated by disease specific meta-analyses. In addition to the role of GFAP as a diagnostic biomarker for chronic disease, there are important data on the prognostic value for acute conditions. The published evidence permits to classify the dominant GFAP signatures in biological fluids. This classification may serve as a template for supporting diagnostic criteria of autoimmune astrocytopathies, monitoring disease progression in toxic gain of function mutations, clinical treatment trials (secondary outcome and toxicity biomarker) and provide prognostic information in neurocritical care if used within well defined time-frames.

  9. Targeted toxicological screening for acidic, neutral and basic substances in postmortem and antemortem whole blood using simple protein precipitation and UPLC-HR-TOF-MS. (United States)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal


    A broad targeted screening method based on broadband collision-induced dissociation (bbCID) ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS) was developed and evaluated for toxicological screening of whole blood samples. The acidic, neutral and basic substances covered by the method were identified in postmortem and antemortem whole blood samples from forensic autopsy cases, clinical forensic cases and driving under the influence of drugs (DUID) cases by a reverse target database search. The screening method covered 467 substances. Validation was performed on spiked whole blood samples and authentic postmortem and antemortem whole blood samples. For most of the basic drugs, the established cut-off limits were very low, ranging from 0.25ng/g to 50ng/g. The established cut-off limits for most neutral and acidic drugs, were in the range from 50ng/g to 500ng/g. Sample preparation was performed using simple protein precipitation of 300μL of whole blood with acetonitrile and methanol. Ten microliters of the reconstituted extract were injected and separated within a 13.5min UPLC gradient reverse-phase run. Positive electrospray ionization (ESI) was used to generate the ions in the m/z range of 50-1000. Fragment ions were generated by bbCID. Identification was based on retention time, accurate mass, fragment ion(s) and isotopic pattern. A very sensitive broad toxicological screening method using positive electrospray ionization UPLC-HR-TOF-MS was achieved in one injection. This method covered basic substances, substances traditionally analyzed in negative ESI (e.g., salicylic acid), small highly polar substances such as beta- and gamma-hydroxybutyric acid (BHB and GHB, respectively) and highly non-polar substances such as amiodarone. The new method was shown to combine high sensitivity with a very broad scope that has not previously been reported in toxicological whole blood screening when using only one injection.

  10. 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...

  11. Fast determination of ethylene glycol, 1,2-propylene glycol and glycolic acid in blood serum and urine for emergency and clinical toxicology by GC-FID. (United States)

    Hložek, Tomáš; Bursová, Miroslava; Čabalaa, Radomír


    A simple, cost effective, and fast gas chromatography method with flame ionization detection (GC-FID) for simultaneous measurement of ethylene glycol, 1,2-propylene glycol and glycolic acid was developed and validated for clinical toxicology purposes. This new method employs a relatively less used class of derivatization agents - alkyl chloroformates, allowing the efficient and rapid derivatization of carboxylic acids within seconds while glycols are simultaneously derivatized by phenylboronic acid. The entire sample preparation procedure is completed within 10 min. To avoid possible interference from naturally occurring endogenous acids and quantitation errors 3-(4-chlorophenyl) propionic acid was chosen as an internal standard. The significant parameters of the derivatization have been found using chemometric procedures and these parameters were optimized using the face-centered central composite design. The calibration dependence of the method was proved to be quadratic in the range of 50-5000 mg mL(-1), with adequate accuracy (92.4-108.7%) and precision (9.4%). The method was successfully applied to quantify the selected compounds in serum of patients from emergency units.

  12. Biological and Pathological Studies of Rosmarinic Acid as an Inhibitor of Hemorrhagic Trimeresurus flavoviridis (habu Venom

    Directory of Open Access Journals (Sweden)

    Masatake Niwa


    Full Text Available In our previous report, rosmarinic acid (RA was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae. The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu. This article presents mechanistic evidence of RA’s neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.

  13. 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.

  14. 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.

  15. Targeted toxicological screening for acidic, neutral and basic substances in postmortem and antemortem whole blood using simple protein precipitation and UPLC-HR-TOF-MS

    DEFF Research Database (Denmark)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal


    -HR-TOF-MS was achieved in one injection. This method covered basic substances, substances traditionally analyzed in negative ESI (e.g., salicylic acid), small highly polar substances such as beta- and gamma-hydroxybutyric acid (BHB and GHB, respectively) and highly non-polar substances such as amiodarone. The new method......A broad targeted screening method based on broadband collision-induced dissociation (bbCID) ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS) was developed and evaluated for toxicological screening of whole blood samples. The acidic, neutral...... was performed on spiked whole blood samples and authentic postmortem and antemortem whole blood samples. For most of the basic drugs, the established cut-off limits were very low, ranging from 0.25ng/g to 50ng/g. The established cut-off limits for most neutral and acidic drugs, were in the range from 50ng...

  16. Studies on the Simultaneous Formation of Aroma-Active and Toxicologically Relevant Vinyl Aromatics from Free Phenolic Acids during Wheat Beer Brewing. (United States)

    Langos, Daniel; Granvogl, Michael


    During the brewing process of wheat beer, the desired aroma-active vinyl aromatics 2-methoxy-4-vinylphenol and 4-vinylphenol as well as the undesired and toxicologically relevant styrene are formed from their respective precursors, free ferulic acid, p-coumaric acid, and cinnamic acid, deriving from the malts. Analysis of eight commercial wheat beers revealed high concentrations of 2-methoxy-4-vinylphenol and 4-vinylphenol always in parallel with high concentrations of styrene or low concentrations of the odorants in parallel with low styrene concentrations, suggesting a similar pathway. To better understand the formation of these vinyl aromatics, each process step of wheat beer brewing and the use of different strains of Saccharomyces cerevisiae were evaluated. During wort boiling, only a moderate decarboxylation of free phenolic acids and formation of desired and undesired vinyl aromatics were monitored due to the thermal treatment. In contrast, this reaction mainly occurred enzymatically catalyzed during fermentation with S. cerevisiae strain W68 with normal Pof(+) activity (phenolic off-flavor) resulting in a wheat beer eliciting the typical aroma requested by consumers due to high concentrations of 2-methoxy-4-vinylphenol (1790 μg/L) and 4-vinylphenol (937 μg/L). Unfortunately, also a high concentration of undesired styrene (28.3 μg/L) was observed. Using a special S. cerevisiae strain without Pof(+) activity resulted in a significant styrene reduction (beer aroma.

  17. Simultaneous and cost-effective determination of ethylene glycol and glycolic acid in human serum and urine for emergency toxicology by GC-MS. (United States)

    Hložek, Tomáš; Bursová, Miroslava; Čabala, Radomír


    A simple, cost-effective, and fast gas chromatography method with mass spectrometry detection (GC-MS) for simultaneous measurement of ethylene glycol, 1,2-propylene glycol and glycolic acid was developed and validated for clinical toxicology purposes. Successful derivatization of glycolic acid with isobutyl chloroformate was achieved directly in serum/urine while glycols are simultaneously derivatized by phenylboronic acid. The entire sample preparation procedure is completed within 10 min. The assay was proved to be quadratic in the range of 50 to 5000 mgL(-1) with adequate accuracy (96.3-105.8%) and precision (CV ≤ 8.9%). The method was successfully applied to quantify the selected compounds in serum of patients from emergency units and the results correlated well with parallel GC-FID measurements (R(2) 0.9933 for ethylene glycol and 0.9943 for glycolic acid). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. Behavioral, clinical, and pathological characterization of acid metalliferous water toxicity in mallards (United States)

    Isanhart, J.P.; Wu, H.; Pandher, K.; MacRae, R.K.; Cox, S.B.; Hooper, M.J.


    From September to November 2000, United States Fish and Wildlife Service biologists investigated incidents involving 221 bird deaths at 3 mine sites located in New Mexico and Arizona. These bird deaths primarily involved passerine and waterfowl species and were assumed to be linked to consumption of acid metalliferous water (AMW). Because all of the carcasses were found in or near pregnant leach solution ponds, tailings ponds, and associated lakes or storm water retention basins, an acute-toxicity study was undertaken using a synthetic AMW (SAMW) formulation based on the contaminant profile of a representative pond believed to be responsible for avian mortalities. An acute oral-toxicity trial was performed with a mixed-sex group of mallards (Anas platyrhynchos). After a 24-h pretreatment food and water fast, gorge drinking was evident in both SAMW treatment and control groups, with water consumption rates greatest during the initial drinking periods. Seven of nine treated mallards were killed in extremis within 12 h after the initiation of dose. Total lethal doses of SAMW ranged from 69.8 to 270.1 mL/kg (mean ?? SE 127.9 ?? 27.1). Lethal doses of SAMW were consumed in as few as 20 to 40 min after first exposure. Clinical signs of SAMW toxicity included increased serum uric acid, aspartate aminotransferase, creatine kinase, potassium, and P levels. PCV values of SAMW-treated birds were also increased compared with control mallards. Histopathological lesions were observed in the esophagus, proventriculus, ventriculus, and duodenum of SAMW-treated mallards, with the most distinctive being erosion and ulceration of the kaolin of the ventriculus, ventricular hemorrhage and/or congestion, and duodenal hemorrhage. Clinical, pathological, and tissue-residue results from this study are consistent with literature documenting acute metal toxicosis, especially copper (Cu), in avian species and provide useful diagnostic profiles for AMW toxicity or mortality events. Blood and

  20. 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.

  1. 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 ...

  2. Handbook of systems toxicology

    National Research Council Canada - National Science Library

    Casciano, Daniel A; Sahu, Saura C


    "In the first handbook to comprehensively cover the emerging area of systems toxicology, the Handbook of Systems Toxicology provides an authoritative compilation of up-to-date developments presented...

  3. National Toxicology Program (United States)

    ... for modern toxicology and molecular biology. A world leader in toxicology research, NTP has evaluated more than 2800 environmental substances for potential human health effects. Learn More About NTP Director Meet NTP's director Linda Birnbaum, Ph.D. Learn ...

  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. Toxicology Education Foundation (United States)

    ... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... In with us, follow our Tweets, choose Toxicology Education Foundation as your preferred charity through Smile.Amazon. ...

  6. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Neida K Mita-Mendoza

    Full Text Available BACKGROUND: Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1, E-selectin (sE-Selectin, thrombomodulin (sTM, tissue factor (sTF and vascular endothelial growth factor (VEGF in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487 and non-cerebral severe malaria (NCSM, n = 68. In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season. We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001. Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043, sICAM-1 (r = 0.255, p<0.0001 and sTM (r = 0.175, p = 0.0001 levels. After adjusting for parasite density, UA levels predict sTM levels. CONCLUSIONS/SIGNIFICANCE: Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of

  7. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria. (United States)

    Mita-Mendoza, Neida K; van de Hoef, Diana L; Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Gu, Wenjuan; Anderson, Jennifer M; Santos-Argumedo, Leopoldo; Rodriguez, Ana; Fay, Michael P; Diakite, Mahamadou; Long, Carole A; Fairhurst, Rick M


    Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels. Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in

  8. Toxicological screening of human plasma by on-line SPE-HPLC-DAD: identification and quantification of acidic and neutral drugs. (United States)

    Mut, Ludmila; Grobosch, Thomas; Binscheck-Domaß, Torsten; Frenzel, Wolfgang


    A multi-analyte screening method for the quantification of 50 acidic/neutral drugs in human plasma based on on-line solid-phase extraction (SPE)-HPLC with photodiode array detection (DAD) was developed, validated and applied for clinical investigation. Acetone and methanol for protein precipitation, three different SPE materials (two electro-neutral, one strong anion-exchange, one weak cation-exchange) for on-line extraction, five HPLC-columns [one C18 (GeminiNX), two phenyl-hexyl (Gemini C6 -Phenyl, Kinetex Phenyl-Hexyl) and two pentafluorophenyl (LunaPFP(2), KinetexPFP)] for analytical separation were tested. For sample pre-treatment, acetone in the ratio 1:2 (plasma:acetone) showed a better baseline and fewer matrix peaks in the chromatogram than methanol. Only the strong anion-exchanger SPE cartridge (StrataX-A, pH 6) allowed the extraction of salicylic acid. Analytical separation was carried out on a Gemini C6 -Phenyl column (150 × 4.6 mm, 3 µm) using gradient elution with acetonitrile-water 90:10 (v/v) and phosphate buffer (pH 2.3). Linear calibration curves with correlation coefficients r ≥ 0.9950/0.9910 were obtained for 46/four analytes. Additionally, this method allows the quantification of 23 analytes for therapeutic drug monitoring. Limits of quantitation ranged from 0.1 (amobarbital) to 23 mg/L (salicylic acid). Inter-/intra-day precisions of quality control samples (low/high) were better than 13% and accuracy (bias) ranged from -14 to 10%. A computer-assisted database was created for automated detection of 223 analytes of toxicological interests. Four cases of multi-drug intoxications are presented.

  9. NTP Toxicology and Carcinogenesis Studies of Lauric Acid Diethanolamine Condensate (CAS NO. 120-40-1) in F344/N Rats and B6C3F1 Mice (Dermal Studies). (United States)


    Lauric acid diethanolamine condensate is widely used in cosmetics, shampoos, soaps, and related consumer products, to which there is extensive human exposure. Because of the lack of information about potential risks associated with long-term exposure, lauric acid diethanolamine condensate, coconut oil acid diethanolamine condensate, and oleic acid diethanolamine condensate were selected as representative of the class of diethanolamides for evaluation of prechronic toxicity and carcinogenic potential. Male and female F344/N rats and B6C3F1 mice were exposed to lauric acid diethanolamine condensate dermally for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until study termination. Final mean body weights and body weight gains of males receiving 200 or 400 mg/kg were significantly less than those of the vehicle control group. Irritation of the skin at the site of application was observed in males receiving 100 mg/kg or greater and in females receiving 200 or 400 mg/kg. Kidney weights of females administered 200 or 400 mg/kg were significantly greater than those of the vehicle control group. There were dose-dependent increases in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, chronic inflammation, parakeratosis, and ulcer. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered 0, 50, 100, 200, 400, or 800 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until the end of the study, and final mean body weights and

  10. [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.

  11. [Nitrilotriacetic acid (NTA)--properties, distribution and behavior in the environment. I. Chemical and toxicological properties of NTA]. (United States)

    Jedra, M; Malanowska, M


    The reason of the interest shown in the properties of NTA is the possibility of its use for the replacement of polyphosphates in washing powders which are the cause of water eutrophization. In the light of literature data the chemical properties of NTA and the conditions influencing the course of the reaction of complex formation with metal ions in aqueous solutions are discussed Equilibrium constants of these reactions are presented, with diagrams obtained in computer assisted analysis of the conditions of equilibrium of NTA reaction with metal ions in the solutions occurring in physiological conditions and in the environment. On the basis of the opinions of expert committees the toxicity of NTA for mammalian organisms are described. It has been shown that NTA has no teratogenic or mutagenic action, however, in 2-year observations of mice and rats the intake of NTA produced lesions of uroepithelium with development of tumours. This effect of NTA has been demonstrated to be closely connected with its property of complex formation with metal ions. Experiments are described in which confirmation was obtained of the hypothesis that pathological lesions of renal tabules are caused by accumulation of zinc and bladder tumours are caused by binding by NTA of calcium from epithelial cells.

  12. 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

  13. Clinical and pathological characteristics of mitochondrial myopathy and the screening value of simplified serum lactic acid exercise test

    Directory of Open Access Journals (Sweden)

    Xiao-fen ZHU


    Full Text Available Objective To analyze clinical and pathological characteristics of mitochondrial myopathy (MM in 15 patients, and to study the value of simplified serum lactic acid exercise test in the screening of mitochondrial myopathy.  Methods A total of 15 patients with mitochondrial myopathy diagnosed clinically and pathologically, 11  patients with other muscular diseases (OM, and 21 normal controls were collected. All subjects went up and down stairs for 5 min with medium effort. Blood samples for serum lactic acid detection were collected from all subjects before exercise, immediately after exercise and 10 min after exercise. Serum lactic acid levels were compared among 3 groups and among 3 time points. Results Patients with mitochondrial myopathy mainly presented as paroxysmally progressive muscular   soreness and weakness. Histopathological examination showed there were 8 cases with the proportion of ragged red fibers (RRF more than 5%. Serum lactic acid level before exercise, immediately after exercise and 10 min after exercise were (3.57 ± 1.88, (10.98 ± 4.84 and (7.87 ± 4.38 mmol/L in MM group, (1.89 ± 0.98, (6.05 ± 4.07 and (4.13 ± 3.14 mmol/L in OM group, (1.91 ± 0.53, (3.37 ± 1.22 and (2.52 ± 0.89 mmol/L in control group. Serum lactic acid level in MM group was significantly higher than that in control and OM groups before exercise (P = 0.000, 0.001, immediately after exercise (P = 0.000, 0.001, and 10 min after exercise (P = 0.000, 0.003. Serum lactic acid level in OM group was significantly higher than that in control group immediately after exercise (P = 0.042. Serum lactic acid level in 3 groups immediately after exercise (P = 0.000, 0.000, 0.003 and 10 min after exercise (P = 0.000, 0.000, 0.013 was significantly higher than that before exercise. Serum lactic acid level immediately after exercise was significantly higher than that 10 min after exercise in 3 groups (P = 0.000, 0.000, 0.003. Serum lactic acid level had most

  14. 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.

  15. 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 ...

  16. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C


    .... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

  17. NTP Toxicology and Carcinogenesis Studies of Oleic Acid Diethanolamine Condensate (CAS No. 93-83-4) in F344/N Rats and B6C3F1 Mice (Dermal Studies). (United States)


    moderate nonneoplastic lesions of the skin at the site of application in dosed rats. These lesioe lesions included epidermal hyperplasia, sebaceous gland hyperplasia, hyperkeratosis, parakeratosis, chronic active dermal inflammation, and ulcer. 2-YEAR STUDY IN MICE: Groups of 55 male and 55 female mice were administered 0, 15, or 30 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 2 years. Five animals from each group were evaluated at 3 months for gross lesions and skin histopathology. Survival, Body Weights, and Clinical Findings: Survival of dosed male and female mice was similar to that of the vehicle control groups. Mean body weights of dosed males and of 15 mg/kg females were similar to those of the vehicle controls throughout the study. Mean body weights of 30 mg/kg females were less than those of the vehicle controls from week 76 until the end of the study. The only significant treatment-related clinical finding was irritation of the skin at the site of application in 30 mg/kg males. Pathology Findings: The incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and chronic active inflammation of the dermis in all dosed groups were significantly increased relative to the vehicle controls at 3 months and at 2 years. The increased incidences of hyperkeratosis in dosed males at 3 months and in dosed males and females at 2 years, of parakeratosis in 30 mg/kg males at 3 months and 2 years, and of ulcer in 30 mg/kg males and exudate in 30 mg/kg males and females at 2 years were also attributed to chem ical administration. GENETIC TOXICOLOGY: Oleic acid diethanolamine condensate was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. In addition, it did not induce mutations in mouse L5178Y lymphoma cells treated with or without S9. CONCLUSIONS: Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenic activity of oleic acid

  18. Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles. (United States)

    Brito, Rodrigo O; Marques, Eduardo F; Silva, Sandra G; do Vale, Maria Luísa; Gomes, Paula; Araújo, Maria J; Rodriguez-Borges, J Enrique; Infante, Maria Rosa; Garcia, Maria Teresa; Ribosa, Isabel; Vinardell, María Pilar; Mitjans, Montserrat


    The design of efficient liposomal systems for drug delivery is of considerable biomedical interest. In this context, vesicles prepared from cationic/anionic surfactants may offer several advantages, mainly due to their spontaneity in formation and long-term stability. There is also an impending need to produce less toxic, more biocompatible amphiphiles, while maintaining the desirable aggregation properties. In this work, we present data for acute toxicity to Daphnia magna (IC(50)), and potential ocular irritation (HC(50)) for some newly prepared ionic surfactants with dodecyl chains, derived from the amino acids tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The micellization behavior of the compounds, evaluated from surface tension measurements, is presented and compared to more conventional ionic amphiphiles. Two types of spontaneouly formed catanionic vesicles, composed either by a dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative mixture, have also been tested for their ecotoxicity and hemolytic potential. All the micelle-forming surfactants as well as the vesicle-containing mixtures are found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the results from hemolysis and hemoglobin denaturation tests show that the Tyr- and Lys-derivatives are moderately irritant, whereas the Hyp- and Ser- ones are just slightly irritant. Even more significantly, the vesicle-containing mixtures exhibit lower hemolytic activity than the neat surfactants, a positive result for their potential use in liposomal formulations.

  19. 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.

  20. 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...

  1. Expression and structural-functional alterations of α-1-acid glycoprotein at the pathological state

    Directory of Open Access Journals (Sweden)

    Kulinich A. O.


    Full Text Available The review analyzes up-to-date knowledge on structure and biological functions of α-acid glycoprotein. The special attention is given to alterations of fucosylation, sialylation and branching of orosomucoid at the acute, chronic inflammation and oncotransformations.

  2. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Hao, Qin; Jørgensen, Henry


    Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from dietinduced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated...... metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome....... by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated...

  3. [Hyaluronic acid (hyaluronan) levels in pathological human saphenous veins. Effects of procyanidol oligomers]. (United States)

    Drubaix, I; Maraval, M; Robert, L; Robert, A M


    We investigated the hyaluronan content in the pathologic human venous wall using an ELSA assay with hyaluronectin according to the method of Delpech et al. The mean hyaluronan content in the 74 fragments from 12 venous walls studied was 596 +/- 528 ng/mg dry weight. These 12 venous walls could be separated in 3 distinct groups according to their hyaluronan content, low (277 +/- 141 ng/mg dry weight), moderate (552 +/- 361 ng/m dry weight) or high (1299 +/- 568 ng/mg dry weight). The differences between these groups are significant (p < 0.001). The presence of a veino-lymphatic oedema was generally associated with a high hyaluronan level (in 65% of cases). The 3H-glucosamine incorporation in cultured venous wall explants showed a 35% increase (p < 0.002) in varicosis as compared with the non or less modified segments of the vein and a 29% (p < 0.001) increase in presence of a veino-lymphatic oedema. The addition of 1 mg/ml of PCO (Procyanidolic Oligomers) to the culture media induced near to 20% decrease of the 3H-glucosamine incorporation and a 34% decrease of the hyaluronan content. Our results confirm the role of local overproduction of hyaluronan in the establishment of oedema and the potential effect of PCO to counteract it.

  4. Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice. (United States)

    Ledesma, Maria Dolores; Prinetti, Alessandro; Sonnino, Sandro; Schuchman, Edward H


    Severe neurological involvement characterizes Niemann Pick disease (NPD) type A, an inherited disorder caused by loss of function mutations in the gene encoding acid sphingomyelinase (ASM). Mice lacking ASM, which mimic NPD type A, have provided important insights into the aberrant brain phenotypes induced by ASM deficiency. For example, lipid alterations, including the accumulation of sphingolipids, affect the membranes of different subcellular compartments of neurons and glial cells, leading to anomalies in signalling pathways, neuronal polarization, calcium homeostasis, synaptic plasticity, myelin production or immune response. These findings contribute to our understanding of the overall role of sphingolipids and their metabolic enzymes in brain physiology, and pave the way to design and test new therapeutic strategies for type A NPD and other neurodegenerative disorders. Some of these have already been tested in mice lacking ASM with promising results. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  5. Brain pathology in Niemann Pick disease type A: Insights from the acid sphingomyelinase knockout mice (United States)

    Ledesma, Maria Dolores; Prinetti, Alessandro; Sonnino, Sandro; Schuchman, Edward H.


    Severe neurological involvement characterizes Niemann Pick disease (NPD) type A, an inherited disorder caused by loss of function mutations in the gene encoding acid sphingomyelinase (ASM). Mice lacking ASM (ASMko), which mimic NPD type A, have provided important insights into the aberrant brain phenotypes induced by ASM deficiency. For example, lipid alterations, including the accumulation of sphingolipids, affect the membranes of different subcellular compartments of neurons and glial cells, leading to anomalies in signalling pathways, neuronal polarization, calcium homeostasis, synaptic plasticity, myelin production or immune response. These findings contribute to our understanding of the overall role of sphingolipids and their metabolic enzymes in brain physiology, and pave the way to design and test new therapeutic strategies for type A NPD and other neurodegenerative disorders. Some of these have already been tested in ASMko mice with promising results. PMID:21214563

  6. 复方硼酸含漱液的药理毒理学研究%Pharmacological and toxicological research of compound boric acid gargle

    Institute of Scientific and Technical Information of China (English)



    ObjectiveTo investigate pharmacology and toxicology of compound boric acid gargle. MethodsA total of 60 rats as study subjects were randomly divided into normal saline group, aspirin group, low, moderate and high compound borax solution groups, with 12 cases in each group. Another 12 rats were taken in acute toxicity test of compound borax solution. Anti-inflammatory, analgesic and bacteriostatic effects by compound borax solution were observed by hot plate test, writhing test and antibacterial experiment in vitro in xylene-induced rat auricle edema and carrageenin-induced rat toe inflammation models. Experimental findings were observed.Results Compound borax solution showed remarkable inhibiting effect on xylene-induced rat auricle edema, and its difference with the normal saline had statistical significance (P<0.05). The difference of improved pain threshold proportion in various compound borax solution dosage groups had statistical significance with the normal saline group (P<0.05). Compound borax solution showed good inhibiting and bactericidal effect on staphylococcus aureus and group A streptococcus, along with high safety and low toxicity.ConclusionCompound boric acid gargle provides remarkable anti-inflammatory, analgesic, and bactericidal effects. It can accelerate early rehabilitation in patients, with precise curative effect and low toxicity.%目的:探讨复方硼酸含漱液的药理毒理学。方法60只小鼠为实验对象,随机分为生理盐水组、阿司匹林组、复方硼酸含漱液低、中、高组,各12只。另选取12只大鼠进行复方硼酸含漱液急性毒性试验。采用二甲苯所致的小鼠耳廓肿胀和角叉菜胶所致大鼠足趾炎症模型、热板法、扭体法以及体外抑菌试验,观察复方硼酸含漱液的抗炎、镇痛以及抑菌作用。观察实验结果。结果复方硼酸含漱液对二甲苯所致的小鼠耳廓肿胀有显著的抑制作用,与生理盐水组比较

  7. TOXNET: Toxicology Data Network (United States)

    ... for over 600 chemicals from authoritative groups worldwide Animal Testing Alternatives ALTBIB Resources on Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing Archived, No Longer Updated ... cancer tests (1980-2011) GENE-TOX Genetic Toxicology ...

  8. 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.

  9. 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.

  10. 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....

  11. 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....

  12. Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation. (United States)

    Maurer, H H; Tauvel, F X; Kraemer, T


    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic and anti-rheumatic drugs, and they are often misused. A gas chromatographic-mass spectrometric (GC-MS) screening procedure was developed for their detection in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons after extractive methylation. The compounds were separated by capillary GC and identified by computerized MS in the full-scan mode. Using mass chromatography with the ions m/z 119, 135, 139, 152, 165, 229, 244, 266, 272, and 326, the possible presence of NSAIDs and their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. This method allowed the detection of therapeutic concentrations of acemetacin, acetaminophen (paracetamol), acetylsalicylic acid, diclofenac, diflunisal, etodolac, fenbufen, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, indometacin, kebuzone, ketoprofen, lonazolac, meclofenamic acid, mefenamic acid, mofebutazone, naproxen, niflumic acid, phenylbutazone, suxibuzone, tiaprofenic acid, tolfenamic acid, and tolmetin in urine samples. The overall recoveries of the different NSAIDs ranged between 50 and 80% with coefficients of variation of less than 15% (n = 5), and the limits of detection of the different NSAIDs were between 10 and 50 ng/mL (S/N = 3) in the full-scan mode. Extractive methylation has proved to be a versatile method for STA of various acidic drugs, poisons, and their metabolites in urine. It has also successfully been used for plasma analysis.

  13. 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.

  14. 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

  15. 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

  16. 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)

  17. 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.

  18. Aspectos toxicológico, clínico-patológico e ultraestrutural das intoxicações iatrogênica e experimental por vitamina D em coelhos Toxicological, clinic-pathological and ultrastructural aspects of iatrogenic and experimental poisoning by vitamin D in rabbits

    Directory of Open Access Journals (Sweden)

    Paulo V. Peixoto


    Full Text Available São descritos aspectos toxicológicos, clínico-patológicos e ultraestruturais de coelhos intoxicados iatrogênica e experimentalmente por vitamina D por via subcutânea. Clinicamente, os animais evidenciaram sinais de insuficiência cardiovascular como ascite e edema pulmonar, hiporexia, anorexia, diarréia mucosa, emagrecimento e apatia. As clássicas alterações de mineralização e, por vezes, osseificação, do sistema cardiovascular, bem como as alterações de rins, pulmões, estômago, entre outros órgãos, foram reproduzidas com administrações subcutâneas de solução oleosa de colecalciferol (vitamina D3 não-ativada.Toxicological, clinic-pathological and ultrastructural aspects of iatrogenic and experimental subcutaneous poisoning in rabbits by vitamin D are described. Clinically the animals showed signs of cardiovascular insufficiency, as ascite and lung edema, hyporexia, anorexia, mucous diarrhoea, loss of weight and apathy. The classical alterations of minera-lization and, occasionally, ossification of the cardiovascular system, as well the lesions of kidneys, lungs, stomach, among other organs, were reproduced by the subcutaneous administration of an oily solution of cholecalciferol (non-activated vitamin D3.

  19. Veterinary Forensic Toxicology. (United States)

    Gwaltney-Brant, S M


    Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.

  20. 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.

  1. Prevalence and symptom pattern of pathologic esophageal acid reflux in patients with functional dyspepsia based on the Rome III criteria. (United States)

    Xiao, Ying-Lian; Peng, Sui; Tao, Jin; Wang, An-Jiang; Lin, Jin-Kun; Hu, Pin-Jin; Chen, Min-Hu


    To determine the prevalence and symptom pattern of pathologic esophageal acid reflux (PEAR) in patients with functional dyspepsia (FD) using the Rome III criteria, and to explore the value of a proton pump inhibitor (PPI) test in distinguishing the patients with and those without PEAR among FD patients. Consecutive FD patients who fulfilled the Rome III criteria without predominant typical reflux symptoms (i.e., heartburn or regurgitation) were enrolled. All patients underwent upper endoscopy and an ambulatory 24-h pH monitoring. PEAR was defined as the percentage total time for which a pH value 4.2% in the distal esophagus. Then, patients were treated with rabeprazole 10 mg twice daily for 28 days. The symptom scores were measured by the frequency score multiplied by the severity scores of the predominant symptom before and at the end of the treatment, and the "PPI test" was defined as positive if the overall scores of the predominant dyspeptic symptom in the fourth week decreased by >50% compared with those of the baseline. One hundred eighty-six FD patients were enrolled, with predominant symptoms of epigastric pain (n=68), epigastric burning (n=47), bothersome postprandial fullness (n=54), and early satiation (n=17). The prevalence of PEAR was 31.7%, with the highest percentage (48.9%) in patients with epigastric burning as their predominant symptom. The prevalence of PEAR in patients with postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were 36.6% (26/71) and 28.7% (33/115), respectively. Overall, 63.4% were positive for the "PPI test"; the rates were 51.5, 85.0, 66.7, and 41.1% in patients with epigastric pain, epigastric burning, bothersome postprandial fullness, and early satiation as their predominant symptoms, respectively (χ(2)=17.59, P=0.001). The positive rates were 65.5 and 60.6% in patients with PDS and EPS, respectively (χ(2)=0.41, P=0.522). The sensitivity and specificity of the "PPI test" in distinguishing FD patients with

  2. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment. (United States)

    Chamanza, R; Wright, J A


    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man.

  3. 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...

  4. 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.

  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 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

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



  8. Course constructions: A case-base of forensic toxicology. (United States)

    Zhou, Nan; Wu, Yeda; Su, Terry; Zhang, Liyong; Yin, Kun; Zheng, Da; Zheng, Jingjing; Huang, Lei; Wu, Qiuping; Cheng, Jianding


    Forensic toxicology education in China is limited by insufficient teaching methods and resources, resulting in students with adequate theoretical principles but lacking practice experience. Typical cases used as teaching materials vividly represent intoxication and provide students with an opportunity to practice and hone resolving skills. In 2013, the Department of Forensic Pathology at Zhongshan School of Medicine began to construct top-quality courses in forensic toxicology, with its first step, creating a base containing typical cases of intoxication. This essay reviews the construction process of said cases-base, which is intended to set an example of forensic toxicology education. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  9. Lymphoid Tissue and Pathological Influences of Toxicants

    NARCIS (Netherlands)

    Schaudien, D.; Harleman, H.; Bouallala, F.; Kuper, C. F.


    Toxicologic pathology plays a crucial role in the identification and interpretation of substance-induced health effects. Histology of lymphoid organs is quite sensitive, although it does not flag every model immunotoxic substance. Subtle interferences of toxic compounds, like transmembrane signaling

  10. 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.

  11. History of wildlife toxicology. (United States)

    Rattner, Barnett A


    The field of wildlife toxicology can be traced to the late nineteenth and early twentieth centuries. Initial reports included unintentional poisoning of birds from ingestion of spent lead shot and predator control agents, alkali poisoning of waterbirds, and die-offs from maritime oil spills. With the advent of synthetic pesticides in the 1930s and 1940s, effects of DDT and other pesticides were investigated in free-ranging and captive wildlife. In response to research findings in the US and UK, and the publication of Silent Spring in 1962, public debate on the hazards of pollutants arose and national contaminant monitoring programs were initiated. Shortly thereafter, population-level effects of DDT on raptorial and fish-eating birds were documented, and effects on other species (e.g., bats) were suspected. Realization of the global nature of organochlorine pesticide contamination, and the discovery of PCBs in environmental samples, launched long-range studies in birds and mammals. With the birth of ecotoxicology in 1969 and the establishment of the Society of Environmental Toxicology and Chemistry in 1979, an international infrastructure began to emerge. In the 1980s, heavy metal pollution related to mining and smelting, agrichemical practices and non-target effects, selenium toxicosis, and disasters such as Chernobyl and the Exxon Valdez dominated the field. Biomarker development, endocrine disruption, population modeling, and studies with amphibians and reptiles were major issues of the 1990s. With the turn of the century, there was interest in new and emerging compounds (pharmaceuticals, flame retardants, surfactants), and potential population-level effects of some compounds. Based upon its history, wildlife toxicology is driven by chemical use and misuse, ecological disasters, and pollution-related events affecting humans. Current challenges include the need to more thoroughly estimate and predict exposure and effects of chemical-related anthropogenic

  12. 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.

  13. Postmortem Biochemistry and Toxicology

    Directory of Open Access Journals (Sweden)

    Robert Flanagan


    Full Text Available The aim of postmortem biochemistry and toxicology is either to help establish the cause of death, or to gain information on events immediately before death. If self-poisoning is suspected, the diagnosis may be straightforward and all that could be required is confirmation of the agents involved. However, if the cause of death is not immediately obvious then suspicion of possible poisoning or of conditions such as alcoholic ketoacidosis is of course crucial. On the other hand, it may be important to investigate adherence to prescribed therapy, for example with anticonvulsants or antipsychotics, hence sensitive methods are required. Blood sampling (needle aspiration, peripheral vein, for example femoral, ideally after proximal ligation before opening the body minimizes the risk of sample contamination with, for example, gut contents or urine. Other specimens (stomach contents, urine, liver, vitreous humor may also be valuable and may be needed to corroborate unexpected or unusual findings in the absence of other evidence. The site of sampling should always be recorded. The availability of antemortem specimens should not necessarily preclude postmortem sampling. Appropriate sample preservation, transport, and storage are mandatory. Interpretation of analytical toxicology results must take into account what is known of the pharmacokinetics and toxicology of the agent(s in question, the circumstances under which death occurred including the mechanism of exposure, and other factors such as the stability of the analyte(s and the analytical methods used. It is important to realise that changes may occur in the composition of body fluids, even peripheral blood, after death. Such changes are likely to be greater after attempted resuscitation, and with centrally-acting drugs with large volumes of distribution given chronically, and may perhaps be minimised by prompt refrigeration of the body and performing the autopsy quickly.

  14. [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.

  15. 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)

  16. [The relationship of the acid-base status of the blood to the electrophoretic mobility of the erythrocytes in liver pathology]. (United States)

    Matiushichev, V B; Shamratova, C G; Gutsaeva, D R


    With cholestatic hepatite, the relationship between acid-alkaline condition of blood and electrophoretic mobility of erythrocytes was studied. It is shown that changes in parameters of the individual mobility distribution are translated into reality independently, and are directed to maintain the steadiness of the index middle level. Dependence of this sign on the pH value, hemoglobin content and bicarbonate-ion concentrating in blood, an on partial pressure of oxygen and carbonic gas was discovered. The intravenous infusion of patients with hemodese restored the middle level of cell electrophoretic mobility previously reduced due to liver pathology. Membrane mechanisms controlling stability of erythrocyte electrokinetic characteristics are discussed.

  17. Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium alborcoremium: chemotaxonomic significance and pathological implications

    DEFF Research Database (Denmark)

    Overy, David Patrick; Larsen, Thomas Ostenfeld; Dalsgaard, P.W.;


    of a barceloneic acid being produced as a secondary metabolite. Tissue extracts created following pathogenicity trials involving P. albocoremium and Allium cepa confirmed the production of these five metabolites in planta. Barceloneic acid B was found to be biologically active against a P388 murine leukemia cell...

  18. Osler's pathology. (United States)

    Pai, S A


    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  19. [Pathological jealousy]. (United States)

    Zacher, A


    Pathological jealousy can make life unbearable for all concerned. The proximity of this condition to obsessive-compulsive phenomena has given rise to the notion that it might respond to substances of proven value in the treatment of obsessive-compulsive disorders. This case history exemplifies the successful treatment of pathological jealousy with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The substance not only proved to be a successful antidepressant, but also effectively mitigated the anguish of the patient's pathological jealousy. On the basis of these findings, fluoxetine--as also other SSRIs--should always be considered as a possible effective pharmacological strategy for the treatment of pathological jealousy.

  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. 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.

  2. 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.

  3. Experimental water toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Andrushaytis, G.P. (ed.)


    The problem of water toxicology and marine ectoxicology, particularly in the Baltic Sea and the Gulf of Riga, are discussed. Emphasis is placed on the problem of creating artificial controlled marine ecosystems for the purpose of utilizing them in ecotoxicological studies and for solving problems in the intensification of bioproduction processes and predicting the functional state of water ecosystems under conditions of water pollution by toxic substances. Investigations were conducted on the effects of pesticides, phenols, and heavy metal ions on planktonic crustacea and fish. Studies were also concerned with the effect of gonadotoxic substances, including detergents, on the gametogenesis process in fish. Morphological changes in the ovicells of fish can lead to a reduction in the sensitivity of the receptor zones of the follicular casings to hormonal substances, as well as infertility.

  4. 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.


    In order to develop a scientifically defensible assessment of the risk for the development of cancer after long-term exposure to xenobiotics, regulatory agencies have adopted a uniform approach which includes the characterization of a carcinogenic mode of action and its biologica...

  6. Toxicologic pathology in a multicultural world--India. (United States)

    Schultze, A Eric; Reddy, Vijayapal R; Donnelly, Kevin B; Berridge, Brian R


    The global practice of drug development is expanding into many different continents and countries. India, in particular, is rapidly emerging as an economic force in this arena by offering ever-expanding opportunities for pharmaceutical market expansion as well as productive drug development partnerships. The key to the country's current socioeconomic success appears to be education, particularly the development of higher and professional education. Also, recent modifications to India's patent laws offer greater protections and incentives for international investment. Increasing numbers of competent contract research organizations create attractive opportunities for large Western pharmaceutical companies with a desire to gain access to burgeoning markets as well as mitigate the rising cost of drug development with less costly services. Well-trained veterinary pathologists are available, appropriate facilities are being constructed, and laboratory capabilities are expanding. Developing a productive partnership with a credible laboratory service in India, as with any new provider, requires due diligence and knowledgeable scrutiny of key elements of the work stream, such as facilities, education and training of laboratory personnel, Good Laboratory Practices, animal care, timelines, and data management. Ultimately and with appropriate management, mutually beneficial drug development partnerships are available in India.

  7. Molecular mechanism study on the toxicological effects of polybrominated diphenyl ethers and perfluoroalkyl acids%多溴联苯醚和全氟烷基酸的分子毒理机制研究

    Institute of Scientific and Technical Information of China (English)

    任肖敏; 张连营; 郭良宏


    Polybrominated diphenyl ethers ( PBDEs) and perfluoroalkyl acids ( PFAAs) are two groups of persistent organic pollutants ( POPs ) which are widely used, broadly existing in the environment, and frequently detected in humans. In 2009 they were added to the POPs list of the Stockholm Convention. However, the toxicological effects and mechanisms of PBDEs and PFAAs are still not well understood. This review summarizes our recent work on the studies of molecular toxicological mechanisms of PBDEs and PFAAs, focusing on their disruption effects on thyroid hormone system, estrogen system and hepatic fatty acid metabolism system. From the molecular, cellular and in vivo level, we investigated the direct binding interaction of these chemicals with hormone nuclear receptors, receptor conformational change after ligand binding, receptor mediated transcriptional activity in cells, and change of gene expression in experimental animals. Based on the results, we established a direct link between receptor binding and change of biological functions in cells and in vivo. Using molecular docking, we investigated the structural basis for the observed agonistic or antagonistic activity. It was found that their activity was determined by the binding geometry with the receptor, and their potency depended on the binding affinity with the protein, which were dominated by the hydrophobic and hydrogen-bond interactions. We also studied the binding interaction of these chemicals with transport proteins, and estimated their potential disruption effect on the in vivo transport of endogenous substances. Through these studies, we put forward a multi-level, multi-target strategy for the investigation of molecular toxicological mechanisms of POPs, established and introduced new methods for the study of POPs interactions with biological macromolecules, identified new binding modes of PBDEs and PFAAs with ER, TR and PPARγnuclear receptors. Our work has provides new information on the molecular

  8. 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. ...

  9. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo


    .... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

  10. 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...

  11. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions. (United States)

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G


    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  12. Mineral Fiber Toxicology (United States)

    The chemical and physical properties of different forms of mineral fibers impact biopersistence and pathology in the lung. Fiber chemistry, length, aspect ratio, surface area and dose are critical factors determining mineral fiber-associated health effects including cancer and as...

  13. Toxicology of drinking water disinfection byproducts from nutrients. Rate studies of destruction of polyunsaturated fatty acids in vitro by chlorine-based disinfectants. (United States)

    Bercz, J P


    As model reactions between unsaturated fats and water disinfectants in the GI tract, relative rates of destruction of seven polyunsaturated fatty acids (L, alpha Ln, gamma Ln, Ara, EPA, DH, and DT) by OCl- and NH2Cl were investigated in vitro. Using millimolar solutions of seven PUFAs combined with various OCl- mole ratios, disappearance of PUFAs was followed by UV spectrophotometry at pH = 9.5 and at 35 degrees C via conjugated hydroperoxydienes at 234 nm. While OCl- rapidly destroyed all PUFAs, NH2Cl was inert. Overall second-order rate constants computed for L at increasing times disclosed that the attack on the cis-CH=CHCH2CH=CH moiety by OCl- does not follow simple second-order kinetics. Using a logit-log transform and second-order polynomial regression analysis of L's disappearance in a stoichiometric ([L] = 1.2 mM; [ClO-] = 2.4 mM) mix, data were analyzed by the time ratio method of Schwemer and Frost. These agreed with a sequential system of at least two irreversible second-order reactions having k1 = 15.6 L.mol-1.s-1 and k2 = 2.6 L.mol-1.s-1. Preliminary GC/MS analysis indicated that the initial product is a mix of chlorohydrin isomers. These undergo second addition of HOCl and/or lose halogens and polymerize. Additional minor products were also C5-C9 mono- and bifunctional carboxylates and mixed acid aldehydes. Studies with mol equiv of Cl- - free 36ClO- allowed estimation of covalent binding of Cl by L at various times, supporting the kinetic findings. For other PUFAs of higher degree unsaturation, the complexity of feasible reactions precluded an analogous approach.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. 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.

  15. 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

  16. Oral pathology. (United States)

    Niemiec, Brook A


    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  17. Pathology Milestones

    Directory of Open Access Journals (Sweden)

    J. Stacey Klutts MD, PhD


    Full Text Available All Accreditation Council for Graduate Medical Education accredited pathology residency training programs are now required to evaluate residents using the new Pathology Milestones assessment tool. Similar to implementation of the 6 Accreditation Council for Graduate Medical Education competencies a decade ago, there have been challenges in implementation of the new milestones for many residency programs. The pathology department at the University of Iowa has implemented a process that divides the labor of the task in rating residents while also maintaining consistency in the process. The process is described in detail, and some initial trends in milestone evaluation are described and discussed. Our experience indicates that thoughtful implementation of the Pathology Milestones can provide programs with valuable information that can inform curricular changes.

  18. Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. (United States)

    Mori, Takashi; Rezai-Zadeh, Kavon; Koyama, Naoki; Arendash, Gary W; Yamaguchi, Haruyasu; Kakuda, Nobuto; Horikoshi-Sakuraba, Yuko; Tan, Jun; Town, Terrence


    Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-β (Aβ) peptides that form β-amyloid plaques in brains of Alzheimer disease (AD) patients. Recent focus has been directed toward a group of naturally occurring anti-amyloidogenic polyphenols known as flavonoids. We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. Consumption of TA for 6 months prevented transgene-associated behavioral impairment including hyperactivity, decreased object recognition, and defective spatial reference memory, but did not alter nontransgenic mouse behavior. Accordingly, brain parenchymal and cerebral vascular β-amyloid deposits and abundance of various Aβ species including oligomers were mitigated in TA-treated PSAPP mice. These effects occurred with decreased cleavage of the β-carboxyl-terminal APP fragment, lowered soluble APP-β production, reduced β-site APP cleaving enzyme 1 protein stability and activity, and attenuated neuroinflammation. As in vitro validation, we treated well characterized mutant human APP-overexpressing murine neuron-like cells with TA and found significantly reduced Aβ production associated with less amyloidogenic APP proteolysis. Taken together, these results raise the possibility that dietary supplementation with TA may be prophylactic for AD by inhibiting β-secretase activity and neuroinflammation and thereby mitigating AD pathology.

  19. Interactions of diorganolead(IV) with 3-(2-thienyl)-2-sulfanylpropenoic acid and/or thiamine: chemical and in vitro and in vivo toxicological results. (United States)

    Casas, José S; Castaño, M Victoria; Sánchez, Agustín; Sordo, José; Torres, M Dolores; Couce, María D; Gato, Angeles; Alvarez-Lorenzo, Carmen; Camiña, M Félix; Castellano, Eduardo E


    The reactions of PbR(2)(OAc)(2) (R = Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H(2)tspa) in methanol or ethanol afforded complexes [PbR(2)(tspa)] that electrospray ionization-mass spectrometry (ESI-MS) and IR data suggest are polymeric. X-ray studies showed that [PbPh(2)(tspa)(dmso)] x dmso, crystallized from a solution of [PbPh(2)(tspa)] in dmso, is dimeric, and that [HQ](2)[PbPh(2)(tspa)(2)] (Q = diisopropylamine), obtained after removal of [PbPh(2)(tspa)] from a reaction including Q, contains the monomeric anion [PbPh(2)(tspa)(2)](2-). In the solid state the lead atoms are O,S-chelated by the tspa(2-) ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa(2-) remains coordinated to PbR(2)(2+) in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe(2)(NO(3))(2) in D(2)O. Prior addition of H(2)tspa protected LLC-PK1 renal proximal tubule cells against PbMe(2)(NO(3))(2); thiamine had no statistically significant effect by itself, but greatly potentiated the action of H(2)tspa. Administration of either H(2)tspa or thiamine to male albino Sprague-Dawley rats dosed 30 min previously with PbMe(2)(NO(3))(2) was associated with reduced inhibition of delta-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H(2)tspa and thiamine only lowered lead concentration in the kidney.

  20. 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.

  1. High dietary consumption of trans fatty acids decreases brain docosahexaenoic acid but does not alter amyloid-beta and tau pathologies in the 3xTg-AD model of Alzheimer's disease. (United States)

    Phivilay, A; Julien, C; Tremblay, C; Berthiaume, L; Julien, P; Giguère, Y; Calon, F


    Dietary consumption of trans fatty acids (TFA) has increased during the 20th century and is a suspected risk factor for cardiovascular diseases. More recently, high TFA intake has been associated with a higher risk of developing Alzheimer's disease (AD). To investigate the impact of TFA on an animal model genetically programmed to express amyloid-beta (Abeta) and tau pathological markers of AD, we have fed 3xTg-AD mice with either control (0% TFA/total fatty acid), high TFA (16% TFA) or very high TFA (43% TFA) isocaloric diets from 2 to 16 months of age. Effects of TFA on plasma hepatic enzymes, glucose and lipid profile were minimal but very high TFA intake decreased visceral fat of non-transgenic mice. Importantly, dietary TFA increased brain TFA concentrations in a dose-related manner. Very high TFA consumption substantially modified the brain fatty acid profile by increasing mono-unsaturated fatty acids and decreasing polyunsaturated fatty acids (PUFA). Very high TFA intake induced a shift from docosahexaenoic acid (DHA, 22:6n-3) toward n-6 docosapentaenoic acid (DPA, 22:5n-6) without altering the n-3:n-6 PUFA ratio in the cortex of both control and 3xTg-AD mice. Changes in levels of Abeta(40), Abeta(42), tau protein, phosphorylated tau protein and synaptic markers were not statistically significant in the three groups of 3xTg-AD mice, despite a trend toward decreased insoluble tau in very high TFA-fed 3xTg-AD animals. In summary, TFA intake modulated brain fatty acid profiles but had no significant effect on major brain neuropathological hallmarks of AD in an animal model.

  2. 三聚氰胺(酸)对肾脏毒性的实验研究%Study the toxicology damage of melamine(cyanuric acid)to rats kidney

    Institute of Scientific and Technical Information of China (English)

    徐明灯; 袁心刚; 吴盛德; 魏光辉


    目的:研究三聚氰胺(酸)对肾脏的毒理损害.方法:将新生鼠和成年鼠分别分为三聚氰胺高剂量组(NM,M),三聚氰胺低剂量组(Nm,m),三聚氰酸高剂量组(NA,A),三聚氰酸低剂量组(Na,a),三聚氰胺-三聚氰酸高剂量组(NMA,MA),三聚氰胺-三聚氰酸低剂量组(Nma,ma)和正常对照组(NN,N).给予相应剂量三聚氰胺(酸)灌胃持续两月,于灌胃3、15、60 d随机处死各组大鼠,称取体重、肾重,检测血液常规生化指标;观测肾脏组织细胞形态和超微结构变化.结果:NMA组及Nma组体重先增加,然后减少.MA组及ma组体重持续减轻.各给药组随着灌胃时间延长,肾脏晶体不断增加.电镜显示含结石肾小管微绒毛减少或消失,粒细胞浸润等炎性反应.各给药组随着灌胃时间的延长,肾体重比、尿素氮、肌酐、尿酸值增加.结论:三聚氰胺(酸)可以在大鼠肾脏形成晶体样结石;三聚氰胺(酸)成年鼠的肾毒性大于新生鼠;三聚氰胺(酸)混合物毒性大于单体;三聚氰胺(酸)形成晶体数量与时间、剂量呈正相关;三聚氰胺(酸)毒性存在个体及窝别差异.%Objective: Study the toxicology damage of melamine (cyanuric acid) to rats' kidney. Methods:Divided the newborn rats and adult rats into high dose group of melamine (NM, M), low dose group of melamine (Nm, m), high dose group of oyanuric acid (NA, A), low dose group of cyanuric acid (Na,a),high dose group of melamine-cyanuric acid (NMA,MA),Iow dose group of melamine-cyanuric acid (Nma,ma) and normal control group (NN,N). The corresponding dose of melamine (cyanuric acid) was given by oral gavage and lasted two months. Rats were killed at 3 day, 15 day and 60 day. The body weight and kidney weight were collected. Renal function was detected and the microscopic and ultra-microscopic renal histology structural changes were observed. Results: The body weight of NMA group and Nma group increased first,and then reduced. The body weight of MA

  3. 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.

  4. Digital pathology

    CERN Document Server

    Sucaet, Yves


    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  5. Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/MpJ-Fas(lpr) mice. (United States)

    Bergamo, Paolo; Luongo, Diomira; Maurano, Francesco; Mazzarella, Giuseppe; Stefanile, Rosita; Rossi, Mauro


    Conjugated linoleic acid (CLA), a naturally occurring peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, exhibits proapoptotic, immunomodulatory, and anticancer properties. In this study, we examined the biological effects of CLA administration in the MRL/MpJ-Fas(lpr) mouse, an animal model of systemic lupus erythematosus (SLE). We found that CLA exerted apparently opposed activities in in vitro experiments, depending on its concentration: 100 microM CLA downregulated IFN gamma synthesis and cell proliferation of splenocytes, in association with apoptosis induction and a decrease of intracellular thiols (GSH + GSSG), whereas 25 microM CLA did not significantly influence cell proliferation but enhanced the expression of gamma-glutamylcysteine ligase catalytic subunit (GCLC) and intracellular GSH concentration. Interestingly, the antiproliferative effect at 100 microM was not inhibited by the PPAR gamma antagonist GW9662. In vivo, CLA administration drastically reduced SLE signs (splenomegaly, autoantibodies, and cytokine synthesis), a condition paralleled by the enhancement of GCLC expression and intracellular GSH content. Moreover, CLA administration significantly downregulated nuclear factor kappaB activity independent of PPAR gamma activation and apoptosis induction. In conclusion, enhanced GSH content and GCLC expression in CLA-treated mice suggest a novel biochemical mechanism underlying its immunomodulatory activity and the beneficial effects on murine SLE signs.

  6. Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: Correlation with clinical and pathological features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young [Department of Radiology and Research Institute of Radiological Science, Yonsei University Severance Hospital, Seoul (Korea, Republic of); Kim, Myeong-Jin, E-mail: [Department of Radiology and Research Institute of Radiological Science, Yonsei University Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Ah; Jeong, Hyeon Tae [Department of Radiology and Research Institute of Radiological Science, Yonsei University Severance Hospital, Seoul (Korea, Republic of); Park, Young Nyun [Department of Pathology, Yonsei University Severance Hospital, Seoul (Korea, Republic of)


    Purpose: To retrospectively determine whether the hyperintense hepatocellular carcinomas (HCCs) seen on the hepatobiliary phase of gadoxetic acid-enhanced MR imaging (EOB-MRI) might have different histologic characteristics from usual hypointense HCCs. Materials and methods: Two hundred three surgically proven HCCs from 192 patients who underwent preoperative EOB-MRI were analyzed. The demographic and histologic characteristics of hyperintense HCCs were compared with usual hypointense HCCs by using the t-test or Fisher's exact test. Results: By visual assessment, 18 (8.8%) tumors were classified as hyperintense HCCs. Patients with hyperintense HCC were significantly (p < 0.05) older (60.1 vs. 55.2 years) than those with hypointense HCCs. Hyperintense HCCs showed significantly lower rate of microvascular invasion (27.8% vs. 53.5%) and significantly higher rate of peliosis (61.1% vs. 30.8%). Hyperintense HCCs were more frequently expanding type, and none showed infiltrative type or scirrhous histologic pattern. Conclusions: Hyperintense HCCs seem to have clinical and histologic features that might be related with more favorable outcomes.

  7. 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.

  8. 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...

  9. Inguinoscrotal pathology (United States)

    Guerra, Luis; Leonard, Michael


    Infants, children, and adolescents with inguinoscrotal pathology comprise a significant proportion of emergency department and outpatient visits. Visits to the emergency department primarily comprise individuals presenting with scrotal pain due to testicular torsion or torsion of the testicular appendages. At such time, immediate urological consultation is sought. Outpatient visits comprise those individuals with undescended testes, hydroceles, and varicoceles. Rare, but important problems, such as pediatric testicular tumours, may also present in the office setting. Many of these outpatient visits are to primary care physicians, who should have an appreciation of the timing and need for referral. The purpose of this review is to familiarize the general urologist and primary care physician with these varied pathologies and give insight into their assessment and management. Some of these same conditions are seen in adult patients, but there are some significant differences in their management in the pediatric group. In addition, the utility of imaging studies, such as ultrasound, are discussed within each pathological entity. It is hoped that this overview will assist our general urology and primary care colleagues in patient management for diverse inguinoscrotal pathologies. PMID:28265317

  10. 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...

  11. 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,...

  12. 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

  13. 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

  14. 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.

  15. Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Takashi Mori

    Full Text Available Amyloid precursor protein (APP proteolysis is required for production of amyloid-β (Aβ peptides that comprise β-amyloid plaques in brains of Alzheimer's disease (AD patients. Recent AD therapeutic interest has been directed toward a group of anti-amyloidogenic compounds extracted from plants. We orally administered the brain penetrant, small molecule phenolic compound ferulic acid (FA to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes and evaluated behavioral impairment and AD-like pathology. Oral FA treatment for 6 months reversed transgene-associated behavioral deficits including defective: hyperactivity, object recognition, and spatial working and reference memory, but did not alter wild-type mouse behavior. Furthermore, brain parenchymal and cerebral vascular β-amyloid deposits as well as abundance of various Aβ species including oligomers were decreased in FA-treated PSAPP mice. These effects occurred with decreased cleavage of the β-carboxyl-terminal APP fragment, reduced β-site APP cleaving enzyme 1 protein stability and activity, attenuated neuroinflammation, and stabilized oxidative stress. As in vitro validation, we treated well-characterized mutant human APP-overexpressing murine neuron-like cells with FA and found significantly decreased Aβ production and reduced amyloidogenic APP proteolysis. Collectively, these results highlight that FA is a β-secretase modulator with therapeutic potential against AD.

  16. 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.

  17. A rapid method for determining arachidonic:eicosapentaenoic acid ratios in whole blood lipids: correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies

    Directory of Open Access Journals (Sweden)

    Corsetto Paola


    Full Text Available Abstract Background Omega-3 and -6 polyunsaturated fatty acids (LCPUFA, are important for good health conditions. They are present in membrane phospholipids. The ratio of total n-6:n-3 LCPUFA and arachidonic acid:eicosapentaenoic acid (AA and EPA, should not exceed 5:1. Increased intake of n-6 and decreased consumption of n-3 has resulted in much higher, ca 10/15:1 ratio in RBC fatty acids with the possible appearance of a pathological "scenario". The determination of RBC phospholipid LCPUFA contents and ratios is the method of choice for assessing fatty acid status but it is labour intensive and time consuming. Aims of the study [i] To describe and validate a rapid method, suitable for large scale population studies, for total blood fatty acid assay; [ii] to verify a possible correlation between total n-6:n-3 ratio and AA:EPA ratios in RBC phospholipids and in whole-blood total lipids, [iii] to assess usefulness of these ratio as biomarkers of LCPUFA status. Methods 1 Healthy volunteers and patients with various pathologies were recruited. 2 Fatty acid analyses by GC of methyl esters from directly derivatized whole blood total lipids and from RBC phospholipids were performed on fasting blood samples from 1432 subjects categorised according to their age, sex and any existing pathologies. AA:EPA ratio and the total n-6:n-3 ratio were determined. Results AA:EPA ratio is a more sensitive and reliable index for determining changes in total blood fatty acid and it is correlated with the ratio derived from extracted RBC phospholipids. Conclusions The described AA:EPA ratio is a simple, rapid and reliable method for determining n-3 fatty acid status.

  18. Toxicology of blast overpressure. (United States)

    Elsayed, N M


    Blast overpressure (BOP) or high energy impulse noise, is the sharp instantaneous rise in ambient atmospheric pressure resulting from explosive detonation or firing of weapons. Blasts that were once confined to military and to a lesser extent, occupational settings, are becoming more universal as the civilian population is now increasingly at risk of exposure to BOP from terrorist bombings that are occurring worldwide with greater frequency. Exposure to incident BOP waves can cause auditory and non-auditory damage. The primary targets for BOP damage are the hollow organs, ear, lung and gastrointestinal tract. In addition, solid organs such as heart, spleen and brain can also be injured upon exposure. However, the lung is more sensitive to damage and its injury can lead to death. The pathophysiological responses, and mortality have been extensively studied, but little attention, was given to the biochemical manifestations, and molecular mechanism(s) of injury. The injury from BOP has been, generally, attributed to its external physical impact on the body causing internal mechanical damage. However, a new hypothesis has been proposed based on experiments conducted in the Department of Respiratory Research, Walter Reed Army Institute of Research, and later in the Department of Occupational Health, University of Pittsburgh. This hypothesis suggests that subtle biochemical changes namely, free radical-mediated oxidative stress occur and contribute to BOP-induced injury. Understanding the etiology of these changes may shed new light on the molecular mechanism(s) of injury, and can potentially offer new strategies for treatment. In this symposium. BOP research involving auditory, non-auditory, physiological, pathological, behavioral, and biochemical manifestations as well as predictive modeling and current treatment modalities of BOP-induced injury are discussed.

  19. Nonclinical safety assessment of recombinant human acid sphingomyelinase (rhASM) for the treatment of acid sphingomyelinase deficiency:the utility of animal models of disease in the toxicological evaluation of potential therapeutics. (United States)

    Murray, James M; Thompson, Anne Marie; Vitsky, Allison; Hawes, Michael; Chuang, Wei-Lien; Pacheco, Joshua; Wilson, Stephen; McPherson, John M; Thurberg, Beth L; Karey, Kenneth P; Andrews, Laura


    Recombinant human acid sphingomyelinase (rhASM) is being developed as an enzyme replacement therapy for patients with acid sphingomyelinase deficiency (Niemann-Pick disease types A and B), which causes sphingomyelin to accumulate in lysosomes. In the acid sphingomyelinase knock-out (ASMKO) mouse, intravenously administered rhASM reduced tissue sphingomyelin levels in a dose-dependent manner. When rhASM was administered to normal rats, mice, and dogs, no toxicity was observed up to a dose of 30mg/kg. However, high doses of rhASM≥10mg/kg administered to ASMKO mice resulted in unexpected toxicity characterized by cardiovascular shock, hepatic inflammation, adrenal hemorrhage, elevations in ceramide and cytokines (especially IL-6, G-CSF, and keratinocyte chemoattractant [KC]), and death. The toxicity could be completely prevented by the administration of several low doses (3mg/kg) of rhASM prior to single or repeated high doses (≥20mg/kg). These results suggest that the observed toxicity involves the rapid breakdown of large amounts of sphingomyelin into ceramide and/or other toxic downstream metabolites, which are known signaling molecules with cardiovascular and pro-inflammatory effects. Our results suggest that the nonclinical safety assessment of novel therapeutics should include the use of specific animal models of disease whenever feasible.

  20. Toxicology of perfluorinated compounds

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)


    Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

  1. 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.

  2. 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.

  3. 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...

  4. 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…

  5. 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...

  6. 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.

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Regulatory forum opinion piece: blind reading of histopathology slides in general toxicology studies. (United States)

    Neef, Natasha; Nikula, Kristen J; Francke-Carroll, Sabine; Boone, Laura


    With the intention of reducing bias, a recent European Food Safety Authority draft guidance document included a recommendation for blinded evaluation of histopathology slides in general toxicology studies (EFSA 2011). Although blinding as to treatment status reduces bias in many types of scientific experiment and is sometimes also appropriate in toxicologic pathology (Holland and Holland 2011), it is most unlikely to help achieve the overall goal of improved human safety when used for routine histopathology evaluation of tissues in general toxicology studies. This is the case because (1) blinding is not applicable to the inductive reasoning process used to identify test article effects in the tissues and would dramatically reduce the chances of these being successfully identified; and (2) in any case, the bias that would be reduced by blinding is actually a bias favoring diagnosis of a toxicological hazard and a conservative safety evaluation, which is appropriate in this context. Other unintended consequences of blinding histopathology evaluation include reductions in sensitivity for a variety of additional reasons and increased subjectivity of the pathology data.

  19. 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.

  20. Curriculum Guidelines for Pathology and Oral Pathology. (United States)

    Journal of Dental Education, 1985


    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  1. Epidemiological Approaches to Metal Toxicology

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Budtz-Jørgensen, Esben


    to their propensity to cause chronic or delayed toxicity, epidemiological studies of metal toxicity have focused on a wide variety of organ systems, subtle effects as well as mortality, and differences in susceptibility. Toxic metals often serve as paradigms of environmental and occupational toxicity....... For these reasons, this chapter highlights the fields within epidemiology that are most relevant to toxic metals and discusses where these substances serve to illustrate important epidemiological concepts. Chapter sections include subjects such as epidemiological terms, study design, study population, exposure......Epidemiological methods are crucial to extract as much valid information as possible from human metal exposures. Thus, modern epidemiological approaches have elucidated human health effects that were not apparent in the past. At the same time, metal toxicology has served as a useful arena...

  2. 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.

  3. Anatomic viral detection is automated: the application of a robotic molecular pathology system for the detection of DNA viruses in anatomic pathology substrates, using immunocytochemical and nucleic acid hybridization techniques. (United States)

    Montone, K. T.; Brigati, D. J.; Budgeon, L. R.


    This paper presents the first automated system for simultaneously detecting human papilloma, herpes simplex, adenovirus, or cytomegalovirus viral antigens and gene sequences in standard formalin-fixed, paraffin-embedded tissue substrates and tissue culture. These viruses can be detected by colorimetric in situ nucleic acid hybridization, using biotinylated DNA probes, or by indirect immunoperoxidase techniques, using polyclonal or monoclonal antibodies, in a 2.0-hour assay performed at a single automated robotic workstation. Images FIG. 1 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 8 FIG. 9 FIG. 10 FIG. 11 PMID:2773514

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. Phytochemical, Toxicological and Pharmacological Studies of ...

    African Journals Online (AJOL)

    Phytochemical, Toxicological and Pharmacological Studies of Asiasari Radix et ... three species of the genus Asarum: A. heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag., ..... third-instar larvae of Culex pipiens pallens. Coquillett ...

  11. 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)

  12. 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.

  13. Data governance in predictive toxicology: A review

    National Research Council Canada - National Science Library

    Fu, Xin; Wojak, Anna; Neagu, Daniel; Ridley, Mick; Travis, Kim


    .... In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise...

  14. Comparative toxicology of intentional and accidental heroin overdose. (United States)

    Darke, Shane; Duflou, Johan; Torok, Michelle


    The demographic and toxicological characteristics of deliberate (SUI, n = 50) and accidental (ACC, n = 927) fatal heroin overdose cases were examined. SUI cases were more likely to be female, had lower body mass indices, were more likely to be enrolled in treatment and less likely to have hepatic pathology. The median blood morphine concentration of SUI cases was significantly higher than that of ACC cases (0.70 vs. 0.40 mg/L, p 1 mg/L were seen among 38.0% of SUI cases compared to 13.9% of ACC cases. Being a member of the SUI group remained a significant independent predictor of higher morphine concentrations after controlling for the effects of potential confounders (p cocaine (p overdose cases, rather than overdose being a parasuicidal phenomenon per se.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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....

  20. 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. PMID:17579968

  1. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B


    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  2. [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.

  3. [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.

  4. 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.

  5. 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.

  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. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  7. Forensic Pathology Education in Pathology Residency (United States)

    Ross, Wayne K.; Domen, Ronald E.


    Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

  8. Data governance in predictive toxicology: A review. (United States)

    Fu, Xin; Wojak, Anna; Neagu, Daniel; Ridley, Mick; Travis, Kim


    Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity) and not in a toxicological sense (e.g. the quality of experimental results). This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality) and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas) of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper, data governance is identified as the new challenge in

  9. Immunology for the toxicologic pathologist. (United States)

    Snyder, Paul W


    The immune system functions primarily as a defense mechanism to provide protective immunity against microbial pathogens and cancer. The resulting protective responses occur through the complex interaction of tissues, cells, proteins, and molecular pathways that act in concert with other systems (e.g., nervous and endocrine) to provide the host with immunologic responses that cause pathologic processes seen primarily as inflammatory reactions. The pathologic responses can be attributed to either normal responses to infectious organisms and cancer cells, misdirected responses as in the case of hypersensitivity or autoimmune diseases, or deficient responses attributable to deficiencies or defects in components of the immune system. Pathologists need to have a basic understanding of the immune system to not only interpret findings as to their likely pathogenesis, but also to predict when the immune system may be a potential target. This review will be limited to a general overview of the basic immunologic responses and primary components involved.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Combination of acid phosphatase positivity and rimmed vacuoles as useful markers in the diagnosis of adult-onset Pompe disease lacking specific clinical and pathological features

    Directory of Open Access Journals (Sweden)

    Claire Dolfus


    Full Text Available Introduction: The clinical and histological presentations of the adult form of Pompe disease may be atypical. In such cases, identifying histological signs that point to the diagnosis would be crucial to avoid a delay in care. The aim of our study was to investigate the presence of rimmed vacuoles and acid phosphatase positivity in muscle biopsies of patients with late-onset Pompe disease. Material and methods: We retrospectively studied muscle biopsies of all cases of the adult form of Pompe disease diagnosed at the University Hospital of Caen. Three of these four cases showed atypical clinical signs, and diagnosis was established tardily based on family history or systematic analysis of acid maltase activity. Results: All biopsies showed some rimmed vacuoles. The acid phosphatase reaction showed positive inclusions and labelled vacuoles in biopsies of all patients. Conclusions: The presence of rimmed vacuoles and acid phosphatase positivity in muscle biopsy should suggest the diagnosis of the adult form of Pompe disease, this is decisive since effective therapy is available.

  15. 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...

  16. Reviews of environmental contamination and toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Ware, G. (ed.)


    Review of Environmental Contamination and Toxicology attempts to provide concise, critical reviews of timely advances, philosophy and significant areas of accomplished or needed endeavour in the total field of xenobiotics, in any segment of the environment, as well as toxicological implications. This edition contains a paper 'Health effects of arsenic, fluorine and selenium from indoor burning of Chinese coal, by Liu Guijian, Zheng Liugen, Nurdan S. Duzgoren-Aydin, Gao Lianfen, Liu Junhua, and Peng Zicheng. Other papers are: Chemistry and fate of simazine; Ethanol production: energy, economic, and environmental losses; Arsenic behaviour from groundwater and soil to crops: impacts on agriculture and food safety; Mercury content of hair in different populations relative to fish consumption; and Toxicology of 1,3-butadiene, chloroprene, and isoprene. 15 ills.

  17. Best practices for clinical pathology testing in carcinogenicity studies. (United States)

    Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L


    The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

  18. 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.

  19. 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.

  20. Toxicology and metabolism of nickel compounds. Progress report, December 1, 1975--November 30, 1976. [Tests made with rats and hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.


    The toxicology and metabolism of nickel compounds (NiCl/sub 2/, Ni/sub 3/S/sub 2/, NiS, Ni powder, and Ni(CO)/sub 4/) were investigated in rats and hamsters. Triethylenetetramine (TETA) and d-penicillamine are more effective than other chelating agents (Na-diethyldithiocarbamate, CaNa/sub 2/-versenate, diglycylhistidine-N-methylamide and ..cap alpha..-lipoic acid) as antidotes for acute Ni(II)-toxicity in rats. The antidotal efficacy of triethylenetetramine (TETA) in acute Ni(II)-toxicity is mediated by rapid reduction of the plasma concentration of Ni(II), consistent with renal clearance of the TETA-Ni complex at a rate more than twenty times greater than the renal clearance of non-chelated Ni(II). Fischer rats are more susceptible than other rat strains (Wistar-Lewis, Long-Evans and NIH-Black) to induction of erythrocytosis after an intrarenal injection of Ni/sub 3/S/sub 2/, and elucidation of the serial pathologic changes that occur in rats after an intrarenal injection of Ni/sub 3/S/sub 2/. When amorphous nickel monosulfide (NiS) and nickel subsulfide (Ni/sub 3/S/sub 2/) were administered by im injection to randomly selected Fischer rats in equivalent amounts under identical conditions, NiS did not induce any tumors whereas Ni/sub 3/S/sub 2/ induced sarcomas in almost all of the rats.

  1. IRIS Toxicological Review of Acrylamide (External Review ... (United States)

    EPA has conducted a peer review by EPA’s Science Advisory Board (SAB) of the scientific basis supporting the human health hazard and dose-response assessment of acrylamide that once finalized will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that the science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. The draft Toxicological Review of Acrylamide provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to a chronic exposure to acrylamide.

  2. [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.

  3. 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.

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

    Maronpot, Robert R


    An era can be defined as a period in time identified by distinctive character, events, or practices. We are now in the genomic era. The pre-genomic era: There was a pre-genomic era. It started many years ago with novel and seminal animal experiments, primarily directed at studying cancer. It is marked by the development of the two-year rodent cancer bioassay and the ultimate realization that alternative approaches and short-term animal models were needed to replace this resource-intensive and time-consuming method for predicting human health risk. Many alternatives approaches and short-term animal models were proposed and tried but, to date, none have completely replaced our dependence upon the two-year rodent bioassay. However, the alternative approaches and models themselves have made tangible contributions to basic research, clinical medicine and to our understanding of cancer and they remain useful tools to address hypothesis-driven research questions. The pre-genomic era was a time when toxicologic pathologists played a major role in drug development, evaluating the cancer bioassay and the associated dose-setting toxicity studies, and exploring the utility of proposed alternative animal models. It was a time when there was shortage of qualified toxicologic pathologists. The genomic era: We are in the genomic era. It is a time when the genetic underpinnings of normal biological and pathologic processes are being discovered and documented. It is a time for sequencing entire genomes and deliberately silencing relevant segments of the mouse genome to see what each segment controls and if that silencing leads to increased susceptibility to disease. What remains to be charted in this genomic era is the complex interaction of genes, gene segments, post-translational modifications of encoded proteins, and environmental factors that affect genomic expression. In this current genomic era, the toxicologic pathologist has had to make room for a growing population of

  5. Zinc toxicology following particulate inhalation

    Directory of Open Access Journals (Sweden)

    Cooper Ross


    Full Text Available The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl 2 inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection.

  6. Toxicological evidence in forensic pharmacology. (United States)

    Ferner, R E


    Laboratory evidence of the presence and concentration of a drug in a person who has come to harm is often helpful in forensic pharmacology, and may be crucial. However, its value depends on two critical interpretations by the expert. First, the expert must make a careful analysis of the relationship between the results as measured in the sample and the drug in the patient at the time that harm occurred. That is especially difficult with post-mortem samples. Secondly, the expert must syntheses the laboratory information with the available clinical history and clinical or pathological findings. Even in the most favourable circumstances, when the sample is correctly obtained, identified, and analyzed, it can be hard to say that beyond reasonable doubt a given concentration had a given effect.

  7. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher


    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  8. Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs: A Comparison With Adolescent and Young Adults. (United States)

    Barnes, J; Cotton, P; Robinson, S; Jacobsen, M


    AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data.

  9. 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...

  11. 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.

  12. 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...

  14. Evolution of Computational Toxicology-from Primitive ... (United States)

    Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 on the Evolution of Computational Toxicology-from Primitive Beginnings to Sophisticated Application

  15. Good cell culture practices &in vitro toxicology. (United States)

    Eskes, Chantra; Boström, Ann-Charlotte; Bowe, Gerhard; Coecke, Sandra; Hartung, Thomas; Hendriks, Giel; Pamies, David; Piton, Alain; Rovida, Costanza


    Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP. The covered aspects comprised the current status of the OECD guidance document on Good In Vitro Method Practices, the importance of quality assurance for new technological advances in in vitro toxicology including stem cells, and the optimized implementation of Good Manufacturing Practices and Good Laboratory Practices for regulatory testing purposes. General discussions raised the duality related to the difficulties in implementing GCCP in an academic innovative research framework on one hand, and on the other hand, the need for such GCCP principles in order to ensure reproducibility and robustness of in vitro test methods for toxicity testing. Indeed, if good cell culture principles are critical to take into consideration for all uses of in vitro test methods for toxicity testing, the level of application of such principles may depend on the stage of development of the test method as well as on the applications of the test methods, i.e., academic innovative research vs. regulatory standardized test method. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. High Throughput Transcriptomics @ USEPA (Toxicology Forum) (United States)

    The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest...

  17. 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.

  18. 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...

  19. 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 ...

  20. [Forensic medicine and the overlap with pathology]. (United States)

    Riepert, T


    Forensic medicine incorporates research, teaching and professional service. In the routine practice this encompasses interdisciplinary cooperation with physicians, natural scientists and the legal profession. Lectures in forensic medicine include the correct performance of an external examination of corpses, which every physician must be capable of, just as medical questions and the evidential documentation of injuries. Clinical forensic medicine encompasses the examination and documentation of living victims of physical and/or sexual violence. For further training to become a specialist for forensic medicine it is mandatory to undertake a 6-month training period in pathology. Fatalities with an unclear or unnatural manner of death must be registered with the police. On suspicion of third party involvement the public prosecutor will request a legal autopsy, which is carried out and documented by two physicians in accordance with the penal code. Imaging procedures are standard for an autopsy. Extensive samples are taken for additional testing, such as toxicological and molecular biological investigations.

  1. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. (United States)

    Gold, Bert; Cankovic, Milena; Furtado, Larissa V; Meier, Frederick; Gocke, Christopher D


    Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided.

  2. Estudo retrospectivo dos níveis de ácido hipúrico urinário em exames de toxicologia ocupacional A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams

    Directory of Open Access Journals (Sweden)

    Kelly Cristina Gonzalez


    Full Text Available O ácido hipúrico é o principal metabólito do tolueno, solvente amplamente utilizado em processos industriais e com importantes efeitos tóxicos, fato que justifica a preocupação em monitorar regularmente sujeitos com risco de exposição ocupacional a este solvente. O objetivo deste trabalho foi avaliar os níveis de ácido hipúrico encontrados em trabalhadores submetidos à monitorização biológica. Foi realizado um estudo retrospectivo com dados dos anos de 2002 a 2005, no qual foram analisados os resultados e a situação do empregado na oportunidade do exame (periódico, demissional e admissional. Os resultados indicam uma redução significativa nos níveis de ácido hipúrico em 2005. Exames periódicos obtiveram resultados superiores aos exames admissionais e demissionais, e não foi verificada diferença significativa nas proporções dos sujeitos agrupados de acordo com a situação funcional em cada um dos intervalos estabelecidos segundo o valor de referência e o índice biológico máximo permitido. Os níveis de ácido hipúrico detectados indicam um baixo de risco de exposição ao tolueno na população avaliada, provavelmente em decorrência da preocupação crescente com a implantação de medidas de higiene ocupacional.Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams. Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant

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

    Goldman, M; Dacre, J C


    Lewisite is an organic arsenical war gas which is a vesicant with attendant toxicities due to its ability to combine with thiol groups which are essential for activity of a variety of enzymes. Although Lewisite has been designated as a "suspected carcinogen," the indictment is not supported by the available scientific evidence. Indeed, the unwarranted conclusion is based on one specific case history of a former German soldier whose lower right leg was exposed to liquid Lewisite in 1940 with subsequent development of intraepidermal squamous cell carcinoma, and the examination of death certificates of former workers at a Japanese factory that manufactured a variety of war gases including mustard gas, hydrocyanic acid, chloracetophenome, phosgene, diphenylcyanarsine and Lewisite. It is difficult to comprehend why Lewisite was selected out of this group of toxic chemicals as one of those responsible for respiratory cancer in these workers. It would appear to be a difficult task, indeed, to disengage a specific worker from one of the other of several gases at the workplace and assign a specific gas-induced death. The evidence that organic arsenicals are carcinogenic is weak. Although the weight of evidence is such that inorganic arsenical derivatives are considered weak mutagens, the evidence that organic arsenicals are mutagenic is poor. Recent examination of the mutagenic potential of Lewisite using the Ames test has shown that Lewisite is not mutagenic under these circumstances. While oral administration of arsenical compounds, whether inorganic or organic, does not induce teratogenicity except at very high dose levels which are associated with some degree of maternal toxicity, parenteral administration has been associated with teratogenicity but information of maternal toxicity has not always been available. Indeed, maternal toxicity should be considered as an important diagnostic tool in assessing whether a chemical is teratogenic. The significance of parenteral

  4. Application of Molecular Pathology in Endocrine Pathology. (United States)

    Linke, Ebru Serinsoz; Tezel, Gaye Güler


    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  5. Post-mortem toxicology in young sudden cardiac death victims

    DEFF Research Database (Denmark)

    Bjune, Thea; Risgaard, Bjarke; Kruckow, Line


    certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological...... findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac...

  6. 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.

  7. 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.

  8. Docosahexaenoic acid promotes dopaminergic differentiation in induced pluripotent stem cells and inhibits teratoma formation in rats with Parkinson-like pathology. (United States)

    Chang, Yuh-Lih; Chen, Shih-Jen; Kao, Chung-Lan; Hung, Shih-Chieh; Ding, Dah-Ching; Yu, Cheng-Chia; Chen, Yi-Jen; Ku, Hung-Hai; Lin, Chin-Po; Lee, Kun-Hsiung; Chen, Yu-Chih; Wang, Jhi-Joung; Hsu, Chuan-Chih; Chen, Liang-Kung; Li, Hsin-Yang; Chiou, Shih-Hwa


    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic (DA) neurons in the midbrain. Induced pluripotent stem (iPS) cells have shown potential for differentiation and may become a resource of functional neurons for the treatment of PD. However, teratoma formation is a major concern for transplantation-based therapies. This study examined whether functional neurons could be efficiently generated from iPS cells using a five-step induction procedure combined with docosahexaenoic acid (DHA) treatment. We demonstrated that DHA, a ligand for the RXR/Nurr1 heterodimer, significantly activated expression of the Nurr1 gene and the Nurr1-related pathway in iPS cells. DHA treatment facilitated iPS differentiation into tyrosine hydroxylase (TH)-positive neurons in vitro and in vivo and functionally increased dopamine release in transplanted grafts in PD-like animals. Furthermore, DHA dramatically upregulated the endogenous expression levels of neuroprotective genes (Bcl-2, Bcl-xl, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor) and protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis in iPS-derived neuronal precursor cells. DHA-treated iPS cells significantly improved the behavior of 6-hydroxydopamine (6-OHDA)-treated PD-like rats compared to control or eicosapentaenoic acid-treated group. Importantly, the in vivo experiment suggests that DHA induces the differentiation of functional dopaminergic precursors and improves the abnormal behavior of 6-OHDA-treated PD-like rats by 4 months after transplantation. Furthermore, we found that DHA treatment in iPS cell-grafted rats significantly downregulated the mRNA expression of embryonic stem cell-specific genes (Oct-4 and c-Myc) in the graft and effectively blocked teratoma formation. Importantly, 3 Tesla-magnetic resonance imaging and ex vivo green fluorescence protein imaging revealed that no teratomas were present

  9. Handheld computing in pathology

    Directory of Open Access Journals (Sweden)

    Seung Park


    Full Text Available Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI, new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology.

  10. Handheld computing in pathology (United States)

    Park, Seung; Parwani, Anil; Satyanarayanan, Mahadev; Pantanowitz, Liron


    Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI), new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology. PMID:22616027

  11. Pathology in Greece. (United States)

    Sakellariou, S; Patsouris, E


    Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

  12. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system. (United States)


    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification....

  13. 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

  14. Chemical constituents and toxicological studies of leaves from Mimosa caesalpiniifolia Benth., a Brazilian honey plant (United States)

    Monção, Nayana Bruna Nery; Costa, Luciana Muratori; Arcanjo, Daniel Dias Rufino; Araújo, Bruno Quirino; Lustosa, Maria do Carmo Gomes; Rodrigues, Klinger Antônio da França; Carvalho, Fernando Aécio de Amorim; Costa, Amilton Paulo Raposo; Lopes Citó, Antônia Maria das Graças


    Background: Mimosa caesalpiniifolia Benth. (Leguminosae) is widely found in the Brazilian Northeast region and markedly contributes to production of pollen and honey, being considered an important honey plant in this region. Objective: To investigate the chemical composition of the ethanol extract of leaves from M. caesalpiniifolia by GC-MS after derivatization (silylation), as well as to evaluate the in vitro and in vivo toxicological effects and androgenic activity in rats. Materials and Methods: The ethanol extract of leaves from Mimosa caesalpiniifolia was submitted to derivatization by silylation and analyzed by gas chromatography-mass spectrometry (GC-MS) to identification of chemical constituents. In vitro toxicological evaluation was performed by MTT assay in murine macrophages and by Artemia salina lethality assay, and the in vivo acute oral toxicity and androgenic evaluation in rats. Results: Totally, 32 components were detected: Phytol-TMS (11.66%), lactic acid-2TMS (9.16%), α-tocopherol-TMS (7.34%) and β-sitosterol-TMS (6.80%) were the major constituents. At the concentrations analyzed, the ethanol extract showed low cytotoxicity against brine shrimp (Artemia salina) and murine macrophages. In addition, the extract did not exhibit any toxicological effect or androgenic activity in rats. Conclusions: The derivatization by silylation allowed a rapid identification of chemical compounds from the M. caesalpiniifolia leaves extract. Besides, this species presents a good safety profile as observed in toxicological studies, and possess a great potential in the production of herbal medicines or as for food consumption. PMID:25298660

  15. 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.

  16. Hip joint pathology

    DEFF Research Database (Denmark)

    Tijssen, M; van Cingel, R E H; de Visser, E


    The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18-6...

  17. Insect γ-aminobutyric acid receptors and isoxazoline insecticides: toxicological profiles relative to the binding sites of [³H]fluralaner, [³H]-4'-ethynyl-4-n-propylbicycloorthobenzoate, and [³H]avermectin. (United States)

    Zhao, Chunqing; Casida, John E


    Isoxazoline insecticides, such as fluralaner (formerly A1443), are noncompetitive γ-aminobutyric acid (GABA) receptor (GABA-R) antagonists with selective toxicity for insects versus mammals. The isoxazoline target in house fly ( Musca domestica ) brain has subnanomolar affinity for [³H]fluralaner and a unique pattern of sensitivity to isoxazolines and avermectin B(1a) (AVE) but not to fipronil and α-endosulfan. Inhibitor specificity profiles for 15 isoxazolines examined with Musca GABA-R and [³H]fluralaner, [³H]-4'-ethynyl-4-n-propylbicycloorthobenzoate ([³H]EBOB), and [³H]AVE binding follow the same structure-activity trends although without high correlation. The 3 most potent of the 15 isoxazolines tested in Musca [³H]fluralaner, [³H]EBOB, and [³H]AVE binding assays and in honeybee (Apis mellifera) brain [³H]fluralaner assays are generally those most toxic to Musca and four agricultural pests. Fluralaner does not inhibit [³H]EBOB binding to the human GABA-R recombinant β₃ homopentamer, which is highly sensitive to all of the commercial GABAergic insecticides. The unique isoxazoline binding site may resurrect the GABA-R as a major insecticide target.

  18. Updates in ophthalmic pathology. (United States)

    Mendoza, Pia R; Grossniklaus, Hans E


    Ophthalmic pathology has a long history and rich heritage in the field of ophthalmology. This review article highlights updates in ophthalmic pathology that have developed significantly through the years because of the efforts of committed individuals and the confluence of technology such as molecular biology and digital pathology. This is an exciting period in the history of ocular pathology, with cutting-edge techniques paving the way for new developments in diagnostics, therapeutics, and research. Collaborations between ocular oncologists and pathologists allow for improved and comprehensive patient care. Ophthalmic pathology continues to be a relevant specialty that is important in the understanding and clinical management of ocular disease, education of eye care providers, and overall advancement of the field.

  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. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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.

  13. [Pathology- a new revival]. (United States)

    Barshack, Iris


    The field of pathology has undergone considerable change in recent years. The editor and editorial board of this journal are to be commended for their decision to devote a special issue to the field of pathology. Pathology deals with the characterization, investigation, and diagnosis of disease and disease processes and as such, has Long been considered one of the foundations of medicine. It is a rich and multi-faceted field which has retained its breadth of scope in the face of ever-increasing specialization and sub-specialization in medicine. In addition to its classic roles in autopsy, case description, and the diagnosis of pathoLogic processes, new and innovative spheres of activity are becoming integral to the field, especially in the realm of molecular pathology. Pathology is a Leading player in the new age of "personalized cancer therapy", where pathologists are responsible not only for diagnosing disease in the tissue, but also for conducting additional tests which may predict its response to specific drug therapies. In this context, moLecular pathology has become essential to the field both in the provision of cLinical service and research. To fully implement this trend, we are witness to the rise of tissue collection and tissue banking initiatives for both diagnostic and research purposes. A national tissue banking project in Israel has recently received considerable attention.

  14. [Gunshot wounds: forensic pathology]. (United States)

    Lorin de la Grandmaison, Geoffroy


    Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

  15. 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

  16. 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

  17. [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.

  18. 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.

  19. Characteristics, circumstances and pathology of sudden or unnatural deaths of cases with evidence of pathological hoarding. (United States)

    Darke, Shane; Duflou, Johan


    The study aimed to determine the characteristics and circumstances of cases sudden or unnatural death (n = 61) with evidence of pathological hoarding, their major organ pathology and toxicology. The mean age was 65·8 yrs (a mean of 16.1 years of potential life lost), 62·3% were male, and 28·2% were obese. 95·1% lived alone, and 96·7% died in their residence, with no medical intervention. In all cases severe squalor and extensive hoarding were noted. The direct cause of death was attributed to disease in 75·4%, heart disease being a significant factor in 52·5%. Accidents causing death directly related to hoarding occurred in two cases. Autopsy revealed extensive pathology: severe coronary artery narrowing (42·4%), myocardial replacement fibrosis (44·1%), emphysema (39·0%), nephrosclerosis (46·6%). Signs of hypothermia were present in 14·8%, and diabetes was diagnosed in 21·3%. The most commonly detected substance was alcohol (32·1%). Medications for heart disease (5·4%) or diabetes (7·1%) were rare. The overall clinical picture was of an isolated group, with a heavy burden of physical disease and, in all probability, a high level of psychiatric disorders, who died alone in their homes.

  20. Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop. (United States)

    The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is det...

  1. Determinants of pathologic mineralization. (United States)

    Kirsch, Thorsten


    Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.

  2. 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 ...

  3. Fatty acids, lipid metabolism and Alzheimer pathology.

    NARCIS (Netherlands)

    Hooijmans, C.R.; Kiliaan, A.J.


    Alzheimer's disease is the most common form of dementia in the elderly. The cause of Alzheimer's disease is still unknown and there is no cure for the disease yet despite 100 years of extensive research. Cardiovascular risk factors such as high serum cholesterol, presence of the Apolipoprotein epsil

  4. Fatty acids, lipid metabolism and Alzheimer pathology.

    NARCIS (Netherlands)

    Hooijmans, C.R.; Kiliaan, A.J.


    Alzheimer's disease is the most common form of dementia in the elderly. The cause of Alzheimer's disease is still unknown and there is no cure for the disease yet despite 100 years of extensive research. Cardiovascular risk factors such as high serum cholesterol, presence of the Apolipoprotein

  5. Profiles in drug metabolism and toxicology: Richard Tecwyn Williams (1909-1979). (United States)

    Jones, Alan Wayne


    This article pays homage to the life and work of a veritable pioneer in toxicology and drug metabolism, namely a Welshman, Richard Tecwyn Williams, FRS. Professor Williams, or RT as he was known, made major contributions to knowledge about the metabolism and toxicology of drugs and xenobiotics during a scientific career spanning nearly 50 years. Author or coauthor of close to 400 research articles and reviews, including a classic book, entitled Detoxication Mechanisms, Williams and his research school investigated virtually all aspects of drug metabolism, especially conjugations. In particular, the concepts of phase 1 and phase II metabolic pathways were introduced by Williams; the biliary excretion of drugs was extensively studied as were species differences in drug metabolism and detoxication. Besides investigating the metabolism of many pharmaceutical drugs, such as sulfonamides and thalidomide, Williams and his group investigated the disposition and fate in the body of organic pesticides and recreational drugs of abuse, such as amphetamine, methamphetamine and lysergic acid diethylamide (LSD).

  6. 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,...

  7. 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...

  8. 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

  9. Evaluation of clinical pathology data: correlating changes with other study data. (United States)

    Everds, Nancy E


    During the conduct of in vivo toxicology studies, in-life, clinical pathology, and anatomic pathology parameters are collected and interpreted. These sets of parameters are evaluated in an integrative manner to determine the overall toxicity of a test article. For clinical pathology parameters, the inherent variability and physiologic factors affecting each analyte must be understood prior to interpretation. Changes in clinical pathology parameters that are considered to be test article-related are then assessed with respect to changes in the concurrent data sets such as clinical signs and anatomic pathology to determine the underlying pathophysiology. In this article, examples of hemolysis and hepatotoxicity are used to demonstrate the relationships among the various parameters and data sets. Whereas there was tight correlation of all data sets in the example of hemolysis in rats, the examples of altered enzymes and other biomarkers indicating liver injury and dysfunction were more often discordant with other data sets.

  10. 78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods... (United States)


    ..., NICEATM, and the Director of the NIEHS and NTP regarding statutorily mandated duties of ICCVAM and... Toxicological Methods (NICEATM), and the Director of the National Institute of Environmental Health Sciences (NIEHS) and NTP regarding statutorily mandated duties of ICCVAM and activities of NICEATM....

  11. 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

  12. Pathological and toxicological findings in glyphosate-surfactant herbicide fatality: a case report. (United States)

    Sribanditmongkol, Pongruk; Jutavijittum, Prapan; Pongraveevongsa, Pattaravadee; Wunnapuk, Klintean; Durongkadech, Piya


    Glyphosate herbicide is promoted by the manufacturer as having no risks to human health, with acute toxicity being very low in normal use. In Thailand, however, poisoning from glyphosate agricultural herbicides has been increasing. A case of rapid lethal intoxication from glyphosate-surfactant herbicide involved a 37-year-old woman, who deliberately ingested approximately 500 mL of concentrated Roundup formulation (41% glyphosate as the isopropylamine salt and 15% polyoxyethylene amine; Mosanto Company). The postmortem examination revealed that the stomach contained 550 mL of yellow fluid. The gastric mucosa of anterior fundus revealed hemorrhage and the small intestines had marked dilatation and thin walls. We used the high-performance liquid chromatography method for determination of serum and gastric content levels of glyphosate. The glyphosate levels of serum and gastric content were 3.05 and 59.72 mg/mL, respectively. Toxic effects of polyoxyethylene amine and Roundup were caused by their ability to erode tissues including mucous membranes and linings of the gastrointestinal and respiratory tracts. A mild degree of pulmonary congestion and edema was observed in both lungs. We proposed that the characteristic picture of microvesicular steatosis of the hepatocytes, seen predominantly in centrilobular zones of the liver, resembled drug-induced hepatic toxicity or secondary hypoxic stress.

  13. The placenta in toxicology. Part III : Pathologic assessment of the placenta

    NARCIS (Netherlands)

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


    This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the gross and histologic normal anatomy of rodent and macaque placentas, including typical organ weights, with comments on differences fro

  14. Toxicological evaluation of proteins introduced into food crops (United States)

    Kough, John; Herouet-Guicheney, Corinne; Jez, Joseph M.


    This manuscript focuses on the toxicological evaluation of proteins introduced into GM crops to impart desired traits. In many cases, introduced proteins can be shown to have a history of safe use. Where modifications have been made to proteins, experience has shown that it is highly unlikely that modification of amino acid sequences can make a non-toxic protein toxic. Moreover, if the modified protein still retains its biological function, and this function is found in related proteins that have a history of safe use (HOSU) in food, and the exposure level is similar to functionally related proteins, then the modified protein could also be considered to be “as-safe-as” those that have a HOSU. Within nature, there can be considerable evolutionary changes in the amino acid sequence of proteins within the same family, yet these proteins share the same biological function. In general, food crops such as maize, soy, rice, canola etc. are subjected to a variety of processing conditions to generate different food products. Processing conditions such as cooking, modification of pH conditions, and mechanical shearing can often denature proteins in these crops resulting in a loss of functional activity. These same processing conditions can also markedly lower human dietary exposure to (functionally active) proteins. Safety testing of an introduced protein could be indicated if its biological function was not adequately characterized and/or it was shown to be structurally/functionally related to proteins that are known to be toxic to mammals. PMID:24164515

  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. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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.

  19. 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

  20. Eponyms in forensic pathology. (United States)

    Nečas, Pavel; Hejna, Petr


    The phenomenon of eponymous terms in forensic pathology is described in this paper. The authors analyzed representative textbooks (monographs) dealing with forensic pathology in both English and German and identified several eponymous terms. The paper aims to present to the reader the most important eponymous terms in forensic pathology. Included in the paper are the following terms: Beckwith's Sign, Casper's Rule, Krönlein's Shot, Lichtenberg's Figures, Nysten's Law, Paltauf's Spots, Puppe's Rule, Sehrt's Sign, Simon's Sign, Sveshnikov's Sign, Tardieu's Spots, Wischnewski Spots, Wydler's Sign. The spread of eponymous terms throughout various languages is mentioned. The linguistic basis of such terms as well as their advantages and disadvantages in specialist fields, and indeed in even wider circles, is discussed. The authors state that the main function of these terms is to facilitate the open flow of unambiguous information among scholars. Eponymous terms in forensic pathology are characteristic for the German speaking countries and for all countries influenced by the German school of forensic pathology. Their usage in the Anglo-Saxon world is much less widespread, meaning they do not occur very often in English monographs and textbooks.

  1. Toxicological evaluation and risk assessment of chemical mixtures

    NARCIS (Netherlands)

    Cassee, F.R.; Groten, J.P.; Bladeren, P.J. van; Feron, V.J.


    A major objective of combination toxicology is to establish whether a mixture of chemicals will result in an effect similar to that expected on the basis of additivity. This requires understanding of the basic concepts of the combined toxicological action of the compounds of the mixture: simple

  2. IRIS Toxicological Review of Methyl Ethyl Ketone (2003 Final) (United States)

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

  3. 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 (

  4. 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...

  5. Toxicological evaluation of the aqueous extract of Allium sativum ...

    African Journals Online (AJOL)

    Toxicological evaluation of the aqueous extract of Allium sativum bulbs on laboratory mice and rats. ... PROMOTING ACCESS TO AFRICAN RESEARCH ... The possible toxicological risks of Allium sativum aqueous extract upon consumption ... FAQ's · News · AJOL jobs · More about AJOL · AJOL's Partners · Contact AJOL ...

  6. 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

  7. Temas 27 a 31. Toxicología de plaguicidas


    García Fernández, Antonio Juan


    Toxicología de los plaguicidas. Intoxicaciones en animales y humanos. Mecanismos de acción. Diagnóstico. Tratamiento. Aspectos legales, alimentarios y ambientales. Presentaciones de los temas 27 a 31 de Toxicología de la licenciatura de Veterinaria


    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.

  9. 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)

  10. IRIS Toxicological Review and Summary Documents for ... (United States)

    Carbon tetrachloride is a volatile haloalkane with a wide range of industrial and chemical applications. It is produced commercially from chlorination of a variety of low molecular weight hydrocarbons such as carbon disulfide, methanol, methane, propane, and ethylene dichloride. It is also produced by thermal chlorination in the production of tetrachloroethylene. Major uses of carbon tetrachloride have been in the recovery of tin from tin plating waste, in formulation of petrol additives and refrigerants, in metal degreasing and agricultural fumigants, in chlorination of organic compounds, in the production of semiconductors, in the reduction of fire hazard, as a solvent for rubber cement, and as a catalyst in polymer technology. Its production has been decreasing and it is no longer permitted in products intended for home use. Despite this ban, carbon tetrachloride has been detected at 314 hazardous waste sites. EPA's assessment of noncancer health effects and carcinogenic potential of carbon tetrachloride was last prepared and added to the IRIS database in 1991. The IRIS program is preparing an assessment that will incorporate health effects information available for carbon tetrachloride, and current risk assessment methods. The IRIS assessment for carbon tetrachloride will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity

  11. 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.

  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. 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.

  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. Interaction of perfluorooctanoic acid with human serum albumin

    Directory of Open Access Journals (Sweden)

    Chen Fang-Fang


    Full Text Available Abstract Background Recently, perfluorooctanoic acid (PFOA has become a significant issue in many aspects of environmental ecology, toxicology, pathology and life sciences because it may have serious effects on the endocrine, immune and nervous systems and can lead to embryonic deformities and other diseases. Human serum albumin (HSA is the major protein component of blood plasma and is called a multifunctional plasma carrier protein because of its ability to bind an unusually broad spectrum of ligands. Results The interaction of PFOA with HSA was investigated in the normal physiological condition by equilibrium dialysis, fluorospectrometry, isothermal titration calorimetry (ITC and circular dichroism (CD. The non-covalent interaction is resulted from hydrogen bond, van der Waals force and hydrophobic stack. PFOA binding to HSA accorded with two-step binding model with the saturation binding numbers of PFOA, only 1 in the hydrophobic intracavity of HSA and 12 on the exposed outer surface. The interaction of PFOA with HSA is spontaneous and results in change of HSA conformation. The possible binding sites were speculated. Conclusion The present work suggested a characterization method for the intermolecular weak interaction. It is potentially useful for elucidating the toxigenicity of perfluorochemicals when combined with biomolecular function effect, transmembrane transport, toxicological testing and the other experiments.

  17. 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.

  18. [Biomechanism-based innovation of toxicology by the fundamental concept of "Signal Toxicity"]. (United States)

    Kanno, Jun


    When Rachel Carson wrote the "Silent Spring" in 1962, the toxicology society was influenced in an indirect way mainly on environmental effects of massive use of pesticides. However, at that time, for those who were studying DDT and other pesticides, the biological effect of such chemicals were understood as a result of their long-lasting toxicants with slow elimination rates from the body; bio- persistency and in some case bio- and environmentally accumulative. And the chronic effects became overt including complex endpoints not only liver toxicity but, reproductive, immune, and neuronal. The impact of Silent Spring on toxicology seems to have established the foundations for scientifically accepting the problems widely raised by the Theo Colborn's "Our stolen future", although its main target was reproductive mechanisms including oestrogen and androgen system. For basic receptor biologists, non-monotonic dose-response curve was a matter of course, but for toxicologists at tnat time, all dose-response curves should be monotonic. With further detailed discussion many toxicologists started to understand that there is a good plausibility that such non-monotonic and low dose effect can happen in wild life and may be in humans under certain conditions. Since then, many toxicologists including us have initiated research on the so-called endocrine disrupting chemicals under new paradigm of receptor mediated- or signal-toxicity. To handle this problem, it became clearer that toxicology has to be innovated towards more biologically mechanistic science. This thinking has linked to the trend of toxicogenomics, where classical pathological findings are used to confirm the results of comprehensive mechanistic analysis data. In contrast our idea of toxicogenomics, designated as Percellome Toxicogenomics Project, was to develop comprehensive and quantitative gene expression networks out of transcriptomic data alone. Existing biological knowledge is used to help understand the

  19. Overview Of Forensic Toxicology, Yesterday, Today And In The Future. (United States)

    Chung, Heesun; Choe, Sanggil


    The scope of forensic toxicology has been tremendously expanded over the past 50 years. From two general sections forensic toxicology can be further classified into 8-9 sections. The most outstanding improvement in forensic toxicology is the changes brought by instrumental development. The field of forensic toxicology was revolutionized by the development of immunoassay and bench-top GC-MS in the 1980's and LC-MS-MS in 2000's. Detection of trace amounts of analytes has allowed the use of new specimens such as hair and oral fluids, along with blood and urine. Over a longer period of time, continuous efforts have been made to efficiently extract and separate drug and poison from biological fluids. International endeavors to develop high quality standards and guidelines for drugs and poisons in biological specimens and to promote them in order to increase reliability of laboratories are also part of the recent advancement of forensic toxicology. Interpretation of postmortem toxicology encompasses various factors including postmortem redistribution and stability. Considering the recent trend, the interpretation of toxicological results should account for autopsy findings, crime scene information, and related medical history. The fields of forensic toxicology will continuously develop to improve analysis of target analytes from various specimens, quality assurance program, and results interpretation. In addition, the development of analytical techniques will also contribute further advancement of forensic toxicology. The societies of forensic toxicologists, such as TIAFT, will play an important role for the advancement of forensic toxicology by collaborating and sharing ideas between toxicologists from both developed and developing countries. Copyright© Bentham Science Publishers; For any queries, please email at

  20. Pathological Gambling Subtypes (United States)

    Vachon, David D.; Bagby, R. Michael


    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  1. Next-Generation Pathology. (United States)

    Caie, Peter D; Harrison, David J


    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  2. Pathological Gambling: Psychiatric Models (United States)

    Westphal, James R.


    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  3. Toxicological Analysis of Opiates from Alternative Matrices Collected from an Exhumed Body. (United States)

    Cippitelli, Marta; Mirtella, Dora; Ottaviani, Giovanni; Tassoni, Giovanna; Froldi, Rino; Cingolani, Mariano


    In this case study, the body of a 45-year-old man was exhumed after 1 year at the request of the public prosecutor to assess whether the death was caused by drug consumption. Toxicological analyses were performed on several matrices, including liver, kidney, and the alternative matrices hair and teeth. The systematic toxicological analysis (STA), which consisted of basic and acid liquid/liquid extraction and gas chromatography-mass spectrometry (GC-MS) analysis, showed the presence of opiates in each of the matrices analyzed. Subsequently, to confirm and quantify the presence of opioids, samples of each of the matrices were subjected to solid-phase extraction and specific GC-MS analysis. The case presented demonstrates the possibility of drug detection in an exhumed body that has been buried for 1 year, despite the problems of quantitative interpretation of the data, and that toxicological results could be useful along with other forensic evidence. © 2017 American Academy of Forensic Sciences.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Toxicology of metals and metalloids: Promising issues for future studies in environmental health and toxicology. (United States)

    Barbosa, Fernando


    The function and behavior of chemical elements in ecosystems and in human health probably comprise one of the most studied issues and a theme of great interest and fascination in science. Hot topics are emerging on an annual basis in this field. Bearing this in mind, some promising themes to explore in the field of metals and metalloids in the environment and in toxicology are highlighted and briefly discussed herein.

  9. 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.

  10. [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.

  11. [Research advances in eco-toxicological diagnosis of soil pollution]. (United States)

    Liu, Feng; Teng, Hong-Hui; Ren, Bai-Xiang; Shi, Shu-Yun


    Soil eco-toxicology provides a theoretical basis for ecological risk assessment of contaminated soils and soil pollution control. Research on eco-toxicological effects and molecular mechanisms of toxic substances in soil environment is the central content of the soil eco-toxicology. Eco-toxicological diagnosis not only gathers all the information of soil pollution, but also provides the overall toxic effects of soil. Therefore, research on the eco-toxicological diagnosis of soil pollution has important theoretical and practical significance. Based on the research of eco-toxicological diagnosis of soil pollution, this paper introduced some common toxicological methods and indicators, with the advantages and disadvantages of various methods discussed. However, conventional biomarkers can only indicate the class of stress, but fail to explain the molecular mechanism of damage or response happened. Biomarkers and molecular diagnostic techniques, which are used to evaluate toxicity of contaminated soil, can explore deeply detoxification mechanisms of organisms under exogenous stress. In this paper, these biomarkers and techniques were introduced systematically, and the future research trends were prospected.

  12. 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.

  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. 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. © 2010 American Academy of Forensic Sciences.

  15. Pathology informatics fellowship training: Focus on molecular pathology

    Directory of Open Access Journals (Sweden)

    Diana Mandelker


    Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  16. 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...

  17. Functional Toxicogenomics: Mechanism-Centered Toxicology

    Directory of Open Access Journals (Sweden)

    Chris D. Vulpe


    Full Text Available Traditional toxicity testing using animal models is slow, low capacity, expensive and assesses a limited number of endpoints. Such approaches are inadequate to deal with the increasingly large number of compounds found in the environment for which there are no toxicity data. Mechanism-centered high-throughput testing represents an alternative approach to meet this pressing need but is limited by our current understanding of toxicity pathways. Functional toxicogenomics, the global study of the biological function of genes on the modulation of the toxic effect of a compound, can play an important role in identifying the essential cellular components and pathways involved in toxicity response. The combination of the identification of fundamental toxicity pathways and mechanism-centered targeted assays represents an integrated approach to advance molecular toxicology to meet the challenges of toxicity testing in the 21st century.

  18. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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


    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......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...

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. The use of kestrels in toxicology (United States)

    Wiemeyer, Stanley N.; Lincer, J.L.; Bird, David M.; Bowen, Reed


    Various species of kestrels have become important bioindicators of environmental quality and test species for comparative toxicology in captivity. At least 7 species of kestrels have been used to document the presence of environmental contamination primarily organochlorines and metals, in at least 15 countries. Captive kestrels have been used in studies involving a wide variety of environmental contaminants and toxicants examining: bioaccumulation; lethal toxicity using acute, chronic, and secondary exposures; effects on reproduction, eggshell thickness, and related enzyme systems; and effects on a wide variety of physiological and biochemical parameters. Field studies have examined the response of kestrels to exposure to insecticides. Kestrels should continue to play a vital role as a bioindicator and raptorial 'white mouse', especially because of their relationship to other falconiformes, several of which have been shown to be extremely sensitive to environmental changes.

  4. Toxicological implications of extended space flights (United States)

    Weiss, Bernard; Utell, Mark; Morrow, Paul


    This paper draws attention to the needs and mechanisms for shielding crewmembers on long-duration space flights from hazards related to chemical toxicants. Specific attention is given to existing data on sources of impaired performance, namely, neurotoxicants, respiratory infections, pulmonary function. The behavioral effects associated with long-term exposure to volatile organic solvents can impair crucial functional parameters of space flight and mission objectives. Respiratory infections contribute to performance decrements of up to 20 percent, and pulmonary function can be impaired by contaminants such as ozone leading to reduced performance. It is concluded that these and other sources of toxicologically induced performance reductions be studied since they impinge on vehicle design and mission objectives.

  5. Toxicological Problems with the Redy System

    DEFF Research Database (Denmark)

    Broch Møller, B.; Bahnsen, M.; Solgaard, Per Bent


    Dialysate from the REDY dialysis system was examined for toxic elements, special attention being paid to the content of zirconium and aluminium. Also investigated was the concentration of formaldehyde in the rinsing fluid of three consecutive washings. The amount of zirconium and aluminium found...... in the dialysate was negligible. The concentration of formaldehyde was alarmingly high after two consecutive washings, a considerable amount (less than 50 mg) still remaining after three washings. It is recommended that at least three consecutive washings be performed, and that, if possible, formaldehyde...... be substituted by another antiseptic. Of special interest was the finding of a very high concentration of boron in the dialysate. It is suggested that this metal, which is a potentially toxic substance, may emanate from the patient. It is concluded that use of the REDY system carries no obvious toxicological...

  6. 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.

  7. Knowledge and Confidence of Emergency Clinicians in Managing Toxicological Presentations

    Directory of Open Access Journals (Sweden)

    Joseph Monteith


    Full Text Available Background: Acute poisonings are common presentations to emergency departments (EDs worldwide and require rapid assessment. Consultant emergency physicians (EPs faced with various toxicological presentations must initiate rapid investigations and empirical management. This study aimed to determine emergency department doctors’ level of knowledge and confidence in toxicological presentations, and factors that predicted these outcomes. Methods: Target participants included members of the Australasian College for Emergency Medicine (ACEM and readers of the emergency medicine website, “Life in the Fast Lane”. The survey was distributed electronically via the ACEM bulletin and posted on Life in the Fast Lane. A survey was designed based on toxicology multiple choice questions (MCQs. The questionnaire comprised 59 items: 10 demographic items; 20 items about confidence; 28 MCQs assessing knowledge of common and serious toxicological presentations. Results: There were 467 consenting respondents from 31 countries, with most residing in Australia (306/467, 66%. Respondents comprised similar proportions of consultant emergency physicians (196/467, 42.0%, and trainees (197/467, 42.2%.  Almost two-thirds (292/467; 62.1% had received formal training in toxicological emergencies, while a third (166/467, 35.5% had participated in a relevant conference or workshop. A total of 284/339 (83.8% participants completing all items achieved a knowledge test score >50%. More than 65% incorrectly answered questions on pharmacology of serotonin syndrome and lithium toxicity, and more than half incorrectly answered questions on use of 12 lead ECG in toxicology, calcium channel antagonist or tricyclic antidepressant toxicities. Predictors of overall knowledge for toxicology were receipt of formal toxicology education, and clinicians’ experience and seniority. Conclusion: The knowledge and confidence of doctors working in emergency departments is varied, yet

  8. Novel and future applications of microarrays in toxicological research. (United States)

    Gant, Timothy W


    Microarray technologies have both fascinated and frustrated the toxicological community since their introduction around a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to chemically mediated stress, and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analysis, and difficulties associated with actually recognising signature gene expression patterns, and discerning mechanisms. Toxicogenomics was predicted to make toxicological assessment and extrapolation easier, faster and cheaper. The reality has been somewhat different; toxicogenomics is difficult. However, its potential when properly applied has been indicated by some well designed toxicogenomics studies, particularly in the differentiation of genotoxins from non-genotoxins. Technology waits though for no man. While the toxicological community has been working to apply transcriptomics (mRNA levels) in toxicology, the technology has moved beyond this application into new arenas. Some have application to toxicology and are reviewed here, except transcriptomics which has been extensively written about before. This review discusses the application of microarray technologies applied to the genome per se (amplifications, deletions, epigenetic change), mRNA translation and its control mechanisms through miRNA. Which of the new genomics technoï¿(1/2)logies will find most application in toxicology? In the opinion of the author there are three potentially major applications: i) arrayCGH in assessment and recognition of genotoxicity; ii) epigenetic assessment in developmental and transgenerational toxicology; and iii) miRNA assessment in all toxicology types, but particularly developmental toxicology.

  9. Feline oral pathology


    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena


    The main pathologies of the oral cavity are of utmost importance, not only by the number of exposed individuals, but also by the consequences which stems. With the development of this work, we intend to conduct a brief approach to the same, since, specifically affecting domestic felines. Feline Lymphoplasmatic Gingivostomatitis (GELF), the Feline Odontoclastic Reabsorption Lesions (LROF) Complex and gingivitis-stomatitis-pharyngitis, have been studied, some of which are considered an enigma i...

  10. Envy's pathology: Historical contexts. (United States)

    Minou, Lina


    This article is concerned with the physicality of envy primarily in early -modern, but also in eighteenth-century health contexts. The discussion brings together descriptions of the effects of envy on the body of the envier, mainly from works of physiology and health preservation, but also from literary and spiritual writings. These depictions of envy are studied beyond their symbolism and with a view to establish whether they are meaningful according to the medical theories of the time in which they occur. The discussion begins by acknowledging the status of envy as a 'disease' and looks to the specific ways in which the discourse of envy conveys this sense. I find that in the early modern discourse envy is always pathological, that is, it is experienced as disease and signifies disease in general and several diseases in particular. Moreover, envy is uniquely placed to convey pathology on account of its being connected to inherently pathogenic elements of the humoural theory. Specifically, envy is physiologically connected to melancholy, and the way it is presented comes close to attributes assigned to black bile. In addition, envy realizes pathology, the occurrence of disease in the body, by impairing the vital process of digestion and thus depriving the person from proper nourishment and sustenance. The analysis further considers how this impairment of the body fits with the physiological manifestation of envy as 'corrosion' and 'consumption'. Finding commonalities with other maladies mediated by these physiological signs the article concludes by considering the function of pathology in the conception of early modern envy.

  11. 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...

  12. International Clinical Guidelines for the Adoption of Digital Pathology: A Review of Technical Aspects. (United States)

    García-Rojo, Marcial


    Digital slides, also called whole-slide images, are being evaluated to replace conventional microscopy, and several guidelines have been published. This paper reviews technical specifications of digital pathology systems that have been included in the guidelines and position papers from the Canadian Association of Pathologists, the College of American Pathologists, the American Telemedicine Association, the Digital Pathology Association, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Centers for Disease Control and Prevention, the Society of Toxicologic Pathology, the European Commission, the Spanish Society of Anatomic Pathology, The Royal College of Pathologists and The Royal College of Pathologists of Australasia. In conclusion, most technical aspects are well covered by these guidelines, although they offer limited information regarding image quality and compression, and file formats.

  13. Masochism and pathological gambling. (United States)

    Rosenthal, Richard J


    That all pathological gamblers have an "unconscious wish to lose," an idea first expressed by Freud and Bergler, is neither true nor useful; wrong as well, however, are the reasons for neglecting masochism in relation to gambling. There is a small but clinically significant subgroup of pathological gamblers who are masochistic. I present clinical vignettes and a more extended treatment account to illustrate its importance. Masochism has been a confusing concept. As used here it refers to the deliberate seeking of pain, loss, suffering, or humiliation. There may be pleasure in pain, or an obligatory combining of pleasure and pain. A sense of power and control may be achieved through suffering. The case material illustrates clinically useful types (sexual masochism, masochistic personality disorder, moral masochism, relational masochism) as well as some common masochistic dynamics encountered in the treatment of pathological gamblers. These masochistic patterns are often identifiable during the initial evaluation. Distinguishing features may include a reversal of normal attitudes about winning and losing, the absence of an early winning phase, sometimes a memorable early loss. Gamblers may sabotage opportunities for success or create unnecessary obstacles for themselves. Losing may be more comfortable than winning or may be overtly sexualized.

  14. 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.

  15. 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...

  16. 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

  17. The clinical features of serum total sialic acid levels in pathological newborn%病理状态新生儿血清唾液酸水平分析

    Institute of Scientific and Technical Information of China (English)

    阮莉莉; 华春珍; 方妍彤; 王晓安


    Objective To investigate the serum sialic acid ( SIA ) levels in pathological newborn and evaluate the correlation between SIA levels and gestational ages or ages .Method Premature newborn and mature newborn were grouped according to gestational ages and not more than 24h subgroup, 25 h~7 d and more than 7d subgroups were defined by day ages .The enzymatic method was used when the contents of serum SIA were detected .The statistical analysis software, SPSS version 17.0 was used in the study.Findings A total of 987 newborn, including 238 (24.1%) pre-term newborns, 737 (75.3%) full term newborns and 6(0.6%)pos-term newborns were included in the study .The serum SIA levels of the ≤24h subgroup, 25 h~7 d subgroup and>7d subgroup in the pre-full newborns group were 27.2 ±8.1mg/dl, 33.3 ±5.8 mg/dl and 32.9 ±6.2 mg/dl respectively,which were significant lower than that in the full term group in which the SIA level were 30.4 ±9.2mg/dl,35.4 ±6.7 mg/dl and 37.6 ±9.0mg/dl instead.Lower SIA level was found in≤24h subgroups compared with the 25 h ~7 d subgroups or >7d subgroups in both pre-term and full term groups . Conclusion There was correlation between serum sialic acid level and day age in newborns in the study .Lower SIA level was identified in pre-full newborn when compared with the full term newborn .%目的:探讨病理状态新生儿血清唾液酸(sialic acids, SIA)水平及其与胎龄和日龄的关系。方法将因病理状态住院的新生儿(987例)分早产儿(238例)和足月儿(743例)两组,每组又根据日龄分24 h以内、25 h~7 d和大于7 d亚组,SIA测定采用神经氨酸苷酶法。结果早产儿各亚组血清SIA水平显著低于足月儿相应亚组( P<0.05);早产儿≤24h亚组血清SIA水平显著低于25 h~7 d亚组(t=4.70,P<0.01);早产儿组和足月儿组中≤24 h亚组血清SIA水平均显著低于25 h~7 d亚组或>7 d亚组。结论本组新生儿血清唾液酸

  18. Mycotoxins and the pet food industry: toxicological evidence and risk assessment. (United States)

    Boermans, Herman J; Leung, Maxwell C K


    Mycotoxin contamination in pet food poses a serious health threat to pets, causing an emotional and economical concern to the pet owners. Aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins and fusaric acid have been found in the ingredients and final products of pet food, resulting in both acute toxicity and chronic health problems in pets. Toxicological interaction among mycotoxins as a natural mixture further complicates the issue. The concepts of "risk assessment", using hazard identification, dose-response assessment, no observable adverse effect level (NOAEL), and lowest observed adverse effect level (LOAEL), should be applied to assess the risk and safety of mycotoxins in pet food, thereby instilling public confidence in the pet food industry.

  19. [The discovery of anaphylaxis: 19 days after an anodyne account of toxicology, it is shown that immunity is perhaps pathogenic]. (United States)

    Richet, G


    While studying the toxicology of various coelenteres fishing filament poisons, Charles Richet and Paul Portier observed cases of rapid death which had no correlation with the injected doses. In dogs, death only occurred in those which, more than 15 days beforehand, had withstood well an injection more concentrated or identical to the later fatal one. The authors created the neologism 'anaphylaxis' which signifies 'non-protection'. Thus, it appeared that an immune response could be pathological. This discovery opened the subject area of immunopathology at a period of time when, in contrast, vaccination and serotherapy researches were prominent.

  20. A forensic toxicological dilemma: the interpretation of post-mortem concentrations of central acting analgesics. (United States)

    Daldrup, Th


    Dora V., a 88-year-old pensioner suffering from a hiatus hernia, died at the home of an orthopaedist and his wife, an anaesthetist, immediately after she had received a dose of 300 mg pethidine via intravenous infusion in a timeframe of about 90 min. One day before her death a befriended notary of the couple visited Dora V. and obtained a blank signature. After her death, a will was forged using this signature, rendering the couple sole heirs of Dora V.'s estate with a value of several million euros. Post-mortem toxicology was performed in three different institutes of legal medicine. The concentrations of pethidine in peripheral venous blood were between 6.1 and 6.5mg/l and 9.5 and 17.2mg/kg in brain. Pharmacokinetic calculation confirms the given dose. There was no doubt that the cause of death was acute pethidine intoxication. The accused couple claimed that this dose of pethidine was indicated to relief pain, and as the pathologists said in their expert opinions that the hiatus hernia could explain her death, the court had to acquit the accused. This very special case demonstrates that preconceived murder of a sick person with suitable analgesics cannot be proven--at least not with the methods available to forensic toxicology and pathology. This has to be taken into consideration if euthanasia will be legalised under special circumstances.

  1. Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL): analysis of overdose cases reported to the Swiss Toxicological Information Centre. (United States)

    Liechti, Matthias E; Kupferschmidt, Hugo


    We analysed 141 cases of Gamma-hydroxybutyric acid (GHB) and Gamma-butyrolactone (GBL) intoxication reported by physicians to the Swiss Toxicological Information Centre between 1995 and 2003. GHB and GBL intoxication are associated with considerable morbidity. Multiple drug use is common. Overdosing frequently results in non-reactive coma, which accounts for the severity of the intoxication and the costs occasioned by management.

  2. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P


    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  3. Pathology Gross Photography: The Beginning of Digital Pathology. (United States)

    Rampy, B Alan; Glassy, Eric F


    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale.

  4. 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...

  5. 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<...

  6. 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.

  7. Space toxicology: protecting 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 while 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 and other purposes. As we begin to explore other celestial bodies, in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

  8. 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/...


    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...

  10. Toxicological evaluation of the aqueous extract of Felicia muricata ...

    African Journals Online (AJOL)



    Mar 20, 2009 ... ... Length Research Paper. Toxicological evaluation of the aqueous extract of .... Development Research Institute (ARDRI), University of Fort Hare. The rats were housed in ..... livingstone, New York, p. 409. Stepp JR, Moerman ...

  11. 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<...

  12. 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.)

  13. 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/...

  14. ToxGuides: Quick Reference Pocket Guide for Toxicological Profiles (United States)

    ... L Lead [PDF, 79KB] M Malathion [PDF, 110KB] Manganese [PDF, 119KB] Methoxychlor [PDF, 107KB] N Nickel [PDF, ... contacting the ATSDR Information Center at: Agency for Toxic Substances and Disease Registry Division of Toxicology and ...

  15. Global warming and environmental contaminants in aquatic organisms: the need of the etho-toxicology approach. (United States)

    Manciocco, Arianna; Calamandrei, Gemma; Alleva, Enrico


    Environmental contaminants are associated with a wide spectrum of pathological effects. Temperature increase affects ambient distribution and toxicity of these chemicals in the water environment, representing a potentially emerging problem for aquatic species with short-, medium- and long-term repercussions on human health through the food chain. We assessed peer-reviewed literature, including primary studies, review articles and organizational reports available. We focused on studies concerning toxicity of environmental pollutants within a global warming scenario. Existing knowledge on the effects that the increase of water temperature in a contaminated situation has on physiological mechanisms of aquatic organisms is presented. Altogether we consider the potential consequences for the human beings due to fish and shellfish consumption. Finally, we propose an etho-toxicological approach to study the effects of toxicants in conditions of thermal increase, using aquatic organisms as experimental models under laboratory controlled conditions.

  16. 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...

  17. 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 (

  18. 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.

  19. The Toxicology Investigators Consortium Case Registry—The 2012 Experience


    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...

  20. 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.

  1. 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.

  2. 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.

  3. Pathology of intrahepatic cholangiocarcinoma (United States)

    Vijgen, Sandrine; Terris, Benoit


    Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation. Recent data pointed out noteworthy degree of heterogeneity in regards of their epidemiology and risk factors, pathological and molecular features, pathogenesis, clinical behaviors and treatment. Notably, several histological variants are described and can coexist within the same tumor. Several different cells of origin have also been depicted in a fraction of iCCs, amongst which malignant transformation of ductules, of hepatic stem/progenitor cells, of periductal glands or through oncogenic reprogramming of adult hepatocytes. A degree of pathological overlap with hepatocellular carcinoma (HCC) may be observed in a portion of iCC. A series of precursor lesions are today characterized and emphasize the existence of a multistep carcinogenesis process. Overall, these new data have brought up in proposal of new histological or molecular classifications, which could soon replace current anatomic-based classification and could have major impact on establishment of prognosis and on development of novel target treatment approaches. PMID:28261592

  4. [(Impending) pathological fracture]. (United States)

    Sutter, P M; Regazzoni, P


    Pathological fractures will be encountered in increasing frequency due to more patients with cancer, surviving a longer period. The skeleton is the third most frequent localization for metastases. Breast cancer is still the most common primary tumor, but bone metastases from lung cancer seem to be diagnosed more and more. Despite of finding metastases most often in the spinal column, fractures are seen mostly at the femoral site. A pathological fracture and, in almost all cases, an impending fracture are absolute indication for operation. An exact definition of an "impending fracture" is still lacking; it is widely accepted, that 50 per cent of bone mass must be destroyed before visualization in X-ray is possible, thus defining an impending fracture. The score system by Mirels estimates the fracture risk by means of four parameters (localization, per cent of destructed bone mass, type of metastasis, pain). Improving quality of life, relieving pain, preferably with a single operation and a short length of stay are the goals of (operative) treatment. For fractures of the proximal femur, prosthetic replacement, for fractures of the subtrochanteric region or the shaft, intramedullary nails are recommended. Postoperative radiation therapy possibly avoids tumor progression. In patient with a good long term prognosis, tumor should be removed locally aggressive.

  5. Pathology of the vestibulocochlear nerve

    Energy Technology Data Exchange (ETDEWEB)

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail:


    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  6. The in vitro toxicology of Swedish snus (United States)

    Coggins, Christopher R. E.; Ballantyne, Mark; Curvall, Margareta; Rutqvist, Lars-Erik


    Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes. PMID:22400986

  7. 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.

  8. Aquaculture: Environmental, toxicological, and health issues. (United States)

    Cole, David W; Cole, Richard; Gaydos, Steven J; Gray, Jon; Hyland, Greg; Jacques, Mark L; Powell-Dunford, Nicole; Sawhney, Charu; Au, William W


    Aquaculture is one of the fastest growing food-producing sectors, supplying approximately 40% of the world's fish food. Besides such benefit to the society, the industry does have its problems. There are occupational hazards and safety concerns in the aquaculture industry. Some practices have caused environmental degradation. Public perception to farmed fish is that they are "cleaner" than comparable wild fish. However, some farmed fish have much higher body burden of natural and man-made toxic substances, e.g. antibiotics, pesticides, and persistent organic pollutants, than wild fish. These contaminants in fish can pose health concerns to unsuspecting consumers, in particular pregnant or nursing women. Regulations and international oversight for the aquaculture industry are extremely complex, with several agencies regulating aquaculture practices, including site selection, pollution control, water quality, feed supply, and food safety. Since the toxicological, environmental, and health concerns of aquaculture have not been adequately reviewed recently, we are providing an updated review of the topic. Specifically, concerns and recommendations for improving the aquaculture industry, and for protection of the environment and the consumers will be concisely presented.

  9. Gaps in aquatic toxicological studies of microplastics. (United States)

    Karami, Ali


    The contamination of aquatic environments with microplastics (MPs) has spurred an unprecedented interest among scientific communities to investigate their impacts on biota. Despite the rapid growth in the number of studies on the aquatic toxicology of MPs, controversy over the fate and biological impacts of MPs is increasingly growing mainly due to the absence of standardized laboratory bioassays. Given the complex features of MPs, such as the diversity of constituent polymers, additives, shapes and sizes, as well as continuous changes in the particle buoyancy as a result of fouling and defouling processes, it is necessary to modify conventional bioassay protocols before employing them for MP toxicity testings. Moreover, several considerations including quantification of chemicals on/in the MP particles, choice of test organisms, approaches for renewing the test solution, aggregation prevention, stock solution preparation, and units used to report MP concentration in the test solution should be taken into account. This critical review suggests some important strategies to help conduct environmentally-relevant MP bioassays. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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.

  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. 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.

  14. No pain, no pathology? (United States)

    Sharma, Devesh; Govind, Abha


    A 22-year-old girl who had a background of reflux nephropathy and urinary tact infection presented during the night with renal angle pain and vomiting. She was treated on the emergency department (ED) pyelonephritis protocol and admitted to the short stay ward. When reviewed the next morning she was aymptomatic and feeling better. It seemed likely that she would be discharged but an ED ultrasound showed right-sided hydronephrosis and some fluid between the liver and the right kidney. CT examination confirmed the suspicion of renal tract obstruction and ruptured calyx. An 8 mm calculus was found to be the cause of the pathology. Urgent urological review was organised and the system formally decompressed with a J-J stent inserted cystoscopically later that day.

  15. Digital pathology: Attitudes and practices in the Canadian pathology community

    Directory of Open Access Journals (Sweden)

    Magdaleni Bellis


    Full Text Available Digital pathology is a rapidly evolving niche in the world of pathology and is likely to increase in popularity as technology improves. We performed a questionnaire for pathologists and pathology residents across Canada, in order to determine their current experiences and attitudes towards digital pathology; which modalities digital pathology is best suited for; and to assess the need for training in digital pathology amongst pathology residents and staff. An online survey consisting of 24 yes/no, multiple choice and free text questions regarding digital pathology was sent out via E-mail to all members of the Canadian Association of Pathologists and pathology residents across Canada. Survey results showed that telepathology (TP is used in approximately 43% of institutions, primarily for teaching purposes (65%, followed by operating room consults (46%. Seventy-one percent of respondents believe there is a need for TP in their practice; 85% use digital images in their practice. The top two favored applications for digital pathology are teaching and consultation services, with the main advantage being easier access to cases. The main limitations of using digital pathology are cost and image/diagnostic quality. Sixty-two percent of respondents would attend training courses in pathology informatics and 91% think informatics should be part of residency training. The results of the survey indicate that Pathologists and residents across Canada do see a need for TP and the use of digital images in their daily practice. Integration of an informatics component into resident training programs and courses for staff Pathologists would be welcomed.

  16. 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

  17. Latin America's present and future challenges in toxicology education. (United States)

    Rojas, M


    Industrialization that Latin America has experienced during the past 50 years, the increase of population and the growth of chemical-related industries has generated a variety of environmental problems that must be addressed. After assessing these profound changes, greater emphasis should be placed on the study of environmental health and toxicology. Latin American countries face many problems that are common to other developing nations. Therefore, there is a demand for safety assessment and regulatory control of chemicals that create a need for increasing numbers of toxicologists. To meet this demand, educational programs in toxicology have to be designed. This paper utilizes a consultation questionnaire that includes toxicology-network members, scientists and educational institutions where toxicology is taught. An analysis of the information collected is made, with an emphasis on what we currently lack and on future challenges for toxicology professionals. Although the response from the study institutions was 65% (13 countries out of 20), the paper aims to assess the present situation of toxicology. The convenience for a certification/recognition for toxicologists is also evaluated. Action needs to be taken to promote scientific development based on regional specific needs that require increasing at the number of toxicology programs, and promoting of cooperation between academics and researchers. Among the limitations we have are the variability of curricula, objectives and priorities. The increasing globalization of markets and regulations requires the harmonization of graduate/postgraduate programs to ensure that risk assessment and management are dealt with uniformly. Cooperation among our countries and international assistance should play a more prominent role in the promotion of regional integration and the more efficient utilization of international experience in defining educational policies.

  18. 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.

  19. Metabolites of lorazepam: Relevance of past findings to present day use of LC-MS/MS in analytical toxicology. (United States)

    Turfus, Sophie C; Braithwaite, Robin A; Cowan, David A; Parkin, Mark C; Smith, Norman W; Kicman, Andrew T


    The advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the sensitivity it confers, permits the analysis of both phase I and II drug metabolites that in the past would have been difficult to target using other techniques. These metabolites may have relevance to current analytical toxicology employing LC-MS/MS, and lorazepam was chosen as a model drug for investigation, as only the parent compound has been targeted for screening purposes. Following lorazepam administration (2 mg, p.o.) to 6 volunteers, metabolites were identified in urine by electrospray ionization LC-MS/MS, aided by the use of deuterated analogues generated by microsomal incubation for use as internal chromatographic and mass spectrometric markers. Metabolites present were lorazepam glucuronide, a quinazolinone, a quinazoline carboxylic acid, and two hydroxylorazepam isomers, one of which is novel, having the hydroxyl group located on the fused chlorobenzene ring. The quinazolinone, and particularly the quinazoline carboxylic acid metabolite, provided longer detection windows than lorazepam in urine extracts not subjected to enzymatic hydrolysis, a finding that is highly relevant to toxicology laboratories that omit hydrolysis in order to rapidly reduce the time spent on gas chromatography-mass spectrometry (GC-MS) analysis. With hydrolysis, the longest windows of detection were achieved by monitoring lorazepam, supporting the targeting of the aglycone with free drug for those incorporating hydrolysis in their analytical toxicology procedures.

  20. Tissue-specific toxicological effects of cadmium in green mussels (Perna viridis): nuclear magnetic resonance-based metabolomics study. (United States)

    Wu, Huifeng; Wang, Wen-Xiong


    Toxicity tests for metals have traditionally focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. Here nuclear magnetic resonance (NMR)-based metabolomics, a system biology tool, was applied to the marine green mussel, Perna viridis, to investigate the toxicological effects of Cd in both digestive gland and adductor muscle tissues. After Cd exposure for either two or four weeks, there was no significant metabolic change in the mussels exposed to Cd at 2 µg/L. At 20 µg/L, there were major metabolite changes related to amino acids, osmolytes, and energy metabolites. Digestive gland tissue was more sensitive to Cd than adductor muscle tissue. The adductor muscle tissue showed elevated levels of glutamine, glutamate, and lactate, and reduced levels of branched chain amino acids, aspartate, phenylalanine, and tyrosine. Overall, four weeks of Cd exposure produced neurotoxicity and metabolic disturbances and disturbed osmoregulation. These results suggest that the adductor muscle tissue of mussels may be a suitable supplemental biomarker for exposure to toxicants. In addition, the results demonstrate that (1) H-NMR-based metabolomic analysis can provide a systematic view of the toxicological effects of metals on mussels, suggesting that it might be employed to investigate the toxicological effects of other marine pollutants. Copyright © 2011 SETAC.

  1. Fraud, errors and gamesmanship in experimental toxicology. (United States)

    Purchase, Iain F H


    We expect moral behaviour from scientists. Morality implies being a good person and being good at one's profession. The general view appears to be that the vast majority of scientists aim to achieve these high standards. Science prides itself on the 'self-correcting' mechanism in the scientific method, namely the requirement to reproduce findings before they are taken seriously. However, when findings are related to the adverse effects of chemicals there are several features that make this less effective than in some other fields of science. First, is the perception that everyone is exposed to chemicals and observations about chemical danger are immediately applicable to many people. Second, it is often easy to summarize adverse findings in attention-getting headlines seen by the lay public before the slow process of replication and interpretation has time to work. Third, most regulatory toxicology studies on a particular compound are only done once to minimise cost and the use of animals. Finally, the question posed about chemicals--are they safe?--is easy to ask but more difficult to test with appropriate studies. Fabrication of data in regulatory studies was found to occur in several contract laboratories in the 1960s and this lead directly to the introduction of Good Laboratory Practice regulations. Now studies submitted for regulatory purposes must comply with GLP regulations and this has virtually eliminated flawed studies due to fraudulent or careless behaviour. It is possible to discern different ways in which the expected standards have not been met. The first is in the intention of the work. Thus reports that the Roodeplaats Research Laboratory in South Africa was seeking to identify toxins that would kill without trace is an example where the intention is unacceptable. The second is in the conduct of the studies. Here the examples of William McBride and Michael Briggs who falsified data are pertinent. The example of the retraction of reports on the

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Incorporating exposure into aquatic toxicological studies: an imperative. (United States)

    Wang, Wen-Xiong


    The field of aquatic toxicology has been expanding rapidly in recent years. The ecotoxicological study of environmental toxicants encompasses three basic frameworks: environmental behavior/transport, bioavailability/bioaccumulation (exposure), and toxicity at different biological levels. Environmental risk assessments are then based on this knowledge to provide sound advice for environmental management and policies. In this article I will highlight the need to further understand the exposure to toxicants and its direct relationship with toxicological responses at different levels. Exposure considerations generally include the route, species, concentration and duration of exposure, among which the importance of the exposure route has been little considered. A typical aquatic toxicological study simply exposes the organisms to toxicants in the water for a certain period of time under different concentrations. This approach may not be environmentally relevant. Future studies should attempt to understand the toxicology under different exposure regimes. Incorporating exposure will allow aquatic toxicology to be placed in a context of environmental relevance and enhance our understanding of the impacts of toxicants on our living environments. 2011 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. [Psychiatric comorbidity in pathological gambling]. (United States)

    Skokauskas, Norbertas; Satkeviciūte, Regina; Burba, Benjaminas


    In this article the peculiarities of psychiatric comorbidity in pathological gambling were investigated. The authors were based both on the data of many foreign scientists and on their own one. Our data on 77 cases of pathological gambling were collected based on interviews of Lithuanian psychiatrists and psychotherapists about their patients with gambling addiction in period from 1991 to 2001. The data that we publish and analyze allows us to make conclusions that pathological gambling can reveal together with very wide spectrum of psychiatric disorders, but more often with alcoholism and depression. The mechanism of psychiatric comorbidity in pathological gambling is very complex.

  11. Recommendations for pathology peer review. (United States)

    Morton, Daniel; Sellers, Rani S; Barale-Thomas, Erio; Bolon, Brad; George, Catherine; Hardisty, Jerry F; Irizarry, Armando; McKay, Jennifer S; Odin, Marielle; Teranishi, Munehiro


    Pathology peer review verifies and improves the accuracy and quality of pathology diagnoses and interpretations. Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies. For pathology peer review conducted before study completion, the peer-review pathologist reviews sufficient slides and pathology data to assist the study pathologist in refining pathology diagnoses and interpretations. Materials to be reviewed are selected by the peer-review pathologist. Consultations with additional experts or a formal (documented) pathology working group may be used to resolve discrepancies. The study pathologist is solely responsible for the content of the final pathology data and report, makes changes resulting from peer-review discussions, initiates the audit trail for microscopic observations after all changes resulting from peer-review have been made, and signs the final pathologist's report. The peer-review pathologist creates a signed peer-review memo describing the peer-review process and confirming that the study pathologist's report accurately and appropriately reflects the pathology data. The study pathologist also may sign a statement of consensus. It is not necessary to archive working notes created during the peer-review process.

  12. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology]. (United States)

    Baliasnyĭ, M M


    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

  13. [The isozymes of stearil-coenzymeA-desaturase and insulin activity in the light of phylogenetic theory of pathology. Oleic fatty acid and realization of biologic functions of trophology and locomotion]. (United States)


    The formation of function of isozymes of stearil-coenzymeA-desaturases occured at the different stages of phylogeny under realization of biologic function of trophology (stearil-coenzymeA-desaturase 1) and biologic function of locomotion, insulin system (stearil-coenzymeA-desaturase 2) billions years later. The stearil-coenzymeA-desaturase 1 transforms in C 18:1 oleic fatty acid only exogenous C 16:0 palmitinic saturated fatty acid. The stearil-coenzymeA-desaturase 2 transforms only endogenic palmitinic saturated fatty acid, synthesized form glucose. The biologic role of insulin is in energy support of biologic function of locomotion. Insulin through expressing stearil-coenzymeA-desaturase 2 transforms energetically non-optimal palmitinic variation of metabolism of substrates into highly effective oleic variation for cells' groundwork of energy (saturated fatty acid and mono fatty acid). The surplus of palmitinic saturated fatty acid in food is enabled in pathogenesis of resistance to insulin and derangement of synthesis of hormone by beta-cells of islets. The resistance to insulin and diabetes mellitus are primarily the derangement of metabolism of saturated fatty acids with mono fatty acids, energy problems of organism and only afterwards the derangement of metabolism of carbohydrates. It is desirable to restrict food intake of exogenous palmitinic saturated fatty acid. The reasons are low expression of independent of insulin stearil-coenzymeA-desaturase 2, marked lipotoxicity of polar form of palmitinic saturated fatty acid and synthesis of non-optimal palmitinic triglycerides instead of physiologic and more energetically more effective oleic triglycerides.

  14. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)


    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. Acute toxicology of components of vegetation smoke. (United States)

    Dost, F N


    Only in recent times, systematic attention has been paid to the occupational health of forest firefighters and workers who manage prescribed fire. Two parts of the effort to learn the impact on worker health are medical observation of those workers, and study of occupational hygiene. It is also necessary to learn what components of smoke are most likely to affect firefighters, and to learn something of the manner in which those substances might compromise health; this review is a step toward that end. The number of possible products of vegetation combustion is almost limitless, and every fuel and condition of burning produces a unique pattern. Nonetheless, it is possible and practical to select a limited number of products that are most likely to be involved in the acute toxicity of smoke. Two products that are almost certainly important are formaldehyde and acrolein. Both appear to occur in all smoke. The toxicology of both is well studied; in particular both are powerful mucosal irritants. Estimates of exposure suggest strongly that concentrations are high enough in smoke to contribute some or all of the irritant activity. There seems to be a reasonable prospect that free radical precursors with half-lives in the tens of minutes are produced when cellulosic materials burn. If so, they will reach the respiratory tract, and liberate free radicals that react immediately on or in pulmonary cells. Ozone is not produced in the fire, but the various hydrocarbons of smoke are substrates for reactions that eventually produce ozone, and that production may continue for miles down-plume. Some measured plume concentrations approach the threshold for human health effects. The effects of the best known component, the particulate material, are unknown in isolation from all of the other substances in smoke. In spite of that ignorance, particulate loading is the principal index of smoke pollution for regulatory purposes, and sometimes is incorrectly used to represent smoke

  20. 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

  1. 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

  2. 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.

  3. Arsenic in the groundwater: Occurrence, toxicological activities, and remedies. (United States)

    Jha, S K; Mishra, V K; Damodaran, T; Sharma, D K; Kumar, Parveen


    Arsenic (As) contamination in groundwater has become a geo-environmental as well as a toxicological problem across the globe affecting more than 100-million people in nearly 21 countries with its associated disease "arsenicosis." Arsenic poisoning may lead to fatal skin and internal cancers. In present review, an attempt has been made to generate awareness among the readers about various sources of occurrence of arsenic, its geochemistry and speciation, mobilization, metabolism, genotoxicity, and toxicological exposure on humans. The article also emphasizes the possible remedies for combating the problem. The knowledge of these facts may help to work on some workable remedial measure.

  4. 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.

  5. 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.

  6. The effect of lead exposure on fatty acid composition in mouse brain analyzed using pseudo-catalytic derivatization. (United States)

    Jung, Jong-Min; Lee, Jechan; Kim, Ki-Hyun; Jang, In Geon; Song, Jae Gwang; Kang, Kyeongjin; Tack, Filip M G; Oh, Jeong-Ik; Kwon, Eilhann E; Kim, Hyung-Wook


    We performed toxicological study of mice exposed to lead by quantifying fatty acids in brain of the mice. This study suggests that the introduced analytical method had an extremely high tolerance against impurities such as water and extractives; thus, it led to the enhanced resolution in visualizing the spectrum of fatty acid profiles in animal brain. Furthermore, one of the biggest technical advantages achieved in this study was the quantitation of fatty acid methyl ester profiles of mouse brain using a trace amount of sample (e.g., 100 μL mixture). Methanol was screened as the most effective extraction solvent for mouse brain. The behavioral test of the mice before and after lead exposure was conducted to see the effect of lead exposure on fatty acid composition of the mice' brain. The lead exposure led to changes in disease-related behavior of the mice. Also, the lead exposure induced significant alterations of fatty acid profile (C16:0, C 18:0, and C 18:1) in brain of the mice, implicated in pathology of psychiatric diseases. The alteration of fatty acid profile of brain of the mice suggests that the derivatizing technique can be applicable to most research fields associated with the environmental neurotoxins with better resolution in a short time, as compared to the current protocols for lipid analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.


    Gutiérrez-Salmeán, Gabriela; Fabila-Castillo, Luis; Chamorro-Cevallos, German


    Undernutrition constitutes a public health problem particularly in developing countries. The utilization of algae, particularly Spirulina, as a functional food was suggested decades ago due to the fact that it is not only a protein-dense food source, but because its amino acid profile is considered as of high biologic-value protein content. Spirulina provides essential fats (e.g., gamma-linolenic oleic acids), concomitant to low content nucleic acids. It also has an exceptionally high content of vitamin B12, is a good source of beta-carotene, iron, calcium and phosphorous. Moreover, Spirulina has also proven to have good acceptance as of its organoleptic properties (thus making it a possible prospect for food or a nutrition supplement) and it has not exhibited neither acute nor chronic toxicities, making it safe for human consumption.

  8. A Nutritional-Toxicological Assessment of Antarctic Krill Oil versus Fish Oil Dietary Supplements (United States)

    Bengtson Nash, Susan M.; Schlabach, Martin; Nichols, Peter D.


    Fish oil dietary supplements and complementary medicines are pitched to play a role of increasing strategic importance in meeting daily requirements of essential nutrients, such as long-chain (≥C20, LC) omega-3 polyunsaturated fatty acids and vitamin D. Recently a new product category, derived from Antarctic krill, has been launched on the omega-3 nutriceutical market. Antarctic krill oil is marketed as demonstrating a greater ease of absorption due to higher phospholipid content, as being sourced through sustainable fisheries and being free of toxins and pollutants; however, limited data is available on the latter component. Persistent Organic Pollutants (POP) encompass a range of toxic, man-made contaminants that accumulate preferentially in marine ecosystems and in the lipid reserves of organisms. Extraction and concentration of fish oils therefore represents an inherent nutritional-toxicological conflict. This study aimed to provide the first quantitative comparison of the nutritional (EPA and DHA) versus the toxicological profiles of Antarctic krill oil products, relative to various fish oil categories available on the Australian market. Krill oil products were found to adhere closely to EPA and DHA manufacturer specifications and overall were ranked as containing intermediate levels of POP contaminants when compared to the other products analysed. Monitoring of the pollutant content of fish and krill oil products will become increasingly important with expanding regulatory specifications for chemical thresholds. PMID:25170991

  9. Preparation and toxicological assessment of functionalized carbon nanotube-polymer hybrids.

    Directory of Open Access Journals (Sweden)

    Nikos D Koromilas

    Full Text Available Novel Carbon Nanotube-Polymer Hybrids were synthesized as potential materials for the development of membranes for water treatment applications in the field of Membrane Bioreactors (MBRs. Due to the toxicological concerns regarding the use of nanomaterials in water treatment as well as the rising demand for safe drinking water to protect public health, we studied the functionalization of MWCNTs and Thin-MWCNTs as to control their properties and increase their ability of embedment into porous anisotropic polymeric membranes. Following the growth of the hydrophilic monomer on the surface of the properly functionalized CNTs, that act as initiator for the controlled radical polymerization (ATRP of sodium styrene sulfonate (SSNa, the antimicrobial quaternized phosphonium and ammonium salts were attached on CNTs-g-PSSNa through non-covalent bonding. In another approach the covalent attachment of quaternized ammonium polymeric moieties of acrylic acid-vinyl benzyl chloride copolymers with N,N-dimethylhexadecylamine (P(AA12-co-VBCHAM on functionalized CNTs has also been attempted. Finally, the toxicological assessment in terms of cell viability and cell morphological changes revealed that surface characteristics play a major role in the biological response of functionalized CNTs.

  10. A Nutritional-Toxicological Assessment of Antarctic Krill Oil versus Fish Oil Dietary Supplements

    Directory of Open Access Journals (Sweden)

    Susan M. Bengtson Nash


    Full Text Available Fish oil dietary supplements and complementary medicines are pitched to play a role of increasing strategic importance in meeting daily requirements of essential nutrients, such as long-chain (≥C20, LC omega-3 polyunsaturated fatty acids and vitamin D. Recently a new product category, derived from Antarctic krill, has been launched on the omega-3 nutriceutical market. Antarctic krill oil is marketed as demonstrating a greater ease of absorption due to higher phospholipid content, as being sourced through sustainable fisheries and being free of toxins and pollutants; however, limited data is available on the latter component. Persistent Organic Pollutants (POP encompass a range of toxic, man-made contaminants that accumulate preferentially in marine ecosystems and in the lipid reserves of organisms. Extraction and concentration of fish oils therefore represents an inherent nutritional-toxicological conflict. This study aimed to provide the first quantitative comparison of the nutritional (EPA and DHA versus the toxicological profiles of Antarctic krill oil products, relative to various fish oil categories available on the Australian market. Krill oil products were found to adhere closely to EPA and DHA manufacturer specifications and overall were ranked as containing intermediate levels of POP contaminants when compared to the other products analysed. Monitoring of the pollutant content of fish and krill oil products will become increasingly important with expanding regulatory specifications for chemical thresholds.

  11. 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...

  12. 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...

  13. FORUM - FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology (United States)

    FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo resp...

  14. 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.

  15. STP Best Practices for Evaluating Clinical Pathology in Pharmaceutical Recovery Studies. (United States)

    Tomlinson, Lindsay; Ramaiah, Lila; Tripathi, Niraj K; Barlow, Valerie G; Vitsky, Allison; Poitout-Belissent, Florence M; Bounous, Denise I; Ennulat, Daniela


    The Society of Toxicologic Pathology formed a working group in collaboration with the American Society for Veterinary Clinical Pathology to provide recommendations for the appropriate inclusion of clinical pathology evaluation in recovery arms of nonclinical toxicity studies but not on when to perform recovery studies. Evaluation of the recovery of clinical pathology findings is not required routinely but provides useful information on risk assessment in nonclinical toxicity studies and is recommended when the ability of the organ to recover is uncertain. The study design generally requires inclusion of concurrent controls to separate procedure-related changes from test article-related changes, but return of clinical pathology values toward baseline may be sufficient in some cases. Evaluation of either a select or full panel of standard hematology, coagulation, and serum and urine chemistry biomarkers can be scientifically justified. It is also acceptable to redesignate dosing phase animals to the recovery phase or vice versa to optimize data interpretation. Assessment of delayed toxicity during the recovery phase is not required but may be appropriate in development programs with unique concerns. Evaluation of the recovery of clinical pathology data for vaccine development is required and, for efficacy markers, is recommended if it furthers pharmacologic understanding.

  16. Workshop on Problems in Chemical Toxicology (United States)


    or so enzymes in snake venom. Enzymes in Snake Venoms Acetylcholinesterase ( Elapidae ) L-Amino Acid Oxidase Araylase Arginine Ester Hydrolase (Not... Elapidae ) Catalase Deo>yribonuclease Endopertidase (Not Elapidae ) Factor X Activator (Not Elapidae ) Glycerophosphatase ( Elapidae ) Hyaluronidase...Kininogenase (Mot Elapidae ) Lactate Oehydrogenase NAD Nucleosidase Phosphodiesterase Phospholipase Ao Phospholipase B ’’hosphomonoesterase

  17. Toxicological evaluation of two pedigrees of clam Ruditapes philippinarum as bioindicators of heavy metal contaminants using metabolomics. (United States)

    Ji, Chenglong; Cao, Lulu; Li, Fei


    Heavy metal pollution has been of great concern in the Bohai marine environment. Manila clam Ruditapes philippinarum has been used as a bioindicator in marine toxicology. In this study, NMR-based metabolomics was used to ascertain whether there were significant biological differences between two dominant pedigrees (White and Zebra) of clam and evaluate the suitability of two pedigrees for marine environmental toxicology, together with antioxidant enzymatic analysis. Our results indicated that there were significant biological differences between White and Zebra clams based on the metabolic profiles and antioxidant enzyme activities. In details, the metabolic profiles showed higher levels of amino acids and succinate in Zebra clam digestive glands and higher levels of ATP in White clam digestive glands, respectively. The superoxide dismutase activities in control White and Zebra clam samples were significantly different. Additionally, White clam was more sensitive to Cd based on the significant accumulation of Cd, antioxidant enzymatic alterations and sensitive metabolic changes. Overall, we concluded that White clam could be a preferable bioindicator for marine environmental toxicology. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Toxicological effects induced by cadmium in gills of Manila clam ruditapes philippinarum using NMR-based metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Linbao; Liu, Xiaoli; You, Liping; Zhou, Di [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); The Graduate School of Chinese Academy of Sciences, Beijing (China); Yu, Junbao; Zhao, Jianmin; Wu, Huifeng [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); Feng, Jianghua [Department of Electronic Science, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen (China)


    Cadmium (Cd) has become an important heavy metal contaminant in the sediment and seawater along the Bohai Sea and been of great ecological risk due to its toxic effects to marine organisms. In this work, the toxicological effects caused by environmentally relevant concentrations (10 and 40 {mu}g L{sup -1}) of Cd were studied in the gill tissues of Manila clam Ruditapes philippinarum after exposure for 24, 48, and 96 h. Both low (10 {mu}g L{sup -1}) and high (40 {mu}g L{sup -1}) doses of Cd caused the disturbances in energy metabolism and osmotic regulation and neurotoxicity based on the metabolic biomarkers such as succinate, alanine, branched chain amino acids, betaine, hypotaurine, and glutamate in clam gills after 24 h of exposure. However, the recovery of toxicological effects of Cd after exposure for 96 h was obviously observed in clam to Cd exposures. Overall, these results indicated that NMR-based metabolomics was applicable to elucidate the toxicological effects of heavy metal contaminants in the marine bioindicator. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Toxicology and pharmacology of sodium ricinoleate. (United States)

    Burdock, George A; Carabin, Ioana G; Griffiths, James C


    Ricinoleic acid constitutes approximately 90% of the fatty acid content of castor oil. Castor oil is known for its purgative effects and can be used to induce labor. Both castor oil and ricinoleic acid are approved for use in food. The mechanistic basis for purgative actions likely includes the membrane-disruptive effects of detergent-like molecules, such as sodium ricinoleate (a 'soap'). These effects have been shown to be dose-related and to exhibit a threshold below which no laxative response was evident, in both animals and in humans. Castor oil was not toxic in subchronic feeding studies in rodents at doses ranging up to 10-20% of the diet. Sodium ricinoleate, as a surfactant, demonstrates predictable skin and mucus membrane irritant effects, and may induce a Type IV dermal sensitization response in those previously sensitized to it. However, food-grade castor oil and sodium ricinoleate are prepared in such a manner as to be free of the castor bean constituents that have been proven to be the source of reported Type I immediate hypersensitivity responses. Feeding studies with castor oil in rodents provide a basis for a no observable adverse effect level (NOAEL) estimate of 7,500 mg/kg/day and 5,000 mg/kg/day in mice and rats, respectively (). Applying an uncertainty factor of 100 to the lesser of these NOAELs, one can thus estimate an acceptable daily intake (ADI) in man to be 50 mg/kg, or 3,000 mg of castor oil per day in an average 60 kg person. As ricinoleic acid constitutes approximately 90% of castor oil, applying this calculation to the 3,000 mg/day estimated ADI in humans for castor oil (given the rapid hydrolysis of castor oil glyceride in the gastrointestinal tract), the acceptable daily intake of ricinoleic acid may be as high as 2,400 mg/person.

  20. Utilization management in anatomic pathology. (United States)

    Lewandrowski, Kent; Black-Schaffer, Steven


    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management.

  1. 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…

  2. 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...

  4. [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.

  5. 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

  6. 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.

  7. Experimental designs and risk assessment in combination toxicology: Panel discussion

    NARCIS (Netherlands)

    Henschler, D.; Bolt, H.M.; Jonker, D.; Pieters, M.N.; Groten, J.P.


    Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prereq

  8. 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...

  9. 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

  10. 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

  11. IRIS Toxicological Review of Ethylene Glycol Mono Butyl ... (United States)

    EPA has finalized the Toxicological Review of Ethylene Glycol Mono Butyl Ether: 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. N/A

  12. Experimental designs and risk assessment in combination toxicology: Panel discussion

    NARCIS (Netherlands)

    Henschler, D.; Bolt, H.M.; Jonker, D.; Pieters, M.N.; Groten, J.P.


    Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A

  13. Correlation Between Physicochemical Characteristics and Toxicological Properties of Nanomaterials (United States)


    Schlager, and Hussain. “Crystal Structure Mediates Mode of Death in TiO2 Nanotoxicity”. J. Nanopart . Res. (2009) 11: 1361-1374. Cho and Biswas...nanoparticle dispersions for toxicological studies. J Nanopart . Res. (on-line June, 2008), 11:77-89, 2009. Kim, SC, Chen, D-R, Qi, C., Gelein RM

  14. (Q)SARs for human toxicological endpoints: a literature search

    NARCIS (Netherlands)

    Hulzebos E; Schielen P; Masilankiewicz L; CSR; NVIC


    The goal here was to describe human toxicological SARs (structure-activity relationships) available in the literature and used by the US EPA (Environmental Protection Agency). The CSR laboratory investigated implementation of SARs for the effect assessment. SARs correlate the molecular structure

  15. 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.

  16. 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.

  17. 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

  18. Correlating toxicological effects of ionic liquids on Daphnia magna with in silico calculated linear free energy relationship descriptors. (United States)

    Cho, Chul-Woong; Yun, Yeoung-Sang


    In silico prediction model for toxicological effects of ionic liquids (ILs) is useful to understand ILs' toxicological interactions and to design environmentally benign IL structures. Actually, it is essential since the types of ILs are extremely numerous. Accordingly, prediction models were developed in this study. For the modelling, well-defined linear free energy relationship (LFER) descriptors - i.e. excess molar refraction (E), dipolarity/polarizability (S), H-bonding acidity (A), H-bonding basicity (B), McGowan volume (V), cation interaction (J(+)) and anion interaction (J(-)) - were in silico calculated using density functional theory and conductor-like screening model. These descriptors were then correlated with the toxicological values of ILs to Daphnia magna. First, a model established by Hoover et al. (2007) using measured LFER descriptors of 97 neutral compounds was applied to the prediction of ILs' toxicity. As expected, the model by Hoover et al. (2007) needs to be amended for ILs. To that end, the difference in toxicological interactions between neutral compounds and ILs was addressed by additional single J(+) or five LFER descriptors of cation i.e. Ec, Sc, Bc, Vc, and J(+). Secondly, a prediction model for only ILs was developed by using the three LFER descriptors Ec, Bc, and J(+). The model had a reasonable predictability and robustness of R(2) = 0.880 for the training set, 0.848 for the test set, and 0.867 for the overall set. The established models can be used to design environmentally benign IL structures and to reduce labour, danger, time, and materials compared to the experiment-based study.

  19. Non-covalent Interaction of Perfluorooctanoic Acid with DNA

    Institute of Scientific and Technical Information of China (English)

    ZHANG, Xian; SHEN, Rong; CHEN, Ling


    Health risk from exposure of perfluorochemicals to wildlife and human has been a subject of concern in many fields such as environmental ecology, toxicology, pathology and life sciences. The interactions of perfluorooctanoic acid (PFOA) with DNA were investigated by equilibrium dialysis, circular dichroism and isothermal titration calorimetry techniques under normal physiological conditions in vitro. The binding of PFOA to DNA was a non-covalent interaction and corresponded to the Langmuir adsorption isotherm in a two-step binding model, in which PFOA climbed along the backbones of DNA and then interacted with the homolateral bases via hydrophobic interactions. The saturation number of PFOA was calculated to be 0.64 per base-pair of DNA. Such an interaction caused the enhancement of circular dichroism spectra of DNA at both 245 and 275 nm, indicating the change of DNA conformation. The acidic media, low electrolyte and temperature ≤35 ℃ are comparatively more favorable for PFOA binding to DNA. This work provides a useful experimental strategy for studying the interactions of perfluorochemicals with biomacromolecules, aiming at a better understanding of the gene toxicity mechanism of perfluorochemicals.

  20. [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?

  1. 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.

  2. MLE's bias pathology motivates MCMLE


    Yatracos, Yannis G.


    Maximum likelihood estimates are often biased. It is shown that this pathology is inherent to the traditional ML estimation method for two or more parameters, thus motivating from a different angle the use of MCMLE.

  3. Systemic disorders affecting dental pathology

    Directory of Open Access Journals (Sweden)

    Knežević Milan R


    Full Text Available A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a congenital dental developmental disorders, (b chromosomal anomalies, (c radiations, (d immune disorders, (e intoxications, (f neurological alterations, (g gastrointestinal diseases, (h osteodystrophy and associated conditions, (i skin diseases, (j metabolic and endocrine disorders, (k craniofacial malformation syndromes and other congenital general malformations. The associated dental pathology is described in each case.

  4. [Methods and methodology of pathology]. (United States)

    Lushnikov, E F


    The lecture gives the state-of-the-art of the methodology of human pathology that is an area of the scientific and practice activity of specialists to produce and systematize objective knowledge of pathology and to use the knowledge in clinical medicine. It considers the objects and subjects of an investigation, materials and methods of a pathologist, and the results of his/her work.

  5. Development of pathology in Turkey

    Directory of Open Access Journals (Sweden)

    Gökhan GEDİKOĞLU


    Full Text Available Autospy is an important tool for the development of pathology as a science. In western civilisation dissection of human body became widespread with Renaissance, in contrast in the Ottoman Empire first dissection was not performed until the 19th century. Mustafa Behçet Efendi, head physician of the Empire, was one of the Ottoman physician who suggested the importance of dissection in the medical education. The first dissection was however performed by Charles Ambroise Bernard, a foreign physician who had been invited to help establishing a new medical school; “Mekteb-i Tıbbiye-i Adliye-i Şâhâne”, in 1843. The first modern medical schools called “Tıphane” and “Cerrahhane-i Amire” which were founded in 1827, did not have pathology courses. Pathology courses began in “Mekteb-i Tıbbiye-i Adliyei Şâhâne”. Dr. Hamdi Suat (Aknar, educated in anatomic pathology in Germany, was the first pathologist who established the modern pathology in Turkey in “İstanbul Darülfünun” medical school. In 1933 “Darülfünün” was closed and İstanbul University was built and the “University Reform Commission” invited many scientists escaping from Nazi government to study in İstanbul University. Dr. Philipp Schwartz had an important role both in the invitation of these scientists and establishment of the pathology department in İstanbul University. Practical courses were increased, clinicopathologic courses were organized for the first time and a lot of autopsies were performed, as high as 1000 autopsy per year, by Dr. Philipp Schwartz. More progress has takes place in Turkey over the years since pathology was first established. Today Turkey has many pathology departments which keep up with the worldwide advances in the field.

  6. Retrospective study of melamine/cyanuric acid-induced renal failure in dogs in Korea between 2003 and 2004. (United States)

    Yhee, J-Y; Brown, C A; Yu, C-H; Kim, J-H; Poppenga, R; Sur, J-H


    In early 2007, American pet food ingredients leading to nephrotoxic renal failure of dogs and cats raised serious concerns about the safety of pet foods. Major pet food companies recalled more than 1,000 commercial pet foods in consideration of pet safety. A similar pet food-associated outbreak of nephrotoxic renal failure occurred in Asia, in late 2003 and 2004, resulting in a similar extensive pet food recall. At that time, contamination of ingredients with a nephrotoxin-producing fungus at a pet food production facility was suspected. However, toxicologic evidence to substantiate a mycotoxicosis was lacking. Moreover, the renal lesions were not typical of those reported with fungal nephrotoxins. During 2003 and 2004, 14 dogs were presented to the Veterinary Medical Teaching Hospital of Konkuk University, Seoul, Korea, with renal failure and distinctive renal pathologic findings. Grossly, the kidneys were greenish in color with greenish uroliths in the renal pelvis or bladder. Histologically, characteristic crystals with pinwheel radiating striations were present in distal tubular segments. Toxicologic analysis identified melamine, cyanuric acid, and ammelide in deparaffinized formalin-fixed kidney samples.

  7. Bone pathology inpsoriatic arthritis

    Directory of Open Access Journals (Sweden)

    V. V. Badokin


    Full Text Available Objective. To study different variants of osteolysis in pts with psoriatic arthritis (PA and to reveal their relationship with other clinico-radiological features of joint damage. Material and methods. 370 pts with definite PA having different variants of joint damage were included. Radiological examination of bones and joints (in some cases large picture frame was performed. Morphological evaluation of synovial biopsies was done in 34 pts with PA and 10 pts with rheumatoid arthritis (RA. Results. Different types of osteolysis were revealed in 80 (21,6% pts. Osteolytic variant of joint damage was present in 29 pts. 33 pts had acral, 48 — intra-articular osteolysis and 16 - true bone atrophy. Frequency and intensity of bone resorption were associated with severity of PA. Acral osteolysis correlated with arthritis of distal interphalangeal joints and onychodystrophy. Intra-articular osteolysis was most often present in distal interphalangeal joints of hands and metacarpophalangeal joints (39,6% and 41,7% respectively. Characteristic feature of PA was combination of prominent resorption with formation of bone ankylosis and periosteal reaction. Ankylosis was present in 33,3% of pts with intra-articular osteolysis and in 60% of pts with combination of different osteolysis variants. Systemic reaction of microcirculation in synovial biopsies was most prominent in osteolytic variant: marked thickening of capillary and venule basal membrane with high level of acid phosphatase, increased capillary and precapillary blood flow with stasis features, vascular lymphocyte and macrophage infiltration, productive vasculitis with annular wall thickening, thrombovasculitis and villi deep layer sclerosis. Conclusion. Different variants of osteolysis show bone involvement in PA. Acral and intra- articular osteolysis association with bone ankylosis and periostitis proves their common pathogenetic entity.

  8. 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.

  9. 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.

  10. Waste Water Disinfection During SARS Epidemic for Microbiological and Toxicological Control

    Institute of Scientific and Technical Information of China (English)



    Objective To evaluate the disinfection of wastewater in China. Methods During the SARS epidemic occurred in Beijing, a study of different disinfection methods used in the main local wastewater plants including means of chlorine, chlorine dioxide, ozone, and ultraviolet was carried out in our laboratory. The residual coliform, bacteria and trihalomethanes, haloacetic acids were determined after disinfection. Results Chlorine had fairly better efficiency on microorganism inactivation than chlorine dioxide with the same dosage. Formation of THMs and HAAs does not exceed the drinking water standard. UV irradiation had good efficiency on microorganism inactivation and good future of application in China. Organic material and ammonia nitrogen was found to be significant on inactivation and DBPs formation. Conclusion Chlorine disinfection seems to be the best available technology for coliform and bacteria inactivation. And it is of fairly low toxicological hazard due to the transformation of monochloramine.

  11. Comprehensive investigation of hydroxypropyl methylcellulose, propylene glycol, polysorbate 80, and hydroxypropyl-beta-cyclodextrin for use in general toxicology studies. (United States)

    Thackaberry, Evan A; Kopytek, Stephen; Sherratt, Phillip; Trouba, Kevin; McIntyre, Barry


    This study was conducted to assess the safety and tolerability of the alternative formulation vehicles polysorbate 80 (PS80), propylene glycol (PG), and hydroxypropyl-beta-cyclodextrin (HPβCD) in general toxicology studies in the mouse, rat, dog, and monkey. Twenty (20) mg/kg of hydroxypropyl methylcellulose (MC, control), 10 mg/kg PS80, 1000 mg/kg PG, 500 mg/kg HPβCD, or 1000 mg/kg HPβCD were administered by oral gavage to mice, rats, dogs, and cynomolgus monkeys for approximately 90 days. The effects of these formulations on clinical observations, body weight and food consumption parameters, clinical pathology, and histopathology were evaluated across all species. The suitability of formulations containing up to 20 mg/kg MC, 10 mg/kg PS80, and 1000 mg/kg PG for use in preclinical safety studies was confirmed by a lack of effects on all parameters examined. However, formulations containing HPβCD produced elevated transaminase (aspartate and alanine aminotransferase) levels in rats and mice and fecal changes (loose and soft stool) in large animals. Although the etiology and toxicological significance of the transaminase elevations in rats and mice is uncertain, this finding could represent a significant liability for a preclinical formulation because of the critical importance of these biomarkers in the risk assessment of novel therapeutic agents. Based on these data, PS80 and PG are considered to be practical alternatives to MC in preclinical toxicology studies. However, formulations containing HPβCD should be used with caution because of the elevations in rodent transaminase levels.

  12. Studies on the metabolism and the toxicological analysis of the nootropic drug fipexide in rat urine using gas chromatography-mass spectrometry. (United States)

    Staack, Roland F; Maurer, Hans H


    Qualitative studies are described on the metabolism and the toxicological analysis of the nootropic fipexide (FIP) in rat urine using gas chromatography-mass spectrometry (GC-MS). FIP was extensively metabolized to 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), 4-chlorophenoxyacetic acid, 1-[2-(4-chlorophenoxy)acetyl]piperazine, N-(4-hydroxy-3-methoxy-benzyl)piperazine, piperazine, N-(3,4-methylenedioxybenzyl)ethylenediamine, and N-[2-(4-chlorophenoxy)acetyl]ethylenediamine. The authors' systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis of one urine aliquot, liquid-liquid extraction and acetylation allowed the detection of FIP via its metabolites in rat urine after administration of a common FIP dose. Therefore, this qualitative procedure should also be suitable for detection of a FIP intake in human urine. Differentiation of an intake of FIP from that of other drugs which form common metabolites is discussed.

  13. Toxicological evaluation of arachidonic acid (ARA)-rich oil and docosahexaenoic acid (DHA)-rich oil. (United States)

    Lewis, Kara D; Huang, Weifeng; Zheng, Xiaohui; Jiang, Yue; Feldman, Robin S; Falk, Michael C


    The safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina was separately evaluated by testing for gene mutations, clastogenicity, and aneugenicity, and by conducting 28-day and 90-day dietary studies in Wistar rats. The results of all genotoxicity tests were negative. The 28-day and 90-day studies involved dietary exposure to 1000, 2500, and 5000 mg per kg bw of the DHA-rich and ARA-rich oils and two control diets: water and corn oil (vehicle control). There were no treatment-related effects of either the DHA-rich or ARA-rich oils on clinical observations, body weight, food consumption, behavior, hematology, clinical chemistry, coagulation, urinalysis parameters, or necropsy findings. Increases in cholesterol and triglyceride levels were considered related to a high oil diet and non-adverse. The no observable adverse effect level (NOAEL) for both the DHA-rich and ARA-rich oils was 5000 mg per kg bw, the highest dose tested. The results confirm that these oils possess toxicity profiles similar to those of other currently marketed oils and support the safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina for their proposed uses in food.

  14. A concise review of carbon nanotube's toxicology

    Directory of Open Access Journals (Sweden)

    Seyed Yazdan Madani


    Full Text Available Carbon nanotubes can be either single-walled or multi-walled, each of which is known to have a different electron arrangement and as a result have different properties. However, the shared unique properties of both types of carbon nanotubes (CNT allow for their potential use in various biomedical devices and therapies. Some of the most common properties of these materials include the ability to absorb near-infra-red light and generate heat, the ability to deliver drugs in a cellular environment, their light weight, and chemical stability. These properties have encouraged scientists to further investigate CNTs as a tool for thermal treatment of cancer and drug delivery agents. Various promising data have so far been obtained about the usage of CNTs for cancer treatment; however, toxicity of pure CNTs represents a major challenge for clinical application. Various techniques both in vivo and in in vitro have been conducted by a number of different research groups to establish the factors which have a direct effect on CNT-mediated cytotoxicity. The main analysis techniques include using Alamar blue, MTT, and Trypan blue assays. Successful interpretation of these results is difficult because the CNTs can significantly disrupt the emission of the certain particles, which these assays detect. In contrast, in vivo studies allow for the measurement of toxicity and pathology caused by CNTs on an organismal level. Despite the drawbacks of in vitro studies, they have been invaluable in identifying important toxicity factors, such as size, shape, purity, and functionalisation, the latter of which can attenuate CNT toxicity.

  15. 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.

  16. NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis. (United States)

    Wu, Huifeng; Wang, Wen-Xiong


    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. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats. (United States)

    Nishizato, Yohei; Imai, Satoki; Yabunaka, Atsushi; Okahashi, Noriko; Kunimatsu, Takeshi; Yabuki, Masashi


    SMP-028 is a new compound for treatment of asthma. Oral administration of SMP-028 to rats was associated with toxicological events in endocrine organs. These events mainly consisted of pathological changes in the adrenal gland, testis, prostate, seminal vesicle, ovaries, and uterus. In this study, we set to clarify whether SMP-028 inhibits steroidogenesis in primary culture cells obtained from rat endocrine organs in vitro. Adrenal cells, testicular cells, and ovarian cells were treated with SMP-028 and the production of steroid hormones, i.e., progesterone, aldosterone, corticosterone, total testosterone, and estradiol from these cells was measured by radioimmunoassay. We found that the production of progesterone from these cells treated with SMP-028 at 1 μM decreased to 16-67% that of the control. These findings indicate that SMP-028 inhibits steroidogenesis in rat endocrine organs in vitro. Considering that free maximum concentration in rats treated with SMP-028 are higher than the IC50 values for the inhibition of steroidogenesis in vitro, it is therefore believed that the toxicological events seen in rats following treatment with SMP-028 are due to inhibition of steroidogenesis in vivo.

  18. 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.

  19. Sulfur: its clinical and toxicologic aspects. (United States)

    Komarnisky, Lioudmila A; Christopherson, Robert J; Basu, Tapan K


    Although there is no known dietary requirement for inorganic sulfur, it is an essential element for all animal species in as much as they all require the sulfur-containing amino acid methionine. There are three predominate forms of organic sulfur in animals and humans: 1). the thiomethyl of methionine residues in protein; 2). the sulfhydryl disulfides of protein; and 3). the compounds containing ester or amide bound sulfates of glycosaminoglycans, steroids, and many xenobiotic metabolites. Thus, sulfur becomes an important constituent of amino acids, proteins, enzymes, vitamins and other biomolecules. Unlike mammalian species, plants can use inorganic sulfur and synthesize methionine from which are synthesized all the other important sulfur compounds. Hence, sulfur deficiency occurs mainly when plants are grown in sulfur-depleted soils and when humans and animals consume low-protein diets. In recent times, however, the increasing prevalence of refining petroleum and smelting sulfur compounds of metallic minerals into free metals are having a large impact on the balance of sulfur in the environment. Sulfur toxicity is associated mainly with high levels of the element and its toxic volatile substances in the environment. Sulfur dioxide (SO(2)), a major air pollutant, may adversely affect animal and human health by causing bronchitis, bronchoconstriction, and increased pulmonary resistance.


    Directory of Open Access Journals (Sweden)

    Parul Dutta


    Full Text Available The hip joint is a large and complex articulation and can be involved by numerous pathologic conditions like congenital and developmental, infective, arthritic, and neoplastic. Early diagnosis and characterisation of pathology has vital role in proper management and follow up of the disease for the clinicians. Present study was conducted in 45 patients who underwent clinical, radiological, and pathological examination in GMCH. Maximum no of patient between age group of 10-30 yrs. male-female ratio was 1.8:1 and 30% cases are unilateral. FSE STAIR images were most useful in delineating pathologies. Gadolinium-enhanced scan were used to evaluate the extent of the disease and the pattern of involvement. AVN was the most common pathology detected comprising 29%. The next common abnormality detected was infective arthritis found in 26% of cases. In case of Legg-Calve-Perthes disease, there was abnormal linear increase in the signal intensity at junction of the epiphyseal cartilage. Ultrasonography is useful for the screening of paediatric hip cases and also for guided aspiration for histopathology. CT scan shows better resolution of soft tissue then the radiograph. The importance of early diagnosis can be gauzed from the fact that early initiation of treatment creates the difference between a responsible, worthwhile life, and a cripple handicapped life. The role of imaging can never be undermined considering the fact that early suspicion and detection is within the realms of imaging.

  1. Fellowship trends of pathology residents. (United States)

    Lagwinski, Nikolaj; Hunt, Jennifer L


    Recent changes in pathology residency education have included a decrease in the program length (from 5 years to 4 years for combined anatomic and clinical pathology training) and a national mandate for programs to assess 6 general competencies of trainees. These have undoubtedly led to changes in program curricula and in residents' desires to seek fellowship training. This study was designed to gather information about what residents are seeking from fellowship training programs. This study used an online survey to assess attitudes of residents in training programs toward fellowship training. The survey instrument had 26 questions pertaining to fellowship choices, motivations for pursuing fellowships, expectations of the fellowships, and postresidency concerns. There were 213 respondents from a mix of program types and representing each postgraduate year. Most residents will seek at least 1 or 2 fellowships after residency training. The most popular first-choice fellowship was surgical pathology (26%), followed by cytopathology (16%), hematopathology (15%), gastrointestinal pathology (10%), dermatopathology (8%), and forensic pathology (5%). The most common reasons for pursuing fellowship training were to "increase marketability" (43%) or to "become an expert in a particular area" (33%). Most trainees got their information about fellowship training programs from Internet sources. Fellowship programs will benefit from an optimally designed Web site because residents seek information predominantly from the Internet. Residents seeking fellowships are particularly concerned with selecting programs that provide job connections, an increase in their marketability, and the opportunity to develop diagnostic expertise.

  2. Communication skills in diagnostic pathology. (United States)

    Lehr, Hans-Anton; Bosman, Fred T


    Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

  3. Metabolism of arsenic and its toxicological relevance. (United States)

    Watanabe, Takayuki; Hirano, Seishiro


    Arsenic is a worldwide environmental pollutant and a human carcinogen. It is well recognized that the toxicity of arsenicals largely depends on the oxidoreduction states (trivalent or pentavalent) and methylation levels (monomethyl, dimethyl, and trimethyl) that are present during the process of metabolism in mammals. However, presently, the specifics of the metabolic pathway of inorganic arsenicals have yet to be confirmed. In mammals, there are two possible mechanisms that have been proposed for the metabolic pathway of inorganic arsenicals, oxidative methylation, and glutathione conjugation. Oxidative methylation, which was originally proposed in fungi, is based on findings that arsenite (iAs(III)) is sequentially converted to monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) in both humans and in laboratory animals such as mice and rats. However, recent in vitro observations have demonstrated that arsenic is only methylated in the presence of glutathione (GSH) or other thiol compounds, which strongly suggests that arsenic is methylated in trivalent forms. The glutathione conjugation mechanism is supported by findings that have shown that most intracellular arsenicals are trivalent and excreted from cells as GSH conjugates. Since non-conjugated trivalent arsenicals are highly reactive with thiol compounds and are easily converted to less toxic corresponding pentavalent arsenicals, the arsenic-glutathione conjugate stability may be the most important factor for determining the toxicity of arsenicals. In addition, "being a non-anionic form" also appears to be a determinant of the toxicity of oxo-arsenicals or thioarsenicals. The present review discusses both the metabolism of arsenic and the toxicity of arsenic metabolites.

  4. [Pathological buying -- a literature review]. (United States)

    Müller, Astrid; Reinecker, Hans; Jacobi, Corinna; Reisch, Lucia; de Zwaan, Martina


    This review summarizes the literature on pathological buying published during the past 15 years. Pathological or compulsive buying is defined as frequent preoccupation with buying or impulses to buy that are experienced as irresistible, intrusive, and/or senseless. The buying behavior causes marked distress, interferes with social functioning, and often results in financial problems. Studies on the phenomenology, diagnosis, classification, comorbidity, epidemiology, and treatment are presented. Pathological buying should be diagnosed as impulse control disorder not otherwise specified (ICD-10 F63.9). Psychiatric comorbidity is frequent, particulary mood, anxiety, substance use, eating, impulse control and obsessive-compulsive disorders. The positive results of pharmacological treatment with antidepressants (usually SSRI) and opioid antagonists could not be confirmed in controlled trials. A disorder specific cognitive-behavioral group treatment manual was published in USA. A controlled study is currently conducted in USA and since 2003 at the Department of Psychosomatics and Psychotherapy at the University Hospital Erlangen.

  5. [Pathology of the vitreomacular interface]. (United States)

    Pop, Monica; Gheorghe, Alina


    Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD.

  6. 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.

  7. Animal models of toxicology testing: the role of pigs. (United States)

    Helke, Kristi L; Swindle, Marvin Michael


    In regulatory toxicological testing, both a rodent and non-rodent species are required. Historically, dogs and non-human primates (NHP) have been the species of choice of the non-rodent portion of testing. The pig is an appropriate option for these tests based on metabolic pathways utilized in xenobiotic biotransformation. This review focuses on the Phase I and Phase II biotransformation pathways in humans and pigs and highlights the similarities and differences of these models. This is a growing field and references are sparse. Numerous breeds of pigs are discussed along with specific breed differences in these enzymes that are known. While much available data are presented, it is grossly incomplete and sometimes contradictory based on methods used. There is no ideal species to use in toxicology. The use of dogs and NHP in xenobiotic testing continues to be the norm. Pigs present a viable and perhaps more reliable model of non-rodent testing.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Pathology Imagebase - A Reference Image Database for Standardization of Pathology. (United States)

    Egevad, Lars; Cheville, John; Evans, Andrew J; Hörnblad, Jonas; Kench, James G; Kristiansen, Glen; Leite, Katia R M; Magi-Galluzzi, Cristina; Pan, Chin-Chen; Samaratunga, Hemamali; Srigley, John R; True, Lawrence; Zhou, Ming; Clements, Mark; Delahunt, Brett


    Despite efforts to standardize histopathology practice through the development of guidelines, the interpretation of morphology is still hampered by subjectivity. We here describe Pathology Imagebase, a novel mechanism for establishing an international standard for the interpretation of pathology specimens. The International Society of Urological Pathology (ISUP) established a reference image database through the input of experts in the field. Three panels were formed, one each for prostate, urinary bladder and renal pathology, consisting of 24 international experts. Each of the panel members uploaded microphotographs of cases into a non-public database. The remaining 23 experts were asked to vote from a multiple-choice menu. Prior to and while voting panel members were unable to access the results of voting by the other experts. When a consensus level of at least 2/3 or 16 votes was reached, cases were automatically transferred to the main database. Consensus was reached in a total of 287 cases across five projects on the grading of prostate, bladder and renal cancer and classification of renal tumours and flat lesions of the bladder. The full database is available to all ISUP members at Non-members may access a selected number of cases. It is anticipated that the database will assist pathologists in calibrating their grading and will also promote consistency in the diagnosis of difficult cases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  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. 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

  17. 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...

  18. 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.

  19. 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

  20. 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 ...